Symptomatic Porphyria Cutanea Tarda Research Articles

Abnormal Serum Porphyrin Levels in Patients With the Acquired Immunodeficiency Syndrome With or Without Hepatitis C Virus Infection

<h3>Objective:</h3> To define the contributions of human immunodeficiency virus (HIV) and hepatitis C virus infections to the development of porphyria cutanea tarda. <h3>Design:</h3> Analysis of serum porphyrin levels in a cohort of 167 subjects. Serum samples were divided into 4 groups corresponding to the status of HIV and hepatitis C virus infections: positive-positive, positive-negative, negative-positive, and negative-negative. <h3>Settings:</h3> Serum samples positive for HIV were obtained from the serum bank of an acquired immunodeficiency syndrome-HIV research center, and HIV-negative samples were obtained from a regional blood center. <h3>Main Outcome Measures:</h3> Spectrofluorometric measurement of serum porphyrin levels. <h3>Results:</h3> The median values of porphyrin were 2.31 nmol/L (interquartile range [difference between the 25th and 75th percentiles]: 4.55) in the positive-positive group, 1.99 nmol/L (interquartile range: 1.63) in the positive-negative group, 1.31 nmol/L (interquartile range: 1.58) in the negative-positive group, and 1.14 nmol/L (interquartile range: 0.92) in the negative-negative group. The fluorescence emission spectra of samples with elevated porphyrin levels were identical with that reported for porphyria cutanea tarda. Elevated porphyrin levels were significantly associated with HIV infection (<i>P</i>&lt;.001) and were observed in patients with an elevated level of alanine aminotransferase (<i>P</i>=.03). Infection with hepatitis C virus was also associated with an elevation in porphyrin levels, although the increase was not statistically significant (<i>P</i>=.16). Porphyrin levels in patients positive for HIV were not correlated with serum urea nitrogen or creatinine levels. None of the patients had symptomatic porphyria cutanea tarda. <h3>Conclusions:</h3> Factors associated with increased serum porphyrin levels included HIV infection, elevated alanine aminotransferase levels, and, to a lesser extent, hepatitis C virus infection. These findings suggest that patients with the above risk factors are potentially predisposed to the development of symptomatic porphyria cutanea tarda on further exposure to hepatotoxic agents. Arch Dermatol. 1996;132:906-910

Abnormal serum porphyrin levels in patients with the acquired immunodeficiency syndrome with or without hepatitis C virus infection

To define the contributions of human immunodeficiency virus (HIV) and hepatitis C virus infections to the development of porphyria cutanea tarda. Analysis of serum porphyrin levels in a cohort of 167 subjects. Serum samples were divided into 4 groups corresponding to the status of HIV and hepatitis C virus infections: positive-positive, positive-negative, negative-positive, and negative-negative. Serum samples positive for HIV were obtained from the serum bank of an acquired immunodeficiency syndrome-HIV research center, and HIV-negative samples were obtained from a regional blood center. Spectrofluorometric measurement of serum porphyrin levels. The median values of porphyrin were 2.31 nmol/L (interquartile range [difference between the 25th and 75th percentiles]: 4.55) in the positive-positive group, 1.99 nmol/L (interquartile range: 1.63) in the positive-negative group, 1.31 nmol/L (interquartile range: 1.58) in the negative-positive group, and 1.14 nmol/L (interquartile range: 0.92) in the negative-negative group. The fluorescence emission spectra of samples with elevated porphyrin levels were identical with that reported for porphyria cutanea tarda. Elevated porphyrin levels were significantly associated with HIV infection (P < .001) and were observed in patients with an elevated level of alanine aminotransferase (P = .03). Infection with hepatitis C virus was also associated with an elevation in porphyrin levels, although the increase was not statistically significant (P = .16). Porphyrin levels in patients positive for HIV were not correlated with serum urea nitrogen or creatinine levels. None of the patients had symptomatic porphyria cutanea tarda. Factors associated with increased serum porphyrin levels included HIV infection, elevated alanine aminotransferase levels, and, to a lesser extent, hepatitis C virus infection. These findings suggest that patients with the above risk factors are potentially predisposed to the development of symptomatic porphyria cutanea tarda on further exposure to hepatotoxic agents.

The Porphyrias and Hepatocellular Carcinoma

Hepatocellular carcinoma probably represents the final step of the effects of the various precipitating agents for porphyria cutanea tarda, such as alcohol, drugs, hormones, and hepatitis C infection. Risk factors associated with its development include male gender, age over 50 years, liver fibrosis or cirrhosis, and a long history (over 10 years) of symptomatic porphyria cutanea tarda.

Evaluation of porphyria cutanea tarda in U.S. workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

A cross-sectional medical study was performed to evaluate whether occupational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-contaminated substances is associated with porphyria cutanea tarda or porphyrinuria. The exposed participants were employed more than 15 years earlier in the manufacture of sodium trichlorophenol and its derivatives. The referent group consisted of individuals with no occupational exposure to phenoxy herbicides. A total of 281 workers and 260 referents participated. The pattern of urinary porphyrin excretion for each participant was assessed to determine if symptomatic or subclinical porphyria cutanea tarda was present. None of the participants were found to have symptomatic porphyria cutanea tarda. No difference was found between workers and referents in the prevalence of subclinical porphyria cutanea tarda (odds ratio [OR] = 0.93, 95% confidence interval [CI] 0.19, 4.54). There were also no differences in the risk between workers and referents for an out-of-range urinary uroporphyrin or coproporphyrin concentration. In conclusion, this study did not find an elevated risk for porphyria cutanea tarda or porphyrinuria among workers with high serum TCDD levels. Our review of the literature indicates that there is insufficient evidence available to convincingly support or refute an association in humans between TCDD exposure and porphyria cutanea tarda or porphyrinuria.

The role of iron in experimental porphyria and porphyria cutanea tarda

Porphyria cutanea tarda (PCT) and experimental porphyria are characterized by a decreased activity of the enzyme uroporphyrinogen decarboxylase, and accumulation of uroporphyrins and heptacarboxylporphyrins in the liver. Iron (Fe) plays an important role in PCT and experimental porphyria. Biochemically and electron microscopically, we examined the relationship between Fe and porphyrins in liver tissue of C57BL/10 mice made porphyric by administration of iron dextran as Imferon (IMF), and in liver biopsies of patients with symptomatic PCT. Accumulation of uroporphyrins and heptacarboxylporphyrins, and an increased amount of Fe were observed in livers of mice treated with IMF and in liver biopsies of patients with PCT. In mice treated with IMF, the activity of uroporphyrinogen decarboxylase was decreased. Both in livers of mice treated with IMF and in livers of patients with PCT, needle-like structures, representing uroporphyrin crystals, were observed by electron microscopy. Uroporphyrin crystals and Fe (as ferritin) were observed in the same hepatocyte. Moreover, there was a striking morphological correlation between uroporphyrin crystals and ferritin-Fe, suggesting a role for (ferritin-)Fe in the pathogenesis of porphyria.

Congenital erythropoietic uroporphyria (Günther's disease) presenting in a middle aged man

1. 1. The third case of erythropoietic uroporphyria of Günther in an adult is reported. A bullous rash and hepatosplenomegaly suggested a diagnosis of symptomatic porphyria cutanea tarda. 2. 2. Evidence of excessive porphyrin metabolism was found in the red cells and their precursors and detailed chemical analyses of plasma, red cell, urinary and faecal porphyrins gave results similar to those for congenital porphyria. 3. 3. The late presentation, as suggested by Pain (1975), may represent the heterozygous state and this is discussed.

Incorporation of (4-14 C) -aminolaevulinate into urinary porphyrins in porphyria cutanea tarda: effect of chloroquine therapy.

1. [4-14C]δ-Aminolaevulinate (ALA) was administered by the oral route to three patients with symptomatic porphyria cutanea tarda as a tracer dose and the incorporation of radioactivity into urinary 8-, 7-, 6-, 5- and 4-carboxyl porphyrins studied as a function of time. In one of these patients the study was repeated after partial depletion of stored liver porphyrins by low-dose chloroquine therapy. 2. Maximal radioactive incorporation into the urinary porphyrins was generally inversely related to the degree of carboxylation. In all instances maximal specific radioactivity of coproporphyrin far exceeded that of uroporphyrin, but was achieved at the same time interval. 3. Chloroquine therapy resulted in a porphyrinuria with a composition substantially similar to that before treatment. After partial depletion of the liver porphyrin stores maximum specific radioactivity of all urinary porphyrins increased as compared with before treatment. 4. Non-porphyric livers, obtained at post-mortem, were analysed for porphyrin content and composition; appreciable performed pools of 8-, 7-, 6-, 5-, 4- and 2- carboxyl porphyrins were found. 5. Results of the radioactive studies are interpreted as consistent with dilution in preformed pools of stored porphyrins of decreasing size. It is suggested that the predominance of 8- and 7-carboxyl porphyrins in the livers and urines of patients with porphyria cutanea tarda is due to rate-limitation of uroporphyrinogen decarboxylation in those liver cells which store free porphyrins.

Aetiological relationship between hepatic siderosis and symptomatic porphyria cutanea tarda. Evidence based on work in Durban.

Aetiological relationship between hepatic siderosis and symptomatic porphyria cutanea tarda. Evidence based on work in Durban.

Pesticides, Chloracne, and Porphyria Cutanea Tarda

<h3>To the Editor:—</h3> The terms, 2,4-dichlorophenol and 2,4,5-trichlorophenol, are the commonly accepted designations for the phenoxy acetic acids of these compounds. It makes no difference if the basic compound is acidified or esterified, or synthesized into a salt. The point is that the benzene ring with two or three chlorine atoms attached is involved in the etiology of chloracne and/or symptomatic porphyria cutanea tarda (PCT). These herbicides are indeed useful. We simply pointed out that, at least in their synthesis, toxic side effects are to be looked for. We have had a report, documented with photographs, of chloracne occurring in an agricultural area where the finished phenoxy compound is being used. This was not stressed in the communication, since we were concerned with the occurrence of PCT and chloracne in the manufacture of herbicides.

INDUSTRIALLY ACQUIRED PORPHYRIA.

To the Editor: Thank you for forwarding us the two letters which were received regarding our recent article on occupationally acquired symptomatic porphyria cutanea tarda. First, the letter from Dr. Ernst Epstein. Our use of the name Watson-Schwartz test , according to our laboratory, referred to a less commonly used test for uroporphyrin and not the more commonly used Watson-Schwartz test for porphobilinogen. In addition, the results were checked with paper chromatography. As to Dr. Epstein's second point, strange as it may seem, no facilities were made available to us for quantitative estimation of porphyrin excretion. This was in spite of the fact that two major teaching centers were approached about this problem. We felt that the publication of this article even without the quantitative tests would be of value, since it would alert others to the possible relationship between the chemicals discussed and the appearance of symptomatic porphyria cutanea tarda.