Disease/Syndrome

Porphyria cutanea tarda

Category

More Research Needed

Acute/Chronic

Chronic

Synonyms

Disorders of porphyrin metabolism

Biomedical References

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Comments

Porphyria cutanea tarda (PCT) is most known for an outbreak of environmental (not occupational) disease in Turkey from 1955 to 1958 when more than 4000 people developed PCT about six months after eating wheat contaminated with the fungicide hexachlorobenzene. There are several other substances associated with disturbance of porphyrin metabolism in humans: 2,4-dichorophenol, 2,4,5-trichlorophenol, 2,3,7,8-tetrachlorodibenzo-p-dioxin, o-benzyl-p-dichlorophenol, 2-benzyl-p-dichlorphenol, vinyl chloride, lead, and aluminum. The two disinfectants (o-benzyl-p-dichlorophenol, 2-benzyl-p-dichlorphenol) were implicated in one case of acquired PCT. Aluminum used in dialysis solutions was thought to be the causal agent in cases of a PCT-like syndrome in patients with renal failure. Workers in polyvinyl chloride production had elevated urinary coproporphyrin levels compared to controls. [LaDou, p. 265-8] "People with metabolic disorders associated with the synthesis of porphyrins (important intermediates in the synthesis of hemoglobin, cytochromes, and vitamin B12), collectively known as porphyrias, are especially susceptible to lead exposure since lead inhibits two critical enzymes, ALAD and ferrochelatase, concerned with heme synthesis in erythrocytes." [ATSDR ToxProfiles: Lead] In another chapter in LaDou, the authors write, "2,3,7,8-TCDD may inhibit uroporphyrinogen decarboxylation, and cases of porphyria cutanea tarda among exposed workers have been reported. However, recent studies have failed to find an association between 2,3,7,8-TCDD and porphyrin levels. No association has been observed among former chlorophenol production workers between 2,3,7,8-TCDD exposure and serum transaminase levels, induction of cytochrome P450 activity, peripheral neuropathy, chronic bronchitis or chronic obstructive pulmonary disease, and porphyria cutanea tarda." [LaDou, p. 519] According to Cecil Medicine, 24th edition, "Porphyrias are due to deficiencies of specific enzymes of the heme biosynthetic pathway and, when clinically expressed, are associated with striking accumulations of heme pathway intermediates. Porphyria cutanea tarda (PCT), the most common of these disorders, is primarily an acquired, iron-related disorder. The others occur only with mutations of an enzyme in the heme biosynthetic pathway." Table 217-1 in Cecil shows that PCT is inherited as an autosomal dominant disease. The presenting symptoms are blistering skin lesions. Exacerbating factors are iron, alcohol, estrogens, hepatitis C virus, and halogenated hydrocarbons. The most important screening test is plasma or urine porphyrins, and treatment is with phlebotomy or low-dose hydroxychloroquine. [Cecil, p. 1363-71] "Porphyria cutanea tarda seems to be a disease in which symptoms develop when residual hepatic uropophyrinogen decarboxylase decrease below a threshold of about 25%. The risk factors that contribute to inactivation or inhibition of this enzyme are mainly alcohol abuse, oestrogeens, hepatitis C, and to a lesser extent HIV infections and genetic haemochromatosis. These precipitating factors act either alone or in combination with hepatic iron overload, an almost universal finding in porphyria cutanea tarda, to generate an iron-dependent oxidative mechanism." [PMID 20226990]

Diagnostic

Initial screening test: plasma and urine porphyrins;

ICD-9 Code

277.1

Reference Link

Environmental chemical exposures and disturbances of heme synthesis.

Related Information in Haz-Map
Agents

Hazardous agents that cause the occupational disease: