Candesartan cilexetil induced pustular psoriasis

ARTICLE

Auteur(s) : Ai KAWAMURA, Toyoko OCHIAI

Department of Dermatology, Surugadai Nihon University Hospital, 1-8-13 kanda-Surugadai, Chiyoda-ku, Tokyo 101-8309, Japan.

Pustular eruptions and psoriasiform drug eruption caused by antihypertensitive drugs are relatively rare [1]. They have been reported with β-adrenergic blocking agents [2, 3], calcium channel blocker [4] and angiotensin converting enzyme (ACE) inhibitors [5-7]. Angiotensin II type 1 (AT1) receptor antagonists, as a new class of drug for hypertension or congestive heart failure, have become an established and popular treatment for hypertension because of good compliance by patients and few side effects [8]. Their antihypertensive efficacy compares well with other drugs. In this study, we found a generalized pustular psoriasis induced by candesartan cilexetil (AT1 receptor antagonists) with a psoriatic background.

Case report

A 67-year-old Japanese woman was referred in February 2002 with a 2-week history of skin eruption on her trunk and extremities. She had had hypertension and diabetes mellitus, for which treatment had been given with several drugs including aspirin, frusemide, glibenclamide, spironolactone, metoprolol and triazolam for 10 years. She had no family history of psoriasis. She also had been treated for erythema on both groins and submammary areas for 5 years. The diagnosis was flexural psoriasis. Topical steroid therapy for several months improved the cutaneous lesions, which subsequently remained quiescent without treatment. Five months before being referred to us, an implantable pacemaker was placed in treatment for her ventriclar arrhythmia, and additional therapy with candesartan cilexetil was initiated for her hypertension. Two weeks before being referred to us, she noticed the eruption on her left groin, which extended to both groins, axillary and submammary areas for several days. Physical examination revealed erythematous, scaling plaques with a large number of pustules and erosion on her trunk, extremities and intertriginous areas (Fig. 1a, b). She had no fever, nor general malaise. Mucosal eruptions were not found. Laboratory studies disclosed the following values: the white blood cell count of 8200/mm³ with a differential count of 65.6% neutrophils, 1.3% eosinophils and 26.4% lymphocytes. The level of c-reactive protein (CRP) was 0.6 mg/dl (normal < 0.3). Other laboratory values were at normal levels. Skin cultures for bacteria and fungi were negative. Histology of a skin biopsy from the erythema with pustules on the left thigh showed the neutrophilic infiltration underneath the stratum corneum with intraepidermic spongiform pustules (Fig. 2). There were perivascular infiltrates of lymphocytes and neutrophils in the dermis. Presumptive diagnosis suggested the possibility of either pustular drug eruption or candesartan cilexetil induced pustular psoriasis. Candesartan cilexetil was discontinued. Subsequently, the erythemas with pustules and erosions healed gradually with scales and pigmentation in the next two weeks. No recurrence of the cutaneous lesion was noted. A patch test and lymphocyte stimulating test (LST) with candesartan cilexetil were negative. Drug challenge test was not performed.

Discussion

We report a rare case of generalized pustular psoriasis induced by AT1 receptor antagonists. It is uncertain yet whether pustular drug eruptions represent a distinct entity or drug-induced generalized pustular psoriasis. Spencer et al. described that pustular drug eruptions represent a distinct entity; the absence of a personal or family history of psoriasis, spontaneous resolution without therapy, the presence of eosinophils in the inflammatory infiltrate, and absence of histological features of conventional psoriasis [10]. In our case, the patient had an episode of flexural psoriasis, and developed generalized pustular eruptions without fever. No inflammatory findings were shown by laboratory tests. Her biopsy specimen did not show features of eosinophilic infiltration. A patch test and lymphocyte stimulating test (LST) with candesartan cilexetil were negative. Clinical improvement of the skin eruption was achieved after candesartan cilexetil was stopped, and no recurrence was noted. These findings suggest that the pustular eruption was caused by psoriatic flares induced by candesartan cilexetil. Roujeau et al. stated that some of the cases previously diagnosed as exanthematous pustular psoriasis may in fact have represented toxic pustuloderma caused either by drugs or infection. In their review of 63 cases, they also reported a higher than expected history of psoriasis in the patients who developed a toxic pustuloderma (11 out of 63), and speculated that this type of drug reaction may be favored by a “psoriatic background” [11]. In our case, the pustular eruption started 4 1/2 months after candesartan cilexetil started. This is still quite a long time, but not impossible for the exacerbation of psoriasis by candesartan cilexetil. Stephan et al. reported that flares of psoriasis occur from 2 weeks to 4 months after initiation of the putative responsible drugs [1].
The precipitation or exacerbation of psoriasis has been rarely recognized during the therapy of cardiovascular diseases. They have been reported with β-adrenergic blocking agents, calcium channel blocker and ACE inhibitors. ACE inhibitors inhibit angiotensin-converting enzyme which metabolizes bradykinin and substance P. ACE inhibitors increase the level of bradykinin, causing the relatively infrequent induction or exacerbation of psoriasis [1]. It is generally believed that AT1 receptor antagonists do not increase the bradykinin level, inhibiting the renin-angintensin system more potently than ACE inhibitor [12]. Although we cannot expect to fully understand the pathogenesis of pustular psoriasis caused by AT1 receptor antagonists, the results of this case show that AT1 receptor antagonists might have some potency as ACE inhibitors, as up-regulators for bradykinin, and might induce generalized pustular eruptions on a psoriatic background. n

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