Hidradenitis Suppurativa: Approaches to Management

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. 

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

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

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. 

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.

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. 

Preventive Strategies and Lifestyle Modifications⁴

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