NEWS - More reports of psoriasis as side effect of TNF inhibitors

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More reports of psoriasis as side effect of TNF inhibitors

Rheumawire

August 9, 2005

Zosia Chustecka

Athens, Greece - Another few cases of psoriasis occurring as an adverse

effect in patients being treated with TNF inhibitors for chronic arthritic

conditions have been reporteda paradoxical side effect, as the TNF

inhibitors have documented benefit in the treatment of psoriasis.

The latest report involves five patients, described by Dr P Sfikakis and

colleagues (Athens University Medical School, Greece) in the August 2005

issue of Arthritis & Rheumatism [1]. Four of the five patients developed a

striking pustular eruption on the palms of their hands and/or the soles of

their feet, as well as plaque-type psoriasis at other skin sites, while the

fifth patient developed thick erythematous scaly plaques localized to the

scalp. Three patients had nail involvement, with oncholysis, yellow

discoloration, and subungual keratosis. Skin biopsies revealed histology

consistent with psoriasis, the researchers comment.

All three marketed products were involved. The skin lesions developed after

six to nine months of treatment with etanercept (Enbrel, Wyeth/Amgen) and

adalimumab (Humira, Abbott), which were being used for long-standing

rheumatoid arthritis (RA), and also with infliximab (Remicade,

Schering-Plough/Centocor), which was being used for ankylosing spondylitis

(AS) and Adamantiades--Behçet's disease (ABD). In the two patients with ABD,

a relapse occurred on retreatment with infliximab, and so the psoriasis was

considered to be a " definite adverse effect, " say the researchers, while in

the three other cases it was a " probable adverse effect of treatment. "

Sfikakis et al cite several papers in the literature describing cases of

psoriasis developing in patients on TNF inhibitors, and they also cite the

cases (in 12 patients) described at the EULAR meeting last year, reported at

the time by rheumawire. " Taken together, these data suggest that the

development of psoriasiform lesions in previously unaffected individuals,

particularly pustular lesions of the palms and soles, represents an adverse

effect of anti-TNF treatment, which is a class effect rather than a

drug-specific effect, " they conclude.

Misdiagnosis of original disease unlikely

The five patients who developed psoriasis were drawn from a cohort of 100

treated with TNF inhibitors for more than six months (47 patients were on

infliximab, 24 on adalimumab, and 29 on etanercept). This 5% incidence

" clearly exceeds the prevalence that may be expected by chance, especially

within such a short period of observation, " Sfikakis et al comment.

One explanation for the finding that the researchers propose but then

dismiss is that these patients may have been originally misdiagnosed: if

they actually had psoriatic arthritis, then the psoriasis that developed

would be part of the disease process. However, the researchers point out

that the patients in this sample had had typical clinical, serologic, and

radiologic features of RA and AS. In addition, no concomitant arthritis

flare was observed in any of these patients, which would be expected given

the similar immunological mechanisms underlying joint and skin involvement

in psoriatic arthritis. In fact, the underlying disease responded well to

anti-TNF therapy, they comment.

Another explanation they offer is that the adverse effect is a result of an

autoimmune mechanism triggered by the TNF antagonists. " Several lines of

evidence suggest that, under certain conditions, anti-TNF treatment promotes

the activation of autoreactive T cells, leading to tissue damage via

autoimmune mechanisms, " they write. One example of this is the common

induction of antinuclear antibodies and the occurrence of autoimmune

syndromes such as cutaneous lupus erythematosus of systemic lupus

erythematosus-like syndromes. Both have been associated with the use of TNF

inhibitors, as previously reported by rheumawire.

The development of psoriasis may follow a similar mechanism, they suggest.

Although this theory contradicts the documented therapeutic benefit of the

anti-TNF drugs in psoriasis, it should be remembered that this disease is

heterogeneous, the researchers comment. Certain variants, for example

palmoplantar pustular psoriasis, may have an immunological background

distinct from that found in typical plaque-type psoriasis.

Source

1. Sfikakis PP, Iliopoulos A, Elezeglou A, et al. Psoriasis

induced by anti-tumor necrosis factor therapy. Arthritis Rheum 2005;

52:2513-2518.

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