Hepatic Porphyrias

A particular instance of iron overload being associated with liver injury, with free radicals again being implicated, is the hepatic porphyria and hepatocarcinoma induced by polyhalogenated aromatic chemicals. This is described separately below. 

Polyhalogenated Aromatic Chemicals, Iron and hepatic Porphyria... 

The toxic effects of the fungicide and environmental pollutant hexachlorobenzene (HCB) were first noted in the 1950s when people were exposed to high doses of HCB through intake of contaminated grain. Intoxicated individuals developed a variety of symptoms including hepatic porphyria, skin lesions, and arthritis. Symptoms were accompanied by infiltrates of inflammatory cells [11, 33],... 

Fulfs JC, Abraham R. 1976. Effects of mirex and chloroquine on PCB-induced hepatic porphyria in the rat. Toxicol Appl Pharmacol 37 119-120. 

Carlson GP. 1977. Chlorinated benzene induction of hepatic porphyria. Experientia 33 1627-1629. 

Porphyria Avoid the use of NSAIDs in patients with hepatic porphyria. 

Fig. 7.3.3a-d Chromatogram of normal urine (a), urine from an individual with acute (in this case intermittent) hepatic porphyria (b), urine from an individual with porphyria cutanea tarda (c), and an undiluted sample from an individual with congenital erythropoietic porphyria (d). See typical pathological values for interpretation... 

Metabolic reactions (hepatic porphyria, disulfiram-like reactions)... 

Adverse Reactions Hypoglycemia Gastrointestinal disturbances (nausea, diarrhea, constipation, gastralgia) Dermatologic reactions (erythema, morbilliform or maculopapular eruptions, urticaria, pruritus, and eczema) Hematologic reactions (leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia, aplastic anemia, pancytopenia) Metabolic reactions (hepatic porphyria, disulfiram-like reactions) Hyponatremia Elevated liver enzymes... 

Clinical manifestations The porphyrias are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in the erythropoietic cells of the bone marrow or in the liver. Hepatic porphyrias can be further classified as acute or chronic. Individuals with an enzyme defect leading to the accumulation of... 

Reynolds NC Jr, Miska RM. Safety of anticonvulsants in hepatic porphyrias. Neurology 1981 31(4) 48CM. 

Bickers DR. Environmental and drug factors in hepatic porphyria. Acta Dermatol Venereol Suppl (Stockh) 1982 100 29-41. 

Smith AG, De Matteis F. Drugs and the hepatic porphyrias. Clin Haematol 1980 9(2) 399-425. 

Goldstein JA, Hickman P, Bergman H, et al. 1973. Hepatic porphyria induced by... 

The tests allow judgement of the propensity of local anesthetics to induce symptoms of hepatic porphyria. The local anesthetics lidocaine, bupivacaine, etido-caine, mepivacaine, prilocaine and pyrocaine belong to this group, but procaine, butacaine, oxybuprocaine, proxymethacaine and tetracaine had no (or very slight) porphyrinogenic effect. 

Adverse hepatic effects have been linked to the use of oral contraceptives, including hepatic dysfunction, cholestatic jaundice, benign hepatic tumours and peliosis hepatis. In addition, oral contraceptives have a number of less common but important effects on the liver. A correlation between the development of the Budd-Chiari syndrome and COCs has been described, and progestational derivatives have been linked to exacerbations of hepatic porphyria [12]. 

Halogenated aromatic hydrocarbons (HAH) cause common toxic and biochemical responses and their mechanism of action is also common [79],but the toxicology of PCDEs is not well known [4,40,46]. Weight loss, hepatic porphyria, chloroacne, and impairment of liver function are typical symptoms caused by HAHs [79]. Toxic effects of higher chlorinated PCDEs may appear as chloroacne and liver damage [12]. 

Porphyria cutanea tarda and chronic hepatic porphyria are characterized by porphyrin fluorescence in the liver cell. For every 1,000 biopsies, there are 3-5 red fluorescent liver specimens. Unfortunately, such UV examinations of the biopsy material are not carried out regularly. In cases of indeterminate diagnosis, red fluorescence can confirm chronic hepatic porphyria that has hitherto remained unidentified, (s. fig. 7.10)... 

An additional three forms should also be mentioned (7.) deficiency of acyl-CoA dehydrogenase, (2.) encephalopathy in Wilson s disease, and (i.) encephalopathy in hepatic porphyria. 

Doss, M., Lange, C.E., Vellman, G. Vinylchloride-induced hepatic coproporphyrinuria with transition to chronic hepatic porphyria. Klin. Wschr. 1984 62 175-178... 

Primary porphyrias are caused by hereditary enzyme defects in haem synthesis. They can be differentiated clinically into acute and chronic porphyrias as well as pathogenetically into hepatic and erythropoietic porphyrias. Secondary porphyrias are symptomatic porphyrias present in various diseases or caused by poisoning or chemical substances, particularly alcohol. Depending on the preferred manifestation site of the enzyme defect, either in the hepatocytes or erythrocytes (bone marrow), the porphyrias are subdivided into hepatic, erythropoietic and hepatoerythropoietic forms. However, this classification is not always strictly applicable. Based on the course of disease, acute and chronic forms may be differentiated in primary hepatic porphyrias. The acute form is characterized by a congenital reg-... 

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