HS is frequently misdiagnosed for 7 to 10 years because its symptoms resemble conditions like inflamed epidermal cysts, nodulocystic acne, and furuncles.
When evaluating a patient for hidradenitis suppurativa (HS), clinicians look for several hallmark features. Common findings include double comedones, sinus tract formation, scarring, deep-seated nodules, and draining pustules.¹ Patients frequently experience pain, itching, unpleasant odor, and discharge.¹ Multiple assessment tools exist to measure disease severity, most of which quantify various lesion types—such as inflammatory and noninflammatory nodules, fistulas or sinus tracts, scarring, and the extent of affected skin.¹ Pain remains one of the most significant measures of disease burden.¹ Among these tools, the Hurley staging system is the most widely used method for categorizing HS severity (Table 1).¹
Diagnosing HS is often challenging because its symptoms overlap with those of other skin conditions, leading to substantial delays—commonly 7 to 10 years—before an accurate diagnosis is made.² Important conditions to rule out include inflamed epidermal inclusion cysts, nodulocystic acne, and furuncles.² In contrast to HS, furuncles and inflamed cysts typically present with a central punctum and are less frequently located in intertriginous, or skin-fold, regions.² Inflamed cysts also tend to arise from previously stable, noninflamed cysts.² Nodulocystic acne mainly involves the face and trunk and generally does not produce sinus tracts.²
Patients with the longest diagnostic delays often saw nearly 5 different providers—most commonly primary care physicians, followed by dermatologists, surgeons, and gynecologists—and received an average of 5 incorrect diagnoses.² A strong correlation was noted between longer diagnostic delays and the number of misdiagnoses.² Because HS commonly affects sensitive body areas, many individuals, particularly those with more advanced disease, postpone seeking medical care due to embarrassment or fear.² Another study showed that prolonged delays in diagnosis are linked to more severe disease upon presentation, reflected by higher Hurley stages, as well as a greater burden of comorbid conditions.² These findings highlight the significant impact that delayed diagnosis has on disease severity and overall patient health.²
Table 1. Hurley Staging for Hidradenitis Suppurativa1
Hurley Stage
Description
I
Solitary or multiple isolated cysts/abscesses. No scarring or sinus tracts.
II
Single, multiple, widely separated, recurrent cysts/abscesses with sinus tract formation and scarring.
III
Multiple interconnected sinus tracts and cysts/abscesses throughout a broad area.
A growing body of research has shown that HS is linked to a broad spectrum of comorbidities shaped by genetic, hormonal, and environmental influences.³ Individuals with HS frequently face additional health concerns, including cardiovascular disease, type 2 diabetes, mental health conditions, and disturbances in sleep and sexual function.³ HS is thought to contribute to heightened systemic inflammation, which may elevate the risk of metabolic and cardiovascular issues and worsen overall clinical outcomes.³
HS also profoundly affects quality of life. One of the most widely used tools to measure this impact is the Dermatology Life Quality Index.4 This 10-item questionnaire assesses how skin disease interferes with daily tasks, work, recreation, and social interactions, offering clinicians valuable insight into the patient’s everyday challenges and disease burden.4
Traditionally, treatment options for patients with mild to moderate HS have been fairly limited. Topical clindamycin 1% remains the only antibiotic with proven effectiveness in controlled trials.5 Small studies also suggest that 1% resorcinol cream, applied twice daily for 12 to 16 weeks, may help in mild to moderate HS, although it is not widely available as a ready-made product.5 Intralesional corticosteroid injections, such as triamcinolone, can also be used as rescue therapy to reduce pain and inflammation and may be administered every 2 weeks.5
Several systemic treatments—including hormonal therapies and retinoids—have shown benefit in clinical studies. Tetracyclines are recommended for mild to moderate HS for a typical 12-week course or as long-term maintenance when appropriate.⁶ A combination of clindamycin and rifampin is considered an effective second-line approach for mild to moderate cases and may also serve as a first-line or adjunctive option in severe disease.⁶ For patients with moderate to severe HS, a regimen of moxifloxacin, metronidazole, and rifampin is suggested as a second- or third-line therapy.⁶ Dapsone may provide long-term maintenance benefits for individuals with Hurley stage I or II HS.⁶
Hormonal therapies—such as estrogen-containing oral contraceptives, spironolactone, cyproterone acetate, metformin, and finasteride—may be suitable for select female patients and can be used alone in mild to moderate disease or in combination with other treatments for more severe cases.⁶ Some reports suggest that progestin-only contraceptives may worsen HS and should be used cautiously.⁶ Evidence for isotretinoin is mixed, so it is best reserved as a second- or third-line therapy, particularly in patients who also have severe acne.⁶ Acitretin may be more effective than isotretinoin for HS, although robust comparative data are lacking; it is likewise considered a second- or third-line medication.⁶
Immunomodulators represent another category of potential treatments. Current evidence does not support methotrexate or azathioprine for HS.⁶ Limited data indicate that combining colchicine with minocycline may help in certain refractory mild to moderate cases, although colchicine alone is not advised.⁶ Cyclosporine may be considered for treatment-resistant moderate to severe disease when other systemic therapies are not effective or feasible.⁶ Short courses of systemic corticosteroids may help manage acute flares or serve as temporary bridging therapy.⁶ In severe cases, long-term systemic steroids—tapered to the lowest effective dose—may be added when standard therapies do not achieve adequate control.⁶
Growing interest has also focused on the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway—a rapid intracellular signaling system that regulates genes involved in inflammation and cancer.⁶ Because multiple cytokines implicated in HS rely on this pathway, JAK inhibition represents a promising therapeutic direction. ⁶
INCB054707, a JAK1 inhibitor, has undergone evaluation in 2 phase 2 trials (NCT04476043; NCT05620836) in patients with moderate to severe HS.⁶ The drug demonstrated good tolerability and clinical response, although significant improvement was seen only with the highest dose (90 mg), where 88% of patients achieved HS clinical response (HiSCR) vs 57% in the placebo arm.⁶
Upadacitinib, a second-generation selective JAK1 inhibitor, has shown promising results in a retrospective cohort study, with 75% of patients achieving HiSCR at 4 weeks and 100% at 12 weeks.⁶ HiSCR75 rates reached 30% at 4 weeks and 95% at 12 weeks.⁶ These findings led to the initiation of a phase 2 randomized controlled trial (NCT04430855), which is still ongoing.⁶ A separate phase 2 study (NCT05635838) is also underway to investigate topical ruxolitinib (a JAK1/JAK2 inhibitor) for early HS lesions.⁶
Biologic therapies have likewise demonstrated substantial benefits for individuals with moderate to severe HS. Table 2 outlines the available biologic options for managing HS.7,8
Table 2. Baseline Patient Characteristics, Efficacy, and Safety From Phase 3 Clinical Trials of Approved Therapies7,8
Adalimumab
Secukinumab
Bimekizumab
Phase 3 trials
PIONEER I (N = 307)
PIONEER II (N = 326)
SUNSHINE (N = 541)
SUNRISE (N = 543)
BE HEARD I (N = 505)
BE HEARD II (N = 509)
Key inclusion criteria
PIONEER I
Hurley stage II/III
≥ 3 inflammatory nodules and/or abscesses at baseline
TNF-α inhibitor naive
No concomitant oral antibiotics
PIONEER II
Hurley stage II/III
TNF-α inhibitor naive
Concomitant oral antibiotic (tetracycline) permitted (stable dose for ≥ 28 days prior to baseline)
SUNSHINE/SUNRISE
≥ 5 inflammatory nodules and/or abscesses for ≥ 1 year
Daily use of topical antiseptic wash
Previous TNF-α experience and concomitant oral antibiotic use permitted
BE HEARD I/II
Hurley stage II/III
≥ 5 inflammatory nodules and/or abscesses at both screening and baseline visits
Documented inadequate response to systemic antibiotics
Previous TNF-α experience and concomitant oral antibiotic use permitted
Key exclusion criteria
PIONEER I/II
Opioid analgesic use for HS-related pain
Draining fistula count > 6
Active ongoing skin condition that could interfere with HS assessment
SUNSHINE/SUNRISE
Draining fistula count > 6
Ongoing active conditions requiring treatment with systemic biologics, live vaccines, or other investigational treatments
BE HEARD I/II
Draining fistula count > 6
Active ongoing skin condition that could interfere with HS assessment
Dosing regimen
PIONEER I
Adalimumab 40 mg once weekly (n = 13)
Placebo (n = 14)
PIONEER II
Adalimumab 40 mg qw (n = 163)
Placebo (n = 163)
SUNSHINE
Secukinumab 300 mg once every 2 weeks (n = 31)
Secukinumab 300 mg once every 4 weeks (n = 30)
Placebo (n = 30)
SUNRISE
Secukinumab 300 mg once every 2 weeks (n = 30)
Secukinumab 300 mg once every 4 weeks (n = 30)
Placebo (n = 33)
BE HEARD I
Bimekizumab 36 mg once every 2 weeks (n = 289)
Bimekizumab 36 mg once every 4 weeks (n = 144)
Placebo (n = 77)
BE HEARD II
Bimekizumab 36 mg once every 2 weeks (n = 291)
Bimekizumab 36 mg once every 4 weeks (n = 144)
Placebo (n = 74)
Primary end point
HiSCR50 at week 12
HiSCR50 at week 16
HiSCR50 at week 16
Efficacy (achievement of primary end point for active treatment vs placebo)
PIONEER I
42% vs 36% (P = .003)
PIONEER II
59% vs 28% (P < .001)
SUNSHINE
(Once every 2 weeks, once every 4 weeks vs placebo)
45%,a 42% vs 34%
SUNRISE
(Once every 2 weeks, once every 4 weeks vs placebo
42%,b 46%a vs 31%
BE HEARD I
(Once every 2 weeks,a once every 4 weeksb vs placebo)
48%, 45% vs 29%
BE HEARD II
(Once every 2 weeks, once every 4 weeks vs placebo)
52%,a 54%a vs 32%
Statistical approach to missing data
PIONEER I/II
Missing assessments handled with nonresponder imputation
Patients requiring rescue therapy with antibiotics considered nonresponders
SUNSHINE/SUNRISE
Missing assessments handled with nonresponder imputation
Patients requiring rescue therapy with antibiotics considered nonresponders
BE HEARD I/II
Missing assessments handled with nonresponder imputation
Patients requiring new systemic antibiotic therapy (among those who were not receiving antibiotics at baseline) or any change in dose of systemic antibiotics (among those who were receiving systemic antibiotics at baseline) were considered non-responders
Common adverse events
PIONEER I/II
Headache (9%–10% in each group)
Nasopharyngitis (6%–11%)
SUNSHINE/SUNRISE
Headache (9%–12%)
Nasopharyngitis (5%–11%)
BE HEARD I/II
Headache (4%–8%)
Diarrhea (1%–8%)
Oral candidiasis (1%–8%)d
HS is a long-standing inflammatory condition that places a significant burden on those who live with it. Numerous studies highlight the many associated comorbidities, including cardiovascular disease, type 2 diabetes, mental health disorders, and disturbances in sleep and sexual function.³ Although newer therapeutic strategies—ranging from topical and surgical treatments to biologic agents and laser therapies—are emerging, many patients still face substantial obstacles in accessing these options. This underscores the need for improved recognition of HS in primary care settings and earlier, evidence-based treatment initiation to optimize patient outcomes.
Ferwa Mohammed, PA-C, MSPAS, is a board-certified physician assistant practicing in Wesley Chapel, Florida.
References
