Case Reports

Hidradenitis Suppurativa and Concomitant Pyoderma Gangrenosum Treated With Infliximab

Cutis. 2015 June;95(6):337-342

Pyoderma gangrenosum (PG) and hidradenitis suppurativa (HS) are rare chronic inflammatory dermatoses of unknown etiologies that often are refractory to conventional treatments. The therapeutic benefits of tumor necrosis factor a (TNF-α) inhibitors have been reported in patients with refractory PG or HS. The copresentation of these 2 diseases has previously been described in several cases in the literature and may present a therapeutic challenge. We present the case of a 51-year-old man who developed widespread inflammatory ulcers affecting approximately 50% of the body surface area and subsequent chronic debilitation from severe pain. He was ultimately diagnosed with concurrent PG and HS. Both diseases remitted in response to treatment with infliximab, which resulted in complete restoration of skin integrity and resolution of his chronic severe pain.

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Practice Points

Pyoderma gangrenosum (PG) and hidradenitis suppurativa (HS) are rare chronic inflammatory dermatoses that may coexist in the same patient.
Infliximab may represent an effective therapeutic option for the treatment of concurrent PG and HS that is refractory to conventional therapies.

References

1. Hsiao JL, Antaya RJ, Berger T, et al. Hidradenitis suppurative and concomitant pyoderma gangrenosum: a case series and literature review. Arch Dermatol. 2010;146:1265-1270.

2. Moschella S. Is there a role for infliximab in the current therapy of hidradenitis suppurativa? a report of three treated cases. Int J Dermatol. 2007;46:1287-1291.

3. Powell FC, Su WP, Perry HO. Pyoderma gangrenosum: classification and management. J Am Acad Dermatol. 1996;34:395-409.

4. Ah-Weng A, Langtry JAA, Velangi S, et al. Pyoderma gangrenosum associated with hidradenitis suppurativa. Clin Exp Dermatol. 2005;30:669-671.

5. Braun-Falco M, Kovnerystyy O, Lohse P, et al. Pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH)—a new autoinflammatory syndrome distinct from PAPA syndrome. J Am Acad Dermatol. 2012;66:409-415.

6. Buckley DA, Rogers S. Cyclosporin-responsive hidradenitis suppurativa. J R Soc Med. 1995;88:289-290.

7. Shenefelt PD. Pyoderma gangrenosum associated with cystic acne and hidradenitis suppurativa controlled by adding minocycline and sulfasalazine to the treatment regimen. Cutis. 1996;57:315-319.

8. Raynor A, Askari AD. Behçet’s disease and treatment with colchicine. J Am Acad Dermatol. 1980;2:396-400.

9. Steinhoff JP, Cilursu A, Falasca GF, et al. A study of musculoskeletal manifestations in 12 patients with SAPHO syndrome. J Clin Rheumatol. 2002;8:13-22.

10. Rosner IA, Richter DE, Huettner TL, et al. Spondyloarthropathy associated with hidradenitis suppurative and acne conglobata. Ann Intern Med. 1982;97:520-525.

11. von den Driesch P. Pyoderma gangrenosum: a report of 44 cases with follow-up. Br J Dermatol. 1997;137:1000-1005.

12. Brooklyn TN, Dunnill MG, Shetty A, et al. Infliximab for the treatment of pyoderma gangrenosum: a randomized, double-blind, placebo-controlled trial. Gut. 2006;55:505-509.

13. Ruocco E, Sangiulliano S, Gravina AG, et al. Pyoderma gangrenosum: an updated review. J Eur Acad Dermatol Venereol. 2009;23:1008-1017.

14. Mortimer P. Management of hidradenitis suppurativa. Clin Exp Dermatol. 2002;27:328.

15. Blanco R, Martinez-Taboada VM, Villa I, et al. Long-term successful adalimumab therapy in severe hidradenitis suppurativa. Arch Dermatol. 2009;145:580-584.

16. Rambhatla PV, Lim HW, Hamzavi I. A systematic review of treatment for hidradenitis suppurativa. Arch Dermatol. 2012;148:439-446.

17. Alecsandru D, Padilla B, Izquierdo JA, et al. Severe refractory hidradenitis suppurativa in an HIV-positive patient successfully treated with infliximab. Arch Dermatol. 2010;146:1343-1345.

18. Alexis A, Strober B. Off-label dermatologic uses of anti-TNF-a therapies. J Cutan Med Surg. 2006;9:296-301.

19. Grant A, Gonzalez T, Montgomery MO, et al. Infliximab therapy for patients with moderate to severe hidradenitis suppurativa: a randomized, double-blind, placebo-controlled crossover trial. J Am Acad Dermatol. 2010;62:205-217.

20. Fardet L, Dupuy A, Kerob D, et al. Infliximab for severe hidradenitis suppurativa: transient clinical efficacy in 7 consecutive patients. J Am Acad Dermatol. 2007;56:624-628.

21. Usmani N, Clayton TH, Everett S, et al. Variable response of hidradenitis suppurativa to infliximab in four patients. Clin Exp Dermatol. 2007;32:204-205.

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Pyoderma gangrenosum (PG) and hidradenitis suppurativa (HS) are rare chronic inflammatory dermatoses of unknown etiologies that often are refractory to conventional treatments. Multiple case reports have described the coexistence of these 2 diseases in the same patient.^1-11 The diagnosis of PG commonly followed the diagnosis of HS by 5 months to 30 years in several of these cases, suggesting that HS may have triggered a possible underlying inflammatory process that resulted in subsequent development of PG. When presenting in the setting of preexisting HS, PG lesions have occurred both in the same sites of the body affected by HS as well as in distinct sites such as the legs.¹

Although the treatment of either PG or HS alone can be difficult, the combination of these 2 diseases presents a further therapeutic challenge. Tumor necrosis factor a (TNF-α) has been implicated in the pathogenesis of both of these diseases, and several cases have demonstrated great potential for the use of TNF-α inhibitors, particularly infliximab, in the treatment of resistant cases of each of these conditions.^2,12 We report a case of severe concurrent PG and HS in a 51-year-old man that was refractory to other treatments but clinically remitted in response to infliximab therapy.

Case Report

A 51-year-old man was transferred to our institution from an outside hospital where he had presented with fevers and a worsening rash that had prevented him from ambulating for several days secondary to severe pain. At the outside facility, he was noted to have extensive ulcerations with granulation tissue on the scalp, face, sacrum, buttocks, and bilateral legs. A skin biopsy performed at the outside facility revealed a neutrophilic dermal infiltrate with abscesses and granulation tissue consistent with PG. He was transferred to our institution for continued local wound care, corticosteroid administration, and hyperbaric oxygen therapy.

On presentation at our institution, continued ulcerative skin lesions were noted in the previously mentioned areas (Figures 1A and 1B), and deeper purulent sinus tracts were noted in the axillae and extending onto the chest (Figure 1C). A biopsy from the chest showed folliculitis with a prominent plasmacytic infiltrate consistent with HS. Cultures from the sinus tracts showed abundant growth of Enterobacter aerogenes, Klebsiella pneumoniae, Enterobacter cloacae, and Proteus mirabilis. The patient was subsequently treated with intravenous ampicillin-sulbactam and vancomycin as well as oral prednisone 80 mg daily for 2 weeks with only mild improvement of the lesions. The prednisone was gradually tapered to a dose of 10 mg daily in preparation for a trial of infliximab. During the early course of his therapy, subsequent cultures from draining sinus tracts grew Pseudomonas aeruginosa and Acinetobacter baumannii, requiring concomitant treatment with oral antimicrobials including doxycycline, sulfamethoxazole-trimethoprim, ciprofloxacin, and amoxicillin–clavulanic acid for control of the superinfection.

^{Figure 1. On initial presentation, extensive areas of ulceration with variable amounts of granulation tissue and rusting were noted on the scalp (A) and legs (B). Sinus tract formation also was evident in the neck (A) and axilla (C).}

The patient received 3 induction infusions of infliximab at a dosage of 5 mg/kg per treatment at weeks 0, 2, and 6. At the time of the first treatment, he was noted to have numerous crusted draining erosions on the head, neck, and chest. The patient reported no adverse effects during or after each treatment. Following completion of the 3 infliximab infusions, the skin lesions showed considerable improvement, with only 1 draining lesion remaining on the left temple and only erythematous plaques remaining on the scalp, upper back, and axillae. Maintenance infusions were continued every 8 weeks with an increased infliximab dose of 7.5 mg/kg.

After 1 year of treatment, the lesions had healed to form cicatrices with no evidence of erythema, drainage, or infection (Figure 2). Doxycycline and prednisone were discontinued, and the infliximab dose was decreased to 5 mg/kg per infusion every 8 weeks. Following sustained improvement after 2 infusions at this lower dose, infliximab was successfully tapered to 2.5 mg/kg every 8 weeks for 2 doses and then was subsequently discontinued; however, the patient’s disease relapsed approximately 7 months after discontinuation of the infliximab and was immediately resumed at a dose of 5 mg/kg per infusion every 8 weeks. He has remained disease free on this dose to date.

^{Figure 2. After 11 infusions with infliximab (dose range, 5–7.5 mg/kg), all previously affected areas showed resolution with cicatrices and postinflammatory hyperpigmentation (A–C), with no evidence of ulceration or active sinus tract formation.}

Comment

Pyoderma gangrenosum is a chronic inflammatory ulcerative skin condition that most commonly occurs on the lower legs.³ In its most common form, PG lesions typically begin as tender erythematous nodules or pustules that evolve into enlarging painful ulcers with raised, undermined, violaceous borders.¹³ Biopsy specimens taken from the edges of the lesions typically show a diffuse neutrophilic infiltrate, and pseudoepitheliomatous hyperplasia also may be seen. Lesions tend to persist for months to years, ultimately healing as cribriform scars. The etiology of PG is unknown and its pathogenesis is poorly understood.¹³ Pyoderma gangrenosum is associated with an underlying systemic disease in approximately 50% of cases, most commonly inflammatory bowel disease, hematologic malignancies, and inflammatory arthritis.³ An underlying immunologic abnormality is therefore postulated to contribute to the pathogenesis of PG, as it is frequently associated with these immune-mediated systemic diseases.