Severe Hidradenitis Suppurativa Treated with Infliximab Infusion

THE CUTTING EDGE

SECTION EDITOR: GEORGE J. HRUZA, MD; ASSISTANT SECTION EDITORS: DEE ANNA GLASER, MD; ELAINE SIEGFRIED, MD Severe Hidradenitis Suppurativa Treated With Infliximab Infusion

David R. Adams, MD, PharmD; Kenneth B. Gordon, MD; Attila G. Devenyi, MD; Michael D. Ioffreda, MD; Penn State Hershey Medical Center, Hershey, Pa (Drs Adams and Ioffreda), Northwestern University, Chicago, Ill (Dr Gordon), and Regional Gastroenterology Associates of Lancaster, Ltd, Lancaster, Pa (Dr Devenyi)

The Cutting Edge: Challenges in Medical and Surgical Therapeutics

REPORT OF A CASE diagnosed 4 months earlier, that was controlled with sul- fasalazine (1 g three times a day) and azathioprine (50 mg/d). A 17-year-old male patient with a 3-year history of hidrad- He took supplemental iron and folic acid (1 mg/d) for ane- enitis suppurativa presented to our dermatology clinic for mia. Figure 1A shows his groin at the initial visit. The more effective treatment. Areas of involvement included prednisone therapy had caused significant adverse effects, the medial aspect of the thighs, scrotum, buttocks, and in- including a cushingoid appearance, obesity (weight, 80.4 framammary folds. His axillae were spared. He also had a kg), striae, gynecomastia, and diabetes mellitus, which had pilonidal cyst and nodulocystic acne. A diagnosis of hi- presented as diabetic ketoacidosis 4 months before he was dradenitis suppurativa was rendered. The patient’s symp- seen in our dermatology office. At that time, his diabetes toms included groin and perineal pain, serous and puru- was treated with insulin and rosiglitazone maleate (4 mg lent discharge, and malodor. His primary care physician twice a day). Six weeks later, his insulin therapy was dis- had been treating him with prednisone (5 mg twice a day) continued, and metformin hydrochloride therapy (500 for more than 2 years and cephalexin (500 mg twice a day) mg/d) was initiated. He also took potassium, magnesium, for 2 weeks. He also had ulcerative colitis, which had been and calcium supplements.

A B

Figure 1. A, Patient at initial presentation to the dermatology clinic. Black arrows indicate draining ulcers and sinus tracts; white arrow indicates a fluctuant nodule. B, At 61⁄2 months after the first infusion, there is complete healing in the area of the medial aspect of the thighs, but there is a new lesion in the left pubic area that appeared 5 months after the initial infusion.

(REPRINTED) ARCH DERMATOL / VOL 139, DEC 2003 WWW.ARCHDERMATOL.COM 1540

©2003 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/29/2021 THERAPEUTIC CHALLENGE Treatment of hidradenitis suppurativa is difficult and of- ten ineffective. Therapeutic intervention is aimed at de- creasing bacterial overgrowth, treating infection, and di- minishing pain, drainage, and odor. Our patient was experiencing substantial symptoms and sought treatment that was more effective than systemic corticosteroids. He had consulted another dermatologist, who had recommended surgery. Despite the use of anti- inflammatory medications, including prednisone, azathioprine, and cephalexin, his condition worsened.

SOLUTION Two of us (D.R.A. and M.D.I.) had previously treated other patients with hidradenitis suppurativa who had re- sponded poorly to therapy with oral and topical antibi- otics and isotretinoin. With this in mind, and because of the severity of our patient’s disease, an alternative treat- A B C ment was sought. Infliximab (Remicade) was chosen based 1 Figure 2. The medial aspect of the right thigh is shown before and during on a report in the gastroenterology literature and be- therapy. A, Patient at initial presentation. B, At 5 weeks after the first cause one of us (K.B.G.) had used infliximab therapy suc- infliximab infusion, there is decreased erythema, healing of the ulcers, and cessfully in another patient. diminution of the fluctuant area. C, At 61⁄2 months after the initial infliximab treatment, the right medial thigh area shows complete resolution, with only Infliximab has been approved by the Food and Drug some residual scarring and postinflammatory hyperpigmentation. Administration for the treatment of Crohn disease. Our patient’s gastroenterologist (A.G.D.) agreed to treat the patient’s hidradenitis suppurativa with infliximab be- areas, ie, the anogenital regions and axillae.2 It is char- cause of his experience with this medication and be- acterized by recurrent abscesses, scarring, and sinus tract cause of his capacity to administer intravenous therapy formation.3 Bacterial overgrowth is a common second- in his practice setting. Before treatment began, a nega- ary process. Historically, treatment with oral antimicro- tive purified protein derivative test result was con- bial agents, topical clindamycin, isotretinoin, systemic firmed. The patient received 3 infliximab infusions (5 mg/ and intralesional corticosteroids, and surgery has been kg) at 0, 2, and 6 weeks. He had no adverse effects during inconsistently effective.3 Other reported interventions in- or after the infusions. At a follow-up appointment 5 weeks clude methotrexate,4 acitretin,5 hormonal therapy with after the first infusion, there was complete resolution of cyproterone acetate and ethinyl estradiol in female pa- the pain and tenderness, purulence, drainage, and odor tients,3 cyclosporine,3 and carbon dioxide laser.6 Hidrad- in his groin and perineal region, and the inflammation enitis suppurativa has been associated with high mor- was greatly decreased. At 5 months after the first inflix- bidity,7 spondyloarthropathy,8 and carcinoma, including imab infusion, he experienced a localized recurrence in squamous cell and verrucous carcinoma, arising in le- 9 the left pubic area, but photographs taken at 61⁄2 months sional sites. A Swedish study found that patients with demonstrated continued healing in the medial aspect of hidradenitis suppurativa have an increased risk of de- both thighs, which had previously been the most se- veloping nonmelanoma skin cancer.10 Herein, we de- verely affected sites (Figure 1B). The inflamed nodule in scribe a patient with severe hidradenitis suppurativa that the pubic area persisted for approximately 2 months, at did not respond to prednisone, azathioprine, or cepha- which time the patient received a fourth infliximab in- lexin therapy; however, after 2 infusions of infliximab, fusion, with a good response documented 1 month later. he had complete relief of his groin and perineal symp- Cultures were not obtained from the nodule. Figure 2 toms and significant improvement in the appearance of shows the morphological appearance of the lesions in the the affected area. He experienced a complete remission right groin area before infliximab therapy (Figure 2A) for 5 months, at which time he developed a focal recur- and at 5 weeks (Figure 2B) and 61⁄2 months (Figure 2C) rence in the pubic area. A fourth infliximab infusion was after the first infliximab treatment. Since the infliximab administered approximately 2 months after the recur- infusions appeared to induce disease remission, main- rence. The persistent inflamed nodule in the pubic area tenance topical or oral therapy for the hidradenitis was resolved within a couple of weeks of a single infusion. not initiated. Our plan is to treat disease flares with in- Infliximab is a chimeric IgG antibody that binds tu- fliximab infusions, if not contraindicated, with the hope mor necrosis factor ␣, thus preventing its proinflamma- of inducing a long-term remission. tory biological effects. It is composed of human-derived constant regions and mouse-derived variable regions. It COMMENT is available for infusion and was approved by the Food and Drug Administration in 1998 for treatment of Crohn Hidradentitis suppurativa is a chronic inflammatory dis- disease and, more recently, rheumatoid arthritis. It has ease of follicular occlusion in apocrine gland–bearing also been advocated for the treatment of numerous in-

(REPRINTED) ARCH DERMATOL / VOL 139, DEC 2003 WWW.ARCHDERMATOL.COM 1541

©2003 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/29/2021 flammatory conditions, including pyoderma gangreno- Center, UPCII, Suite 4300, 500 University Dr, Hershey, PA sum, psoriasis, severe pustular psoriasis, toxic epider- 17033 (e-mail: [email protected]). mal necrolysis, graft-vs-host disease, SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome, REFERENCES Sjo¨gren syndrome, Sneddon-Wilkinson disease, adult Still

disease, sarcoidosis, Behc¸et syndrome, progressive sys- 1. Martinez F, Nos P, Benlloch S, Ponce J. Hidradenitis suppurativa and Crohn’s temic sclerosis, Wegener granulomatosis, giant cell ar- disease: response to treatment with infliximab. Inflamm Bowel Dis. 2001;7:323- teritis, myelodysplastic syndrome, celiac disease, anky- 326. losing spondylitis, spondyloarthropathy-related uveitis, 2. Brown TJ, Rosen T, Orengo IF. Hidradenitis suppurativa. South Med J. 1998;91: and ulcerative colitis.11,12 1107-1114. 3. Mortimer P. Management of hidradenitis suppurativa [abstract]. Clin Exp Der- A detailed search of the literature failed to reveal an matol. 2002;27:328. association between ulcerative colitis and hidradenitis sup- 4. Jemec GB. Methotrexate is of limited value in the treatment of hidradenitis suppurativa. However, the coexistence of Crohn disease and purativa. Clin Exp Dermatol. 2002;27:528-529. hidradenitis suppurativa is well known.13 A case report 5. Scheman AJ. Nodulocystic acne and hidradenitis suppurativa treated with acitretin: a case report. Cutis. 2002;69:287-288. of a 30-year-old woman with both Crohn disease and ax- 6. Lapins J, Sartorius K, Emtestam L. Scanner-assisted carbon dioxide laser sur- illary and perianal hidradenitis suppurative that were re- gery: a retrospective follow-up study of patients with hidradenitis suppurativa. sistant to usual therapy was treated with 2 infusions of J Am Acad Dermatol. 2002;47:280-285. infliximab (5 mg/kg per dose) and azathioprine (2.5mg/kg 7. von der Werth JM, Jemec GB. Morbidity in patients with hidradenitis suppura- per day). After the first dose, there was significant im- tiva. Br J Dermatol. 2001;144:809-813. 8. Leybishkis B, Fasseas P, Ryan KF, Roy R. Hidradenitis suppurativa and acne con- provement in the axillary and perianal areas. During the globata associated with spondyloarthropathy. Am J Med Sci. 2001;321:195- second infusion, the patient experienced a “generalized 197. erythematous eruption” and dyspnea, which abated af- 9. Cosman BC, O’Grady TC, Pekarske S. Verrucous carcinoma arising in hidrad- ter discontinuation of the infusion. After the second dose, enitis suppurativa. Int J Colorectal Dis. 2000;15:342-346. 10. Lapins J, Ye W, Nyren O, Emtestam L. Incidence of cancer among patients with the patient had nearly complete resolution of the le- hidradenitis suppurativa. Arch Dermatol. 2001;137:730-734. sions and was still in remission at the 6-month fol- 11. Fleischmann R, Iqbal I, Nandeshwar P, Quiceno A. Safety and efficacy of disease- low-up visit.1 modifying anti-rheumatic agents: focus on the benefits and risks of etanercept. Another case report described a 30-year-old man with Drug Saf. 2002;25:173-197. fistulizing Crohn disease and axillary hidradenitis sup- 12. Tan MH, Gordon M, Lebwohl O, George J, Lebwohl MG. Improvement of pyoderma gangrenosum and psoriasis associated with Crohn’s disease with anti– purativa that were resistant to methylprednisolone, aza- tumor necrosis factor ␣ monoclonal antibody. Arch Dermatol. 2001;137:930- thioprine, and isotretinoin therapy; he was then treated 933. with infliximab, with a very good response. After 2 years, 13. Ostlere LS, Langtry JAA, Mortimer PS, Staughton RCD. Hidradenitis suppura- the hidradentis had practically disappeared, leaving only tiva in Crohn’s disease. Br J Dermatol. 1991;125:384-386. 14 14. Katsanos KH, Christodoulou DK, Tsianos EV. Axillary hidradenitis suppurativa scars. successfully treated with infliximab in a Crohn’s disease patient. Am J Gastro- Infliximab infusion may prove to be a reasonable op- enterol. 2002;97:2155-2156. tion for treating resistant severe hidradenitis suppura- 15. Sandborn WJ, Hanauer SB. Antitumor necrosis factor therapy for inflammatory tiva. A purified protein derivative test is recommended bowel disease: a review of agents, pharmacology, clinical results, and safety. before therapy to avoid reactivation of latent tuberculo- Inflamm Bowel Dis. 1999;5:119-133. 16. Van Assche G, Rutgeerts P. Anti-TNF agents in Crohn’s disease. Expert Opin sis. It must be administered in a controlled setting with Investig Drugs. 2000;9:103-111. personnel who are knowledgeable of, and able to respond to, adverse effects, particularly anaphylaxis. An- other concern is the potential immunogenicity of inflix- Submissions imab’s anti–tumor necrosis factor antibody, which can result in the formation of human antichimeric antibodies, as well as autoantibodies, rarely causing drug- Clinicians, local and regional societies, residents, and fel- induced lupus.15,16 The risk of forming human antichi- lows are invited to submit cases of challenges in man- meric antibodies may be mitigated by the coadministration agement and therapeutics to this section. Cases should of immunosuppressive agents. Other potential adverse follow the established pattern. Submit 4 double-spaced copies of the manuscript with right margins nonjusti- effects of anti–tumor necrosis factor therapies include de- fied and 4 sets of the illustrations. Photomicrographs and layed hypersensitivity reactions and the risk of lympho- illustrations must be clear and submitted as positive color 15,16 proliferative disease. To determine if infliximab is a transparencies (35-mm slides) or black-and-white prints. worthwhile and safe therapy for hidradenitis suppura- Do not submit color prints unless accompanied by origi- tiva, additional experience is needed. nal transparencies. Material should be accompanied by the required copyright transfer statement, as noted in “In- Accepted for publication May 2, 2003. structions for Authors.” Material for this section should The authors have no relevant financial interest in this be submitted to George J. Hruza, MD, Laser and Der- article. matologic Surgery Center Inc, 14377 Woodlake Dr, Suite Corresponding author: David R. Adams, MD, PharmD, 111, St Louis, MO 63017. Department of Dermatology, Penn State Hershey Medical

(REPRINTED) ARCH DERMATOL / VOL 139, DEC 2003 WWW.ARCHDERMATOL.COM 1542