Zehn Skin and Health

Hidradenitis suppurativa (HS), sometimes referred to as acne inversa, is a prevalent, chronic inflammatory skin condition affecting a notable portion of the global population. Estimates suggest that 1-4% of individuals experience HS, highlighting its significant impact. This condition manifests as painful, deep-seated lesions primarily in intertriginous areas—regions where skin folds and rubs together, such as the armpits, groin, buttocks, and under the breasts. These lesions can take various forms, including nodules, abscesses, and tunnels beneath the skin, often resulting in substantial scarring. The impact of HS on an individual’s quality of life is profound, often likened to or even exceeding that of severe conditions like psoriasis and the challenges faced by heart transplant candidates.

Unraveling the Causes: A Multifactorial Etiology

The precise cause of HS remains elusive, but current scientific understanding points towards a multifactorial etiology. This means HS likely arises from a complex interplay of several factors, including:

• Genetic Predisposition:
  • A significant portion of individuals with HS, approximately 33% to 40%, report having a first-degree relative with the condition, suggesting a strong hereditary component. The inheritance pattern is believed to be autosomal dominant, meaning the condition can be passed down even if only one parent carries the responsible gene. Recent genetic studies are actively identifying specific genes that may increase susceptibility to HS, aiming to clarify the genetic architecture of the disease.
• Hormonal Influences:
  • Hormones are suspected to play a role, particularly in women, as HS often flares around menstruation and can be influenced by hormonal therapies. However, the exact hormonal mechanisms are still being investigated. Research is ongoing to understand how androgens, estrogens, and other hormones may contribute to HS development and progression.
• Environmental Factors:
  • Environmental elements are also considered contributors. Smoking is a well-established risk factor, with studies showing a strong association between smoking and both the development and severity of HS. Obesity is another significant environmental factor, as increased weight and skin folds can exacerbate friction and inflammation in susceptible areas, promoting HS lesions. Research continues to explore other environmental triggers, such as specific dietary components or occupational exposures.
• Immunological Dysregulation:
  • The immune system’s role is increasingly recognized as central to HS. The condition is characterized by chronic inflammation, and research has identified abnormal immune activation within HS lesions. Key inflammatory mediators, such as tumor necrosis factor-alpha (TNF-α) and various interleukins, are found in elevated levels in affected skin, driving the inflammatory cycle. Immunological research is crucial to pinpoint specific immune pathways that can be targeted for more effective therapies.
• Skin Barrier Dysfunction:
  • Emerging research suggests that a compromised skin barrier may also contribute to HS. A dysfunctional skin barrier can increase susceptibility to bacterial colonization and inflammation within hair follicles, potentially initiating the HS disease process. Studies are investigating the specific defects in skin barrier function in HS patients and how these defects can be addressed therapeutically.
• Altered Microbiome:
  • The skin microbiome, the community of microorganisms residing on the skin, is also under investigation. An altered local microbiome, with imbalances in bacterial populations within hair follicles, may contribute to the inflammatory cascade in HS. Research is exploring the specific microbial profiles in HS lesions and whether manipulating the microbiome could offer therapeutic benefits.

Pathophysiology: A Step-by-Step Breakdown

The development of HS lesions is a complex process, often initiated by follicular occlusion, the blockage of hair follicles. This blockage is not simply due to poor hygiene, but rather a consequence of the aforementioned factors, including abnormal immune responses, skin barrier issues, and changes in the local microbiome.

1. Follicular Occlusion: The process likely begins with the plugging of hair follicles, potentially due to abnormal keratinization or other factors.
2. Inflammation and Rupture: The blockage traps sebum, bacteria, and cellular debris within the follicle, creating an inflammatory environment. This triggers an immune response, leading to the formation of painful nodules and abscesses. The inflamed follicle can rupture, releasing its contents into the surrounding skin and intensifying the inflammatory reaction.
3. Tunnel Formation and Chronic Inflammation: As the condition progresses, repeated cycles of inflammation and rupture can lead to the formation of tunnels, or sinus tracts, under the skin. These tunnels connect lesions and contribute to chronic, persistent inflammation. The inflammatory process is fueled by an increase in pro-inflammatory cytokines, perpetuating the cycle of lesion formation and tissue damage.

Hurley Staging System: Assessing Severity

The Hurley staging system is the most widely used classification to describe the severity of HS. It helps clinicians categorize the extent of the disease and guide treatment decisions. The Hurley stages are:

• Hurley Stage I:
  • Characterized by isolated abscesses without sinus tracts (tunnels) or scarring. This is the mildest form of HS.
• Hurley Stage II:
  • Defined by recurrent abscesses with sinus tracts and scarring. Lesions may be single or multiple but are typically widely separated. This stage represents moderate HS.
• Hurley Stage III:
  • Indicates diffuse or broad involvement across a region with multiple interconnected sinus tracts and abscesses. This is the most severe form of HS.

While the Hurley staging system is valuable, it is important to note that it primarily reflects the anatomical extent of the disease. Other scoring systems, such as the Hidradenitis Suppurativa Clinical Response (HiSCR) and the Sartorius score, are also used in clinical practice and research to assess disease activity and treatment response. These scoring systems may incorporate factors beyond anatomical staging, such as lesion counts, pain levels, and patient-reported outcomes, providing a more comprehensive assessment of HS severity and impact. Research continues to refine and validate these scoring systems to improve clinical management and research outcomes in HS.

Conclusion:

Understanding the complex interplay of genetic, hormonal, environmental, immunological, skin barrier, and microbial factors is crucial for developing more targeted and effective therapies for HS. Ongoing research continues to unravel the intricate mechanisms driving this debilitating condition.

References

Hidradenitis Suppurativa: Molecular Etiology, Pathophysiology, and Management—A Systematic Review – MDPI, accessed February 8, 2025, https://www.mdpi.com/1467-3045/45/5/280

Hidradenitis Suppurativa – StatPearls – NCBI Bookshelf, accessed February 8, 2025, https://www.ncbi.nlm.nih.gov/books/NBK534867/

Review of Comorbidities of Hidradenitis Suppurativa: Implications for Daily Clinical Practice, accessed February 8, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC6994573/

Hidradenitis suppurativa: from pathogenesis to diagnosis and treatment – PMC, accessed February 8, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC5402905/

HS and hormones: The connection – No BS About HS, accessed February 10, 2025, https://www.nobsabouths.com/hs-and-hormones

Smoking and hidradenitis suppurativa: Is there a link? – MedicalNewsToday, accessed February 8, 2025, https://www.medicalnewstoday.com/articles/smoking-and-hidradenitis-suppurativa

HS and weight loss: Can it help? – MedicalNewsToday, accessed February 8, 2025, https://www.medicalnewstoday.com/articles/hs-and-weight-whats-the-link

Hidradenitis Suppurativa (HS) Causes and Inflammation, accessed February 8, 2025, https://www.hsdiseasesource.com/hs-causes

Skin Homeostasis is Impaired in Hidradenitis Suppurativa Lesions: A Comparative Study. https://www.sciencedirect.com/science/article/pii/S0001731024005982#:~:text=The%20barrier%20function%20has%20been,nodules%2C%20abscesses%2C%20and%20fistulas.