Discussion
Psoriasis is a chronic cutaneous inflammatory disease
characterised by hyperproliferation of keratinocytes
and infiltration of activated T lymphocytes into the
epidermis which are responsible for the release of mul-
tiple cytokines. These cytokines are predominantly of
the Th 1 profile and include IL-2, interferon-c, IL-12
and TNF-a. The latter is present in high levels in pso-
riatic plaques and serum of patients with psoriasis as
well as in the joint fluid of patients with psoriatic
arthritis.
1
At the cellular level, TNF-astimulates expression of
ICAM-1 on keratinocytes and their production of IL-8
and transforming growth factor-a, and E-selectin on
endothelial cells.
2
This suggests that TNF-aplays a role
in pathogenesis of psoriasis by activating T lymphocytes,
enhancing the infiltration of T lymphocytes into the
epidermis and augmenting keratinocyte proliferation.
TNF-ainhibitors therefore have the potential to improve
psoriasis by reducing inflammation and normalisation
of keratinocyte proliferation.
Infliximab is a chimeric (mouse-human) monoclonal
antibody that binds to TNF-awith high affinity and
neutralises the biological activity of this cytokine.
3
Infli-
ximab is already licensed for treatment of rheumatoid
arthritis and Crohn’s disease in the UK.
In a randomised double-blind placebo-controlled trial
of infliximab in patients with moderate or severe psoria-
sis 17 out of 22 patients were clear or almost clear of
their disease at week 10 following 3 infusions.
4
Another
recent study by Schopf et al also using infliximab as
monotherapy confirmed the efficacy of this treatment for
severe psoriasis. However the psoriasis tended to relapse
about 8 weeks after the last infusion.
5
Infliximab is not a human monoclonal antibody and
therefore has a potential for inducing neutralising anti-
bodies when used on a long-term basis. It has been
shown that concomitant use of infliximab and low-dose
methotrexate (MTX) of 7.5 mg weekly for the treatment
of rheumatoid arthritis diminished the appearance of
human antichimeric antibodies and also potentiated
its clinical response.
6
The treatment is well tolerated
in the short term, although long-term safety profile of
infliximab needs to be studied. Infliximab was reported
to be used successfully in combination with MTX in
treatment of recalcitrant psoriasis.
7, 8
Our patient was treated with a combination of infli-
ximab with hydroxyurea. The latter drug is a hydro-
xylated derivative of urea and is an antineoplastic agent
that inhibits DNA synthesis and repair.
9
Hydroxyurea
is known to be effective as a monotherapy for severe
psoriasis in doses ranging from 0.5 to 1.5 g daily.
Layton et al found that 52 of 85 patients with extensive
chronic plaque psoriasis who were unresponsive to
conventional topical therapy achieved a satisfactory
remission during treatment with hydroxyurea without
significant adverse effects.
12
Therapy was discontinued
in 33 patients due to inadequate response or adverse
effects. In our patient the use of hydroxyurea in com-
bination with anti-TNFaagent appeared to produce a
beneficial effect by promptly inducing and maintain-
ing clearance of psoriasis and resolution of the sym-
ptoms of psoriatic arthritis. This combination therapy
for refractory psoriasis has not previously been des-
cribed. Hydroxyurea is known to have the potential to
suppress B cell responses
10, 11
and may therefore inhibit
the antibody response to infliximab in the same way
as methotrexate, as well as demonstrating a synergistic
therapeutic effect on the psoriasis.
Conclusion
This combined regimen may prove to be a useful new
treatment option for patients suffering from severe
psoriasis and/or psoriatic arthritis.
References
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J E Gach and Berth-Jones Recalcitrant psoriasis treated with infliximab and hydroxyurea
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