Boil-like swellings are the hallmark of hidradenitis suppurativa (HS), a chronic, recurrent inflammatory skin disease of the hair follicle. Painful, inflamed nodules are connected via sinus tracts and fistulae. Infection of a nodule can lead to the formation of foul-smelling pus with residual tissue destruction and scarring following nodule rupture.1,2 Common sites of infection are within skin folds such as the armpit, the groin, under the breasts, under folds of the stomach in obese people, and gluteal and perianal areas.
 
Symptoms of HS generally start in early adulthood, although rare cases have been reported in pediatric patients. The disease can persist for decades.3 Genetic predisposition to HS increases risk, mainly if disease onset occurs at puberty. A family history of HS is observed in approximately 30% of patients with the condition, and gene mutations have been identified in patients with the condition.3 Lifestyle and medical conditions also appear to correlate with HS; 99% of patients are a current or former smoker, 50% are obese, and approximately 40% have metabolic syndrome.3
 
The precise pathophysiology of HS is unknown, although the disorder is thought to be driven by a complex cascade of proinflammatory cytokines and anti-inflammatory mediators, which may contribute to the systemic comorbidities, including metabolic syndrome, type 2 diabetes mellitus, atherosclerosis, spondyloarthropathy, and inflammatory bowel disease. These complications are associated with substantially increased mortality.2,3 The associated pain of HS can be disabling and can restrict movement; wounds heal slowly, and repeated flares are sometimes refractory to treatment. The impact of HS is devastating on quality of life and contributes to poor economic and mental health status, thus increasing the risk of depression, anxiety, and substance use disorder. The suicide rate among people with HS is 2.4 times that of the general population.4

The precise prevalence and incidence of HS are unknown, partly due to the challenge of standardized reporting of the disease. A recent global study, based on 118,760,093 cases of HS, report a pooled prevalence rate of 0.3% (0.2-0.6).5 However, regional differences in HS prevalence have been reported (Figure 1).5 Sex differences have also been reported globally; the prevalence of HS is lower in US men vs women (odds ratio [OR], 0.403; 95% CI, 0.37-0.439; P <.001) and lower in the United States than in Europe (OR, 0.635; 95% CI, 0.397-1.015; P =.08) but higher in men in the Asia-Pacific region (OR, 0.936; 95% CI, 0.319-2.751; P =.78).3,5
 
In the United States, registry data suggest increasing HS incidence, possibly due to improved diagnosis and reporting. Additionally, the incidence of HS has increased over the past 10 years, with the condition disproportionately involving young adults, women, and Black individuals.6



Early and accurate HS diagnosis is essential for prompt treatment and to minimize progression and associated comorbidities. Failure to diagnose and treat HS promptly can result in several complications (Table 1). The simultaneous presence of multiple types of lesions — including inflammatory nodules, abscesses, inflamed and draining sinus tracts or fistulae, and rope-like scarring — can challenge accurate diagnostic evaluation. The differential diagnosis, particularly in the presence of early HS lesions, can also be challenging because the presentation often mimics other disorders, including bacterial and fungal infections, cysts, acne conglobata, dissecting cellulitis of the scalp, pilonidal sinus, and cutaneous Crohn disease.3
 
Consequently, missed diagnosis and misdiagnosis are not uncommon, and a diagnostic delay of as long as 7 years has been reported.7 Despite the significant impact of HS on quality of life, treatment options are limited. Recently, however, the first biologic, adalimumab, has been approved for HS, and other targeted therapies are areas of active research. 


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Helpful Approaches (And Some Not-So-Helpful Approaches) to the Diagnostic Evaluation of HS

The clinical diagnosis of HS is based on the nature and localization of skin lesions and the disease course. Lesions can be persistent (lasting ≥6 months) or recurrent (2 or more skin lesions occurring or recurring within 6 months).3 Full-body skin examination is required to assess the extent and severity of HS and determine appropriate treatment. Magnetic resonance imaging can, potentially, help preoperative assessment of fistulation in the anogenital area by excluding the presence of fistulae that communicate with the rectum or anal canal. Classification of HS disease severity is based on several scoring systems; their advantages and disadvantages are summarized in Table 2.2,3


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Although the available scoring tools are helpful, they have limitations. Most are not detailed enough for precise descriptions of disease severity or to assess treatment outcomes. Scores based on lesion counts might not help patients who have lesions that are extensively inflamed with areas lacking clear, individual, countable nodules (found frequently in patients with Hurley stage III disease). Other scoring systems have been proposed, including the refined Hurley score8 and the Severity Assessment of Hidradenitis Suppurativa scoring system.9
 
Blood biomarkers have been used to assess deep-seated inflammatory processes that cannot be seen near the skin surface. The erythrocyte sedimentation rate and increased expression of several proteins, including chitinase-3-like protein 1 (YKL-40), interleukin (IL)-6, and C-reactive protein, correlate with the extent of inflammatory skin alterations.3
 
Patient-reported outcome measures have also been used in diagnostic evaluations. Commonly used measures include the Dermatology Life Quality Index (DLQI) to assess the impact of skin disease and the Visual Analogue Scale or Numeric Rating Scale (a segmented numerical version of the Visual Analogue Scale) to assess pain and itch; the DLQI is also helpful for assessing the impact of HS on daily life.3,10 Less commonly used outcome measures are the Hidradenitis Suppurativa Global Assessment Scale, the Hospital Anxiety and Depression Scale, the Work Ability Index, and Work Productivity and Activity Impairment. An HS burden-of-disease tool has also been described but is not fully validated.3,11
 
Not all assessments are helpful, however, in the setting of HS.3,4

  • Skin biopsy is usually not required for the diagnosis of HS; however, it might be useful to exclude other disorders, such as pyoderma gangrenosum, squamous cell carcinoma, and lymphomas.
  • Routine bacterial culture is not recommended in HS; however, it can help in cases suggestive of infection rather than HS or with infection secondary to HS.
  • Ultrasonography is typically not required but sometimes may be useful in obese patients in whom clinically undetectable lesions might be discovered.
  • Blood tests are not used because the various blood proteins tested are not HS-specific when elevated.

Management

Although HS is primarily a dermatologic disease, it has a multisystem manifestation. Therefore, optimal management must involve a multidisciplinary approach to address all facets of HS presentations (Figure 2).1 Current management approaches include pharmacotherapy, surgery, lifestyle modification, patient education, supportive care for pain management and psychological well-being, and treatment of superinfection, in addition to an individualized approach based on disease severity. 



Pharmacotherapy3,4,12,13

  • Systemic antibiotics
    • Oral tetracyclines are the first-line treatment (eg, at 500 mg twice daily) for mild to moderate, multifocal HS.
    • Clindamycin plus rifampin combination is the first-line treatment for patients with moderate to severe HS or second-line treatment for mild disease. Patients aged 50 years and older or ever-smokers are less likely to tolerate this combination.
    • Metronidazole plus moxifloxacin plus rifampin can be used as second- and third-line treatment in mild to moderate HS.
    • Dapsone is reserved for third-line treatment in patients with mild to moderate disease.
    • Ertapenem via intravenous dosing is reserved for severe, treatment-refractory HS and can be used as a bridge to surgery or consolidation medical treatment.
  • Corticosteroids
    • Intralesional triamcinolone acetonide can be used for HS nodules, abscesses, and draining sinuses.
    • Systemic corticosteroids must be used with caution in patients with comorbidities, such as hypertension, diabetes mellitus, osteopenia and osteoporosis, and psychiatric disorders.
  • Hormonal therapy
    • Antiandrogen contraceptives. Progesterone-only contraception can exacerbate HS; however, combined oral contraceptives can help female patients whose primary HS treatment is unsafe in pregnancy and can reduce adverse effects of spironolactone (see below).
    • Finasteride is a useful adjunct in patients with mild to moderate HS that fails to respond to first- and second-line therapies.
    • Metformin can be considered in patients with diabetes, pregnant patients, and patients with polycystic ovarian syndrome.
    • Spironolactone can be considered as adjunctive therapy in young, healthy women with mild to moderate HS.
  • Systemic retinoids
    • Isotretinoin is not recommended for routine treatment of HS. It can be considered for healthy-weight women with acne and milder HS, which is more likely to respond to treatment.
    • Acitretin can be used as second- or third-line therapy to treat moderate to severe HS in patients without childbearing potential.
  • Biologic therapy
    • Adalimumab is a tumor necrosis factor-alpha (TNF-α) inhibitor that is the only biologic treatment approved by the US Food and Drug Administration (FDA) as first-line therapy for patients aged 12 years and older with moderate to severe HS. Adalimumab was shown to be effective in large randomized controlled trials. Results from the PIONEER I and PIONEER II (ClinicalTrials.gov Identifier:NCT01468207 andNCT01468233, respectively) phase 3 randomized controlled trials, which studied adalimumab in 633 patients, support the use of weekly subcutaneous injection. Although current data are not available for COVID-19 risk in patients with HS, data from PIONEER I and PIONEER II might provide important insight into the risk of infectious complications in this unique patient population. Infection data from PIONEER can be used to make informed treatment decisions for patients with HS during the ongoing COVID-19 pandemic.14,15
    • Infliximab, golimumab, and etanercept are TNF-α inhibitors that have been explored for the treatment of HS, although evidence is limited to small-scale studies.
      • Infliximab is not approved by the FDA, although it has been used as second-line therapy in patients with severe HS. It might prove helpful for patients in whom treatment with adalimumab was unsuccessful, possibly due to greater dosing flexibility.
      • A few reports suggest benefit in using golimumab at higher dosages (eg, 200 mg IV followed by 100 mg IV every 4 weeks).
      • No significant improvement in patient- or physician-reported outcomes has been documented with etanercept. The HS ALLIANCE expert working group recommends against using etanercept in HS.13
    • Apremilast is a phosphodiesterase-4 inhibitor that can be used as second-line treatment for patients with mild to moderate disease.
    • Anakinra (an IL-1-receptor inhibitor) and secukinumab (an IL-17 inhibitor) can be used to treat moderate to severe HS.
    • Ustekinumab may be more effective in patients with moderate disease than in those with severe disease, as well as in patients with lower expression of leukotriene A4 hydrolase.
    • Guselkumab has been reported to ameliorate refractory moderate to severe HS, although at least 4 months of treatment might be required before seeing improvement.
  • Other medical treatments
    • Zinc gluconate. Patients with HS often have a low zinc level. Two case series have demonstrated modest clinical improvement in DLQI in patients with Hurley stages I and II HS treated with zinc gluconate 90 mg/d with or without topical triclosan 2% twice daily.
    • Colchicine. A prospective case series of 20 patients demonstrated improvement in DLQI and patient global assessment using a regimen of minocycline 100 mg/d plus colchicine 0.5 mg twice daily for 6 months, followed by colchicine 0.5 mg twice daily for 3 months.
    • Cyclosporine. A retrospective case series of 18 patients treated with cyclosporine 2.0-3.5 mg/kg showed some benefit in half of patients.

Adalimumab adverse effects
Flip
Adverse effects most commonly reported include infection (eg, upper respiratory tract and sinuses), injection site reaction, headache, and rash.

Although progress has been made in the management of HS, treatment options remain limited. Evidence linking HS to an immune-mediated disease has created opportunities to explore new therapies targeting various pathways, including IL-1, IL-17, and IL-12/23 inhibitors. Several agents are being evaluated in ongoing clinical trials (Table 3), which might uncover the complex underlying HS pathophysiology, possibly involving multiple pathways, thus suggesting a combination of targeted therapies.3,12 These studies also suggest that new treatment options might become available for HS in the future.


IL, interleukin.

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Response to treatment is typically assessed with the Hidradenitis Suppurativa Clinical Response (HiSCR), the gold standard primary outcome measure for HS clinical trials. HiSCR is an HS-specific binary scoring system for patients with 3 or more abscesses or inflammatory nodules.16 Response is defined as an at least 50% reduction in inflammatory lesion count (abscesses plus inflammatory nodules) and no increase in abscesses or draining fistulae compared with baseline. HiSCR has recently been used to assess the effectiveness of treatment with biologics; however, HiSCR does not assess the presence of draining tunnels, which is a common finding in advanced disease.16,17

Surgical and Laser Management of HS

Surgery might be indicated for patients with severe lesions refractory to treatment and for those with tunnels, scarring, and skin contractures.3,12 For patients with low inflammatory activity, surgery should be done promptly; however, patients with high inflammatory activity should be initially treated with systemic antibiotics or adalimumab, or both, before surgical intervention.3 Several surgical techniques are used in the management of HS. 

  • De-roofing involves surgical removal of the skin covering a tunnel, with natural healing of the exposed wound. This procedure is used in patients with a recalcitrant draining tunnel.
  • Skin ablation of lesions (electrosurgery) can be used to remove diseased tissue, followed by natural healing of the wound.
  •  Excision involves complete removal of all affected lesions, including a 1- to 2-cm lateral margin of healthy skin. The procedure is performed on patients with very severe Hurley stage III disease.4

Preventive Strategies and Lifestyle Modifications4

These components of management include:

  • Patient education
  • Regular body inspection
  • Weight reduction (sports activities might be challenging because of the pain caused by friction during exercise); because extensive weight loss might create loose skin, resulting in increased friction, reconstructive plastic surgery might be needed in concerned patients
  • Smoking cessation
  • Avoidance of situations and environments of increased humidity, heat, and risk of microbial colonization
  • Avoidance of dairy foods, brewer’s yeast, tight clothing, and shaving

Conclusion and Clinical Implications

HS is a chronic disease with a devastating impact on quality of life. Disease onset can be as early as puberty and the disease can span several decades, requiring ongoing management. The disease can improve with early diagnosis and effective treatment; however, challenges persist with the differential diagnosis, delayed diagnosis, and limited pharmacotherapeutic options.
 
Topical, oral, and targeted injectable therapies continue to be developed as improved understanding of pathogenesis of HS emerges. Although primarily a skin condition managed by dermatologists, several systemic comorbidities are seen in patients with HS and require a multidisciplinary team approach to optimally address all facets of HS presentations.

References

1. Narla S, Lyons AB, Hamzavi IH. The most recent advances in understanding and managing hidradenitis suppurativa. F1000Res. 2020;9:F1000 Faculty Rev-1049. doi:10.12688/f1000research.26083.1

2. Scuderi N, Monfrecola A, Dessy LA, Fabbrocini G, Megna M, Monfrecola G. Medical and surgical treatment of hidradenitis suppurativa: a review. Skin Appendage Disord. 2017;3(2):95-110. doi:10.1159/000462979

3. Sabat R, Jemec GBE, Matusiak Ł, Kimball AB, Prens E, Wolk K. Hidradenitis suppurativa. Nat Rev Dis Primers. 2020;6(1):18. doi:10.1038/s41572-020-0149-1

4. Orenstein LAV, Nguyen TV, Damiani G, Sayed C, Jemec GBE, Hamzavi I. Medical and surgical management of hidradenitis suppurativa: a review of international treatment guidelines and implementation in general dermatology practice. Dermatology. 2020;236(5):393-412. doi:10.1159/000507323

5. Phan K, Charlton O, Smith SD Global prevalence of hidradenitis suppurativa and geographical variation—systematic review and meta-analysis. Biomedical Dermatology.
2020;4(2):1-6. doi:10.1186/s41702-019-0052-0

6. Garg A, Lavian J, Lin G, Strunk A, Alloo A. Incidence of hidradenitis suppurativa in the United States: a sex- and age-adjusted population analysis. J Am Acad Dermatol. 2017;77(1):118-122. doi:10.1016/j.jaad.2017.02.005

7. Saunte DM, Boer J, Stratigos A, et al. Diagnostic delay in hidradenitis suppurativa is a global problem. Br J Dermatol. 2015;173(6):1546-1549. doi:10.1111/bjd.14038

8. Horváth B, Janse IC, Blok JL, et al. Hurley staging refined: a proposal by the Dutch Hidradenitis Suppurativa Expert Group. Acta Derm Venereol. 2017;97(3):412-413. doi:10.2340/00015555-2513

9. Hessam S, Scholl L, Sand M, Schmitz L, Reitenbach S, Bechara FG. A novel severity assessment scoring system for hidradenitis suppurativa. JAMA Dermatol. 2018;154(3):330-335. doi:10.1001/jamadermatol.2017.5890

10. Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI). April 1992. Accessed April 4, 2021. www.bad.org.uk/shared/get-file.ashx?id=1653&itemtype=document. Accessed March 30, 2021.

11. Pinard J, Vleugels RA, Joyce C, Merola JF, Patel M. Hidradenitis suppurativa burden of disease tool: pilot testing of a disease-specific quality of life questionnaire. J Am Acad Dermatol. 2018;78(1):215-217.e2. doi:10.1016/j.jaad.2017.08.030

12. Goldburg SR, Strober BE, Payette MJ. Hidradenitis suppurativa: current and emerging treatments. J Am Acad Dermatol. 2020;82(5):1061-1082. doi:10.1016/j.jaad.2019.08.089

13. Zouboulis CC, Bechara FG, Dickinson-Blok JL, et al. Hidradenitis suppurativa/acne inversa: a practical framework for treatment optimization – systematic review and recommendations from the HS ALLIANCE working group. J Eur Acad Dermatol Venereol. 2019;33(1):19-31. doi:10.1111/jdv.15233

14. Blaszczak A, Trinidad JCL, Cartron AM. Adalimumab for treatment of hidradenitis suppurativa during the COVID-19 pandemic: safety considerations. J Am Acad Dermatol. 2020;83(1):e31. doi:10.1016/j.jaad.2020.04.030

15. Frew JW, Jiang CS, Singh N, et al. Clinical response rates, placebo response rates, and significantly associated covariates are dependent on choice of outcome measure in hidradenitis suppurativa: a post hoc analysis of PIONEER 1 and 2 individual patient data. J Am Acad Dermatol. 2020;82(5):1150-1157. doi:10.1016/j.jaad.2019.12.044
16. Kimball AB, Jemec GEB, Yang M et al. Assessing the validity, responsiveness and meaningfulness of the Hidradenitis Suppurativa Clinical Response (HiSCR) as the clinical endpoint for hidradenitis suppurativa treatment. Br J Dermatol. 2014;171(6):1434-1442. doi:10.1111/bjd.13270

17. Kimball AB, Sobell JM, Zouboulis CC, et al. HiSCR (Hidradenitis Suppurativa Clinical Response): a novel clinical endpoint to evaluate therapeutic outcomes in patients with hidradenitis suppurativa from the placebo-controlled portion of a phase 2 adalimumab study. J Eur Acad Dermatol Venereol. 2016;30(6):989-994. doi:10.1111/jdv.13216

Posted by Haymarket’s Clinical Content Hub. The editorial staff of Dermatology Advisor had no role in this content’s preparation.

Reviewed August 2021