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3 Things You Should Know About HS Pathology and Management

Dermatology TimesDermatology Times, May 2024 (Vol. 45. No. 05)
Volume 45
Issue 05

Earn CME credit and learn how to optimize a multimodal treatment approach for hidradenitis suppurativa.

This activity was written by PER® editorial staff based on an online activity developed with Chovatiya, Hawkes, and Porter.

This activity was written by PER® editorial staff based on an online activity developed with Chovatiya, Hawkes, and Porter.

Learning Objectives

Upon successful completion of this activity, you should be better prepared to:

  • Explain the evidence supporting the current understanding of hidradenitis suppurativa as an immune-mediated inflammatory disease
  • Assess disease severity using recommended instruments and evaluations in clinical practice
  • Optimize disease management using a multimodal treatment approach

Acknowledgment of Commercial Support

This activity is supported by educational grants from Novartis Pharmaceuticals and Incyte Corporation.


Chronic inflammation causes patients with hidradenitis suppurativa (HS) to develop painful skin lesions in regions including the axillae, groin, and inframammary areas. Disease onset can occur between ages 30 and 40, often impacting the most productive years of patients’ lives.1 Various treatments, such as lifestyle modification, topical and systemic pharmacologic therapy, surgical intervention, and pain management, are appropriate based on severity.2 Biologic agents now permit targeted immunomodulatory therapy, including the recent FDA approval of secukinumab, an inhibitor of interleukin (IL)-17A.3

Here are 3 things you should know about the pathology and management of HS.

1. Dysregulated immune responses are a hallmark of HS pathology.

A comprehensive understanding of HS pathobiology is still being developed, but genetics, the cutaneous microbiome, hormonal fluctuations, metabolic syndrome, and immune dysregulation are all thought to contribute to the disease.4-6 Environmental drivers of HS lesion formation and progression also include mechanical irritation of the skin, diet, and smoking.5

The HS disease process involves dilation and rupture of hair follicles occluded with keratin, triggering an inflammatory response. Proinflammatory cytokines like tumor necrosis factor alpha (TNF-α) induce the release of chemokines, which results in attraction of immune cells to the lesion site. TNF-α also mediates T-cell production of interferon gamma and IL-17. Patients with HS have elevated levels of IL-17 throughout the skin, indicating the presence of subclinical inflammation even in unaffected regions. Lesions have elevated levels of IL-23, which suggests involvement of the IL-23/IL-17 axis in HS.7 The IL-1β pathway has also been linked to HS pathogenesis, contributing to both systemic and local inflammation.8

2. Accurate assessment of disease severity directs management.

Clinical characteristics that form the basis for diagnosing HS are lesion morphology, distribution, and chronicity/recurrence.9 Following diagnosis, several staging systems are used to determine HS severity and to select appropriate treatment. Hurley staging is the most common system, with stage I (mild) indicated by ≥1 nodules and/or abscesses. Recurring nodules and/or abscesses with scarring and sinus tracts indicate Hurley stage II (moderate). Interconnected sinus tracts and abscesses along with scarring over an entire anatomical region are present in Hurley stage III (severe).1

Other staging systems include the Sartorius HS Score (HSS), which determines severity through assignment of points for affected regions, nodules, and sinus tracts. The HSS may be better at detecting inflammation than Hurley staging but can be too time consuming for a typical office visit.10 The Severity Assessment of HS score is a similar points-based system that includes physician- and patient-reported items, including pain.11 International HS Severity Score is another weighted quantitative measure of disease severity.1 The HS Area and Severity Index Revised assesses disease severity based on extent of involvement, rather than lesion count.12 Pain and disease burden can also be assessed with the Visual Analog Scale for pain and the Dermatology Life Quality index.13 Ultrasonography may also aid in identification of fistulous tracts and signs of active inflammation.14

HS Clinical Response (HiSCR) is used as a treatment end point in clinical trials. HiSCR is defined as the percentage of improvement in count of abscesses and inflammatory nodules, with no increases in abscesses or draining fistulae relative to baseline. HiSCR50, for example, is reached when the count of abscesses and nodules is 50% lower than at baseline, with no new abscesses and draining fistulae.15

Selection of Appropriate Treatment Depends on HS Disease Severity

Selection of Appropriate Treatment Depends on HS Disease Severity

3. Multimodal treatments shape the evolving management landscape.

Unlike mild HS, which may be responsive to topical or adjuvant therapy, moderate to severe HS may require systemic therapy or surgical intervention. Recently, targeted immunomodulatory therapy for HS has grown as an area of interest. Adalimumab, an anti–TNF-α monoclonal antibody, was the first biologic to receive FDA approval for the treatment of moderate to severe HS in adults and adolescents whose conventional treatment has failed.16,17 Approval was based on significant clinical response following adalimumab treatment (42%) versus placebo (26%; P = .003) in the phase 3 PIONEER I (NCT01468207) and PIONEER II (NCT01468233) trials.18

In October 2023, secukinumab received FDA approval as the first anti-IL17A monoclonal antibody to treat moderate to severe HS in adults.19

This approval was based on results of the pivotal phase 3 SUNSHINE (NCT03713619) and SUNRISE (NCT03713632) trials (n = 545). Patients received a 300-mg secukinumab injection or placebo every 2 or 4 weeks following initial weekly loading doses. Significantly more patients on a 2-week dosing interval in both trials achieved the primary end point of HiSCR50 at week 16 versus placebo (SUNSHINE: 44.5% vs 29.4% [P < .05]; SUNRISE: 38.3% vs 26.1% [P < .05]).20 At week 52, an even greater proportion of patients on the 2- and 4-week dosing regimens achieved HiSCR50, respectively, SUNSHINE: 56.4%, 56.3%; SUNRISE: 65.0%, 62.2%.21 Safety was consistent with previous reports, with no new safety signals identified.20

Other investigational agents in phase 2 and 3 trials are targeted at various immune molecules including IL-17 (bimekizumab, izokibep, sonelokimab), IL-1 (lutikizumab), phosphodiesterase-4 (orismilast, roflumilast), Bruton's tyrosine kinase (remibrutinib), Janus kinase (upadacitinib, povorcitinib, ruxolitinib), IL-1 receptor-associated kinase 4 (KT-474), CD-40 (iscalimab), IL-36 (spesolimab), leukotriene A4 (LYS-006), chemokines that bind to CXCR1 or CXCR2 (eltrekibart), and heat shock protein 90 (MC2-32).2

Although there is no uniform treatment strategy for HS, recommendations for management of moderate to severe or suboptimally controlled disease include surgical interventions, like deroofing or local excision, and biologic therapy.9 Recent approvals and ongoing investigation of other immunomodulators are likely to provide patients with more options for targeted treatment.

“The treatment of hidradenitis suppurativa (HS) presents a major challenge for patients and dermatologists alike. We are now beginning to unravel the complex pathogenesis and clinical manifestations of this disease, and based on the encouraging data released at the 2024 AAD Annual Meeting, I am optimistic that [we] are closer than ever to having multiple safe and effective options that can provide long-term control of HS.”

—Raj Chovatiya, MD, PhD, MSCI, FAAD

Key References

7.Del Duca E, Morelli P, Bennardo L, Di Raimondo C, Nisticò SP. Cytokine pathways and investigational target therapies in hidradenitis suppurativa. Int J Mol Sci. 2020;21(22):8436. doi:10.3390/ijms21228436

18.Zouboulis CC, Okun MM, Prens EP, et al. Long-term adalimumab efficacy in patients with moderate-to-severe hidradenitis suppurativa/acne inversa: 3-year results of a phase 3 open-label extension study. J Am Acad Dermatol. 2019;80(1):60-69.e62. doi:10.1016/j.jaad.2018.05.040

20.Kimball AB, Jemec GBE, Alavi A, et al. Secukinumab in moderate-to-severe hidradenitis suppurativa (SUNSHINE and SUNRISE): week 16 and week 52 results of two identical, multicentre, randomised, placebo-controlled, double-blind phase 3 trials. Lancet. 2023;401(10378):747-761. doi:10.1016/S0140-6736(23)00022-3

For a full list of references go to: https://gotoper.com/hs24pathology-postref

Claim Your CME Credit at:

Faculty, Staff, and Planners’ Disclosures

In accordance with ACCME Guidelines, PER® has identified and resolved all conflict of interest for faculty, staff, and planners prior to the start of this activity by using a multistep process.

Disclosures (Chovatiya): Consultant: AbbVie, Amgen, Apogee Therapeutics, Arcutis Biotherapeutics, Argenx, Aslan Pharmaceuticals, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Dermavant Sciences, Eli Lilly and Company, Fide, Galderma, Genentech, GSK, Incyte, LEO Pharma, L’Oréal, Nektar Therapeutics, Novartis, Opsidio, Pfizer, Regeneron Pharmaceuticals, Sanofi, Sitryx, UCB. Speakers’ Bureau: AbbVie, Arcutis Biotherapeutics, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant Sciences, Eli Lilly and Company, Incyte, LEO Pharma, Novan, Pfizer, Regeneron Pharmaceuticals, Sanofi, UCB.

Disclosures (Hawkes):

Disclosures: Consultant: AbbVie, Arcutis Biotherapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi, Sun Pharmaceutical Industries, UCB; Speakers’ Bureau: Boehringer Ingelheim, Bristol Myers Squibb, Regeneron Pharmaceuticals, Sanofi, UCB; Other (spouse, employment): Regeneron Pharmaceuticals.

Disclosures (Porter):

Grant/Research Support: AbbVie, Acelyrin, AnaptysBio, Bayer, Bristol Myers Squibb, Eli Lilly and Company, Incyte, Janssen, Lilly, MoonLake, Novartis, Pfizer, Prometheus Laboratories, Regeneron, Sanofi, Sonoma Biotherapeutics, UCB; Consultant: Acelyrin, Alumis, Eli Lilly and Company, Incyte, Janssen, Novartis, Pfizer, Prometheus Laboratories, Sanofi, Sonoma Biotherapeutics, Trifecta Clinical, UCB; Other: Royalties: Beth Israel Deaconess Medical Center.

The staff of Physicians’ Education Resource,® LLC, have no relevant financial relationships with ineligible companies.

To learn more about this topic, including information on managing hidradenitis suppurativa (HS), go https://gotoper.com/go/hs24dfk-activity

Release Date: May 1, 2024

Expiration Date: May 1, 2025

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