Hiroko Irifune

Relationship between Porphyria Cutanea Tarda (PCT) and Viral Hepatitis

Recent reports have revealed the high prevalence of serological markers of viral hepatitis in porphyria cutanea tarda (PCT). We present two cases of PCT associated with hepatitis C and discuss the relationship between PCT and viral hepatitis. Case 1: A 50‐year‐old Japanese male noticed blisters, erosions, and fragility on sun‐exposed areas of his skin in November of 1990. He had no history of excessive alcohol intake. He had been taking analgesics for eighteen years. Case 2: A 64‐year‐old Japanese male was referred in October of 1989 because of pigmentation on sun‐exposed areas of his skin. He had been drinking alcohol excessively for 43 years. The hepatitis C virus (HCV) antibody was present in each case. Tests for the HCV antibody and hepatitis B serological markers were run in 5 other patients. HCV antibody was present in 3 of them. The two cases negative for the HCV antibody exhibited the hepatitis B antibody. We speculated that viral hepatitis infection may play an important role in precipitating PCT in cases with a history of a long term excessive intake of alcohol or chemicals.

Quantitative analysis of ferrochelatase mRNA in blood cells of erythropoietic protoporphyria patients

Ferrochelatase (FC; heme synthetase, EC 4.99.1.1.) catalyses the synthesis of heme from protoporphyrin IX, the final step in the heme synthetic pathway. The hereditary deficiency of this enzyme gives rise to erythropoietic protoporphyria (EPP). We developed a rapid, non-radioactive means of measuring human FC mRNA levels in the EPP patients. It is based on the reverse transcriptase-polymerase chain reaction (RT-PCR) performed on the RNA obtained from peripheral blood. The amplified DNA was detected by agarose gel electrophoresis with ethidium bromide staining and the fluorescent intensity was measured by scanning densitometry applied directly to Polaroid 665 negative film. The relative expression level of FC mRNA, compared with that of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNA, was estimated at several points in the exponential phase of PCR cycles or at a point in the exponential phase of PCR performed on serially diluted the cDNA samples. The estimate of the FC mRNA by this method correlated well with the level of the FC mRNA measured by Northern blotting in the EB virus-transformed lymphocytes of the same patients. The level of the FC mRNA appeared to vary among the patients in whom a decreased level of enzymatic activity was indicated.

Mechanism of Blister Formation in Porphyria Cutanea Tarda: I. Histopathological Observation of Blisters in Three Cases of Porphyria Cutanea Tarda

We performed a histopathological investigation of the bullous lesions in 3 cases of porphyria cutanea tarda. All cases showed subepidermal bullae by light microscopy. PAS positive materials were present on the roof of the bullae and partially present on their bases. Electron‐microscopically, the basal lamina was clearly recognized on the base. From these results, we suggest that the blister in porphyria cutanea tarda occurs initially within the junctional zone; this initial bulla may quickly change into a dermolytic bulla with additional stimulation.

The influence of ursodeoxycholic acid (UDCA) on griseofulvin (GF)-induced protoporphyria

To investigate the influence of ursodesoxycholic acid (URSO) on griseofulvin (GF)-induced protoporphyria mice, analysis of hepatic, erythrocytic, and fecal porphyrin levels and histopathological examinations were performed in dd-Y strain mice treated with 0.5% GF and/or 0.5% URSO. We observed no difference of hepatic and fecal porphyrin levels between the GF group and GF with URSO group, although an elevation of erythrocytic porphyrin levels was seen in the GF with URSO group. However, remarkable hepatic atrophy revealed in the GF with URSO group. Furthermore, a strong emission of red fluorescence was observed in the liver under long wave ultraviolet. Histopathologically, many focal necrosis was found in the liver specimen treated with GF and URSO. We expected that URSO might facilitate the excretion of porphyrin from bile to feces because of suppression of transfer from serum to erythrocyte like cholic acid (CA). But, the action of URSO appears to be different from that of CA. We consider that the 0.5% concentration of URSO plays a role in the cytotoxic effect to the liver.

Biochemical Study of Fecal Porphyrin in Porphyria Cutanea Tarda

Fecal, urinary and erythrocyte porphyrin analyses using the solvent extraction method were performed in 26 patients with porphyria cutanea tarda (PCT) and 144 normal controls. The levels of fecal uroporphyrin (UP) and coproporphyrin (CP) were markedly increased in the PCT group, especially in comparison with the protoporphyrin (PP) level. The values of the UP/PP and CP/PP ratios in the feces were also elevated over those in the control group. It appears that fecal porphyrin excretion is basically similar to urinary porphyrin excretion in PCT. The analysis of fecal porphyrins and the observation of fecal UP/PP and CP/PP ratios may be helpful in the biochemical diagnosis of PCT. In particular, the elevation of CP/PP ratio is characteristic of PCT.

Relationship between N-Acetyltransferase (NAT) Activity and Liver Protoporphyrin Level in Experimental Porphyria

The results of our previous studies demonstrated that isonicotinic acid hydrazide (INH) can aggravate griseofulvin (GF)‐induced protoporphyria in mice. To elucidate this phenomenon, we studied the relationship between liver protoporphyrin (PP) levels and N‐acetyltransferase (NAT) activity, which is known to be a major catabolic enzyme of INH metabolism in the liver.