Bullous Dermatosis in End Stage Renal Disease: Role of Aluminum
S. Smetana MD. Head of the Department of Nephrology Z. Katzir MD. Senior Nephrologist 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.
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