BULLOUS DERMATOSIS OF END-STAGE RENAL-DISEASE - A POSSIBLE ASSOCIATION BETWEEN ABNORMAL PORPHYRIN METABOLISM AND ALUMINUM

Background. Bullous dermatosis (BD) is becoming increasingly recognize d in patients with end-stage renal disease (ESRD). It is clinically re miniscent of porphyria cutanea tarda, but its detailed pathogenesis re mains unclear. Studies have shown increased porphyrin levels in dialys is patients, and this may partly explain the skin lesions and photosen sitivity evident in these patients. In experimental studies, aluminium can induce various abnormalities in porphyrin and haem metabolism. Th is study investigated a possible involvement of porphyrin metabolism a nd aluminium in the development of bullous dermatosis in chronically d ialysed patients. Methods. Three groups were studied (12 healthy contr ols; 12 patients on chronic dialysis without BD and six patients on ch ronic dialysis with BD). Clinical characteristics of these patients we re evaluated and the levels of plasma porphyrins, erythrocyte porphyri ns and enzymes involved in the porphyrin chain were determined. Result s. The patients with BD were predominantly male, 50% had ADPKD, all ha d been on dialysis for a long period of time (7.8 +/- 2.1 years) and a ll were anuric. CAPD and haemodialysis were used equally in the affect ed patients. Aminolaevulinic dehydratase activity was significantly re duced in all ESRD patients (892 +/- 47 versus 302 +/- 36 versus 408 +/ - 37 nmol/ml RBC/h). Plasma uroporphyrins as well as RBC protoporphyri n 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 mu mol/l) respectively. Serum Al levels w ere markedly elevated in patients with BD (28.3 +/- 10.0 mu g/l). Both uroporphyrin and protoporphyrin were significantly more elevated in E SRD 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 ther apy to remove them. These elevated porphyrin levels may lead to the de velopment of porphyria cutanea tarda symptoms. Elevations in plasma ur oporphyrin, red blood cell protoporphyrin, and elevated Al levels sugg est a possible relationship between an Al 'load' and abnormal porphyri n metabolism in the development of overt skin disease in the dialysed patient.