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, aluminum can induce various abnormalities in porphyrin and haem metabolism. This study investigated a possible involvement of porphyrin metabolism and aluminum 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 mumol/l) respectively. Serum A1 levels were markedly elevated in patients with BD (28.3 +/- 10.0 micrograms/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 A1 levels suggest a possible relationship between an A1 'load' and abnormal porphyrin metabolism in the development of overt skin disease in the dialysed patient.