Psoriasis exacerbation after a flu-like syndrome during anti-TNF-alpha therapy

ARTICLE

Auteur(s) : Nicoletta CASSANO, Carmela COVIELLO, Francesco LOCONSOLE, Antonio MIRACAPILLO, Gino Antonio VENA

Department of Internal Medicine, Immunology and Infectious Diseases – 2nd Dermatology Clinic, University of Bari, Policlinico - Piazza Giulio Cesare, 11 70124 Bari, Italy
<g.vena@dermatologia.uniba.it>

A 35-year-old man had a severe plaque psoriasis and a disabling psoriatic arthritis, which had been poorly controlled by conventional systemic therapies. The patient’s history revealed an unstable course of psoriasis with recurrent episodes of erythroderma or pustular exanthematic psoriasis after intercurrent infections and/or inadequate topical treatments. The patient underwent treatment with s.c. etanercept 25 mg twice per week; baseline Psoriasis Area and Severity Index (PASI) was 24. After 8 weeks of treatment, the patient consulted us because of a sudden aggravation of skin lesions (figure 1), despite the disappearance of joint pain and stiffness. Diffuse skin lesions were noted (PASI: 36) and some areas showed signs of pustulation. There was a modest sub-mandibular lymphadenopathy and a slight hyperpyrexia (38-38.5 °C). Routine laboratory examinations showed a modest neutrophilic leucocytosis with a slight increase of the erythrocyte sedimentation rate. ANA and anti-DNA antibodies were normal. Extensive searches for infectious foci failed to disclose any abnormal finding. Human immunodeficiency virus (HIV) serology was also negative. Histological features were consistent with psoriasis and immunofluorescence analysis of skin samples was negative. After repeated questioning, the patient reported that 10 days prior to the skin changes, he had suffered from flu-like symptoms with upper respiratory tract involvement. Despite this event, the patient had continued treatment with etanercept. He denied the use of other drugs.
After discontinuation of etanercept, the patient was initially treated with topical therapy (liniments, diluted antiseptic solutions, and corticosteroids) and oral paracetamol for one week until the fever faded away. Thereafter, treatment with methotrexate 10 mg weekly and cyclosporin 2.5 mg/kg was introduced, which caused the regression of pustular lesions and a per day noticeable reduction of erythema after 2 months. However, articular symptoms reappeared and treatment with etanercept was restarted with a good clinical response and without any complications.
Infectious foci are traditionally included among the factors which can elicit or worsen psoriasis, although a pathogenic role has been proved only for a few types of infections, such as streptococcal and HIV infections. An epidemiological survey has recently supported the existence of a subgroup of psoriasis patients, who are prone to disease exacerbation following infections, especially those of the upper respiratory tract [1]; the risk of infection-triggered exacerbation was associated with an unstable and severe course of psoriasis. In our patient, the aggravation of psoriasis skin lesions occurred after a flu-like syndrome during treatment with etanercept, a recombinant human TNF receptor:Fc fusion protein whose effectiveness in psoriatic arthritis and plaque psoriasis is well established [2]. This event did not appear to be directly related to etanercept, as the patient’s history included previous episodes of psoriasis flare after intercurrent infections. The analysis of clinical trials does not show an increased incidence of infections in patients treated with etanercept as compared with a placebo group. However, considering the mechanism of action, etanercept should not be administered to patients with sepsis or active infections, including chronic or localized infections [2]. The reaction which occurred in our patient suggests that extreme caution is also advisable when focal infections develop in patients treated with anti-TNF-alpha therapy, especially in those with unstable psoriasis, in whom a temporary withdrawal is recommended.
There are only sporadic reports of paradoxical de novo appearance or aggravation of psoriasis in patients treated with anti-TNF-alpha biologicals [3-6], but, to the best of our knowledge, the association with an intercurrent infection has never been reported. Possibly, this correlation may have been underestimated because focal infections can be neglected or ignored by patients, as in our case. Interestingly, the persistence of an excellent response on arthritis in spite of the aggravation of skin lesions indicates that the mechanisms triggering psoriasis may be, at least in some situations, different from those responsible for the exacerbation of psoriatic arthritis. n

1. Blok S, Vissers WH, van Duijnhoven M, van de Kerkhof PC. Aggravation of psoriasis by infections: a constitutional trait or a variable expression? Eur J Dermatol 2004; 14: 259-61.

2. Goffe B, Cather JC. Etanercept: An overview. J Am Acad Dermatol 2003; 49 (2 Suppl): S105-11.

3. Thurber M, Feasel A, Stroehlein J, Hymes SR. Pustular psoriasis induced by infliximab. J Drugs Dermatol 2004; 3: 439-40.

4. Dereure O, Guillot B, Jorgensen C, Cohen JD, Combes B, Guilhou JJ. Psoriatic lesions induced by antitumour necrosis factor-alpha treatment: two cases. Br J Dermatol 2004; 151: 506-7.

5. Grinblat B, Scheinberg M. Unexpected onset of psoriasis during infliximab treatment: comment on the article by Beuthien et al. Arthritis Rheum 2005; 52: 1333-4.

6. Starmans-Kool MJ, Peeters HR, Houben HH. Pustular skin lesions in patients treated with infliximab: report of two cases. Rheumatol Int 2005; 25: 550-2.