New onset or worsening of psoriasis following biologic therapy: A case series.

Biologic therapies may cause so-called "paradoxical side-effects," that is, the onset or exacerbation of new symptoms/diseases for which biological treatment should be effective. Among these, psoriatic skin lesions have been described. We report a case series of ten patients with either new onset (seven cases) or worsening (three cases) of psoriasis occurring during a biologic therapy. Six patients were receiving a biologic monotherapy, while four patients were in combination treatment with methotrexate (MTX). Psoriasis remission was observed in two patients who discontinued biologic therapy. In the six patients in whom biologic therapy was not discontinued, a complete disappearance or a partial improvement of skin lesions was achieved following topic steroid therapy in two patients and three patients, respectively. In the remaining patient, psoriasis developed during Adalimumab monotherapy, which completely disappeared when the Infliximab and MTX combination was started. The potential pathogenetic mechanisms were shortly reviewed.

Biologic drugs are increasingly used in clinical practice for management of different chronic <span class="Disease">inflammatory disorders, such as <span class="Disease">rheumatologic and intestinal diseases.[1] Although relatively safe, biologic therapy may cause side-effects, including so-called “paradoxical side-effects.”[2] These consist of the onset or exacerbation of new symptoms/diseases for which biological treatment should be effective, including psoriatic skin lesions, uveitis, sarcoidosis, and Crohn’s disease.[2] Different pathogenetic mechanisms have been hypothesized.

Our case series consisted of ten patients with onset or worsening of psoriatic lesions during biologic treatment (Table 1). In detail, three patients have a personal history of psoriasis, including two patients with psoriatic arthritis and one patient with psoriatic spondiloarthritis. Therefore, there were seven new onsets and three worsenings of psoriasis occurring during biologic therapy (mean, 11.1 ± 3.4 months). Psoriatic lesions included two pustulosis form, two guttate form, five plaque form, and one erythrodermic. All patients were receiving a biologic therapy (adalimumab, infliximab, abatacept, golimumab, and certolizumab), including six as monotherapy and four in combination treatment with methotrexate (MTX). At follow-up, a variable outcome was observed. In detail, a remission (complete or partial) was observed in three patients who discontinued biologic therapy. In six patients in whom biologic therapy was not discontinued, a complete disappearance of skin lesions was achieved in two patients following topic steroid therapy, while only a partial improvement was observed in three patients. Of note, in the remaining patient, psoriasis developed during Adalimumab monotherapy, which completely disappeared when the infliximab and MTX combination was started.

Table 1.

Demographic and clinical characteristics of patients.

Case	Age	Sex	Disease	Biologic therapy	Family history	Personal history	Psoriasis form
1	46	F	RA	Adalimumab + MTX	Not	Not	Palmoplantar pustulosis
2	30	F	RA	Adalimumab + MTX	Not	Not	Guttate (palmoplantar/pubic)
3	68	F	RA	Abatacept	Not	Not	Guttate (legs/elbows)
4	32	F	CD	Infliximab	Not	Not	Palmoplantar pustulosis
5	59	F	PA	Adalimumab	Not	Yes	Plaque (legs/arms)
6	55	F	SpA	Adalimumab	Not	Yes	Erythrodermic
7	57	F	PA	Golimumab	Not	Yes	Plaque (legs/trunk)
8	53	F	RA	Certolizumab	Not	Not	Plaque (legs/trunk)
9	39	M	PA	Adalimumab + MTX	Yes	Not	Plaque (scalp)
10	64	F	RA	Abatacept + MTX	Not	Not	Plaque (legs/arms)

CD, Crohn’s disease; MTX, methotrexate; PA, psoriatic arthritis; RA, rheumatoid arthritis; SpA, spondilo-arthritis.

Demographic and clinical characteristics of <span class="Species">patients.

CD, Crohn’s disease; MTX, <span class="Chemical">methotrexate; PA, <span class="Disease">psoriatic arthritis; RA, rheumatoid arthritis; SpA, spondilo-arthritis.

The induction or exacerbation of <span class="Disease">psoriasis in <span class="Species">patients treated with anti-tumor necrosis factor (TNF)-α therapy is a well-established phenomenon.[2] Indeed, psoriasiform skin lesions are recognized as the most frequent paradoxical side-effects of biological therapies. A systematic literature review describing 150 cases of psoriasis development or worsening during biologic therapy in rheumatologic and inflammatory bowel diseases patients has been published.[3] Overall, a large predominance of female patients was found and the mean age at onset was 30−45 years.[3] It has been found that psoriasis may occur during different biologic therapies, including infliximab, adalimumab, certolizumab, golimumab, tocilizumab, abatacept, etanercept, anakinra, ustekinumab, and, more rarely, rituximab.[3,4] Therefore, the atypical adverse events appear to be dependent on a class-effect of these agents rather than on a specific drug and they seem to be independent from the biologic therapy duration. Indeed, psoriasis may occur following a single biologic therapy administration or following several years of treatment. Plaque and palmoplantar psoriasis represents the more frequent lesions. Complete resolution following treatment interruption has been reported and nearly half the patients responded satisfactorily to topical therapy, while an alternative anti-TNF was successful in only 15% of cases. Clinical characteristics of patients included in our case series are in keeping with data previously reported. In detail, all but one patient were female, the psoriatic lesions developed following different biologic drugs, and the partial or total resolution was achieved with either biologic interruption or topic therapy.

Although the pathogenesis of such a paradoxical side-effects remains unclear, a role for the IFN-α has been proposed. Indeed, IFN-α has been found to be a psoriasis inductor in patients with either HCV hepatitis or inflammatory bowel disease, as well as in animal models.[5] In detail, during biologic therapy, an unbalanced proportion between TNF-α and IFN-α occurs, triggering psoriasis in some genetically predisposed patients.[2] Moreover, IFN-α stimulates IL-17 production, a cytokine involved in psoriasis pathogenesis.[6] However, this phenomenon cannot be invocated in the onset of psoriasis reported during biologic therapy different from anti-TNF-α, such as rituximab, tocilizumab, anakira, and efalizumab.[2] The onset of various auto-antibodies (antinuclear antibodies, anti-double-strained DNA, antiphospholipid antibodies, etc.) may occur during these biologic therapies, which may trigger auto-immune diseases. Therefore, the psoriasis may develop during biologic therapy in genetically predisposed subjects due to an intrinsic effect of these drugs. It has been suggested that the intrinsic potential in triggering autoimmune disease of biologics could be reduced by a concomitant MTX therapy. Our data do not seem to support such a hypothesis, since drug-induced psoriasis occurred in as many as four (40%) out of our patients despite simultaneous MTX therapy, as reported in a recent systematic review.[6] In conclusion, the paradoxical onset or exacerbation of psoriasis may occur during a biologic therapy, particularly in female patients.