Treatment of acquired perforant dermatoses with allopurinol / Tratamento de dermatose perfurante adquirida com alopurinol

Perforating dermatoses are papulonodular cutaneous pathologies characterized by transepithelial extrusion of components of the extracellular matrix of the dermis, by inflammation or degeneration. When secondary, the systemic diseases are called Acquired Perforating Diseases. Our letter aims to report a case of acquired perforating dermatoses secondary to chronic renal dialysis. The treatment with Allopurinol proved to be effective in this case. Allopurinol would act as an antioxidant, reducing the inflammatory reaction in tissues and consequent damage to the collagen fibers (AU)

Dermatoses perfurantes são patologias cutâneas papulonodulares que se caracterizam pela extrusão transepitelial de componentes da matriz extracelular da derme, por inflamação ou degeneração. Quando são secundárias as doenças sistêmicas são chamadas Doenças Perfurantes Adquiridas. Nossa carta tem como objetivo relatar caso de dermatose perfurante adquirida secundária a insuficiência renal crônica dialítica. O tratamento com Alopurinol se mostrou eficaz neste caso. O Alopurinol atuaria como antioxidante, reduzindo a reação inflamatória nos tecidos e consequentes danos nas fibras colágenas (AU)

Antihyperuricemic activity of polar fractions of Pili (Canarium ovatum) leaves

Background@#One of the causes of inflammatory arthritis is excessive production of uric acid or hyperuricemia. It is a painful disease that is treated with a commercial xanthine oxidase inhibitor to decrease uric acid synthesis. However, the treatment is associated with adverse side effects and thus, there is interest in medicinal plants that could have similar therapeutic effects with minimal side effects. There are many reported indigenous plants and trees in the Philippines that are reported to have therapeutic and bioactive compounds. One such plant is Canarium ovatum or locally called pili. This study aimed to determine the antihyperuricemic activity of the ethanolic extract of the leaves of C. ovatum. @*Objective@#Determine the antihyperuricemic activity of the crude ethanolic extract of C. ovatum leaves and its partially purified fractions through inhibition of xanthine oxidase and its effect on the blood uric acid level of oxonate-induced hyperuricemic mice. @*Methodology@#The crude ethanol extract from C. ovatum leaves and its partially purified fractions obtained through column chromatography were tested for their in vitro xanthine oxidase (XO) inhibitory activity by measuring spectrophotometrically the uric acid formation from xanthine as the substrate. The crude ethanol extract and the fraction with the most XO inhibitory activity were then tested for their in vivo XO inhibitory activity in oxonate-induced hyperuricemic mice by measuring their blood uric acid levels using uric acid test strips. @*Results@#The crude ethanolic extract of C. ovatum leaves at 100ppm showed 83.62±2.05% in vitro inhibition of XO while the most active fraction showed 80.30±4.00% inhibition. Both were comparable (p>0.05) to the positive control, allopurinol, which showed 91.47±5.64% inhibition. In vivo, the crude extract and the fraction that showed the highest XO inhibitory activity at 200 mg/kg significantly (p<0.01 and p<0.05) respectively reduced the serum uric acid levels of the hyperuricemic mice one hour after induction as compared to the negative control. Moreover, their antihyperuricemic activity were not statistically significant as compared to that of allopurinol (p<0.0001). @*Conclusion@#The crude ethanolic extract of C. ovatum leaves and its most active fraction showed statistically significant in vitro xanthine oxidase inhibition and in vivo antihyperuricemic activity. The activities shown by both crude and active fraction were not statistically different from that determined for allopurinol. Therefore, further studies can be conducted to isolate the most active compound and study its pharmacokinetic properties.

Síndrome DRESS secundária ao uso de alopurinol: um relato de caso / DRESS syndrome secondary to the use of allopurinol: a case report

A Síndrome de DRESS (do inglês, Drug Rash with Eosinophilia and Systemic Symptoms) é uma patologia rara que consiste em uma severa reação medicamentosa mediada por células T. O presente relato de caso retrata uma paciente do sexo feminino, 59 anos, que apresentou icterícia, febre não termometrada, acolia, colúria, mialgia, placas hipercrômicas e lesões pruriginosas. Referiu uso recente de alopurinol, paracetamol e nimesulida, apresentando melhora importante e espontânea após a suspensão das medicações. A extensão do tempo de exposição ao medicamento agressor ocasiona um maior período de internação e risco de mortalidade. Além disso, os dados restritos sobre a Síndrome de DRESS impõe desafios ao seu diagnóstico. Sendo assim, este estudo busca destacar a importância do diagnóstico clínico precoce, a suspensão do medicamento agressor e a instituição da terapêutica adequada para um prognóstico favorável

The Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) Syndrome is a rare pathology that consists of a severe drug reaction mediated by T cells. The present case report depicts a female patient, 59 years old, who presented jaundice, non thermometered fever, acholia, choluria, myalgia, hyperchromic plaques and pruritic lesions. She mentioned recent use of allopurinol, paracetamol and nimesulide, showing significant and spontaneous improvement after discontinuation of medications. The extension of time of exposure to the offending drug causes a longer period of hospitalization and risk of mortality. In addition, the restricted data on DRESS Syndrome poses challenges to its diagnosis. Therefore, this study seeks to highlight the importance of early clinical diagnosis, suspension of the offending drug and the institution of appropriate therapy for a favorable prognosis

Síndrome Dress relacionada ao uso de Alopurinol: relato de caso / Dress Syndrome related to the use of allopurinol: case report

A síndrome DRESS é uma reação adversa a medicamentos pouco conhecida dentro da prática clínica, porém com grande potencial de letalidade devido a combinação de manifestações cutâneas e envolvimento de múltiplos órgãos. Objetivo: identificar possíveis reações adversas graves e incomuns secundárias ao uso de medicações usadas frequentemente na prática clínica. Métodos: Trata-se de um relato de caso construído com base em levantamento de dados do prontuário do paciente e análise a partir de um referencial teórico para comprovação de sua relevância na prática clínica. Resultado: Enfatizou-se a importância de um reconhecimento precoce dessa condição, a fim de evitar desfechos graves

The DRESS syndrome is an adverse drug reaction that is unsual in clinical practice, but with a high potential for lethality, due to the combination of cutaneous manifestations and involvement of multiple organs. Objective: identify possible serious and unusual adverse reactions secondary to the use of medications frequently used in clinical practice. Methods: This is a case report built on the basis of data collection from the patient's medical record and analysis from a theoretical framework to prove its source in clinical practice. Outcome: The importance of early recognition of this condition was emphasized, in order to avoid serious outcomes

Brief topical and intraluminal use of Carolina rinse solution does not attenuate experimental ischemia and reperfusion injury in rabbit jejunum / [O uso tópico breve e intraluminal da solução de Carolina rinse não atenua a injúria de isquemia e reperfusão experimental no jejuno de coelhos ]

Fifteen New Zealand adult rabbits were randomly allocated into three groups: Sham-operated (group A), Ischemia and Reperfusion (group B) and Carolina Rinse Solution (CRS) (group C). Groups B and C were subjected to one hour of ischemia and two hours of reperfusion. In group C, ten minutes before reperfusion, the bowel lumen was filled with CRS, and the segment immersed in CRS. Necrosis and loss of integrity of the villi were visible in groups B and C. Edema of the submucosa and circular muscle was observed in all groups. Hemorrhage was observed in different layers for groups B and C, but group C showed more severe hemorrhage in different layers during reperfusion. All groups showed polymorphonuclear leukocyte infiltration on the base of the mucosa, submucosa, and longitudinal muscle, in addition to polymorphonuclear leukocytes margination in the mucosal and submucosal vessels. Necrosis of enterocytes, muscles, crypts of Lieberkühn and myenteric plexus was observed in groups B and C during reperfusion. Topical and intraluminal Carolina Rinse Solution did not attenuate the effects of ischemia and reperfusion in the small intestine of rabbits.(AU)

Quinze coelhos da raça Nova Zelândia foram alocados em três grupos: instrumentado (grupo A), isquemia e reperfusão (grupo B) e solução de Carolina rinse (CRS) (grupo C). Os grupos B e C foram submetidos a uma hora de isquemia e a duas horas de reperfusão. No grupo C, 10 minutos antes da reperfusão, o segmento isolado foi imerso e teve seu lúmen preenchido com CRS. Os grupos B e C apresentaram necrose e perda progressiva da integridade das vilosidades. Foi observado edema na submucosa e na camada muscular circular em todos os grupos. Nos grupos B e C, foi observada hemorragia em diferentes camadas, mas, no grupo C, a hemorragia foi mais intensa durante a reperfusão. Todos os grupos apresentaram infiltrado de PMN na base da mucosa, na submucosa e na camada muscular longitudinal e marginação de PMN nos vasos da mucosa e da submucosa. Durante a reperfusão, foi observada necrose dos enterócitos, das camadas musculares, das criptas de Lieberkühn e do plexo mioentérico nos grupos B e C. O uso tópico e intraluminal de CRS não atenuou os efeitos da isquemia e da reperfusão no intestino delgado de coelhos.(AU)

Síndrome de DRESS secundario a alopurinol / DRESS syndrome secondary to allopurinol

RESUMEN El síndrome de hipersensibilidad por fármacos, también conocido como síndrome de DRESS, es una farmacodermia grave que se caracteriza por una erupción polimorfa diseminada, fiebre y compromiso multiorgánico. Este padecimiento tiene una incidencia que oscila entre el 0,1 % y el 0,01 % de las exposiciones farmacológicas, con una probabilidad de fallecimiento de un 20 % al 30 %. Fue descrito por primera vez en el año 1936, como una reacción adversa a la fenitoína. En la actualidad se reconoce que puede estar asociado a otros fármacos como: abacavir, metronidazol, doxiciclina, isoniazida, carbamacepina, fenobarbital, beta-bloqueadores, dapsona, ranitidina, antiinflamatorios no esteroideos y el alopurinol. Se presenta un paciente de 69 años de edad que desarrolló un síndrome de DRESS secundario a alopurinol. El paciente mostró signos poco frecuentes de esta rara enfermedad: linfocitos atípicos, hepatomegalia y afección renal; falleció poco después debido a un choque séptico por estafilococo áureo.

ABSTRACT Drug hypersensitivity syndrome, also known as DRESS syndrome, is a severe pharmacodermia characterized by a polymorphous disseminated rash, fever, and multi-organ involvement. Its incidence ranges between 0.1 to 0.01% from the pharmacological exposures, with a probability of death ranging from 20 to 30%. It was first described in 1936 as an adverse reaction to phenytoin. Nowadays, it is known that it can also be associated with other drugs such as abacavir, metronidazole, doxycycline, isoniazid, carbamazepine, phenobarbital, beta-blockers, dapsone, ranitidine, nonsteroidal anti-inflammatory drugs and allopurinol. We present a 69-year-old male patient who developed a DRESS syndrome secondary to alupurinol. The patient showed unusual signs of this rare disease such as atypical lymphocytes, hepatomegaly and kidney disease; he dies shortly after from a septic shock due to Staphylococcus aureus.

Comparative study between fructose 1-6 bisphosphate and histidine-tryptophan-ketoglutarate in liver preservation in rats submitted to total cold ischemia

Abstract Purpose To compare Fructose-1,6-Bisphosphate (FBP) to Histidine-Tryptophan-Ketoglutarate (HTK) in liver preservation at cold ischemia. Methods Male rats (Sprague-Dawley: 280-340g) divided into three groups (n=7): Control; Fructose-1,6-bisphosphate (FBP); Histidine-Tryptophan-Ketoglutarate (HTK). Animals underwent laparotomy-thoracotomy for perfusion of livers with saline. Livers were removed and deposited into solutions. Mitochondria were isolated to determine State 3 (S3), State 4 (S4), Respiratory Control Ratio (RCR) and Swelling (S). Liver enzymes (AST, ALT, LDH) were determined in solution. At tissue, Malondialdehyde (MDA) and Nitrate (NOx) were determined. All parameters were analyzed at 0.6 and 24 hours of hypothermic preservation. Statistics analysis were made by Mann-Whitney test (p<0.05). Results Regarding ALT, there was a difference between FBP-6h/HTK-6h, lower in HTK. Regarding AST, there was a significant difference between FBP-24h/HTK-24h, lower in FBP. Regarding NOx, there was a difference between 0h and 6h, as well as 0h and 24h for both solutions. Regarding S3, there was a significant difference in 24h compared to Control-0h for both solutions, and a significant difference between FBP-6h/FBP-24h. Regarding S4, there was a difference between Control-0h/HTK-24h and FBP-24h/HTK-24h, higher in HTK. There was a difference between Control-0h/FBP-24h for Swelling, higher in FBP. Conclusion Fructose-1,6-Bisphosphate showed better performance at nitrate and aspartate aminotransferase compared to histidine-tryptophan-ketoglutarate.

A Case of Cutaneous Leukocytoclastic Vasculitis Associated with Granulocyte Colony-Stimulating Factor: An Unusual Presentation

Drug-induced vasculitis is an inflammation of small-sized blood vessel caused by the use of drugs. It accounts for approximately 10% of acute cutaneous vasculitis. Propylthiouracil, hydralazine, and allopurinol have been widely known as causative agents. The most common clinical feature of drug-induced vasculitis is palpable purpura on lower extremities. A 66-year-old Korean female presented with erythematous nodules on upper chest and back. She had been on medication for multiple myeloma. Laboratory results showed neutropenia. After a single injection of filgrastim (recombinant granulocyte colony-stimulating factor), she developed cutaneous lesions with concurrent increase in absolute neutrophil count. A skin biopsy revealed leukocytoclastic vasculitis. After discontinuation of filgrastim injection, her skin lesions disappeared spontaneously.

Altered T cell and monocyte subsets in prolonged immune reconstitution inflammatory syndrome related with DRESS (drug reaction with eosinophilia and systemic symptoms)

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe cutaneous adverse reaction involving various internal organs. Flare-ups after recovery from the initial presentation of DRESS are caused by relapse of drug-induced T-cell-mediated reactions. However, the specific underlying mechanism is unclear. Here, we report a case of a 60-year-old man with allopurinol-induced DRESS who suffered recurrent episodes of generalized rash with eosinophilia, which mimicked immune reconstitution inflammatory syndrome. Analysis of immunological profiles revealed that the percentages of T lymphocytes and regulatory T cells in the patient with DRESS were higher than those in healthy controls. In addition, there was a notable change in the subtype of monocytes in the patient with DRESS; the percentage of nonclassical monocytes increased, whereas that of classical monocytes decreased. Upon viral infection, nonclassical monocytes exhibited strong pro-inflammatory properties that skewed the immune response toward a Th2 profile, which was associated with persistent flare-ups of DRESS. Taken together, the results increase our understanding of the pathogenesis of DRESS as they suggest that expansion of nonclassical monocytes and Th2 cells drives disease pathogenesis.

Drug hypersensitivity reactions in Asia: regional issues and challenges

There are geographical, regional, and ethnic differences in the phenotypes and endotypes of patients with drug hypersensitivity reactions (DHRs) in different parts of the world. In Asia, aspects of drug hypersensitivity of regional importance include IgE-mediated allergies and T-cell-mediated reactions, including severe cutaneous adverse reactions (SCARs), to beta-lactam antibiotics, antituberculous drugs, nonsteroidal anti-inflammatory drugs (NSAIDs) and radiocontrast agents. Delabeling of low-risk penicillin allergy using direct oral provocation tests without skin tests have been found to be useful where the drug plausibility of the index reaction is low. Genetic risk associations of relevance to Asia include human leucocyte antigen (HLA)-B*1502 with carbamazepine SCAR, and HLA-B*5801 with allopurinol SCAR in some Asian ethnic groups. There remains a lack of safe and accurate diagnostic tests for antituberculous drug allergy, other than relatively high-risk desensitization regimes to first-line antituberculous therapy. NSAID hypersensitivity is common among both adults and children in Asia, with regional differences in phenotype especially among adults. Low dose aspirin desensitization is an important therapeutic modality in individuals with cross-reactive NSAID hypersensitivity and coronary artery disease following percutaneous coronary intervention. Skin testing allows patients with radiocontrast media hypersensitivity to confirm the suspected agent and test for alternatives, especially when contrasted scans are needed for future monitoring of disease relapse or progression, especially cancers.

A case of toxic epidermal necrolysis induced by cytomegalovirus infection followed by DRESS (drug reaction with eosinophilia and systemic symptoms)

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions. Although viral reactivation is associated with DRESS syndrome, its role in TEN remains unclear. An 80-year-old woman visited our hospital because of fever and skin eruption. DRESS syndrome was diagnosed and was thought to caused by the use of the drug allopurinol. She was treated by discontinuation of the drug and administration of systemic steroids. She recovered from DRESS syndrome and was discharged from the hospital with tapering doses of steroids prescribed. One week after discharge, she visited our hospital again as the skin rash recurred and oral pain as well as oral and ocular mucosal lesions developed. In addition to the skin rash, blisters and Nikolsky's sign that were different from the skin lesions present in the previous DRESS syndrome were observed. Unlike those in DRESS syndrome, the viral serological test results were positive for anti-cytomegalovirus (CMV) IgM and CMV polymerase chain reaction. Therefore, it was thought that TEN was due to reactivation of CMV and she was treated this with ganciclovir and intravenous immunoglobulin. Here, we report a case of TEN caused by viral reactivation after DRESS syndrome developed after use of allopurinol which recovered after steroid treatment.

The effect of graft application and allopurinol treatment on calvarial bone defect in rats

Abstract Purpose: To investigate the effects of allopurinol administration on osteoinductive reaction and bone development with graft material. Methods: Thirty-six Wistar albino rats were divided into 3 groups. In the control group, calvarial bone defect was only created without any treatment. In the Defect + Graft group, allograft treatment was performed by forming 8 mm calvarial bone defect. In the Defect + Graft + Allopurinol group, alloplastic bone graft was placed in the calvarial bone defect and then, allopurinol (50 mg/kg/day) treatment was intraperitoneally applied for 28 days. Results: Histopathological examination revealed inflammation, congestion in the vessels, and an increase in osteoclast cells in the defect area. We also observed that new osteocyte cells, increase in connective tissue fibers, and new bone trabeculae. Osteopontin expression was positive in osteoblast cells and lacunated osteocyte cells were located in the periphery of the new bone trabeculae. Osteopontin expression was also positive in osteoblasts and osteocytes cells of new bone trabeculae in the graft site. Conclusion: It has been shown that allopurinol treatment in rat calvaria defects may induce osteoblastic activity, matrix development, mature bone cell formation and new bone formation when used with autogenous grafts.

Benzbromarone in the treatment of gout

Abstract Background Benzbromarone is a uricosuric drug that has been used in the treatment of gout over the last 30 years. Due to its potent inhibition of the dominant apical (luminal) urate exchanger in the human proximal tubule URAT1, it reduces the urate reabsorption, diminishing serum urate levels and therefore preventing gout flares. Main body of the abstract Through several clinical trials, Benzbromarone has been proved effective and safe, inclusive in patients with chronic kidney disease and as combination therapy with allopurinol. Due to hepatotoxicity reports, it was withdrawn from the European market by the manufacturer, however many authors have questioned the product's withdrawal due to a lack of clinical evidence in order to support its hepatotoxicity. Benzbromarone is still available in several European countries, New Zealand, Brazil and several other countries. Despite the product's marketing over more than 20 years after the first hepatotoxicity reports, we have found only five reports in our literature search, and no prospective or retrospective study correlating hepatotoxicity with benzbromarone use. Short conclusion Benzbromarone is a safe and effective molecule for the treatment of gout. However, due to in vitro and in vivo data related to hepatotoxicity, it is prudent to prescribe it with some caution, especially for patients with an already known liver condition.

Severe Cutaneous Adverse Reactions: A Single-Center Retrospective Study of 173 Patients in China

BACKGROUND: Severe cutaneous adverse reactions (SCAR) to drugs are a crucial public health issue and the use of systemic corticosteroids in SCAR has been controversial. OBJECTIVE: To analyze clinical features, causative drugs, treatment, outcomes, and prognostic factors of SCAR in the case-series of 173 patients, and add more information to the debate of using systemic corticosteroids in SCAR management. METHODS: A retrospective study of 173 SCAR patients diagnosed with drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) or acute generalized exanthematous pustulosis (AGEP) at a tertiary care institution in China between January 2014 and December 2017 was conducted. RESULTS: Of 173 patients, allopurinol, carbamazepine, and antibiotics are the most frequently implicated drugs for DRESS (40.4%), SJS/TEN (26.0%), and AGEP (40.0%) respectively. Moreover, there is a strongly negative correlation between early corticosteroids use and the progression (p=0.000) and severity (p=0.01) of skin lesions. However, there is no association between early corticosteroids use and the mortality of SCAR (odds ratio: 1.01, 95% confidence interval: 0.95~1.08). In addition, lymphadenopathy, eosinophilia, and interval from onset to corticosteroids treatment were correlated with SCAR prognosis. CONCLUSION: Prompt short-course systemic corticosteroids use is associated with early-stage skin lesions remission without influencing the disease mortality. Lymphadenopathy and eosinophilia were the independent poor prognostic factors of SCAR.

Analysis of Individual Case Safety Reports of Severe Cutaneous Adverse Reactions in Korea

PURPOSE: Despite morbidities and fatalities, nationwide epidemiologic data for severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS), are not widely available. We aimed to investigate SCAR epidemiology over the last two decades in Korea. MATERIALS AND METHODS: We analyzed individual case safety reports (ICSRs) of SCARs in the Korea Adverse Event Reporting System from 1988 to 2013. Administered drugs, demographic profiles, and causality assessment according to the World Health Organization-Uppsala Monitoring Center system were analyzed. RESULTS: A total of 755 SCAR cases (508 SJS/TEN, 247 DRESS) were reported. The number of SCAR ICSRs has been increasing with increasing ICSRs for overall adverse drug events. Since 2010, the number of SCAR ICSRs has increased up to 100 cases/year. Allopurinol was the most common causative drug (SJS/TEN: 10.2%; DRESS: 11.3%; SCAR ICSRs: 10.6%), followed by carbamazepine (SJS/TEN: 8.7%; DRESS: 9.7%; SCAR ICSRs: 8.6%). Regarding drug groups, antiepileptics (19.5%) and antibiotics for systemic use (12.7%) were common causative drug groups. Twenty SCAR-related deaths were recorded. Antibacterials were the most common causes of deaths (8 cases), followed by antiepileptics (5 cases). The potential risk of SCARs was not specified in the drug information leaflet for 40.2% of drugs causing SJS/TEN and 82.5% causing DRESS syndrome in Korea. CONCLUSION: The number of SCAR ICSRs has increased rapidly with recent active pharmacovigilance programs in Korea. Allopurinol and antiepileptics are the most common individual and categorical causative agents, respectively.

Ocular manifestations of leishmaniasis in a cat: first case report from Brazil / Manifestações oculares da leishmaniose em um gato: primeiro relato de caso do Brasil

An 8-year-old domestic short hair female cat initially presented with bilateral uveitis with pseudotumoral appearance. The patient tested negative for feline immunodeficiency virus (FIV), feline leukemia virus (FeLV) and Toxoplasma gondii. Histopathology of a granulomatous lesion on the upper left conjunctiva revealed amastigotes compatible with Leishmania spp. Aqueous humor was aspired and the diagnosis was confirmed after isolation of promastigotes cultivated in biphasic NNN medium and by positive polymerase chain reaction (PCR) for Leishmania infantum. Treatment with allopurinol (10mg/kg/ BID/PO) was commenced and a natural insect repellent was prescribed. Six months of treatment with allopurinol associated with the initial topical medications helped to improve ocular signs. Leishmaniasis should be considered as a differential diagnosis in cats presenting uveitis with pseudotumoral appearance. To our knowledge, this is the first report of feline leishmaniasis with ocular manifestation in Brazil, in which diagnosis was confirmed by aqueous humor analysis.(AU)

Uma gata, sem raça definida, de oito anos de idade, foi atendida inicialmente com uveíte bilateral, com aparência pseudotumoral em íris. Foi realizado teste para o vírus da imunodeficiência felina (FIV), da leucemia felina (FeLV) e de Toxoplasma gondii, obtendo-se resultados negativos. O exame histopatológico da conjuntiva superior do olho esquerdo revelou amastigotas compatíveis com Leishmania spp. Foi realizada paracentese, e promastigotas foram isoladas no humor aquoso, cultivadas em meio NNN bifásica. Reação em cadeia da polimerase (PCR) confirmou diagnóstico positivo para Leishmania infantum. Tratamento com alopurinol (10mg/kg/BID/PO) foi iniciado, e um repelente natural de insetos foi prescrito. Seis meses de tratamento com alopurinol associado aos medicamentos tópicos iniciais ajudaram a melhorar os sinais oculares. Leishmaniose deve ser considerada como um diagnóstico diferencial nos gatos que apresentam uveíte com aparência pseudotumoral de íris. Até o presente momento, este é o primeiro relato de leishmaniose felina com manifestação exclusivamente ocular da doença no Brasil cujo diagnóstico foi confirmado por meio de análise de humor aquoso.(AU)

Genetic markers of severe cutaneous adverse reactions

Adverse drug reactions can cause considerable discomfort. They can be life-threatening in severe cases, requiring or prolonging hospitalization, impeding proper treatment, and increasing treatment costs considerably. Although the incidence of severe cutaneous adverse reactions (SCARs) is low, they can be serious, have permanent sequelae, or lead to death. A recent pharmacogenomic study confirmed that genetic factors can predispose an individual to SCARs. Genetic markers enable not only elucidation of the pathogenesis of SCARs, but also screening of susceptible subjects. The human leukocyte antigen (HLA) genotypes associated with SCARs include HLA-B*57:01 for abacavir (Caucasians), HLA-B*58:01 for allopurinol (Asians), HLA-B*15:02 (Han Chinese) and HLA-A*31:01 (Europeans and Koreans) for carbamazepine, HLA-B*59:01 for methazolamide (Koreans and Japanese), and HLA-B*13:01 for dapsone (Asians). Therefore, prescreening genetic testing could prevent severe drug hypersensitivity reactions. Large-scale epidemiologic studies are required to demonstrate the usefulness and cost-effectiveness of screening tests because their efficacy is affected by the genetic differences among ethnicities.

HLA DRB1*04:03 and Drug Reaction with Eosinophilia and Systemic Symptoms Induced by Oxcarbazepine: A Case Report / 대한소아신경학회지

Drug reaction with eosinophilia and systemic symptoms(DRESS), which occurs 2–8 weeks after taking a medication is a rare and potentially life-threatening drug-induced hypersensitivity reaction, which includes skin eruption, hematologic abnormalities, lymphadenopathy, and internal organ such as liver, lung, kidney involvement. Antiepileptic agents (e.g., carbamazepine, lamotrigine, phenytoin, and phenobarbital) and allopurinol are the most commonly reported causes. However, new antiepileptic agents, such as oxcarbazepine, rarely cause drug reaction with eosinophilia and systemic symptoms. A 11-year-old boy who was administered oxcarbazepine for 34 days developed widespread rashes, facial edema, fever, cough, nasal stuffiness, tonsillitis, and cervical lymphadenopathy. Laboratory test results showed leukocytosis, eosinophilia, thrombocytosis, elevated c-reactive protein, and elevated liver transaminase levels. As we suspected drug reaction with eosinophilia and systemic symptoms, we immediately withdrew oxcarbazepine and commenced corticosteroid therapy. The patient's skin lesions and abnormal laboratory results slowly improved. Before change the antiepileptic agents, we performed human leukocyte antigen (HLA) typing to assess the genetic risk factors of the drug reaction and the result was positive for HLA DRB1*04:03 known to cause severe acute drug hypersensitivity, such as Stevens-Johnson syndrome by oxcarbazepine in Koreans. We have presented the first report of drug reaction with eosinophilia and systemic symptoms associated with oxcarbazepine in a patient with HLA DRB1*04:03. Although DRESS by oxcarazepine is extremely rare and unpredictable, when suspected clinical symptoms occur, it is necessary to interrupt the causative drug rapidly and confirming the patient's HLA typing may help to select a safer alternative drug.

Tratamento da Gota na Atenção Primária à Saúde / Treatment of Gout in the Primary Health Care / Tratamiento de la Gota en la Atención Primaria de la Salud

Objetivo: O objetivo desta revisão é fornecer informação atualizada e orientações práticas sobre a abordagem da gota na Atenção Primária à Saúde. Métodos: Foram pesquisadas normas de orientação clínica, revisões sistemáticas, meta-análises e estudos originais publicados entre 1 janeiro de 2011 e 31 dezembro de 2016, nas línguas inglesa, portuguesa e espanhola. Resultados: Os fármacos de primeira linha no tratamento da gota aguda são os anti-inflamatórios não esteroides, a colchicina e os corticoides, em monoterapia ou associação. Na gota crônica são usados hipouricemiantes, sendo a primeira linha o alopurinol. O febuxostate e os uricosúricos são alternativas ao alopurinol em casos de intolerância ou ineficácia. A profilaxia das crises de gota agudas está recomendada quando se inicia o tratamento hipouricemiante durante pelo menos 6 meses. Conclusão: A abordagem correta da gota deve fazer parte das competências de um médico especialista em Atenção Primária à Saúde de modo a prestar cuidados adequados à comunidade.

Objective: The objective of this review is to provide updated information and practical guidelines on the approach of gout in Primary Health Care. Methods: We conducted a survey of clinical guidelines, systematic reviews, meta-analyses and original studies published between January 1, 2011 and December 31, 2016 in the English, Portuguese and Spanish languages. Results: First-line drugs in the treatment of acute gout are non-steroidal anti-inflammatory drugs, colchicine and corticosteroids, in monotherapy or combination. In chronic gout, the first-line of hypouricemic therapy is allopurinol. Febuxostat and uricosurics are alternatives to allopurinol in cases of intolerance or ineffectiveness. The prophylaxis of acute attacks is recommended when starting hypouricemic treatment for at least 6 months. Treatment of asymptomatic hyperuricemia is not recommended. Conclusion: The correct approach to gout should be part of the skills of a Primary Care physician in order to provide adequate care to the community.

Objetivo: El objetivo es proporcionar información actualizada y orientación práctica sobre la terapéutica de la gota en la Atención Primaria de Salud. Métodos: Se estudiaron las guías clínicas, revisiones sistemáticas, meta-análisis y estudios originales publicados entre el 1 de enero de 2011 y el 31 de diciembre de 2016, en el inglés, portugués y español. Resultados: Los fármacos de primera línea en el tratamiento de la gota aguda son anti-inflamatorios no-esteroides, la colchicina y los corticosteroides, solos o en combinación. En la gota crónica son utilizados hipouricemiantes, y el alopurinol es lo fármaco de primera línea. Febuxostat y uricosúricos son alternativas al alopurinol en los casos de intolerancia o ineficacia. Se recomienda la profilaxis de las crisis agudas en el tratamiento hipouricemiante durante al menos 6 meses. No se recomienda el tratamiento de la hiperuricemia asintomática. Conclusión: La terapéutica de la gota debe formar parte de las competencias de un médico especialista en Atención Primaria de Salud a fin de proporcionar la atención adecuada a la comunidad.