allopurinol and Pruritus

There is a major clinical need for new therapies for the treatment of chronic itch. Many of the molecular components involved in itch neurotransmission are known, including the neuropeptide NPPB, a transmitter required for normal itch responses to multiple pruritogens in mice. Here, we investigated the potential for a novel strategy for the treatment of itch that involves the inhibition of the NPPB receptor NPR1 (natriuretic peptide receptor 1). Because there are no available effective human NPR1 (hNPR1) antagonists, we performed a high-throughput cell-based screen and identified 15 small-molecule hNPR1 inhibitors. Using in vitro assays, we demonstrated that these compounds specifically inhibit hNPR1 and murine NPR1 (mNPR1). In vivo, NPR1 antagonism attenuated behavioral responses to both acute itch- and chronic itch-challenged mice. Together, our results suggest that inhibiting NPR1 might be an effective strategy for treating acute and chronic itch.

Topics: Animals; Behavior, Animal; Cell-Free System; Dermatitis, Contact; Disease Models, Animal; Ganglia, Spinal; Humans; Mice, Inbred C57BL; Mice, Knockout; Neurons; Pruritus; Receptors, Atrial Natriuretic Factor; Reproducibility of Results; Signal Transduction; Small Molecule Libraries

We report the case of a 60-year old patient with a 1-month history of hyperuricemia treated with allopurinol. The patient presented to the Department of Dermatology with acute rash on the face and the lower limbs associated with fever, arthralgias and myalgias. Clinical examination showed symmetric macular erythema on the face at the level of the cheeks with discreet edema (A), erythematous plaques at the level of both legs with healthy skin areas extending progressively from the bottom-up. Lesions were very itchy with burning sensation (B). The examination of the oral cavity showed very painful erosive lesions at the level of the internal face of the cheeks. Lymph nodes were free. Paraclinical tests showed leukocyte counts at 20000, elevated transaminases > 100 IU, eosinophil counts at 1500, HHV6 serology was negative. The diagnosis of DRESS syndrome was retained. The patient underwent corticosteroid therapy at a dose of 1 mg/kg/day associated with symptomatic treatment. Treatment evolution was marked by spectacular improvement after 06 days (C and D) with regression of skin lesions and gradual normalization of laboratory results.

Topics: Adrenal Cortex Hormones; Allopurinol; Drug Hypersensitivity Syndrome; Female; Gout Suppressants; Humans; Hyperuricemia; Middle Aged; Pruritus

To evaluate the use of prospective screening for the HLA-B*58:01 allele to identify Taiwanese individuals at risk of severe cutaneous adverse reactions (SCARs) induced by allopurinol treatment.. National prospective cohort study.. 15 medical centres in different regions of Taiwan, from July 2009 to August 2014.. 2926 people who had an indication for allopurinol treatment but had not taken allopurinol previously. Participants were excluded if they had undergone a bone marrow transplant, were not of Han Chinese descent, and had a history of allopurinol induced hypersensitivity. DNA purified from 2910 participants' peripheral blood was used to assess the presence of HLA-B*58:01.. Incidence of allopurinol induced SCARs with and without screening.. Participants who tested positive for HLA-B*58:01 (19.6%, n=571) were advised to avoid allopurinol, and were referred to an alternate drug treatment or advised to continue with their prestudy treatment. Participants who tested negative (80.4%, n=2339) were given allopurinol. Participants were interviewed once a week for two months to monitor symptoms. The historical incidence of allopurinol induced SCARs, estimated by the National Health Insurance research database of Taiwan, was used for comparison. Mild, transient rash without blisters developed in 97 (3%) participants during follow-up. None of the participants was admitted to hospital owing to adverse drug reactions. SCARs did not develop in any of the participants receiving allopurinol who screened negative for HLA-B*58:01. By contrast, seven cases of SCARs were expected, based on the estimated historical incidence of allopurinol induced SCARs nationwide (0.30% per year, 95% confidence interval 0.28% to 0.31%; P=0.0026; two side one sample binomial test).. Prospective screening of the HLA-B*58:01 allele, coupled with an alternative drug treatment for carriers, significantly decreased the incidence of allopurinol induced SCARs in Taiwanese medical centres.

Topics: Allopurinol; Chronic Disease; Drug Eruptions; Exanthema; Female; Genetic Testing; Genotype; Gout Suppressants; Heterozygote; HLA-B Antigens; Humans; Male; Middle Aged; Prospective Studies; Pruritus; Taiwan

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare, severe adverse drug reaction. The aim of this study was to characterize the aetiology, clinical features, laboratory findings, and management of patients with DRESS, diagnosed from January 2005 to April 2010 in a tertiary centre in Thailand. Twenty-seven patients were included in the study with a mean age of 52 years. Phenytoin, allopurinol, and nevirapine were the most commonly implicated medications. Mean duration of drug administration before the onset of symptoms was 34 days. The latent period was longer for allopurinol (103 days) and shorter for nevirapine (10 days). Skin rash was seen in all patients, while fever and lymphadenopathy were found in 88.9% and 22.2%, respectively. Hepatic and haematological involvement were the two most common systemic complications, occurring in 96.3% and 85.2%, respectively. Most patients were treated with systemic corticosteroids, for a mean duration of 49 days. The mortality rate in this study was 3.7%. Early detection and discontinuation of the suspected drug are the key steps of management.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Anti-HIV Agents; Anti-Inflammatory Agents; Anticonvulsants; Dexamethasone; Drug Eruptions; Edema; Enzyme Inhibitors; Eosinophilia; Face; Female; Fever; Humans; Liver; Male; Middle Aged; Nevirapine; Phenytoin; Prednisolone; Pruritus; Recurrence; Retrospective Studies; Thailand; Time Factors; Withholding Treatment; Young Adult

Topics: Adolescent; Adult; Allopurinol; Anti-Infective Agents; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Carbamazepine; Child; Drug Combinations; Drug Eruptions; Eosinophilia; Exanthema; Female; Glucosamine; Gout Suppressants; Humans; Male; Middle Aged; Pruritus; Retrospective Studies; Sulfasalazine; Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

The authors present a case of acquired reactive perforating collagenosis developed in a nondiabetic hemodialysis patient, who was treated successfully with allopurinol. Treatment of acquired reactive perforating collagenosis is difficult and often ineffective. The patient had been unresponsive to conventional treatments, but the pruritus was controlled, and skin lesions subsequently resolved after the treatment with allopurinol. Possible mechanisms of allopurinol treatment for acquired reactive perforating collagenosis are discussed.

Topics: Allopurinol; Collagen Diseases; Enzyme Inhibitors; Humans; Male; Middle Aged; Pruritus; Renal Dialysis; Skin Diseases, Metabolic

Topics: Allopurinol; Collagen Diseases; Female; Free Radical Scavengers; Humans; Middle Aged; Pruritus

To determine the efficacy and safety of slow oral desensitization in the management of allopurinol-related pruritic cutaneous eruptions.. Nine patients with renal insufficiency and chronic tophaceous gouty arthritis, who had to interrupt their allopurinol therapy because of an allergic-type pruritic maculopapular eruption, were enrolled in an allopurinol oral desensitization protocol using a schedule of gradually increasing doses.. Cautious reinstitution of allopurinol was successfully accomplished in all nine patients, but four individuals required dose adjustment because of development of a mild, recurrent, macular rash early during the protocol at allopurinol doses of less than or equal to 5 mg/d. Transient, postdesensitization cutaneous reactions occurred in two patients, one of whom also had an early rash.. Oral desensitization to the minor rashes induced by allopurinol is a feasible and acceptably safe approach to therapy, particularly for those with renal insufficiency in whom no substitute urate-lowering drug is available.

Topics: Administration, Oral; Adolescent; Adult; Aged; Allopurinol; Chronic Disease; Desensitization, Immunologic; Drug Eruptions; Female; Gout; Humans; Kidney Failure, Chronic; Male; Middle Aged; Pruritus

Topics: Aged; Allopurinol; Busulfan; Drug Eruptions; Drug Therapy, Combination; Exanthema; Humans; Male; Pruritus

Topics: Allopurinol; Chemical and Drug Induced Liver Injury; Drug Hypersensitivity; Female; Humans; Middle Aged; Necrosis; Pruritus; Uric Acid; Urticaria

Topics: Acute Disease; Allopurinol; Arthritis; Biopsy; Dermatitis, Exfoliative; Drug Hypersensitivity; Eosinophilia; Eosinophils; Female; Gout; Humans; Liver; Male; Middle Aged; Prednisone; Pruritus; Skin; Time Factors