make your diagnosis
http://www.kidney-international.org & 2013 International Society of Nephrology Kidney International (2014) 85, 987–988; doi:10.1038/ki.2013.242
The Case | A hemodialysis patient with bullous skin lesions Elie H. Maalouf1, Ismae¨l I. Maatouk1, Roy R. Moutran2, Ge´rard A. Abadjian3 and Euge´nie A Halaby1 1 Dermatology Department, Hoˆtel-Dieu de France Hospital, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon; 2Dermatology Department, Mount Lebanon Hospital, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon and 3Pathology Department, Hoˆtel-Dieu de France Hospital, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon
Correspondence: Ismae¨l I. Maatouk, Dermatology Department, Hoˆtel-Dieu de France Hospital, Beirut, Lebanon. E-mail: [email protected]
Figure 1 | Erosions and crusts over the face.
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 1735 mg/l (normal 40–250 mg/l), and normal metal screen (aluminum, zinc, and lead). Screening for hepatitis C was negative. Liver enzyme levels were elevated (AST 70 U/l; ALT 70 U/l; and AP 530 U/l).
What is your diagnosis? SEE NEXT PAGE FOR ANSWERS Kidney International (2014) 85, 987–988
987
make your diagnosis
EH Maalouf et al.: Hemodialysis patient with bullous skin lesions
The Diagnosis | Porphyria cutanea tarda
Figure 2 | Subepidermal separation of the skin with minimal inflammation. Note the elastosis seen in the papillary and reticulated dermis.
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 170 nmol/g of dry weight (normal o41) with a predominance of isocoproporphyrin, and elevated levels of predialysis plasma uroporphyrin were observed (1100 nmol/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 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 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.
988
Pseudoporphyria is a term used to describe patients with normal porphyrin levels, but with clinical and histological features similar to PCT.1,2 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 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 and kidney transplantation.
REFERENCES 1.
2. 3.
Poh-Fitzpatrick MB, Masullo AS, Grossman ME. Porphyria cutanea tarda associated with chronic renal disease and hemodialysis. Arch Dermatol 1980; 116: 191–195. Sassa S. Modern diagnosis and management of the porphyries. Br J Haematol 2006; 135: 281–292. Pandya AG, Nezafati KA, Ashe-Randolph M et al. Deferasirox for porphyria cutanea tarda: a pilot study. Arch Dermatol 2012; 148: 898–901.
Kidney International (2014) 85, 987–988
http://www.kidney-international.org & 2013 International Society of Nephrology Kidney International (2014) 85, 987–988; doi:10.1038/ki.2013.242
The Case | A hemodialysis patient with bullous skin lesions Elie H. Maalouf1, Ismae¨l I. Maatouk1, Roy R. Moutran2, Ge´rard A. Abadjian3 and Euge´nie A Halaby1 1 Dermatology Department, Hoˆtel-Dieu de France Hospital, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon; 2Dermatology Department, Mount Lebanon Hospital, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon and 3Pathology Department, Hoˆtel-Dieu de France Hospital, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon
Correspondence: Ismae¨l I. Maatouk, Dermatology Department, Hoˆtel-Dieu de France Hospital, Beirut, Lebanon. E-mail: [email protected]
Figure 1 | Erosions and crusts over the face.
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 1735 mg/l (normal 40–250 mg/l), and normal metal screen (aluminum, zinc, and lead). Screening for hepatitis C was negative. Liver enzyme levels were elevated (AST 70 U/l; ALT 70 U/l; and AP 530 U/l).
What is your diagnosis? SEE NEXT PAGE FOR ANSWERS Kidney International (2014) 85, 987–988
987
make your diagnosis
EH Maalouf et al.: Hemodialysis patient with bullous skin lesions
The Diagnosis | Porphyria cutanea tarda
Figure 2 | Subepidermal separation of the skin with minimal inflammation. Note the elastosis seen in the papillary and reticulated dermis.
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 170 nmol/g of dry weight (normal o41) with a predominance of isocoproporphyrin, and elevated levels of predialysis plasma uroporphyrin were observed (1100 nmol/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 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 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.
988
Pseudoporphyria is a term used to describe patients with normal porphyrin levels, but with clinical and histological features similar to PCT.1,2 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 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 and kidney transplantation.
REFERENCES 1.
2. 3.
Poh-Fitzpatrick MB, Masullo AS, Grossman ME. Porphyria cutanea tarda associated with chronic renal disease and hemodialysis. Arch Dermatol 1980; 116: 191–195. Sassa S. Modern diagnosis and management of the porphyries. Br J Haematol 2006; 135: 281–292. Pandya AG, Nezafati KA, Ashe-Randolph M et al. Deferasirox for porphyria cutanea tarda: a pilot study. Arch Dermatol 2012; 148: 898–901.
Kidney International (2014) 85, 987–988
