Among the predisposing factors are genetic, physiologic, and environmental components. Approximately 40% of HS cases have a familial origin. Mutations can be categorized into: (1) mutations in genes encoding proteins of the γ-secretase complex and the Notch signaling pathway, and (2) mutations that cause inflammasome dysfunction.

The genes of the γ-secretase complex subunits with important mutations associated with HS described so far include PSENEN (presenilin enhancer), NCSTN (nicastrin), and PSEN1 (presenilin). One function of γ-secretase is to cleave the Notch protein to regulate this pathway. If cleavage occurs at the wrong site, signaling pathways are abnormally activated. Dysregulation of the Notch pathway causes altered keratinization and contributes to the development of the characteristic HS lesions. Some patients receiving γ-secretase inhibitors for Alzheimer disease may develop lesions identical to those observed in HS.

Mutations in the PSTPIP1 gene increase the activity of the inflammasome and of interleukins associated with this immune signaling pathway. Increased inflammasome activity has been observed in syndromic forms of HS.

The etiopathogenesis of HS has not yet been fully elucidated. HS begins around the hair follicle, and the etiopathogenic sequence classically described includes: (1) hyperkeratosis, occlusion, and dilation of the hair follicle, along with recruitment of immune cells in the dermis; (2) follicular rupture and release of its contents into the dermis (keratin, follicular fragments, PAMPs, and DAMPs), triggering an immune response and increased inflammation; and (3) tissue destruction, follicular fusion, epidermal acanthosis, pus formation, and development of tunnels (Fig. 1). Other theories propose that an inflammatory process is the initial pathogenic event, which subsequently leads to follicular occlusion, placing HS within the group of autoinflammatory keratinization diseases (AiKD).

Clinical signs of the disease usually include inflammatory lesions that are painful and commonly affect, although not exclusively, body areas rich in apocrine glands. These dynamic lesions are often accompanied by noninflammatory lesions such as scars, dry tunnels, and double comedones.

The main elementary lesions of HS are described in Tables 1 and 2.

In recent years, the importance of correctly identifying different lesion types has become evident to reduce interobserver variability that could affect therapeutic planning. The use of ultrasonography and the clinical-ultrasound definition of elementary lesions (Tables 1 and 2) has proven to be a fundamental tool, demonstrating its ability to reduce such variability.

Tunnel development is an inherent sign of HS and distinguishes it from other cutaneous diseases. These lesions are immunologically active and represent a source of inflammation in HS, associated with significant morbidity (pain and purulent drainage), and are considered predictors of poorer response to optimal medical therapy (OMT).26 Tunnel classification into 4 subtypes (Table 2) is particularly relevant (type A and type B tunnels may respond to OMT in up to 96% and 65% of cases, respectively). The presence of fibrosis (assessed morphologically and by shear-wave elastography) and the epithelium lining the tunnel walls—described on ultrasound as the “double rail sign”—have become highly useful findings for identifying which type B tunnels may respond to OMT.

According to data from the HS Delphi study conducted in Spain, the most frequent locations are the axillae (63.6%), groin (59.0%), buttocks (39.5%), perianal area (22.0%), and genital/pubic region (24.1%). Less frequent sites include the chest and breasts (15.1%), thighs (14.2%), abdomen (6.9%), back (6%), and facial area (4.8%). Differences may occur depending on the HS phenotype and the presence of comorbidities or associated risk factors.

Patients with HS report an average of 2–3 symptoms, and those with more severe disease tend to report a greater number of symptoms. The most common include inflammation/redness of lesions or abscesses (45.8%), pain or discomfort (39.8%), pain while sitting (32.2%), drainage from lesions (31.6%), pruritus (27.4%), impaired mobility or pain with limb movement (27.1%), malodorous discharge (19.3%), depression or low mood (17.5%), infection of lesions (17.2%), and sleep disturbances (11%).

To date, several classifications of patients with HS have been described. In 2013, Canoui-Poitrine et al.33 defined 3 phenotypes based on the analysis of different variables (demographic and clinical) in a cohort of >600 patients: LC1 (axillary–mammary), LC2 (follicular), and LC3 (gluteal).

In 2015, Van der Zee et al.34 proposed another descriptive classification into 6 phenotypes according to clinical and epidemiological characteristics: (1) normal type; (2) frictional furuncle type; (3) scarring folliculitis type; (4) conglobata type; (5) syndromic type; and (6) ectopic type (Fig. 2a). According to this publication, the presence of lesions in certain anatomical locations (gluteal, perianal, scrotal, facial, scalp) may be associated with a higher risk of disease progression.

Fig. 2.

Upper panel (A) HS phenotypes; adapted from González-Manso et al.25 Lower panel (B) proposal integrating all described models; adapted from Martorell et al.35

In 2020, Martorell et al.35 established 3 phenotypes: follicular or type A (nonprogressive), mixed or type B (slow progression), and inflammatory or type C (rapid progression). These phenotypes, associated with specific epigenetic profiles, provide a practical approach that helps identify patients eligible for biologic therapy.36,37 Recently validated by Frew et al.,36 this model is currently the most widely used phenotyping system for decision-making in disease management.

In 2021, González-Manso et al. proposed a classification into 2 endotypes, C1 (primarily follicular etiology) and C2 (primarily inflammatory etiology), based on cluster analysis. This model incorporates not only clinical signs of the disease but also demographic variables and their correlation with underlying biomarkers, guiding clinicians in selecting the most appropriate targeted therapy for each patient (Fig. 2a). Recently, it has been suggested that the gluteal phenotype could be subdivided into 2 subphenotypes with different clinical profiles, prognosis, and management strategies. Fig. 2b integrates the different proposed classifications.

Although all classifications have advantages and disadvantages, there is a physiopathologic, genetic, and epigenetic correlation between phenotypes38 and lesion type, number, and distribution, which ultimately guides therapeutic decision-making.39

HS is frequently associated with comorbidities such as rheumatologic diseases, inflammatory bowel disease (IBD), psychiatric or psychological disorders, and cardiometabolic diseases. Some share physiopathologic mechanisms or genetic bases with HS, whereas in other cases the association has not been clearly established.42,43 Chronic systemic inflammation associated with HS likely contributes to the increased frequency of these comorbidities.

Regarding rheumatologic diseases, the prevalence of joint involvement or arthropathies in patients with HS is higher than in the general population.44 Literature suggests that 2–28% of patients with HS present symptoms of spondyloarthropathies.45 Key elements in HS pathophysiology, such as Th17 cells and inflammatory cytokines, have also been identified as central effectors in the immunopathogenesis of other immune-mediated inflammatory diseases (IMID).40 Accordingly, 1–13% of patients with HS present IBD, 1–17% Crohn disease, and 1–9% ulcerative colitis.42,43,46,47 Psychiatric disorders such as depression, anxiety, and addictions including smoking and alcohol use occur in 5–36% of patients with HS.48–50

The increased prevalence of cardiometabolic comorbidities in patients with HS is partly explained by the significant association between cardiovascular risk factors (obesity, smoking) and, independently, by systemic inflammation associated with HS per se.51 Patients with HS have a higher risk of major adverse cardiovascular events (MACE) and cardiovascular mortality.39,52 Accordingly, patients with HS frequently present metabolic syndrome (40–51%),53 cardiovascular disease,51,52,54,55 metabolic-associated fatty liver disease,56 and diabetes mellitus (9–30%).57,58 Other comorbidities frequently associated with HS include polycystic ovary syndrome (9–14%),59 squamous cell carcinoma (5%),60 other neoplasms (Hodgkin lymphoma and oral or pharyngeal cancer),61 and Down syndrome (3%).62

This scale is the most widely used for classifying patients and provides qualitative information about the structural severity of the disease at a specific time point. It is simple and useful for surgical planning but is not suitable for evaluating therapeutic response to medical treatment and is not useful in clinical trials. The Hurley scale classifies patients into 3 severity stages, where stage I is the mildest form and stage III the most severe.63 It is considered useful in the noninflammatory phase of the disease to define the best surgical strategy.64

The modified Hurley scale subdivides the first 2 stages of the Hurley scale (I and II) into 3 subcategories according to severity: mild (A), moderate (B), and severe (C).65,66 It was designed to evaluate patient eligibility for immunomodulatory treatment, with the following stages considered eligible for biologic therapy: Ic, IIb, IIc, and III.

IHS4 is currently the most widely used scale and allows assessment of disease severity in clinical practice. The scale assigns 1 point for each nodule, 2 points for each abscess, and 4 points for each draining tunnel. The final score classifies disease severity as mild (≤3), moderate (4–10), or severe (≥11). The presence of a single draining tunnel automatically gives 4 points and is considered moderate disease, constituting a clinical criterion for biologic eligibility according to the most recent therapeutic guidelines.64,67 IHS4 is currently considered the most appropriate tool for assessing patients in the inflammatory phase of the disease, both at baseline and during follow-up.64

The IHS4-55 scale was developed to assess treatment success in a dichotomous manner. The threshold reduction in the IHS4 score required to achieve the therapeutic objective and the best correlation with other parameters previously validated in clinical trials, such as HiSCR50, were calculated. The optimal cutoff was determined to be a 55% reduction in the IHS4 score.97,98

The HiSCR score is the most widely used scale in clinical trials. It counts inflammatory nodules, abscesses, and tunnels and compares them with baseline values.68,69

HiSCR50, HiSCR75, and HiSCR90 are used and defined as a reduction of at least 50%, 75%, or 90%, respectively, in the total count of abscesses and inflammatory nodules, without an increase in the number of abscesses or draining tunnels vs baseline.

This score has some important limitations: it cannot be calculated in patients with fewer than 3 abscesses or nodules, and it does not adequately weigh the reduction in the number of draining tunnels, as it only considers whether they increase or not.

In addition to evaluating the disease signs per se, it is necessary to assess pain, pruritus, odor/exudate, and patient quality of life (QoL). To assess QoL, in addition to general instruments such as the Dermatology Life Quality Index (DLQI), specific scales for HS have been developed: HiSQOL (HiSQoL, HiSQoL adolescents, HiSQoL mini, HiSQoL-24). Of these, a validated Spanish version is available, HSQoL-24.70,71 Pain, pruritus, and odor/exudate are recommended to be evaluated using a visual analog scale (VAS) or a numeric rating scale (NRS).72

Ultrasonography allows evaluation of lesion type with high specificity and accuracy and can detect subclinical lesions in a noninvasive manner.73 Clinical evaluation has been shown to systematically underestimate lesion severity; therefore, ultrasonography is the recommended imaging technique for diagnosis, staging, and follow-up.74 However, its use has not yet become widespread in global clinical practice and has not been used in most clinical trials.

High-frequency ultrasonography (15–22MHz) is the most widely used modality for diagnosis, lesion classification, staging, and follow-up of patients with HS.75,76

Very high-frequency ultrasonography (>30MHz) can detect early signs of the disease that are significantly associated with severity, as well as two types of keratin fragmentation that may promote the formation and persistence of tunnels and secretions.77 Although ultrasound resolution does not allow detection of lesions<0.1mm, all HS lesions—including tunnels—can be classified using color Doppler ultrasonography. This technique allows identification of the anatomical characteristics, location, and classification of lesions, as well as detection of active inflammation.78

Shear-wave elastography has emerged as a useful tool for quantifying fibrosis within tunnels.79,80

Ultrasonography is also useful for guiding intralesional treatments,81 and with the help of color Doppler it can also define the relationship with vascular structures prior to surgery.82

For ultrasound staging, the SOS-HS scale, recently modified (mSOS-HS), was developed. It classifies HS into 3 stages (I–III) according to ultrasound findings. Its use is recommended in routine clinical practice to adequately characterize disease severity. Additionally, the US-HSA scale allows evaluation of disease activity by ultrasonography. Both scales may provide useful information for staging, clinical decision-making, and research purposes.76

Magnetic resonance imaging (MRI) has a limited role in the diagnosis and staging of HS.83 It is mainly used for genital, gluteal, and perianal lesions to differentiate perianal tunnels associated or not associated with Crohn diseasefrom HS lesions. MRI also plays a role in defining surgical strategy, particularly in patients with Hurley stage III areas, and as supportive imaging in clinical research trials.

Although the diagnosis of HS is clinical, complementary studies may occasionally be necessary to differentiate it from other conditions. Depending on the stage of disease evolution, lesions may resemble those of other pathologies. Establishing an appropriate differential diagnosis is important to distinguish early or late HS lesions from other diseases.23

Since HS is frequently associated with certain comorbidities, screening should be performed for the following: cardiovascular risk factors, spondyloarthritis, inflammatory bowel disease, syndromic HS, and psychological or psychiatric disorders,41 and uveitis should be evaluated if compatible symptoms are present.