Occurrence of psoriatic plaques on previous adalimumab injection sites during disease relapse in a patient with pustular psoriasis
Authors: Ting-Shun Wang, Tsen-Fang Tsai
Journal: Journal of the American Academy of Dermatology (2014)

To the Editor: Psoriasis has been reported after tumor necrosis factor (TNF) inhibitor treatment in patients with rheumatic diseases.1Joyau C. Veyrac G. Dixneuf V. Jolliet P. Anti-tumour necrosis factor alpha therapy and increased risk of de novo psoriasis: is it really a paradoxical side effect?.Clin Exp Rheumatol. 2012; 30: 700-706PubMed Google Scholar Recently, we observed a patient with pustular psoriasis in whom psoriatic plaques developed on previous adalimumab injection sites during disease relapse. This 45-year-old man suffered from severe acrodermatitis continua for 25 years and had initially presented with subungual pustules and a few scaly plaques on the back. The following year, he experienced 3 episodes of generalized pustules and fever. Afterward, his psoriasis remained confined to the digits, left hand, forearm, legs, and skin folds. He had been treated with oral etretinate (later acitretin) for 20 years and had received other systemic and topical agents, including ustekinumab and systemic corticosteroids, with limited benefit. Adalimumab was initiated 5 years ago, and his condition improved, but treatment was discontinued after 2 years for financial reasons. Acitretin was discontinued months later due to hyperlipidemia, and his psoriasis eventually flared. Pustules recurred on his legs and left palm, and thin plaques on the left forearm were studded with tiny pustules. Two isolated psoriatic plaques developed in abdominal skin where adalimumab had been injected previously (Fig 1). No typical psoriatic plaques occurred elsewhere. Although he had generalized pustular psoriasis 18 years earlier, he had not suffered from typical psoriatic plaques in this area. After the reintroduction of adalimumab and acitretin treatment, the psoriatic plaques on his abdomen resolved completely. Psoriasiform dermatosis developing after TNF inhibitor treatment could present as de novo psoriasis, an exacerbation of previous psoriasis, or a phenotype switch of psoriasis. The paradoxical development of psoriasis is suggested to be due to the production of unopposed interferon-alpha by plasmacytoid dendritic cells and the disruption of the cytokine milieu.2Liu J. Marino M.W. Wong G. Grail D. Dunn A. Bettadapura J. et al.TNF is a potent anti-inflammatory cytokine in autoimmune-mediated demyelination.Nat Med. 1998; 4: 78-83Crossref PubMed Scopus (494) Google Scholar However, the appearance of typical psoriatic plaques on previously uninvolved skin during disease relapse on previous adalimumab injection sites has not been reported. Although the exact pathogenesis is unknown, it is clear that TNF blockers are effective in the treatment of psoriasis, while TNF is also a potent anti-inflammatory cytokine.2Liu J. Marino M.W. Wong G. Grail D. Dunn A. Bettadapura J. et al.TNF is a potent anti-inflammatory cytokine in autoimmune-mediated demyelination.Nat Med. 1998; 4: 78-83Crossref PubMed Scopus (494) Google Scholar We speculate that the key cytokine in pustular psoriasis may be different from plaque type psoriasis (IL-36 versus IL-17).3Marrakchi S. Guigue P. Renshaw B.R. Puel A. Pei X.Y. Fraitag S. et al.Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis.N Engl J Med. 2011; 365: 620-628Crossref PubMed Scopus (668) Google Scholar, 4Chiu H.Y. Huang P.Y. Tsai T.F. Th17 in psoriasis: from basic immunology to clinical practice.Dermatol Sinica. 2012; 30: 136-141Abstract Full Text Full Text PDF Scopus (42) Google Scholar A 6-month remission duration usually exists after adalimumab treatment.5Chiu H.Y. Wang T.S. Chang C.Y. Tsai T.F. The effectiveness and safety of adalimumab in the treatment of non-reimbursed patients with mild-to-moderate psoriasis.J Eur Acad Dermatol Venereol. 2012; 26: 991-998Crossref PubMed Scopus (15) Google Scholar It is likely that the residual effects of adalimumab set the previous injection sites more vulnerable to the effect of the early initiating cytokines (IL-36) of pustular psoriasis. However, because TNF is important in the maintenance of the plaque lesions that formed subsequently, the patient's psoriasis responded again to adalimumab treatment. Koebner phenomenon from repeated injections is another possibility. However, it is less likely because the size of the psoriatic plaques exceeded far beyond the injection points, and the patient did not observe psoriatic lesions on other areas of his recent trauma. In conclusion, we reported the occurrence of psoriatic lesions on previously unaffected adalimumab injection sites during disease relapse. The exact mechanism awaits further investigation.