Long-Term Results of Isotretinoin in the Treatment of 68 Patients with Hidradenitis Suppurativa

Long-term results of isotretinoin in the treatment of 68 patients with hidradenitis suppurativa

Jurr Boer, MD, PhD, and Mirjan J. P. van Gemert, MD Deventer, The Netherlands

Background: Oral isotretinoin has been used to treat mild to severe hidradenitis suppurativa (HS). Objective: We reviewed the results of low-dose isotretinoin for 4 to 6 months in the treatment of 68 patients with HS. Methods: This is a retrospective study. Data are presented in terms of response rate, long- term follow-up, and the relation between response rate and severity. Results: In 16 patients (23.5%), the condition completely cleared during initial therapy and 11 patients (16.2%) maintained their improvement during the follow-up period. Treatment was more successful in the milder forms of HS. Conclusion: Monotherapy with isotretinoin for patients with HS usually has a limited ther- apeutic effect. (J Am Acad Dermatol 1999;40:73-6.)

Hidradenitis suppurativa (HS) is a chronic PATIENTS AND METHODS inflammatory disorder, usually located in the axil- The details of the patients at the start of the study are lae and genitocrural areas. Histopathologic studies shown in Table II. In the last 10 years, 68 patients (59 suggest that HS is a disease of the follicles with women, 9 men) with long-standing HS were treated apocrine involvement as a secondary event,1-4 so with oral isotretinoin as monotherapy for 4 to 6 months, the term acne inversa has been suggested.3,4 In as used in the treatment of acne vulgaris.5,11 In women some patients antibiotic and corticosteroid therapy of child-bearing age, effective contraception without or surgical management can control the disease. antiandrogens such as cyproterone acetate was used Isotretinoin is an effective treatment for acne con- throughout the treatment period. The severity of HS was 12 globata, with good long-term results,5 but the graded clinically according to O’Loughlin et al as response in HS is less well established. A few mild, moderate, or severe. Twenty patients (Table III) did not complete the prescribed minimum course of 4 investigators have evaluated the effects of months’ treatment. They dropped out for a variety of isotretinoin on HS, with mixed results. These case reasons including side effects (3 of 20 patients), poor reports and the results of studies with small num- response (7 of 20), a combination of side effects and bers of patients are summarized in Table I.6-10 poor response (7 of 20), and loss of motivation (3 of In an initial report we described our results from 20). Table III summarizes the treatment data. Clinical administration of low-dose isotretinoin to 21 status was judged by both the patients and the physician patients with HS; patients were observed for up to according to Dicken, Powell, and Spear,7 and was 24 months.9 In the present study we enrolled 68 scored as no change, improvement, marked improve- patients, including the already mentioned 21 ment, or clear, and graded accordingly from 0 to +3. patients, and focused on the response rate, long- After the completion of treatment, patients were term follow-up, and the possibility of a relation reexamined up to 6 months later. After this, data on clin- between response rate and severity. ical status and subsequent treatment for HS were col- lected by physical examination, status surveys, or tele- phone interviews. In our long-term follow-up we could identify an improvement score of +3 (virtually clear), From the Department of Dermatology, Deventer Hospital. but the remaining scores (+2, +1, etc) could not be Reprint requests: J. Boer, MD, PhD, Department of Dermatology, scored reliably by the physician or the patient. Deventer Hospital, Postbox 5001, 7400 GC Deventer, The Netherlands. Six patients received an intralesional injection of Copyright © 1999 by the American Academy of Dermatology, Inc. corticosteroid once for an abscesslike swelling during 0190-9622/99/$8.00 + 0 16/1/93164 isotretinoin treatment and four after the treatment

73 Journal of the American Academy of Dermatology 74 Boer and van Gemert January 1999

Table I. Summary of previously published studies of isotretinoin therapy for hidradenitis suppurativa (HS)

Duration of Duration Improvement No. of Dose treatment Follow-up of Severity score* Author(s) patients (mg/kg/d) (mo) (mo) HS (y) of HS (No. of patients)

Jones, Cunliffe, 3 1.0 4 — 20-30 Severe 0 (3) and King6 (1982) Dicken, Powell, 8 0.71-1.2 4 2-6 5-35 Extensive +3 (1), +2 (3), +1 and Spear7 (1984) and active (1), 0 (2), –1 (1) Norris and 6 1.0 4 2 Many Severe 0 (6) Cunliffe8 (1986) years Boer9 (1988) 21 0.5-0.67 4-6 3-24 1-25 Mild to +3 (6), +2 (5), severe +1 (3), 0 (1), dropped out (6) Brown, Gallup, 1 1.0 4 4 3 Severe +3 (1) and Brown10 (1988) *Improvement score: +3 = clear, +2 = marked improvement, +1 = improvement, 0 = no change, –1 = worse.

Table II. Patient and disease characteristics at Table III. Isotretinoin treatment of hidradenitis baseline suppurativa No. of patients 68 (F, 59; M, 9) No. of patients treated 68 Mean age and range (y) 32.6 (15-54) No. of patients who completed 48 Mean duration of HS and range (y) 4.8 (1-30) treatment No. of patients with HS alone 60 Mean daily dose of isotretinoin No. of patients with HS and acne 8 and range (mg/kg body weight) 0.56 (0.50-0.81) conglobata Mean duration of treatment and 5 (4-6) Affected areas (No. of patients) range (mo) Genitocrural 45 Mean duration of follow-up and 46 (6-107) Axillary 6 range (mo) Axillary and genitocrural 17

remaining 32 patients with a score of +2, +1, or 0 course. Patients who required any further therapy were at the end of treatment, an exact score at the end of rated as treatment failures. The chi-square test and the the follow-up period of this retrospective study Wilcoxon two-sample test were used to compare the was difficult to obtain and of no relevance, because outcomes for patients with initially different severity of all these patients were dissatisfied with their disease. response. At the end of the therapy with isotretinoin, none RESULTS of the patients with severe HS scored +3, compared In the present trial 68 patients were treated with with 16 patients with mild and moderate forms of isotretinoin, of whom 20 (29.4%) did not complete HS, a statistically significant difference (P < .01, the minimum initial 4 months of therapy. Table IV chi-square test). Furthermore, Table V indicates that shows that 16 (23.5%) of the 68 patients achieved patients with initially mild forms of HS were more a score of +3 (clear) at the end of treatment, 14 likely to achieve improvement scores of +2 and +3 (20.6%) of the 68 scored +2, 11 (16.2%) scored than were patients with moderate and severe forms; +1, and 7 (10.3%) scored 0. In 11 of the 16 respon- this difference was statistically significant (P < .05, ders with a score of +3 this response persisted Wilcoxon two-sample test). throughout the follow-up period (range, 6 to 107 months; mean, 57 months). The scores of the DISCUSSION remaining 5 patients decreased from +3 to +2 (3 The many different therapies used to treat HS patients), +1 (1 patient), or 0 (1 patient). For the indicate an absence of a standard and universally Journal of the American Academy of Dermatology Volume 40, Number 1 Boer and van Gemert 75

Table IV. Long-term response of HS to Table V. Responses to isotretinoin therapy in isotretinoin treatment (68 patients) patients with HS of different severities at base-

No. of patients line Improvement score At the end At the end Mean duration Clinical grading of the severity of treatment of of follow-up of HS at baseline 0 +1 +2 +3 Response HS (4-6 mo) follow-up and range (mo) Mild 0 0 2 4 +3 16 (23.5%) 11 (16.2%) 57 (6-107) Moderate 5 6 2 12 +2 14 (20.6%) NR NR Severe 2 5 10 0 +1/0 18 (26.5%) NR NR Drop-outs 20 (29.4%) Improvement score: +3 = clear, +2 = marked improvement, +1 = improvement, 0 = no change. NR, No relevance. disease. Furthermore, these authors advocated surgical intervention as the treatment of choice. They recommended the use of oral isotretinoin because accepted therapy. Because isotretinoin is effective of its antiinflammatory activity during the weeks for acne it seems reasonable to suppose that or months before surgery and perhaps also postop- isotretinoin might also be effective in HS. However, eratively. We agree that surgical treatment is the our experience with low-dose isotretinoin as first choice for all intertriginous lesions. Until monotreatment in 68 patients over a period of recently, wide excisions, well beyond the clinical almost 9 years confirms our early impression and borders of activity were recommended. The disad- previous reports (Table I) that isotretinoin is only vantages of surgery are the often long hospitaliza- moderately effective in the management of HS. Our tion and not always cosmetically acceptable study lacks a control group treated with antibiotics results. However, there are other, relatively simple as a comparison, so no statement as to relative effi- surgical treatments with excellent results such as 13 cacy can be made. However, many patients in our the deroofing technique and CO2 excision, both study had not responded to oral antibiotics or with second-intention healing.14 surgery, or had relapsed after such treatment. These It can be concluded from this study that response rates are less favorable than those monotherapy with isotretinoin is of limited value achieved in the treatment of acne conglobata. for HS. Severe acne conglobata can also be resistant to REFERENCES isotretinoin, because of the multiple, dissecting 5 1. Ackerman AB. Folliculitis and perifolliculitis. In: sinus tracts. Layton et al confirmed the finding that Histological diagnosis of inflammatory skin diseases. truncal acne responds less well than facial acne. 2nd ed. Philadelphia: Lea & Febiger; 1978. p. 641-713. Why truncal acne and HS respond less well to 2. Lever WF, Schaumburg-Lever G. Bacterial disease. In: isotretinoin and antibiotic treatment is unknown. Histopathology of the skin. 7th ed. Philadelphia: JB Lippincott; 1990. p. 322. Furthermore, it is known that patients with severe 3. Plewig G, Steger M. Acne inversa (alias acne triad, acne acne relapse more readily.5,11 The present study tetrad, or hidradenitis suppurativa). In: Marks R, Plewig indicated that the response of HS to isotretinoin is G, editors. Acne and related disorders. London: Martin Dunitz; 1989. p. 345-57. also related to the severity of the disease. 4. Boer J, Weltevreden EF. Hidradenitis suppurativa or acne It is unlikely that the dose of isotretinoin for HS inversa: a clinicopathological study of early lesions. Br J is important. In the treatment of acne a total cumu- Dermatol 1996;135:721-5. 5. Layton AM, Knaggs H, Taylor J, Cunliffe WJ. lative dose of more than 120 mg/kg produces sig- Isotretinoin for acne vulgaris—10 years later: a safe and nificantly better results than lower dosage regi- successful treatment. Br J Dermatol 1993;129:292-6. mens.5 In our study none of the patients with HS 6. Jones DH, Cunliffe WJ, King K. Hidradenitis suppurati- achieved this threshold dose of 120 mg/kg. va—lack of success with 13-cis-retinoic acid [letter]. Br J Dermatol 1982;107:252. However, as almost all studies in Table I show, it is 7. Dicken CH, Powell ST, Spear KL. Evaluation of doubtful whether higher dosage regimens would isotretinoin treatment of hidradenitis suppurativa. J Am produce significantly better results.6-8,10 Acad Dermatol 1984;11:500-2. 3 8. Norris JFB, Cunliffe WJ. Failure of treatment of familial Plewig and Steger stated that isotretinoin is, by widespread hidradenitis suppurativa with isotretinoin. itself, with rare exceptions, insufficient to stop the Clin Exp Dermatol 1986;11:579-83. Journal of the American Academy of Dermatology 76 Boer and van Gemert January 1999

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