Microbiota Perturbations in Hidradenitis Suppurativa

Introduction

Hidradenitis suppurativa (HS) is a disabling chronic inflammatory disease with significant comorbidities that affects an estimated 1% of the Western population. A poor understanding of HS biology has limited the development of uniformly effective treatments. The characteristic lesions of HS in conjunction with disease improvement with broad spectrum antibiotic therapy have implicated bacteria in HS pathogenesis and suggested novel areas for consideration of therapeutic development.

Role of Bacteria in Hidradenitis Suppurativa Biology

HS is characterized by painful recurrent abscesses, malodorous purulent drainage, dermal tunnel formation, and disfiguring scarring involving intertriginous body sites including the axillae, breasts, groin, and buttocks. The clinical characteristics of HS lesions have implicated bacteria in HS biology, which has guided the variably successful use of broad-spectrum antibiotics for HS. Despite its clinical presentation, however, HS is not thought to be an infectious disease for several reasons. First, bacterial organisms common to all HS lesions have not been identified and proven to be pathogenic. Second, HS is not reproducible upon inoculation of an unaffected susceptible host. Third, HS responds to immunomodulatory therapy, including tumor necrosis factor (TNF) inhibitors and intralesional steroids, which would presumably worsen an infectious condition. Disease response to immunomodulatory therapies suggests an important role for immune dysregulation in HS pathogenesis.

Limited studies have implicated dysregulated immune responses in HS, including elevations in TNF, interleukin (IL)-1β, IL-12/23, and IL-17, and activation of the JAK pathway. Furthermore, TNF inhibitor adalimumab is currently the only US Food and Drug Administration-approved drug for HS, thus underscoring the important role of TNF in HS-related inflammation. Initial studies have also suggested a role for humoral immunity in HS pathogenesis. These findings have collectively guided the study of novel interventional treatments and the clinical use of biologic agents for HS.

Taken together, these observations suggest that chronic dysregulated immune responses to abnormal and pathogenic microbial colonization of the mucocutaneous surfaces, also known as microbial perturbations or dysbiosis , may result in persistent tissue inflammation in HS.

Bacteriology of Hidradenitis Suppurativa

Until the last decade, culture-based approaches were the standard for characterizing microbial diversity on the skin and at other body sites. Conventional culture-based methods for characterizing microbes are limited, however, because less than 1% of bacterial species are cultivatable under standard laboratory conditions. Fastidious growth requirements of some bacteria make isolation and cultivation difficult. This is underscored by the fact that historically, skin microbial research focused on investigation of a small number of cultivatable microbial species that were associated with common skin disorders. Resultantly, differential recovery of skin microbes using culture-based approaches can lead to misinterpretation of the true relative abundance of bacterial species in a given sample.

Although the presence of abscesses and malodorous drainage has implicated microorganisms in HS pathogenesis, no consistent organism has been cultivated from HS lesions using conventional culture-based methods. Polymicrobial flora, including coagulase-negative Staphylococci , mixed anaerobes, Staphylococcus aureus , and Corynebacterium species, have been identified in only approximately 50% of HS lesions using conventional culture-based methods. These findings have largely guided the use of broad spectrum topical and systemic antimicrobial therapy—including antiseptic washes and antibiotics—as first-line management for HS management.

Although antibiotic therapy can be effective for HS management, treatment strategies that rely on repeated and lengthy antibiotic courses may induce antibiotic-resistant bacterial species. In a single center study, antibiotic therapy with topical clindamycin, oral ciprofloxacin, and trimethoprim/sulfamethoxazole were associated with cultivation of antibiotic resistant organisms. These data caution antibiotic stewardship in the management of HS.