Oral Allopurinol Research Articles

Comparison of Intralesional Meglumine Antimoniate Plus Oral Allopurinol with Intralesional Meglumine Antimoniate Alone for the Treatment of Cutaneous Leishmaniasis- A Prospective Study

Objective: To evaluate the efficacy of the combination of oral allopurinol plus intralesional meglumine for thetreatment of Cutaneous Leishmaniasis.Study Design: A prospective study.Place and Duration of Study: The study was carried out at the Department of Dermatology, Combined MilitaryHospital, Multan, Pakistan from 18th September 2021 to 18th March 2022.Methods: The study was conducted on a total of 60 patients (30 in each group) who fulfilled the inclusioncriteria. Patients in group A were given oral allopurinol (15mg/kg/day) and intralesional meglumineantimoniate (2-5 ml). Patients in group B were given intralesional meglumine antimoniate (2-5 ml). All patientswere given 2 injections each week and were followed up for 8 weeks. The efficacy of the treatment was noted bythe disappearance of induration of the lesion and complete reepithelization of the ulcer. Healing wascharacterized by scar formation and was recorded.Results: Results showed that the cure rate in Group B was 16.6% (5), while in Group A it was 56.6% (17) (P<0.03).There was no significant difference in efficacy between both groups when stratified based on age, number oflesions per patient, and lesion location. However, the cure rate of ulcers and papules was significantly higher ingroup A compared to group B.Conclusion: It was concluded that the combination of intralesional meglumine antimoniate and oral allopurinolhas higher efficacy than intralesional meglumine antimoniate alone in the treatment of patients withcutaneous leishmaniasis. How to cite this: Qayyum N, Gul P, Zainab A, Jawaid M, Azam M, Sattar S. Comparison of Intralesional Meglumine Antimoniate Plus Oral Allopurinol with Intralesional Meglumine Antimoniate Alone for the Treatment of Cutaneous Leishmaniasis- A Prospective Study. 2024; 5(2): 181-186. doi: http://doi.org/10.37185/LnS.1.1.511

Treatment of Cutaneous Leishmaniasis with Allopurinol Plus Itraconazole in Iran.

Cutaneous leishmaniasis (CL) is a serious tropical disease and a neglected health challenge in Iran. Although limited data are available regarding anthroponotic CL, cases resistant to meglumine antimoniate (Glucantime) are increasingly being reported. Via an open-label noncontrolled case series, allopurinol (10 mg/kg/day) plus itraconazole (3-4 mg/kg/day) were orally administered for 1 month to 27 patients (56 lesions) with anthroponotic CL, most of whom were resistant to Glucantime. A mean lesion size of 3.5 ± 1.9 cm at baseline was reduced to 0.6 ± 1.0 after 1 month of treatment. Excellent treatment response was observed in 85.7% of lesions after 1 month. Recurrence only occurred in one patient in the 3-month follow-up session. This study presents preliminary evidence that oral allopurinol plus itraconazole could be an effective treatment in patients with anthroponotic CL.

Granulomatous tattoo reaction treated with topical allopurinol.

Granulomatous reactions to tattoo ink have been frequently associated with exogenous pigment, although sometimes they are the manifestation of a cutaneous or an underlying systemic sarcoidosis. We report a case of a granulomatous reaction to a black tattoo pigment treated with 3% topical allopurinol for three months. We observed complete resolution without any side effects. Complementary examinations and follow-up ruled out sarcoidosis. Oral allopurinol has been proven to be effective for the management of granulomatous reactions to tattoos. Based on the significant improvement we have described in our patient, we recommend new studies to reveal all the potential benefits of the topical use of allopurinol for the treatment of granulomatous reactions to tattoo ink.

Senescent CD4+CD28null cells are increased in chronic hyperuricemia, show aberrant effector phenotypes, and are reversed after allopurinol therapy: a proof-of-concept pilot study.

To characterize CD4+CD28null cells in chronic hyperuricemia and investigate whether allopurinol could restore CD28 expression and the balance of T helper phenotypes. Asymptomatic individuals with chronic hyperuricemia and ultrasonographic findings evocative of urate deposition in the joints. Age- and gender-matched normouricemic individuals were also studied. Oral allopurinol at 150mg/day for 4weeks, followed by 300mg/day through week 12. Color-flow cytometry on peripheral blood mononuclear cells (PBMC) with antibodies against CD4, CD28, T-bet (Th1), GATA-3 (Th2), and RORγt (Th17). Six patients (five men, median age of 53years) and seven controls were studied. At baseline, hyperuricemic patients had more CD4+CD28null/CD4+ cells than normouricemic subjects (36.8% vs. 6.1%; p = 0.001), with a predominance of T-bet+ cells (98.5% vs. 6.6%; p = 0.001) and few RORγt+ cells (0.7% vs. 89.4%; p = 0.014). In hyperuricemic patients, the number of CD4+ cells/10,000 PBMC was similar before and after allopurinol (3378 vs. 3954; p = 0.843). Conversely, CD4+CD28null cells decreased from 36.8% (23.0-43.7) to 15.8% (4.7-28.1; p = 0.031). CD4+CD28nullT-bet+ cells decreased from 98.5% (95.0-99.4) to 88.3% (75.2-98.9; p = 0.062), CD4+CD28nullGATA-3+ cells increased from 0% (0-4.0) to 2.8% (0.1-15.6; p = 0.156), and CD4+CD28nullRORγt+ cells increased from 0.7% (0.4-7.0) to 4.5% (1.3-28.1; p = 0.031). The CD4+CD28null cell subset is abnormally expanded in chronic hyperuricemia, despite the absence of overt urate-related disease. Allopurinol may partially restore CD28 expression on CD4+ cells while enhancing the homeostatic balance of T helper phenotypes. ClinicalTrials.gov, number NCT04012294.

Xanthine oxidase inhibition and white matter hyperintensity progression following ischaemic stroke and transient ischaemic attack (XILO-FIST): a multicentre, double-blinded, randomised, placebo-controlled trial.

People who experience an ischaemic stroke are at risk of recurrent vascular events, progression of cerebrovascular disease, and cognitive decline. We assessed whether allopurinol, a xanthine oxidase inhibitor, reduced white matter hyperintensity (WMH) progression and blood pressure (BP) following ischaemic stroke or transient ischaemic attack (TIA). In this multicentre, prospective, randomised, double-blinded, placebo-controlled trial conducted in 22 stroke units in the United Kingdom, we randomly assigned participants within 30-days of ischaemic stroke or TIA to receive oral allopurinol 300mg twice daily or placebo for 104 weeks. All participants had brain MRI performed at baseline and week 104 and ambulatory blood pressure monitoring at baseline, week 4 and week 104. The primary outcome was the WMH Rotterdam Progression Score (RPS) at week 104. Analyses were by intention to treat. Participants who received at least one dose of allopurinol or placebo were included in the safety analysis. This trial is registered with ClinicalTrials.gov, NCT02122718. Between 25th May 2015 and the 29th November 2018, 464 participants were enrolled (232 per group). A total of 372 (189 with placebo and 183 with allopurinol) attended for week 104 MRI and were included in analysis of the primary outcome. The RPS at week 104 was 1.3 (SD 1.8) with allopurinol and 1.5 (SD 1.9) with placebo (between group difference-0.17, 95% CI-0.52 to 0.17, p=0.33). Serious adverse events were reported in 73 (32%) participants with allopurinol and in 64 (28%) with placebo. There was one potentially treatment related death in the allopurinol group. Allopurinol use did not reduce WMH progression in people with recent ischaemic stroke or TIA and is unlikely to reduce the risk of stroke in unselected people. The British Heart Foundation and the UK Stroke Association.

Allopurinol versus usual care in UK patients with ischaemic heart disease (ALL-HEART): a multicentre, prospective, randomised, open-label, blinded-endpoint trial

Allopurinol is a urate-lowering therapy used to treat patients with gout. Previous studies have shown that allopurinol has positive effects on several cardiovascular parameters. The ALL-HEART study aimed to determine whether allopurinol therapy improves major cardiovascular outcomes in patients with ischaemic heart disease. ALL-HEART was a multicentre, prospective, randomised, open-label, blinded-endpoint trial done in 18 regional centres in England and Scotland, with patients recruited from 424 primary care practices. Eligible patients were aged 60 years or older, with ischaemic heart disease but no history of gout. Participants were randomly assigned (1:1), using a central web-based randomisation system accessed via a web-based application or an interactive voice response system, to receive oral allopurinol up-titrated to a dose of 600 mg daily (300 mg daily in participants with moderate renal impairment at baseline) or to continue usual care. The primary outcome was the composite cardiovascular endpoint of non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death. The hazard ratio (allopurinol vs usual care) in a Cox proportional hazards model was assessed for superiority in a modified intention-to-treat analysis (excluding randomly assigned patients later found to have met one of the exclusion criteria). The safety analysis population included all patients in the modified intention-to-treat usual care group and those who took at least one dose of randomised medication in the allopurinol group. This study is registered with the EU Clinical Trials Register, EudraCT 2013-003559-39, and ISRCTN, ISRCTN32017426. Between Feb 7, 2014, and Oct 2, 2017, 5937 participants were enrolled and then randomly assigned to receive allopurinol or usual care. After exclusion of 216 patients after randomisation, 5721 participants (mean age 72·0 years [SD 6·8], 4321 [75·5%] males, and 5676 [99·2%] white) were included in the modified intention-to-treat population, with 2853 in the allopurinol group and 2868 in the usual care group. Mean follow-up time in the study was 4·8 years (1·5). There was no evidence of a difference between the randomised treatment groups in the rates of the primary endpoint. 314 (11·0%) participants in the allopurinol group (2·47 events per 100 patient-years) and 325 (11·3%) in the usual care group (2·37 events per 100 patient-years) had a primary endpoint (hazard ratio [HR] 1·04 [95% CI 0·89-1·21], p=0·65). 288 (10·1%) participants in the allopurinol group and 303 (10·6%) participants in the usual care group died from any cause (HR 1·02 [95% CI 0·87-1·20], p=0·77). In this large, randomised clinical trial in patients aged 60 years or older with ischaemic heart disease but no history of gout, there was no difference in the primary outcome of non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death between participants randomised to allopurinol therapy and those randomised to usual care. UK National Institute for Health and Care Research.

Allopurinol treatment reduced vascular remodeling and improved vascular functions in monocrotaline-induced pulmonary hypertensive rats

Increased oxidative stress and high uric acid are implicated in the pathogenesis of pulmonary hypertension (PH). This provides opportunity to benefit from drugs like allopurinol which suppresses both contributing factors. Therefore, we aimed to investigate the effects of allopurinol in preventing as well as reversing the pathological changes occurring in monocrotaline (MCT)-induced rat model of PH. Male rats were assigned into three groups based on the follow-up time: 7, 21 and 35 days. Time-matched controls of each group received single injections of MCT (60 mg/kg) intraperitoneally. Test groups consisted of rats who were treated with MCT on day 0 plus oral allopurinol (60 mg/kg) daily for 7 or 21 days. 35-day group received allopurinol for two weeks starting on the 22nd day following MCT injection. At the end of all-time points, rats were killed and basal pulmonary perfusion pressure, Fulton index, pulmonary arterial wall thickness and pulmonary arterial relaxations along with oxidative stress markers (MDA, SOD, XO), NO and uric acid levels were measured in all groups. MCT-injected rats had evidence of raised oxidative stress (high MDA and XO, low SOD levels) which was reversed by allopurinol co-treatment in all-time groups. Marked elevation of uric acid seen in 21- and 35 day-groups was also reversed by allopurinol. Reduced NO levels of 21 and 35 days were unchanged in allopurinol treated groups. Apart from an increase in arterial wall thickening which was maintained in all-time groups, no alterations in other cardiovascular parameters were observed in 7-day group. However, basal lung perfusion pressure and Fulton index significantly increased, while arterial relaxations decreased in 21- and 35-day groups. Co-treatment with allopurinol for 21 days improved these functional alterations, whereas late allopurinol treatment failed to affect them. Our results indicate that early treatment of MCT-induced PH with allopurinol ameliorated the impaired functional characteristics via suppressing the increased oxidative stress and uric acid, while treatment started after progression of the disease had no significant effect.

Clinical Effect of the Guizhi Shaoyao Zhimu Decoction in the Treatment of Hyperuricemia.

Traditional Chinese Medicine (TCM) is a medical system with a distinctive theoretical framework and extensive experience in identification and treatment acquired by the Chinese people in long-term medical practice and life practice. It is a complete, integrated, and complex knowledge system in epistemology. This study is aimed at exploring the clinical effectiveness of TCM called the Guizhi Shaoyao Zhimu Decoction in the treatment of hyperuricemia. A total of 100 patients with hyperuricemia at the Medical College of the Second Clinical College, Shandong, China, from January 2019 to January 2022 are selected as the research subjects and divided into group A and group B according to the random table method, with 50 cases in each group. Group A is treated with oral allopurinol tablets, 100 mg, 2 times a day, and group B is treated with the modified Guizhi Shaoyao Zhimu Decoction based on group A. For observation, serum uric acid (SUA) levels, urinary uric acid (UUA) levels, levels of serum inflammatory response factors (IL-6, CRP, and TNF-α), vascular endothelial function indexes (serum malondialdehyde (MDA) content, nitric oxide (NO) content), an acute attack of gout, and the incidence of adverse reactions are measured. Results show that after 2 w and 4 w of treatment, the levels of blood uric acid in each group gradually decreased compared with those before treatment, and group B is lower than group A (P < 0.05). After treatment, the vascular endothelial function indexes and inflammatory factor levels in each group are significantly improved compared with those before treatment, and the indexes in group B are better than those in group A. There is no significant difference in the incidence of related adverse reactions and acute attack of gout (P > 0.05). This shows that the TCM Guizhi Shaoyao Zhimu Decoction has a significant curative effect in the treatment of patients with hyperuricemia, which is worthy of clinical reference application.

Allopurinol attenuates postoperative pain and modulates the purinergic system in patients undergoing abdominal hysterectomy: a randomized controlled trial.

Allopurinol is a potent inhibitor of the enzyme xanthine oxidase used primarily in the treatment of hyperuricemia and gout. The aim of this study was to compare the analgesic efficacy of preanesthetic allopurinol versus placebo on postoperative pain and anxiety in patients undergoing abdominal hysterectomy. This is a prospective, double-blinded, placebo-controlled, randomized clinical trial. We investigated 54 patients scheduled to undergo elective abdominal hysterectomy. Patients were randomly assigned to receive either oral allopurinol 300mg (n = 27) or placebo (n = 27) the night before and 1h before surgery. Patients were submitted to evaluation of pain and anxiety before the treatment, for 24h postoperatively, 30 and 90days after surgery. Cerebrospinal fluid was collected at the time of the spinal anesthesia to perform the measurement of the central levels of purines. Preoperative administration of allopurinol was effective in reducing postoperative pain 2h after surgery. Allopurinol caused a reduction of approximately 40% in pain scores measured by the visual analogue pain scale after surgery (p < 0.05). No differences were found between groups in anxiety scores after surgery. There was a significant change in the cerebrospinal fluid concentrations of xanthine and uric acid before surgery (p < 0.01). This study showed a short-term benefit of the use of allopurinol as a preanesthetic medication since it was related to a reduction on pain scores 2h after surgery. The purinergic system is a potential target for new analgesic drugs. New studies investigating more selective purine derivatives in the management of pain should be performed. Brazilian Registry of Clinical Trials-ReBEC #RBR-9pw58p.

Effect of Serum Urate Lowering With Allopurinol on Blood Pressure in Young Adults: A Randomized, Controlled, Crossover Trial.

To determine whether serum urate reduction with allopurinol lowers blood pressure (BP) in young adults and the mechanisms mediating this hypothesized effect. We conducted a single-center, randomized, double-blind, crossover clinical trial. Adults ages 18-40 years with baseline systolic BP ≥120 and <160 mm Hg or diastolic BP ≥80 and <100 mm Hg, and serum urate ≥5.0 mg/dl for men or ≥4.0 mg/dl for women were enrolled. Main exclusion criteria included chronic kidney disease, gout, or past use of urate-lowering therapies. Participants received oral allopurinol (300 mg daily) or placebo for 1 month followed by a 2-4 week washout and then were crossed over. Study outcome measures were change in systolic BP from baseline, endothelial function estimated as flow-mediated dilation (FMD), and high-sensitivity C-reactive protein (hsCRP) levels. Adverse events were assessed. Ninety-nine participants were randomized, and 82 completed all visits. The mean ± SD age was 28.0 ± 7.0 years, 62.6% were men, and 40.4% were African American. In the primary intent-to-treat analysis, systolic BP did not change during the allopurinol treatment phase (mean ± SEM -1.39 ± 1.16 mm Hg) or placebo treatment phase (-1.06 ± 1.08 mm Hg). FMD increased during allopurinol treatment periods compared to placebo treatment periods (mean ± SEM 2.5 ± 0.55% versus -0.1 ± 0.42%; P < 0.001). There were no changes in hsCRP level and no serious adverse events. Our findings indicate that urate-lowering therapy with allopurinol does not lower systolic BP or hsCRP level in young adults when compared with placebo, despite improvements in FMD. These findings do not support urate lowering as a treatment for hypertension in young adults.

Allopurinol for fibromyalgia pain in adults: A randomized controlled trial.

Allopurinol is a potent inhibitor of the enzyme xanthine oxidase used in the treatment of hyperuricemia and gout. Because it is well known that purines exert multiple affects on pain transmission, we hypothesized that the inhibition of xanthine oxidase by allopurinol could be a valid strategy to treat pain in humans. This study aimed to compare the analgesic efficacy of oral allopurinol versus placebo as an adjuvant therapy in patients displaying fibromyalgia. This randomized, double-blinded, placebo-controlled study included 60 women with the diagnosis of fibromyalgia. Patients were randomly assigned to receive either oral allopurinol 300mg (n=31) or placebo (n=29) twice daily during 30days. The patients were submitted to evaluation for pain sensitivity, anxiety, depression, and functional status before treatment, and 15 and 30days thereafter. Oral administration of allopurinol 300mg twice daily was ineffective in improving pain scores measured by several tools up to 30days of treatment (P>0.05). Additionally, no significant effects of allopurinol over anxiety, depressive symptoms, and functional status of fibromyalgia patients were observed in the present study. Although previous findings indicated that allopurinol could present intrinsic analgesic effects in both animals and humans, this study showed no benefit of the use of oral allopurinol as an adjuvant strategy during 30days in women displaying fibromyalgia. However, considering previous promising results, new prospective studies are still valid to further investigate allopurinol and more selective purine derivatives in the management of pain syndromes.

The effects of Allopurinol on levels of cardiac troponin Following Non-ST Elevation Myocardial Infarction: A Pilot Randomized Clinical Trial

Purpose: Given the potential anti-ischemic effects of allopurinol, we aimed to assess whether allopurinol administration may reduce myocardial injury following non-ST elevation myocardial infarction (NSTEMI). Methods: A randomized clinical trial (RCT) was conducted on 100 individuals with NSTEMI. The intervention group (n=50) received 600 mg oral allopurinol at the time of diagnosis of NSTEMI, followed by 300 mg every day for two next days and the standard treatment of NSTEMI, while the control group (n=50) received only the standard treatment. Serum concentrations of cardiac troponin I (cTnI) were measured at baseline, and 8, 16, 24, and 32 hours after the treatment. Results: The baseline demographic and clinical data of the patients were not statistically different between the intervention and control groups (all P &gt; 0.05). The comparing estimated marginal mean ± standard error for cardiac troponin I (cTnI) levels revealed no significant difference between the study groups (2.93 ± .27, 2.25 ± .27; P=0.082). The linear mixed model results showed that the interaction of time and group was not statistically different (P=0.751). Moreover, there was a decreasing trend over time for cTnI in both groups (P=0.039). Conclusion: The present pilot RCT did not support the potential cardio-protective benefits of allopurinol administration on decreasing myocardial injury following NSTEMI.

Structure of the parotid gland in natural infection by Leishmania infantum in Canis familiaris

ObjectiveThe objective of this study was to perform a histopathological, morphometric and proteomic study of the parotid gland of dogs naturally infected with Leishmania infantum treated and not treated with Allopurinol. DesignParotid glands from 14 dogs were used, divided into two groups: untreated and treated with oral allopurinol (20 mg / kg, once daily for 90 days). After adequate dissection, the organs were submitted to histopathological, histomorphometric and immunohistochemical techniques, using the monoclonal anti-β-catenin antibody. ResultsHistopathological evaluation of treated and untreated groups showed acinar hypertrophy, structural disorganization of the nucleus and cytoplasm. There was an increase in the area and perimeter of the parotid acini in the experimental groups. The immunostaining of the β-catenin protein in the membrane was severely reduced in the treated and untreated groups. ConclusionsThese findings suggest that Leishmania infantum infection and treatment with Allopurinol alter the tissue structure of the parotid gland in dogs, promoting an increase in the acinar volume and a decrease in the expression of β-catenin in cell membranes.

P271 Prophylactic administration of allopurinol with standard IV hydration in preventing contrast-induced nephropathy in patients undergoing cardiac catheterization: a meta-analysis and systematic review

Abstract Funding Acknowledgements None BACKGROUND Current advancements has made contrast-guided coronary interventions widely available, however these procedures entail the risk of developing Contrast-induced nephropathy which is associated with increased morbidity and mortality of patients. One of the mechanisms that has been investigated in the development of CIN is the presence of hyperuricemia. Elevated uric acid levels may injure the microscopic tubules causing kidney injury and may induce the production of inflammatory factors furthering damage. Thus, it has been postulated that using urate lowering agents may be beneficial in preventing CIN. OBJECTIVE To determine the efficacy of giving oral prophylactic allopurinol along with standard IV hydration in reducing the incidence of contrast-induced nephropathy. METHODS We conducted a systematic literature search using PUBMED, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Kidney and Transplant register of Studies, Google Scholar, and Research Gate. Studies fulfilling the inclusion and exclusion criteria were quality assessed based on the criteria provided in the Cochrane Handbook for Systematic Reviews of Interventions. The incidences ofContrast-Induced Nephropathy were combined and analyzed using a fixed-effect model in Review Manager (Rev Man) Version 5.3 with 95% confidence interval. RESULTS Five studies were included with a total of 753 patients. Results showed that there is a 63% decrease in CIN [RR = 0.37 (0.25 to 0.54, 95% CI, Z = 5.10, p &amp;lt; 0.00001)] after prophylactic administration of allopurinol with standard IV hydration as compared to those who received hydration alone. When adjusted for heterogeneity, there remains a 35% decrease in the incidence of CIN [RR = 0.65 (0.43 to 0.99, 95% CI, Z = 2.02, p = 0.04) in patients given prophylactic allopurinol. CONCLUSION Oral prophylactic allopurinol administration may be protective in the development of CIN in patients undergoing coronary interventions. However larger, multi-centered randomized-controlled trials are needed to validate this claim. Abstract P271 Figure. Forrest Plot of Study Results

Allopurinol therapy provides long term clinical improvement, but additional immunotherapy is required for sustained parasite clearance, in L. infantum-infected dogs

There is little evidence that current control strategies for canine leishmaniosis (CanL), the veterinary disease caused by L. infantum infection, are having a positive impact. This is of critical importance because dogs are a primary reservoir for L. infantum and a significant source of parasite transmission to humans. Drugs intended primarily for human use are prohibited for the treatment of CanL because of concerns over the propagation of resistant parasites. Although allopurinol effectively decreases parasite burden in CanL the treatment needs to be maintained for life. We hypothesized that during the allopurinol-induced parasite reduction dogs may become capable of developing a more robust immune response that may permit more effective control of parasites. To test this, we investigated the clinical and parasitological impact of short-term treatment with allopurinol, either alone or in combination with a defined subunit vaccine, on dogs naturally infected with L. infantum. A total of 28 dogs were distributed as follows: untreated; oral allopurinol alone (20 mg/kg, once each day for 90 days); or allopurinol with immunization with the Leish-F2 antigen formulated with the Toll-like receptor (TLR) 4 agonist Second generation Lipid Adjuvant (SLA) in stable emulsion (SE; SLA-SE). Dogs that did not receive treatment had a progressive decline in their clinical condition and an increase in their infection levels, while treatment with allopurinol alone alleviated the clinical symptoms of CanL but did not generate sustained reduction in parasites. Concomitant immunization with Leish-F2 + SLA-SE, however, improved clinical condition while also providing long-term clearance of L. infantum from lymphoid tissues and systemic organs. These results have important implications for both the management of CanL and for limiting L. infantum transmission to humans.

2400 An Unusual Case of Spontaneous Reactivation of Hepatitis B in Adult T-Cell Lymphoma/Leukemia

INTRODUCTION: Reactivation of hepatitis B (HBV) is typically triggered by immunosuppressive therapy of cancer, autoimmune disease, or organ transplantation. Here we report a rare case of spontaneous reactivation of hepatitis B in a patient newly diagnosed with adult T-cell lymphoma/leukemia without any exposure to immunosuppressive therapy of cancer. CASE DESCRIPTION/METHODS: A 34-year-old African American male was transferred from an outside institution for further management of probable T-cell lymphoma/leukemia as severe lymphocytosis was initially noted. Presenting symptoms included weakness and fatigue as well as bilateral conjunctival redness. His abdomen was mildly distended, and hepatomegaly was noted. Of interest, he was found to have elevated liver function tests (LFTs) and hepatitis panel showed acute hepatitis B with bloodwork significant for positive hepatitis B surface antigen, negative hepatitis B surface antibody, negative hepatitis B core IgM, positive hepatitis B core antibody and hepatitis B viral load of 16,954. Labs for hepatitis A and C were negative. He denied any known risk factors for hepatitis. Abdominal imaging showed peripancreatic concern of mass or swelling, mild hepatomegaly, splenomegaly and marked lymphadenopathy in the celiac, perigastric, pancreatic and aortocaval regions. Of note, he has not been on any immunosuppressive therapy or steroids prior to hospital admission. On hospitalization day #5, he was started on tenofovir and subsequently liver function tests continued to improve. He was also started on IV Solu-Medrol 1 g per day for 3 days with IV hydration and oral allopurinol. He continued to undergo diagnostic work-up as per hematology and Oncology prior to starting chemotherapy. On the day of discharge (day #17), remarkable improvement in his LFTs was noted. He was seen in GI clinic about 3 weeks later and his hepatitis B viral load was 760 and ALT was within normal limits. DISCUSSION: HBV reactivation is common following chemotherapy and is associated with a high mortality, however spontaneous HBV reactivation in the absence of cancer chemotherapy or transplantation is a rare clinical entity. Adult T-cell lymphoma/leukemia likely contributes to immune suppression or alteration in immune function causing spontaneous HBV reactivation. This case highlights the importance of screening all patients who are to undergo cancer chemotherapy, marked immunosuppressive treatments or solid organ or bone marrow transplantation for evidence of ongoing or previous hepatitis B.

Successful treatment of acquired reactive perforating collagenosis induced by pregnancy with allopurinol: A case report with review of literature

Acquired reactive perforating collagenosis (ARPC) is a rare condition caused by transepidermal elimination of collagen, elastin fibers and keratin. To date, the pathogenesis of ARPC remains unknown. Different hypotheses were proposed, including superficial microtrauma due to pruritus and subsequent scratching, diabetes-induced microangiopathy, epidermal and dermal abnormalities in metabolic disorders, dermal microdeposits in patients with chronic renal failure and vasculopathy underlying chronic venous insufficiency and hypertension. In the past two decades, oral allopurinol had been found to be effective in treating ARPC. We report a case of a 36-year-old pregnant woman with itchy skin lesions on the trunk and four limbs since 36 weeks of her gestation. Initially, she was prescribed with oral antihistamine and topical steroid but did not respond well. Skin biopsy was performed and was compatible with ARPC. Normal renal and liver function tests were noted, and the HLA-B5801 test was negative. We treated the patient with allopurinol. Significant improvement was noticed at 1-month follow-up. To the best of our knowledge, this is the first case successfully treating ARPC induced by pregnancy with allopurinol. On careful follow-up of laboratory data and HLA-B5801 test screening, allopurinol may be another effective treatment option for ARPC patients after pregnancy.

Xanthine Oxidoreductase Function Contributes to Normal Wound Healing.

Chronic, nonhealing wounds result in patient morbidity and disability. Reactive oxygen species (ROS) and nitric oxide (NO) are both required for normal wound repair, and derangements of these result in impaired healing. Xanthine oxidoreductase (XOR) has the unique capacity to produce both ROS and NO. We hypothesize that XOR contributes to normal wound healing. Cutaneous wounds were created in C57Bl6 mice. XOR was inhibited with dietary tungsten or allopurinol. Topical hydrogen peroxide (H2O2, 0.15%) or allopurinol (30 μg) was applied to wounds every other day. Wounds were monitored until closure or collected at d 5 to assess XOR expression and activity, cell proliferation and histology. The effects of XOR, nitrite, H2O2 and allopurinol on keratinocyte cell (KC) and endothelial cell (EC) behavior were assessed. We identified XOR expression and activity in the skin and wound edges as well as granulation tissue. Cultured human KCs also expressed XOR. Tungsten significantly inhibited XOR activity and impaired healing with reduced ROS production with reduced angiogenesis and KC proliferation. The expression and activity of other tungsten-sensitive enzymes were minimal in the wound tissues. Oral allopurinol did not reduce XOR activity or alter wound healing but topical allopurinol significantly reduced XOR activity and delayed healing. Topical H2O2 restored wound healing in tungsten-fed mice. In vitro, nitrite and H2O2 both stimulated KC and EC proliferation and EC migration. These studies demonstrate for the first time that XOR is abundant in wounds and participates in normal wound healing through effects on ROS production.

Allopurinol desensitization with A 2weeks modified protocol in an elderly patients with multiple comorbidities: a case report.

BackgroundAllopurinol is an effective urate-lowering drug that is well tolerated by the majority of patients. Patients with chronic renal insufficiency have an increased risk of hypersensitivity reactions with allopurinol.Case presentation75 year old male patient with gout, renal insufficiency, history of metastatic colorectal carcinoma status post-resection was referred to Allergy clinic for a maculopapular eruption that developed 1 week after initiating therapy with allopurinol. The rash resolved with discontinuation of allopurinol. However, his serum urate level rose to 19.9 mg/dl. We initially proposed a slow 4 week oral allopurinol desensitization. The treating nephrologist felt it was critical to lower urate more rapidly. As a result, we modified the dose and standard 4 week protocol down to 2 weeks. A suspension of allopurinol was prepared by the allergy nurse practitioner with a 300 mg allopurinol tablet. The sensitization protocol was modified as a starting dose of 0.3 mg escalating to a final dose of 300 mg/day in 2 weeks. There was no reaction during or after the desensitization. The patient’s urate level normalized (6.3 mg/dl) and has continued on 300 mg allopurinol daily without reaction.ConclusionA 2 week modified allopurinol desensitization protocol is a safe alternative for elderly patients with multiple comorbidities.

The effects of allopurinol on metabolic acidosis and endothelial functions in chronic kidney disease patients.

Hyperuricemia and metabolic acidosis have emerged as important risk factors for progression of kidney disease. In this study, we aimed to investigate the effects of allopurinol on metabolic acidosis and endothelial functions in hyperuricemic stage 2-4 chronic kidney disease (CKD) patients. Thirty patients with stage 2-4 CKD and serum uric acid levels over 5.5 mg/dl were included in the study group. They were prescribed 300 mg/day per oral allopurinol treatment for three months. Age- and gender-matched CKD patients (n = 30) with similar clinical characteristics were taken as the control group and were not given allopurinol treatment. Endothelial functions were measured via flow-mediated dilatation (∆FMD %) over the forearm. pH and HCO3 levels in venous blood, Cr clearance and proteinuria levels were calculated in all patients at baseline and in the third month. Serum uric acid levels significantly decreased in the study group from 7.9 ± 1.6 to 6.4 ± 1.7 (p < 0.001). Cr clearance (from 43.4 ± 20.1 to 51.4 ± 24.9, p = 0.011), serum bicarbonate levels (from 21.4 ± 3.4 to 23.0 ± 3.4, p = 0.007) and ΔFMD % values (from 5.8 ± 2.5 to 6.2 ± 2.7, p = 0.006) increased significantly in the allopurinol group. There were no significant changes except for ∆FMD % values (decreased from 6.27 ± 1.62 to 5.71 ± 1.90, p = 0.005) in the control group. ∆FMD % variations within the two groups were clearly significant in the repeated ANOVA general linear model. We assume that decreasing uric acid levels with allopurinol treatment seems to be helpful in restoring endothelial functions, preventing metabolic acidosis and slowing down the progression of CKD.