ICD-11

Porphyrias constitute a group of diseases characterised by intermittent neuro-visceral manifestations, cutaneous lesions or by the combination of both. All porphyrias are caused by a deficiency in one of the enzymes of the heme biosynthesis pathway resulting in an accumulation of porphyrins and/or their precursors in the liver or bone marrow. Clinical signs of the disease usually appear in adulthood, but some porphyrias affect children. Porphyrias can be classified according to the main location of the metabolic anomaly. Direct or indirect neurotoxicity may cause neurological manifestations. Transmission of hereditary porphyrias is autosomal and either dominant with weak penetrance or recessive with complete penetrance. Diagnosis is mainly based on the measurement of porphyrins and their precursors in biological samples.

Porphyrias constitute a group of eight hereditary metabolic diseases characterized by intermittent neuro-visceral manifestations, cutaneous lesions or by the combination of both. Prevalence depends on the type of porphyria. Clinical signs of the disease usually appear in adulthood, but some porphyrias affect children. Porphyrias can be classified into two groups, hepatic and erythropoietic (see these terms), according to the main location of the metabolic anomaly. Chronic hepatic porphyrias (see this term) and erythropoietic porphyrias manifest with bullous cutaneous lesions or acute pain in areas exposed to the sun (photo-algic lesions). Neurological symptoms do not occur. On the other hand, neuro-visceral attacks do occur with acute hepatic porphyrias. These attacks manifest as intense abdominal pain (very often associated with nausea, vomiting and constipation), and neurological and psychological symptoms. Two acute hepatic porphyrias (variegate porphyria and hereditary coproporphyria; see these terms) can equally present with cutaneous photosensibility. All porphyrias are caused by a deficiency in one of the enzymes of the heme biosynthesis pathway. These deficiencies result in an accumulation of porphyrins and/or their precursors (delta-aminolevulinic acid, ALA and porphobilinogen, PBG) in the liver or bone marrow. The neurological manifestations are caused by these precursors, PBG and especially ALA (direct or indirect neurotoxicity). The enzyme deficiencies are a result of mutations of the correspondingly coded genes. Transmission of hereditary porphyrias is autosomal and either dominant with weak penetrance or recessive with complete penetrance. Diagnosis is mainly based on the measurement of porphyrins and their precursors in biological samples (urine, stools, blood). Differential diagnoses include, when patients present with acute attacks, Guillain-Barré syndrome (see this term) and all causes of acute abdominal pain, and, when patients present with cutaneous signs, photodermatoses. Genetic counseling should be offered to affected families to identify individuals susceptible to developing and transmitting the disease. Acute attacks should be treated urgently with an injection of human hemin and/or perfusion of carbohydrates. The treatment of cutaneous manifestations is mainly by phlebotomy and/or small doses of chloroquine. Prognosis depends on the type of porphyria.

Porphyria cutanea tarda (PCT) is due to an accumulation of uroporphyrins in plasma from blockage of the normal haem synthetic pathway in the liver at the level of uroporphyrinogen decarboxylase (URO-D). The majority of cases are sporadic and frequently associated with iron overload. PCT manifests as skin fragility and blistering in light-exposed skin, particularly on the dorsa of the hands, together with hypertrichosis.

Porphyria cutanea tarda (PCT) is the most common form of chronic hepatic porphyria (see this term). It is characterized by bullous photodermatitis. The prevalence in western Europe is estimated at about 1/25,000 and men are more affected than women. The disease manifests in adulthood. PCT is acquired (75% of cases) or familial (25% of cases). Generally manifestations of the disease appear earlier in familial cases. Some risk factors can precipitate symptoms: excessive consumption of alcohol, hepatitis C, estrogen, and mutations of the genes that control iron metabolism, leading to iron overload (hemochromatosis). The main clinical symptoms include firstly, extremely fragile skin and, subsequently, bullous cutaneous lesions on the surface of skin exposed to the sun (hands, face). Scarring is slow and often followed by hyper and hypopigmentation. The presence of cutaneous lesions of varying ages is very characteristic of the disease. With age, the disease manifestations can be accompanied by hypertrichosis (mainly facial) and sclerodermic signs. Hepatic lesions can also develop (siderosis, steatosis, necrosis and chronic inflammatory disorders). PCT is caused by a deficiency of uroporphyrinogen decarboxylase (URO-D; the fifth enzyme in the heme biosynthesis pathway). This deficiency, in the familial form of the disease, is a result of heterozygous mutations of the URO-D gene, coding for URO-D, and leads to an accumulation of porphyrins (URO and 7-carboxyl porphyrins) in the liver. Transmission is autosomal dominant and penetrance is weak. Diagnosis is based on the evidence of elevated concentrations of isocoproporphyrins in stools, a situation specific to PCT. Evidence of a deficiency of URO-D in red blood cells confirms a diagnosis of the familial form of PCT. Differential diagnosis is mainly variegate porphyria (see this term), diagnosis of which rests on evidence of the characteristic fluorometric peak in plasma. Genetic counseling should be offered to families affected by the familial form of PCT to identify individuals susceptible to developing or transmitting the disease. Management includes firstly, the suppression of triggering factors, and subsequently, phlebotomy and/or taking a small dose of chloroquine (100mg twice a week). This allows complete remission whether or not there iron overload. A relapse is always possible, and treatment remains the same. Concomitant treatment of hepatitis C and cessation of alcohol consumption and use of hormonal contraceptives is essential for remission to occur. PCT is not life-threatening and the prognosis is favorable. However, it is a recognized risk factor for the development of hepatocellular carcinoma.