Bullous dermatosis of end-stage renal disease: A possible association between abnormal porphyrin metabolism and aluminium

Background, Bullous dermatosis (BD) is becoming increasingly recognized in patients with end-stage renal disease (ESRD). It is clinically reminiscent of porphyria cutanea tarda, but its detailed pathogenesis remains unclear. Studies have shown increased porphyrin levels in dialysis patients, and this may partly explain the skin lesions and photosensitivity evident in these patients. In experimental studies, aluminium can induce various abnormalities in porphyrin and haem metabolism. This study investigated a possible involvement of porphyrin metabolism and aluminium in the development of bullous dermatosis in chronically dialysed patients. Methods. Three groups were studied (12 healthy controls; 12 patients on chronic dialysis without BD and six patients on chronic dialysis with BD). Clinical characteristics of these patients were evaluated and the levels of plasma porphyrins, erythrocyte porphyrins and enzymes involved in the porphyrin chain were determined. Results. The patients with BD were predominantly male, 50% had ADPKD, all had been on dialysis for a long period of time (7.8 ± 2.1 years) and all were anuric. CAPD and haemodialysis were used equally in the affected patients. Aminolaevulinic dehydratase activity was significantly reduced in all ESRD patients (892 ± 47 versus 302 ± 36 versus 408 ± 37 nmol/ml RBC/h). Plasma uroporphyrins as well as RBC protoporphyrin were significantly elevated in ESRD patients (1.7 ± 0.6 versus 21.6 ± 4.7 versus 43.4 ± 12.0 nmol/l) and (1.43 ± 0.14 versus 2.4 ± 0.42 versus 4.19 ± 2.44 μmol/l) respectively. Serum Al levels were markedly elevated in patients with BD (28.3 ± 10.0 μg/l). Both uroporphyrin and protoporphyrin were significantly more elevated in ESRD patients with BD compared to ESRD patients without BD. Conclusions. Elevated plasma porphyrin levels in ESRD patients are caused by lack of urinary excretion and the inability of haemodialysis and CAPD therapy to remove them. These elevated porphyrin levels may lead to the development of porphyria cutanea tarda symptoms. Elevations in plasma uroporphyrin, red blood cell protoporphyrin, and elevated Al levels suggest a possible relationship between an Al 'load' and abnormal porphyrin metabolism in the development of overt skin disease in the dialysed patient.