T helper (Th)17 radiation-induced hidradenitis suppurativa (2018)

To the Editor: We read with interest the case report describing the development of hidradenitis suppurativa (HS) lesions after radiation treatment in a patient with uterine adenocarcinoma.1Haber R. Gottlieb J. Zagdanski A. Battistella M. Bachelez H. Radiation-induced hidradenitis suppurativa: a case report.JAAD Case Rep. 2017; 3: 182-184Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar The authors provided several thoughts on the possible mechanism behind radiation-induced HS. The purpose of this letter is to provide additional insight about the likely immunologic mechanisms behind radiation-induced HS. The reported case is an example of an abscopal-like effect2Postow M.A. Callahan M.K. Barker C.A. et al.Immunologic correlates of the abscopal effect in a patient with melanoma.N Engl J Med. 2012; 366: 925-931Crossref PubMed Scopus (1536) Google Scholar sharing adenocarcinoma antigens to antigens of apocrine glands of the groin. Abscopal effect is an immune-mediated phenomenon that has been heavily discussed in metastatic melanoma, whereby there is regression of nonirradiated metastatic lesions after irradiation of a distant melanoma tumor location.3Espenel S. Vallard A. Rancoule C. et al.Melanoma: last call for radiotherapy.Crit Rev Oncol. 2017; 110: 13-19Crossref PubMed Scopus (32) Google Scholar, 4Dany M. Sphingosine metabolism as a therapeutic target in cutaneous melanoma.Translational Res. 2017; 185: 1-12Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar Abscopal effects were also recently reported in advanced melanoma patients after immunotherapy, highlighting the therapeutic implications of this phenomenon.5Sharabi A.B. Lim M. DeWeese T.L. Drake C.G. Radiation and checkpoint blockade immunotherapy: radiosensitisation and potential mechanisms of synergy.Lancet Oncol. 2015; 16: e498-509Abstract Full Text Full Text PDF PubMed Scopus (509) Google Scholar As the authors point out, apoptosis can be induced by irradiation.1Haber R. Gottlieb J. Zagdanski A. Battistella M. Bachelez H. Radiation-induced hidradenitis suppurativa: a case report.JAAD Case Rep. 2017; 3: 182-184Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar It is likely that apoptotic uterine adenocarcinoma cells result in T-cell cross priming after radiation6Morisada M. Moore E.C. Hodge R. et al.Dose-dependent enhancement of T-lymphocyte priming and CTL lysis following ionizing radiation in an engineered model of oral cancer.Oral Oncol. 2017; 71: 87-94Crossref PubMed Scopus (19) Google Scholar and activate Th17 subset. A recent article points out that Th17 is an important subset in the immunopathogenesis of HS,7Matusiak Ł. Szczęch J. Bieniek A. Nowicka-Suszko D. Szepietowski J.C. Increased interleukin (IL)-17 serum levels in patients with hidradenitis suppurativa: implications for treatment with anti-IL-17 agents.J Am Acad Dermatol. 2017; 76: 670-675Abstract Full Text Full Text PDF PubMed Scopus (105) Google Scholar, 8Dany M. Elston D. Gene expression of sphingolipid metabolism pathways is altered in hidradenitis suppurativa.J Am Acad Dermatol. 2017; 77: 268-273.e6Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar like it is in psoriasis.9Di Cesare A. Di Meglio P. Nestle F.O. The IL-23/Th17 axis in the immunopathogenesis of psoriasis.J Invest Dermatol. 2009; 129: 1339-1350Abstract Full Text Full Text PDF PubMed Scopus (830) Google Scholar This case and the article by Matusiak et al7Matusiak Ł. Szczęch J. Bieniek A. Nowicka-Suszko D. Szepietowski J.C. Increased interleukin (IL)-17 serum levels in patients with hidradenitis suppurativa: implications for treatment with anti-IL-17 agents.J Am Acad Dermatol. 2017; 76: 670-675Abstract Full Text Full Text PDF PubMed Scopus (105) Google Scholar make a strong case that HS, like psoriasis, is an autoimmune disease with Th17 and the attendant polymorphonuclear leukocytes involved. Oppman et al10Oppmann B. Lesley R. Blom B. et al.Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12.Immunity. 2000; 13: 715-725Abstract Full Text Full Text PDF PubMed Scopus (2280) Google Scholar identified the p19 third subunit of interleukin (IL)-12, and designated it as IL-23. This finding predicted the potential for treating psoriasis with anti–IL-12 ustekinumab and anti–IL-23 (guselkumab). This case of radiation-induced HS is likely to predict a positive outcome with clinical trials for HS with ustekinumab (IL-12 antagonist),11Leonardi C.L. Kimball A.B. Papp K.A. et al.Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1).Lancet. 2008; 371: 1665-1674Abstract Full Text Full Text PDF PubMed Scopus (1397) Google Scholar secukinumab (IL-17 antagonist),12McInnes I.B. Mease P.J. Kirkham B. et al.Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial.Lancet. 2015; 386: 1137-1146Abstract Full Text Full Text PDF PubMed Scopus (627) Google Scholar and guselkumab (IL-23 antagonist).13Sofen H. Smith S. Matheson R.T. et al.Guselkumab (an IL-23–specific mAb) demonstrates clinical and molecular response in patients with moderate-to-severe psoriasis.J Allergy Clin Immunol. 2014; 133: 1032-1040Abstract Full Text Full Text PDF PubMed Scopus (229) Google Scholar Radiation-induced hidradenitis suppurativa: A case reportJAAD Case ReportsVol. 3Issue 3PreviewHidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by abscesses, fistulas, and scarring affecting the groin, anogenital area, and axillae. HS has an estimated prevalence of 1%, and moderate-to-severe forms have a high disease burden.1 The disease is a combination of homeostasis abnormalities of the pilosebaceous unit and dysregulation of the skin immune responses. Pathogenesis involves the interaction between a person's genetic background (potentially heterozygous mutations of genes belonging to the gamma secretase complex) and environmental triggers, among which are the skin microbiome, cigarette smoking, and obesity. Full-Text PDF Open Access