SEDIKIT INFO!!!!!!!!!
Bullous Dermatosis in End Stage Renal Disease: Role of Aluminum
S. Smetana MD. Head of the Department of Nephrology Z. Katzir MD.
H.E. Eliahou MD. Dept of Medicine
Edith Wolfson Medical Center, Holon 58100 and the Tel-Aviv University Sackler School of Medicine, Tel-Aviv 69978, Israel.
Bullous dermatosis (BD-ESRD) vs. Porphyria Cutanea Tarda (PCT)
The ESRD patient with Bullous Dermatosis (BD-ESRD) usually presents with multiple bullae on the extensor surface of the hands. These bullae are prone to rupture, which causes pain or secondary infection. Spontaneous remissions and exacerbations have been described. It has been shown that BD in ESRD is both clinically and histologically similar to porphyria cutanea tarda (PCT) (1-5). Although porphyrin plasma levels in BD-ESRD patients may resemble those of true PCT, the elevated levels are due to the impairment of renal porphyrin excretion and not because of uroporphyrin overproduction as in the patient with PCT. Regardless of the mechanisms leading to the increased plasma porphyrin concentration, the elevated level may result in skin photosensitivity and thus contribute to the development of BD (6,7).
Plasma and RBC porphyrin levels in BD-ESRD
The pathogenesis of BD-ESRD remains unclear. Conflicting results concerning the level of plasma porphyrins in BD-ESRD patients have been reported. In some cases normal values were found (1-4), whereas in others raised levels have been reported (5-7) suggesting that they contribute to the development of BD-ESRD (6,7). Increased erythrocyte coproporphyrin and protoporphyrin levels have been described in ESRD patients, suggesting that they also may play a role in causing BD-ESRD (8-11).
Serum aluminum levels and BD-ESRD
Recently, Gafter et al (12) suggested that elevated serum aluminum (Al) levels have a possible relationship to BD-ESRD. They found associations among Al load, abnormal porphyrin metabolism, and the development of overt BD-ESRD skin lesions (12). They studied 6 BD-ESRD patients. Three were being treated by haemodialysis and 3 with CAPD. In the BD-ESRD patients, a significantly higher concentration of plasma uroporphyrin was present as compared to patients without BD-ESRD. Coproporphyrin and protoporphyrin concentrations in the RBCs were increased in both groups of ESRD patients (with and without BD), as compared to healthy controls, but they did not differ between ESRD patients with and without BD. The activity of uroporphyrinogen decarboxylase in the RBC of both groups of ESRD patients were not significantly different from the activity in the controls. Al concentration in the 7 patients with BD-ESRD were substantially higher than in ESRD patients without BD (28.3 +/- 10 versus 6.7 +/- 0.9 ug/L respectively, p < 0.05). Normal serum aluminum levels ranged from 0 to 3 ug/L in the control group with intact kidney function.
Effect of aluminum on porphyrin metabolism
In rats, administration of Al leads to the induction of experimental porphyria (13). In hemodialyzed patients a correlation between the level of Al and the concentration of RBC protoporphyrin has been reported (14). Al interferes with heme synthesis. Following oral administration of Al, rats expressed a marked increase in the activity of heme oxygenase (16). Al can also induce an increased porphyrin synthesis (6) and can cause a significant elevation in the activity of aminolaevulinate synthase, the rate limiting enzyme of heme biosynthesis (16). Intraperitoneal administration of Al in rats causes an abnormal excretion of porphyrins in the urine. This effect is more pronounced in partially nephrectomized rats (13).
Aluminum and BD-ESRD: Response to chelation therapy
In 3 hemodialyzed patients with Al toxicity and BD-ESRD, skin manifestations resolved (19) following long-term treatment with desferrioxamine. Desferrioxamine chelates both iron and aluminium, and therefore Al removal could have played a role in the success of therapy (20,21).
Other features of BD-ESRD
Although high Al concentration in the dialysis water has been reported to cause overt PCT (15), BD in ESRD patients lacks the associated manifestations of hypertrichosis or sclerodermoid features of true PCT (17). Interestingly, most of the BD-ESRD patients were men consistent with the male preponderance of PCT (18). A high percentage of adult polycystic kidney disease was found in these patients. Affected patients had been on dialysis for a substantial period of time (mean nearly 8 years) and all were anuric. Patients on CAPD were affected as much as patients on haemodialysis.
Conclusions
In conclusion, a high serum Al concentration in ESRD patients may affect enzymes in the heme biosynthetic pathway leading to an overproduction and an accumulation of porphyrins. This, coupled with the reduction in removal of porphyrins from the plasma due to a very low or non-existent GFR, may partially explain the formation of BD in the ESRD population.
References:
1. Gilchrest B, Rowe JW, Mlhm MC jr. Bullous dermatosis of hemodialysis. Ann Int Med 1975;83:480-483.
2. Keczkes K, Farr M. Bullous dermatosis of chronic renal failure. Br J Dermatol 1976;95:541-546.
3. Thivolet J, Euvrard S, Perrot H. La pseudo-porphyrie cutanee tardive des hemodialyses. Ann Derm Venereal 1977;104:12-17.
4. Brivet F, Drueke T, Guillemette J. Porphyria cutanea tarda-like syndrome in hemodialyzed patients. Nephron 1978; 20:258-266.
5. Pob-Fitzpatrick MB, Masullo AS, Grossman ME. Porphyria cutanea tarda associated with chronic renal disease and hemodialysis. Arch Dermatol 1980;116:191-195.
6. Day RS, Eales L, Disler PB. Porphyria and the kidney. Nephron 1981; 28:261-267.
7. Seubert S, Suebert A, Rumph KW, Kiffe H. A porphyria cutanea tarda like distribution pattern of porphyrins in plasma, hemodialysate, hemofiltrate and urine of patients on chronic haemodialysis. J Invest Dermatol 1985;85; 107-109.
8. Yalouris AG, Lyberatos C, Chalevelakis G, Theodosiadou E, Billis A, Raptis S. Some parameters in heme synthesis in dialyzed and non-dialyzed uremic patients. Scand J Haematol 1986;37:404-410.
9. Anderson CD, Rossi E, Garcia-Webb P. Porphyrin studies in chronic renal failure patients on maintenance hemodialysis. Photodermatol 1987;4:14-22.
10. Gebril M, Weinkove C, Ead R, McDonald K, Morton R. Plasma porphyrins in chronic renal failure. Nephron 1990;55:159-163.
11. Fontanellas A, Coronel F, Santos JL. Heme biosynthesis in uremic patients on CAPD or haemodialysis. Kidney Int 1994;45:220-223.
12. Gafter U, Mamet R, Korzets A, Malachi T, Schoenfeld N. Bullous dermatosis of end-stage renal disease: possible association between abnormal porphyrin metabolism and aluminium. Nephrol Dial Transplant 1996;11:1787-1791.
13. Berlyne GM, Yagil R, Aluminium-induced porphyria in rats. Lancet 1973;2:1501-1502.
14. Bia MJ, Coopert K, Schall S. Aluminum-induced anemia . Pathogenesis and treatment in patients on chronic hemodialysis. Kidney Int 1989;36:852-858
15. King J, Day RS, Milne ILJ, Bezwoda WR, Viljoen JD, Kramer S. Delayed onset of overt porphyria cutanea tarda in a patient on long-term hemodialysis. SA Med J 1983;63:743-746.
16. Chmielnicka J, Nasiadek M, Lewandowska-Zyndal E.The effect of aluminum chloride on some steps of heme biosynthesis in rats after oral exposure. Biol Trace Element Res 1994;127-136.
17. Polb-Fitzpatrick MB, Porphyria, pseudoporphria, pseudo-pseudo porphyria....? Arch Dermatol 1986;122:403-404.
18. Elder GH, Gray CH, Nicholson DC.The porphyrias: A review. J Clin Pathol 1972;25:1013-1033.
19. McCarthy JT, Milliner DS, Johnson WJ, Clinical experience with desferrioxamine in dialysis patients with aluminum toxicity. Q J Med 1990;74(275):257-276.
20. Praga M, DeSalamanca RE, Andres A. Treatment of hemodialysis related PCT with desferrioxamine. N Eng J Med 1987;316:547-548.
21. Stocken Bauer F, Kurtz R, Grimm G, Moser G, Balcke P. Successful treatment of haemodialysis-related PCT with desferrioxamine. Nephron 1990;55:321-324.
November, 1966
0 komentar:
Catat Ulasan