Out of the Tunnel: Understanding Hidradenitis Suppurativa

Just two years ago, the medical literature added 2893 articles on psoriasis. Comparatively, 396 articles in 2018 focused on another inflammatory skin disease: hidradenitis suppurativa (HS).¹ The seven-fold difference in peer-reviewed publications between the two immune-mediated diseases is further illuminated by a similar difference in the number of FDA-approved treatments. While knowledge gaps persist, HS is beginning to come to the forefront of dermatologic research, bringing a much-needed concentration to a long underrecognized and undertreated disease.

Characterizing HS
“HS has been underrecognized for so long, and outside of dermatology, I think it still is, but it is really exciting to see people pay more attention,” said Haley Naik, MD, MHSc, FAAD. Dr Naik is an assistant professor of dermatology and director of the Hidradenitis Suppurativa Program at University of California, San Francisco. Her background includes numerous research articles regarding the diagnosis, treatment, and management of HS as well as multiple clinical translational studies to identify its biological characteristics. In collaboration with the Hidradenitis Suppurativa Foundation, Dr Naik also leads the Hidradenitis Suppurativa PRospective Observational REgistry and bioSpecimen repoSitory (HS PROGRESS), a multicenter cohort study aimed at comprehensively characterizing the clinical and biological features of HS.

The disease, also known as acne inversa, features chronic, painful, and deep-seated inflammatory nodules often occurring in intertriginous areas. The current pathophysiologic theory centers on follicular occlusion with hyperkeratosis and plugging. Mechanical stresses on the plugged follicular duct result in rupture, subsequently spilling the duct contents into the surrounding dermis and attracting immune system stimuli to cause an inflammatory response.^2,3 As the disease progresses, its early nodules form abscesses, sinus tracts, and scarring (Table). Early stage disease is often associated with misdiagnosis, with an average delay in diagnosis of 7 years⁴; common differential diagnoses include folliculitis, infectious abscesses, intergluteal pilonidal disease, and Crohn disease.³ HS notably affects women and Black Americans  disproportionately in comparison with its approximately 1% prevalence
in the general population,⁵ and it has been shown to be associated with family history,³ obesity, smoking,⁴ and inflammatory bowel disease.⁶

“There is great work being done to understand the biology of HS, which will ultimately lead to the identification of new biomarkers and novel treatments that will hopefully be even more efficacious than the treatments that currently exist today,” said Dr Naik. “There’s also good work currently being done to understand the conditions that are associated with HS and ways that we can think about managing HS and those comorbid conditions to improve patient quality of life. We are also looking at the impact of HS in the setting of pregnancy and breastfeeding.”

She also noted how quality of life continues to be a main pillar of current HS research. In particular, studies are aimed at understanding how to best manage HS-related pain, which is the most common patient-reported HS flare symptom.^7,8 Patients describe their nociceptive and neuropathic pain as their most impactful symptom of HS,^9-11 beating out other commonly reported flare symptoms of lesional drainage, itch, and bleeding.⁷

“Thankfully, we’re now seeing significant support from federal agencies for this ongoing research,” Dr Naik said. “In fact, the National Institute of Arthritis and Musculoskeletal and Skin Diseases has two disease-specific funding announcements dedicated to HS, and there’s great enthusiasm in the private sector as well. I think people are beginning to understand the true burden of HS in both the US population and in the global population. We are very much on the verge of developing new effective treatments and better understanding this disease.”

Intersection of HS and COVID
Research may be working toward completing the picture of disease pathophysiology, but a more immediate, pressing need to understand the intersection of HS and COVID-19 has taken precedent.

In addition to her ongoing research, Dr Naik serves as the principal investigator of the Global Hidradenitis Suppurativa COVID-19 Registry. The project was launched by an international team of investigators and patient partners from the United States, Canada, United Kingdom, Australia, Italy, and Denmark in collaboration with the US Hidradenitis Suppurativa Foundation, Canadian Hidradenitis Suppurativa Foundation, Asia-Pacific Hidradenitis Suppurativa Foundation, Hope for HS, and the Hidradenitis Suppurativa Warriors patient support groups. The registry aims to identify predictors of COVID-19 outcomes in adult and pediatric patients with HS in order to improve their care by collecting anonymous data regarding confirmed or suspected infection in patients with HS. Both health care providers and patients or their caregivers can input cases into the registry from any global location. The data are critical to developing short- and long-term treatment strategies as medicine continues to grapple with the pandemic, especially given the significant comorbidities in this special patient population.

“First, although HS typically affects younger individuals, it’s associated with diabetes and obesity, which are comorbidities that might predispose to more severe infection,” said Dr Naik. “Second, many patients with HS are on immunomodulating biologic agents such as [tumor necrosis factor (TNF)] inhibitors, and patients with TNF inhibition broadly are more susceptible to infection.” Early data seem to indicate TNF inhibitors do not increase hospitalization or mortality,¹² but more complete data are needed.

Further, HS and COVID-19 share a common ground in racial-ethnic minority patients. COVID-19 is noted to disproportionately affect racial and ethnic minorities, who are at an increased risk of infection, hospitalization, and death.^13,14 Similarly, the prevalence of HS is highest in Black Americans.^15,16 These characteristics, in combination with limited health care resources during the pandemic, give clinicians cause for concern about the care of patients with HS. However, early data do not indicate an increase in negative outcomes.

“In spite of all the related concerns for patients with HS, they seem to be doing quite well from the perspective of both contracting COVID and then their disease course,” said Dr Naik. “Many of the clinicians that we have been working with from across the globe who have specialty HS clinics have informed us that they surprisingly do not have many or even any cases of patients who have contracted COVID-19. This may suggest that these patients are really just doing a great job of social distancing and wearing masks.”

In addition, Dr Naik reports that cases in the registry seem to be overall mild. So far, the data suggest that patients with HS who get COVID-19 have an overall mild course of disease. Many of the registry-reported cases have not required hospitalization or additional therapy. Nonetheless, Dr Naik stressed that registry data are limited. There is a vital need for more participation to better understand how the pathophysiology and management of HS may be influenced by an acute COVID-19 infection. 

Providing Pandemic Care to Patients
Achieving adequate patient care during the pandemic can be a difficult task, and ongoing management of HS is no different than other dermatologic diseases in this regard. “We are hearing from patients that they are having difficulties getting in to see specialists and doctors who are familiar with their condition during this time,” said Dr Naik. She recommended that providers and patients consult the US Hidradenitis Suppurativa Foundation website for recommendations to preemptively address potential flares as well as for information regarding evidence-based practices and expert insight on care during the pandemic.¹⁷ She also stated that health care providers and patients should develop a plan to help patients better advocate for themselves as well as determine when to contact their doctor regarding their HS.

“One of the big things that we’re trying to really get out there, both to patients and providers in terms of their HS management during this pandemic, is that patients who are well-controlled on a stable treatment regimen should continue that regimen, including patients who are on immunomodulating agents,” Dr Naik said. Patients who receive adalimumab or infliximab should continue those treatments, as the potential flare after cessation of therapy could lead to exposure to infection during a visit to a health care setting. “The (potential) exception here is for patients who are on broad immunosuppressive therapy such as prednisone or methotrexate, drugs that really confer a higher theoretical risk of susceptibility to infection. For patients who are on those medications and who do contract COVID-19, we advocate that those individuals see their doctors and get some advice on whether they should continue or stop those medications.”

Another important consideration for this patient group during the pandemic is their high prevalence of anxiety, depression, and suicidal ideation.¹⁸ These patients often exhibit significant social isolation already due to their condition, so it is important to monitor their mental health as well as their cutaneous symptoms.

“Mental health and quality of life are intricately connected with the experience of being a patient with HS,” said Molly Stout, MD, a dermatology resident at department of dermatology, Feinberg School of Medicine, Northwestern University in Chicago, IL. “The unpredictability of flares can be completely demoralizing. I always ask patients how HS affects their day to day life from their job, to their relationships, to tasks such as exercising or playing with their kids. Patients with HS need a support system.”

Dr Stout is part of a research team that evaluated the role of virtual support groups for patients with HS.¹⁹ The team coordinated three support groups, from which they gathered qualitative data for their needs assessment study, and then facilitated an unchaperoned virtual support group for previous attendants. Each support group concluded with an opportunity for participants to share any final thoughts. “The feedback we received was very positive, both to connect with others with such an isolating disease and also to connect with others during the isolating time of the COVID-19 pandemic,” said Dr Stout. She encouraged dermatologists to provide an opportunity for patients with HS or other morbid dermatologic diseases to connect with others through support groups, either virtually or in-person.

“The key to a successful support group is all about the group of patients who are both open to talking about their often deeply personal struggles with such challenging diseases and desire to help build up others going through a similar journey,” Dr Stout said. “I think the latter happens naturally when participants are brave enough to be a little vulnerable, and something about the virtual video chatting interface might facilitate that. It’s important for facilitators establish ground rules for a judgement-free and confidential forum from the outset.”

For providers who do not routinely organize support groups, they can encourage their patients to visit resources such as Hope for HS (https://hopeforhs.org/) to find a community that understands the emotional burden of the disease.

Outside of managing HS specifically, Dr Naik emphasized the continued need for health care providers to remind patients of diligent protective measures against infection. “We have to continually counsel patients about social distancing, sheltering at home, using good hand hygiene several times a day, wearing masks in public, and avoiding touching surfaces in public settings,” she said. “At the end of the day, whether it is for this patient population with HS or other skin conditions, these basic practices are the most important ways to mitigate the transmission of illness.”

When medicine underscores preventative measures to transmission, patients with HS and other dermatologic diseases can worry less about severe infection and focus on maintaining their overall health—something research in HS continues to explore.

To contribute to the Global Hidradenitis Suppurativa COVID-19 Registry, visit https://hscovid.ucsf.edu/. 

References

1. Naik HB, Lowes MA. A call to accelerate hidradenitis suppurativa research and improve care--moving beyond burden. JAMA Dermatol. 2019;155(9):1005-1006. doi:10.1001/jamadermatol.2019.1105

2. Frew J. Pathophysiology of hidradenitis suppurativa. Presented at: American Academy of Dermatology Virtual Meeting Experience; June 12-14, 2020; virtual.

3. Ingram JR. Hidradenitis suppurativa: pathogenesis, clinical features, and diagnosis. UpToDate. April 9, 2020. Accessed October 30, 2020. https://www.uptodate.com/contents/hidradenitis-suppurativa-pathogenesis-clinical-features-and-diagnosis

4. Ballard K, Shuman VL. Hidradenitis suppurativa. In: StatPearls. StatPearls Publishing; 2020. Updated August 10, 2020. Accessed October 30, 2020. https://www.ncbi.nlm.nih.gov/books/NBK534867/

5. Naik H. Introduction to hidradenitis suppurativa. Presented at: American Academy of Dermatology Virtual Meeting Experience; June 12-14, 2020; virtual.

6. Lloyd-McLennan AM, Ali S, Kittler NW. Prevalence of inflammatory bowel disease among pediatric patients with hidradenitis suppurativa and the potential role of screening with fecal calprotectin. Pediatr Dermatol. Published online October 25, 2020. doi:10.1111/pde.14417

7. Fernandez JM, Thompson AM, Kirby JS, Hsiao JL, Shi VY. Characterizing physical symptoms of flare in hidradenitis suppurativa: a patient survey. Br J Dermatol. Published online July 23, 2020. doi:10.1111/bjd.19412

8. Savage KT, Singh V, Patel ZS, et al. Pain management in hidradenitis suppurativa and a proposed treatment algorithm. J Am Acad Dermatol. Published online September 17, 2020. doi:10.1016/j.jaad.2020.09.039

9. Nielsen RM, Lindsø Andersen P, Sigsgaar V, Theur Riss P, Jemec GB. Pain perception in patients with hidradenitis suppurativa. Br J Dermatol. 2020;182(1):166-174. doi:10.1111/bjd.17935

10. Matusiak Ł, Szczęch, Kaaz K, Lelonek E, Szepietowki JC. Clinical characteristics of pruritus and pain in patients with hidradenitis suppurativa. Acta Derm Venereol. 2018;98(2):191-194. doi:10.2340/00015555-2815

11. von der Werth JM, Jemec GBE. Morbidity in patients with hidradenitis suppurativa. Br J Dermatol. 2001;144(4):809-813. doi:10.1046/j.1365-2133.2001.04137.x

12. Yousaf A, Gayam S, Feldman S, Zinn Z, Kolodney M. Clinical outcomes of COVID-19 in patients taking tumor necrosis factor inhibitors or methotrexate: a multicenter research network study. J Am Acad Dermatol. Published online September 11, 2020. doi:10.1016/j.jaad.2020.09.009

13. Hospitalization and death by race/ethnicity. Centers for Disease Control and Prevention. August 18, 2020. Accessed November 2, 2020. https://www.cdc.gov/coronavirus/2019-ncov/covid-data/investigations-discovery/hospitalization-death-by-race-ethnicity.html

14. Dyer O. Covid-19: Black people and other minorities are hardest hit in US. BMJ. 2020;369:m1483. doi:10.1136/bmj.m1483

15. Garg A, Kirby JS, Lavian J, Lin G, Strunk A. Sex- and age-adjusted population analysis of prevalence estimates for hidradenitis suppurativa in the United States. JAMA Dermatol. 2017;153(8):760-764. doi:10.1001/jamadermatol.2017.0201

16. Garg A, Wertenteil S, Baltz R, Strunk A, Finelt N. Prevalence estimates for hidradenitis suppurativa among children and adolescents in the United States: a gender- and age-adjusted population analysis. J Invest Dermatol. 2018;138(10):2152-2156. doi:10.1016/j.jid.2018.04.001

17. Frequently asked questions about hidradenitis suppurativa (HS) and COVID-19. HS Foundation. Updated April 6, 2020. Accessed October 30, 2020. https://www.hs-foundation.org/hidradenitis-suppurativa-treatment-and-covid-19-coronavirus/

18. Garg A, Neuren E, Cha D, et al. Evaluating patients’ unmet needs in hidradenitis suppurativa: results from the Global Survey of Impact and Healthcare Needs (VOICE) project. J Am Acad Dermatol. 2020;82(2):366-376. doi:10.1016/j.jaad.2019.06.1301

19. Stout M. The role of virtual support groups for patients with hidradenitis suppurativa during the COVID-19 pandemic. Int J Womens Dermatol. 2020;6(3):154-155. doi:10.1016/j.ijwd.2020.04.009