Diagnosis: Porphyria cutanea tarda
Our patient had porphyria cutanea tarda (PCT), which results from reduced uroporphyrinogen decarboxylase (UROD) activity. PCT is the most common of the porphyrias and can be either acquired (type I) or inherited (type II). In type I, UROD deficiency is seen only in the liver, while in type II, UROD is reduced in both the liver and the RBCs.
The acquired form of PCT is much more common; patients typically have experienced multiple comorbid hepatic insults, including a variety of liver diseases, iron overload, and exposure to certain chemicals or medications. Predisposing conditions include chronic hepatitis (especially due to hepatitis C virus [HCV]), hepatic tumors, HIV, a genetic defect of hemochromatosis, and diabetes mellitus. Ethanol use, estrogens, oral iron, and fungicides are some of the implicated external triggers. The resultant metabolic effect is excess circulating porphyrins, which trigger a phototoxic reaction on exposure to UVA (wavelength 410 nm). Skin fragility and blistering are the most common clinical effects of this photoreaction. The dorsal hands and forearms are generally affected, as they are commonly exposed to sunlight. Other cutaneous changes include scarring, formation of milia, a sclerodermalike transformation, and a characteristic hypertrichosis of the temples.
Laboratory abnormalities are common, including tests for liver function, HCV, and iron overload. Wood’s lamp examination of urine may reveal the typical orange-red fluorescence of urinary porphyrins. Histopathologic examination of a skin biopsy reveals a subepidermal bulla with papillary dermal festooning and vessel-wall thickening. Although immunofluorescence frequently shows increased deposition of immunoglobulins and complement proteins, autoimmunity is not believed to play a role in this disease. The diagnosis is confirmed through quantitative evaluation of urinary porphyrins from a 24-hr collection.
Treatment requires avoidance of triggers, such as sunlight and ethanol, and discontinuation of implicated medications. Because iron excess appears to play a role in the pathogenesis of the clinical picture, phlebotomy is the intervention of choice. Medical therapies may include low-dose hydroxychloroquine, iron chelators, and possibly recombinant erythropoietin to mobilize iron stores. Because these medications may cause disease flare, caution is necessary. However, they can be used judiciously in combination with phlebotomy or alone when phlebotomy is contraindicated. Treatment of the underlying liver disease must also be considered.
In our patient, serial phlebotomies resulted in a drop in serum ferritin, with eventual resolution of his blisters. He was then referred for rehabilitation and scheduled to start treatment for his HCV.