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Acne Vulgaris
Acne Vulgaris· GEOR GE C. ANDR EWS, M.D., F.A.C.P.*
Acne vulgaris is a common chronic inflammatory disease of the of pilosebaceous follicles that occurs chiefly on the face, chest and back s nodule s, adolescents. It is characterized by comedones, papules, pustule young of and cysts. It may produce unsigh tly scarring. About 90 per cent in people are affected more or less by acne and it may develop or persist women in adults. Acne has been experimentally produced in castrat es and nate. treated for mamm ary cancer by injections of testosterone proprio the of Acne and hirsutism are also encountered in masculinizing tumors ACTH adrenal gland, pituita ry gland or gonads, or from treatm ent with sexes or cortisone. The role of androgens in the production of acne in both ens is generally accepted. The adrena l glands supply the circulating androg s in the female. Another source of supply is the corpus luteum which secrete progesterone during the luteinizing stage of the menstrual cycle. Proges testosterone chemically resembles testosterone and can be converted into of ations exacerb ual menstr that le probab is It tissue. terone by ovarian acne are caused by the androgenic action of progesterone. Although androgenic stimula tion may increase sebum production and is no probably also produces qualita tive alterati ons in the sebum, there has It ed. produc sebum of ty quanti the to related is evidence that acne sebum ing decreas of capable are ns estroge that long been established the production, reducing the size of the sebaceous glands of the face and Serum tus. appara aceous piloseb facial entire the functional activity of may cholesterol levels in acne are normal althoug h androgenic stimula tion levels eroid -ketost 17 y Urinar blood. the in erol cause an increase in cholest are also normal in acne patient s. The sebaceous glands are holocrine. It is the retenti on of sebum that of produces the comedo (blackhead). The comedo is the elementary lesion may comedo The follicle. us sebaceo the of orifice acne. It is a plug at the result from failure of a rudime ntary hair to penetra te the follicular orifice. Physicia ns and Surgeons, * Clinical Professor of Dermato logy (Retired), Collegetoofthe Presbyte rian Hospita l, Columb ia Univers ity; Consult ing Dermato logist Columb ia-Presb yterian Medical Center, New York, N.Y.
737
738
GEORGE
C.
ANDREWS
It has been postulated that in acne there is a faulty anatomic structure or faulty function of the pilosebaceous unit that leads to increased keratinization at the follicular orifice. Foreign-body reaction or secondary bacterial infection of the follicle results in inflammation and pustulation. An oily seborrheic condition of the skin often precedes or accompanies acne, although acne may occur outside the usual seborrheic areas and without seborrhea. In men seborrhea and acne are often associated with concomitant onset of the male pattern of baldness in which there is a loss of scalp hair most pronounced on the temples and vertex. There is undoubtedly an hereditary factor in acne. The disease is so common that it is difficult to identify this factor. In some families there is a tendency toward severe acne with unsightly scarring. A pituitary hormone that acts as a specific trophic factor on the sebaceous glands has been demonstrated in rats, but not so far in humans.
CLINICAL TYPES
Acne is best understood by visualizing the many different clinical types which may overlap one another in unlimited combinations. Comedo. The eruption is composed almost entirely of blackheads. Usually the skin is oily. Acne Papulosa. Small papules are profuse, being superimposed upon large comedones that have become inflamed. The skin of the face is frequently more or less diffusely erythematous. Acne Excoriee des J eunes FiZZes. This is a special type of superficial acne described by Brocq. It is caused by the neurotic habit of picking the face and squeezing out blackheads that are too small to be seen on close scrutiny. It is evidence of emotional conflicts in adolescents, usually girls. Often there are some feelings of inferiority which may extend into spells of crying, withdrawal from social contacts, inversion and depression. This type of acne should be treated largely by sedatives and psychotherapy. Patient listening and encouragement are necessary. Practical points are the avoidance of unreasonable efforts at cleanliness, and prohibiting the use of magnifying mirrors and of long fingernails. Small doses of meprobamate, phenobarbital and prednisone are useful remedies, but should be carefully regulated and discontinued before becoming a permanent crutch. Acne Atrophica. Infrequently in the small papular cases, after the lesions disappear, tiny pitted scars are left. These produce numberless minute depressions which are disfiguring. Acne Pustulosa. This is a type of small, superficial pustular acne that occurs frequently in young girls with fair skins. There are few comedones and the eruption seems to be caused largely by the staphylococcus. Acne Indurata. Papular acne often progresses into an indurated type, due to secondary staphylococcus infection. The lesions then are deep-
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seated and destructive, and either papular, nodular, pustular or mixed. If the eruption has been present for some length of time, scarring often becomes severe. Acne Cystica. This type may develop either in association with indurated acne, or subsequent to an inflammatory type of acne that has left an oily seborrhea and inspissated comedones. The cysts are a form of tissue reaction about small hard deposits of sebum, which act as foreign bodies. The cyst usually contains a jelly-like, blood-tinged fluid. Acne Cachecticorum. This variety is characterized by indolent, soft, scarcely infiltrated, pustular lesions almost lacking in inflammatory reaction, cyst abscesses, nodules and scarring. The disease may appear in any location where the pilosebaceous follicles are present, and in this type the comedones are sometimes barely noticeable. Acne cachecticorum usually occurs in debilitated patients and in those who have grown rapidly. Acne Conglobata. This is a rare form of the disease in which the comedones-many of which are double-papules and pustules are accompanied by large indolent abscesses, cysts and connecting sinuses, which heal slowly and leave pronounced scars that are frequently keloidal. Because of the clinical resemblance to scrofuloderma, this type of acne was for years erroneously considered to be related to tuberculosis. Acne Keloidalis. This is a type of acne with hypertrophic scarring. It may be subdivided into more or less definite clinical varieties. 1. Numerous small keloidal scars of the face as a result of small papular acne. This is most frequently seen in the Negro race. It is not infrequent in adult colored males on the bearded region, where it is perhaps augmented by shaving. 2. Keloids accompanying cystic acne are uncommon. The areas affected are usually the face, ears, chest and back. 3. Folliculitis keloidalis is usually located on the nape of the neck. The underlying cause is the presence of numerous large comedones, which are often double, forming little tunnels beneath the skin. Infection is present leading to follicular pustules and formation of sinuses. In the course of years the elementary lesions tend to coalesce and form keloidal thickenings. 4. Keloids occurring sporadically in acne vulgaris. This group includes miscellaneous cases not encompassed by the three preceding forms. Acne Neonatorum (Infantile Acne). This type is usually present at birth or appears within a few weeks or months after birth, being more frequent in boys than in girls. In most instances, typical lesions are noticed by the third month. There are comedones that vary in number and size, and occasional papules and pustules. Nodules and cysts are rare. The eruption usually occurs on the cheeks, but sometimes on the forehead and chin. The disease is usually mild and tends to improve and resolve in the early years of life, sometimes leaving little pitted scars. Tropical Acne. This variety is a severe type that occurs in the tropics.
740
GEORGE
C.
ANDREWS
It differs from acne vulgaris in several ways. It affects an older age group, is located chiefly on the back, buttocks and thighs, and is pustular, cystic and nodular. Comedones are not visible or they are sparse. Treatment is ineffective, unless there is a change to a cooler climate.
PATHOLOGY There is an intrafollicular hyperkeratosis that appears first in the excretory ducts of the sebaceous glands which are enlarged. The keratin collects in the follicular lumen and, combined with sebum, forms the comedo. After the comedo is produced, the hypertrophic sebaceous gland becomes smaller and ultimately atrophic. Coagulase-positive staphylococci are usually found on culture from acne lesions. Whether the myriads of Propionibacterium organisms present take part in the inflammation is unknown. It seems in some cystic cases that a virus, as hypothecated by Melczer in pyoderma vegetans, may be a factor, although there is no proof of this conjecture. TREATMENT Treatment varies according to the severity of the disease, the age, and the type of the patient's skin. In mild cases in which comedones and a few papules and pustules are present, expression of the comedones, topical lotions, and hot compresses twice weekly of Vleminckx's solution probably will clear up the skin condition. An antiseborrheic shampoo may be indicated. In more extensive cases in which there is a good deal of inflammation and pustulation, sulfamethoxazole (Madribon) or sulfadimethonine (Gantanol) should be given internally for a few weeks. The dose of Madribon required is usually one tablet (0.5 gm.) morning and night for two weeks, and then a reduced dose of one tablet daily for three to four weeks. The dose of Gantanol is two tablets (0.5 gm.), two or even three times a day for two weeks, followed by two tablets morning and night for one month. The Vleminckx's compresses may be used three times a week, or even oftener, care being exerted not to provoke excessive dryness. Rarely patients cannot tolerate sulfonamides. In such cases tetracyclines may be substituted. Drainage of pustules and expression of comedones at weekly intervals is an important part of treatment. Severe cases are in two categories: 1. There are cases of long duration in which scarring is a prominent feature and pustules and nodules persistently recur. The face, the submandibular regions, the back of the neck, the upper back and the chest are favorite locations. In this type of case a search for focal infections
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should be made. Teeth, tonsils, sinuses, etc. should be cleared of infection. Acne surgery and hot Vleminckx's compresses should be utilized. These hot compresses may be given daily for an hour or two. Cultures and antibiotic sensitivity tests should be made and appropriate sulfa drugs or antibiotics prescribed. X-ray treatment may be desirable, especially in acne of the back of the neck, upper back and chest. After the acne is cleared, dermabrasion may be indicated for pitted scars of the face, but should not be used on the back or chest. 2. Cystic and nodular eruptions which are recalcitrant to most forms of treatment are encountered. Many such patients have had desultory courses of antibiotics, steroids, x-rays and hormones. Sometimes such patients have had to give up college and are invalided, being unable to sleep because of painful sores on the back, face and neck. Such patients may run a temperature off and on for a couple of years, and become addicted to narcotics given for pain, or to steroids. There are cases of acne that are mutilating and repulsive. These may justly produce a state of mental despair and frustration that interferes with normal social contacts. Each such case requires individual consideration. Study with antibiotic sensitivity tests may help in finding an antibiotic that is specific. It may be sodium oxacillin (Prostaphlin), tetracycline-amphotericin-B (Mysteclin F), or just oral penicillin. Whatever it is, it must be continued for perhaps a year or more, as long as it keeps the patient well and comfortable. In other cases no antibiotic does any good. One may discover that the patient had an inadequate dosage of x-ray and upon administering the remaining permissible quota the acne is cured. Some parents are so frightened about the dangers of radiation that they do not give permission for x-ray treatment until their child has been subjected to years of great suffering and tremendous doses of antibiotics and cortisone treatment. Hot compresses of Vleminckx's solution, diluted, are usually effective and may be used every alternate day or daily for an hour or more. In the foregoing discussion of the treatment of acne, little has been said about diet and about the use of corticosteroids and estrogens. These subjects are covered now.
Diet The importance of diet is a debatable question. Acne is a glandular disease. Androgens are the important etiological factors. Whether diet has any influence is a matter of personal opinion. It is customary to avoid chocolate, shellfish, nuts and ice cream. The intake of fried foods, pastry and candy should be limited. Eggs, cream, milk, butter, cheese, pork and bacon should be eaten in moderation. In general some kind of fruit should be eaten at breakfast and either two green vegetables or a green vegetable and a salad at both luncheon and dinner.
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ANDREWS
Systemic Treatment CORTICOSTEROIDS. It is a paradox that corticosteroids which may produce acne are also effective anti-inflammatory agents in its treatment. In some cases of severe cystic and nodular acne with much foreign body type of inflammatory reaction, corticosteroid treatment is more effective than antibiotic treatment. In chronic disease states, like acne, it must be realized that once corticosteroid therapy is started, it is difficult to stop. The unfortunate results of corticosteroid therapy are that patients eventually realize that nothing else helps and become actually addicted to corticosteroids. The dosage required is usually small, but the ultimate onset of Cushingoid symptoms makes one wonder whether, after all, it has been worthwhile to cause the temporary disappearance of horrible and mutilating types of acne. Small doses and free intervals are advisable but less than one-half the average therapeutic dose for other diseases is useless. The benefits are sometimes augmented by simultaneous antibiotic therapy, although most of the cases in which corticosteroids have been used are those that failed to be completely cleared by antibiotic and other standard therapy. ESTROGENS, NORETHYNODREL, VACCINES. Cyclic estrogen therapy is extremely effective for acne in a small number of girls. However, the author rarely uses estrogcn therapy because it generally upsets the menstrual cycle and only rarely accomplishes the desired effect. Treatment of acne in older women has been successful by the use of the oral contraceptive, norethynodrel and similar products, which inhibit the secretion of gonadotropin by the anterior pituitary gland and thus suppress ovulation. When ovulation is suppressed, no corpus luteum is formed. Being absent, it produces no progesterone. The cyclic use of estrogens and progestins to mimic the normal female menstrual cycle now has become a standard practice. By the use of this sequential therapy in which estrogen is given orally for 20 days and progestin daily for the last five days of the cycle, fertility is controlled and the irregularities of the duration, occurrence and amount of withdrawal bleeding that occurred with cyclic estrogen therapy alone have been largely avoided. Administration of progestational agents for five or more days of the terminal part of the cycle produces a sharp definite withdrawal bleeding period. Although the anovulatory effects of norethynodrel and similar products are reliable, the anti-acne effects are less dependable. In fact, acne is often worsened during the first few months of contraceptive therapy. This unfavorable result is probably due to the progesterone contained in the contraceptive. This augmentation of the acne combined with nausea, enlargement and tenderness of the breasts, gain in weight and other side effects of contraceptive therapy dampens one's enthusiasm for it, although results are often excellent.
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Vaccine therapy is occasionally of value in persistent pustular types, if used only to supplement other more reliable methods.
Local Treatment Specific admonitions regarding cleansing of the skin are important. Cleansing should be accomplished by soap and water. When the skin is extremely oily, the patient in addition should cleanse the skin with an alcoholic lotion. Towels and pillowcases should be fresh and clean. The dermatologist should regulate the use of all proprietary cosmetics. Whenever infection is present, creams and greasy cleansing agents should not be used. Facial massage should never be used in the presence of infection. Local therapy is directed to the drying of the skin and to the inhibition of sebaceous gland activity. Sulfur in various forms, still the most effective topical remedy, is incorporated into most of the preparations compounded by the pharmacist and in the modern commercial medications. In addition to sulfur, such substances as resorcinol, antibacterial agents, estrogens and peeling chemicals are used in cosmetically elegant lotions and creams. The modern commercial preparations are too numerous to list. These have overshadowed the use of the still effective medications such as Saturated Lotio Alba. In swere pustular and cystic cases, the liberal use of hexachlorophene locally is, all too seldom, beneficial. The purpose is to keep staphylococci at a minimum upon the skin. The authors' directions are as follows: Wash face for five minutes. Take a tub bath with pHisoHex each night or morning, washing all over for 15 minutes, especially the armpits and anogenital region. It is important to keep the skin surgically clean. Keep the fingernails short and clean also. Shampoo twice a week with pHisoHex. Keep the teeth well cleaned and use dental floss after each meal. Sublesional injections of corticosteroids for keloids, cysts and inflammatory nodules will cause rapid disappearance. Often after such an injection the site becomes depressed below the surface, but this is temporary and usually levels out within a few weeks. SLUSH TREATMENT. Hyperemia and peeling may be produced by solid carbon dioxide slush. The author does not incorporate sulfur into the slush. The solid carbon dioxide is finely powdered by placing it into a strong canvas bag, such as a bank money bag, and pulverizing the ice with a mallet. The powdered dry ice is placed onto four layers of gauze 8 inches square. The corners are gathered together, and a rubber band secures the dry ice in a ball. Using the gathered corners as a handle, it is dipped into a cup containing acetone, just enough to moisten it. It is then touched to a towel to take away the excess acetone. The bag is then gently rubbed over the treatment site, care being exercised to avoid overtreatment, ~ince severe burns may be caused. This treatment causes some inflamJnatory reaction with edema, followed by desquamation. It may be repeated ~nce or twice weekly.
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ANDREWS
SURGICAL TREATMENT. Local surgical treatment is imperative to bring about quick resolution of the pustules and to empty the pores of comedones, which may act as foreign bodies. The surface of the lesion is nicked with a No. 11 Bard-Parker scalpel and then the contents are expressed with a comedone extractor. Several types of these instruments are available. The incisions should follow Langer's lines. Scarring is not produced when the incision is performed with care. HOT COMPRESSES. Of the local remedial applications, hot compresses of dilute Vleminckx's solution (lime sulfurated solution) are most effective. One or two tablespoonfuls of the solution to one pint of hot water are used. Compressing is done for twenty minutes once or twice weekly in the case of average severity. In severe cases the compressing may be done oftener, even daily, and for longer periods extending to two or three hours. Excessive compressing may lead to extreme dryness and peeling. In patients who cannot tolerate sulfur, hot boric acid compresses may be substituted. These are also used for mild cases of acne that do not require the Vleminckx's solution compresses. Detailed Directions for Hot Vleminckx's Solution Compresses To 1 pint of hot water add 1 tablespoonful of Vleminck.x's solution. Make 2 compresses out of a double thickness of flannel and have them large enough to cover the entire face. Heat the solution in a saucepan, then soak the compresses in the solution and apply them to the face, changing one for the other every minute for 20 minutes. Protect eyelids by a thick coat of Vaseline. To avoid burning the fingers, a towel may serve as a wringer, or you may use compresses with hem at each end into which a stick can be inserted. Unless otherwise directed, it is permissible to use the same pieces of flannel again and again for these treatments. Frequency of application-twice weekly. Note: Use old saucepan as solution will soil saucepan.
For pustular and moist exudative cystic lesions on the chest and back, hot potassium permanganate solution baths may be helpful. Five or six 30-mg. tablets are put into half a tub of hot water in which the patient lies for 20 to 30 minutes. SCALP. The treatment of acne is frequently directed against concomitant seborrheic dermatitis of the scalp. Selsun suspension (Abbott) is the best remedy. Occasionally other medicated shampoos and lotions are useful.
X-ray Therapy All kinds of statements in favor of and opposed to x-ray treatment of acne have been made during the last 35 years. The author has constantly endeavored to avoid prejudice in this matter and as a result his opinion has changed through the years. In all of his writings he has never questioned the effectiveness of x-rays, as some with less experience have done. His chief concern has been possible injuries from radiation. Like Communism
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it is a hazard we must face. We are exposed to it day and night, from all sides, in all places. Whether we like it or not, it is there and one electron collision can produce a mutation just as one radical can kill a president. Since time immemorial all living creatures have been bombarded by radiation and without radiation life would never have developed or survived on this planet. The author practically never gives x-ray therapy to acne patients because he wishes to be conservative and shares, perhaps with more enlightenment than the public, the general fear of radiation. Roentgen therapy of acne is withheld until other methods of treatment have been used and then applied only in severely invaliding and mutilating cases. TECHNIQUE. An arbitrary outline of x-ray dosage for treatment of acne must necessarily be subject to individual variation. Fortunately, severe acne rarely occurs in those who have fair skins that are sensitive. The severe cases of acne are found chiefly in brunets and mostly young men are so afflicted. As x-rays are used only in such severe cases the dosages recommended are those suitable for coarse brunet male skin. The number of treatments will depend upon the dosage given each treatment, the anode-skin distance and the quality of radiation. One must understand the exit dose and in treatment about the face count how much the exit dose adds to each exposure. Cones are used except upon the back where overlapping is desirable. The number of exposures is thus also governed by the sum total of the doses of all exposures and by the clinical changes in the skin which appear during the course of treatment. Improvement usually manifests itself by lessened development of new lesions, by an inhibition of the secretions of the sebaceous glands causing a diminution in the amount of oil on the skin. These changes are first manifest at the point of focus of the central beam of x-rays. The quality of radiation should be in the realm of HVL 0.6 to 1.0 mm. aluminum. This is produced by voltages ranging from 60 to 100 kv. The less penetrating radiation exerts a more superficial action than the more penetrating qualities but has less exit dose. Roentgen-ray dosage should be fractional. The classical dose is 75 r given weekly to the affected areas with the gonads, trunk, eyes, eyebrows, scalp, hair and thyroid shielded. Midface exposures should never be combined with sideface exposures. A course of 8 to 10 treatments will suffice in many instances but 2 or 3 more may be necessary. The sum dosage of all exposures should not exceed 1000 r to anyone area. As previously stated, this applies to young men with brunet oily skin. The anode-skin distance influences not only the spread of the beam but also the exit dose and the depth dose. A distance of 15 to 25 cm. is recommended. The operator cannot be guided solely by such measurements, but must carefully study the biologic response of the skin at each visit, paying particular attention to the parts of the skin in the path of the direct beam. Scrutiny should be made for cessation of new lesions, erythema, and a drying up of exudation.
REFERENCES Andrews, G. C.: Acne. Ohio State M. J. 59: 910-913 (Sept.) 1963; A.M.A. Arch. Dermat. 84: 711-716 (Nov.) 1961.
Andrews, G. C., Domonkos, A. N. and Post, C. F.: Treatment of acne vulgaris. J.A.M.A. 146: 1107-1112 (July 21) 1951.
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Finkelstein, R. A., Forchielli, E. and Dorfman, R. I.: Estimation of testosterone in human plasma. J. Clin. Endocrinol. 21: 98-101 (Jan.) 1961. Kurtin, A.: Corrective surgical planing of skin. A.M.A. Arch. Dermat. & Syph. 58: 389-397 (Oct.) 1953. Lasher, N., Lorincz, A. L. and Rothman, S.: Hormonal effects on sebaceous glands in the white rat: Ill. Evidence for the presence of a pituitary sebaceous gland trophic factor. J. Invest. Dermat. 24: 499-505 (May) 1955. Melczer, M.: On the etiology of localized pyoderma papillaris and exulcerans and generalized pyodermitis vegetans. Dermat. Tropica 1: 61-74 (July) 1962. Palitz, L. L.: Abstract of a preliminary report on norethynodrel (Enovid) in the control of acne in the female. Tr. Bronx Derm. Soc., Arch. Dermat. 86: 237-238, 1962. Palitz, L. L., Milberg, I. L. and Kantor, 1.: Enovid for acne in the female. Skin 3: 243245 (Aug.) 1964. Pincus, G., Chang, M. C, Zarrow, M. X., Hafez, E. S. E. and Merrill, A.: Studies on the biological activity of certain 19-norsteroids in female animals. Endocrinology 59: 695 (Dec.) 1956. Smith, M. A. and Waterworth, P. M.: Bacteriology of acne vulgaris in relation to treatment with antibiotics. Brit. J. Dermat. 73: 152-159 (April) 1961. Strauss, J. S. and Pochi, P. E.: Effect of Enovid on sebum production in females. Arch. Dermat. 87: 366-368 (March) 1963. Strauss, J. S. and Pochi, P. E.: Effect of progestin-estrogen therapy in acne. J.A.M.A. 190: 815-819 (Nov. 30) 1964. Strauss, J. S., Kligman, A. M. and Pochi, P. E.: Pathologic patterns of the sebaceous glands. J. Invest. Dermat. 30: 51-61, 1958. Strauss, J. S., Kligman, A. M. and Po chi, P. E.: Effect of androgens and estrogens on human sebaceous glands. J. Invest. Dermat. 39: 139-156, 1962. 115 East 61st Street New York, N.Y. 10021
Acne vulgaris is a common chronic inflammatory disease of the of pilosebaceous follicles that occurs chiefly on the face, chest and back s nodule s, adolescents. It is characterized by comedones, papules, pustule young of and cysts. It may produce unsigh tly scarring. About 90 per cent in people are affected more or less by acne and it may develop or persist women in adults. Acne has been experimentally produced in castrat es and nate. treated for mamm ary cancer by injections of testosterone proprio the of Acne and hirsutism are also encountered in masculinizing tumors ACTH adrenal gland, pituita ry gland or gonads, or from treatm ent with sexes or cortisone. The role of androgens in the production of acne in both ens is generally accepted. The adrena l glands supply the circulating androg s in the female. Another source of supply is the corpus luteum which secrete progesterone during the luteinizing stage of the menstrual cycle. Proges testosterone chemically resembles testosterone and can be converted into of ations exacerb ual menstr that le probab is It tissue. terone by ovarian acne are caused by the androgenic action of progesterone. Although androgenic stimula tion may increase sebum production and is no probably also produces qualita tive alterati ons in the sebum, there has It ed. produc sebum of ty quanti the to related is evidence that acne sebum ing decreas of capable are ns estroge that long been established the production, reducing the size of the sebaceous glands of the face and Serum tus. appara aceous piloseb facial entire the functional activity of may cholesterol levels in acne are normal althoug h androgenic stimula tion levels eroid -ketost 17 y Urinar blood. the in erol cause an increase in cholest are also normal in acne patient s. The sebaceous glands are holocrine. It is the retenti on of sebum that of produces the comedo (blackhead). The comedo is the elementary lesion may comedo The follicle. us sebaceo the of orifice acne. It is a plug at the result from failure of a rudime ntary hair to penetra te the follicular orifice. Physicia ns and Surgeons, * Clinical Professor of Dermato logy (Retired), Collegetoofthe Presbyte rian Hospita l, Columb ia Univers ity; Consult ing Dermato logist Columb ia-Presb yterian Medical Center, New York, N.Y.
737
738
GEORGE
C.
ANDREWS
It has been postulated that in acne there is a faulty anatomic structure or faulty function of the pilosebaceous unit that leads to increased keratinization at the follicular orifice. Foreign-body reaction or secondary bacterial infection of the follicle results in inflammation and pustulation. An oily seborrheic condition of the skin often precedes or accompanies acne, although acne may occur outside the usual seborrheic areas and without seborrhea. In men seborrhea and acne are often associated with concomitant onset of the male pattern of baldness in which there is a loss of scalp hair most pronounced on the temples and vertex. There is undoubtedly an hereditary factor in acne. The disease is so common that it is difficult to identify this factor. In some families there is a tendency toward severe acne with unsightly scarring. A pituitary hormone that acts as a specific trophic factor on the sebaceous glands has been demonstrated in rats, but not so far in humans.
CLINICAL TYPES
Acne is best understood by visualizing the many different clinical types which may overlap one another in unlimited combinations. Comedo. The eruption is composed almost entirely of blackheads. Usually the skin is oily. Acne Papulosa. Small papules are profuse, being superimposed upon large comedones that have become inflamed. The skin of the face is frequently more or less diffusely erythematous. Acne Excoriee des J eunes FiZZes. This is a special type of superficial acne described by Brocq. It is caused by the neurotic habit of picking the face and squeezing out blackheads that are too small to be seen on close scrutiny. It is evidence of emotional conflicts in adolescents, usually girls. Often there are some feelings of inferiority which may extend into spells of crying, withdrawal from social contacts, inversion and depression. This type of acne should be treated largely by sedatives and psychotherapy. Patient listening and encouragement are necessary. Practical points are the avoidance of unreasonable efforts at cleanliness, and prohibiting the use of magnifying mirrors and of long fingernails. Small doses of meprobamate, phenobarbital and prednisone are useful remedies, but should be carefully regulated and discontinued before becoming a permanent crutch. Acne Atrophica. Infrequently in the small papular cases, after the lesions disappear, tiny pitted scars are left. These produce numberless minute depressions which are disfiguring. Acne Pustulosa. This is a type of small, superficial pustular acne that occurs frequently in young girls with fair skins. There are few comedones and the eruption seems to be caused largely by the staphylococcus. Acne Indurata. Papular acne often progresses into an indurated type, due to secondary staphylococcus infection. The lesions then are deep-
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seated and destructive, and either papular, nodular, pustular or mixed. If the eruption has been present for some length of time, scarring often becomes severe. Acne Cystica. This type may develop either in association with indurated acne, or subsequent to an inflammatory type of acne that has left an oily seborrhea and inspissated comedones. The cysts are a form of tissue reaction about small hard deposits of sebum, which act as foreign bodies. The cyst usually contains a jelly-like, blood-tinged fluid. Acne Cachecticorum. This variety is characterized by indolent, soft, scarcely infiltrated, pustular lesions almost lacking in inflammatory reaction, cyst abscesses, nodules and scarring. The disease may appear in any location where the pilosebaceous follicles are present, and in this type the comedones are sometimes barely noticeable. Acne cachecticorum usually occurs in debilitated patients and in those who have grown rapidly. Acne Conglobata. This is a rare form of the disease in which the comedones-many of which are double-papules and pustules are accompanied by large indolent abscesses, cysts and connecting sinuses, which heal slowly and leave pronounced scars that are frequently keloidal. Because of the clinical resemblance to scrofuloderma, this type of acne was for years erroneously considered to be related to tuberculosis. Acne Keloidalis. This is a type of acne with hypertrophic scarring. It may be subdivided into more or less definite clinical varieties. 1. Numerous small keloidal scars of the face as a result of small papular acne. This is most frequently seen in the Negro race. It is not infrequent in adult colored males on the bearded region, where it is perhaps augmented by shaving. 2. Keloids accompanying cystic acne are uncommon. The areas affected are usually the face, ears, chest and back. 3. Folliculitis keloidalis is usually located on the nape of the neck. The underlying cause is the presence of numerous large comedones, which are often double, forming little tunnels beneath the skin. Infection is present leading to follicular pustules and formation of sinuses. In the course of years the elementary lesions tend to coalesce and form keloidal thickenings. 4. Keloids occurring sporadically in acne vulgaris. This group includes miscellaneous cases not encompassed by the three preceding forms. Acne Neonatorum (Infantile Acne). This type is usually present at birth or appears within a few weeks or months after birth, being more frequent in boys than in girls. In most instances, typical lesions are noticed by the third month. There are comedones that vary in number and size, and occasional papules and pustules. Nodules and cysts are rare. The eruption usually occurs on the cheeks, but sometimes on the forehead and chin. The disease is usually mild and tends to improve and resolve in the early years of life, sometimes leaving little pitted scars. Tropical Acne. This variety is a severe type that occurs in the tropics.
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It differs from acne vulgaris in several ways. It affects an older age group, is located chiefly on the back, buttocks and thighs, and is pustular, cystic and nodular. Comedones are not visible or they are sparse. Treatment is ineffective, unless there is a change to a cooler climate.
PATHOLOGY There is an intrafollicular hyperkeratosis that appears first in the excretory ducts of the sebaceous glands which are enlarged. The keratin collects in the follicular lumen and, combined with sebum, forms the comedo. After the comedo is produced, the hypertrophic sebaceous gland becomes smaller and ultimately atrophic. Coagulase-positive staphylococci are usually found on culture from acne lesions. Whether the myriads of Propionibacterium organisms present take part in the inflammation is unknown. It seems in some cystic cases that a virus, as hypothecated by Melczer in pyoderma vegetans, may be a factor, although there is no proof of this conjecture. TREATMENT Treatment varies according to the severity of the disease, the age, and the type of the patient's skin. In mild cases in which comedones and a few papules and pustules are present, expression of the comedones, topical lotions, and hot compresses twice weekly of Vleminckx's solution probably will clear up the skin condition. An antiseborrheic shampoo may be indicated. In more extensive cases in which there is a good deal of inflammation and pustulation, sulfamethoxazole (Madribon) or sulfadimethonine (Gantanol) should be given internally for a few weeks. The dose of Madribon required is usually one tablet (0.5 gm.) morning and night for two weeks, and then a reduced dose of one tablet daily for three to four weeks. The dose of Gantanol is two tablets (0.5 gm.), two or even three times a day for two weeks, followed by two tablets morning and night for one month. The Vleminckx's compresses may be used three times a week, or even oftener, care being exerted not to provoke excessive dryness. Rarely patients cannot tolerate sulfonamides. In such cases tetracyclines may be substituted. Drainage of pustules and expression of comedones at weekly intervals is an important part of treatment. Severe cases are in two categories: 1. There are cases of long duration in which scarring is a prominent feature and pustules and nodules persistently recur. The face, the submandibular regions, the back of the neck, the upper back and the chest are favorite locations. In this type of case a search for focal infections
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should be made. Teeth, tonsils, sinuses, etc. should be cleared of infection. Acne surgery and hot Vleminckx's compresses should be utilized. These hot compresses may be given daily for an hour or two. Cultures and antibiotic sensitivity tests should be made and appropriate sulfa drugs or antibiotics prescribed. X-ray treatment may be desirable, especially in acne of the back of the neck, upper back and chest. After the acne is cleared, dermabrasion may be indicated for pitted scars of the face, but should not be used on the back or chest. 2. Cystic and nodular eruptions which are recalcitrant to most forms of treatment are encountered. Many such patients have had desultory courses of antibiotics, steroids, x-rays and hormones. Sometimes such patients have had to give up college and are invalided, being unable to sleep because of painful sores on the back, face and neck. Such patients may run a temperature off and on for a couple of years, and become addicted to narcotics given for pain, or to steroids. There are cases of acne that are mutilating and repulsive. These may justly produce a state of mental despair and frustration that interferes with normal social contacts. Each such case requires individual consideration. Study with antibiotic sensitivity tests may help in finding an antibiotic that is specific. It may be sodium oxacillin (Prostaphlin), tetracycline-amphotericin-B (Mysteclin F), or just oral penicillin. Whatever it is, it must be continued for perhaps a year or more, as long as it keeps the patient well and comfortable. In other cases no antibiotic does any good. One may discover that the patient had an inadequate dosage of x-ray and upon administering the remaining permissible quota the acne is cured. Some parents are so frightened about the dangers of radiation that they do not give permission for x-ray treatment until their child has been subjected to years of great suffering and tremendous doses of antibiotics and cortisone treatment. Hot compresses of Vleminckx's solution, diluted, are usually effective and may be used every alternate day or daily for an hour or more. In the foregoing discussion of the treatment of acne, little has been said about diet and about the use of corticosteroids and estrogens. These subjects are covered now.
Diet The importance of diet is a debatable question. Acne is a glandular disease. Androgens are the important etiological factors. Whether diet has any influence is a matter of personal opinion. It is customary to avoid chocolate, shellfish, nuts and ice cream. The intake of fried foods, pastry and candy should be limited. Eggs, cream, milk, butter, cheese, pork and bacon should be eaten in moderation. In general some kind of fruit should be eaten at breakfast and either two green vegetables or a green vegetable and a salad at both luncheon and dinner.
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Systemic Treatment CORTICOSTEROIDS. It is a paradox that corticosteroids which may produce acne are also effective anti-inflammatory agents in its treatment. In some cases of severe cystic and nodular acne with much foreign body type of inflammatory reaction, corticosteroid treatment is more effective than antibiotic treatment. In chronic disease states, like acne, it must be realized that once corticosteroid therapy is started, it is difficult to stop. The unfortunate results of corticosteroid therapy are that patients eventually realize that nothing else helps and become actually addicted to corticosteroids. The dosage required is usually small, but the ultimate onset of Cushingoid symptoms makes one wonder whether, after all, it has been worthwhile to cause the temporary disappearance of horrible and mutilating types of acne. Small doses and free intervals are advisable but less than one-half the average therapeutic dose for other diseases is useless. The benefits are sometimes augmented by simultaneous antibiotic therapy, although most of the cases in which corticosteroids have been used are those that failed to be completely cleared by antibiotic and other standard therapy. ESTROGENS, NORETHYNODREL, VACCINES. Cyclic estrogen therapy is extremely effective for acne in a small number of girls. However, the author rarely uses estrogcn therapy because it generally upsets the menstrual cycle and only rarely accomplishes the desired effect. Treatment of acne in older women has been successful by the use of the oral contraceptive, norethynodrel and similar products, which inhibit the secretion of gonadotropin by the anterior pituitary gland and thus suppress ovulation. When ovulation is suppressed, no corpus luteum is formed. Being absent, it produces no progesterone. The cyclic use of estrogens and progestins to mimic the normal female menstrual cycle now has become a standard practice. By the use of this sequential therapy in which estrogen is given orally for 20 days and progestin daily for the last five days of the cycle, fertility is controlled and the irregularities of the duration, occurrence and amount of withdrawal bleeding that occurred with cyclic estrogen therapy alone have been largely avoided. Administration of progestational agents for five or more days of the terminal part of the cycle produces a sharp definite withdrawal bleeding period. Although the anovulatory effects of norethynodrel and similar products are reliable, the anti-acne effects are less dependable. In fact, acne is often worsened during the first few months of contraceptive therapy. This unfavorable result is probably due to the progesterone contained in the contraceptive. This augmentation of the acne combined with nausea, enlargement and tenderness of the breasts, gain in weight and other side effects of contraceptive therapy dampens one's enthusiasm for it, although results are often excellent.
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Vaccine therapy is occasionally of value in persistent pustular types, if used only to supplement other more reliable methods.
Local Treatment Specific admonitions regarding cleansing of the skin are important. Cleansing should be accomplished by soap and water. When the skin is extremely oily, the patient in addition should cleanse the skin with an alcoholic lotion. Towels and pillowcases should be fresh and clean. The dermatologist should regulate the use of all proprietary cosmetics. Whenever infection is present, creams and greasy cleansing agents should not be used. Facial massage should never be used in the presence of infection. Local therapy is directed to the drying of the skin and to the inhibition of sebaceous gland activity. Sulfur in various forms, still the most effective topical remedy, is incorporated into most of the preparations compounded by the pharmacist and in the modern commercial medications. In addition to sulfur, such substances as resorcinol, antibacterial agents, estrogens and peeling chemicals are used in cosmetically elegant lotions and creams. The modern commercial preparations are too numerous to list. These have overshadowed the use of the still effective medications such as Saturated Lotio Alba. In swere pustular and cystic cases, the liberal use of hexachlorophene locally is, all too seldom, beneficial. The purpose is to keep staphylococci at a minimum upon the skin. The authors' directions are as follows: Wash face for five minutes. Take a tub bath with pHisoHex each night or morning, washing all over for 15 minutes, especially the armpits and anogenital region. It is important to keep the skin surgically clean. Keep the fingernails short and clean also. Shampoo twice a week with pHisoHex. Keep the teeth well cleaned and use dental floss after each meal. Sublesional injections of corticosteroids for keloids, cysts and inflammatory nodules will cause rapid disappearance. Often after such an injection the site becomes depressed below the surface, but this is temporary and usually levels out within a few weeks. SLUSH TREATMENT. Hyperemia and peeling may be produced by solid carbon dioxide slush. The author does not incorporate sulfur into the slush. The solid carbon dioxide is finely powdered by placing it into a strong canvas bag, such as a bank money bag, and pulverizing the ice with a mallet. The powdered dry ice is placed onto four layers of gauze 8 inches square. The corners are gathered together, and a rubber band secures the dry ice in a ball. Using the gathered corners as a handle, it is dipped into a cup containing acetone, just enough to moisten it. It is then touched to a towel to take away the excess acetone. The bag is then gently rubbed over the treatment site, care being exercised to avoid overtreatment, ~ince severe burns may be caused. This treatment causes some inflamJnatory reaction with edema, followed by desquamation. It may be repeated ~nce or twice weekly.
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SURGICAL TREATMENT. Local surgical treatment is imperative to bring about quick resolution of the pustules and to empty the pores of comedones, which may act as foreign bodies. The surface of the lesion is nicked with a No. 11 Bard-Parker scalpel and then the contents are expressed with a comedone extractor. Several types of these instruments are available. The incisions should follow Langer's lines. Scarring is not produced when the incision is performed with care. HOT COMPRESSES. Of the local remedial applications, hot compresses of dilute Vleminckx's solution (lime sulfurated solution) are most effective. One or two tablespoonfuls of the solution to one pint of hot water are used. Compressing is done for twenty minutes once or twice weekly in the case of average severity. In severe cases the compressing may be done oftener, even daily, and for longer periods extending to two or three hours. Excessive compressing may lead to extreme dryness and peeling. In patients who cannot tolerate sulfur, hot boric acid compresses may be substituted. These are also used for mild cases of acne that do not require the Vleminckx's solution compresses. Detailed Directions for Hot Vleminckx's Solution Compresses To 1 pint of hot water add 1 tablespoonful of Vleminck.x's solution. Make 2 compresses out of a double thickness of flannel and have them large enough to cover the entire face. Heat the solution in a saucepan, then soak the compresses in the solution and apply them to the face, changing one for the other every minute for 20 minutes. Protect eyelids by a thick coat of Vaseline. To avoid burning the fingers, a towel may serve as a wringer, or you may use compresses with hem at each end into which a stick can be inserted. Unless otherwise directed, it is permissible to use the same pieces of flannel again and again for these treatments. Frequency of application-twice weekly. Note: Use old saucepan as solution will soil saucepan.
For pustular and moist exudative cystic lesions on the chest and back, hot potassium permanganate solution baths may be helpful. Five or six 30-mg. tablets are put into half a tub of hot water in which the patient lies for 20 to 30 minutes. SCALP. The treatment of acne is frequently directed against concomitant seborrheic dermatitis of the scalp. Selsun suspension (Abbott) is the best remedy. Occasionally other medicated shampoos and lotions are useful.
X-ray Therapy All kinds of statements in favor of and opposed to x-ray treatment of acne have been made during the last 35 years. The author has constantly endeavored to avoid prejudice in this matter and as a result his opinion has changed through the years. In all of his writings he has never questioned the effectiveness of x-rays, as some with less experience have done. His chief concern has been possible injuries from radiation. Like Communism
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it is a hazard we must face. We are exposed to it day and night, from all sides, in all places. Whether we like it or not, it is there and one electron collision can produce a mutation just as one radical can kill a president. Since time immemorial all living creatures have been bombarded by radiation and without radiation life would never have developed or survived on this planet. The author practically never gives x-ray therapy to acne patients because he wishes to be conservative and shares, perhaps with more enlightenment than the public, the general fear of radiation. Roentgen therapy of acne is withheld until other methods of treatment have been used and then applied only in severely invaliding and mutilating cases. TECHNIQUE. An arbitrary outline of x-ray dosage for treatment of acne must necessarily be subject to individual variation. Fortunately, severe acne rarely occurs in those who have fair skins that are sensitive. The severe cases of acne are found chiefly in brunets and mostly young men are so afflicted. As x-rays are used only in such severe cases the dosages recommended are those suitable for coarse brunet male skin. The number of treatments will depend upon the dosage given each treatment, the anode-skin distance and the quality of radiation. One must understand the exit dose and in treatment about the face count how much the exit dose adds to each exposure. Cones are used except upon the back where overlapping is desirable. The number of exposures is thus also governed by the sum total of the doses of all exposures and by the clinical changes in the skin which appear during the course of treatment. Improvement usually manifests itself by lessened development of new lesions, by an inhibition of the secretions of the sebaceous glands causing a diminution in the amount of oil on the skin. These changes are first manifest at the point of focus of the central beam of x-rays. The quality of radiation should be in the realm of HVL 0.6 to 1.0 mm. aluminum. This is produced by voltages ranging from 60 to 100 kv. The less penetrating radiation exerts a more superficial action than the more penetrating qualities but has less exit dose. Roentgen-ray dosage should be fractional. The classical dose is 75 r given weekly to the affected areas with the gonads, trunk, eyes, eyebrows, scalp, hair and thyroid shielded. Midface exposures should never be combined with sideface exposures. A course of 8 to 10 treatments will suffice in many instances but 2 or 3 more may be necessary. The sum dosage of all exposures should not exceed 1000 r to anyone area. As previously stated, this applies to young men with brunet oily skin. The anode-skin distance influences not only the spread of the beam but also the exit dose and the depth dose. A distance of 15 to 25 cm. is recommended. The operator cannot be guided solely by such measurements, but must carefully study the biologic response of the skin at each visit, paying particular attention to the parts of the skin in the path of the direct beam. Scrutiny should be made for cessation of new lesions, erythema, and a drying up of exudation.
REFERENCES Andrews, G. C.: Acne. Ohio State M. J. 59: 910-913 (Sept.) 1963; A.M.A. Arch. Dermat. 84: 711-716 (Nov.) 1961.
Andrews, G. C., Domonkos, A. N. and Post, C. F.: Treatment of acne vulgaris. J.A.M.A. 146: 1107-1112 (July 21) 1951.
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Finkelstein, R. A., Forchielli, E. and Dorfman, R. I.: Estimation of testosterone in human plasma. J. Clin. Endocrinol. 21: 98-101 (Jan.) 1961. Kurtin, A.: Corrective surgical planing of skin. A.M.A. Arch. Dermat. & Syph. 58: 389-397 (Oct.) 1953. Lasher, N., Lorincz, A. L. and Rothman, S.: Hormonal effects on sebaceous glands in the white rat: Ill. Evidence for the presence of a pituitary sebaceous gland trophic factor. J. Invest. Dermat. 24: 499-505 (May) 1955. Melczer, M.: On the etiology of localized pyoderma papillaris and exulcerans and generalized pyodermitis vegetans. Dermat. Tropica 1: 61-74 (July) 1962. Palitz, L. L.: Abstract of a preliminary report on norethynodrel (Enovid) in the control of acne in the female. Tr. Bronx Derm. Soc., Arch. Dermat. 86: 237-238, 1962. Palitz, L. L., Milberg, I. L. and Kantor, 1.: Enovid for acne in the female. Skin 3: 243245 (Aug.) 1964. Pincus, G., Chang, M. C, Zarrow, M. X., Hafez, E. S. E. and Merrill, A.: Studies on the biological activity of certain 19-norsteroids in female animals. Endocrinology 59: 695 (Dec.) 1956. Smith, M. A. and Waterworth, P. M.: Bacteriology of acne vulgaris in relation to treatment with antibiotics. Brit. J. Dermat. 73: 152-159 (April) 1961. Strauss, J. S. and Pochi, P. E.: Effect of Enovid on sebum production in females. Arch. Dermat. 87: 366-368 (March) 1963. Strauss, J. S. and Pochi, P. E.: Effect of progestin-estrogen therapy in acne. J.A.M.A. 190: 815-819 (Nov. 30) 1964. Strauss, J. S., Kligman, A. M. and Pochi, P. E.: Pathologic patterns of the sebaceous glands. J. Invest. Dermat. 30: 51-61, 1958. Strauss, J. S., Kligman, A. M. and Po chi, P. E.: Effect of androgens and estrogens on human sebaceous glands. J. Invest. Dermat. 39: 139-156, 1962. 115 East 61st Street New York, N.Y. 10021