Saira J George, MD; Heather L Anderson, MD; Sylvia Hsu, MD 

Dermatol Online J.  2006;12(2) ?2006 Arthur C. Huntley, MD

A 41-year-old woman with a 15-year history of plaque-type psoriasis failed treatment with topical steroids and was unable to tolerate methotrexate because of gastrointestinal side effects. She was started on infliximab but developed dyspnea during the first 5 minutes of her infusions, requiring significant slowing of the infusion rate. The patient was switched to adalimumab therapy (40 mg subcutaneously twice a week for 2 weeks, weekly for the next 10 weeks, then every other week). She reported a wheal-like injection site reaction with each injection followed approximately 10 hours later with a pruritic, urticarial eruption, primarily on her neck and arms (Fig. 1). She required no treatment for the eruption, which became progressively less severe with each injection until her tenth injection, when the only skin reaction was at the injection site. Her psoriasis responded dramatically to therapy.

Figure 1. 

Urticarial plaques on the neck

     

The biologic agents have revolutionized the treatment of psoriasis but as their use grows, so does our understanding of their immunologic side effects. Infliximab, an infusible chimeric human-mouse TNF-α antibody, has been associated with numerous immunogenic reactions, including infusion reactions, serum sickness-like syndrome, and human antichimeric and antinuclear antibody development.^[1] Urticaria has also been reported with infliximab therapy. For example, in a study of infliximab and methotrexate, three of sixteen patients had urticaria classified as a serious adverse event.^[2] In another study of infliximab four of 340 patients (1 %) had urticaria, with one unable to continue the infusion.^[3]

Unlike infliximab, adalimumab contains no nonhuman sequences, making it indistinguishable in structure and function from naturally occurring human IgG1.^[4] As expected, allergic reactions to adalimumab appear to be rare. Despite its fully human composition, however, some degree of immunogenicity to the drug does develop. About 5 percent (58/1062) of adults in phase I, II, and III studies developed low-titer antibodies to adalimumab at least once during treatment, which, although neutralizing in vitro, did not correlate clinically with adverse effects. Allergic reactions overall (including allergic rash, anaphylactoid reaction, fixed drug reaction, nonspecific drug reaction, and urticaria) have been observed in 1 percent of patients treated with the medication in clinical trials.^[5] These reactions suggest that potential immunogenic sites may develop when adalimumab complexes with TNF-α. Urticaria resulting from adalimumab appears to be uncommon. However, as the use of the medication for a variety of rheumatologic conditions and psoriasis increases, so too should our awareness of this potential cutaneous side effect of therapy.

Han PD, Cohen RD. Managing immunogenic responses to infliximab: treatment implications for patients with Crohn's disease. Drugs. 2004;64(16):17. Feletar M, Brockbank JE, Schentag CT, Lapp V, Gladman DD. Treatment of refractory psoriatic arthritis with infliximab: a 12 month observational study of 16 patients. Ann Rheum Dis. 2004 Feb;63(2):156-61. Maini RN, Breedveld FC, Kalden JR, Smolen JS, Davis D, Macfarlane JD, Antoni C, Leeb B, Elliott MJ, Woody JN, Schaible TF, Feldmann M. Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. Arthritis Rheum. 1998 Sep;41(9):1552-63. Chew AL, Bennett A, Smith CH, Barker J, Kirkham B. Successful treatment of severe psoriasis and psoriatic arthritis with adalimumab. Br J Dermatol. 2004 Aug;151(2):492-6. HUMIRA (adalimumab) [package insert]. North Chicago, IL: Abbott Laboratories; 2004.

Reprint Address

Sylvia Hsu, MD, Email: shsu@bcm.edu