An old dog with a new trick: High dose intralesional steroids in hidradenitis suppurativa
By Warren R. Heymann, MD, FAAD
February 2, 2022
Vol. 4, No. 5
Hidradenitis suppurativa (HS) is hitting its stride academically — deservedly so. In 2000 there were 2 publications about HS in the Journal of the American Academy of Dermatology; in 2010, 9 manuscripts; and, in 2020, 69 articles were published.
HS is characterized by chronic deep-seated nodules, abscesses, fistulae, sinus tracts, and scars in the axilla, inguinal area, submammary folds, and perianal area. Quality of life is diminished because this disfiguring disease is accompanied by pain and embarrassment. The pathogenesis of HS remains to be determined, but likely involves the interplay of follicular hyperkeratosis within the pilosebaceous-apocrine unit with inflammatory cytokines and other contributing factors, such as genetics, hormones, and pathogenic microorganisms. (1)
HS usually presents after puberty with a mean age of onset between 20 to 24 years. A bimodal age of onset has been demonstrated, with the first peak in the late teens and a second peak in the mid 40s; for classic HS the mean age at diagnosis is later in male than female patients. (2) HS may affect the pediatric population. HS is a disorder of disparities, more frequently affecting women and children of color. (3)
Patients with HS may have significant comorbidities (obesity, metabolic syndrome, diabetes, and arthritis) and increased all-cause mortality. (4) HS may be associated with inflammatory bowel disease (Crohn disease and ulcerative colitis) (5) and other autoinflammatory syndromes involving a dysregulated innate immune system with abnormal interleukin (IL)-1 signaling leading to sterile neutrophilic inflammation (pyoderma gangrenosum, acne, and hidradenitis suppurativa (PASH), pyoderma gangrenosum, acne, pyogenic arthritis, and hidradenitis suppurativa (PAPASH), and psoriatic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa (PsAPASH). (6)
Management of HS is challenging, including medical and surgical approaches, which must often be combined for best outcomes. Therapeutic approaches include the use of topical therapies, systemic antibiotics, hormonal therapies, and a wide range of immunomodulating and biologic medications. Lifestyle changes, pain management, and emotional/psychiatric issues must also be addressed. Please see references 7 and 8 for complete details (7,8)
Dr. Ginette Okoye was our recent Grand Rounds speaker at Cooper Medical School of Rowan University, offering a fabulous discussion of HS management. It was not the newest biologic that got my attention — it was her advocacy of intralesional steroids for HS, at higher doses (10 mg/cc and higher) than I had been accustomed to, that got my attention. Have I been underdosing intralesional triamcinolone (ILTAC; Kenalog, ILK) all these years?
I was dumbfounded to learn that after four decades of dermatology, something as straightforward as ILK in HS is actually controversial. Although clinicians have long-used this modality, Riis et al recognized that its administration was based on expert consensus, not clinical studies. The authors prospectively assessed the outcomes of routine treatment using ILTAC (10 mg/mL) for acute flares (nodules or abscesses) in 36 patients with HS. Statistically significant reductions in physician-assessed erythema edema, suppuration and size were demonstrated at follow-up. A significant difference in patient-reported pain visual analog scale scores was observed. The authors concluded that intralesional injection of corticosteroids is perceived as beneficial by physicians and patients in the management of HS flares by reducing pain after 1 day and signs of inflammation approximately 7 days later. (9)
Garelik et al note that the optimal therapeutic dose has not been determined. They investigated the utility of high-dose ILTAC 20 mg/ml (ILTAC-20) or 40 mg/ml (ILTAC-40), for inflammatory lesions of HS. Of 54 patients interviewed who received either treatment, (average age was 36.9; 36 [66.7%] female), 40 patients (76.9%) were very satisfied (n = 19) or satisfied (n = 21). Fifty patients (92.6%) demonstrated improvements in disease state, and 41 patients (75.9%) experienced enhanced quality of life. Forty-four patients (86.3%) were amenable to additional injections of high-dose ILTAC, if clinically indicated. No adverse effects of therapy were reported. (10) High-dose ILTAC (40 mg/cc) has also been shown to be efficacious when aided by ultrasound guidance. (11) Dautriche et al reported on the successful use of tumescent triamcinolone in a 16 year-old woman with recalcitrant HS and Crohn disease.
Intralesional corticosteroid therapy was not effective in a randomized, double-blind, placebo-controlled 3-arm trial evaluating the efficacy of intralesional triamcinolone injection. Thirty-two patients were divided in 3 groups: triamcinolone 10 mg/mL, 40 mg/mL, or normal saline (placebo). There was no statistically or clinically significant difference in the number of days to lesion resolution in either treatment arm compared with the placebo arm. (13)
Now that I’m officially “senior,” I find myself rooting for older therapies and people to show they can still do the job. I never thought I would cheer for Tom Brady, but I found myself doing so during Super Bowl LV. Despite the conflicting data, I will still use ILK in HS — albeit at higher doses.
Point to Remember: Intralesional triamcinolone may be highly effective in treating acute lesions of hidradenitis suppurative at higher doses.
Our expert’s viewpoint
Steven R. Cohen, MD, MPH, FAAD
Professor and Chief Emeritus
Division of Dermatology (Medicine)
Director, Hidradenitis Suppurativa Center
Co-Director, Dermatopharmacology Section
Albert Einstein College of Medicine
Montefiore Medical Center
It is difficult to change and advance established treatment paradigms for any disease. In his seminal text, The Structure of Scientific Revolutions, Thomas Kuhn observed that, “novelty emerges only with difficulty, manifested by resistance, against a background provided by expectation (14).” Resistance comes in many forms, such as generalizing a conclusion based on an unrecognized or flawed assumption. Consider the frequently cited, randomized control trial (RCT) of Fajgenbaum et al (15), ostensibly demonstrating no benefit associated with intralesional triamcinolone (ILTAC) at concentrations of 0 (placebo), 10 and 40 mg/mL. However, this study utilized a fixed volume of triamcinolone, 0.1 mL, regardless of lesion size. In striking contrast, our treatment model shows profoundly augmented efficacy of high-dose ILTAC-20 and ILTAC-40 for acute HS flares, most likely due to our adjusted treatment volumes based on lesion size and severity.
Intralesional corticosteroid therapy is widely accepted as a standard of care for acute flares of HS; nonetheless, limited efficacy of ILTAC-10 led us to explore the higher doses of 20 mg/mL and 40 mg/mL. Given the decisive findings reported in our retrospective chart review and telephone survey, we are now conducting a prospective RCT in which 0.025-0.05 mL of ILTAC (and placebo) will be administered every 3 mm along the widest axis of a target lesion (e.g., a 12 mm abscess would receive 0.3-0.6 mL. In the treatment arms of our trial this represents 3 to 6 times the dosage used by Fajgenbaum et al (15) for a lesion of similar size.)
Extreme debilitation, adverse impact on quality of life, and poor treatment outcomes associated with HS were catalysts to establish an HS Center at Albert Einstein. By confronting the ‘resistance’ to change existing treatment paradigms, we have explored new anti-inflammatory (16), anti-hormonal (17), and antibiotic regimens (18). While a true ‘paradigm shift’ in understanding and treating HS is the ‘quest,’ we are gratified that Dr. Heymann remains convinced about the utility of ILTAC and plans to consider the new dosing proposal for his HS patients.
Goldburg SR, Strober BE, Payette MJ. Hidradenitis suppurativa: Epidemiology, clinical presentation, and pathogenesis. J Am Acad Dermatol. 2020 May;82(5):1045-1058. doi: 10.1016/j.jaad.2019.08.090. Epub 2019 Oct 9. PMID: 31604104.
Liy-Wong C, Kim M, Kirkorian AY, Eichenfield LF, Diaz LZ, Horev A, Tollefson M, Oranges T, Philips R, Chiu YE, Ghafari G, Arnold JD, Sprague J, Nguyen H, Wan S, Atenafu EG, Pope E, Hamilton J, Naik HB, Lara-Corrales I. Hidradenitis Suppurativa in the Pediatric Population: An International, Multicenter, Retrospective, Cross-sectional Study of 481 Pediatric Patients. JAMA Dermatol. 2021 Feb 24. doi: 10.1001/jamadermatol.2020.5435. Epub ahead of print. PMID: 33625473.
Kirby JS, Zaenglein AL. Recognizing the Effects and Disparities of Pediatric Hidradenitis Suppurativa. JAMA Dermatol. 2021 Feb 24. doi: 10.1001/jamadermatol.2020.5434. Epub ahead of print. PMID: 33625471.
Saunte DML, Jemec GBE. Hidradenitis Suppurativa: Advances in Diagnosis and Treatment. JAMA. 2017 Nov 28;318(20):2019-2032. doi: 10.1001/jama.2017.16691. PMID: 29183082.
Chen WT, Chi CC. Association of Hidradenitis Suppurativa With Inflammatory Bowel Disease: A Systematic Review and Meta-analysis. JAMA Dermatol. 2019 Jul 10;155(9):1022–7. doi: 10.1001/jamadermatol.2019.0891. Epub ahead of print. PMID: 31290938; PMCID: PMC6625071.
Vinkel C, Thomsen SF. Autoinflammatory syndromes associated with hidradenitis suppurativa and/or acne. Int J Dermatol. 2017 Aug;56(8):811-818. doi: 10.1111/ijd.13603. Epub 2017 Mar 27. PMID: 28345207.
Alikhan A, Sayed C, Alavi A, Alhusayen R, Brassard A, Burkhart C, Crowell K, Eisen DB, Gottlieb AB, Hamzavi I, Hazen PG, Jaleel T, Kimball AB, Kirby J, Lowes MA, Micheletti R, Miller A, Naik HB, Orgill D, Poulin Y. North American clinical management guidelines for hidradenitis suppurativa: A publication from the United States and Canadian Hidradenitis Suppurativa Foundations: Part I: Diagnosis, evaluation, and the use of complementary and procedural management. J Am Acad Dermatol. 2019 Jul;81(1):76-90. doi: 10.1016/j.jaad.2019.02.067. Epub 2019 Mar 11. PMID: 30872156.
Alikhan A, Sayed C, Alavi A, Alhusayen R, Brassard A, Burkhart C, Crowell K, Eisen DB, Gottlieb AB, Hamzavi I, Hazen PG, Jaleel T, Kimball AB, Kirby J, Lowes MA, Micheletti R, Miller A, Naik HB, Orgill D, Poulin Y. North American clinical management guidelines for hidradenitis suppurativa: A publication from the United States and Canadian Hidradenitis Suppurativa Foundations: Part II: Topical, intralesional, and systemic medical management. J Am Acad Dermatol. 2019 Jul;81(1):91-101. doi: 10.1016/j.jaad.2019.02.068. Epub 2019 Mar 11. PMID: 30872149.
Riis PT, Boer J, Prens EP, Saunte DM, Deckers IE, Emtestam L, Sartorius K, Jemec GB. Intralesional triamcinolone for flares of hidradenitis suppurativa (HS): A case series. J Am Acad Dermatol. 2016 Dec;75(6):1151-1155. doi: 10.1016/j.jaad.2016.06.049. Epub 2016 Sep 28. PMID: 27692735.
Garelik J, Babbush K, Ghias M, Cohen SR. Efficacy of high-dose intralesional triamcinolone for hidradenitis suppurativa. Int J Dermatol. 2021 Feb;60(2):217-221. doi: 10.1111/ijd.15124. Epub 2020 Aug 17. PMID: 32808305.
Salvador-Rodríguez L, Arias-Santiago S, Molina-Leyva A. Ultrasound-assisted intralesional corticosteroid infiltrations for patients with hidradenitis suppurativa. Sci Rep. 2020 Aug 7;10(1):13363. doi: 10.1038/s41598-020-70176-x. Erratum in: Sci Rep. 2020 Oct 13;10(1):17551. PMID: 32770058; PMCID: PMC7414138.
Dautriche CN, Mamalis A, Lai Y, Heilman E, Glick SA, Siegel D. Tumescent triamcinolone infiltration: A new approach for the management of recalcitrant hidradenitis suppurativa. JAAD Case Rep. 2020 Oct 12;6(12):1310-1312. doi: 10.1016/j.jdcr.2020.10.004. PMID: 33294572; PMCID: PMC7701001.
Goldburg SR, Strober BE, Payette MJ. Hidradenitis suppurativa: Current and emerging treatments. J Am Acad Dermatol. 2020 May;82(5):1061-1082. doi: 10.1016/j.jaad.2019.08.089. Epub 2019 Oct 9. PMID: 31604100.
Kuhn, TS. The Structure of Scientific Revolutions, 2nd Edition, Enlarged. Foundations of Science. Vol II (2), International Encyclopedia of Unified Science, The University of Chicago Press, 1970: 64.
Fajgenbaum K, Crouse L, Dong L, Zeng D, Sayed C. Intralesional Triamcinolone May Not Be Beneficial for Treating Acute Hidradenitis Suppurativa Lesions: A Double-Blind, Randomized, Placebo-Controlled Trial. Dermatol Surg 2020;46(5):685-689.
Ghias MH, Johnston AD, Kutner AJ, Micheletti RG, Hosgood HD, Cohen SR. High-dose, high-frequency infliximab: A novel treatment paradigm for hidradenitis suppurativa. J Am Acad Dermatol. 2020 May;82(5):1094-1101. doi: 10.1016/j.jaad.2019.09.071. Epub 2019 Oct 4. PMID: 31589948.
Babbush KM, Ghias MH, Andriano TM, Cohen SR. Anti-androgen therapy in HS: finasteride as an alternative to spironolactone. Virtual Poster Presentation. 5th Annual Symposium on Hidradenitis Suppurativa Advances. Montreal, QC, Canada. October 2020.
Nosrati A, Babbush KM, Ghias MH, Pacific KP, Hosgood HD, Cohen SR. Short-lived efficacy of ertapenem for refractory hidradenitis suppurativa. Oral and Poster Presentation. Annual Meeting of the American Academy of Dermatology. Denver, CO. March 2020.
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