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.

Variegate porphyria is a form of acute hepatic porphyria characterised by the occurrence of neuro-visceral attacks with or without the presence of cutaneous lesions (bullous photodermatitis).

Variegate porphyria is a form of acute hepatic porphyria (see this term) characterized by the occurrence of neuro-visceral attacks with or without the presence of cutaneous lesions. Prevalence is around 1/100,000 in European countries and much higher in South Africa due to a founding effect. Generally the disease manifests after puberty and preferentially affects women. In 60% of cases the only sign of the disease are cutaneous lesions that result from photosensitivity (bullous photodermatitis). These lesions predominate in areas exposed to the sun (hands, face) and manifest as bullae that cause differing degrees of pain and that leave scars that are often hyperpigmented. In 20% of cases, patients present with both cutaneous lesions and neuro-visceral attacks. Finally, 20% of patients present with only neuro-visceral attacks. Attacks can persist for several weeks and manifest as intense abdominal pain, and neurological and psychological symptoms. The abdominal pain is often associated with lumbago irradiating to the thighs, and with nausea, vomiting and constipation. Psychological symptoms are variable: irritability, emotionality, depression, considerable anxiety and, more rarely, auditory and visual hallucinations, disorientation, mental confusion. Neurological manifestations can affect the central nervous system as much as the peripheral nervous system and can lead to severe complications such as motor paralysis. The attacks are most commonly triggered by exogenous factors (porphyrinogenic drugs, alcohol, infections, a hypo-calorific diet, stress), and/or endogenous factors (hormonal, linked to menstrual cycle). Variegate porphyria is caused by a deficiency in protoporphyrinogen oxidase (PPOX; the penultimate enzyme in the heme biosynthesis pathway) that leads to an accumulation of porphyrins and their precursors in the liver (delta-aminolevulinic acid, ALA and porphobilinogen, PBG). The enzyme deficiency is due to mutations in the PPOX gene coded for PPOX. Transmission is autosomal dominant. Diagnosis of acute attacks is based on evidence of elevated concentrations of PBG and ALA in urine and of elevated concentrations of coproporphyrin and, especially, protoporphyrin in stool. Differential diagnoses include acute intermittent porphyria and, particularly, porphyria cutanea tarda (see these terms). The presence of a fluorometric peak (626-628 nm) in plasma is pathognomonic and allows a definitive diagnosis of variegate porphyria rather than porphyria cutanea tarda. Genetic counseling should be offered to patients and families. Acute attacks should be urgently treated with an injection of human hemin. Management includes both the prevention of attacks (warning against triggering factors) and pain relief (opiates). Phlebotomy and taking chloroquine are rarely effective at treating cutaneous manifestations. Micro-phlebotomy is beneficial for some patients. It is necessary to protect the skin from sources of light. With early diagnosis and treatment acute attacks are rarely fatal and the disease is rarely progressive. However, variegate porphyria is a risk factor for the development of hepatocellular carcinoma.