Cutaneous Porphyria Research Articles

2 Central nervous system disease

Porphyrias are a group of eight metabolic disorders characterized by defects in heme biosynthesis. Porphyrias are classified into two major categories: 1) the acute or inducible porphyrias and 2) the chronic cutaneous porphyrias. The acute hepatic porphyrias are further classified into acute intermittent porphyria (AIP), hereditary coproporphyria, variegate porphyria, and porphyria due to severe deficiency of delta-aminolevulinic acid (ALA) dehydratase (ALADP).AIP is the most common, and ALADP is the least common acute porphyria. The clinical presentations of acute porphyrias are nonspecific. There are no pathognomonic signs or symptoms. The most frequent presenting symptom is abdominal pain, but pain in the chest, back, or lower extremities may also occur. Hyponatremia is the most common electrolyte abnormality during acute attacks, and hypomagnesemia is also common. Both are risk factors for development of seizures, which occur in ∼ 20–30% of acute attacks.Once suspected, the diagnosis of porphyria can be rapidly established by checking random urinary porphobilinogen. Initial management of acute porphyria includes discontinuation of all potentially harmful drugs and management of symptoms. Acute attacks should be treated emergently with intravenous heme and glucose to avoid considerable morbidity and mortality. Acute attacks last a few days, and the majority of patients are asymptomatic between attacks. Prognosis is good if the condition is recognized early and treated aggressively.

Protein binding of salicylate in cutaneous hepatic porphyria.

(1) Plasma protein binding of salicylate was studied in 14 patients with cutaneous hepatic porphyria (CHP) and 11 normal subjects using ultrafiltration with centrifugation (membrane cones) and continuous ultrafiltrations. (2) Albumin and haemoglobin levels were significantly reduced in patients with CHP, and salicylate binding by ultrafiltration/centrifugation was 65% compared with 84% in normal subjects. (3) Plasma porphyrin levels were raised, but did not correlate with salicylate binding, and protoporphyrin or uroporphyrin added to plasma did not alter the amount of drug bound. (4) Palmitate added to plasma reduced salicylate binding by 9 to 20% but a crossover of patient and normal plasma proteins and ultrafiltrates confirmed that no other ultrafiltrable metabolites present in patient plasma appeared to cause decreased binding. (5) Scatchard plots obtained by continuous ultrafiltration for normal and patient plasma showed a reduction in the number of primary and secondary binding sites and an increase in the intrinsic association constants for both these sites. (6) It was concluded that the decreased salicylate binding in CHP was due to a reduced albumin concentration and altered salicylate albumin interaction.

Repair of DNA damage in light sensitive human skin diseases.

Repair of UV-light induced DNA damage and changes in the semiconservative DNA synthesis were studied by in vitro autoradiography in the skin of patients with lightdermatoses (polymorphous light eruption, porphyria cutanea tarda, erythropoietic protoporphyria) and xeroderma pigmentosum as well as in that of healthy controls. In polymorphous light eruption the semiconservative DNA replication rate was more intensive in the area of the skin lesions and in the repeated phototest site, the excision repair synthesis appeared to be unaltered. In cutaneous porphyrias a decreased rate of the repair incorporation could be detected. Xeroderma pigmentosum was characterized by a strongly reduced repair synthesis.

Lymphocytotoxic antibodies in lightdermatoses.

Occurrence of lymphocytotoxic antibodies of the "cold type" was studied in 92 cases with various lightdermatoses. They were detected in the sera of 39% of the patients with cutaneous porphyrias and never in cases with polymorphous light eruption and other photodermatosis. Correlations between their presence and the duration of the porphyria as well as the severity of hepatopathy could be observed. The results indicate the importance of a long-standing tissue damage in the production of these antibodies. In addition the findings confirm the hypothesis according to which polymorphous light eruption does not belong to the lupus erythematosus entity.

Malignant hepatoma associated with acquired hepatic cutaneous porphyria

Malignant hepatoma associated with acquired hepatic cutaneous porphyria

Malignant Hepatoma Associated With Acquired Hepatic Cutaneous Porphyria

A 60-year-old woman with a three-year history of an acquired hepatic cutaneous porphyria was discovered to have a porphyrin-producing malignant hepatoma. An attempt was made to treat her with fluorouracil perfused through a hepatic artery catheter. It did not produce shrinkage of the tumor, but the patient remains alive and ambulant a year after the infusion, although her skin lesions (scarring, bulla formation, and hyperpigmentation) on the fingers, back of hands, and face persist and she continues to excrete abnormally high quantities of porphyrin in her feces.

The effect of treatment on plasma uroporphyrin levels in cutaneous hepatic porphyria.

Seven patients undergoing treatment for cutaneous hepatic porphyria had serial measurements of their plasma uroporphyrin. In each case there was a progressive fall during treatment but even in remission the levels did not return to normal. There was a significant correlation between urinary and plasma uroporphyrin concentrations.

Letter: Order contraceptives and the liver.

The occurrence of porphyria cutanea tarda symptomatica (PCTS) in 5 patients aged 20-31 who were taking oral contraceptives is reported. None of the patients had a history of previous liver disease, other family members with porphyria, or other than infrequent social drinking. The porphyria appeared within 6 months of starting oral contraceptives in 3 of the patients. It is suggested that the estrogenic component of the oral contraceptives precipitates PCTS in these patients, since the syndrome also occurs in those treated with natural and synthetic estrogens for carcinoma of the prostate or menopausal symptoms. Appropriate laboratory tests on urine and feces samples are necessary to distinguish between PCTS and variegate porphyria when a young woman presents with the skin lesions characteristic of cutaneous hepatic porphyrias.

Hexachlorobenzene contamination: its effects in a Louisiana population.

Plasma hexachlorobenzene (HCB) residues in a Louisiana population exposed through the transportation and disposal of chemical waste containing HCB averaged 3.6 plus or minus 4.3 parts per billion (ppb) in a sample of 86 people. The highest level was 345 ppb in a waste disposal facility worker while the highest level in the general population was 23 ppb. There was no evidence of cutaneous porphyria by history or skin examination. Males had significantly higher residues than females (4.71 vs. 2.79 ppb) but there were no age differences. A possible association between HCB residues and coproporphyrin and lactic dehydrogenase was found. Only 2 of 48 meals sampled were positive for HCB. There was a correlation between HCB levels in household dust and plasma levels. Perchloroethylene and carbon tetrachloride production workers had plasma HCB levels of up to 233 ppb.

Hexachlorobenzene exposure from contaminated DCPA in vegetable spraymen.

Hexachlorobenzene (HCB) blood residues were found in 19 of 20 vegetable spraymen exposed to HCB-contaminated dimethyl-1-2, 3, 5, 6-tetrachloroterephthalate (DCPA). The mean level was 40 ± 63 parts per billion (ppb) with a range of 0 to 310 ppb. No definite physical or biochemical effects of this exposure were discovered. Specifically there was no evidence of cutaneous porphyria or abnormalities of uroporphyrin or coproporphyrin excretion. A positive correlation (P<.05) was found for HCB levels and δ-aminolevulinic acid excretion but this was interpreted skeptically.

Liposome model experiment for the study of assumed membrane damage in porphyria cutanea tarda

In the early stages of toxic porphyria induced by organic chloro compounds, the amount of coproporphyrins firstly rises. In this phase of the disease, the porphyrins are secreted from the liver via the bile duct; in contrast, in “porphyria cutanea tarda” and the porphyria of the cutanea tarda type resulting from the action of hexachlorobenzene, the various examinations show a diffuse porphyrin accumulation in the entire liver, extending also to the interstice. Accordingly, in hepatic cutaneous porphyrias the liver cells secrete porphyrin not only into the bile capillaries, but also into the intercellular substance; this, however, assumes the pathological change of the cell-membrane permeability. A model experiment was performed to test this hypothesis. A liposome membrane was prepared from phospholipid extracted from egg yolk. The permeability of this to glycine was compared with the permeability of a similar membrane which had been modified with hexachlorobenzene. The permeabilities to glycine of membranes “poisoned” with two different hexachlorobenzene concentrations at two temperatures (6 and 38 °C) were clearly larger (for the same diffusion mechanism) than that of the control, proving the correctness of the hypothesis. It must be noted, however, that the development of porphyria cutanea tarda is probably not the consequence of only the one aetiological factor, cell-membrane lesion.

Latent cutaneous porphyria, type PCT, in a caucasian woman

A case of latent cutaneous porphyria associated with a severe hemolytic anemia is reported. A complete family investigation showed no signs of heredity. The porphyrias may occur in association with malignant diseases, autoimmune conditions and other rare diseases. The relationship between skin photosensitivity and porphyrins does not seem to be a simple one.

Identification of a group of tetracarboxylate porphyrins, containing one acetate and three propionate -substituents, in faeces from patients with symptomatic cutaneous hepatic porphyria and from rats with porphyria due to hexachlorobenzene.

1. Three tetracarboxylate porphyrins, apart from coproporphyrin, were isolated from the faeces of patients with symptomatic cutaneous hepatic porphyria and of rats with porphyria caused by hexachlorobenzene poisoning. The porphyrins were not present in the urine of the porphyric rats or in the faeces of control rats. 2. Two of the porphyrins were identified as tris-(2-carboxyethyl)-carboxymethyl ethyl trimethyl porphin (isocoproporphyrin) and tris-(2-carboxyethyl)-carboxymethyl trimethyl porphin (de-ethyliso-coproporphyrin). 3. The third porphyrin, previously reported to be an analogue of coproporphyrin in which one propionate group is replaced by an alpha- or beta-hydroxypropionate group, was shown to be tris-(2-carboxyethyl)-carboxymethyl-(1-hydroxyethyl)-trimethyl porphin (hydroxyisocoproporphyrin). 4. The order of beta-substituents around the porphin ring could not be determined for any of the compounds. 5. Evidence for the existence of a fourth porphyrin, tris-(2-carboxyethyl)-carboxymethyl trimethyl vinyl porphin (dehydroisocoproporphyrin), a postulated precursor of the others, is described. 6. It is suggested that dehydroisocoproporphyrinogen is produced by decarboxylation-dehydrogenation of one of the propionate groups of pentacarboxylate porphyrinogen III.

Evaluation of growth rate in height over periods of less than one year.

Fine needle aspiration biopsy smears from 19 patients with porphyria cutanea tarda were studied by fluorescence microscopy. Fluorescence was arbitrarily graded from 0 to 4. All patients—those with clinically manifest as well as those with latent disease—showed bright red fluorescence of porphyrin type in the liver cells, though in latent cases the fluorescence commonly was of a low grade. In patients with manifest disease fluorescence of grade 3 or 4 was present. In patients with fluorescence of grades 1 or 2 the uroporphyrin excretion in urine was normal or slightly increased. At higher grades all levels of porphyrin excretion were encountered. Of 22 control subjects, only one showed hepatic fluorescence of a porphyrin character. The control patient with a positive finding was found to have definitely increased urinary uroporphyrin excretion and probably has latent porphyria cutanea tarda. The procedure described should be useful as a screening test for hepatic cutaneous porphyria.

Ocular Involvement in Cutaneous Porphyria

THE AUTHORITATIVE description of the eye in porphyria1lays emphasis on the clinical features. Stokes2has described in some detail the clinical features of the conjunctiva, sclera, and cornea in a case of porphyria, and the histological features of a conjunctival biopsy. This appears to be the first histological description of an entire eye associated with a case of proven porphyria, as noted by N. Ashton and L. Zimmerman (written communications, Oct 21 and 23, 1969). Report of a Case A male Negro, aged 51 years, gave a history of gradual loss of vision in his left eye over a ten-year period. A similar deterioration of vision in the right eye began on Sept 9, 1969, one year prior to admission. No ocular pain was experienced, but bitemporal headaches were common and persistent. On inquiry, a history of recurrent blistering and superficial abrasions of hands was given

The treatment of cutaneous porphyria with chloroquine or D-penicillamine.

British Journal of DermatologyVolume 83, Issue 6 p. 702-703 The Treatment of Cutaneous Porphyria with Chloroquine or D-Penicillamine G. A. Hunter, G. A. Hunter 195 North Terrace Adelaide South Australia 5000Search for more papers by this authorG. F. Donald, G. F. Donald 195 North Terrace Adelaide South Australia 5000Search for more papers by this author G. A. Hunter, G. A. Hunter 195 North Terrace Adelaide South Australia 5000Search for more papers by this authorG. F. Donald, G. F. Donald 195 North Terrace Adelaide South Australia 5000Search for more papers by this author First published: December 1970 https://doi.org/10.1111/j.1365-2133.1970.tb15770.xCitations: 4AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume83, Issue6December 1970Pages 702-703 RelatedInformation

Isolation of an hydroxylated porphyrin from urine and faeces of patients with cutaneous hepatic porphyria

Isolation of an hydroxylated porphyrin from urine and faeces of patients with cutaneous hepatic porphyria

Porphyria. Successful treatment by alkalinization of urine with sodium bicarbonate assessed by experimental suction blister apparatus.

Summary— Coproporphyrin but not uroporphyrin is excreted by the kidneys by a pH dependent mechanism. Alkalinization of the urine using 4–6 G. of sodium bicarbonate daily greatly increases the output of coproporphyrin. Three months treatment can be expected to improve the clinical signs of blistering of the skin in cutaneous hepatic porphyria. The coproporphyrin levels in the urine fall rapidly to be followed by the uroporpbyrin. An objective assessment of this improvement can be measured by applying controlled mechanical trauma to the skin using a suction apparatus. Skin fragility is lessened by treatment.

Phlebotomy Therapy in Cutaneous Porphyria

Porphyria cutanea tarda is often associated with hypersiderosis. Weekly or biweekly phlebotomy of 500 ml of blood depletes iron stores by mobilizing iron for hemoglobin formation to augment erythropoiesis. Uroporphyrin and coproporphyrin values were reduced to normal or near normal with regression of skin lesions and loss of cutaneous fragility. Remission has persisted up to 18 months. With phlebotomy serum iron and copper values were reduced and serum zinc and magnesium levels remained unchanged. Deferoxamine mesylate did not cause sufficient urinary iron excretion to justify its therapeutic use.

Phlebotomy therapy in cutaneous porphyria. Effect on iron and trace metals

Phlebotomy therapy in cutaneous porphyria. Effect on iron and trace metals