Dihydropyrimidine dehydrogenase deficiency [DPD] in GI malignancies: experience of 4-years

5-Fluorouracil [5-FU] is an integral part of treatment of GI malignancies. While normal DPD enzyme activity is rate limiting in 5-FU catabolism, its deficiency could increase concentrations of bioavailable 5-FU anabolic products leading to 5-FU related toxicity syndrome. Twenty-three patients were tested for DPD deficiency after excessive toxicities from 5-FU and/or capecitabine. DPD activity was evaluated by Peripheral Blood Mononuclear Cell [PBMC] radioassay, genotyping of DPYD gene by Denaturing High Performance Liquid Chromatography [DHPLC], or 2-13C uracil breath test [UraBT]. Of 23 patients with excessive toxicities from 5-FU and/or capecitabine, 7 [30%] were DPD deficient with a median age of 66 years, M:F ratio = 1.3:1 and ethnicities included Caucasian [71%], African-American [14%] and South-Asian [14%]. DPD activity ranged from 0.064 - 0.18nmol/min/mg. Three patients were treated with bolus 5-FU/LV, two with capecitabine, and two with high dose bolus 5-FU with 2', 3', 5'-tri-O-acetyluridine. Toxicities included mucositis [71%], diarrhea [43%], skin rash [43%], memory loss/altered mental status [43%], cytopenias [43%], nausea [29%], hypotension [14%], respiratory distress [14%] and acute renal failure [14%] Re-challenge with capecitabine in one patient after the Mayo regimen caused grade 3 hand-foot syndrome. Genotypic analysis of the DPYD gene in one patient with severe leucopenia demonstrated a heterozygous mutation [IVS14+1 G>A, DPYD]. The UraBT in two patients revealed 1 to be DPD-deficient [DOB50 of 112.8; PDR of 49.4%] and borderline normal values [DOB50 of 130.9; PDR of 52.5%] in a second patient. There were 2 toxicity-related deaths among DPD-deficient patients [28%]. DPD deficiency was observed in several ethnicities. Akin to 5-FU, capecitabine can also lead to severe toxicities in DPD-deficient patients. Screening patients for DPD deficiency prior to administration of 5-FU or capecitabine using UraBT could potentially lower risk of toxicity. Future studies should validate this technique

Occupational dermatoses in Sharkia Governorate an epidemiological study

With industrialization and increased use of new chemical compounds, occupational dermatoses constitute the largest percentage of all work related illness. The aim of this study was to assess the problem of occupational dermatoses in Sharkia Governorate. Six hundred and seventy five workers were included in the study, 160 of whom were in the floor tile plants, 225 in an oil and soap factory and 290 in the road paving station. Complete history taking and dermatological examination were carried out and workers in the floor tile plants were patch tested to test sensitivity to different allergens. We have noticed that the prevalence of occupational dermaloses was about 23.3% ranging from 9.3% in the road paving stations to 63.1% in floor tile plants. The most prevalent type noticed was callosities and the commonest site was the hands. Young age, long duration of exposure, low level of education, fair skin and poor personal hygiene were associated with occupational dermatoses. Finally patch test results confirmed the association of chromium hypersensitivity and contact dermatitis