Aetiology and Pathogenesis of Hidradenitis Suppurativa

K. Wolk; O. Join-Lambert; R. Sabat

Disclosures

The British Journal of Dermatology. 2020;183(6):999-1010. 

In This Article

Abstract and Introduction

Abstract

Hidradenitis suppurativa (HS) is a chronic inflammatory disorder. Patients develop inflamed nodules and abscesses and, at later stages of disease, epithelialized tunnels and scars in skinfolds of axillary, inguinal, gluteal and perianal areas. Quality of life is affected due to severe pain, purulent secretion, restricted mobility and systemic involvement. Genetics and lifestyle factors including smoking and obesity contribute to the development of HS. These factors lead to microbiome alteration, subclinical inflammation around the terminal hair follicles, and infundibular hyperkeratosis, resulting in plugging and rupture of the follicles. Cell-damage-associated molecules and propagating bacteria trigger inflammation and lead to massive immune cell infiltration that clinically manifests as inflamed nodules and abscesses. The immune system plays a key role also in the progression and chronification of skin alterations. Innate proinflammatory cytokines (e.g. interleukin-1β and tumour necrosis factor-α), mediators of activated T helper (Th)1 and Th17 cells (e.g. interleukin-17 and interferon-γ), and effector mechanisms of neutrophilic granulocytes, macrophages and plasma cells are involved. Simultaneously, skin lesions contain anti-inflammatory mediators (e.g. interleukin-10) and show limited activity of Th22 and regulatory T cells. The inflammatory vicious circle finally results in pain, purulence, tissue destruction and scarring. Chronic inflammation in patients with HS is also frequently detected in organs other than the skin, as indicated by their comorbidities. All these aspects represent a challenge for the development of therapeutic approaches, which are urgently needed for this debilitating disease. This scholarly review focuses on the causes and pathogenetic mechanisms of HS and the potential therapeutic value of this knowledge.

Introduction

Hidradenitis suppurativa (HS),[1] also known as acne inversa, is an inflammatory disorder affecting about 1% of the general population (discussed in a parallel scholarly review). The disease manifests in skinfolds of mostly axillary, inguinal, gluteal and perianal body areas. Starting around hair follicles, inflammation evolves into painful nodules, abscesses and, at a later stage, pus-discharging tunnels (sinus tracts or fistulas) and extensive scars. In patients with HS, inflammation is also frequently detected in internal organs, as reflected by the frequent association with metabolic syndrome, arteriosclerosis, spondyloarthritis and spondyloarthropathy, and inflammatory bowel disease.[2–5] Due to severe pain, purulent secretion, limitations in patients' mobility, and systemic involvement, HS has a profoundly negative influence on the quality of life of patients (discussed in a parallel scholarly review).[6] Furthermore, the metabolic and cardiovascular alterations contribute to the substantially reduced life expectancy of patients with HS.[7]

Despite the high burden on patients, the therapeutic options for HS are currently limited.[1] In order to improve that, a profound understanding of the aetiology and pathogenesis of HS is necessary. Our current understanding of the disease mechanisms is incomplete and largely based on descriptive data of HS lesions. In contrast, ex vivo mechanistic investigations and comparative studies involving other diseases are rare. The comparison with other cutaneous inflammatory disorders appears very relevant to the authors in terms of the estimation of the extent and the specificity of molecular and immunological alterations detected in HS. Clinical studies targeting selected immune mediators could deliver the ultimate proof of the pathogenetic relevance of specific molecules.

The following sections are devoted to the disease-predisposing factors, the pathogenetic processes, and the presentation of pathogenetic mediators. Our review did not aim to discuss every published article on the subject, but rather we have selected the most important ones, in our opinion.

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