Diagnosis: Porphyria cutanea tarda
Based on the clinical presentation and the patient’s history of smoking and alcohol consumption, we suspected that this was a case of porphyria cutanea tarda (PCT). Laboratory studies, including a complete blood count, basic metabolic panel, iron studies, and liver function tests, were ordered. These revealed elevated levels of serum alanine transaminase (116 IU/L; reference range, 20-60 IU/L), aspartate aminotransferase (184 IU/L; reference range, 6-34 IU/L in men), and ferritin (1594 ng/mL; reference range, 12-300 ng/mL in men), consistent with PCT. Total porphyrins were then measured and found to be elevated (128.5 mcg/dL; reference range, 0 to 1 mcg/dL), which confirmed the diagnosis. Further testing revealed that the patient was positive for both hepatitis C virus (HCV) and hepatitis B virus infection.
While PCT is the most common porphyria worldwide, it is nonetheless a rare disorder that results from deficient activity (< 20% of normal) of uroporphyrinogen decarboxylase (UROD), the fifth enzyme in the heme synthetic pathway.1,2 It is typically (~75% cases) an acquired disorder of mid- to late adulthood and more commonly affects males.1 In the remainder of cases, patients have a genetic predisposition—a mutation of the UROD or HFE gene. Patients with a genetic predisposition may present earlier.2,3 Susceptibility factors for both forms of PCT include chronic alcohol use, HCV and/or human immunodeficiency virus (HIV) infection, estrogen therapy, and a history of chronic/heavy smoking.1,4
Cutaneous manifestations of PCT are caused by the accumulation of porphyrins, which are photo-oxidized in the skin.1 Findings include photosensitivity, skin fragility, blistering, scarring, hypo- or hyperpigmentation, and milia in sun-exposed areas, such as the dorsum of the hands, forearms, face, ears, neck, and feet.1,2 Hypertrichosis can occur, particularly on the cheeks and forearms.1 Elevated transaminases often accompany cutaneous findings, due to porphyrin accumulation in hepatocytes and the hepatotoxic effects of alcohol, HCV infection, or iron overload.5 Iron overload, in part due to dysregulation of hepcidin, can lead to increased serum ferritin, iron, and transferrin saturation.1
Differential includes autoimmune and autosomal conditions
Diseases that manifest with blistering, elevated porphyrins or porphyrin precursors, and iron overload should be included in the differential diagnosis.
Bullous pemphigoid is an autoimmune subepithelial blistering disorder that occurs when antibodies attack hemidesmosomes in the epidermis. It commonly manifests in the elderly and classically presents with tense bullae, typically on the trunk, abdomen, and proximal extremities. Serologic testing and biopsy can confirm the diagnosis.6
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