Background: Fixed drug eruption (FDE) represents a drug-related cutaneous reaction.Many drugs been associated with this clinical entity, with continually evolving documentation of implicated agents and clinical presentations. A bullous form can occur although it is rare.Objectives: To assess the epidemiological and clinical characteristics of FDE. Methods: We retrospectively analysed all FDE cases who presented to the ClinicalPharmacology Department at the University Hospital, Monastir, Tunisia, for allergy workup.Results: The mean age of the 41 confirmed FDE cases was 43.8 ± 15.5 years. The time between first lesion onset and FDE diagnosis was less than 1 month for 13 patients (31.7%). Fifteen patients had bullous lesions. The upper limbs were the most common location (65.9% of cases). The patch tests were positive in 27 cases; a provocation test yielded a positive response in the four cases tested. Nonsteroidal anti-inflammatory drugs (NSAIDs) were involved in 51.2%, antibiotics in 24.4%, and other analgesics in 19.5%. The most common offending drug was mefenamic acid in 24.4% of cases. Bullous lesions were significantly associated with paracetamol intake (P = .014; odds ratio 16.7; 95% confidence interval: 1.76-158).Conclusions: NSAIDs and antibiotics were the most implicated in inducing FDE; paracetamol was associated with bullous lesions. K E Y W O R D Sepidemiology, fixed drug eruption, oral rechallenge, patch test

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Our data support a critical role of the CYP3A5 6986A>G and CYP3A4 -392A>G polymorphisms on the variation of Tac exposure during the early and the late PT phase, respectively. The establishment of customized Tac doses, according to CYP3A4/CYP3A5 genotype combination and the PT time, may allow preventing graft rejection and improving the safety profile of this drug. Further studies are needed to investigate this issue.

Background: Non-steroidal anti-inflammatory drugs constitute a main cause of fixed drug eruption (FDE). A few cases of piroxicam-induced FDE have been reported; however, the crossreactivity among oxicams has rarely been evaluated.Objectives: To describe a series of patients with piroxicam-induced FDE, mostly confirmed by a positive patch test reaction, in whom cross-reactivity to meloxicam was assessed. Methods:We included all cases of piroxicam-induced FDE diagnosed in the department of pharmacovigilance of Monastir. Patch tests for piroxicam and meloxicam were performed in the involved skin according to the European Network on Drug Allergy recommendations. Oral provocation tests (OPTs) were performed for patients with negative skin test results.Results: Seven patients were included in this study. FDE was multiple for five patients and solitary for two. Bullous eruption was noticed in two cases. Lesional patch tests for piroxicam gave positive results in six patients. To assess cross-reactivity with meloxicam, this was patch tested.The test gave a positive result in only one patient. OPTs with meloxicam gave positive results in two patients with negative patch test results.Conclusion: Meloxicam is not a safe alternative for the treatment of piroxicam-induced FDE, and OPTs can be used to confirm tolerance before this drug is prescribed as a safer alternative.

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Previous studies have shown controversial results on whether acetylator status causes isoniazid-induced hepatotoxicity (IIH). Moreover, the contribution of CYP2E1, a hepatic enzyme implicated in the formation of hepatotoxins, to the risk of developing IIH remains unclear. The objectives of this study were (i) to assess the quantitative relationship between the level of isoniazid serum concentration and the incidence of IIH and (ii) to evaluate the extent of implication of the N-acetyltransferase-2 (NAT2) and CYP2E1 polymorphisms genes to induce this disorder. Seventy-one patients with tuberculosis receiving a conventional antituberculosis regimen were included. NAT2 and CYP2E1 genotypes were determined using polymerase chain reaction. Three restriction enzymes, RsaI, PstI and DraI were used to detect CYP2E1 RFLP and four different restriction enzymes, KpnI, TaqI, BamHI and Ddel were used to determine NAT2 acetylator status. Therapeutic drug monitoring (TDM) of isoniazid (serum concentration performed 3 h after the morning dose: C3) was performed. Cases of isoniazid-induced hepatotoxicity were diagnosed according to Benichou et al. Receiver Operating Characteristics curve analysis was used to evaluate the relationship between risk factors and the incidence of IIH. Eleven (15.4%) patients have developed IIH. Demographic factors, including age, weight and gender were not associated with the incidence of hepatotoxicity. High serum concentration of isoniazid (C3) was found to be a risk factor of IIH (area under the curve: 0.74, P=0.007, 95% confidence interval (95% CI): 0.56-0.93), with a cutoff value at 3.69 mg l (odds ratio (OR): 13.2, P=0.0007, 95% CI: 2.9-59). Multivariate analysis showed that only a C3 over 3.69 mg l remains a risk factor of IIH. NAT2 and CYP2E1 variants were not found to increase the risk of IIH when analyzed separately. However, combined analysis of the NAT2/CYP2E1 gene polymorphisms showed that patients with both DraI C/D and slow acetylator have an increased risk of IIH compared with other combined NAT2/CYP2E1 genotype profiles (OR: 8.41, P=0.01, 95% CI: 1.54-45.76). Our results suggest that a serum concentration of isoniazid over 3.69 mg l and a combined genotype CYP2E1 DraI(C/D)/slow acetylator are major risk factors for IIH. Therefore, TDM of isoniazid and the determination of both NAT2 and CYP2E1 genotypes could be useful for the prediction and prevention of IIH in Tunisian tuberculosis patients.

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We report a case of acute generalized exanthematous pustulosis (AGEP) after cefotaxime use confirmed by a positive patch test. A 30-year-old woman received cefotaxime, fosfomycin and ciprofloxacin for sinusitis. Twelve days after drug initiation, she developed an extending pustular erythema associated with fever. Laboratory investigations showed marked leukocytosis. His blood chemistry was normal. The histological examination showed parakeratosis, spongiosis and nonfollicular intra-epidermal pustules consistent with AGEP. All medications were withdrawn. The symptoms resolved within 11 days after cefotaxime discontinuation. Patch tests were positive to cefotaxime after 48 h, while ciprofloxacin and fosfomycin yielded negative findings. Based on the Naranjo algorithm, it is probable that AGEP reaction was caused by cefotaxime. To our knowledge, this is the first reported case of AGEP associated with positive cefotaxime patch testing.