Background
To date, no study has identified a clear relationship between drug and a specific clinical presentation of DRESS.
Objectives
To investigate the particularities of DRESS and analyze the ...variation of DRESS pattern according to culprit drugs.
Methods
We analyzed cases of DRESS notified to the Department of Clinical Pharmacology at the University Hospital of Monastir over a 15-year period. The statistical study was performed using the comparative and multivariate analysis.
Results
DRESS was mostly induced by anticonvulsive agents (27%) followed by allopurinol (26.3%) and antibiotics (24%): For anticonvulsive agents, the occurrence of lymphadenopathy was higher, renal involvement was rare and mild, and positive skin tests were more frequent. The allopurinol group was associated with the patient’s older age and a lower incidence of lymphadenopathy and kidney injury. For antibiotics, eosinophilia rate was lower, time to recovery was shorter, and RegiSCAR score was low. The multivariate analysis showed a link of allopurinol with severe renal impairment, antibiotics with short latency period and low RegiSCAR score, and anticonvulsants with high propensity of positive skin test.
Conclusion
We report the largest African and south Mediterranean cohort of DRESS and evaluated the usefulness of skin tests in identifying the culprit drug. The prominent finding was that latency period and renal involvement may independently differ according to culprit drugs.
•To the authors’ knowledge, this paper reports the first pharmacokinetic model for isoniazid (INH) for use in North African patients with tuberculosis.•Only acetylator status was found to affect the ...pharmacokinetic parameters in this population.•This model allows individualized INH doses to be established based on acetylator status.•Initial doses of at least 225 mg/24 h and at least 450 mg/24 h allow attainment of a therapeutic concentration in >80% of patients in the slow acetylator group and rapid/intermediate acetylator group, respectively.
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To develop a pharmacokinetic model of isoniazid (INH) concentration taking into account demographic factors and genetic variables N-acetyltransferase 2 (NAT2) genotype, and to propose an initial INH dosage that could maximize the probability of achieving the desired INH concentration.
A retrospective analysis was undertaken of INH concentration data collected from patients with tuberculosis in Tunisia.
In total, 118 patients were included in this study. The one-compartment model volume of distribution (V), elimination rate (Ke) was found to have good predictive performance. Multi-variate analysis showed that NAT2 affected both V and Ke significantly, but age, gender and weight did not. Internal validation of the final model showed correlation of 0.95 between individual predicted INH concentration 3 h after drug intake (C3) and observed C3. External validation showed that percentage mean absolute prediction error and percentage root mean squared error were 9.11% (range 0.62–35.8%) and 11.6%, respectively. Monte-Carlo simulation showed that doses of at least 225 mg/24 h and at least 450 mg/24 h attained a therapeutic concentration in >80% of patients in the NAT2 slow acetylator group and the NAT2 rapid/intermediate acetylator group, respectively.
The pharmacokinetic model allowed optimization of individual dosing regimens of INH in patients with tuberculosis in Tunisia. This tool may facilitate improved efficacy of INH and prevent its toxicity in this population.
Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe and rare adverse drug reaction. Several drugs are known to induce DRESS. Furosemide, a sulfonamide loop diuretic drug, is ...known to induce hypersensitive reactions such as bullous eruptions, acute generalized exanthematous pustulosis and lichenoid eruptions, but rarely DRESS. We describe herein a case of furosemide-induced DRESS that recurred after bumetanide administration.
A 67-year-old man was admitted to the nephrology department for hypertension, gout and chronic renal failure. He received a multidrug therapy including captopril, nifedipine, allopurinol and furosemide. Six weeks after starting this treatment, he developed a maculopapular itchy and edematous skin reaction, facial edemaand fever. The laboratory findings showed 2200/mm3 of eosinophils (20%). Creatinine clearance decreased from 18.9 to 14.4 mL/min. Lactate dehydrogenase was at 600 IU/L (normal range 190-390 IU/L). Chest X-ray showed an interstitial lung injury. Skin biopsy findings were in accordance with a hypersensitive reaction. Furosemide was withdrawn and symptoms resolved completely three weeks later. A patch test with furosemide performed six weeks later was negative. The patient was given bumetanide, another sulfonamide loop diuretic, with recurrence of symptoms two months later. Bumetanide was withdrawn with a complete resolution of both clinical and biological symptoms within three weeks.
We add to the literature another case of furosemide-induced DRESS with the particularity of cross reactivity with bumetanide.
ObjectiveThis paper aims to assess the socioeconomic determinants of a high 10 year cardiovascular risk in Tunisia.SettingWe used a national population based cross sectional survey conducted in 2005 ...in Tunisia comprising 7780 subjects. We applied the non-laboratory version of the Framingham equation to estimate the 10 year cardiovascular risk.Participants8007 participants, aged 35–74 years, were included in the sample but effective exclusion of individuals with cardiovascular diseases and cancer resulted in 7780 subjects (3326 men and 4454 women) included in the analysis.ResultsMean age was 48.7 years. Women accounted for 50.5% of participants. According to the Framingham equation, 18.1% (17.25–18.9%) of the study population had a high risk (≥20% within 10 years). The gender difference was striking and statistically significant: 27.2% (25.7–28.7%) of men had a high risk, threefold higher than women (9.7%; 8.8–10.5%). A higher 10 year global cardiovascular risk was associated with social disadvantage in men and women; thus illiterate and divorced individuals, and adults without a professional activity had a significantly higher risk of developing a cardiovascular event in 10 years. Illiterate men were at higher risk than those with secondary and higher education (OR=7.01; 5.49 to 9.14). The risk in illiterate women was more elevated (OR=13.57; 7.58 to 24.31). Those living in an urban area had a higher risk (OR=1.45 (1.19 to 1.76) in men and OR=1.71 (1.35 to 2.18) in women).ConclusionsThe 10 year global cardiovascular risk in the Tunisian population is already substantially high, affecting almost a third of men and 1 in 10 women, and concentrated in those more socially disadvantaged.
Hepatic involvement in the form of hepatocellular injury was the most common visceral abnormality and it was present in 4 cases with sulfasalazine and in 3 cases with allopurinol.
Introduction Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, also known as drug induced hypersensitivity syndrome (DIHS), is a severe and potentially life-threatening disease with ...mortality rates of up to 10%.
Abstract Nodular lymphoid hyperplasia (NLH) of the gastrointestinal tract is a rare disease usually reported in patients with congenital or acquired immunodeficiency and chronic gastrointestinal ...infections. However, no case of NLH in a patient receiving immunosuppressive therapy has been reported to date. We describe the case of a woman who developed chronic diarrhea related to NLH 9 years after liver transplantation. Other causes of diarrhea and NLH were excluded. Her immunosuppressive regimen consisted on mycophenolate mofetil (MMF) and tacrolimus. Reduction of MMF dose improved symptoms but led to a rising aminotransferase level. Given the risk of graft rejection, MMF at full dose was resumed and she was started on symptomatic treatment for diarrhea. The role of immunosuppressive drugs in the pathogenesis of NLH may be related to the reduction of T- and B-lymphocyte proliferation and decreasing antibody production. NLH will further develop to compensate functionally inadequate lymphoid tissue, as reported in congenital immunodeficiency states.
Highlights • Hepatic lesions have been infrequently reported in Alagille syndrome. • Most of them have been described as hepatocellular carcinoma. • Focal liver hyperplasia can also be a cause of ...focal lesion. • Magnetic resonance imaging features can reliably differentiate them.
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