Acne Conglobata

Use of Cortisone and Corticotropin in Therapy

EUGENE M. FARBER, M.D., San Francisco, and EARL R, CLAIBORNE, M.D., Oakland

ACNE CONGLOBATA is a disease characterized by the

presence of cystic abscesses, confluent follicular and perifollicular inflammations and intercommunicating cysts. These lesions affect primarily the face, neck, chest and shoulders and are the cause of serious and disfiguring scars. Patients with this disease are usually from 15 to 25 years of age and have an antecedent history in most cases of acne vulgaris of varying degrees of severity. Acne conglobata may have a fulminating onset and course. Conventional therapy, consisting of anti. biotics, local measures and roentgen irradiation, is frequently disappointing. Because of the explosive nature of the lesions and the seemingly disproportionate scarcity of bacterial infection in them, the possibility of underlying Arthus or Shwartzman reaction was considered. On this presumption, the authors administered cortisone and corticotropin to six patients with acne conglobata. The patients ranged in age from 13 to 18 years. Four were male and two female. A cardiolipin blood test for syphilis was done in all. cases and in all the results were negative. The total number of leukocytes in the blood was within normal limits in all cases, as were the differential leukocyte count, hemoglobin content, sedimentation rate, urinary 17-ketosteroid determinations, basal metabolic rate, serum cholesterol and results of urinalysis. No abnormalities were noted in x-ray films of the chest. In five cases staphylococci grew on cultures of purulent exudate from the cysts, and in one the culture was sterile. Antibiotics were employed and the agent used in each case was the one to which the organism was found to be most sensitive as determined by sensitivity studies. CASE 1. An 18-year-old male who had had acne vulgaris for four years, had explosive onset of acne conglobata in Julv 1953. Papules, pustules and intercommunicating cysts 1 to 2 cm. in diameter involved the chest, face and upper back. Previous intensive therapy had been relatively unsuccessful. Treatment consisted of daily intravenous infusions of 40 units of corticotropin (ACTH) in 500 cc. of
From the Division of Dermatology, Department of Medicine, Stanford University School of Medicine. Presented before the Section on Dermatology and Sy1philology at the. 83rd Annual Session of the California Medical Association, Los Angeles, May 9-13, 1954.

* Six patients with acne conglobata were treated with cortisone and adrenocorticotropic hormone. Definite immediate improvement was observed in all of them. In three cases control of the disease was maintained on relatively low doses of steroid.,In one case there was response to superficial x-ray therapy after the acute phase of the disease had subsided in response to steroids. Resistance to steroid therapy apparently developed in one patient after approximately 18 months of treatment. One patient responded to treatment and then remained well (for two months when last observed) although steroids and all other treatment were discontinued. The combined use of antibiotics and steroids in the patients treated gave the best results.
5 per cent dextrose in distilled water. Definite improvement was noted within two days. The patient was discharged from the hospital one week after admission, greatly improved. Relapse occurred after dismissal from the hospital. At the time of report, therapy consisted of 40 units of corticotropin gel given intramuscularly two times -a week, supplemented with achromycin by mouth. The lesions again were reduced in size and the general appearance of the patient was improved. CASE 2. A 16-year-old girl who for three years had had acne vulgaris, had explosive onset of acne conglobata. There were many papules, cysts, pustules and keloid-like lesions on the face, back -and chest. Therapy carried on over a four-month period was unsuccessful. Prompt response was noted within 72 hours after three daily intravenous infusions of 20 units of corticotropin in 500 cc. of 5 per cent dextrose in distilled water. The patient was also given 2 gm. of terramycin daily. She was discharged from the hospital after five davs, considerably improved. A mild exacerbation occurred two days after leaving the hospital. CASE 3. A 13-year-old girl had acne vulgaris for six months prior to an explosive onset of acne conglobata involving the face, chest and shoulders. Previous therapy had been relatively unsuccessful. Administration of 75 mg. of cortisone and 1 gm. of aureomycin by mouth daily was begun. ImproveCALIFORNIA MEDICINE

76

Figure 1.-Left, cystic and keloid lesions of the face (Case 6) before steroid therapy. Right, after steroids were added to treatment for a period of two weeks.

Figure 2.-Left, crusting and hypertropic scars on back (Case 6) before addition of steroids to therapy. Right, after two weeks of steroid therapy.

ment was noted after five days and was maintained for six weeks. On discontinuance of the therapy there was mild exacerbation of the lesions. CASE 4. A boy 18 years of age had acne vulgaris for six years, when an explosive onset of acne conglobata occurred. All previous therapy had been unsuccessful. Many pustules, pitted scars, keloids and cysts were noted on the upper back, chest and

face. Treatment consisting of 150 mg. of cortisone given daily for six days by mouth resulted in definite improvement, in that the cysts decreased in size and no new ones appeared. CASE 5. A 14-year-old boy who was examined in the Stanford University outpatient clinic in July
VOL. 81. NO. 2 * AUGUST 1954

1952, had had acne vulgaris for one year. In March of 1952 acne conglobata developed explosively over the face, chest and upper back. Numerous pustules, cysts and intercommunicating keloid-like lesions practically covered the face. Previous therapy, including superficial x-ray treatment, had been unsuccessful. The patient was hospitalized and given 200 mg. of cortisone daily and 500 mg. of erythromycin four times daily. There was response to therapy within 48 hours, manifested by flattening of the cysts and a decrease in the number of pustules and keloids. The patient continued to improve for the next four months while doses of cortisone and terramycin were gradually reduced. Additional x-ray therapy

77

was administered with heavier- filtration and the disease remained under control for the next ten months. An exacerbation occurred in December 1953 and the patient was hospitalized and given 40 units of corticotropin in 500 cc. of 5 per cent dextrose in distilled water intravenously over an eight-hour period. Improvement was slight but definite and the patient was discharged from the hospital after one week. Administration of cortisone, 75 mg. -daily, and erythromycin, 600 mg. daily, was continued. New lesions developed after discharge from the hospital and apparently resistance to the therapeutic effects of the steroid had developed. CASE 6. A 15-year-old boy had acne vulgaris for six months before an explosive onset of acne conglobata occurred. There were many hypertrophic crusted lesions, depressed scars, keloids and fluctuant cysts on the back, central portion of the chest, face and scalp. Corticotropin gel (30 units) and terramycin were administered in addition to local therapy in the form of hot compresses. The patient was discharged from the hospital, considerably improved, after ten days of this therapy. The medication was gradually withdrawn and, when observed two months later, the patient had been asymptomatic without treatment of any kind.
DISCUSSION

There were certain common factors in the six cases here reported. The patients were between the ages of 13 and 18 and all had acne vulgaris before the development of acne conglobata. All, had improvement within two to six days after steroid therapy was begun. The rate of response appeared to be influenced by the route of administration of the drug -earlier when given intravenously than intramuscularly or orally. The route of administration was determined by the severity of the disease process. It was further significant that staphylococcae were cultured from exudate in five of the six cases. Although the influence of adrenal cortical hormones upon hypersensitivity is still in the early stage of evaluation, it seems inevitable that studies of these agents will reveal basic fundamental information concerning the immunological and hypersensitivity states observed in clinical medicine.5 The mechanisms involved in the use of cortisone and adrenocorticotropic hormone in hypersensitivity reactions are poorly understood. In rabbits antigenantibody union is blocked if steroids are given in massive dosage. There does not appear to be a human counterpart, for the small dosage which is

clinically effective in man does not consistently inhibit or suppress antibody formation. Furthermore, if preformed antibody is given, it disappears too slowly to explain the dramatic clinical improvement observed early in patients who receive steroid therapy.3 Conversely, antibodies produced by previous vaccination have been shown to decrease by as much as 25 per cent under the influence of cortisone.' This would suggest that there is a suppression of antibody formation. "It is not completely clear why the passive Arthus phenomenon is unaffected, whereas in the Shwartzman phenomenon, a histologically similar reaction, the effects of the preparatory dose of toxin induces an unusually severe reaction whereas the second, or challenge dose of toxin, is inhibited."3 Neither has blood vessel damage, which is believed to be a constant change in hypersensitivity reactions, such as the Arthus and Shwartzman phenomena, been exhibited in biopsy specimens from any of the cases observed by the authors. When administered in therapeutic doses cortisone suppresses adrenal cortex activity by inhibiting pituitary adrenocorticotropic output.6 The urinary 17ketosteroid determinations usually reflect a decrease in androgen secretion,4 especially in females. In the six patients in the present study the values for urinary excretion of 17-ketosteroids were normal before and during steroid therapy. Although it is impossible in the light of known experimental data to explain the improvement noted in the cases here reported upon, it was probably owing to the steroids, especially when the dramatic response to treatment and the exacerbations upon discontinuance of such therapy is considered.
Stanford Lane Hospital.

REFERENCES

1. Carlisle, J. M., Gibson, A., and Schmatolla, E.: Cortisone, Postgrad. Med., 2:113, 1950. 2. Germuth, F. G., Jr., Oyama, J., and Ottinger, B.: The mechanism of action of Compound E and ACTH in experimental hypersensitivity in rabbits, J. Exper. Med., 94:139170, 1951. 3. Kass, E. H., Finland, M.: Adrenocortical hormones in infection and immunity, An. Rev. Microbiol., 7:373, 1953. 4. Mercadel, P. J., Targ, G. M., and Bassas, G. M.: The investigation of urinary 17-ketosteroids and pregnandiol in juvenile acne, Acta-dermo-sifilogr., 9:819, 1952. 5. Raffel, S.: Factors Influencing Immunity, Immunity Hypersensitivity-Serology, chap. 12, p. 192, 1953. 6. Sprague, R. G., et al.: Observations on the physiologic effects of cortisone and ACTH in man, Arch. Int. Med., 85: 199-258, 1950.

78

CALIFORNIA MEDICINE