Case 6 -

Porphyria Cutanea Tarda (PCT) Kim M. Hiatt University of Arkansas for Medical Sciences Little Rock, AR

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Clinical History A 57 year old man has scarring and erosions on the dorsum of both hands. He hasreceived occasional therapeutic phlebotomy for iron overload. Case 6 - Figure 1 - This low power image shows an acanthotic and hyperkeratotic epidermis on sun exposed skin with exuberant solar-elastosis. . Case 6 - Figure 2 - On higher powerof the dermal-epidermal junction you should notice basal vaculopathy and mild spongiosis as well as changes in the vessels of the superficial dermis. These superficial vessels have a thickened, eosinophilic wall. Case 6 - Figure 3 - On high power of the superficial dermis you note increased vascularity, a mild lymphocytic infiltrate and increased collagen deposition, changes characteristic of wound healing. Note also the vascular changes described with figure 2 and the abundant solar elastosis. Histological findings: Eosinophilic hyaline deposits in walls of blood vessels, especially in the papillary dermis, accentuated with PAS Paucicellular subepidermal blister Globular eosinophilic basement membrane material, "caterpillar bodies", may be found on the roof of the blister Deposits in the walls of the papillary dermal vessels result in these vessels projecting into the blister cavity causing "festooning" of the floor of the blister Epidermal changes, when present, are usually mild and include acanthosis or atrophy. Direct immunofluorescence may show IgG and C3 deposits around papillary dermal vessels and faint staining in the lamina lucida and the dermal-epidermal junction. Diagnosis: Porphyria cutanea tarda (PCT) Discussion: Porphyrias result from a deficiency in one of the enzymes involved in heme biosynthesis resulting in accumulation of heme precursors (porphyrins). The accumulated products are ring structures which absorb light resulting in excited states. These excited forms release free-radicals causing lipid peroxidation and protein cross-linking which ultimately lead to cell membrane damage and cell death. PCT is the most common porphyria and is composed of both acquired (type I) and genetic (type II) etiologies. Most PCT is acquired and multifactorial in origin. All have in common reduced activity of uroporphyrinogen decarboxylase enzyme which results in elevated uroporphyrins. Iron is an inhibitor of this enzyme, accordingly, PCT maybe seen in any entity causing iron overload. Porphyrin abnormalities are known to occur in: lead poisoning, sideroblastic anemia, hemolytic anemia, iron deficiency, renal failure including in dialysis patients because of their poor clearance of porphyrins, cholestasis, liver disease, hemochromatosis, and gastrointestinal hemorrhage. HCV and HIV infection and estrogen have been strongly implicated in the precipitation of acquired PCT. Most patients present with lesions on sun exposed skin, most commonly the dorsum of the hands, face and scalp. The lesions are worse in summer months and, because of increased skin fragility, result from only minor trauma. The lesions heal with scarring, pigment alteration and milia. Two main patterns of skin damage are seen: 1) accumulation of water-soluble uro and coproporpyrins lead to blistering and 2) accumulation of lipophilic protoporphyrin causing burning sensation on exposure to light. Differential diagnosis: Epidermolysis bullosa - paucicellular subepidermal blister also seen in areas of trauma, but not associated with sun-exposure. Hyaline deposits and basement membrane duplication are not seen. Bullous pemphigoid – cell-poor bullous pemphigoid more commonly presents on trunk and extremities. Hyaline deposits and basement membrane duplication are not seen. Direct immunofluorescence will show linear IgG and C3 deposits along the asement membrane. Bullous amyloidosis – non-inflammatory blisters may form over cutaneous amyloid depostis in the skin. These are not seen in association with sun-exposure and the amyloid deposits will be birefringent with Congo Red, unlike the hyaline deposits in PCT. References Bleasel NR, Varigos GA. Porphyria cutanea tarda. Australas J Dermatol. 2000; 41:197-206; quiz 207-198. Kolanko E, Bickle K, Keehn C, et al. Subepidermal blistering disorders: A clinical and histopathologic review. Semin Cutan Med Surg. 2004; 23:10-18. O'Connor WJ, Badley AD, Dicken CH, et al. Porphyria cutanea tarda and human immunodeficiency virus: Two cases associated with hepatitis c. Mayo Clin Proc. 1998; 73:895-897.