ACNE VULGARIS

A Study of One Thousand Cases

Jerome Kearney Fisher, M.D., Med. Sc. D.

            This study was set up to learn some of the possible influencing factors in acne vulgaris as are found in the adolescent.  The patients were only those which have been seen personally this past ten years by the author in his private practice and the study does not include the secondary involvement of the comedo by pyogenic organisms which produce pustules and scarring.  The cases in this report were taken consecutively from the files and not picked at random.  Detailed histories were taken on all cases at time of the initial visit.

            This paper involves 1088 cases of acne vulgaris.  Of these, 721 were females and 367 were males.  It is seen that a preponderance of twice as many females sought treatment for their acne as males.  However, this should not be interpreted to mean that only half as many young men develop acne vulgaris as young women.  Unless the eruption becomes conspicuously active in the male, he very likely will not seek medical aid.  This is probably due to the fact that he is not developed or matured to the same degree as the female of the same age.  Nor is he influenced so much by the social implications of his condition.

            As will be shown further on, the activity of the eruption was much more severe in the male than in the female in its development.  Also, medical treatment is sought at an earlier age in the female and the eruption, although milder in the female, does persist much longer than in the male.

           In the etiology of acne vulgaris one finds that many factors have been considered by numerous investigators.  These have included allergies to food 13, 14, 15, 18, nutrition 6, 9, 16, 17, 19, 20, 21, 22, 23, 24, 25, 26, drugs 27, water balance 20, 28, 29, 30, 31, stress and emotions 7, 32, 33, 34, hereditary tendencies 35, infection 62, and various hormones of the pituitary 36, 37, 38, 39, 40, the adrenals 20, 48, 49, 50, 51, 52, 32, 33, and the gonads 8, 10, 20, 33, 41, 42, 43, 44, 45, 46, 47.  A few of these factors are considered primary; the others are secondary or contributory.

            This presentation will be divided into three parts; first, a review of the many factors that have been found to influence acne in young people, second, a report of the analysis of my own cases and third, a discussion based on the findings under these two headings.

Part I  RESUMÉ OF THE LITERATURE

Incidence of Acne Lesions

            In studying the incidence of acne vulgaris in adolescence Bloch3 in 1931 found in his study of 2136 individuals that 96.6 per cent of girls at 17 years of age and 99.5 per cent of boys at 18 years of age were affected with acne.  Goldzieher8 in 1947 found an incidence of acne vulgaris in 67 per cent of his patients between the ages of 15 to 18 years of age.  Robinson6 reported in 1949 on 2083 patients with acne; of these 130 were 15 years of age or younger; 1583 were between 16 and 25 years old.  Then in 1958 Warshaw11 reported in a study of 1981 boys and girls the incidence of acne in boys and girls 17 to 18 years of age; this was 44 per cent for the boys and 30 per cent for the girls.

Incidence in the Male

            Forbes12 in 1946 gave a very comprehensive report of the incidence of acne in 2500 men in service from ages 18 to 49 years.  The accompanying table is taken from his paper.

Incidence in Men Ages 18 to 49

Ages                No. of Men     Comedones Only        Comedones with Papules or Pustules

18-19                     189                        51 (27%)                                             49%

20-24                     568                        147 (26%)                                           33%

25-29                     626                        141 (23%)                                           21%

30-39                     906                        142 (16%)                                           13%

40-49                     211                          15  (7%)                                              8%

Variations of Activity of Acne

            Henricksen and Ivy2 in 1938 observed that the peak of activity of acne appeared earlier in girls than in boys but the most severe cases were in the latter.

            Goldzieher8 in 1947 has noted that acne does not subside in the female at maturity as it does in the male.  He explains this observation by stating that the skin of the female is more sensitive to androgens than the male.  Also he noted that acne in the male is a self-limiting disease because the sensitivity subsides at maturity.  Belisario7 in 1951 also pointed out that acne in women in contrast to its presence in men may continue throughout the reproductive period.

Age Limit of Eruption

            Bloch3 stated in 1931 that acne is seldom seen after 30 years of age.  In 1942 Lowenthal moved the age limit up to 40 years.  Then Stillians5 in 1947 found that 63 per cent of 174 women with tuberculosis between the ages of 27 and 50 years had acne lesions; 4 of 10 of his tuberculous patients between the ages of 51 and 60 years still had acne vulgaris.  Strauss and Kligman87 report finding acne and sebaceous gland enlargement in many young females one or two years prior to menarche.

Location

            Lynch53 in 1939 made a study of the location of the activity of acne vulgaris.  He found the face the most common site in a group of 277 boys and 219 girls.  The trunk was involved much more often among the boys than the girls, and the back much more than the chest.

Elements of the Eruption, the Sebaceous Glands

            The pilosebaceous apparatus is the fundamental unit in formation of lesions of acne vulgaris42.  If comedo is not present, a clinical diagnosis of acne vulgaris cannot be made9.  The red papular lesion of acne usually develops from the microscopic comedones of the pilosebaceous apparatus of the skin and rarely from the large comedones.  Lorincz9 in 1963 stated that there is evidence that the acne lesions evolve only in those pilosebaceous follicles which are in the resting phase (telogen) of the hair cycle.

            Rothman10 had pointed out earlier that natural juvenile acne has two main pathogenic factors:  one, sebaceous gland hypertrophy and two, excessive follicular keratinization at the orifice which occludes the pore and hinders the expulsion of sebum.  The sebaceous glands are relatively small in childhood and attain full bloom at puberty; this is believed to be the principal factor in juvenile acne vulgaris58.

            Sebaceous glands are holocrine and are usually multiple acinar glands44.  They are most numerous on the scalp, forehead, face and chin, with fewer on the back and chest.  The hair follicle and sebaceous gland are invaginations of the surface epithelium.  The cells of the sebaceous gland become specialized so that the cells of the gland undergo fatty alterations; they throw off these altered cells and debris in the form of sebum42 into the cavity of the cystic sebaceous gland and its duct leading to the surface.

            Removal of the pituitary gland in rats results in the reduction in the size of the sebaceous glands; this is only partially counteracted by progesterone and testosterone therapy.  The pituitary then is itself necessary for the proper maintenance of sebaceous glands58.  Lorincz59 in 1963 confirms this observation by stating that among these hormonal factors, clinical experience and animal experiments indicate that androgenic steroids or progesterone in the presence of pituitary sebotrophic factor are the key endocrine stimuli which promote sebaceous glandular activity.

            At puberty an increase in sebaceous gland volume occurs with enlargement of lobules and possible formation of new lobules.  The pubertal stimulus acts by promoting mitotic division of the basal cells in the sebaceous glands.  No further growth of the sebaceous glands takes place shortly after puberty; an equilibrium is established even though the endocrine stimulus persists.  The maintenance of the sebaceous glands is under endocrine influence60. 

            The role of testicular hormones in the male as affecting the sebaceous glands has long been recognized mainly on the basis of three observations:

1.      Prepubertal castrates and eunuchoid males do not develop seborrhea or acne, a disease which is invariably connected with sebaceous gland hypertrophy.

2.      Castrate and eunuchoid males develop acne if they are treated with testosterone.

3.      Normal males and females may develop acne if they are treated with large doses of testosterone60.

Haskin, Lasher, and Rothman61 in 1953 proved that 10 mg. of progesterone given daily for 15 days in the white rat produced a 360 per cent increase in the size of its sebaceous glands.  A dose of 1 mg. daily of testosterone to white rats for 30 days produced a 500 per cent increase in the animals' sebaceous glands.

            From the available data one may conclude that pubertal development of sebaceous glands is an effect of testicular hormone in the male and of progesterone in the female.  Both exert a proliferative stimulus on the matrix of the cells of these glands.  There is no increase in the number of glands and the size of the single cells does not change in this hyperplasia.  However, the alveoli of the glands enlarge greatly55.  This experiment has given rise to the hypothesis that in the human female adolescent acne is incited by the progesterone of the corpus luteum and not by the previously implicated adrenal androgens58.

            English and Witkowski62 in 1964 have shown that androgens applied to the skin of eunuchs will cause sebaceous gland enlargement.  When the topical androgens are withdrawn from the eunuchs and prepubertal children, the sebaceous gland gradually returns to its original size.

            Rony and Zakon63 in 1943 gave 6 prepubertal boys injections of testosterone proprionate for two weeks.  When biopsies taken from the pubic area 2 to 3 days after therapy were compared with those taken 2 to 3 days before the injection, a decided increase in both size and number of sebaceous glands was noted in all cases.

            Ebner30 in 1956 commented that since the frequency of acne is in adolescence and worse during menstruation that a hormonal influence must be present.

            Pochi, Strauss and Mescon67 in 1963 proposed further that two steroids are required at the same time to produce acne.  Dehydro-epiandrosterone is the adrenal steroid hormone most active in stimulating sebaceous gland activity while glucocorticoids act in a permissive capacity with physiologic amounts being necessary for sebaceous gland response to androgens.

Formation of Sebum

            Montagna44 states that the sebaceous glands of man (and no other animal) in the fetal stage contains glycogen; however it disappears at 6 months of fetal life.  In cells undergoing sebaceous transformation, glycogen decreases at the same rate that lipid increases.  The distribution of glycogen is precisely correlated with lipid storage and it is likely that sebaceous transformation takes place by a conversion of carbohydrates to lipids rather than by an accumulation of fat from the blood.  Contarow and Trumper38 are of the same opinion and explain that neutral fat which is ingested is taken up by adipose tissue while the fats forming sebum are synthesized in situ from carbohydrates and protein in the holocrine glandular cells.

            Whatever fat that is rapidly mobilized or stored seems to be through glycogen phase; this similarity of the sebaceous glands to adipose tissue, and particularly to brown fat makes possible the suggestion that the sebaceous lipids may be synthesized in part by local oxidative breakdown of glycogen.  The presence of glycogen in the fat of animals which have been starved and then fed a high carbohydrate diet is known.  In the normal rat, fat cells are ordinarily devoid of stainable glycogen; but after the injection of a single large dose of insulin, glycogen is present in large amounts in both the brown and the white fat.  The fat of diabetic animals contains no glycogen44.

            Nicholas (quoted by Montagna54) believes in the beginning of sebaceous differentiation that lipid droplets appear first within the mitochondria filaments of the individual sebaceous gland cells.  As the lipid droplets become larger and coalesce, the accompanying mitochondria are said to decrease in number.  Mitochondria seem to play a direct role in the synthesis of the sebaceous lipids; they are not transformed into lipids.  This lipid accumulation and fragmentation characterizes the end point of sebaceous cells54.

            Histologic evidence strongly suggests that sebum lipids are built from protoplasm of the sebaceous glands basal cells.  Constituents of sebum probably are built from small carbon fragments which are formed in catabolic processes by the cells55 and not excreted as lipids extracted from the blood.  Sebum is composed of glycerides and large amounts of esters of fatty acids with higher alcohols such as cholesterol20.  Normal human sebaceous glands contain no free cholesterol, but the stagnant sebum of comedones and of early acne cysts contain an abundance of it57.

            Montagna54 in 1956 reported that treatment with estrogen increases the mitotic activity but the sebaceous glands become smaller.  Andrews49 stated in 1965 that estrogens are capable of decreasing sebum production.

            Sebum is different from tissue fats in being composed partly or entirely of waxes.  Thus a number of unusual substances not found elsewhere in the body must be synthesized within the sebaceous glands.  The composition of sebum differs from species to species; cholesterol and large amounts of free fatty acids are perhaps the only substances which occur constantly44.

            The origin of free fatty acid in surface lipids might be explained in terms of lipases which are known to be present in the sebaceous glands and the epidermis44.

            The sebum of man contains squalene; its origin and function are unknown44.  It is related to wool fat of sheep in that squalene chemically is an acyclic tri-terpene while wool fat is a cyclic tri-terpene.

            Vitamin D. may be formed in the sebum44.

            Sweating seems to be a prime factor in the spread of sebum over the body44.

Infection
            The Gram positive anaerobic diphtheroid bacillus produces proprionic acid from sebum62.  This bacterium has been termed Proprionbacterium Cornybacterium acnes, or acne bacillus.

            The secondary invader of staphylococcus with its coagulan positive actions is the organism that follows so many times after the appearance of the red acne papule to infect the comedo and do so much destruction and scarring.  This condition comes late in the formation of the severe red, pustular and scarring eruption.  Many factors such as susceptibility to infection, hygiene, local trauma, resistance to infection, and the number of initial papular comedones that have developed play a large role in the activity of this infection.

            The usual sequence of events is:  (1)  the sebaceous gland duct becomes plugged with sebum or detritus which hardens, (2) the local tissues try to remove this newly formed foreign body in situ by an inflammatory process, and (3) this draws blood to the site and plasma and lymph fluid leak out into the sebaceous gland structure.  And finally since this is open to the skin surface by way of the sebaceous gland duct, the whole pilosebaceous apparatus then is a culture for surface bacteria with culture medium in the form of serum present in the inflamed tissue.

Androgens

            Since Hamilton's20 paper in 1941, the study of androgens as a direct and primary cause of acne has received a growing impetus as a factor in the etiology of acne vulgaris.  He pointed out that eunuchoids are individuals who do not mature sexually and never have acne.  Androgen is a secretagogue for the pilosebaceous apparatus and in the eunuchoid treatment with testosterone must be continued for three or six weeks before acne will appear.  Estrogens are low in patients with acne but eunuchoids have a lower level of estrogens than the individual with acne.  Rothman10 demonstrated in 1954 that the sebaceous glands in rats atrophy after castration and regenerate again on implantation of testicular tissue or on the administration of male hormone.

            The female, like the eunuchoid, is also able to respond to testosterone with the formation of comedones and papules20.  It is at the time of sexual maturity that urinary levels of androgens become elevated20.  Androgens can suppress both the production and some of the actions of estrogens.  Hamilton concludes further that androgens increase vascularization, cause cutaneous pigmentation, hold salt and water in the tissues and produce stimulation of sebaceous secretion.  Testosterone is conjugated in the liver to androsterone  before being excreted by the urine and is then biologically inactive43.

            In 1963 Hamilton and Mester64 found no acne in 91 eunuchoids nor in 11 oophorectomized females during age of adolescence; the eruption present at time of castration persisted for several months after operation.

            Hooker et al41 in 1943 demonstrated that the skin of estrogen treated rats became thin and the sebaceous glands were much reduced in size; however animals that received both estrogen and androgen were completely protected against these changes and the sebaceous glands were even more numerous and larger than in the untreated animals.  Goldzieher8 in 1947 next showed that the skin of the female is more sensitive to androgens than that of the male.  Also the female skin holds this sensitivity until later in life than the male.

            Sulzberger and Witten42 in 1951 stated that it was generally held that it is the ratio of circulating androgens to estrogens which is important as related to acne vulgaris rather than alterations of one or the other components alone.

            The observation of Palitz47 et al in 1964 that acne is more severe and more prevalent in males than in females advances a possible theory in favor of androgens as a cause.

Sources of Androgens

            In the male the interstitial cells of Leydig of the testes secrete testosterone by stimulation from the luteinizing hormone of the anterior pituitary.  It is believed by some that about 2/3 of the androgenic substance in the urine of the male originates in the adrenal cortex43.  But this hypothesis does not seem to hold in the case of the eunuchoid whose adrenals may be intact.  Androgens are present in the urine of females up to three-fourths of that of males.  The adrenal cortex has been thought by some43, 49 in 1955 to be the source of all circulating androgenic hormone in the female.  But Palitz et al47 in 1964 state that both adrenal glands and the corpus luteum are sources of androgens in the female; progesterone is secreted by the corpus luteum during the luteinizing stage of the menstrual cycle.  The corpus luteum is the counter-part of the cells of Leydig in the male.  Polycystic ovaries have been shown in 1964 to synthesize more androgen than normal ovaries.  Virilism is associated with ovarian tumors which contain lutein tissue (producing progesterone); thus there is good evidence to believe that luteinized ovarian cells are potential sources of androgen8.

            Lorincz9 in 1963 feels that there is clearly an individual susceptibility factor to acne and this tends to be familial.  The individual susceptibility is well illustrated when adults are given large doses of androgens; severe acne tends to develop only in those who earlier in life had pronounced acne.

Pituitary Stimulation

            Cushing70 in 1912 wrote that in hyper-pituitarism the skin is thick and coarse with enlargement and increased activity of the skin glands.  Semon and Herrmann66 stated in 1940 their belief that pituitary basophilism is the primary cause of acne.  While Cohen37 stated the following year that oily skin and comedones occur in acromegaly and gigantism, a disturbance of the acidophilic cells of the pituitary.  He further quotes Desaux in saying that seborrhea occurs in pituitary acidophilic activity.  Here we have two opposing views expressed twenty-five years ago.

            More recently, Butterworth and Chamberlain39 in 1957 found that acne lesions are suppressed after pituitary irradiation.  The three gonadotrophic hormones affected in the pituitary secretion are:

The follicle stimulating hormone which causes the development of the follicles in the ovaries.  In the male it stimulates the testes with development of the semeniferous tubules and spermatogenesis. 
Luteinizing or interstitial cell stimulating hormone which promotes secretion of progesterone in the female.  In the male it stimulates the interstitial testicular tissues to secrete testosterone. 
Luteotrophic hormone (prolactin or lactogenic hormone) which in conjunction with estrogen stimulates proliferation of the mammary gland.  This latter hormone also initiates milk secretion in the mammary gland post partum71.
Chorionic gonadotrophin is produced in the placenta but differs from the pituitary gonadotrophin.  It is almost entirely gone from the blood and urine one week after delivery43.

            Pituitary growth hormone is elaborated by the acidophilic cells of the anterior pituitary lobe.  The basophilic cells also present in the anterior lobe produce follicle stimulating, luteinizing, thyrotrophic and adreno-corticotrophic hormones.  Pituitary growth hormone acts directly on body structures as an anabolic hormone that promotes growth.  Warshaw69 suggests that this hormone may have some relation to the postulated pituitary hormone "sebotrophin" of Rothman.  Since estrogens at puberty cause maturation and oppose the effect of the pituitary growth hormone, a low estrogen titer allows free play of pituitary growth hormone.  Thyroxin increases the secretion of the pituitary growth hormone.68  Progesterone, according to Goldzieher in 1964, does not suppress human urinary gonadotrophin excretion; progesterone apparently acts directly on the ovaries to suppress follicle formation.

            The pituitary follicle stimulating hormone and the luteinizing hormone are suppressed by the feed-back mechanism of the estrogen75.

Adrenals

            The adrenal glands have been associated with the formation of acne lesions because of the androgenic effects of some of their hormones.  The adrenal cortex secretes estrogen, progesterone, adrenosterone, dehydro-iso-androsterone and aldosterone (the salt retention hormone)68.  Asel93 in 1965 stated that dehydroepic-androsterone is secreted at the rate of 30 mg. a day by the adrenals; it may be the most important androgen secreted by the gland.  Dehydorepic-androsterone 100 mg. was given three times weekly to an adult male whose sebum had been previously suppressed by estrogen stimulated sebaceous activity.  Bruno Bloch3 in 1931 stated that it has long been recognized that in the female the adrenal cortical hormones are the important "androgenic" agents and must account for the growth of the pubic and axillary hairs, the stimulus of the pilosebaceous structures, the development of the apocrine glands as well as the concomitant appearance of acne.  Precocious development of adult characteristics of a masculine nature in a girl with adrenal cortical tumor may be accompanied by pronounced acne20.  In adrenal virilism the urinary androgens were in level with normal women but their estrogens were low20.  Hypertrichosis may develop in pregnancy and subside after childbirth or it may be associated with enlargement of the ovaries due to the lutein body cysts or extensive theca luteinization8.  Belisario7 observed that acne in the female with an adrenal tumor disappears after the removal of that tumor.  English and Witkowski45 in 1954 stated that masculinizing tumors such as those which involve the ovaries, adrenals, pituitary and pineal glands can be responsible for acneform lesions?especially when all lesions are at the same stage.

            Androgenic turmore include the adreno-cortical syndrome, ovarian tumor, pineal tumor and testicular tumors33.  Androgenic tumors in the adult female include Cushing's Disease, virilizing tumors and adrenal hyperplastia33.  Sulzberger and Witten42 add such masculinizing conditions as menopause and arrhenoblastomas as having acnegenic effects.

            Haskin et al61 in 1953 reported that patients treated with adreno-corticotrophin developed acneform eruptions which were not identical with juvenile acne because they lacked the usual seborrhea and comedones.  Clinically and histologically in these eruptions the major component is excessive follicular keratinization; little if any evidence of sebaceous gland hyperfunction is present.

            Endogenous androgen production is a prerequisite to the development of steroid acne; therefore acne does not occur with oral steroids before puberty95.  It is the author's belief that it is this corticoid stimulation of keratin in the follicles on the thighs and upper arms that is the cause of keratosis pilaris in young people.  No sebaceous activity is present in the lesion of keratosis pilaris either.  So that this eruption on the arms and legs may be a corticoid acne-like eruption.  But this will be the subject of another study.

Estrogen

            Nathanson et al72 first reported in 1939 that during catamenia the estrogens are low while the androgens do not fluctuate significantly.  In 1940 Lawrence and Werthessen73 demonstrated a decrease from normal in urinary estrogen excretion by women with acne.  Wile at al76 as early as 1939 demonstrated in acne patients an increase in urinary excretion of androgen and a moderate decrease in urinary excretion of estrogen in both sexes.  Lawrence and Werthessen51 in 1942 reported a decrease in the urinary estrogen excretion with a definite androgenic preponderance.  They concluded that comedones in acne were the result of an increase in the androgen-estrogen ratio.  Treatment with ethinyl estradiol or diethyl stilbestrol for 2 to 6 months cleared 15 of their 25 acne patients.

            Sulzberger and Witten42 in 1951 said it has been calculated that the estrogen blood level in normal menstruating women is at its highest plateau from about the 10th to the 22nd day post-menstrually.  The lowest level of estrogens is reached a few days before menses.  The exacerbation of acne tends to occur at precisely those times when the androgen-estrogen ratio tends to be highest.

            Estrogen is conjugated in the liver to glucuronides and sulfates of estriol, estrone and estradiol then excreted in the urine43.  Estrogen as such is increased in the urine in liver disease if hepatic function is impaired as in cirrhosis or hepatitis43; the increase is caused by diminished destruction or inactivation by the liver cells.  The excess estrogen then causes gynecomastia and menstrual disorders.  It caused testicular atrophy in males.  Malnutrition and vitamin B deficiency may interfere with hepatic inactivation causing premenstrual tension and cystic mastitis43.

            Estrogen excretion is diminished in the male castrate indicating that a portion of the estrogen in the normal male urine is of testicular origin43.

            Estrogen activity in girls' urines has been determined for as long as 18 months before menarche.  Boys and girls before the age of 11 years secrete about the same amount of estrogenic material in the urine74.

            Greenblatt et al75 in 1964 found the highest estrogen secretion in normal non-pregnant adult occurs around the time of ovulation; the lesser peak occurs about the 21st day of the cycle. Estrogen secretion decreases rapidly in many, slowly in others.

            The Medical Letter77 recently reported that estrogens can lower blood lipids.

Progesterone

            Progesterone, the hormone of the lutein body (granulosa lutein cells), is slightly androgenic.  It is secreted in significant amounts by the corpus luteum and by the placenta in the human75.  It differs from testosterone chemically only in the short side-chain at the 17 position of the D-ring88.  It is secreted by the corpus luteum and appears in the urine as pregnanediol the day after ovulation; it is also produced by the syncytial cells of the placenta and is formed in the adrenal cortex43.  This androgenic effect is likely brought about by the conversion of progesterone into androsterone as reported by Dorfman and Hamilton in 1940.  Greene et al78 have shown that when progesterone is given subcutaneously to castrated rats in the dosage of 2 mg. daily it is definitely androgenic; however it is less effective if given intraperitoneally.  Mason and Engstrom32 state that hydroxy-progesterone is androgenic.

            Sunderman and Boerner80 have reported that progesterone increases in the blood level from the mid-period intermenstrually until the premenstrual phase when the amount decreases even to the point of completely disappearing 24 to 48 hours before the onset of menses.

            Culiner81 stated in 1945 that some of the active steroids seem to come from the ovary; evidence points towards the lutein body and luteinized theca or stroma cells as their most likely source of origin.  As a matter of fact, symptoms of masculinization such as facial hypertrichosis have been observed in cases in which the ovary was the site of extensive or pathological luteinization (progesterone origin).

            Forbes82 in 1950 reported that plasma level studies of progesterone showed that the progesterone did not disappear until after onset of menses.  Meltzer83 in 1951 found that progesterone appears in the blood stream on the 14th day of the menstrual cycle and reaches the highest level on the 22nd day; then it gradually disappears at the end of the cycle.  The ovaries secrete 200 to 600 units more progesterone than estrogen74.  The females have recurrent flares synchronous with the elevation of the progesterone level in the blood.  The ratio of the estrogen-androgen level changes to a relative androgenicity.

            Aron-Brunatiere84 in 1953 noticed that acne is worse during the second half of the menstrual cycle and during the first few weeks of pregnancy?two stages characterized by progesterone secretion.  Because of the well recognized androgenic activity of progesterone, he suggested that in acne progesterone may be the factor in females analogous to testosterone in males.  He also noticed an aggravation of acne when he administered progesterone in doses of 20 to 30 mg. in 2 or 3 injections between the 21st and the 25th days of the menstrual cycle. 

           Haskin et al61 reported that 10 mg. of progesterone daily to rats gave the same sebaceous gland stimulus as was obtained with 1 mg. of testosterone.  Rothman10 stated that because of the powerful effect of progesterone as found by Haskin et al, it was hypothesized that pubertal development of sebaceous glands and occurrence of seborrhea and acne vulgaris in the female depend on the production of corpus luteum hormone in the same way they depend on the production of corpus luteum hormone in male.  This hypothesis, since it does not implicate the adrenals, is consistent with the observation that hypogenital males and females do not develop seborrhea or acne.  Smith85 in 1959 found progesterone as effective as testosterone in stimulating the sebaceous glands of the elderly.  But Jarrett86 also in 1959 gave progesterone in dosage of 25 mg. intramuscularly daily for 10-17 days in 3 males and produced no change in acne.

            Strauss and Kligman87 in 1961 showed by their work that physiological amounts of progesterone given intramuscularly have been excluded as a source of stimulation to sebaceous glands.  Norlutin or acetate ester (a synthetic) in doses of 10 mg. will stimulate sebaceous glands where the smaller dose of 5 mg. is ineffective88.  Human sebaceous glands can be directly stimulated by androgens even in the presence of large amounts of estrogens.  Pincus89 on the contrary stated that endogenous produced progesterone exhibits strong androgenic properties whereas the synthetic progestational substance, norethynodrel, has been shown to have no androgenic properties.  However, he does not state his dosage.

Biologically, progesterone has been converted to testosterone in vitro by rat testicular tissue, by human ovarian tissue, and by human interstitial cell carcinoma tissue88.

            Lorincz90 in 1962 stated that the effect of progesterone is indirect on the sebaceous glands because female adult spayed rats showed increased sebaceous gland activity by volume of the glands.  Hypophysectomized spayed female rats had decreased sebaceous gland activity.

            Ebling91 in 1962 showed that estradiol when implanted for 280 days in normal and hypophysectomized or adrenalectomized female rats caused a significant reduction in sebaceous glands.  In castrated and in hypophysectomized castrated rats, testosterone promoted sebaceous gland cell proliferation and mitosis only in the presence of pituitary gland.  He also showed that the simultaneous administration of testosterone and estradiol produced a smaller gland than normal but one which had an increased number of mitotic cells.  Progesterone had no effect on sebaceous gland size, cellular proliferation or turnover time in intact or spayed mature or immature female rats.  Large doses of progesterone caused an increase in sebaceous gland size in castrated male rats.

            In agreement, Andrews92 in 1963 stated that progesterone is known to have androgenic properties in that it can maintain spermatogenesis in the hypophysectomized rat.

            Progesterone is rapidly metabolized in the body and therefore its administration should be every 8 to 12 hours75.  Alkaline phosphatase activity is diminished by progesterone too75.  Asel93 in 1965 stated that progesterone in large doses may be converted to active androgen which will incite the acne process.  Therefore an increase in circulating androgens produced by the endogenous transformation of progesterone to an androgen could explain the exacerbation of acne during the luteal phase of the menstrual cycle47.  If it were possible to eliminate the corpus luteum and thus the major source of progesterone, an important factor in the cause of acne in the female might be controlled47.  Andrews49 in 1965 explains the action of contraceptive tablets which suppress ovulation by the suppression of the secretion of gonadotrophin (folliculin) of the anterior pituitary with the contraceptive pills; no corpus luteum is formed because no follicule is formed in the ovary and subsequently no corpus luteum body develops and being absent, no progesterone is secreted.

            By the sudden withdrawal or decrease of progesterone and estrogen, menses appears.  In larger doses progesterone exerts androgenic effects perhaps by conversion to androgenic metabolites43.  Strauss and Pochi94 in 1964 point out that the prevention of ovulation per se does not appear to be related to any effect upon the sebaceous glands; if it were, the use of a progestin alone, i.e. norethyndrel would have been expected to cause more consistent decrease in sebaceous gland activity.

Stress and Emotions as Factors
            Stress and emotions are factors which are often difficult to prove as definite causes because they cannot be treated in a way so that they are applied or removed at will.  Stokes and Sternberg96 in 1939 said that endocrine changes influence the skin in acne vulgaris through the emotions.  The reverse effect was shown by Mason and Engstrom32 in 1950 when psychotic men did not respond to a test of hot and cold stress with a rise in their 17-ketosteroid urinary excretion as did normal men.  Blackburn33 in 1951 made the observation that androgens lay the fire for acne and emotions or other secondary factors light the fire.  Belisario7 in 1950 stated that psychosomatic relationship is unquestionably present in acne and that after the emotional conflicts are rationalized, the acne subsides.

            Larenz et al34 in studying 30 patients in 1953 found a close relationship between life situations giving rise to a characteristic affective pattern and an increase in the acne pustule of these patients.  Stressful interviews with acne patients were associated with increased sebum secretion when "anger" was elicited and with decreased sebum secretion when the patient responded with "remorse."  Larenz then offers the thought that abrupt phasic alterations in activity of sebaceous glands may play an important part in comedo formation. 

Almost any type of stress or strain placed on the body tends to alter the function of the adrenals68.  The regulation of secretion of adreno-corticotrophic hormone is of significant physiological and clinical importance71.  Augmented release of endogenous hormone is evident following any one of a wide variety of diverse and unrelated stimuli; they are trauma, emotional stress, drugs, chemical or bacterial toxic agents or substances normally present in the body, namely, insulin, thyroxine, vasopressin and epinephrine71.  The anatomical site of this mechanism appears to be the hypothalamus.  Experimental evidence suggests that this structure releases a humoral agent that reaches the adenohypophysis via the hypophyseal portal vessels.  The nature of this agent is as yet unknown but its stimulation of the pituitary results in release of ACTH71.  Harris et al as quoted by Williams68 has shown that it is the portal blood circulation entering the hypophysis which carries the humoral substance and not through nerve impulses.  This was proved by section of the connecting nerve stock between the pituitary and the brain.  With acute or severe stress ACTH secretion may be increased within a few seconds68.  However a lesion of certain centers of the hypophysis will prevent ACTH release following stress38.

            The hypothalamic centers involved are activated through the cerebral cortex by specific stresses or psychic reactions68.  The afferent impulses may arise in one of the organs of special sense or in the general sensory nerve endings.  Many of the effects of sensory stimuli on gonadal responses are well known.  For example, egg-laying of hens may be increased by prolonging the duration of exposure of the animal to light; red light being more effective than certain other colors.  Rabbits tend to ovulate only after coitus or with some other form of sexual stimulation.  The cycle of stimulus in the rabbit is as follows:  Genital stimulation?central nervous system?anterior pituitary?ovaries?uterine changes.  Suckling is associated with the following psychic changes:  Suckling?central nervous stimulation?pituitary?lactation.  At the time of adolescence the following stimulus cycle is found:  central nervous system?anterior pituitary?gonads?genitalia and body tissues.  The olfactory effects on gonadal stimulation are readily appreciated in the dog, bull and many other animals68.  The effect of psychogenic influences on the endocrines can be illustrated by the responses to marked fear; there is an increased elaboration of epinephrine which increases the function of the pituitary, thyroid, adrenal cortex and pancreas68.  Hypothalamic lesions have been known to be associated with decreased thyroid function but the main problem has been the mechanism by which the hypothalamus influences pituitary function68.

            Lesions in certain portions of the hypothalamus can cause precocious or delayed puberty depending upon whether there is an increased or decreased stimulation of the pituitary gland.  Sebaceous gland hyperplasia develops in encephatitis lethargica.  Rothman10 has suggested that the encephatitis process may disturb the pituitary hormonal balance via nerve tracts leading to the pituitary.

            Goodman and Gilman114 state that caffeine excites the central nervous system at all levels.  Cocoa contains 50 mg. caffeine and theobromine per cup.  Cola nut used in the preparation of cola drinks gives about 35 to 50 mg. caffeine per bottle.  Children are more susceptible than adults to excitation by xanthines.

17 - Ketosteroids

            The term 17-ketosteroids refers to those steroids possessing a ketone group on the 17th carbon atom.  They are all determined by the urinary excretion where they are excreted as esters.  Except for estrone which is removed at the time of urinary analysis, these steroids are termed urinary "androgens."  The chief 17-ketosteroid of normal and of abnormal urines is androsterne38.  They are believed to represent the excretory transformation products of certain adrenal and testicular hormones.  The quantity excreted in the male serves as an index of the combined steroid secretory activity of the adrenal cortex and the testis and in the female chiefly of the adrenal cortex38.  Normal men excrete more 17-ketesteroid than do normal women32. These compounds are discussed here principally as a means for possible study of patients with acne.

            Nathanson and Towney99 in 1941 found increases in estrogens and 17-ketosteroids in urines of both sexes from the ages of 3 to 7 years.  From 8 to 11 years of age there was further increase but the 17-ketosteroids increased more rapidly in the female.  In prepubertal period 17-ketosteroids probably are derived almost entirely from adrenal cortex102.

            The close association of acne and masculinizing tumors and high androgen titers suggests that an excess of 17-ketosteroids is the determining factor in acnegenesis51.  Pincus101 found that 17-ketosteroids were depressed during sleep, whether by night or by day, and were elevated promptly after waking.

            Mason and Engstrom32 in 1950 found that orchectomy did not abolish excretion of 17-ketosteroids.  About one-third of 17-ketosteroids in normal male originate in the testes38, 69.  They report that Kirschmann isolated the same quantity of urinary 17-ketosteroids from ovariectomized women as from the urine of normal women.  In women with Addison's disease, 17-ketosteroid almost entirely disappears from urine.  Hamblen observed decreases of 14 to 26 per cent in the excretion of 17-ketosteroid when estrogens were given to 22 women with various grades of ovarian failure who excreted moderately elevated amounts of 17-ketosteroid before treatment32.  McCullogh reports 5 eunuchoids excreted amounts of 17-ketosteroid which were about half the average of normal male32.  Callow, Callow and Emmens also found that the average 17-ketosteroid were less in eunuchoids than normal males32.  Mason and Engstrom32 found that total starvation for four days decreased the excretion of 17-ketosteroids 50 per cent in 3 normal men and one obese woman.  ACTH stimulates the increased excretion of 17-ketosteroids32.

            White and Lehman52 in 1952 treated 14 young men with diethyl stilbestrol and studied their 17-ketosteroid excretion; the average pretreatment 17-ketosteroids were 13.6 mg. per 24 hours; during treatment the average was 9.4 mg. with a drop of 4.2 mg. or 31 per cent per 24 hours.  But this was not correlated with clinical improvement!  In contrast English and Witkowski62 in 1954 showed that in individuals receiving estrogen sufficient to suppress sebum production the androgens, as measured by the urinary 17-ketosteroids, remained unchanged.

            Rothman10 has found it hard to accept the view that all of the 17-ketosteroids in the female originate in the adrenal cortex because male castrates and most ovarian deficient females have well functioning adrenal glands; yet they do not develop seborrhea or acne.

            Tomovitch et al103 in 1963 found that infantile acne was not due to ketosteroids.  Patients have normal plasma corticoids.

            Andrews49 states that 17-ketosteroids levels are normal in acne patients.  And Pochi and Strauss104 mention that 17-ketosteroids are a poor index of androgenicity in that they are principally metabolites of adrenal cortical hormones which possess little androgenic potency.  Yet the adrenal secretions are considered the principal androgens by many others in both the male and female.

            It has been assumed that 17-ketosteroid determination is a measure of androgen production; an increased excretion of urinary 17-ketosteroids in acne would indicate androgen over-production and this accounts at least in part for the pathogenesis of acne104.

            Henricksen and Ivy2 in 1938 found that 46 per cent of girls in a children's home had flare-up of their acne lesions before or during their menses.  The acne eruption in 72 per cent of the girls in a university clinic were worse before or during menses.  Robinson6 found 111 exacerbations of acne before or during menses in his series.  Mason and Engstrom32 state that during normal menstrual cycles there is no evidence of cyclic variations in the excretion of 17-ketosteroids.  They believe the small fluctuations which occur bear no relation to the cycle.  Hamblen32 suggests that late or intercurrent ovarian failure for 6 months or more precipitates androgenic hyperfunction of the adrenal cortex.

            Blackburn33 in 1951 stated that 17-ketosteroids include the excretion products of the androgens and parallel the activity of acne.  In view of the acnegenic effect of the androgens, the chemical relationship of the testicular ketosteroids and the adrenal steroids is a strong additional argument in favor of certain adrenocortical steroids being fundamentally involved in the production of acne in females and perhaps to some degree in males too42.  And since the exacerbation of acne tends to occur at precisely those times when the androgen-estrogen ratio tends to be highest, it is possible that androgens may be elevated at a time when estrogen is lowest.

            In most cases the urinary 17-ketosteroid outputs are a poor index of ovarian endocrine activity but since assays of testosterone are not readily available, they are the only available test65.

Other Hormonal Observations in Acne
            Cohen37 in 1941 noted that acne may disappear or become worse during pregnancy.  Andrews49 in 1965 stated that acne is often worsened during the first few months of contraceptive therapy and this unfavorable result is probably due to the progesterone contained in the contraceptive; later the progesterone will have suppressed the pituitary so that no corpus luteum is formed.

            Acne eruptions are part of the adreno-genital syndrome and in neoplasm of the adrenal cortex, surgical removal clears the acne and masculinization8.  Treatment of both male and female patients with testosterone is likely to bring on acne8.

            In menopause the ovary becomes less responsive to pituitary gonadotrophic stimulation which causes an increased demand of follicle-stimulating variety38.

Previous Laboratory Studies and Incidental Observations in Patients with Acne
            Knowles and Decker105 in 1926 reported they found no difference in the titrations of gastric secretion of acne and non-acne patients.

            Leving and Kahn in 1922 and Greenbaum in 1931 reported separately that the glucose tolerance curve revealed no definite difference between individuals with or without acne.

            Wortes in 1937 gave 10 units of insulin to acne patients while fasting and allowed the patients to remain hypoglycemic; this cleared the acne.  Starvation decreases blood thyrotrophin along with other adenohypophyseal hormones except ACTH but its mode of action is not clear68.

            Lynch53 in 1939 found that girls with acne had lower basal metabolic rates than boys with acne.  Higher basal metabolic rates were reported for both sexes when the eruption was extensive.  Smith et al in 1951 found that 42.5 per cent of 353 acne patients had a basal metabolic rate less than a minus 10 while 2.3 per cent had a basal metabolic rate greater than plus ten.

            Stokes and King35 in 1932 found the incidence of acne in parents of patients with acne is 26 times that of the parents of persons who have never had acne.  In a coverage with replies by mail, Ratzer found marriage brought about improvement in 43 per cent of 415 women; 53 per cent noted no change.  The largest percentage improved after the birth of a child10.

Nutrition
            Since the early studies in the cause of acne, nutrition has held a high place in discussion.  Buckley111 in 1906 noted that bananas and nuts frequently aggravated acneiform eruptions.  Wells17 in 1932 cited cheese, eggs, pork and chocolate as factors in acne and White18 in 1933 found that chocolate, milk, wheat, oranges, tomatoes and nuts were the foods most frequently incriminated.  Sulzberger et al112 in 1934 showed that patients with acne responded uniformly with an eruption when potassium iodide was ingested (This is a reaction seldom found in persons without acne diathesis.  Does this change unsaturated fats to saturated fats?).  Rowe13 in 1936 reported cure of acne patients with the elimination of certain foods.  Cormia14 in 1940 reported decided improvement in 30 patients treated strictly by a milk diet; also improvement occurred in several patients on a strictly milk diet in whom no evidence of food sensitivity could be determined.  (Does the combination of milk and other foods cause reaction?)  Cormia also found the foods producing the largest number of lesions were:  wheat, tomatoes, milk, chocolate, nuts and spinach.  Semon and Herrmann19 in 1940 found that a group of 11 patients with acne showed a lag in return of blood glucose tolerance curve after ingestion of 50 gm. of glucose; testing was done at half hour intervals.  When 3 to 5 units of protamine zinc insulin by hypodermic injection was given two to three times weekly improvement was noted; relapse occurred when the insulin was not given.

            Hamilton20 in 1941 observed that no food stuffs seem to offer a common denominator in the induction of acne although exacerbations may be produced.

            Tobias22, Andrews23, Sutton, Jr.24, and White21 have all advised the elimination of milk in acne diet.

            Lutz25 in 1944 believed that overloading the gastro-intestinal tract with carbohydrates (flour, potatoes, bread) was an important factor in the efflorescence of acne eruptions in 12 to 24 hours; nuts, cheese and sausage can cause this eruption in initially sensitive and persistent deep acne papules.

            Flood113 found from a study of previous papers and by clinical observations that foods commonly causing trouble are milk, pork, chocolate, tomatoes, oranges and nuts.

            Robinson6 reported in 1949 that the milk products, in his experience, were the most frequent cause of exacerbation with some patients drinking 2 to 3 quarts of milk a day; cola drinks and beer have also seemed to have aggravated the acne lesions.  In an acne case milk drinking may be a precipitating factor.

            Sutton, Jr.24 in his 1949 edition believes the lipochrome pigments of tomato juice and orange juice, carrots, egg yolk and cod liver oil had as bad effect as butter fats.

            Andrews, Domonkos and Post23 say the foods to avoid are chocolate, nuts, ice cream, egg yolk and cheese.

            Rothman10 reports Serrati as finding that an excessive fat and later carbohydrate intake produced an increase in liquid sebum in normal patients and in those with acne; 12 normal patients produced 15.4 mg. of liquid sebum over 40 sq. cm. of skin.  An excess of fat raised this to 21.0 mg. and when on carbohydrate it rose to 22 mg.  An acne patient on regular diet excreted 29 mg. of fat.  When fat was given, this same area produced 36 mg. and when on carbohydrate diet, 36.8 mg. were excreted.

            Rothman states further that forced feeding of animals with fats resulted in excretion of increased amounts of sebum.  The nutrient fat constituents were excreted unchanged?70-119% in two weeks.  In comparable overfeeding with carbohydrates, the increase was only 11-38 per cent.  Interestingly, when the abnormal type of feeding was continued there was a tendency for the amounting sebum to decline again.

            Kalz et al115 in 1951 found the average total serum lipids in 50 fasting patients with acne to be 690 mg. per cent while the averages for 10 normal patients was 616 mg. per cent.  The free serum cholesterol studies in the same 50 patients with acne averaged 81.92 mg. per cent while 10 normals averaged 68.8 mg. per cent.  However the lecithin averaged 264.3 mg. per cent for the patients with acne and 313 mg. per cent for the normal patients.  Some experiments suggest that extremely high fat or carbohydrate diets enhance sebum production10.

Water Balance in the Skin
            Stokes and Sternberg96 in 1939 stated that increased water retention in the skin leads to infection.  Barber in 1948 also observed that fluid retention in the skin favored bacterial infection.

            Hamilton20 said that sodium chloride and water retained by adrenal cortical substance, androgens, estrogens or luteal substances may make acne worse.  Progesterone favors the retention of sodium and water in the tissues38.  Water retention also accompanies adrenal-cortical hyperfunction30.  Patients with Addison's Disease rarely have acne or eczema according to Ebner30.

            Aldosterone is the salt-retention hormone68.  And an excess of this hormone (aldosterone) may lead to a hypertensive syndrome68.

            Cohen37 in 1941 felt that the position of water balance with regard to acne was obscure but that there was sufficient evidence to suggest that changes in the water metabolism may be of some importance in acne.

            Wirth117 in 1938 had 32 patients on a low salt diet which resulted in improvement in their acne in two years.

            Sodium and chloride are the extra-cellular electrolytes118.

            In absence of adrenal hormones the renal tubules (epithelial cells) appear to be unable to resorb Na (also Ca and K) adequately from the glomerular filtrate in spite of a low Na plasma38.

            Williams68 says that somatotrophin produces a retention of sodium, potassium and chloride but causes diuresis of water.

Milk Drinking as a Secondary Factor in Acne
            As has been mentioned previously in this paper, many dermatologists have observed that milk-drinking is a factor in causing activity of the eruption of acne.  Sutton120 in 1956, in commenting on acneform eruption due to corticotrophin, said that it is interesting that there is another chemical, like androgen and progesterone, which stimulates sebaceous glands to hypertrophy and over activity.  He feels this hormone is present in the mammary secretion of the cow and is in skimmed milk as well as whole milk.  This endocrine substance, then, is effective in stimulating the sebaceous glands of the human being when it is ingested. 

            Examinations of milk as pointed out by Munch121 in 1954 show that estrogens are present in the milk of brown mountain cattle but no androgens were evident.  Estrogen levels are markedly increased in the pregnant cow as compared with the non-pregnant cow and are secreted almost entirely by the placenta as shown by Gorski122 et al in 1957 when they demonstrated that only a small amount of esogenous estrogen is necessary to bring the ovariectomized heifers into estrus.  Short123 had shown previously in 1956 that the bovine placenta secretes no progesterone showing that it comes from corpus luteum.  Relatively high quantities of estrogens in the late placenta coupled with rather constant levels of progestins in the ovaries126 and blood127 of the bovine is in contrast to the increasing levels of both groups of steroids in the human placenta during gestation128, 129. Williams124 in 1962 has found progesterone in cow's milk in measurable amounts after a definite amount of radioactive progesterone was given intravenously.

            Pigato and Guzzonato125 in 1956 did studies on bovine milk from the third to seventh month of the pregnancies.  They studied the milk of five cows with the following results:

Table No. 2
              17-Ketosteroids        20-Ketosteroids               Folliculin            Estrogen

Animal                       in milk                      in milk                        in milk               in milk
           (androgen structure) (progesterone structure)
 
 

   #1     44.7 mg. per liter         4.0 mg. per liter              0.596 mg./liter   1.913 mg./liter

   #2     43.2   "    "     "            5.1   "     "     "                0.610   "      "     2.225   "      "

   #3     41.9   "    "     "            7.3   "     "     "                0.796   "      "     2.770   "      "

   #4     40.4   "    "     "            8.1   "     "     "                0.796   "      "     3.164   "      "

   #5     35.8   "     "    "            9.6   "     "     "                0.906   "      "     3.123   "      "

            Further study of cow's milk shows the comparison with human milk in the following table130.

Table No. 3
 

 Protein 
 Fat 
 Lactose 
 Ash Salt 
  Water

 Human
  1.4%
  3.7%
  7.2%
  0.2%
  87.5%

 Bovine
 3.4% 
 3.9% 
 4.9% 
 0.7% 
 87.1% 
 
 

            It is seen here that the ash content of bovine milk is three and a half times that of human milk which is 7 Gm. per liter; of this 1.37 to 1.94 Gm. is sodium chloride131.  It is also seen from the above table that a liter of cow's milk contains about 40 Gm. of fat.

            Milk also contains 0.6 gamma of cobalt per liter and 540 gammas of iodine131.

            Meyrowitz et al119 in 1938 made a study of milk-drinking habits of 5227 boys and girls 11 through 18 years of age.  This was conducted in upper New York City.  Of this number, 46 per cent were boys and 54 percent were girls.  They found that 88 per cent of the boys and 80 per cent of the girls were milk drinkers.  Those findings are shown in the two following tables.

Quantity Taken Daily
                                                                Male               Female

            4 glasses milk daily     24.5 per cent   20.5 per cent

            5      "        "       "        10.0   "     "        4.3   "     "

            6      "        "       "          7.2   "     "        1.1   "     "
 
 

Median Number of Glasses Milk consumed Daily

Age                 Glasses Daily              Age Distribution of the 5227 Boys and Girls
13 or less           2.9 glasses                                         7.2 per cent

14                      2.7      "                                             15.6  "     "

15                      2.6      "                                             25.4  "     "

16                      2.3      "                                             29.2  "     "

17                      2.2      "                                             17.0  "     "

18                      1.8      "                                               4.6  "     "
 
 
 

PART II
The Tabulated Observations of the Study of 1088 Cases of Acne Vulgaris
Age of Onset

            As is shown in Table No. 4A, the earliest appearance of acne lesions in the female was 4 years of age while in the male as shown in Table No. 4B it was 9 years of age.  No cases were found in the male after 21 years of age while an occasional female appeared with onset of comedones as late in life as 25 to 41 years.  The male overtook the female at the age of 13 years in the number of onset of acne and continued through the 17th, when they matched.  After 17 years of age the females had more initial onsets than the males.  Forty-one and a half per cent of the 337 male patients had their onset of acne at 13 and 14 years of age.  In the female the greatest percentage of onsets was in the years 12 and 13; this represented 30 per cent of the 712 female patients.

Table No. 4B
337 Males:  Age of Onset

Years of Age               7      8      9      10      11      12      13      14      15
No. of Cases               0      0      2        5       12      33      70      71      55

Percentage of Cases                  0.6   1.47    3.56   9.8     20.4   21.1   16.3
 
 

Years of Age               16      17      18      19      20      21      22

No. of Cases               41      26      12        4        4         2      0

Percentage of Cases    12.2   7.7    3.56    1.17   1.17   0.59
 
 

Table No. 4A
712 Females:  Age of Onset

Years of Age               3       4       5       6       7       8       9       10       11       12
No. of Cases               0       1       0       1       1       8      15      32       82       95

Percentage of Cases    0     .14      0     .14   .14    1.12   2.1     4.5     11.5    13.3
 
 

Years of Age               13      14      15      16      17      18      19      20      21

No. of Cases               118     84      84      42      50      29      15      15      12

Percentage of Cases    16.6   11.8   11.8    5.9    7.0     4.07    2.1     2.1     1.68 
 
 

Years of Age               22       23       24       25       26       27       28       29       30       31

No. of Cases                 3         9         0         3         2         2         1         0         0         1

Percentage of Cases    0.42    1.26      0      0.42     .28      .28      .14        0         0      .14
 
 

Years of Age               32      33      34      35      36      37      38      39      40      41      42

No. of Cases                 1        1        2        1        0        0        1        0        0        1        0

Percentage of Cases    .14      .14     .28    .14       0        0      .14       0        0      .14       0
 
 
 

Table No. 4
Comparison of 337 Males and 712 Females as to Their Ages at Onset of Acne

Years of Age               3       4       5       6       7        8        9       10      11
Males Percentage                                                               0.6    1.47   3.56

Females Percentage             .14            .14     .14    1.12    2.1     4.5    11.5
 
 

Years of Age               12       13       14       15       16       17       18       19

Males Percentage        9.8      20.4    21.1    16.3    12.2    7.7     3.56    1.17

Females Percentage     13.3     16.6    11.8    11.8     5.9     7.0     4.07    2.1
 
 

Years of Age               20        21        22       23       24       25       26       27

Males Percentage        1.17    0.59

Females Percentage     2.1      1.68     0.42    1.26     0     0.42     0.28     0.28
 
 

Years of Age               28       29       30        31       32       33       34       35

Males Percentage

Females Percentage     0.14       0        0       0.14    0.14    0.14    0.28    0.14
 
 

Years of Age               36       37       38       39       40       41       42       43

Males Percentage

Females Percentage       0          0     0.14       0         0      0.14       0         0
 
 
 

The Number of Years Acne Present Before First Medical Visit
            Table No. 5A shows the number of years the male patients had their acne before the first visit.  Over ten percent came in during the first year of the eruption; 29 per cent came in after having the condition a year, so that over one-third of the male patients saw the physician by the end of the first year.  None of the males had acne over sixteen years before seeking treatment.  Ninety per cent sought attention within five years.

Table No. 5A
332 Males:  Years That Acne Was Present Before First Visit

Years Acne Present           Within Year        1        2        3        4        5        6        7
No. of Patients                                        34           97      92      31      25      20      13        5

Percentage of All Patients        10.5        29.2    27.7    9.3    7.5      6.0    3.9      1.5
 
 

Years Acne Present                      8           9       10       11       12       13       14       15      16

No. of Patients                                         3           2         7         4         1         0         0         1        1

Percentage of All Patients          0.9       0.6      2.1      1.2       .3         0         0        .3       .3

Table No. 5B shows that 10 percent of the females also sought attention before the end of the first year.  But during the first five years only 75 per cent of the females are accounted for as compared with 90 per cent of the males for this same period.  Also the females continued having their first visits for seven years longer than the males.  The longest time for a female to have her eruption before her initial office visit was 23 years.

Table No 5B

691 Females:  Years That Acne Was Present Before First Visit

Years Acne Present                 Within a year         1         2          3          4          5         6
No. of Patients                                                72            126      116       82       74        48       41

Percentage of All Patients                  10.4       18.25    16.8    11.85   10.7    6.95    5.93
 
 

Years Acne Present                     7          8          9         10         11         12         13         14

No. of Patients                                       19        18       11         23         12          9            3           6

Percentage of All Patients      2.75      2.6       1.6       3.33      1.74       1.3       0.39     0.87
 
 

Years Acne Present                    15       16       17    18     19       20      21      22      23     24

No. of Patients                                       10        3        6       2       3         4         0        2        1       0

Percentage of All Patients        1.45    0.43    .86    .29    .43     .58        0      .29    .145     0

            Table No. 5 shows the percentage comparison of males and females for the years the acne was present on their first visits.  It will be seen that 18 per cent of the females had their acne for a year before receiving medical care as compared with 29 per cent of the males.
 

 Table No. 5

Comparison of Initial Visits of Males and Females After Onset of Acne

Years Before First Visit            0         1         2         3         4         5         6
Males Percentage                    10.5    29.2    27.7     9.3      7.5      6.0      3.9

Females Percentage                 10.4   18.25   16.8   11.85   10.7    6.95    5.93
 
 

Years Before First Visit             8         9         10         11         12         13         14         15

Males Percentage                    0.9     0.6        2.1       1.20        0.3         0           0         0.3

Females Percentage                 2.6     1.6       3.33      1.74       1.3        0.39      0.87     1.45
 
 

Years Before First Visit          16      17      18      19      20      21      22      23      24      25

Males Percentage                    0.3       0        0        0        0        0        0        0        0        0

Females Percentage                 .43      .86     .28     .43     .58       0      .29     .14       0        0

Age of Patient at First Visit
            In addition to the tabulation of the age of onset of the acne and the years the condition was present before the first visit, the patients' ages when they first came to the dermatologist were analyzed.  The mode was determined for both sexes for the age at first visit when the greatest number came to the physician.  The ages 14, 15, 16, 17, and 18 years in the male all had about the same number of first visits.  The number at these ages totaled 67 per cent of all the male patients seen.  The range of ages of first visits extends from 9 to 32 years.  The mode was 15 years, 16.3 per cent of these 362 males were seen at this age.

Table No. 6A

362 Males:  Age at First Visit

Years of Age               6       7       8       9       10       11       12       13       14       15       16
No. of Cases               0      0       0       1         0         1       10       22       43       59       40

Percentage                   0      0       0     .552      0     .276    2.76     6.1    11.86   16.3    11.0
 
 

Years of Age               17       18       19       20       21       22       23       24       25       26

No. of Cases               52       48       23       16       11        7         8          1        6         8

Percentage                   14.4   13.2    6.35    4.42     3.4     1.93    2.51     .276   1.66     2.51
 
 

Years of Age               27     28     29     30     31     32     33     34     35     36     37      38

No. of Cases                  2       1       1       0       0       1       0       0       0       0       0        0

Percentage                   .55    .276   .276    0       0    .276     0       0       0       0       0        0 

            The range for the age at the first visit for the females is from 6 years to 44 years as seen in Table No 6B.  Forty-eight percent of the females were seen from the ages of 14 to 18 years inclusive, while 67 per cent of the males were seen within the same five year period.  Sixteen years of age was the mode for the female?age of greatest number of patients first seen.  It also represents the age of 10.4 percent of the group seen.
 
 
 

Table No. 6B
713 Females:  Age at First Visit

Years of Age               6        7        8        9        10        11        12        13        14        15
No. of Cases               1        0        3        4         8         14        31        48        57        73

Percentage                   .138    0      .42    .56      1.12    1.96      4.35     6.73      8.0      10.2
 
 

Years of Age               16       17       18       19       20       21       22       23       24       25

No. of Cases               74       70       53       43       32       29       28       20       21       19

Percentage                   10.4   9.8    7.43     6.0      4.5      4.7      3.94     2.8      2.94    2.66
 
 

Years of Age               26       27       28       29       30       31       32       33       34       35

No. of Cases               8        17       11        8        11         4        6        5           6        1

Percentage                   1.12   2.38   1.55    1.12     1.55     .56     .84      .7         .84     .14
 
 

Years of Age               36      37      38      39      40      41      42      43      44      45      46

No. of Cases                 2        2        1        0       2        0        1        0        1

Percentage                   .28     .28     .14       0     .28       0      .14       0      .14

            For comparison Table No. 6 shows the percentage of the number of patients of each age group of both sexes which were seen at the first visit.
 
 
 

Table No. 6
Comparison Percentagewise of Age of 362 Males and 713 Females at First Visit

Years of Age                  6         7         8         9         10         11         12         13
Male Percentage                                            .552        0       .276       2.76      6.1

Female Percentage      .138       0       .42      .56       1.12     1.96       4.35     6.73
 
 

Years of Age                 14         15         16         17         18         19         20

Male Percentage          11.86     16.3     11.0      14.4      13.2      6.35       4.42

Female Percentage        8.0       10.2     10.4       9.8       7.43        6.0        4.5 
 
 

Years of Age                 21         22         23         24         25         26         27

Male Percentage          3.4        1.93      2.51      .276     1.66      2.51       .55

Female Percentage      4.7        3.94       2.8       2.94     2.66      1.12      2.38
 
 

Years of Age                 28         29         30         31         32         33         34         35

Male Percentage          .276      .276          0          0        .276         0           0           0

Female Percentage      1.55      1.12       1.55      0.56      .84        .70        .84        .14 
 
 

Years of Age                 36       37       38       39       40       41       42       43       44       45

Male Percentage

Female Percentage      .28       .28      .14        0      .28         0       .14         0      .14         0
 

Menarche in Relation to Onset of Acne

            Of the 328 young women with acne whose history of onset of menarche could be obtained, 24 or 7.3 per cent had not yet shown signs of menstruating by the time of the onset of acne.  Of the whole group all had had menarche by the age of 17 years.  As shown by Table 7, the youngest to menstruate was nine years.  The greatest number had onset of their menses at twelve and thirteen years of age.  Table 7 also shows the number of patients of various ages in this group whose onset of acne was at the different age levels.

Table No. 7
328 Females:  Age at Menarche in Relation to Onset of Acne

Age at Menarche                        0        8        9        10        11        12        13        14       15
Number of Acne Patients

    with Menarche                    24        0        3        12        71        95        94        19         7
 
 

Number with Onset of Acne
   in Above Age Group                       3       10        18        53        60        63        39       34
 
 

Age at Menarche                     16       17       18       19       20       21       22        23        24

Number of Acne Patients

   with Menarche                     2         1          0        0         0         0         0          0          0
 
 

Number with Onset of Acne

   in Above Age Group           15       11         5        4         7         2         1          1          0
 
 
 

Home Treatment Before First Visit
            Many of the patients had used topical home medication before seeking medical advice.  Of 362 males, 252 or 69.6 per cent were in this category.  And of 700 females, where their histories could be obtained, 368 or 54.5 per cent were using home or advertised medication before coming to the physician.  Many of the young people who had used the advertised cosmetics did not see a physician until after extensive permanent damage in the way of scarring had been done.  Obviously these figures are based on cases ultimately coming to the doctor for help.  It is impossible to estimate how many young people are lured into the false security of home medication, and never seek a doctor's help.  The tragedy is that untold numbers of them suffer prolonged or even permanent psychic effect of such unnecessarily delayed improvement in their developing years.

Location of Lesion, Severity and Scarring Before Treatment
            The location of the lesions, their severity and the degrees of scarring were studied on the initial visits and compared in the separate groups of males and females.  The lesions occurred almost exclusively on the face, back and chest.  They were in that order of activity, face, back and chest.  Only an occasional patient with an eruption over the deltoid regions or buttocks was observed.  Tables 8, 9 and 10 show the distribution of the active lesions and the scars in 347 males; the severity is also graded in four categories, mild, moderate, severe and quite severe for each location for both the activity of the eruption and its residual scars.
 
 

Table 8
Location of Lesions, Scarring and Severity in 347 Males

Before Treatment

Severity of Acne of Face
Degree             No. Cases        Percentage       Total Cases      Total Percentage
mild                      42                 12.7%

moderate            148                 43.4

severe                 133                 39.0

quite severe         18                    5.27                 341                          98%

none                      6

Severity of Scarring on Face
Degree             No. Cases        Percentage       Total Cases      Total Percentage
mild                      21                    14.0

moderate              76                    50.8

severe                   45                    30.0

quite severe            8                      5.3                 150                         43.3%

Table 9
Severity of Acne on Back

Degree             No. Cases        Percentage       Total Cases      Total Percentage
mild                      86                   38%

moderate              95                   42 

severe                   39                   17.2

quite severe            7                    3.09                  227                        65.5%

none                    120

Severity of Scarring on Back
Degree             No. Cases        Percentage       Total Cases      Total Percentage
mild                        6                    8.85%

moderate               33                  49.3

severe                   24                   35.8

quite severe            4                     5.9                   67                          19.5%

Table 10
Severity of Acne on Chest

Degree             No. Cases        Percentage       Total Cases      Total Percentage
mild                      83                   52.0%

moderate              54                   33.8

severe                  19                   11.8

quite severe            4                     2.5                     160                         46.0%

none                   189
 
 

Severity of Scarring on Back
Degree             No. Cases        Percentage       Total Cases      Total Percentage
mild                        9                   23.1%

moderate              15                    38.4

severe                   12                    30.8

quite severe           3                      7.7                    39                         11.1%

            Tables 11, 12 and 13 show a similar distribution of the categories for the 696 females.  It can be seen that the total facial eruptions on the initial examinations were approximately the same for both sexes, 98 per cent and 99 per cent for males and females respectively.  Sixty-five and half per cent of the males had lesions over the back as compared with 49.2 per cent for the females.  The chest lesions were 46 per cent in the male as compared with 30.8 per cent in the female.

Table No. 11
Location of Lesions, Scarring and Severity in 696 Females

Before Treatment

Severity of Acne of Face

Degree             No. Cases        Percentage       Total Cases      Total Percentage

mild                      101                 14.6%

moderate              367                 53.0

severe                   218                 31.5

quite severe             6                    0.86                  692                       99+%

none                        4
 
 

Severity of Scarring on Face

Degree             No. Cases        Percentage       Total Cases      Total Percentage
mild                      61                   25.8%

moderate            145                   61.4

severe                   29                   12.3

quite severe            1                     0.4                  236                         33.8%

Table No. 12
Severity of Acne on Back

Degree             No. Cases        Percentage       Total Cases      Total Percentage
mild                     135                   30.4%

moderate             167                   48.7

severe                    41                   11.9

quite severe             0                     0                      343                       49.2%
 
 

Severity of Scarring on Back
Degree             No. Cases        Percentage       Total Cases      Total Percentage
mild                       8                    28.7%

moderate              15                   53.5

severe                     5                   17.8

quite severe            0                      0                       28                        4.0%
 
 

Table No. 13

Severity of Acne on Chest

Degree             No. Cases        Percentage       Total Cases      Total Percentage
mild                     125                  58.5%

moderate               77                  36.0

severe                     8                    3.85

quite severe            4                    1.87                   214                       30.8%

none                     487

Severity of Scarring on Chest
Degree             No. Cases        Percentage       Total Cases      Total Percentage
mild                        1                     16.7%

moderate                4                     66.6

severe                     0                       0

quite severe            1                     16.7                  6                           .863%

            Of the scarring which had already developed on the face in the male before the first visit, 43.3 per cent was in 348 males as compared with 33.8 per cent in 696 females.  The scars on the back were 19.5 per cent in the male as compared with 4 per cent in the female.  And finally the males had 11.1 per cent chest scars as compared with less than one per cent in the female.

            It is shown here by comparison in the tabulation in Tables 14, 15 and 16 that the activity is more severe in all categories for the male and that likewise the scarring is more extensive in the male.  Acne eruptions on the back were found to be 25 per cent more prevalent in the male than in the female and 50 per cent more common on the chest.  From these same tables it is observed that scarring is also much more prevalent in the male than his opposite sex in all categories.  The male had a total of 30 per cent more facial scars.  Also he has five times more residual scarring over his shoulders and back.  More than ten times the severity of scarring was present over his chest than that of the female.

            These same tabulations 14, 15 and 16 show the severity of the eruptions and scarring present on the initial visits.  The quite severe acne facial lesions were 5.27 per cent in the male as compared to 0.9 per cent in the female.  The severe and quite severe facial scarring were 35.3 per cent in the male as compared with 12.7 per cent in the female.

            The incidence of acne activity on the back was 20.3 per cent in the male as compared with 11.9 per cent in the female; in this observation the males had 3 per cent quite severe lesions on the back while the females had none.

            The chest activity showed the males to have 14.3 per cent severe and quite severe activity as compared with the females' 5.9 per cent.
 
 

Table No. 14
Percentage Comparison of 347 Males and 696 Females

Before Treatment

            Acne?Face                                                    Scarring?Face
Degree             Male    Female                         Degree             Male    Female

mild                 12.7     14.6                            mild                 14.0     23.8

moderate         43.4     53.0                            moderate         50.8     61.4

severe              39.0     31.5                            severe              30.0     12.3

quite severe     5.37      0.86                           quite severe       5.3        0.4

total                 98.0%  99.0%                         total                 43.3%    33.8%

Table No. 15
            Acne?Back                                                   Scarring?Back

Degree             Male    Female                         Degree             Male    Female

mild                 38.0       39.4                           mild                   8.85     28.7

moderate         42.0       48.7                           moderate         40.3      53.5

severe              17.2       11.9                           severe              35.8      17.8

quite severe       3.1         0.0                           quite severe        5.9        0.0

total                 65.5%    49.2%                        total                 19.5%     4.0%

Table No. 16

            Acne?Chest                                                  Scarring?Chest
Degree             Male    Female                         Degree             Male    Female

mild                 52.0       58.5                           mild                 23.1       16.7

moderate         33.8       36.0                           moderate         38.4       66.6

severe              11.8        3.85                          severe              30.8          0

quite severe       2.5        1.87                          quite severe       7.7       16.7

total                 46.0%    30.8%                        total                 11.1%       .863%

            The severity of the scarring percentagewise shown in the above tables in the severe and quite severe categories was also greater in the male than the female; for the face 35.3 per cent compared to 12.7 per cent; back, 41.7 per cent to 17.8 per cent; and chest, 38.5 per cent to 16.7 per cent.

            The severe activity of the lesions is shown to be greater in the male for all areas as are the resulting scars from the secondary bacterial infection.

Relation of Atopy to Acne Vulgaris
            Acne in relation to atopy was studied in 362 males and 709 females with acne in various stages of activity.  Atopy was present in 122 of the males or 29.7 per cent and in 199 of the females or 23.8 per cent.  These figures are about the same for the general population.  This is in comparison with 13 per cent as reported by Stokes and King36 in their patients with acne.

            In comparing the percentage as shown in Tables 17 and 18 it is obvious that atopic dermatitis is more prevalent (14.15 per cent) in females than in males (5.8 percent).  Hay fever is about the same in both:  58.8 per cent in males and 55 per cent in females.  However the males have more asthmatics, 18.4 per cent as compared with 11.28 per cent in the females.  The other figures in the table are comparable.

Table No. 17
Male Acne Patients with Atopy

122 Atopics Found in 362 Male Acne Patients (29.7%)

Shock Tissue               No. of Cases               Percentage of Total Atopics with Acne
atopic dermatitis                  8                                                   5.88%

hay fever                             80                                                58.8

asthma                                 25                                                18.4

hives                                    21                                                15.47

migraine                               2                                                    1.475

Table No. 18
Female Acne Patients with Atopy

199 Atopics in 709 Acne Female Patients

Shock Tissue               No. of Cases               Percentage of Total Atopics with Acne

atopic dermatitis                52                                                 14.15%

hay fever                           180                                                55.0

asthma                                37                                                11.28

hives                                    56                                                17.0

migraine                               4                                                    1.58
 

What Has Made Acne Worse?
            "What has made your acne worse?"  was a questions put to all the patients.  Many were not able to observe any particular condition that caused onset or exacerbation of their eruptions.  However the answers of those who had noticed changes were tabulated.  What part of these observations were secondary infection which had set in after the initial comedo had developed and its local foreign body reaction of an inflamed papule had formed was not clearly discernible.  The quantities of the exciting factors were not obtained in the histories in all of the cases, so most of the categories given will have to be considered as variables.

            Of 362 cases of acne in the male where information was obtained from 74 patients, Table No. 19 gives the items accused as exciting factors and the number of patients naming the factors.  It can be seen that several of these could be listed together under one category such as athletics and football, etc.
 
 

Table No. 19
Item                 Times Accused                                    Item                 Times Accused
chocolate                     15                                            tension                         3

nervousness                 7                                             athletics                       3

sweets                         5                                             beer or alcohol             3

"college"                     4                                             shaving                        3

milk                             3                                             certain foods               2

fried foods                  3                                              picking                                    2

football                        3

            The remainder scored one each:  rich food, no sleep, tired, winter, chlorine in pool water, emotions, not washing, sweating, S.S.S. tonic (supposedly contains potassium iodide), hair oil, some medicines, cakes, oranges, dry scalp, nuts, when worried, greasy foods, fruit.

            In quizzing 709 females, 370 (52%) offered causes as to what made their acne worse.  These are listed in Tables 21, 22 and 23.  First on the list was just "menses" in 110 cases, "before menses" in 59 and "after menses" in 10; this is a total of 179 out of 370 cases or 48.5 per cent of women blame this one factor alone.  It is my belief that if all adolescent women could be tabulated it would be found that a higher percentage than 48.5 would have some sort of papular eruption about their menstrual time.  Table 21 shows the distribution of other more common causes of flare-ups of lesions of acne in women.

Table 21
At Menses                   179                                          Pan Cake Make-up      6
Chocolate                    52                                           "Some Foods"             5

"Nerves"                     19                                           Tired                            4

Sweets                         12                                           "No Sleep"                  4

Emotions                     12                                           Cakes                          4

Tension                        10                                           Diet                             3

After Delivery                9                                           "Work"                        3

            Table 22 shows the causes of exacerbation in at least two cases each of the 370 patients.
 
 

Table No. 22
"When in Hawaii"                   After Marriage                        Nuts
Fatty Foods                             Heat                                        Peanut Butter

Hormones                                Scalp Hair on Cheeks              Oranges

Noxzema                                 Cheese                                     Stopping Enovid

Excitement                              Milk                                         Dandruff

            And Table 23 shows the causes in at least one female for a flare-up of her acne.

Table 23
Late Menses                            Fried Foods                             Husband in Service
Worried                                   School Pressure                       Hysterectomy

Winter                                     Cod Liver Oil                          After Male Hormones

Butter                                      Anemia                                    After Appendectomy

Ice Cream                                Pies                                          At Ovulation Time

Sinus Headache                      Vitamin B6                             "Moved to California"

What Has Improved the Acne?
            A similar question was asked on the initial visit as to what made the eruption of acne better or improved it.  Of the 362 male patients with acne, observations of remissions were made by 62 patients.  Table 24 shows this distribution into several categories.  It is of interest to learn that 77.5 per cent of the males found improvement in the summer, in the sun, or at the beach?obviously relaxation and ultraviolet light.

Table No. 24

Remissions of Acne Lesions in 62 Male Patients

                                    Summer, sun or at beach                     48
                                    Treatment                                              3

                                    Antibiotics                                            2

                                    Swimming                                             2

            Table 25 shows the categories in which at least one patient noticed improvement.

Table No. 25
Improvement in One Each of 62 Male Patients

                                                            Low Fat Diet

                                                            No School

                                                            Using Antiseptic Soap

                                                            Niacin

                                                            Washing

                                                            Ultraviolet Exposure

                                                            "Pills"

            Seven hundred nine (709) women with acne were queried as to what improved or cleared their acne.  Of these 709, 135 observed periodic remissions.  They, like the men, showed improvement in 86 cases (61.5 per cent) when in the sun, during the summer or at the beach.  Eruptions improved or cleared in 17 women during pregnancy.  Antibiotics improved 9 of the 86; x-rays helped 4.  In 4, their acne was improved after menses and in one during menses.  Washing and "diet" help three each.  This is shown in Table 26.

 Table No. 26

Periodic Remissions Other Than After Menstrual Period in 135 Females with Acne

                                    Summer, Sun or Beach           86 cases
                                    During Pregnancy                   17     "

                                    Antibiotic Therapy                  9      "

                                    X-Ray Treatment                    4      "

                                    Washing                                  3      "

                                    Diet                                         3      "

            The remaining list had one patient each with improvements.

Table No. 27
No Chocolate                          Low Fat Diet                          Ultra Violet Irradiation
When in Mountains                 When Rested                          When in Phoenix, Arizona

When on Vacation                  Home From College                Carbon Dioxide Treatment

After Marriage                        After a Fever                           Ten Hours Sleep Every Night

Treatment

The Milk-Drinking Habit As An Influence on Acne
            Although a few of the patients themselves observed that milk-drinking seemed to make their acne eruption worse, it was bought out in taking the histories that many of the severest eruptions of acne, particularly in the male, were in those who drank from one to four quarts of milk daily.  On the advice of the physician that their milk consumption be reduced to one glassful a day, many of these severe cases promptly improved.  With this observation in mind, a record was made of all of the patients' milk consumption.
 
 

            It is of interest that 4 of the males or 1.2 per cent of the males and 50 females or 6.5 per cent of the females studied were non-drinkers of milk.  In a study in upper New York City119 of "Milk Drinking Habits of Young People" in which 5227 interviews were made of males and females from the age of 11 years through 18 years, 415 said they disliked milk and an additional 100 did not drink milk but not because they did not like it.  This shows a percentage of 10 per cent of young people as a whole who do not consume milk as compared in patients with acne in which 44 in 958 or 4.5 per cent did not drink milk:  So it is seen that two and a half times as many people with acne drink milk as normal young people in the general population.

            The number of glasses of milk consumed in the New York study119 on the day before the questionnaire was recorded is given in Table 32A.  It is seen that the students who drank the most milk?4, 5 and 6 glasses a day?were boys. 

Table No. 32A
                        Number of Glasses Milk         % Boys            % Girls
                                        0                                4.9                   7.1

                                        1                                8.2                 10.0

                                        2                              16.2                22.7

                                        3                              27.5                32.0

                                        4                              24.5                20.5

                                        5                              10.0                   4.3

                                        6                                 7.2                   4.1

                                    No Answer                     1.5                   1.4

            The average amount consumed in 2.9 glasses a day and the median amount was 2.5 glasses a day.  The study also showed that as young people grew older they drank less milk.  Table 32 gives the median numbers of glasses of milk consumed per day per age.

Table No. 32
                        13 years of age or less             2.9 Glasses per day

                        14     "          "          "              2.7       "       "     "

                        15     "          "          "              2.6       "       "     "

                        16     "          "          "              2.3       "       "     "

                        17     "          "          "              2.2       "       "     "

                        18+   "          "          "              1.8       "       "     "

            In the New York study it was found that 88.8 per cent of the males and 80.0 per cent of the females of the normal population were confirmed milk drinkers.  In our own study 98.8 per cent of the males and 93.5 per cent of the females were milk addicts, an increase of 10 per cent in the boys and 13.5 per cent in the girls.

            Table No. 28 and Table No. 29 show the number of glasses of milk the males and females separately drank per day on the initial visit in the author's study.
 
 

Table No. 28
Number of Glasses (250 ml.) of Cow's Milk Consumed Daily by 341 Males
Number of Glasses of Milk     0         1         2         3           4        5         6         7

Number of Cases                    4         10        35        31        122      24        36        10

Percentage of Total Cases       1.17     2.92     12.0     9.0       35.6     7.0       10.8     2.9
 
 

Number of Glasses of Milk     8         9         10        11        12        13        14        15 

Number of Cases                    54        0         4         0         5

Percentage of Total Cases       15.7     0         1.17     0         1.46
 
 

Number of Glasses of Milk     16        17        18        19        20

Number of Cases                    1                                             1

Percentage of Total Cases       .29                                           .29

Table No. 29
Number of Glasses (250 ml.) of Cow's Milk Consumed Daily by 617 Females

Number of Glasses of Milk     0         1           2          3          4        5         6         7

Number of Cases                    40        58        122      111      190      15        18        2

Percentage of Total Cases       6.5       9.4       19.6     18.0     30.8     2.44     2.92     .32
 
 

Number of Glasses of Milk     8         9         10

Number of Cases                    9         0         1

Percentage of Total Cases       1.46     0         .16

            Table No. 30 is a comparison of the percentages of milk consumed in the males and females.  More girls drank milk in the 1, 2 or 3 glass category than boys, but from then on the boys took the lead up to five quarts a day.  Seventy-five or 22 per cent of the males drank more than six glasses of milk a day while only 12 females or 1.94 per cent drank more than six glasses of milk a day.

Table No. 30
Comparison in Males and Females of the Percentages of Milk Consumed

Glasses                                      0          1           2         3          4          5          6          7
Percentage in Males                1.17     2.92     12.0     9.0      36.6     7.0      10.8     2.9

Percentage in Females             6.5      9.4      19.6     18.0     30.8     2.44    2.92    .32
 
 

Glasses                                      8          9        10       11       12       13       14       15

Percentage in Males                15.7       0        1.17        0       1.46       0          0          0

Percentage in Females             1.46      0        .162       0          0         0          0          0
 
 

Glasses                                    16       17         18        19        20

Percentage in Males                .29         0          0          0         .29

Percentage in Females               0           0          0          0          0

            Table 31 shows that for the years of age the male drinks more glassfuls of milk a day than the female and unlike the New York study, milk-drinking in the male patient with acne does not diminish at 18 as the study of New York City found in the normal individual.  Since we did not see any male acne patients whose acne appeared initially after the age of 21 years, it is not possible to say if these individuals continue to drink milk in later years as was found in the female who drank 3 glasses of milk a day at the age of 28 years when first seen.

Table No. 31

A Comparison of the Daily Intake of Cow's Milk in Number of Glasses (250 ml.)

Of Males and Females
 

Age at Onset of Acne                                     4          5          6          7          8          9
Ave. Daily Glasses of Milk Per Male             0          0          0          0          0          3.5

Ave. Daily Glasses of Milk Per Female          3          0          0          3          3          3.08

New York Study Median Number                 0          0          0          0          0            0
 
 

Age at Onset of Acne                                     10        11        12        13        14        15

Ave. Daily Glasses of Milk Per Male             3.2       3.6       4.2       5.5       4.8       4.95

Ave. Daily Glasses of Milk Per Female          3.17     3.4       3.3       3.26     3.7       3.3

New York Study Median Number                   0        0         3.0       2.9       2.7       2.6
 
 

Age at Onset of Acne                                     16        17        18        19        20        21

Ave. Daily Glasses of Milk Per Male             4.8       5.6       4.9       5.3       5.3       5

Ave. Daily Glasses of Milk Per Female          3.0       2.94     2.7       2.58     3.5       2.3

New York Study Median Number                 2.3       2.2       1.8
 
 

Age At Onset of Acne                                                22        23        24        25        26      27     28 

Ave. Daily Glasses of Milk Per Male 

Ave. Daily Glasses of Milk Per Female          1.3       2.84                             4.5             3.0

            It is seen above in Table 31 that the median number of glasses of milk for the normal New York youth is much smaller than the average number of glasses that were drunk by either males or females with acne.

Determinations of 17-Ketosteroids in Females with Cyclic Flare-up of Acne
            Because so many young women have exacerbations of their acne lesions before or during their catamenia, 17-ketosteroid urinary determinations were made on a small group.  Since the test required a whole 24-hour specimen and since none of these women was hospitalized, they were supplied with a suitable container containing preservative and the specimen was collected from 7 a.m. on the Sunday before the following menses until 7 a.m. Monday, discarding the 7 a.m. Sunday specimen but including the 7 a.m. Monday specimen.  This same procedure was used the first Sunday after the period for a second determination of 17-ketosteroids.  In this way an analysis was made of the steroids before and after menses.

            In 21 such menstrual cycles tested in different females, 16 showed a higher level of 17-ketosteroid before the menses than after the period while 6 showed the reverse.  An average increase of 1.3 mg. per 24 hours occurred where the determination was higher before menses than afterwards.  In the reverse where the increase was higher after the menses the difference between the before-and after-menses-test was 0.7 mg. per 24 hours.  The present age, the age of onset of acne or the menarche could not be found to be factors in the variations.
 
 
 

Table No. 33
Patient             Age     17-Ketosteroid                           Age                  Age             Severity
                                    before      after                        at onset              at onset          of acne
                                    menses   menses          of acne                        of menarche
                                         MG/24 hrs.               years                   years

NH                  20        9.2           9.0                 18                      15                   +
SR                   13        3.5           2.9                  12                     13                   +

KB                  25        4.8           3.5                  15                     12                   ++

KH                  19        10.8          6.2                  14                     13                   +++

CG                  19        9.2           7.8                  14                     13                   ++

DD                  14        4.3           3.3                  12                      9                    ++

SB                   20        7.0           6.3                  13                    12                    ++++

DM                  17        3.9           3.2                  14                                            ++

NG                  34        8.8           7.7                  14                    13                    ++

LN                   13        8.7           7.0                  12                    12                    +

FM                  18        4.6           3.2                  17                    14                    +

PH                   13        4.8           3.4                  12                    11                    +

CA                  21        6.7           4.7                  16                    12                    ++

LB                   24        8.0           7.0                  23                    12                    +

DH                  28        11.5          9.7                  18                    13                    ++

JM                   30        11.1         11.5                 16                    14                    +

JS                    10        7.3           8.0                  10                    10                    +

CV                  19        1.9           2.5                  18                    11                    ++

JG                    15        8.2           8.6                  15                                            +

NM                  14        5.1           6.9                  12                    12                    +
SH                   17        8.6           9.0                  11                    12                    +++
 
 

Part III
Discussion

            A comprehensive review of the literature and an intensive study of my own cases have led me to some definite conclusions about the mechanism of the exacerbation of acne lesions beyond the condition of secondary infection.  These conclusions and other factors for discussion are given in Table C.
 
 

Table C
                                    Pituitary-Adrenal-Gonadal Complex
                                    Anatomical Predisposition

                                    Androgens

                                    Estrogen

                                    Acne as a Normal Physiological Adjustment in the Adolescent

                                    Acne Surgery

                                    Ultraviolet Irradiation

                                    Stress and Emotion

                                    Seborrhea

                                    Food Allergy

                                    Sodium Chloride

                                    Thyroid Extract and Thyroxin

                                    17-Ketosteroids

                                    The Milk Drinking Habit

Pituitary-Adrenal-Gonadal Complex
            The primary cause of the activity of the lesion in acne is in all probability to be found in the pituitary-adrenal-gonadal complex which may not always be in tune during the growing period of young people.  Some of these glands may also be out of balance and may affect the sebaceous glands.

Anatomical Variation
            An anatomical hereditary factor evidenced by the presence of enlarged or overly active sebaceous glands seems present in many families.  This same anatomical inheritance may also include the pituitary-adrenal-gonadal group whose secretions directly or indirectly have such a profound influence on the oil glands of the skin.

Androgens
            As has been reviewed in the first part of this paper and proved rather conclusively, various androgens are the direct stimulus for the pilosebaceous apparatus.  This stimulus has been proved by the giving of testosterone to eunuchoids and to females for a few months with the subsequent appearance of lesions of acne vulgaris.  The adrenal secretions influence the growth of pubic and axillary hair, the coarsening of lanugo hairs and the development of apocrine glands.

            As also mentioned previously in this paper, the urinary androgens as determined by 17-ketosteroids are derived solely in the female from the adrenals.  But since progesterone of corpus luteum belongs to a 20-carbon atomic arrangement of the steroid nucleus, its presence is not determined by this analysis.  In the male two-thirds of the urinary androgens as 17-ketosteroids is derived from the adrenals and the remaining one-third is derived from the interstitial testicular cellular tissue.

            In eunuchoids or castrated prepubertal males and oophorectomized prepubertal females who do not develop acne lesions, adrenal glands are still intact.  So it seems difficult to believe that the adrenal secretions are the cause by themselves of the appearance of acne.  Since progesterone of the female has been shown by several investigators to have androgenic effect, it must be testosterone in the male and progesterone in the female that are the additional stimuli to the pubertal skin.  This still does not account for the acne eruptions in the premenarchal girl unless progesterone is formed by the theca cells of the ovary without ovulation and menstrual cycle.

Estrogens
            Just as testosterone has been shown to produce lesions of acne, so by mass action estrogen has been given to suppress the androgen activity and shrink the sebaceous glands.  These studies have been confirmed through work in both animals and in human beings.  This treatment is not without occasional side effects, some of which are undesirable, particularly is this so in the male who may develop gynecomastia of testicular atrophy.  Females under this treatment may have spotting between menses or have a period earlier than the calculated time.

Is Acne Vulgaris Normal?
            Is acne vulgaris a normal physiological adjustment in the adolescent?  If acne vulgaris is primarily a by-product in the normal development of the endocrine system in an adolescent, any tampering with that system may interfere with his mental or physical development.  We are then left with the problem of trying to correct the exacerbations without stopping or changing an almost normal physiological adjustment that is taking place within the adolescent which affects the sebaceous glands.  The main part of this discussion will have to do with the consideration of the exacerbations.

Nutrition
            Since the comedo?the prime lesion of acne?is a cast of sebum and keratinized glandular material which clogs the pore of the gland, the principal factor in the control of acne would be to suppress the activity of the sebaceous gland.  And since sebum is composed of fats and waxes not found elsewhere in the body, it must be produced at the site within the gland.  Because the matured cells of these holocrine sebaceous glands rupture and liberate this sebum, it must be formed within the sebaceous basal cell structure.  Separate investigators have arrived at the same answer as to this mechanism of the formation of sebum:  it is formed by the mitochondria of the gland cell by synthesis from carbohydrates and protoplasm of the basal cells of the sebaceous gland and not extracted as a fat or a wax from the blood stream.  As has been pointed out previously in this paper, the overfeeding of carbohydrates has produced an increase in liquid sebum in both normal individuals and in patients with acne.  However, the acne patient secreted the greater amount of sebum.

            Increased ingestion of fats would also cause an increase of liquid sebum on the skin surface as was demonstrated by Serrati.  Fat that is mobilized or stored in the system goes through a glycogen phase; it is apparently in this glycogen phase that the holocrine cells of the sebaceous glands take the carbon particles to build the waxes needed for sebum.  Thus fat in the diet is another factor that acts to stimulate the synthesis of sebum secretion.

            Neutral fat that is ingested is taken up by adipose tissue while the fats forming sebum are synthesized in situ.

            Cow's milk contains about 40 Gm. of butter fat per liter, consequently several quarts of milk a day adds significantly to the fat of the diet.

Stress and Emotions
            The literature has shown how the eruption of acne is made worse by androgenic hormones.  It has also been reported that the eruption of acne is worse during or after emotional stress or strain.

Diag. #1          The release and regulation of stimulating hormones for most of our ductless glands are under the control of the pituitary.  This is brought about by chemical action on the hypophysis or by impulses from the cerebral cortex indirectly through the hypothalamus.  The pituitary hormone acting directly on the adrenals and on the gonads releases androgenic hormones that stimulate the sebaceous glands.

            Emotions originating in the cerebral cortex whether by psychic stimulation or by chemical substances excite the hypothalamus directly; this part of the brain then through the pituitary portal venous system activates the pituitary gland, not by nervous fiber connections, but by hormones.

            Young people of both sexes of high school or college age readily recognize that their eruptions of acne and oiliness of the skin will be made worse by an intense study session or by the preparation for a severe examination.  Any stimulating medications or toxins would have the same effect; this, then, would mean that anything containing an appreciable amount of caffeine, a cerebral xanthine stimulant, (coffee, "cokes," chocolate and tea) should be eliminated.  Sufficient alcohol could have a similar effect.  Amphetamines would also give the same cerebral exciting result.  Alcohol might be initially stimulating in the same way followed by a toxic effect on the brain.  Because alcohol is a carbohydrate it would have an over-feeding effect directly on the sebaceous glands.  It should also be remembered that young people are more susceptible to stimulants than their elders.

            And finally any excitement (sexual or otherwise), emotion or tension have their effects on the cerebral centers.  Many of these reactors cannot be controlled very well by the patient.  But they should be recognized as a cause.  The condition of the skin will then subside when the factors of stress or conflict are resolved.

            A typical example:  one of the high school patients under observation who had been in conflict with her parents and who had had acne for years cleared promptly after psychiatric therapy for only several weeks.

Seborrhea
            What has already been said about nutrition, stress and emotion in this discussion as to the exciting factors of acne vulgaris can be applied to cases of seborrhea.  Irregularities in the estrogen blood levels in women may also be found to be a cause.

Food Allergy
            Food allergies were not found to be an influencing factor in any flare-ups of the acne in this study.  The exacerbations of acne lesions from foods in many of the patients were observed to be the result of over eating, for by reducing the concentrated and refined food intake in their diets, the eruption became less severe.  No patient made the observation himself that his acne was influenced by an allergy to any food.

Sodium Chloride
            By osmotic pressure sodium chloride will hold water in the extracellular spaces of the tissues; this has been observed to lead to infection when in the skin.  Patients with acne who were kept on low salt diets have shown improvement in their eruption.  Since aldosterone is the salt retention adrenal hormone, it is conceivable that psychic or chemical cerebral stimuli would, through the hypothalamus, affect the pituitary to cause this adrenal secretion.  Some patients achieve a high salt intake by salting their food heavily at table.  Others get large amounts of salt in their food and are not aware of it.  Three readily available sources are cow's milk, salt butter and breads.  Preserved meats are usually heavily salted too.  Every liter of cow's milk has from 1.5 Gm. to 2.0 Gm. of sodium chloride.  Gonadal hormones which are present in milk also cause retention of salt and water in the tissues.

            Ebner30 in 1956 stated that acne may be alleviated by the restriction of the intake of salt (sodium chloride), salt-containing meats and other foods that contain a high content of sodium chloride.

Thyroid Extract and Thyroxine
            Thyroxine and androgens act synergistically thereby increasing the effect of androgens.132  Thyroxine also increases the secretion of pituitary growth hormone68 which in turn influences the hypertrophy of sebaceous glands.

            Iodide in the form of potassium iodide has been observed to cause acne eruptions to be more severe.  It may be the mechanism of forming more thyroxine from iodine that aids the androgens in stimulating the sebaceous glands.

17-Ketosteroids

            In the light of the review of the literature the significance of the drop of urinary 17-ketosteroids immediately after menses is not clearly understood.  If the adrenal-androgen levels are constant in the normal female, as previous investigators have reported, this change should not have occurred.  Our figures seem to be within the limits of normal laboratory error.  More study is justified from these observations because the elevated part of the titres occurred at the times when the acne was more severe.

The Milk Drinking Habit
            This study of acne patients and the comparative review of a normal group of milk drinkers show that patients with acne consume more milk than the normal population.  It is seen also that the patients with acne, both males and females, continue drinking milk longer and in a larger quantity daily than other individuals.  Boys drink more milk than girls and they also have more severe acne lesions with more scarring.

            It was interesting to find that 10 per cent of normal population and only 4.5 per cent of the patients with acne were non-drinkers of milk.

            All of these observations as pointed out earlier and developed above show that the average adolescent with acne can be associated with the group of youngsters who consume more milk than the normal population of his own age.

            In addition to the high intake of fat and sodium chloride that is ingested daily when large amounts of cow's milk are consumed, many gonadal and sebaceous gland stimulating hormones as previously shown are also taken in the milk.  Any one of these substances (fat, salt or hormones) would make it undesirable to drink the massive quantities of milk that are consumed every day by the patients with acne.

Recommendations for Treatment
            With the completion of this study one comes to some definite conclusions as to treatment.  This therapy must be

 tailored to the age and the condition of the patient.

            Although acne surgery has not been a part of this investigation, the first and most natural treatment to consider in practically every case is the removal of the unsightly pustules and caseous plugs in the skin; this is part of a recognized surgical procedure in any cutaneous infection or treatment of a foreign body in the skin.  The comedo plug must be considered a foreign body stopping the elimination of sebum through the sebaceous gland pore.  The comedo and the pus must also be removed to prevent the subsequent scarring on healing that develops from the bacterial toxins present in the pus; these toxins destroy the surrounding tissue cells.

            Since the cosmetic appearance of the patient and any possible resulting scarring from the condition are major effects of this disease, the removal of any pustules and accompanying comedones surgically results in a great deal of improvement.  Shampooing should be frequent enough to keep the hair and scalp free of oiliness.  The hair should be kept off the forehead and face at all times.  The facial eruption will not improve as long as scalp or hair remain oily.

            The concern of the patient that removing the comedo or its infected pustular material will leave a scar is a fallacy; the longer the pustule remains in a particular site, the more destruction with resulting scarring will be present on the ultimate healing.

            This acne surgery should be done with the tip of the smallest eye knife and followed by a bowl-shaped comedone expressor that resembles a small doughnut.  It should be done in the physician's office and not by the patient because he, the patient, may not use a sterile instrument or follow a sterile technique.  Surgical removal or squeezing attempted by the patient often leads to further infection.  This results in making the condition and the scarring worse.  Many physicians have a tendency to neglect this surgical part of the treatment because it is time consuming.

            The localized irritation that often accompanies surgical expression of sebaceous gland when any of the sebum extravasates into the surrounding tissue is due mostly to the presence of proprionic acid in the secretion which has been given off there by the presence of a proprionic-acid-producing bacillus, Cornybacterium acnes45.

Infection
            Infection was not considered as such in the etiology of acne vulgaris; however, if infection is present, antibiotics should be given at any age.  The safest one at the moment is erythromycin with the dosage regulated to the condition of the infection.  Topical sulfur astringents and germicide facial lotions should be used.  Oily skin on the face should be washed several times a day to keep the skin dry.  Shampooing should be frequent enough to keep the scalp and hair from being oily.
 
 

Estrogens
            Young women who have reached their full physical maturity may be given estrogen for their acne.  This is usually given daily from the day of ovulation for about two weeks or until the following catamenia (whichever is first).  This therapy is repeated every month.  Premarin 0.625 mg. daily has been found satisfactory.

            Treatment with estrogens will reduce the seborrhea in females.

            Progestins when used as therapy for various conditions if given in sufficient amounts, will increase the comedo stimulation because of their androgenic hormonal effects.  Therefore these side effects may be expected where this medication has to be used in acne-susceptible women.

Nutrition
            Since the sebaceous glands synthesize their own sebum and since overfeeding of carbohydrates and of fats has been shown to increase sebum production, these foods in excess should be reduced in quantity in the diet and given in small and frequent amounts so that the blood stream does not get an over-supply in peaks.  Therefore, smaller meals and frequent feedings are recommended with the reduction in intake of sugar, heavy starchy meals, alcohol and fatty foods.  It is important to remember that cow's milk contains 40 Gm. of fat per liter.

Stress and Emotion
            Although in the treatment of acne it would not be common practice to give pituitary gland roentgen irradiation to reduce the gland's activity, the secretion of its hormonal products may be controlled indirectly at times by eliminating the cerebral
 
 
 

                                                                                                                        81

stimulating factors.  It was mentioned earlier that androgens "lay the fire for acne and the emotions or other secondary factors light that fire."  This appears to be true.

            Vacations, elimination of mental stimulating drugs and the control of anything that puts a strain on the emotions are all factors that will lessen the activity of acne vulgaris.  Coffee, "cokes," chocolate, tea, alcohol and medications containing amphetamine or similar cerebral excitants should be avoided.  Different living conditions or psychiatric therapy may be required in some cases.

Sodium Chloride
            Because of the unfavorable water balance in the tissue that an excessive amount of sodium chloride produces, the use of salt foods or the use of salt at table should be discouraged.

            Chlorthiazides have been found helpful in older women if taken a week or so before each menstrual period.

Thyroid Extract or Thyroxin
            Unless there is a definite thyroid deficiency, not just a slightly minus basal metabolic rate, therapy with thyroid extract should be withheld because it will increase the activity of the patient's own androgens.  Not only that but the effect of thyroid extract on the pituitary will be to produce growth hormone, a stimulant for the already hypertrophied sebaceous glands.

17-Ketosteroids

            From the observations of the females whose acne was worse premenstrually and whose urinary 17-ketosteroids were elevated premenstrually, it would appear that these
 
 
 

                                                                                                                        82

are the patients who would benefit definitely from a two week premenstrual course of daily estrogens.

Ultraviolet and Roentgen Irradiation
            Almost two-thirds of the females and over three-fourths of the males observed improvement in their acne eruptions with exposure to the "sun" or "when at the beach."  It would seem then that this is a natural treatment.  Unless a patient has rather severe reactions to ultraviolet rays, this therapy could be used regularly with benefit.  However, a heavy growth of lanugo hairs has been observed at times over the face in women who have received intensive ultraviolet therapy over a long period of time.

            Roentgen therapy for acne vulgaris has practically gone into disuse in most parts of this country because of the fear present in the public mind of side effects, local or genetic.  However, it still remains one of the best methods for achieving atrophy of the sebaceous glands for reducing their activity.

Milk Drinking
            Milk drinking is a habit that has been foisted on young people since infancy.  As children grow older they cling to the habit because it is a quick and effortless way of getting nourishment.  It does not have to be chewed, can be swallowed at once and by filling the stomach gives a temporary feeling of satisfaction.  Many drink milk hoping to gain weight not realizing that it is over 87 per cent water.

            Milk is primarily a childhood food and drink.  In the adolescent as a food habit it should be curtailed for the benefit of improvement of the lesions of acne.  It may be used
 
 
 

                                                                                                                        83

in cooking and as food at table as needed.  But the use of milk as a beverage should be discouraged.

            Parents often inquire about a substitute when the child's intake of milk is reduced and what will he do for calcium?  The protein and calcium can be supplied through cottage cheese which may be eaten daily:  Water is the best substitute as a drink and so that the patient knows his milk is not entirely removed, allow one glassful of milk to drink for each three glassfuls of water he has.  Diluted fruit juices are good substitutes for adolescents if they do not contain too much sugar; grape juice diluted 6 to 8 times with water gives water a little flavor which has been found acceptable as a drink.

Conclusions

            This study demonstrates that acne lesions were found before treatment to be definitely more extensive, more severe and with greater scarring in the males than in the females.  However acne starts earlier in the female and remains active longer but at a less severe condition in the female than in the male.  Males do not seek treatment as early as females apparently because it is of less social importance to him at this age.

            As a result of anatomical pre-disposition, endocrine development, variations in emotional disturbances and in dietary and living conditions, the etiology of acne vulgaris and therefore its treatment involves factors that are individual to every patient.

Adrenals
            Although the adrenal glands secrete androgens, some other stimulus must be present to activate the sebaceous glands.  Corticoid stimulation before puberty may be the cause of keratosis pilaris.  The mature development of the sebaceous glands occurs before
 
 
 

                                                                                                                        84

full development in the female of the gonadal system.  This shows that the sebaceous glands are more sensitive to stimulation of hormones than the sexual glands.

Nutrition
            Since the demonstration showed that an excessive intake of fats or of carbohydrates causes an increase in the oiliness of the skin, smaller meals and frequent feedings with reduction in the intake of sugar, alcohol, fatty foods and heavy starchy meals seems advisable.

Stress and Strain
            The observation that the eruptions of acne are made worse by chemical cerebral stimulants and by emotional stress and strain with clearing when the conflicts are resolved, indicates the significance of the nervous factor as a secondary influence in acne vulgaris.

            And since aldosterone is the adrenal salt-retention hormone, it is conceivable that normal adrenal stimulation from the pituitary under cerebral stress or emotion would cause sodium chloride to be withheld in the tissues and probably cause exacerbation of the lesions of acne through imbalance of the fluid level in the skin.

Sodium Chloride
            On the basis of sodium chloride and water retention in the skin, exacerbations should be relieved by the periodic administration of oral diuretics.

Seborrhea
            The same factors of nutrition and emotion that affect acne vulgaris also influence seborrhea.
 

Atopy (Familial Allergy)

            The percentages of atopic individuals were the same in this study as occur in normal population, so no allergic conditions could be considered responsible for exacerbations of acne vulgaris.

Acne Surgery
            The regular surgical removal of comedones and pustules results in a great deal of improvement both cosmetically during the activity of the eruption and for the prevention or reduction of subsequent scarring.

Menses, Acne Exacerbations and 17-Ketosteroids
            In view of the fact that most of the flare-ups of acne in women are accompanied by an elevation of urinary 17-ketosteroids before menses, it would seem that these women would benefit from estrogen therapy given from time of ovulation each month to onset of menses.  However, more studies are justified from these urinary 17-ketosteroid findings.

Milk Drinking
            Milk drinking as a beverage adds an excessive quantity of butter fat, sodium chloride and hormones to the diet and is out of proportion to a normally balanced food intake. Acne patients were found to drink from 50 per cent to 300 per cent more milk than individuals of the same age of normal population.  However this fact does not incriminate milk-drinking as a sole secondary factor in acne exacerbation because 4.5 per cent of the acne patients were non-drinkers of milk.

            The excess salt intake as would occur in a large daily consumption of cow's milk seems undesirable because of the edema created in the extracellular tissue spaces.  It would make the skin more susceptible to secondary infection.

            With the large quantities of progesterone that are produced during gestation of the cow, the possibility of progesterone being present in cow's milk along with the other hormones is highly probable.  And while the pregnant cow is still with the milking herd of any dairy, the pooled milk of these lactating pregnant cows will get into the milk for general delivery.

            Since I have observed in practice that the consumption of an abnormally large amount of cow's milk is often associated with active fluctuations of acne lesions, I believe the use of milk as a beverage in the adolescent with acne should be discouraged for benefit of improvement of the lesions.  This part of the acne patient's diet should be studied further to learn of the influencing factors that are in milk.

                I have studies now in progress for the continued investigation of the content of hormones that may be excreted in cow's milk and which I should like to report on at a later date.
 
 
 

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19.  Semon, H. C. and Herrmann, F.:  Some Observations on the Sugar Metabolism in

Acne Vulgaris and Its Treatment by Insulin.  British J. Derm. and Syph.  57:  123,

1940.
 
 

20.  Hamilton, J. B.:

            J. Clin. End. 1:  570, 1941.
 
 

21.  White, C.:  Acneform Eruptions on the Face, Etiologic Importance of Specific 

Foods.  J.A.M.A. 103:  1277, 1934.
 
 

22.  Tobias, N.:  Essentials of Dermatology.  J. B. Lippincott Co., Philadelphia, 1944.
 
 

23.  Andrews, G. C., Domonkos, A. N., and Post, C. F.:  Treatment of Acne Vulgaris.

            J.A.M.A. 146:  1107, 1951.
 
 

24.  Sutton, Richard L., Jr.:  Handbook of Diseases of the Skin.  C. V. Moshy Co., St.

Louis, Mo., 400-408, 1949.
 
 

25.  Lutz, von W.:

            Dermatologia 89:  17-24, 1944.
 
 

26.  Serrati quoted by Rothman
 
 

27.  Sulzberger, M.A., Rostenberg, A. and Sher J.:

                        New York State J. Med. 34:  899, 1934.
 
 

28.  Stokes, J. H. and Sternberg, T. H.:

            Arch. Derm. and Syph. 40:  345, 1939.
 
 

29.  Cohen, E. L.:  Endocrine Factors in Acne Vulgaris Part II.  British J. Derm. and 

Syph. 53:  277, 1941.
 
 

30.  Ebner, N.:  Beitrag Zur Akne-und Ekzem-behanalung.  Wein. Klin. Wchnschr, 68:

995, 1956.
 
 

31.  Wirth, Lothar:  Acne Vulgaris and Chlorides.  Military Medicine 5:  122, 1958.
 
 

32.  Mason, H. L. and Engstrom, W. W.:  The 17-Ketosteroids:  Their Origin, 

Determination and Significance.  Physiological Reviews 30:  321, 1950.
 
 

33.  Blackburn, C. R. B.:  The Physician's Prospect of the Aetology of Acne.

Australian J. Derm.  1:  112, 1951.
 
 

34.  Larenz, T. H., Graham, D. T., and Wolf, S.:

                        J. Lab. and Clin. Med. 41:  11, 1953.
 
 

35.  Stokes, J. H. and King, A. D.:  Acne Vulgaris; Heredity in the Etiologic 

Background.  Arch. Derm. and Syph. 26:  456, 1932.
 
 

36.  Cushing, H.:  The Pituitary Body and Its Disorders.

            Philadelphia, 1912.
 
 

37.  Cohen, E. L.:  Endocrine Factors in Acne Vulgaris Part I.  British J. Dermat. and 

Syph. 53:  231, 1941.
 
 

38.  Cantarow, A. and Trumper, M.:  Clinical Biochemistry.  W. B. Saunders Co.,

Philadelphia, 1955.
 
 

39.  Butterworth, J. and Chamberlain, G. W.:

            Arch. Dermat. 75:  502, 1957.
 
 

40.  Goldzieher, J. W.:  Newer Drugs in Oral Contraception.  Med. Clin. No. America

48:  529, 1964.
 
 

41.  Hooker, C. W. and Pfeiffer, C. A.:  Effects of Sex Hormones Upon Body Growth,

Skin, Hair and Sebaceous Glands in Rats.  Endocrinology 32:  69, 1943.
 
 

42.  Sulzberger, M. B. and Witten, V. H.:  Hormones and Acne Vulgaris.  Med. Clin.

No. America    , 1951.
 
 

43.  Clinical Biochemistry. Saunders,  1955.
 
 

44.  Montagna, W.:  The Structure and Function of the Skin.  Academic Press, Inc.,

New York, N. Y., p. 288, 1956.
 
 

45.  English, R. S. and Witkowski, J. A.:  Etiological Factors in Acne.  The W. Virginia

Med. J. 60:  178, 1964.
 
 

46.  Cook, J. T. and Lorincz, A. L.:  Absence of Steroid Acne in Children.  Arch. Dermat.

and Syph.  89:  442, 1964.

47.  Palitz, L. L., Milberg, I. L., and Kantor, I.:  Enovid for Acne in the Female.  SKIN

            3:  243, 1964.
 
 

48.  Asel, N. D.:  Acne; A Review.  Missouri Med.  62:  277; 1965.
 
 

49.  Andrews, G. C.:  Acne Vulgaris.  Med Clin. No. America 49:  737, 1965.
 
 

50.  Nathanson, J. T. and Towney, L. E.:  Sex Hormones in Urine and Acne.

Endocrinology 28:  851, 1941.
 
 

51.  Lawrence, C. H. and Werthessen, N. T.:  Treatment of Acne with Orally 

Administered Estrogens.  J. Clin. Endocrinology 2:  636, 1942.
 
 

52.  White, C. B. and Lehmann, C. F.:  Diethyl Stilbestrol Therapy in Young Men with

Acne.  Arch. Dermat. and Syph.  65:  601, 1952.
 
 

53.  Lynch, F. W.:  A Clinical Study of Acne in University Students.  J.A.M.A. 113:

1793, 1939.
 
 

54.  Montagna, W.:  The Structure and Function of the Skin.  Academic Press, Inc.,

New York, N. Y., p. 258, 1956.
 
 

55.  Rothman, S.:  Physiology and Biochemistry of the Skin.  The University of

Chicago Press, Chicago, p. 303, 1954.
 
 

56.  Ibid, p. 291.
 
 

57.  Montagna, W.:  The Structure and Function of the Skin.  Academic Press, Inc.,

New York, N. Y., p. 271, 1956.
 
 

58.  Montagna, W., p. 288.  Ibid.
 
 

59.  Lorincz, A. L.:  Pathogenetic Factors of Acne Vulgaris.  Illinois Med. J. 124:        ,

            1963.
 
 

60.  Rothman, S.:  Physiology and Biochemistry of the Skin.  The University of Chicago

            Press, Chicago, pp. 297-298, 1954.
 
 

61.  Haskin, D., Lasher, N., and Rothman, S.:  Some Effects of ACTH, Cortisone, 

            Progesterone and Testosterone on Sebaceous Glands in the White Rat.  J. Invest.

            Derm. 20:  207, 1953.
 
 

62.  English, R. S. and Witkowski, J. A.:  Etiological Factors in Acne.  The W. Virginia

Med. J. 60:  178, 
 
 

63.  Rony, H. R. and Zakon, S. J.:  Effect of Androgen on Sebaceous Glands of Human

Skin.  Arch. Dermat. and Syph. 48:  601, 1943.
 
 

64.  Hamilton, J. B. and Mester, G. E.:  Effect of Orchiectomy and Oophorectomy.

            J. Invest. Derm. 41:  249, 1963.
 
 

65.  Hertel, N.:  Androcorticol Function Tests.  Medical Science p. 54, Aug. 1954.
 
 

66.  Semon, H. C. and Hermann, F.:

            Brit. J. Derm. 52:  132, 1940.
 
 

67.  Pochi, P. E., Strauss, J. S. and Mescon, H.:  The Role of Andrenocortical Steroids in

the Control of Human Sebaceous Gland Activity.  J. Invest. Derm. 41:  391, 1963.
 
 

68.  Williams. R. H.:  Textbook of Endocrinology.  W. B. Saunders Company, 

Philadelphia, 1955.
 
 

69.  Warshaw, T. G.:  Etiologic Factors in Acne Vulgaris.  New York State J. Med. 58:

            2960, 1958.
 
 

70.  Cushing, H.:  The Pituitary Body and Its Disorders.  Philadelphia, 1912.
 
 

71.  White, A.:  Hormones of the Hypophysis.  International Forum, Parke, Davis

& Company 4:  283,         .
 
 

72.  Nathanson, I. T., Towne, L. E. and Aub, J. C.

            Endocrinology 24:  335, 1939.
 
 

73.  Lawrence, C. H. and Werthessen, N. T.:  The Endocrine Dipsrasias of Acne Vulgaris

in Women.  Endocrinology 27:  755, 1940.
 
 

74.  Smith, G. V.:  The Ovaries.  Textbook of Endocrinology, W. B. Saunders Co.,

            Philadelphia, 1955.
 
 

75.  Greenblatt, R. B., Mahesh, V. B. Rigas, L. C. and Shapiro, S. T.

            Arch. Derm. 89:  846, 1964.
 
 

76.  Wile, U. J., Snow, J. S. and Bradbury, J. T.:  Studies in Sex Hormones in Acne. 

II Urinary Excretions of Androgenic and Estrogenic Substances.  Arch. Dermat. 

and Syph. 39:  195, 1939.
 
 

77.  The Medical Letter
 

                                                                                                                                   6
 
 

78.  Greene, R. R. Burrill, M. W. and Thomson, D. M.:  Further Studies on the

Androgenicity of Progesterone.  Endocrinology 27:  469, 1940.
 
 

79.  Dorfman, R. I. and Hamilton, J. B.:  Concerning the Metabolism of Testosterone

to Androsterone.  J. Biol. Chem.  133:  753, 1940.
 
 

80.  Sanderman, F. W. and Boerner, F.:  Normal Values in Clinical Medicine.  W. B.

            Saunders Company, Philadelphia, 1941.
 
 

81.  Culiner, A.

            J. Obs. and Gyn.  British Empire 52:  545, 1945.
 
 

82.  Forbes, T. R.:  Systemic Plasma Progesterone Levels During the Human Menstrual

            Cycle.  Am. J. Obst. and Gyn.  60:  180, 1950.
 
 

83.  Meltzer, Leonard:  Endocrine Hypersensitivity.  Annals of Allergy 9:  753, 1951.
 
 

84.  Aron-Brunatiere, R.:  An Attempt at a Physiological Explanation of Seborrhea and

            Acne Vulgaris, Therapeutic Results.  Brit. J. Dermat. 65:  157, 1953.
 
 

85.  Smith, J. G.

            Arch. Dermat. and Syph. 80:  663, 1959.
 
 

86.  Jarrett, A.:  The Effects of Progesterone and Testosterone on Surface Sebum and

            Acne Vulgaris.  Brit. J. Derm.  71:  102, 1959.
 
 

87.  Strauss, J. S. and Kligman, A. M.:  Effect of Progesterone and Progesterone-like

            Compounds on Human Sebaceous Gland.  J. Invest. Derm.  36:  309, 1961.
 
 

88.  Strauss, J. S. and Kligman, A. M.:  Androgenic Effects of Progestational Compound

            17-Alpha-Ethynyl-19-Nortestosterone (Norlutin) on Human Sebaceous Glands.

            J. Clin. Endocr. 21:  215-219, 1961.
 
 

89.  Pincus, G.:  Clinical Experience within and Practical Techniques for Use of Enovid

            in Ovulation Control (A. F. Guttmacher, Chairman).  A closed circuit T. V.

            Symposium Sponsored by G. D. Searle & Co.  Jan. 18, 1961.
 
 

90.  Lorincz, A. L.:

            Advan. Biol. Skin 4:  188, 1962.
 
 

91.  Ebling, J. F.:

            Advan. Biol. Skin 4:  200, 1962.
 

                                                                                                                                    7
 
 

92.  Andrews, G. C.:  Dermatology Principles of Therapy, A Symposium.  Ohio State

Med. J. 59:  910, 1963.
 
 

93.  Asel, N. D.:  Acne:  A Review.  Missouri Medicine 62:  277, 1965.
 
 

94.  Strauss, J. S. and Pochi, P. E.:  Effects of Cyclic Progestin-Estrogen Therapy in 

Sebum and Acne in Women.  J.A.M.A. 190:  815, 1964.
 
 

95.  Cook, T. J. and Lorincz, A. L.:  Absence of Steroid Acne in Children.  Arch. Dermat.

 89:  442, 1964.
 
 

96.  Stokes, J. H. and Sternbery, T. H.:

            Arch. Dermat. and Syph. 40:  345, 1939.
 
 

97.  Andrews, G. C., Post, C. F. and Domonkos, A. N.:  Advances in the Treatment of 

            Seborrheic Dermatitis and Acne Vulgaris.  Aust. J. of Derm. 1:  11, 1951.
 
 

98.  Pearlman, W. H.:  The Hormones.  Academic Press, New York 1:  351, 1908.
 
 

99.  Nathanson, J. T. and Towney, L. E.:  Sex Hormones in Urine and Acne.

            Endocrinology 28:  851, 1941.
 
 

100.  White, C. B. and Lehman, C. F.:  Diethyl Stilbestrol Therapy in Young Men with

Acne.  Arch. Dermat. and Syph. 65:  601, 1952.
 
 

101.  Pincus, G.:  Recent Progress in Hormone Research.  Academic Press, New York 1:

            123, 1947.
 
 

102.  Dorfman, R. A. and Shipley, R. A.:  Androgens.  John Weley and Sons Inc., New

York:  p. 396, 1956
 
 

103.  Tomovitch, T. Z., Abrams, A. A., and Jacobs, P. H.:  Acne in Infancy.  Am. J. Dis.

Child.  106:  144, 1963.
 
 

104.  Pochi, P. E. and Strauss, J. I.:  Sebum Production, Causal Sebum Levels, Titratable

            Acidity of Sebum and Urinary Fractional 17-Ketosteroid Excretion in Males

            With Acne.  J. Invest. Derm. 43:  383, 1964.
 
 

105.  Knowles, F. and Decker, H.:

            Arch. Dermat. and Syph. 13:  215, 1926.
 
 

106.  Levin, O. and Kahn, N.:

            Amer. J. M. Sc. 164:  374, 1922.
 
 
 

 107.  Greenbaum, S. S.:

            Arch Dermat. and Syph. 23:  1064, 1931.
 
 

108.  Wartes, J.:  Common Acne and Insulin Hypoglycemia.  J.A.M.A. 108:  971, 1937.
 
 

109.  Smith, S. C. Young, J. and Smith, D. C.:  The Basal Metabolic Rate in Acne

Vulgaris.  J. Invest. Derm. 17:  13, 1951.
 
 

110.  Ratzer, M. A.:  The Influence of Marriage, Pregnancy and Childbirth on Acne

            Vulgaris.  British J. Dermat. 75:  165, 1964.
 
 

111.  Buckley, L. D.:  Skin Disorders and Internal Disorders.  Rebman and Co., New 

            York, 1906.
 
 

112.  Sulzberger, M. A. and Rostenberg, A. and Sher, J.:  New York State J. Med. 34:

            899, 1934.
 
 

113.  Flood,  James M.:  The Factor of Food Allergy in Acne.  The Pennsylvania Med. J. 

51:  533, 1947.
 
 

114.  Goodman, L. A. and Gilman, A.:  The Pharmacological Basis of Therapeutics.  The

            Macmillan Co., New York, p. 355, 1965.
 
 

115.  Kalz, F., Janauskas, A., Faurnier, C.:  Studies in Sebum Lipids in Acne Vulgaris.

            J. of Invest. Dermat.  17:  273, 1951.
 
 

116.  Barber, H. W.:  (In R. M. B. Mackerna's Modern Trends in Dermatology).

Butterworth & Co., Ltd, London, p. 106, 1948.
 
 

117.  Wirth, Lothar:  Acne Vulgaris and Chlorides, Military Medicine 5:  122, 1958.
 
 

118.  Howard, J. E. and Scott, W. W.:  Textbook of  Endocrinology.  W. B. Saunders Co.,

            Philadelphia, 1955.
 
 

119.  Meyrowitz, Alvin:  Milk Drinking Habits Among People.  Milk Research Council,

            Inc., University of Newark Research Centre, Newark, New Jersey, Aug. 1938.
 
 

120.  Sutton, Richard, Jr.:  In Comments Acneform Eruption Due to Corticotropin.  Arch.

            Dermat. and Syph. 73:  123, 1956.
 
 

121.  Munch, V.:  Secretions of Natural Androgens and Estrogens in Milk. 

            Milchwissinschaft, 9:  150, 1954.
 

122.  Gorski, J., Erb, R. E. and Brinkman, D. C., Jr.:

            Animal Science, 16:  698, 1957.
 
 

123.  Short, R. V.:

            Nature, 178:  743, 1956.
 
 

124.  Williams, W. F.:  Progesterone Secretion in Milk.  J. Dairy Science 45:  1541, 1962.
 
 

125.  Pigato, E. and Guzzonato, G.:  Hormones in Cow's Milk in Relation to Pregnancy.

            Progr. Vet. (Italian) 11:  60, 1956.
 
 

126.  Gorski, J. Erb, R. E., Dickinson, W. and Butter, H.:  Progesterine in Ovaries of

Cow.  J. Dairy Science (submitted) 1958.
 
 

127.  Short, R. V.:  Progestin Blood Level.  J. Endocrinology 16:  426, 1958.
 
 

128.  Zander, J., Forbes, T. R., Munstermann, A. M. and Neher, R.:  J. Clinic. Endocrinal.

            and Metabolism 18:  337, 1957.
 
 

129.  Diczfalusy, E. Acta Endocrinal, Supplementum 12:  1953.
 
 

130.  Remington's Pharmaceutical Science XIII.  Mack Publ. Co., Easton, Penna.,

p. 1638, 1965.
 
 

131.  Attman, P. L.:  Blood and Other Body Fluids.  Federation Am. Soc. of Exp.

 Biology, Washington, D. C., p. 459, 1961.
 
 

132.  Morris, D. M.:

            Endocrinology, 48:  257, 1951