Hidradenitis Suppurativa (HS), also known as acne inversa, is a chronic, painful, and often debilitating inflammatory skin condition. It is characterized by recurring lesions that typically form in areas where skin rubs together, such as the armpits, groin, and under the breasts. HS profoundly impacts a patient’s quality of life due to persistent pain, drainage, and scarring. Defining the underlying immune mechanisms is necessary for developing the most effective and targeted therapies.
How Hidradenitis Suppurativa Presents
HS manifests as deep-seated, painful nodules that resemble boils but are sterile, meaning they are not primarily caused by a bacterial infection. These lesions often rupture, releasing foul-smelling pus and leading to significant discomfort. Over time, the chronic inflammation and healing process cause the formation of characteristic interconnected tunnels beneath the skin, known as sinus tracts or draining tunnels.
The disease primarily affects the apocrine gland-rich areas of the body, including the axillae (armpits), inguinal folds (groin), perineum, and inframammary regions. The severity and progression of HS are commonly assessed using the Hurley Staging system. Stage I involves isolated abscesses without sinus tracts or scarring. Stage II introduces recurrent abscesses, scarring, and scattered sinus tracts. The most severe form, Stage III, involves diffuse or near-diffuse involvement with multiple interconnected sinus tracts, extensive scarring, and abscesses across an entire area.
The Difference Between Autoimmune and Autoinflammatory Conditions
The question of whether HS is an autoimmune disease is common, but the current scientific consensus classifies it primarily as an autoinflammatory condition. Autoimmune diseases, such as Rheumatoid Arthritis or Lupus, involve the adaptive immune system. This system generates specific T and B cells and produces autoantibodies that mistakenly target self-antigens and tissues. This response is memory-driven and precisely misdirected against the body’s own components.
Autoinflammatory conditions are driven by an overactive innate immune system, the body’s first, non-specific line of defense. This innate system involves cells like neutrophils and macrophages and pathways such as the inflammasomes, which trigger inflammation without the need for external triggers or autoantibodies. The immune response is considered “misregulated” or “overactive” rather than misdirected against a specific self-antigen.
HS is considered a chronic autoinflammatory disorder because its primary features involve the hyper-responsiveness of the innate immune system and elevated levels of innate immune cells in the lesions. While some features of adaptive immunity, such as T-cell involvement, are also present, the fundamental mechanism aligns more closely with dysregulated innate pathways. This classification helps focus research on the specific cellular pathways that drive the inflammation.
Specific Mechanisms That Drive the Disease
The pathogenesis of HS begins with the blockage, or occlusion, of the hair follicle (the pilosebaceous unit). Inflammation causes hyperkeratosis, an overgrowth of the follicular lining, leading to a buildup of keratin and follicular contents. Pressure eventually causes the hair follicle wall to rupture, spilling contents into the surrounding dermis.
The spillage acts as a danger signal, triggering a massive, uncontrolled inflammatory cascade characteristic of autoinflammation. This process recruits an overwhelming number of innate immune cells, particularly neutrophils, leading to the formation of pus-filled abscesses. The resulting inflammation is amplified by the release of specific pro-inflammatory cytokines that reinforce the autoinflammatory nature of the disease.
Key inflammatory messengers such as Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-17 (IL-17) are significantly upregulated in HS lesions. TNF-α and IL-17 are potent drivers of inflammation, recruiting more immune cells and promoting the tissue destruction that results in scarring and the formation of the deep sinus tracts. The sustained activation of these pathways makes HS a chronic, systemic inflammatory condition rather than just a localized skin infection.
How Classification Guides Treatment Strategies
Understanding HS as primarily an autoinflammatory disease with secondary adaptive involvement has fundamentally changed its treatment landscape. Since the pathology is driven by specific inflammatory messengers, therapies are designed to block these overactive pathways rather than broadly suppressing the entire immune system. This approach allows for targeted intervention with higher efficacy and fewer systemic side effects than older treatments.
Biologic medications, manufactured proteins that target specific parts of the immune system, exemplify this strategy. For instance, drugs that block TNF-α, such as adalimumab, are approved for moderate-to-severe HS because they directly neutralize one of the most prominent inflammatory cytokines driving the disease. Newer biologics that target the IL-17 pathway, such as secukinumab and bimekizumab, also show promise, further confirming the central role of these specific autoinflammatory pathways.
The knowledge that HS involves dysregulated innate immunity guides clinicians to use a combination of medical and surgical approaches. Medical therapy focuses on reducing systemic inflammation and preventing new lesions. Surgery is often necessary to remove irreversible tissue damage, such as extensive sinus tracts and scarring, caused by the chronic inflammatory process.