Answer to Dermacase continued from page 749
3. Porphyria cutanea tarda
Porphyrias are genetic metabolic disorders resulting from deficient or absent enzymes in heme biosynthesis (which primarily occurs in bone marrow erythroblasts and hepatocytes).1,2 Porphyrias can be classified into acute hepatic porphyrias and nonacute porphyrias. In general, acute porphyrias are associated with neurologic symptoms, whereas nonacute subtypes are associated with cutaneous photosensitivity to UV radiation in the Soret band (400 to 410 nm). Accumulation of porphyrins or porphyrin precursors, combined with exposure to UV radiation, results in the production of reactive oxygen species that destroy cell membranes and cause cell lysis.1–3 Acute hepatic porphyrias involve heme pathway dysregulation, while chronic hepatic porphyrias result in porphyrin accumulation4 (Table 11,2,5,6). Porphyria can be an indicator of and is often associated with underlying systemic disease resulting in considerable morbidity and mortality if it goes undiagnosed or untreated. However, recognizing this condition can be challenging without clinical suspicion of the entity.
General overview of heme synthesis
Acute hepatic porphyrias
Acute hepatic porphyrias include intermittent acute porphyria, aminolevulinic acid dehydratase deficiency porphyria, hereditary coproporphyria, and variegate porphyria. Porphobilinogen deaminase deficiency is rarely seen before puberty1,5 (Table 21,2,5,7). With the exception of variegate porphyria, acute hepatic porphyrias typically present with systemic symptoms rather than cutaneous findings.
Overview of acute hepatic porphyrias
Nonacute porphyrias
Nonacute porphyrias are further subclassified into erythropoietic porphyrias (ie, congenital erythropoietic porphyria and erythropoietic protoporphyria) and chronic hepatic porphyrias (ie, porphyria cutanea tarda and hepatoerythropoietic porphyria) as summarized in Tables 3 and 4, respectively.1,2,5,7 These nonacute porphyrias demonstrate cutaneous manifestations and systemic findings, but are typically not associated with any neurologic symptoms.
Overview of nonacute erythropoietic porphyrias
Overview of nonacute hepatic porphyrias
Discussion
Porphyria cutanea tarda (PCT) is the most common porphyria. History and clinical examination reveal photosensitivity, skin fragility, and bullae formation, as well as healed scars with milia formation and hyper-pigmentation on photodistributed regions of the body, particularly the dorsa of the hands and arms, and, less commonly, hypertrichosis and sclerodermoid skin changes.5 Clinical symptoms and a positive urinary porphyrin profile are often adequate to make the diagnosis of PCT.5 Porphyrin excretion ceases in the remission phase.2 Uroporphyrinogen decarboxylase activity in erythrocytes can also be measured in some laboratories. A skin biopsy is considered unnecessary; however, histologic examination will demonstrate subepidermal, cell-poor bullae with festooning of the dermal papillae.5
Differential diagnoses for porphyrias include other blistering disorders such as polymorphic light eruptions, bullous lupus erythematosus, epidermolysis bullosa acquisita, photoinduced bullous drug reactions, solar urticaria, and hydroa vacciniforme. All of these conditions have normal (ie, negative) urine, fecal, and serum porphyrin levels.
Management of PCT includes UV protection, avoidance of triggers (the most common being excessive alcohol consumption or estrogens), biweekly phlebotomy (ie, approximately 500 mL every 2 weeks) to reduce serum ferritin, and treatment of underlying conditions (eg, hepatitis, hemochromatosis, HIV). Low-dose hydroxychloroquine or chloroquine (125 mg twice weekly) to chelate porphyrins is also useful, but ineffective in patients with associated hemochromatosis.1,2,5–7 Alcohol consumption is associated with flares in porphyria as the ethanol molecule decreases the activity of several enzymes including aminolevulinic acid dehydratase, uroporphyrinogen decarboxylase, coproporphyrinogen oxidase, and ferrochelatase.4 We suspect that substantial alcohol intake (ie, 2 to 4 alcoholic beverages per day) precipitated PCT in our patient.
Finally, it is important to distinguish between acute and nonacute porphyrias, as the former are associated with substantial morbidity, such as neurologic decline (eg, paralysis), respiratory failure, coma, and possibly death, if acute attacks are inadequately managed. Medical history and biochemical porphyrin profiles will help distinguish among the various forms of porphyria. In the future, advances in molecular genetics might be useful for rapid diagnosis and identification of carriers of inherited porphyrias.1
Footnotes
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Competing interests
None declared
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