Porphyria Cutanea Tarda

Abstract

A 44-year-old man with human immunodeficiency virus infection, untreated hepatitis C virus infection, and active alcohol abuse presented with bilateral blistering on the dorsal hands of 2 months’ duration (Figure 1). The blisters were pruritic and photoexacerbated and resolved spontaneously with scarring. Examination revealed tense bullae limited to the dorsal hands in various stages of healing, including milia and scarring. Biopsy specimens for histopathologic evaluation and direct immunofluorescence revealed pauci-inflammatory subepidermal clefting and homogeneous deposition along the basement membrane and within walls of superficial dermal vessels with multiple conjugates, consistent with porphyria cutanea tarda (PCT; Figure 2). The patient’s baseline ferritin concentration was found to be higher than 800 ng/dL (to convert to pmol/L, multiply by 0.02247). Serum porphyrins demonstrated increased total porphyrins; fractionation showed increased uroporphyrin, confirming PCT.Figure 2A pauci-inflammatory subepidermal blister on histopathologic examination (hematoxylin and eosin, magnification ×200).View Large Image Figure ViewerDownload Hi-res image Download (PPT) PCT, the most common type of porphyria, is caused by inhibition of hepatic uroporphyrinogen decarboxylase (UROD). Pathogenesis involves cutaneous phototoxicity due to deposition of alternative metabolic products from excess hepatic porphyrinogen accumulation. Approximately 20% of cases are associated with familial UROD mutations,1Badenas C. To-Figueras J. Phillips J.D. Warby C.A. Muñoz C. Herrero C. Identification and characterization of novel uroporphyrinogen decarboxylase gene mutations in a large series of porphyria cutanea tarda patients and relatives.Clin Genet. 2009; 75: 346-353Crossref PubMed Scopus (28) Google Scholar,2Singal A.K. Porphyria cutanea tarda: recent update.Mol Genet Metab. 2019; 128: 271-281Crossref PubMed Scopus (17) Google Scholar whereas 80% of patients present with acquired PCT with absence of UROD mutations. These patients often have liver damage, frequently from alcohol, hepatitis C, human immunodeficiency virus infection, or hemochromatosis.2Singal A.K. Porphyria cutanea tarda: recent update.Mol Genet Metab. 2019; 128: 271-281Crossref PubMed Scopus (17) Google Scholar, 3Jalil S. Grady J.J. Lee C. Anderson K.E. Associations among behavior-related susceptibility factors in porphyria cutanea tarda.Clin Gastroenterol Hepatol. 2010; 8 (302.e1): 297-302Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar, 4Gisbert J.P. Garcia-Buey L. Pajares J.M. Moreno-Otero R. Prevalence of hepatitis C virus infection in porphyria cutanea tarda: systematic review and meta-analysis.J Hepatol. 2003; 39: 620-627Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar, 5Ellervik C. Birgens H. Tybjærg-Hansen A. Nordestgaard B.G. Hemochromatosis genotypes and risk of 31 disease endpoints: meta-analyses including 66,000 cases and 226,000 controls.Hepatology. 2007; 46: 1071-1080Crossref PubMed Scopus (113) Google Scholar Typical presenting features include bullae and dyspigmentation of sun-exposed areas. First-line treatment is therapeutic phlebotomy of 450 mL every 2 weeks until ferritin concentration is less than 20 to 25 ng/dL.2Singal A.K. Porphyria cutanea tarda: recent update.Mol Genet Metab. 2019; 128: 271-281Crossref PubMed Scopus (17) Google Scholar Additional management recommendations include broad-spectrum sun protection, alcohol cessation, and hepatitis C treatment. Hydroxychloroquine can be used when phlebotomy is contraindicated.2Singal A.K. Porphyria cutanea tarda: recent update.Mol Genet Metab. 2019; 128: 271-281Crossref PubMed Scopus (17) Google Scholar Although PCT is readily treated and nonfatal, relapses may follow successful treatment.2Singal A.K. Porphyria cutanea tarda: recent update.Mol Genet Metab. 2019; 128: 271-281Crossref PubMed Scopus (17) Google Scholar Thank you to Dr Scott Tuttle for his contributions to this report.