Disease progression in hidradenitis suppurativa: A multidimensional framework

Hidradenitis suppurativa (HS) is increasingly recognized as a progressive inflammatory disease in which recurrent follicular inflammation, tunnel formation and systemic inflammation drive cumulative, largely irreversible tissue damage, quality-of-life impairment and cardiometabolic comorbidity. Despite this, no consensus definition of disease progression exists. This review synthesizes current evidence to propose a working, multidimensional framework for progression in HS and to map its determinants, detection tools and consequences. We frame progression along six complementary dimensions grouped in three blocks-objective severity (Hurley transition, International Hidradenitis Suppurativa Severity Score System [IHS4] category shift), anatomical extension (extra- and intraregional spread) and cumulative disease burden (secondary complications and patient-reported impact)-aligned with current European guidelines for therapeutic escalation. Available longitudinal data show that incidence and speed of progression depend strongly on care setting and assessment method, with tertiary cohorts assessed clinically and by ultrasound reporting incidences of approximately 37% over ~2 years and self-reported community cohorts substantially lower. Independent risk factors cluster into demographic-familial, phenotypic-anatomical, lifestyle-metabolic, laboratory and comorbidity domains, with early-onset disease, smoking, inflammatory bowel disease, Down syndrome and pilonidal sinus as the most consistent signals. Phenotype frameworks converge on a higher-risk profile of male, smoker patients with severe acne and lower-body involvement. Genotype shapes phenotype, with γ-secretase/Notch variants driving an occlusion-dominant course and inflammasome variants (PASH, PAPASH, PAPA, SAPHO) a more systemic one; heritability approaches 77%. Ultrasound refines staging, detects subclinical microtunnels and identifies the inflamed non-draining tunnel that defines a within-lesion window of opportunity. Progression has tangible cutaneous, psychosocial, systemic, metabolic and cardiovascular consequences, making early recognition a clinical imperative; disease modification within a limited therapeutic window remains a plausible and testable paradigm rather than a demonstrated fact.