beta-carotene and Porphyrias

The porphyrias comprise a group of disorders of the haem biosynthesis pathway that can present with acute neurovisceral symptoms, skin lesions or both. Acute porphyrias present with severe abdominal pain, confusion and seizures which may be life-threatening. Specific treatment with haem preparations should be instituted as soon as possible following confirmation of increased excretion of porphobilinogen in the urine. Supportive treatment includes opiate analgesia, monitoring for and treating complications such as hypertension and hyponatraemia. Follow-up should include counselling on lifestyle modification involving avoidance of alcohol, smoking and known porphyrogenic drugs and diet. Identification and counselling of at risk relatives is essential. The cutaneous porphyrias result from porphyrin-induced photosensitivity and can present with either acute photosensitivity or skin fragility and blisters. All cutaneous porphyrias can be alleviated by avoidance of sunlight. Treatment of erythropoietic protoporphyria involves administering large doses of beta-carotene, which may improve tolerance to sunlight. Porphyria cutanea tarda can be effectively treated by phlebotomy or low dose chloroquine. Congenital erythropoietic porphyria is a rare, early onset, severe, photomutilating condition for which bone marrow transplantation has been shown to be successful.

Topics: Arginine; beta Carotene; Chloroquine; Estrogens; Ethanol; Heme; Humans; Phlebotomy; Porphyria Cutanea Tarda; Porphyria, Acute Intermittent; Porphyrias; Sunlight

There are seven porphyrias which are caused by defective functions of the enzymes in the haem biosynthesis. The clinical classification of porphyrias are divided into three types which are neuroporphyria, neurocutaneous porphyria and cutaneous porphyria. For acute porphyric attack of neuroporphyria and neurocutaneous porphyria, the treatments of choice are administration of glucose and/or hematin, haem arginate and tinprotoporphyrin. Porphyria cutanea tarda in cutaneous porphyria is controlled by removal of iron by phrebotomies or low-dose chloriquine. A novel approach of intravenous administration of interferon may be useful to control the associated case of chronic hepatitis type C. Skin symptoms in erythropoietic protoporphyria can be alleviated with beta carotene. Hepatic failure due to protoporphyria may need a liver transplantation. Cimetidine, a H2-receptor antagonist, may be useful in the treatment of acute porphyric attack and in remission stage in neuroporphyrias, neurocutaneous porphyrias and cutaneous porphyrias such as porphyria cutanea tarda and protoporphyria.

Topics: beta Carotene; Bloodletting; Carotenoids; Cimetidine; Female; Glucose; Hemin; Humans; Interferons; Liver Transplantation; Male; Porphyrias

The pharmacological basis for the treatment of photosensitivity diseases is poorly understood. The supposed pathogenesis of photosensitivity reactions is reviewed, and the mechanism of action of drugs known to be efficient in this type of reaction (antimalarials, beta-carotene, thalidomide, PUVA therapy) discussed.

Topics: Antigens; Antimalarials; beta Carotene; Carotenoids; DNA; Female; Humans; Immunosuppression Therapy; Male; Niacinamide; Pellagra; Photosensitivity Disorders; Porphyrias; Porphyrins; PUVA Therapy; Skin Diseases; Sunlight; T-Lymphocytes; Thalidomide; Ultraviolet Rays; Uroporphyrinogen Decarboxylase; Uroporphyrins; Urticaria

This paper describes the development of the use of carotenoid pigments in the treatment of light-sensitive skin diseases. It also discusses the animal and human studies involved in determining whether carotenoids have any anti-cancer activity. The possible mechanisms of carotenoid photoprotective and anti-cancer actions are briefly discussed.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Adolescent; Adult; Animals; Bacteria; Bacterial Physiological Phenomena; beta Carotene; Canthaxanthin; Carotenoids; Child; Child, Preschool; Diet; Humans; Infant; Light; Neoplasms; Neoplasms, Experimental; Photochemistry; Photosensitivity Disorders; Porphyrias; Protoporphyrins; Skin Diseases; Skin Neoplasms; Sunburn; Sunlight; Ultraviolet Rays

A review of published trials with beta-carotene and/or canthaxanthin treatment of erythropoietic protoporphyria is presented. Increased tolerance to sunlight is reported in about 85% of the cases in uncontrolled studies. In the only controlled trial on record no difference was found between beta-carotene and placebo. Correlations between the results of carotenoid treatment and phototests have been reported in some studies, but denied in others. During treatment the protoporphyrin levels in erythrocytes were significantly increased in one study, but decreased or unaffected in others. A possible mechanism of photoprotection by beta-carotene is briefly presented. To date no serious side effects or hypervitaminosis-A induced by beta-carotene have been reported.

Topics: Adult; beta Carotene; Canthaxanthin; Carotenoids; Clinical Trials as Topic; Erythropoiesis; Humans; Male; Photosensitivity Disorders; Porphyrias; Protoporphyrins; Skin Diseases

Topics: beta Carotene; Female; Humans; Pigmentation Disorders; Porphyrias

Topics: Abnormalities, Drug-Induced; Adult; beta Carotene; Counseling; Female; Humans; Infant, Newborn; Male; Porphyrias; Pregnancy; Pregnancy Outcome; Retinoids; Teratogens; Vitamin A

Topics: Adolescent; Adult; beta Carotene; Carotenoids; Child; Edetic Acid; Female; Humans; Japan; Male; Middle Aged; Porphyrias; Prognosis

Topics: beta Carotene; Carotenoids; Humans; Photosensitivity Disorders; Phototherapy; Porphyrias; Skin Diseases

The effect of terfenadine on the response to irradiation with blue light was measured in seven patients with erythropoietic protoporphyria. Terfenadine caused significant inhibition of the immediate flare reaction, but did not alter the erythemal response localized to the irradiation sites. Treatment with beta-carotene had no effect on the flare and erythemal responses. However, the flare reaction was still inhibited by terfenadine during treatment with beta-carotene. These results show that histamine release is involved in the mechanism of porphyrin photosensitivity. H1 receptor antagonists may be of use in the treatment of patients with erythropoietic protoporphyria.

Topics: Adolescent; Adult; Benzhydryl Compounds; beta Carotene; Carotenoids; Child; Drug Therapy, Combination; Erythropoiesis; Histamine H1 Antagonists; Humans; Male; Photosensitivity Disorders; Porphyrias; Protoporphyrins; Terfenadine

Carotenoid pigments have been found to have a protective function against photosensitization in green plants. This protective ability has been exploited in the administration of high doses of beta-carotene to patients with erythropoietic protoporphyria to ameliorate the photosensitivity associated with this disease. The carotenoids seem to exert their light-protective function by quenching excited species such as singlet oxygen and free radicals.

Topics: Animals; Bacteria; beta Carotene; Carotenoids; Humans; Light; Photosensitivity Disorders; Porphyrias; Skin Diseases

The porphyrias are caused by hereditary defects in the synthesis of heme. Each porphyria is characterized by a unique enzyme defect and measurable elevations of specific heme precursors. While qualitatively normal, these precursors accumulate to cause protean signs and symptoms. Photosensitivity should raise the suspicion of a porphyria, especially in a child or a young adult. The skin, teeth and eyes may provide clues to the diagnosis in some cases.

Topics: Adolescent; Adult; Aminolevulinic Acid; beta Carotene; Bloodletting; Carotenoids; Child; Child, Preschool; Chloroquine; Humans; Infant; Liver Diseases; Male; Middle Aged; Porphobilinogen; Porphyrias; Skin; Skin Diseases; Skin Diseases, Vesiculobullous; Sunlight; Uroporphyrins

At present, three classes of compounds are used as systemic photoprotective agents, but only for specific indications, not for general use in healthy individuals. Beta-carotene prevents or lessens photosensitivity in most patients with erythropoietic protoporphyria and in some patients with other photosensitivity diseases. The antimalarial drugs can clear up skin lesions in patients with polymorphous light eruption and solar urticaria who cannot obtain relief with topical sunscreens and in some patients with porphyria cutanea tarda. Oral psoralens and controlled exposure to sunlight or artificial sources of UVA radiation can increase tolerance to sunlight in fair-skinned individuals and in certain patients with vitiligo or polymorphous light eruption.

Topics: Administration, Oral; Administration, Topical; Antimalarials; beta Carotene; Carotenoids; Erythropoiesis; Evaluation Studies as Topic; Furocoumarins; Humans; Photosensitivity Disorders; Porphyrias; Protoporphyrins

Twenty-five patients (erythropoietic protoporphyria 23, polymorphous light eruption 1, "cosmetics" 1) were re-examined 2-10 months after therapy with beta-carotene and canthaxanthine was discontinued. Dark adaptation and ERG parameters had normalized, whereas crystalline retinopathy and pigment epithelial defects showed no signs of reversibility.

Topics: beta Carotene; Canthaxanthin; Carotenoids; Dose-Response Relationship, Drug; Drug Combinations; Electroretinography; Fluorescein Angiography; Follow-Up Studies; Humans; Photosensitivity Disorders; Porphyrias; Porphyrins; Protoporphyrins; Retinal Diseases; Skin Diseases

We investigated the effect of UV light (320-460 nm) on total hemolytic CH50 activity and C3 cleavage in sera obtained from 14 patients with porphyria cutanea tarda. Irradiation with 5, 10, or 50 J/cm2 resulted in a 12%-60% loss of CH50 and a 5%-30% cleavage of native C3 as estimated by planimetric evaluation of the immunoelectrophoretic C3 pattern. The complement changes were most pronounced in sera from patients with active disease and were minimal or absent in patients who were in remission. In all cases, the decrease of CH50 and C3 cleavage was proportional to the plasma-porphyrin concentration and the dose of radiation. After exposure to 320- to 460-nm light, similar changes were seen in normal human serum (NHS) to which exogenous uroporphyrin had been added. Beta-carotene and chloroquine had no inhibitory effect on the photodynamic complement activation. The C3 cleavage in irradiated NHS containing uroporphyrin was not affected by 10 mM EGTA, but was partially inhibited in the presence of 30 mM EDTA, thus indicating that the interaction of photoexcited uroporphyrin with the complement system differs from classical-pathway complement activation.

Topics: Aged; beta Carotene; Carotenoids; Chloroquine; Complement Activation; Complement C3; Complement System Proteins; Edetic Acid; Egtazic Acid; Female; Humans; Immunoelectrophoresis, Two-Dimensional; Male; Middle Aged; Porphyrias; Porphyrins; Skin Diseases; Ultraviolet Rays; Uroporphyrins

Topics: beta Carotene; Blood Transfusion; Carotenoids; Cholestyramine Resin; Erythrocyte Transfusion; Erythropoiesis; Hemin; Humans; Plasmapheresis; Porphyrias; Porphyrins; Protoporphyrins; Skin Diseases

Topics: beta Carotene; Canthaxanthin; Carotenoids; Drug Therapy, Combination; Humans; Photosensitivity Disorders; Porphyrias; Porphyrins; Protoporphyrins; Skin Diseases

Topics: Animals; beta Carotene; Canthaxanthin; Carotenoids; Dicarbethoxydihydrocollidine; Griseofulvin; Light; Mice; Mice, Nude; Porphyrias; Skin; Skin Diseases

We have found that beta-carotene, when administered in sufficiently high doses, can be an effective therapy for ameliorating the photosensitivity associated with EPP. Other workers have confirmed our findings, using either beta-carotene, canthaxanthin or combinations of these two carotenoids. Carotenoids may be of some use in congenital porphyria, if given in high doses and started when the patient is very young. Carotenoid treatment seems of limited use in polymorphous light eruption, solar urticaria, hydroa aestivale and hydroa vacciniforme: we would recommend their use in these conditions only after the more standard treatments for these diseases have proven ineffective for a given patient. Carotenoid treatment seems to be of no use in porphyria cutanea tarda and actinic reticuloid.

Topics: Age Factors; Animals; beta Carotene; Carotenoids; Dose-Response Relationship, Drug; Erythrocytes; Humans; Mice; Photosensitivity Disorders; Porphyrias; Porphyrins; Protoporphyrins

Topics: beta Carotene; Carotenoids; Combined Modality Therapy; Erythropoiesis; Humans; Liver Diseases; Porphyrias; Porphyrins; Protoporphyria, Erythropoietic; Protoporphyrins; Skin Diseases

The retinas of twenty-six patients with protoporphyria who had received treatment with beta-carotene for periods ranging from 1 to 10 years were examined for the presence of yellow crystalline deposits, similar to those recently reported in and around the maculae of individuals ingesting the related carotenoid compound canthaxanthin. No crystalline deposits were observed in any of our patients.

Topics: Adolescent; Adult; Aged; beta Carotene; Carotenoids; Child; Crystallins; Humans; Middle Aged; Porphyrias; Protoporphyrins; Retinal Diseases; Skin Diseases

Six patients with protoporphyria had mildly elevated triglyceride levels (200 to 300 mg/dl) on serum chemistry screening panels. Measurement of fasting plasma lipid profiles indicated that triglyceride levels were mildly elevated in 22 patients with protoporphyria compared with the values of a age- and sex-matched population of the Lipid Research Clinics prevalence study (p = 0.021). The effect of ingestion of the retinoid precursor beta-carotene on plasma triglyceride levels was assessed in 13 of these patients, both during carotene therapy and during therapy-free intervals. There was no significant increase in plasma triglyceride levels during administration of carotene; eight of 13 patients had lower levels during therapy. There was no significant correlation between plasma triglyceride levels at p less than or equal to 0.05 and serum carotene or blood protoporphyrin levels. Our results indicate that mild hypertriglyceridemia occurs with increased frequency in patients with protoporphyria, but not as a direct result of beta-carotene therapy.

Topics: Adolescent; Adult; beta Carotene; Carotenoids; Child; Cholesterol; Cholesterol, HDL; Erythrocytes; Female; Humans; Lipoproteins, HDL; Male; Middle Aged; Porphyrias; Porphyrins; Protoporphyrins; Seasons; Skin Diseases; Triglycerides

A 21-year-old patient was observed with oedematous-purpura-like skin changes since earliest childhood occurring in areas with short-term exposure to sunlight. The history suggested erythropoetic protoporphyria and the diagnosis was established by demonstration of fluorocytes in peripheral blood and subsequent porphyrin analysis. Whereas chronic persistent skin changes characteristic of erythropoetic protoporphyria were largely absent, histologic and immunohistologic findings were typical. The patient had been considered a "neurotic outsider" for many years because of his aversion to light which was considered abnormal.

Topics: Adult; beta Carotene; Carotenoids; Humans; Liver Cirrhosis; Male; Photosensitivity Disorders; Porphyrias; Protoporphyrins; Skin Diseases

Topics: Adult; beta Carotene; Carotenoids; Child; Female; Humans; Male; Photosensitivity Disorders; Porphyrias; Porphyrins; Protoporphyrins; Skin Diseases

Topics: beta Carotene; Carotenoids; Drug Evaluation, Preclinical; Erythropoiesis; Humans; Photosensitivity Disorders; Porphyrias; Skin Diseases

Topics: Acute Disease; beta Carotene; Carotenoids; Female; Genes, Dominant; Humans; Male; Pedigree; Porphyrias; Skin Diseases