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Adalimumab for the Treatment of Refractory Acne Conglobata

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Adalimumab for the Treatment of Refractory Acne Conglobata Research Case Report/Case Series | THE CUTTING EDGE Adalimumab for the Treatment of Refractory Acne Conglobata Freja Lærke Sand, BSc; Simon Francis Thomsen, MD, PhD umor necrosis factor (TNF) inhibitors have become which was later increased to 1.0 mg/kg/d in combination important components of the treatment of multiple with prednisolone, 1.0 mg/kg/d for 2 months; and oral T chronic inflammatory disorders such as psoriasis, isotretinoin, 0.75 mg/kg/d in combination with dapsone, psoriatic arthritis, rheumatoid arthritis, ankylosing spondy- 50 mg, twice daily for 2 months. litis, juvenile idiopathic arthritis, Crohn disease, and ulcer- ative colitis. Furthermore, off-label use of TNF inhibitors has been reported for a variety of other diseases. We report a Therapeutic Challenge and Treatment case of refractory acne conglobata treated with the TNF inhibitor adalimumab. The patient was diagnosed as having severe acne conglo- bata, which is unresponsive to doxycycline, isotretinoin, prednisolone, and dapsone. We initiated monotherapy with Report of a Case adalimumab using an initial loading dose of 80 mg, followed by 40 mg twice monthly. A marked decrease was observed An 18-year-old otherwise healthy man presented with a in the size and degree of inflammation of the nodular 4-year history of multiple painful inflammatory nodular lesions already 4 weeks after initiating treatment, and after lesions and sinus tracts on the face (Figure, A). His skin 12 weeks of therapy, all nodular lesions had disappeared lesions were confined to the face; he did not present with (Figure, B). At last follow-up, the patient had received con- fever; and he had no symptoms or signs indicating a sys- tinuous monotherapy with adalimumab, 40 mg, twice temic inflammatory disease such as inflammatory bowel monthly for a total of 12 months, and he had sustained effi- disease or arthritis. Prior to admission, he had received cacy without recurrence of acne lesions. No adverse events unsuccessful therapy with doxycycline, 100 mg, twice daily were recorded, and all routine laboratory test results were for 6 months; oral isotretinoin, 0.5 mg/kg/d, for 3 months, within normal limits. Figure. Facial Acne Conglobata Before and After Treatment With Adalimumab A B A, Study patient with severe facial nodular inflammatory acne. B, Clearance 3 months after initiation of treatment with adalimumab, 40 mg, twice monthly. 1306 JAMA Dermatology November 2013 Volume 149, Number 11 jamadermatology.com Copyright 2013 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 Adalimumab for Refractory Acne Conglobata Case Report/Case Series Research Tumor necrosis factor inhibitors have been used success- Discussion fully to treat patients with SAPHO syndrome, characterized by synovitis, acne, pustulosis, hyperostosis, and osteitis. Skin To our knowledge, this is the first time adalimumab has been manifestations in patients with SAPHO syndrome may be acne used successfully as monotherapy in a patient with therapy- fulminans, acne conglobata, palmoplantar pustulosis, or hi- resistant acne conglobata. Previously, 1 patient with facial acne dradenitis suppurativa. In several case reports and patient se- conglobata responded rapidly to treatment with etanercept1; ries, TNF inhibitors, mainly infliximab, have proved effective another patient with acne conglobata and concomitant rheu- in patients with SAPHO syndrome. One patient with severe matoid arthritis responded to infliximab in combination with SAPHO syndrome responded to a combination of isotretinoin oral isotretinoin2; and finally, a patient with severe nodular in- and adalimumab.6 flammatory acne and ulcerative colitis, which was in com- Patients with pyogenic sterile arthritis, pyoderma gan- plete remission with azathioprine treatment, was treated suc- grenosum, and acne (PAPA) have a hereditary autoinflamma- cessfully with infliximab.3 tory syndrome characterized by increased production of TNF Acne is an inflammatory condition marked by elevations in by mononuclear cells, and in 1 case, treatment with etaner- certain cytokines, including tumor necrosis factor (TNF), inter- cept resulted in sustained clinical remission.7 Similarly, therapy leukin 1β, and granulocyte-macrophage colony stimulating fac- with infliximab and adalimumab has also demonstrated effi- tor. Propionibacterium acnes has been a suggested trigger of this cacy in patients with PAPA.8,9 inflammation by stimulating production of TNF from PASH syndrome (pyoderma gangrenosum, acne and sup- keratinocytes.4 The upregulation of TNF in acne therefore theo- purative hidradenitis), which is distinctly different from PAPA retically supports the use of TNF inhibitors for this indication. in that arthritis is absent, has recently been described. Inter- Enigmatically, acne has been reported as a paradoxical ad- estingly, all dermatologic and rheumatologic manifestations verse reaction to treatment with TNF inhibitors, primarily in completely resolved following treatment with infliximab in a patients with inflammatory bowel disease.5 Similarly, para- patient with PASH.10 doxical induction of psoriasis in patients with inflammatory Because acne is part of the clinical manifestations of bowel disease or rheumatoid arthritis has also been observed SAPHO, PAPA, and PASH, and because the efficacy of TNF in- in patients treated with TNF inhibitors, and substituting the hibitors has been demonstrated in all 3 syndromes, it is pro- offending agent with a different TNF inhibitor may not nec- posed that this group of agents could be considered also in se- essarily alleviate symptoms. These observations indicate a lected patients with severe primary recalcitrant acne. The complex role of TNF in the inflammatory response in several patient described herein was treated continuously for 12 skin diseases such as acne and psoriasis and signal that the deli- months with adalimumab and had sustained and marked re- cate balance between several cytokines may be important for duction in symptoms. However, durability of remission is un- the induction of disease and for the response to treatment. Re- known, and therefore the present evidence does not support search aimed at elucidating these mechanisms is warranted. a curative role of TNF inhibitors in acne. ARTICLE INFORMATION Conflict of Interest Disclosures: None reported. 6. Garcovich S, Amelia R, Magarelli N, Valenza V, Author Affiliations: Department of Dermatology, Additional Contributions: We are indebted to Nis Amerio P. Long-term treatment of severe SAPHO Bispebjerg Hospital, University of Copenhagen, Kentorp, clinical photographer, for producing the syndrome with adalimumab. Am J Clin Dermatol. Denmark. illustrations. Mr Kentorp received no financial 2012;13(1):55-59. Corresponding Author: Simon Francis Thomsen, remuneration for his contribution. 7. Cortis E, De Benedetti F, Insalaco A, et al. MD, PhD, Department of Dermatology, Bispebjerg Abnormal production of tumor necrosis factor Hospital, DK-2400 Copenhagen NV, Denmark REFERENCES (TNF)-alpha and clinical efficacy of the TNF ([email protected]). 1. Campione E, Mazzotta AM, Bianchi L, Chimenti S. inhibitor etanercept in a patient with PAPA Severe acne successfully treated with etanercept. syndrome [corrected]. J Pediatr. 2004;145(6): Section Editor: Edward W. Cowen, MD, MHSc; 851-855. Assistant Section Editors: Murad Alam, MD; Ruth Acta Derm Venereol. 2006;86(3):256-257. Ann Vleugels, MD. 2. Shirakawa M, Uramoto K, Harada FA. Treatment 8. Tofteland ND, Shaver TS. Clinical efficacy of etanercept for treatment of PAPA syndrome. J Clin Accepted for Publication: July9,2013. of acne conglobata with infliximab. J Am Acad Dermatol. 2006;55(2):344-346. Rheumatol. 2010;16(5):244-245. Published Online: September 18, 2013. 9. Lee H, Park SH, Kim SK, Choe JY, Park JS. doi:10.1001/jamadermatol.2013.6678. 3. Schuttelaar ML, Leeman FW. Sustained remission of nodular inflammatory acne after Pyogenic arthritis, pyoderma gangrenosum, and Author Contributions: Both authors had full access treatment with infliximab. Clin Exp Dermatol. acne syndrome (PAPA syndrome) with E250K to all of the data in the study and take responsibility 2011;36(6):670-671. mutation in CD2BP1 gene treated with the tumor for the integrity of the data and the accuracy of the necrosis factor inhibitor adalimumab. Clin Exp data analysis. 4. Graham GM, Farrar MD, Cruse-Sawyer JE, Rheumatol. 2012;30(3):452. Study concept and design: Both authors. Holland KT, Ingham E. Proinflammatory cytokine production by human keratinocytes stimulated 10. Bruzzese V. Pyoderma gangrenosum, acne Acquisition of data: Thomsen. conglobata, suppurative hidradenitis, and axial Analysis and interpretation of data: Both authors. with Propionibacterium acnes and P. acnes GroEL. Br J Dermatol. 2004;150(3):421-428. spondyloarthritis: efficacy of anti-tumor necrosis Drafting of the manuscript: Sand. factor α therapy. J Clin Rheumatol. Critical revision of the manuscript for important 5. Cleynen I, Vermeire S. Paradoxical inflammation 2012;18(8):413-415. intellectual content: Both authors. induced by anti-TNF agents in patients with IBD. Statistical analysis: Thomsen. Nat Rev Gastroenterol Hepatol. 2012;9(9):496-503. Study supervision: Thomsen. jamadermatology.com JAMA Dermatology November 2013 Volume 149, Number 11 1307 Copyright 2013 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021.
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