Hidradenitis Suppurativa and Concomitant Pyoderma Gangrenosum Treated With Infliximab

There is no specific and uniformly effective treatment of PG, but the main therapeutic goals include the reduction of inflammation to promote wound healing, pain reduction, and the treatment of any comorbid diseases that may contribute to the severity of PG, all while minimizing adverse side effects. Systemic corticosteroids and cyclosporine have been reported to produce the most effective results,¹³ but due to the side effects and toxicities of these drugs, they are often reserved for severe cases in which the benefits of their use outweigh the risks for other comorbidities. Other reported treatments include antimicrobial agents, topical and intralesional corticosteroids, steroid-sparing immunosuppressive agents, colchicine, hyperbaric oxygen therapy, and more recently drugs that function via immune modulation such as TNF-α inhibitors.

Hidradenitis suppurativa is a chronic suppurative inflammatory disease of follicular occlusion in apocrine gland–bearing areas of the skin such as the groin, axillae, and anogenital region. Hidradenitis suppurativa is characterized by recurrent skin abscesses, sinus tract and fistula formation, and subsequent fibrosis with bacterial overgrowth as a common secondary process.¹⁴ The pathogenesis of HS remains poorly understood, but histology typically shows a nonspecific inflammatory process with or without concomitant infection.¹⁵ Treatment of HS is complex and usually is transiently effective at best.¹⁴ In 2012, Rambhatla et al¹⁶ discussed the efficacy of various treatments of HS, including systemic and topical antimicrobial agents (eg, clindamycin-rifampicin combination treatment, tetracycline, topical clindamycin phosphate, isotretinoin, dapsone), antiandrogenic agents, biologic agents (eg, infliximab, etanercept, adalimumab, efalizumab), laser surgery (CO₂ laser, Nd:YAG laser), and excisional surgery of sinus tracts. Other therapies include cryotherapy, photodynamic therapy, finasteride, zinc gluconate, topical resorcinol, and acitretin.¹⁶

Both PG and HS are categorized as chronic inflammatory disorders with nonspecific histopathologic findings. Although the etiologies of these 2 disorders remain poorly understood, several case reports have suggested an association between PG and HS.^1,4 In many of the reported cases of concurrent HS and PG, HS preceded the diagnosis of PG by several years and no correlation in disease activity was observed between the 2 conditions.^1-4,6-8 Additionally, the clinical triad of PG, acne, and suppurative hidradenitis, known as PASH syndrome, has been described, which may represent a new entity within the spectrum of autoinflammatory syndromes.⁵ It is not uncommon for either PG or HS to be refractory to conventional therapies, and therefore the management of concomitant PG and HS presents an even further therapeutic challenge.

Recently, biologic agents such as TNF-α inhibitors have been used with increased frequency as novel treatments for severe dermatologic diseases including psoriasis and pemphigus vulgaris, among others.¹⁷ Furthermore, several reports have presented convincing results in the off-label use of TNF-α inhibitors in the treatment of isolated PG as well as in the treatment of HS.^12,14,17-22 Infliximab, a chimeric anti–TNF-α monoclonal antibody, has been used with particular success in recalcitrant cases of these conditions.^12,17,19-21

In a double-blind, placebo-controlled, crossover trial analyzing 38 patients with moderate to severe refractory HS, Grant et al¹⁹ found that treatment with infliximab was associated with a significantly greater improvement in pain intensity (P<.001), disease severity (P<.001), and quality of life (P=.003), with concomitant reduction in clinical markers of inflammation compared to placebo. Similarly, a randomized, double-blind, placebo-controlled trial by Brooklyn et al¹² evaluated 30 patients with refractory PG. In this study, infliximab was shown to be superior to placebo for rapid clinical response in patients with PG irrespective of the existence of concomitant inflammatory bowel disease.¹²

On the contrary, lack of efficacy and/or adverse reactions associated with infliximab and other TNF-α inhibitors in the treatment of PG and HS also have been reported in the literature. Fardet et al²⁰ reported that 2 of 7 (28.6%) HS patients treated with at least 3 infusions of infliximab (5 mg/kg) at weeks 0, 2, and 6 had minimal or nonexistent improvement by week 6. Additionally, adverse events occurred in 3 of 7 (42.9%) HS patients, including abdominal pain caused by colon cancer, multifocal motor neuropathy with conduction block, and a severe allergic reaction.²⁰ Usmani et al²¹ described 1 HS patient who developed an infliximab-induced lupus reaction, 1 who experienced a hypersensitivity reaction to infliximab, and 2 who had poor response to treatment despite 3 infusions. Kleinpenning et al²² reported a case of PG that failed consecutive trials of etanercept and adalimumab. Wolbing et al²³ reported a case of septic shock after treatment of PG with infliximab. Shareef et al²⁴ reported progression of IgA gammopathy to myeloma following infliximab treatment for PG in 1 patient.

Of the reported cases of concurrent HS and PG, 3 were treated with TNF-αinhibitors, both alone and in conjunction with other treatment modalities, with varying results. One patient demonstrated a partial response to treatment with etanercept followed by infliximab, 1 was resistant to treatment with infliximab as well as adalimumab, and 1 exhibited clinical improvement following treatment with infliximab.^1,2