Porphyria Cutanea Tarda Clinical Presentation
- Author: Maureen B Poh-Fitzpatrick, MD; Chief Editor: Dirk M Elston, MD more...
The most common initial symptoms of porphyria cutanea tarda are cutaneous fragility and blistering of the hands, forearms, and, sometimes, the face. Discolored urine may also be reported, but this information may need to be elicited. Changes in hair growth and pigmentation may be noted spontaneously or only after inquiry. Patients with porphyria cutanea tarda often do not realize the role of sunlight exposure in the subsequent appearance of lesions.
In familial porphyria cutanea tarda, other affected relatives may be known. However, most related carriers of the mutant gene remain silent, and patients may be unaware of the familial nature of their disease.
In both familial and sporadic porphyria cutanea tarda, a history of exposure to one or more environmental or medicinal inducers (eg, ethanol, estrogens, hepatitis) can often be elicited. Paradoxically, proven carriers of the same mutation as that of a symptomatic relative with exposure to a known inducer may remain clinically and biochemically silent despite similar exposure. In symptomatic familial porphyria cutanea tarda, occasionally none of the common inducing agents is discoverable. Childhood onset of porphyria cutanea tarda should suggest either heterozygous or homozygous familial forms of the disease, unless observed in the context of environmental exposure to a chemical hepatotoxin.
Porphyria cutanea tarda–like disease in multiple members of populations exposed to polyhalogenated aromatic hydrocarbons should suggest epidemic toxic porphyria.
The most common presenting sign of porphyria cutanea tarda is fragility of sun-exposed skin after mechanical trauma, leading to erosions and bullae, typically on hands and forearms and occasionally on face or feet. Healing of crusted erosions and blisters leaves milia, hyperpigmented patches, and hypopigmented atrophic scars.
Hypertrichosis is often observed over temporal and malar facial areas and may also involve arms and legs. Pigmentary changes include melasmalike hyperpigmentation of the face. An erythematous suffusion or plethora of the central face, neck, upper chest, and shoulders may be present. Scarring alopecia and separation of nail plates from their beds (photo-onycholysis) can be seen in more severely affected patients.
Indurated, waxy, yellowish plaques that resemble lesions of scleroderma can develop over the chest and the back but are most prominent in the preauricular and nuchal areas. These plaques may develop dystrophic calcification. Rarely, the only physical sign of porphyria cutanea tarda is a hyperpigmented sclerodermoid appearance.
In severely affected individuals, particularly familial hepatoerythropoietic or toxic epidemic cases in children, digital shortening, atrophy, and contractures resembling those of dystrophic epidermolysis bullosa have occurred.
A urine sample is often, but not always, grossly discolored with a tea- or wine-colored tint.
The unifying underlying cause of all forms of porphyria cutanea tarda is reduction of UROD activity to a critical point during hepatic heme synthesis.[10, 11, 21] Genetic, environmental or infectious contributory or susceptibility factors, acting singly or more often in concert,[22, 23, 24] inhibit UROD activity to that point of insufficiency, resulting in the onset of clinical symptoms.
Alcohol effects on hepatocytes may precipitate porphyria cutanea tarda by making stored hepatic iron more available for catalyzing oxidation reactions, by generation of reactive oxygen species, or by induction of hepatic cytochromes, all of which may facilitate oxidation of uroporphyrinogen to UROD inhibitors.
The role of estrogen in inhibition of UROD activity is not firmly established, it but may be similar to that of alcohol in generating toxic oxygen or inducing cytochromes, thus potentiating uroporphyrinogen oxidation.
A strong association between porphyria cutanea tarda and hereditary hemochromatosis genes causing hepatic siderosis has been established.[6, 22, 26, 27, 28, 29]
Hepatitis virus infections are frequently associated with porphyria cutanea tarda.[26, 30, 31, 32] Hepatitis C occurs with a rate of greater than 50% in populations studied in several European countries and in the United States, while in other regions, the concordance is less frequent. Increased hepatic iron often is found in patients with hepatitis C infection.
Association with HIV infection has been noted. Although multiple risk factors are often present among individuals with HIV infection and porphyria cutanea tarda, leading to some uncertainty whether HIV infection is an independent risk factor, some investigators argue that the association is more than simply coincidental.
Tobacco smoking is a behavioral characteristic frequently observed among patients with porphyria cutanea tarda.[22, 24] Smoking has been associated with earlier onset of symptoms in sporadic porphyria cutanea tarda, with a putative mechanism involving induction of an hepatic cytochrome that may contribute to oxidation of uroporphyringen, but evidence for smoking as an independent pathogenic factor is not yet robust.
Environmental exposure to aromatic polyhalogenated hepatotoxins also induces hepatic cytochromes, thus potentiating production of oxidation products capable of inhibiting UROD activity.
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