Dermatology · Metabolic Dermatoses
The facts most likely to be tested
Porphyria Cutanea Tarda is caused by a deficiency of uroporphyrinogen decarboxylase (UROD).
Patients present with photosensitivity characterized by vesicles and bullae on sun-exposed areas like the dorsum of the hands.
Classic physical exam findings include skin fragility, hyperpigmentation, and hypertrichosis on the face.
The condition is strongly associated with Hepatitis C infection, hemochromatosis, and excessive alcohol consumption.
Diagnosis is confirmed by finding elevated uroporphyrins in a 24-hour urine collection.
Urine samples in Porphyria Cutanea Tarda typically exhibit a tea-colored or dark brown appearance.
First-line treatment involves phlebotomy to reduce iron stores or hydroxychloroquine to increase porphyrin excretion.
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A 52-year-old male with a history of chronic alcohol use disorder presents to the clinic complaining of skin lesions on his hands. He reports that his skin easily blisters and peels after spending time outdoors. Physical examination reveals vesicles and bullae on the dorsal surfaces of both hands, along with hypertrichosis on his cheeks and hyperpigmentation of the skin. His urine is noted to be dark brown in color. Laboratory studies reveal elevated serum ferritin and positive anti-HCV antibodies.
What is the most likely diagnosis?
Porphyria Cutanea Tarda
The patient's presentation of photosensitive bullae, hypertrichosis, and dark urine in the setting of alcohol use and Hepatitis C is classic for Porphyria Cutanea Tarda, which is tested via the association with UROD deficiency and iron overload.
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High yield triage
Etiology / Epidemiology
Most common porphyria; associated with HFE gene mutations (hemochromatosis), Hepatitis C, and alcohol abuse.
Clinical Manifestations
Painless blisters on sun-exposed areas, fragile skin, and hypertrichosis on the face.
Diagnosis
Elevated urinary uroporphyrins; wood's lamp shows coral-red fluorescence in urine.
Treatment
Phlebotomy or hydroxychloroquine; avoid alcohol and estrogens.
Prognosis
Increased risk of hepatocellular carcinoma; requires long-term liver surveillance.
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Epidemiology & Etiology
PCT is the most common porphyria, often triggered by hepatic iron overload. Key associations include Hepatitis C, hemochromatosis, and chronic alcohol consumption. It typically presents in middle-aged adults.
Pertinent Anatomy
The liver is the primary site of pathology due to the deficiency of the enzyme uroporphyrinogen decarboxylase (UROD).
Pathophysiology
Deficiency of UROD leads to the accumulation of uroporphyrinogens in the liver. These porphyrins are oxidized to porphyrins, which circulate in the plasma and deposit in the skin. Upon exposure to UV light, these porphyrins generate reactive oxygen species, causing subepidermal bullae and tissue damage.
Clinical Manifestations
Patients present with painless blisters and erosions on the dorsum of the hands. Chronic cases exhibit milia, skin fragility, and facial hypertrichosis. Red flag: urine may appear dark or tea-colored due to porphyrin excretion.
Diagnosis
The gold standard is the measurement of urinary porphyrin fractionation, showing a massive elevation of uroporphyrins. A Wood's lamp examination of the urine reveals coral-red fluorescence. Serum ferritin and iron studies should be ordered to screen for underlying hemochromatosis.
Treatment
First-line therapy is serial phlebotomy to reduce hepatic iron stores. For patients who cannot tolerate phlebotomy, low-dose hydroxychloroquine is the preferred alternative. Contraindications include alcohol and estrogen use, which exacerbate porphyrin production.
Prognosis
Patients have a significantly increased risk of hepatocellular carcinoma. Regular abdominal ultrasound or MRI screening is mandatory for long-term management.
Differential Diagnosis
Pseudoporphyria: clinically identical but normal porphyrin levels
Variegate porphyria: presents with neurovisceral symptoms
Hereditary coproporphyria: associated with abdominal pain and neuro symptoms
Epidermolysis bullosa: lacks the metabolic porphyrin profile
Bullous pemphigoid: autoimmune blistering with negative porphyrin studies