NEWS:Psoriasis with TNF inhibitors: Is there an infectious etiology?

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Psoriasis with TNF inhibitors: Is there an infectious etiology?



Sep 28, 2005



Zosia Chustecka



Tampa, FL - Psoriasis occurring in patients with chronic arthritic

conditions treated with TNF inhibitors has been described as an

adverse effect of these drugs—a paradoxical side effect, because TNF

inhibitors have documented benefit in the treatment of psoriasis. But

are these skin lesions really psoriasis? A more plausible explanation

for these observations may exist, says US rheumatologist Dr

(University of South Florida, Tampa).

No other example exists in modern medicine of a drug that can both

cause and treat the same disease, he says. " It is much more likely

that this paradoxical adverse reaction is actually a manifestation of

reactive arthritis [ReA], " says, suggesting that the skin

lesions are keratoderma blennorrhagicum (KB). This condition is

indistinguishable from pustular psoriasis, he tells rheumawire, but

occurs in the setting of ReA after exposure to certain causative

bacteria, such as Chlamydia trachomatis.

However, a group of researchers who reported psoriasis as a side

effect of TNF inhibitors disagrees and says that this explanation for

the skin lesions observed is " highly unlikely. " After the latest

report of psoriasis as a side effect of TNF inhibitors,

www.jointandbone.org carried a poll question for a month to gauge

readers' experience: 63% of respondents answered " yes " when asked

" Have you seen psoriasis or other skin reactions in patients on TNF

inhibitors? "

wrote to www.jointandbone.org after reading its news reports

on psoriasis in patients on TNF inhibitors. The phenomenon was

described by two separate groups of German researchers at last year's

EULAR meeting, and the details of one series of nine patients was

published online September 8, 2005 in the ls of Rheumatic

Diseases [1]. In addition, a group of Greek researchers reported five

cases in the in the August 2005 issue of Arthritis & Rheumatism [2].

They said four of the five patients developed striking pustular

eruptions on the palms of their hands and/or the soles of their feet,

as well as a 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 onycholysis,

yellow discoloration, and subungual keratosis.

comments that the majority of referenced cases of KB have

presented in a similar fashion, and onycholysis and subungual

keratosis are " classic for KB. " The condition almost always involves

the soles and palms, but it also involves the nails, scalp, and

extremities.

TNF inhibition is known to increase risk of infection and to unmask

latent infections, points out. The latter has been well

documented in the case of tuberculosis following reactivation of the

persistent obligate intracellular bacteria Mycobacterium

tuberculosis. Interestingly, C trachomatis and Chlamydia pneumoniae

are also persistent obligate intracellular bacteria, and chlamydia is

a known cause of KB in the setting of ReA.

suggests that psoriasis described as an adverse effect could

be new exposure to these causative organisms or reactivation of the

persistent state. TNF inhibition would increase the risk of becoming

symptomatic in either scenario. " This would also explain why the skin

lesions resolved after stopping the medication, " he adds.

Chlamydia-induced ReA is often unrecognized

has a long-standing research interest in chlamydia-induced ReA

and has conducted a clinical trial showing that a combination of

antibiotics produced dramatic improvement [3]. There is a theory that

a combination of antibiotics can eradicate the persistent state of

chlamydia and its sequelae, he explains, although he adds that the

use of antibiotics in the treatment of chlamydia-induced ReA remains

controversial.

" It is my opinion that chlamydia-induced ReA often goes unrecognized

or misdiagnosed by physicians, including rheumatologists, "

tells rheumawire. There are more than two million new chlamydia

infections in the US alone every year, he points out. Approximately

4% of these patients develop ReA, and about half develop chronic ReA.

These numbers roughly equate to an annual incidence that rivals that

for rheumatoid arthritis, he says. " I can assure you that the number

of patients actually diagnosed with ReA is far lower than the number

diagnosed with RA. The numbers don't lie. We are simply missing the

diagnosis. "

says he is vigilant about searching for the signs and symptoms

of ReA (specifically chlamydia-induced ReA) in all his patients and

sees KB " rather often. " A partial explanation may be that, because of

his specific interest, he is referred patients from other physicians,

but he also makes a point of looking at the palms and soles of all

his patients; this is something he urges all rheumatologists to do.

Mild cases may go unrecognized by the patient, or they may think it

is " dry skin " or some other benign skin condition and not think of

mentioning it during a visit for arthritis, he adds.

Disagreement: This is an " unlikely explanation "

However, the Greek researchers who reported the five cases of

psoriasis as a paradoxical side effect of TNF inhibitors disagree and

say that KB is an " unlikely explanation. " Contacted by rheumawire for

comment, Dr Petros Sfikakis (Laikon General Hospital, Athens,

Greece), together with rheumatologist Dr A Iliopoulos (General

Military Hospital of Athens, Greece) and dermatologist Dr A Stratigos

(s Sygros Hospital, Athens, Greece), emailed a joint response

to the suggestion.

" The hypothesis that the skin lesions we described resulted from new

exposure to chlamydia, one of the triggering factors of reactive

arthritis, is highly unlikely. None of our patients had any symptoms

or signs suggestive of reactive arthritis, such as urethritis, oral

ulcerations, circinate erosions in the genital area, or

conjunctivitis, " they write. " Furthermore, three of the five patients

were sexually inactive. "

" The same argument holds true for the possibility of a reactivated

chlamydial infection, " they continue, noting that none of the

patients had a history of ReA. " Moreover, there is no published

evidence that treatment with anti-TNF agents predisposes [a person]

to such a reactivation. With an estimated chlamydial seropositivity

of more than 10% in the general population and with the current

widespread use of anti-TNF agents, one would expect the hypothesis of

reactivation to be confirmed in everyday clinical practice. "

Similar concerns about possible reactivation of the triggering

organisms after anti-TNF therapy in patients with ReA have been

expressed before, but no such cases have been reported, Sfikakis and

colleagues point out. " In contrast, anti-TNF therapy has already been

used successfully in patients with refractory reactive arthritis. "

The Greek researchers also highlight differences between the lesions

of KB and the ones that they saw in their patients. KB has a variety

of clinical morphologies, they comment, but the typical lesion starts

off as a red macule, papule, or papulovesicle, with a predilection

for the soles, that evolves into a thickened hyperkeratotic plaque,

often with an erythematous halo or a horny excrescence ( " oyster

shell " -like lesion).

" In our cases, the lesions resembled the more common type of pustular

psoriasis [and had] a good response to topical treatment, " Sfikakis

et al comment. They also highlight a recent paper [4], already

reported by rheumawire, that found a high incidence of skin lesions

in patients on anti-TNF therapy. This was a prospective study of 289

rheumatoid-arthritis patients on anti-TNF therapy, amassing a total

of 911 patient-years of follow-up: psoriatic eruptions were recorded

in three patients, but there were no cases of KB, they point out.

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