Adalimumab-induced psoriasis of the scalp with diffuse alopecia: A severe potentially irreversible cutaneous side effect of TNF-alpha blockers

To the Editor: Anti-tumor necrosis factor (TNF) agents have revolutionized the treatment of chronic inflammatory bowel disease. Adalimumab, a recombinant human IgG monoclonal antibody, selectively blocks TNF-alpha (TNF-α) and has been successfully used in the treatment of Crohn's disease (CD). Regimens with early use of biologic therapy are under discussion because they might alter the natural history of CD.1 Physicians treating patients with TNF-α blockers should be aware that possible complications of biologic therapy are not only opportunistic infections and the development of malignant tumors, but also cutaneous side effects.2 In the recent literature there is evidence that adalimumab may induce psoriasis in individuals who have no personal or family history of psoriasis. Clinical presentations include plaque or guttate psoriasis or palmoplantar pustulosis. We herein report two cases of severe and diffuse alopecia due to scalp psoriasis. Psoriasiform alopecia under adalimumab therapy may be severe and diffuse and, most important, irreversible. A 19-year-old woman with a 3-year history of CD was started on adalimumab monotherapy (40 mg, every 2–3 weeks) after failing to respond to various therapy regimens, including mesalofalk, azathioprine, and infliximab. Three months after the initiation of adalimumab the patient observed diffuse alopecia and erythematous scaly plaques on the scalp, abdomen, trunk, and extremities. Clinical examination revealed intense erythema with exudative discharge and severe alopecia over most of the scalp (Fig. 1a). Two biopsies from the scalp showed the characteristic features of psoriasis, without any evidence of a scarring alopecia. The scalp lesions cleared with complete hair regrowth after withdrawal of adalimumab. a: Extensive nonscarring exudative alopecia and erythema with scaly plaques on the scalp. b: Patient 2: severe scarring alopecia associated with scalp erythema and psoriasiform scaling. The second patient was a 31-year-old woman with a 2-year history of CD. Treatment with sulfasalazine and systemic steroids were discontinued because of poor clinical results. After 2 months of treatment with adalimumab she reported moderate clinical results for gastrointestinal symptoms, but had a severe flare-up of scalp psoriasis with progressive alopecia. Clinical examination showed confluent areas of scaly psoriatic plaques with shiny and atrophic skin and loss of follicular orifices. Histopathology of the scalp was compatible with psoriasis and an associated scarring alopecia. Early introduction of anti-TNF-α therapy in the treatment of CD has shown great clinical efficacy and probably has the potential to alter the natural course of the disease.1 An increased risk of infection and the occurrence of malignancy are one of the major concerns of biologic therapy. Less concerning, but very distressing to the patient, are cutaneous side effects, such as the development of new-onset psoriasis. Usually patients develop guttate or chronic plaque psoriasis on the trunk and extremities or show features of palmoplantar pustulosis.2 The occurrence of a severe alopecia associated with scalp psoriasis with the potential of being irreversible is an unusual, so far undescribed observation. We found only one previous description of psoriatic scalp disease under adalimumab therapy.3 TNF-α plays a key role in the development of psoriasis.4 The observation of new-onset psoriasis in patients with rheumatologic conditions without a prior history of psoriasis under TNF-blockers is therefore an unexpected event. There are speculations on the mechanism of this paradoxical effect and 1 of them concerns the interplay between TNF-α and interferon-alpha (IFN-α). Plasmacytoid dendritic cells, the main source of IFN-α, have been increasingly found in early psoriatic skin lesions and seem to initiate psoriasis via IFN-α production.5 IFN-α subsequently upregulates the expression of CXCR3 on T cells, which leads to recruitment of T cells into the skin. IFN-α also activates the secretion of proinflammatory cytokines by myeloid dendritic cell. Clinical evidence that supports the close relationship of IFN-α and psoriasis are the development or exacerbation of psoriasis after injections of recombinant IFN-α or after topical application of imiquimod, a potent IFN-α inducer.6, 7 Interestingly, IFN-α is only detected in the early stages of psoriatic lesions, and cannot be detected in chronic plaque psoriasis. TNF-α, on the other hand, is known to decrease IFN-α production by 2 mechanisms: it inhibits the maturation of plasmacytoid dendritic cells and subsequently suppresses IFN-α release.8 Therefore, if one blocks TNF-α, IFN-α levels may rise, explaining the new-onset psoriasis in patients with rheumatologic disorders and underlines the complexity of the TNF-α and IFN-α interplay. Why some, but not all, patients under TNF blockers develop psoriasiform eruptions, and why some get palmoplantar pustulosis, or as our patients, a nonscarring and scarring alopecia due to psoriatic scalp disease is another challenging question, which might involve TNF receptor polymorphisms.