Hidradenitis suppurativa (HS), also known as acne inversa, is a chronic skin condition characterized by deep-seated, painful lumps and abscesses under the skin. These lesions commonly develop in areas where skin rubs together, such as the armpits, groin, inner thighs, and under the breasts. The condition involves recurrent flares and often progresses to form draining tunnels beneath the skin, known as sinus tracts, and leaves behind scarring. The associated pain, discharge, and scarring can profoundly limit daily activities and negatively impact an individual’s quality of life. Understanding the mechanisms behind this disorder is a subject of ongoing research, particularly concerning how it relates to broader categories of immune-mediated diseases.
Autoimmune versus Autoinflammatory Diseases
The confusion surrounding HS often stems from its classification relative to other immune disorders. Autoimmune diseases involve the adaptive immune system, using specific T and B cells to recognize and attack the body’s own healthy tissues. These disorders, such as systemic lupus erythematosus or rheumatoid arthritis, often produce autoantibodies as the immune system mistakenly sees a “self” component as a foreign threat.
Autoinflammatory diseases, by contrast, are driven by dysregulation of the innate immune system, the body’s first and less specific line of defense. This innate system becomes hyperactive, leading to episodes of excessive inflammation without the involvement of autoantibodies or antigen-specific T cells. Familial Mediterranean Fever is a well-known example. HS is now largely classified within this group because its pathology is rooted in the uncontrolled, non-specific activation of the innate immune response.
The Primary Mechanism of Hidradenitis Suppurativa
HS is an autoinflammatory disorder, not a classical autoimmune one, due to its connection to the innate immune system. The process begins with the occlusion, or blockage, of the hair follicle opening, the primary structure involved in the disease. This follicular blockage causes the follicle to dilate and ultimately rupture beneath the skin surface.
When the follicle wall breaks, its contents, including keratin and bacteria, are released into the surrounding dermis. This event triggers an uncontrolled inflammatory reaction by the innate immune system. The body reacts to the released material as a danger signal, initiating a self-perpetuating cycle of inflammation.
This chronic inflammation is sustained by the excessive production of specific signaling proteins known as pro-inflammatory cytokines. Key players include Tumor Necrosis Factor-alpha (TNF-α), Interleukin-1 beta (IL-1β), and Interleukin-17 (IL-17). The continuous presence of these mediators drives the formation of the painful nodules, abscesses, and deep sinus tracts characteristic of the condition.
Genetic and Environmental Contributing Factors
The development of HS is influenced by a combination of internal and external factors, though the mechanism centers on immune dysregulation. Genetic predisposition plays a role, with 30% to 40% of patients reporting a family member who also has the condition. This familial clustering suggests that inheriting certain gene alterations increases the risk of developing the disorder.
Some cases of HS have been linked to mutations in genes like NCSTN and PSEN1, which are involved in the function of the gamma-secretase complex. This complex is important for cellular signaling, and its dysfunction can contribute to the initial follicular occlusion. However, HS does not follow a simple, single-gene inheritance pattern, indicating a complex interplay with other factors.
Environmental and lifestyle elements are also influential in both the onset and severity of the condition. Smoking is a well-established risk factor, with 70% to 90% of individuals with HS being smokers. Obesity is another contributor, as it increases skin friction, which can aggravate lesions, and is linked to systemic inflammation that worsens the disease. The onset of HS typically occurs after puberty, suggesting that hormonal fluctuations also contribute.
How Classification Guides Treatment Decisions
The understanding that HS is driven by specific inflammatory mediators of the innate immune system has shaped its treatment approach. Since the pathology centers on the overproduction of cytokines like TNF-α and IL-17, treatments are designed to target and neutralize these molecules. This approach differs from the broader immunosuppression often required for classical autoimmune diseases.
Targeted therapies, known as biologics, are now a cornerstone of treating moderate-to-severe HS. Anti-TNF-α agents, such as adalimumab, block the action of Tumor Necrosis Factor-alpha to dampen the sustained inflammatory response. Newer treatments, including anti-IL-17 agents like secukinumab and bimekizumab, are also approved to target other specific pathways driving the autoinflammation.
While long-term systemic antibiotics and surgical drainage remain important for managing secondary infection and severe lesions, the use of targeted anti-inflammatory biologics addresses the underlying immune dysfunction. This therapeutic strategy, focusing on interrupting the cytokine cascade, reflects the classification of HS as a primary autoinflammatory disorder.