The Case | A hemodialysis patient with bullous skin lesions
Authors: Elie H. Maalouf, Ismaël I. Maatouk, Roy R. Moutran, Gérard A. Abadjian, Eugénie A. Halaby
Journal: Kidney International (2014)

A 65-year-old woman with end-stage kidney disease secondary to diabetes on hemodialysis for 5 years presented with a several-week history of skin lesions over her face and hands. She had then noted fluid-filled lesions following minor trauma to her hands. The patient did not report any history of skin disease. On clinical examination, multiple erosions with crusting were noted over her cheeks and glabella, dorsal hands, and feet, where she also had some milia (Figure 1). There were no hypertrichosis, sclerodermoid lesions, or any other skin abnormalities. Laboratory analysis showed increased serum ferritin levels to 1735mg/l (normal 40–250mg/l), and normal metal screen (aluminum, zinc, and lead). Screening for hepatitis C was negative. Liver enzyme levels were elevated (AST 70U/l; ALT 70U/l; and AP 530U/l). What is your diagnosis? Skin biopsy and pathology examination of the lesions showed subepidermal separation of the skin with minimal associated inflammation (Figure 2). Direct immunofluorescence of perilesional skin reveals linear IgG, C3, and fibrinogen both along the dermoepidermal junction and around blood vessels. Stool coproporphyrin increased to 170nmol/g of dry weight (normal <41) with a predominance of isocoproporphyrin, and elevated levels of predialysis plasma uroporphyrin were observed (1100nmol/l; normal 0–1.4). All these findings were consistent with porphyria cutanea tarda (PCT). PCT, a disorder of heme biosynthesis, is characterized by the development of tense vesicles and bullae in a photodistributed pattern, often favoring dorsal hands and forearms, but the face, feet, or other sun-exposed skin may be involved. Crusting and erosions result from external trauma to the blisters; the lesions heal with scarring and milia formation. Facial hypertrichosis and sclerodermoid skin can also be seen.1.Poh-Fitzpatrick M.B. Masullo A.S. Grossman M.E. Porphyria cutanea tarda associated with chronic renal disease and hemodialysis.Arch Dermatol. 1980; 116: 191-195Crossref PubMed Scopus (56) Google Scholar In PCT, a deficiency of the uroporphyrinogen decarboxylase enzyme causes accumulation of porphyrins (especially water-soluble uroporphyrins) in the liver, plasma, and skin, where it generates oxidative free radicals when exposed to sunlight, resulting in photosensitivity, blisters, and scarring.1.Poh-Fitzpatrick M.B. Masullo A.S. Grossman M.E. Porphyria cutanea tarda associated with chronic renal disease and hemodialysis.Arch Dermatol. 1980; 116: 191-195Crossref PubMed Scopus (56) Google Scholar The pathogenesis of PCT in hemodialysis patients is not completely understood, but it is probably from hepatic iron overload, decreased urinary excretion, and the ineffective removal of porphyrins. Pseudoporphyria is a term used to describe patients with normal porphyrin levels, but with clinical and histological features similar to PCT.1.Poh-Fitzpatrick M.B. Masullo A.S. Grossman M.E. Porphyria cutanea tarda associated with chronic renal disease and hemodialysis.Arch Dermatol. 1980; 116: 191-195Crossref PubMed Scopus (56) Google Scholar,2.Sassa S. Modern diagnosis and management of the porphyries.Br J Haematol. 2006; 135: 281-292Crossref PubMed Scopus (154) Google Scholar Laboratory analysis is necessary to differentiate PCT from pseudoporphyria, which remains the main differential diagnosis. In anuric patients, evaluation of stool for elevated levels of isocoproporphyrin III and plasma for uroporphyrin is diagnostic.2.Sassa S. Modern diagnosis and management of the porphyries.Br J Haematol. 2006; 135: 281-292Crossref PubMed Scopus (154) Google Scholar The other subepidermal blistering disorders such as bullous pemphigoid, bullous lupus erythematous, and epidermolysis bullosa acquisita can be eliminated by direct immunofluorescence of perilesional skin, which reveals linear IgG, C3, and fibrinogen both along the dermoepidermal junction and around blood vessels. Standard hemodialysis does not efficiently remove uroporphyrins, but high-flux hemodialysis can increase porphyrin removal. Phlebotomy and erythropoietin (to decrease hepatic iron content) have been used. Patients should avoid precipitating factors such as alcohol, estrogens, iron supplements, and sunlight. Other treatment options are iron-chelating agents such as deferoxamine and deferasirox,3.Pandya A.G. Nezafati K.A. Ashe-Randolph M. et al.Deferasirox for porphyria cutanea tarda: a pilot study.Arch Dermatol. 2012; 148: 898-901PubMed Google Scholar and kidney transplantation.