Neuroendocrine-Immune Model Explains Hidradenitis Suppurativa Pain, Pruritus, and Hormonal Triggers

Hidradenitis suppurativa (HS) is a chronic, debilitating inflammatory skin disease characterized by lesions in intertriginous areas. However, current dermatologic models fail to adequately explain the severe, often intractable pain and pruritus that patients experience, which frequently persist even between flares. These symptoms are also notably exacerbated by psychological stress and hormonal fluctuations, particularly during menstrual cycles in women. This highlights a critical gap in understanding HS pathogenesis, necessitating a broader conceptual framework that integrates the complex interplay between the neuroendocrine and immune systems.

Researchers developed a comprehensive neuroendocrine-immune model for Hidradenitis suppurativa (HS) by synthesizing existing literature on disease pathogenesis, patient symptomatology, and the dynamic communication between the nervous, endocrine, and immune systems. This conceptual framework was designed to address the limitations of purely dermatologic models, which often fail to fully account for the prominence of chronic pain, pruritus, and the fluctuation of symptoms with patients' stress and hormonal cycles. The review proposes a paradigm shift, recognizing that these systems do not function in isolation but rather engage in bidirectional communication that profoundly shapes disease progression and symptom expression.

The proposed neuroendocrine-immune model posits that dynamic, bidirectional communication between the nervous, endocrine, and immune systems fundamentally shapes Hidradenitis suppurativa (HS) pathogenesis, extending beyond visible skin lesions. It highlights how psychological stress and hormonal fluctuations, particularly during menstrual cycles, significantly exacerbate debilitating symptoms like chronic pain and pruritus, which often persist despite control of visible inflammation. The model emphasizes that sex hormones function as modulators rather than sole drivers of the disease, explaining HS occurrence in men, prepubertal children, and postmenopausal women. This integrated framework provides a robust explanation for the severe, often intractable pain and pruritus in HS, linking them to neuroendocrine-immune dysregulation rather than solely to dermatologic inflammation. The model also accounts for the observed 3:1 female-to-male predominance in Western cohorts by integrating menstrual cycle-associated flares, while acknowledging the broader relevance of these neuroendocrine-immune mechanisms to all HS patients. This paradigm shift offers a more holistic understanding of the disease's complex and often disproportionate symptomatology.