allopurinol and Psoriasis

As the current antipsoriatic medications are commonly associated with deleterious side-effects, a determined search for safer agents, which could be used alone or in combination with current antipsoriatic drugs, would be very imperative. Psoriasis is believed to be characterized by a type 1 cytokine pattern; interferon-gamma, interleukin (IL)-2 and tumour necrosis factor (TNF)-alpha are predominantly expressed in this disorder. Nitric oxide, reactive oxygen species, histamine, leukotriene B4, and decreased [corrected] keratinocyte cyclic adenosine monophosphate/cyclic guanosine monophosphate (cAMP/cGMP) ratio are supposed to play roles in the pathogenesis of this disorder. Based on the immunopathogenesis of psoriasis, this paper introduces three novel, potential treatments for this clinical conundrum: (i) cannabinoids, which exert inhibitory effects on antigen processing and macrophage/T-cell interaction and also on the release of IL-2, TNF-alpha and nitric oxide from immune cells; (ii) loratadine, which is an antihistamine capable of increasing [corrected] the cAMP/cGMP ratio and the production of leukotriene B4; and (iii) allopurinol, which scavenges free radicals, inhibits the production of TNF-alpha, and downregulates the expression of intercellular adhesion molecule-1 and P2X7 receptors on monocytes/macrophages, which are involved in antigen presentation and production of the inflammatory response, respectively. Importantly, allopurinol, especially in combination with cyclosporin, has been shown to be effective against experimental autoimmune uveitis, which, like psoriasis, is a cell-mediated autoimmune disorder.

Topics: Allopurinol; Cannabinoids; Free Radical Scavengers; Histamine H1 Antagonists, Non-Sedating; Humans; Loratadine; Psoriasis

Topics: Allopurinol; Arthritis; Arthritis, Rheumatoid; Diagnosis, Differential; Female; Humans; Immunoglobulin A; Immunoglobulin M; Male; Nails, Malformed; Prognosis; Psoriasis; Radiography; Spondylitis, Ankylosing

Topics: Adult; Allopurinol; Clinical Trials as Topic; Dermatitis, Exfoliative; Drug Eruptions; Female; Hospitalization; Humans; Male; Middle Aged; Nails; Placebos; Psoriasis; Uric Acid

Topics: Adult; Aged; Allopurinol; Clinical Trials as Topic; Female; Humans; Male; Middle Aged; Psoriasis; Purines; Uric Acid; Xanthine Oxidase

Topics: Acute Kidney Injury; Adult; Aged; Allopurinol; Arthritis, Rheumatoid; Clinical Trials as Topic; Duodenal Ulcer; Enzyme Therapy; Female; Gout; Humans; Male; Middle Aged; Psoriasis; Sulfinpyrazone; Uric Acid; Xanthine Oxidase

Topics: Adult; Allopurinol; Drug Evaluation; Female; Humans; Male; Middle Aged; Psoriasis; Uric Acid

The potential etiologic relationship between uric acid in its microcrystalline monosodium urate form and psoriasis was examined by 1) substantiating the reported correlation between hyperuricemia and psoriasis using the phosphotungstate method; 2) examining psoriatic tissue samples for the presence of urates under a microscope using polarized light and a compensator; 3) attempting to induce psoriasis-like symptoms in laboratory animals with purine-to-uric acid metabolism by increasing serum uric acid level; and 4) observing psoriasis-hyperuricemic patients following treatment for their hyperuricemia with Allopurinol. As expected, both men and women psoriatics had higher uric acid levels than did their counterparts in a control group. Monosodium urate crystals were found in samples from psoriatic plaques by both methods used. They were clustered particularly around sweat pores and Munro abscesses, but were found only occasionally in epidermal tissue taken from nonpsoriatics. Psoriasis-like symptoms were induced in laboratory animals (the South American boa, Constrictor constrictor) when they were fed doses of uric acid. Patients with psoriasis and hyperuricemia showed marked improvement in psoriasis when treated for their hyperuricemia. Psoriasis, like gout, may be, at least partly, a result of disorder of purine metabolism and monosodium urate crystals may be responsible for the cell proliferation that is characteristic of psoriatic plaques. Monosodium urate crystals were found by the author to be strikingly segmented. This structure may result in ease of fragmentation, thus increasing the difficulty in identifying urates in any tissue.

Topics: Allopurinol; Animals; Crystallization; Humans; Psoriasis; Purines; Skin; Snakes; Uric Acid

Topics: Adult; Aged; AMP Deaminase; Epidermis; Guanine Deaminase; Humans; Middle Aged; Psoriasis; Purine Nucleotides; Purine-Nucleoside Phosphorylase; Skin; Xanthine Oxidase

Xanthine oxidase and guanase activities in normal and psoriatic epidermis were demonstrated and accurately assayed by the new micro-assay methods which rely on the isolation of 14C-labelled end-products, xanthine and uric acid, from the substrates, hypoxanthine and guanine, by electrophoresis on cellulose acetate membrane using 0.1 M borate buffer, pH 9.0. The average specific activities of xanthine oxidase and guanase in normal epidermis were 10.2 and 55.0 pmol/min/mg protein, respectively, and in psoriatic epidermis, 52.1 and 980.6 pmol/min/mg protein, respectively. Increased activities of these enzymes in psoriatic epidermis suggested that urate formation might be enhanced in the psoriatic lesions resulting from an increased turn-over of nucleic acids.

Topics: Adult; Aged; Aminohydrolases; Female; Guanine Deaminase; Humans; Male; Middle Aged; Psoriasis; Skin; Uric Acid; Xanthine Oxidase

Topics: Allopurinol; Arthritis, Rheumatoid; Benzofurans; Diagnosis, Differential; Gout; Humans; Ketones; Psoriasis; Rheumatic Fever; Uric Acid

Topics: Administration, Oral; Adult; Aged; Allopurinol; Antimalarials; Arthritis; Aspirin; Female; Humans; Male; Middle Aged; Psoriasis; Triamcinolone

Topics: Arthritis; Female; Humans; Middle Aged; Psoriasis; Purine-Pyrimidine Metabolism, Inborn Errors; Xanthine Oxidase; Xanthines

Topics: Adult; Allopurinol; Child; Diabetes Mellitus; Female; Glycogen Storage Disease; Gout; Humans; Hypertension; Kidney Failure, Chronic; Male; Myxedema; Nutritional Physiological Phenomena; Pre-Eclampsia; Pregnancy; Psoriasis; Purines; Uric Acid; Uricosuric Agents

A case of xanthinuria is briefly described, and the results of in vivo studies with (14)C-labeled oxypurines are discussed. The data demonstrate that the rate of the turnover of uric acid is normal, despite an extremely small uric acid pool. Xanthine and hypoxanthine pools were measured and their metabolism evaluated. The bulk of the daily pool of 276 mg of xanthine, but only 6% of the 960 mg of hypoxanthine, is excreted. Thus, xanthine appears to be a metabolic end product, whereas hypoxanthine is an active intermediate. Biochemical implications of this finding are discussed.

Topics: Arthritis; Carbon Isotopes; Creatinine; Female; Guanine; Humans; Hypoxanthines; Metabolism, Inborn Errors; Middle Aged; Psoriasis; Purines; RNA; Spectrophotometry; Urate Oxidase; Uric Acid; Xanthine Oxidase; Xanthines

Topics: Adult; Allopurinol; Clioquinol; Dermatitis, Contact; Enteritis; Enzyme Therapy; Humans; Male; Psoriasis; Xanthine Oxidase