R eview y RDS \, .. hidradenitis suppurativa, · · follicular occlusion, review Hidradenitis suppurativa Hulradenii-is suppurativa. Anupdate A. J. Papadopoulos, G. Kihiczak and R. A. Schwartz SUMMARY Hidradenitis suppurativa is a chronic and often disabling disease characterized by intermittent periods of inflammation and abscess formation in apocrine sweat gland-containing skin. Various therapies have been implemented in its treatment with variable results. Pathogenesis, histopathology and therapy of this disease are reviewed. Introduction Hiclradenitis suppurativa (HS) is a chronic disease of unknown etio logy that mainly affects the genito- femoral, perianal and axilla1y regions (1-4). The disease is believed to be fo ll icular in origin (1). HS has a higher prevalence in women than men ancl is estimatecl to affect 4 percent of women in the gen eral population (5) . Etiology HS often occurs in multiple members within fa milies, suggesting a genetic preclisposition (5). Various etiolo- gical agents have been associated. The increased inci- dence ofI-IS in obese women with acne led to the theo1y ofHS being associated with an hyperandrogenic endo- crine disorder (6,7) . One stucly clicl not find evidence for biochemical hyperanclrogenism in women affectecl with HS (8). Thus, th e role of androgens in HS is stili not clear. Smoking (9), lithium (10) ancl oral contra- ceptives (11) may also b e associatecl w ith HS, possibly as triggering factors . Nonetheless, the etiology of the clisease is unknown. Pathogenesis Historically, apocrinitis was believed to be the cle- fining histologic feature ancl pathogen~tic mechan ism of HS (12,13). Characteristic lobular abscesses in the apocrine glancl, clemonstrated histologically, seemecl to further implicate apocrine giand involvement in the manifestation of disease (12-14). Recently, histological evidence points to HS being a follicular disease (1,15- 19). Histological examination in the majority of speci- Acta Dermatoven APA Vol 9, 2000, No 4 ----- ~---------- - - 131 Hidradenitis suppurativa mens reveals follicular involvement, including poral occlusion and folliculitis (1). Apocrinitis as the dominant histological feature is found in only a small number of specimens (1,17). Furthermore, a paucity of apocrine glancls was demonstrated in the genitofemoral region, one area commonly affected by HS (1). This fincling supports the theory that apocrine glancl inflammation is not the etiological and pathogenetic mechanism of I-IS, but rather a seconda1y manifestation of follicular involvement (1). Glinical features HS may arise singularly or multifocally in the genito- femoral, perianal and axilla1y areas (1-4). The lesions are painful and have a foul odor attributed to bacterial colonization. Erythematous dermal abscesses form that measure up to 2 cm in cliameter. Untreatecl abscesses will graclually increase in size and may drain to the surface. The course of HS is chronic ancl remitting, with new abscesses arising in previously unaffected areas or in regions of past involvement. Scarring, fibrosis and sinus tract formations are manifestations of late clisease. Strictures can occur seconda1y to sinus tracts; fistulas may also complicate I-IS. Squamous cel! carcinoma is a rare sequella oflongstanding HS (20-24). These cancers may be locally aggressive with distant metastases and a high mortality rate (25). Glinical associations The follicular occlusion triad consists of HS, acne conglobata and perifolliculitis capitis abscedens et suffo- diens (26-28). Arthritis ofperipheral joints and the axial skeletion may rarely be associated with HS (29-32) . HS has also been linked to Crohn's disease (33-35) . One study reported 24 out of 61 patients with I-IS w ere also diagnosed with Crohn's clisease, which predated the HS by an average of 3.5 years (35) . Acanthosis nigricans and Fox-Fordyce disease may predispose to HS (36). Pyoderma gangrenosum (3 7, 38) and p yode rma vegetans (27) have also been associated with hic.lra- denitis suppurativa. Therapy Treatment ofhidraclenitis suppurativa is challenging. Late stage disease , evidenced by the formation of sinus tracts, fibrosis and scarring, usually necessitates surgical intervention. Early HS is often best treated with antibio- tics in our experience, although few clinical trials are available (39). Three months ' of treatment with topical clindamycin decreased the number of abscesses, infla- mmatory nodules and pustules in twenty-seven patients with chronic HS ( 40). Systemic tetracycline therapy bas shown similar clinical effectiveness (39). Others and also we oft:en recommend intrealesional corticosteroids in early stage disease ( 41). The use of cyproterone acetate and ethinyl estradiol achieved successful clinical results in four women with chronic HS (42); clinical impro- vement with cyproterone acetate and ethinyl estradiol was also described in another study (43). Isotretinoin is only slightly effective in controlling the c.lisease ; clinical improvement is seen in patients with mile! HS ( 44). The clearing of chronic, refractory perianal HS was seen after treatment with cyclosporin for conco- mitant pyoderma gangrenosum (38). Medica! therapy is of limited value once HS has progressed past its early stage (2). The surgical option of choice for late stage HS is wide local excision w ith healing by secondary intention (41) . One study examined patients with chronic HS who lud undergone surge1y between the years of 1976 and 1997 (4) . An estimated 72-month follow-up revealed that 45% of the patients had recurrence of loca l HP (4) . A 100% recurrence rate was reported after drainage procedures , while limitecl ancl wicle local excision techniques hacl a recurrence rate of 42.8% anc.l 27%, respectively ( 4). More recently, carbon c.lioxide laser excision has been propo- sed asa better alternative to conventional surge1y (2,45) . Carbon dioxide laser excision offers better hemostasis and visualization of abscessecl tissue than conventional surgical techniques, allowing more accurate excision (2) . l. Jemec GB, Hansen U. Histology of hidradenitis suppurativa. J Am Acad Dermatol 1996; 34: 994-9. 2. Finley EM, Ratz Jl. Treatment of hidradenitis suppurativa with carbon dioxide laser excision and second-intention healing. J Am Acad Dermatol 1996; 34: 465-9. 3. Boer J, van Gemert M]. Long-term results of isotretinoin in the treatment of 68 patients with hidradenitis suppurativa. J Am Acad Dermatol 1999; 40: 73-6. Review 132 Acta Dermatoven APA Vol 9, 2000, No 4 Review Acta Dermatoven APA Vol 9, 2000, No 4 Hidradenitis suppurativa 4. Ritz JP, Runkel N, Haier J, Buhr HJ. Extent of surgery and recurrence rale of hidradenitis suppurativa. IntJ Colorectal Dis 1998; 13:164-8. 5. Jemec GB. The symptomatology of hidradenitis suppurativa in women. Br J Dermatol 1988; 119: 345- 50. 6. Harrison BJ, Read GF, Hughes LE. Endocrine basis for the clinical presentation of hidradenitis suppurativa. Br J Surg 1988; 75: 972-5. 7. Mortimer PS, Dawber RP, Gales MA, Moore RA. Mediation of hidradenitis suppurativa by androgens. Br Med J 1986; 292: 245-8. 8. BarthJH, Layton AM, Cunliffe WJ. Endocrine factors in pre- and postmenopausal women with hidradenitis suppurativa. Br J Dermatol 1996; 134: 1057-9. 9. Konig A, Lehmann C, Rompel R, Happle R. Cigarette smoking as a triggering factor of hidradenitis suppurativa. Dermatology (Basel) 1999; 198: 261-4. 1 O. Gupta AK, Knowles SR, Gupta MA et al . Lithium therapy associated with hidradenitis suppurativa: case repo rt and a review of the dermatologic side effects of lithium. J Am Acad Dermatol 1995; 32 (2 Pt 2): 382-6. 11. Stellon AJ, Wakeling M. Hidradenitis suppurativa associated with use of oral contraceptives. BMJ 1989; 298: 28-9. 12. Brunsting HA. Hidradenitis suppurativa: abscess of the apocrine sweat gland. Arch Dermatol Syphilol 1939; 39: 108-20. 13. Benedek T. Hidradenitis suppurativa. Acta Derm Venereol (Stockh) 1957; 37 (suppl 37): 1-47. 14. Ebling FJ. Apocrine glands in health and disorder. IntJ Dermatol 1989; 28: 508-11. 15.Jemec GB, Thomsen BM, Hansen U. The homogeneityofhidradenitis suppurativalesions. Ahistological study of intra-individual variation. APMIS 1997; 105: 378-83. 16. Boer J, Weltevreden EF. Hidradenitis suppurativa or acne inversa. A clinicopathological study of early lesions. Br J Dermatol 1996; 135: 721-5. 17. Yu CC, Cook MG. Hidradenitis suppurativa: a disease of follicular epithelium, rather than apocrine glands. Br J Dermatol 1990; 122: 763-9. 18. Attanoos RL, Appleton MA, Douglas-Jones AG. The pathogenesis ofhidradenitis suppurativa: a closer look at apocrine and apoeccrine glands. Br J Dermatol 1995; 133: 254-8. 19. Jansen T, Plewig G. ChL~sification of suppurative hidradenitis. Hautarzt 1994; 45: 652-3. 20. Manolitsas T, Biankin S, Jaworski R, Wain G. Vulva! squamous cell carcinoma arising in chronic hidradenitis suppurativa. Gynecol Oncol 1999; 75: 285-8. 21. Shukla VK, Hughes LE. A case of squamous cell carcinoma complicating hidradenitis suppurativa. Eur J Surg Oncol 1995; 21: 106-9. 22. Perez-Diaz D, Calvo-Serrano M, Martinez-Hijosa E et al. Squamous cell carcinoma complicating perianal hidradenitis suppurativa. Int J Colorectal Dis 1995; 10: 225-8. 23. Mendonca H, Rebelo C, Fernandes A et al. Squamous cell carcinoma arising in hidradenitis suppurativa. J Dermatol Surg Oncol 1991; 17: 830-2. 24. Zachary LS, Robson MC, Rachmaninoff N. Squamous celi carcinoma occurring in hidradenitis suppurativa. Ann Plast Surg 1987; 18: 71-3. 25. Dufresne RG Jr, RatzJL, Bergfeld WF, Roenigk RK. Squamous cell carcinoma arising from the follicular occlusion triad. J Am Acad Dermatol 1996; 35: 475-7. 26. Llbow LF, Friar DA. Arthropathy associated with cystic acne, hidradenitis suppurativa, and perifolliculitis capitis abscedens et suffodiens: treatment with isotretinoin. Cutis 1999; 64: 87-90. · 27. Boyd AS, Zemtsov A. A case of pyoderma vegetans and the follicular occlusion triad. J Dermatol (Tokyo) 1992; 19: 61-3. 28. Chicarilli ZN. Follicular occlusion triad: hidradenitis suppurativa, acne conglobata, and dissecting cellulitis of the scalp. Ann Plast Surg 1987; 18: 230-7. - ------------- - --~133 Revie w AUTHORS' ADDRESSES Hidradenitis suppurativa 29. Hamoir XL, Francois RJ, Van den Haute V, Van Campenhoudt M. Arthritis and hidradenitis suppurativa diagnosed in a 48-year-old man. Skeleta! Radiol 1999; 28: 453-6. 30. Bhalla R, Sequeira W. Arthritis associated with hidradenitis suppurativa. Ann Rheum Dis 1994; 53: 64-6. 31. Rosner IA, Burg CG, Wisnieski JJ et al. The clinical spectrum of the arthropathy associated with hidradenitis suppurativa and acne conglobata. J Rheumatol 1993; 20: 684-7. 32. Vasey FB, Fenske NA, Clement GB et al. Immunological studies of the arthritis of acne conglobata and hidradenitis suppurativa. Ciin Exp Rheumatol 1984; 2: 309-11. 33. Roy MK, Appleton MA, Delicata RJ et al. Probable association between hidradenitis suppurativa and Crohn's disease: significance of epithelioid granuloma. Br J Surg 1997; 84: 375-6. 34. Tsianos EV, Dalekos GN, Tzermias C et al. Hidradenitis suppurativa in Crohn's disease. A further support to this association. J Ciin Gastroenterol 1995; 20: 151-3. 35. Church JM, Fazio VW, Lavery IC et al. The differential diagnosis and comorbidity of hidradenitis suppurativa and perianal Crohn's disease. IntJ Colorectal Dis 1993; 8: 117-9. 36. Stone OJ. Hidradenitis suppurativa following acanthosis nigricans. Report of two cases. Arch Dermatol 1976; 112: 1142. 37. Shenefelt PD. Pyoderma gangrenosum associated with cystic acne and hidradenitis suppurativa controlled by adding minocycline and sulfasalazine to the treatment regimen. Cutis 1996; 57: 315-9. 38. Buckley DA, Rogers S. Cyclosporin-responsive hidradenitis suppurativa. J R Soc Med 1995; 88: 289P-290P. 39. Jemec GB, Wendelboe P. Topical clindamycin versus systemic tetracycline in the treatment of hidradenitis suppurativa. J Am Acad Dermatol 1998; 39: 971-4. 40. Clemmensen OJ. Topical treatment of hidradenitis suppurativa with clindamycin. Int J Dermatol 1983; 22: 325-8. 41. Banerjee AK. Surgical treatment of hidradenitis suppurativa. Br J Surg 1992; 79: 863-6. 42. Sawers RS, Randall VA, Ebling FJ. Control of hidradenitis suppurativa in women using combined antiandrogen (cyproterone acetate) and estrogen therapy. Br J Dermatol 1986; ll5: 269-74. 43. Mortimer PS, Dawber RP, Gales MA, Moore RA. A double blind controlled crossover tria! of cyproterone acetate in females with hidradenitis suppurativa. Br J Dermatol 1986; 115: 263-8. 44. BoerJ, van GemertMJ. Lang-term results of isotretinoin in the treatment of 68 patients with hidradenitis suppurativa. J Am Acad Dermatol 1999; 40: 73-6. 45. Bratschi HU, Altermatt HJ, Dreher E. Therapy of suppurative hidradenitis using the CO2-laser. Case report and literature review. Schweiz Rundsch Med Prax 1993; 82: 941-5. Anthony J. Papadopoulos MD, Dermatology, New Jersey Medica! School, 185 South OrangeAvenue, Newark, Newlersey07103-2714 George Kihiczak MD, smne address RobertA. Schwartz MD, MPH, projessor and chairman, same.address Acta Dermatoven APA Vol 9, 2000, No 4 --- --------c-------------13J