History Of Gout Research Articles

Colonic Intramural Hematoma: A Rare Cause of Lower Gastrointestinal Bleeding

Intestinal intramural hematomas are rare. Their endoscopic appearance and treatment are not well understood. Here we report a case of acute severe lower gastrointestinal bleed from an intramural colonic hematoma in an adult patient with acquired hemophilia. A 64-year-old female with a history of hypertension, diabetes, gout and hemorrhoids presented with acute onset of severe right lower extremity pain, as well as frequent rectal bleeding. Physical exam was notable for large superficial hematoma in the right calf and labs were notable for partial thromboplastin time (PTT) 90 (normal 24-37). Hematology workup revealed low factor VIII activity with factor-specific inhibitor, consistent with acquired hemophilia, for which she was started on cyclophosphamide and prednisone. One week into her hospitalization, she had a large episode of hematochezia with associated syncope, hemoglobin (Hb) decrease from 10 to 7.5 and lactate of 5. Her Hb, PTT and factor VIII levels improved with 2 units of packed red blood cells and recombinant factor VII. Her high-volume hematochezia persisted along with ongoing coagulopathy with transfusion requirements. The risks and benefits of proceeding with endoscopic evaluation were discussed and ultimately pursued. Colonoscopy revealed a large subepithelial hematoma near the hepatic flexure that involved two-thirds of the circumference of the wall and extended proximally at least 10 cm (Image), without evidence of active bleeding. Cross-sectional imaging ruled out transmural involvement or bowel necrosis. She was started on aminocaproic acid and rituximab, but remained in the hospital for over one month receiving recombinant factor VII for ongoing intermittent bleeding. Intestinal intramural hematomas are rare but account for approximately 5% of GI bleeds in patients with hemophilia. They can also be seen in patients on anticoagulation, with vasculitis, or following blunt trauma, and are thought to be due to rupture of a terminal artery arising from the mesentery which dissects the muscularis mucosa. In addition to GI bleed, intramural hematomas can present with mass-like or obstructive symptoms. It is important to keep intestinal intramural hematomas on the differential diagnosis in patients with the risk factors outlined above, and it is essential to be able to recognize them endoscopically and on cross-sectional imaging.2009 Figure 1 No Caption available.

Memantine-Induced DILI

Presentations of drug-induced liver injury (DILI) are highly variable. While biochemical evidence of cholestasis is common, the extent of aminotransferase elevations and patterns of liver injury vary. Asymptomatic patients may never be diagnosed. Memantine is an increasingly used therapy in Alzheimer's dementia, reported here to cause cholestatic liver injury in an elderly male. An 86-year-old man with a history of coronary artery disease, atrial fibrillation, prostate cancer, hypothyroidism, gout and Alzheimer's disease presented with incidental elevated aminotransferases up to ten times the upper limit over 2 months. He did not have fever, chills, abdominal pain, nausea, vomiting, jaundice, pruritus or mental status changes. Longstanding medications included donepezil, lisinopril, carvedilol, apixaban, atorvastatin, levothyroxine, allopurinol and omeprazole. Memantine was initiated 2 months prior to presentation. He denied history of tobacco or alcohol use. Physical exam was unremarkable including negative Murphy's sign. The serum aspartate aminotransferase (AST) was 438 U/L, alanine aminotransferase (ALT) was 439 U/L, total and direct bilirubin were 0.9 mg/dL and 0.5 mg/dL respectively, and alkaline phosphatase (ALP) was 169 U/L. Memantine was immediately discontinued. Evaluations for viral, autoimmune, and metabolic etiologies for liver injury were unremarkable, except positive ANA (1:160 dilution), normal IgG (1376 mg/dL). Right upper quadrant ultrasound revealed only cholelithiasis. Three months after memantine withdrawal, the levels of AST (168 U/L) and ALT (140 U/L) and ALP (58 U/L) decreased significantly. Six months after memantine withdrawal, all liver associated enzymes returned to normal. The diagnosis of DILI requires a strong index of suspicion, meticulous history taking and exclusion of other etiologies. This patient was asymptomatic, presenting with a hepatocellular pattern of liver injury of unclear etiology. Although autoimmune hepatitis (AIH) remained on the differential, the decision was made to forego liver biopsy given his comorbidities. The patient's Revised Original Scoring System of the International Autoimmune Hepatitis Group score was 4 (without including liver histology or response to therapy), making AIH unlikely. Memantine induced liver injury has been rarely reported in the literature. Consideration of this diagnosis should prompt immediate discontinuation of this medication while excluding other etiologies.

Images in clinical medicine: gouty arthritis with osteomyelitis

Gout is one of the most common inflammatory arthropathies, characterized by the deposition of monosodium urate crystals in the synovial membrane, articular cartilage and periarticular tissues and leading to inflammation. The natural history of articular gout is typically composed of four periods: asymptomatic hyperuricemia, episodes of acute attacks of gout (acute gouty arthritis) with asymptomatic intervals (intercritical gout), and chronic tophaceous gout. Tophi develop in 12-35% of gouty patients without adequate control of uricemia. Initially, they do not cause significant complaints or function limitation of the nearby joints. However, if they become larger, joint instability and movement range limitation, joint function impairment and bone erosions and infection at the sites of their penetration can develop.We report a case of a poorly controlled polyarticular tophaceous gout complicated by osteomyelitis.

Uric Acid Control in Advanced Chronic Kidney Disease in a Southeastern US Urban Cohort.

Uric acid (UA) control may be insufficient in chronic kidney disease (CKD) patients in the current era. It is unclear, however, whether this is the result of environmental effects, patient anthropometrics or insufficient dosing of medical therapy (allopurinol). We have collected data on multiple clinical and laboratory parameters of 114 CKD clinic patients attending the nephrology clinic of the University of Mississippi Medical Center with an estimated glomerular filtration rate <45 mL · min-1 · 1.73 m2. We assessed the correlates of UA levels and the allopurinol doses along with achieved serum UA and urine pH. The cohort consisted of middle-aged to elderly patients with a mean (± standard deviation) age of 62.1 (11.6) years; 45.6% were female, 68.4% were African American and 47.4% had a history of gout. The mean UA level was 7.7 (2.49) mg/dL (range 3.1-16), allopurinol dose was 192 (99) mg/day (range 50-450) and estimated glomerular filtration rate was 23.8 (11.3) mL · min-1 · 1.73 m2. While the overall serum bicarbonate level was 25 (3.2) mEq/L, urine pH was <6 in 60.5% of the cohort. Significant univariate correlates of the administered doses of allopurinol were weight (r 0.317, P = 0.001), body mass index (BMI; r 0.313, P = 0.001), and female sex (r -0.198; P = 0.035). Achieved UA levels correlated directly with BMI (r 0.201, r = 0.036) but inversely with the allopurinol dose (r -0.196; P = 0.036). During logistic regression analysis with stepwise selection, only weight (β 0.313, P = 0.001) and sex (β -0.190, P = 0.039) proved to be predictive of the allopurinol dose; as for the achieved UA level, only BMI (β 0.271, P = 0.006) and the allopurinol dose (β -0.258; P = 0.009) had a significant effect. In patients with advanced CKD, conventional dosing recommendations for allopurinol are unlikely to suffice in reaching target serum UA goals. In our cohort, larger-than-usual allopurinol doses were well tolerated.

Brief Report: Monosodium Urate Monohydrate Crystal Deposits Are Common in Asymptomatic Sons of Patients With Gout: The Sons of Gout Study.

ObjectiveTo estimate the prevalence and distribution of asymptomatic monosodium urate monohydrate (MSU) crystal deposition in sons of patients with gout.MethodsPatients with gout were mailed an explanatory letter with an enclosed postage‐paid study packet to mail to their son(s) age ≥20 years old. Sons interested in participating returned a reply form and underwent telephone screening. Subsequently, they attended a study visit at which blood and urine samples were obtained and musculoskeletal ultrasonography was performed, with the sonographer blinded with regard to the subject's serum urate level. Images were assessed for double contour sign, intraarticular or intratendinous aggregates/tophi, effusion, and power Doppler signal. Logistic regression was used to examine associations. Adjusted odds ratios (OR adj) and 95% confidence intervals (95% CIs) were calculated.ResultsOne hundred thirty‐one sons (mean age 43.8 years, mean body mass index 27.1 kg/m2) completed assessments. The serum urate level was ≥6 mg/dl in 64.1%, and 29.8% had either a double contour sign or intraarticular aggregates/tophi in ≥1 joint. All participants with MSU deposition had involvement of 1 or both first metatarsophalangeal joints. Intratendinous aggregates were present in 21.4% and were associated with intraarticular MSU crystal deposits (OR adj 2.96 [95% CI 1.17–7.49]). No participant with a serum urate level of ≤5 mg/dl had MSU crystal deposition seen on ultrasonography, and 24.2% of those with serum urate levels between 5 and 6 mg/dl had ultrasonographic MSU deposition. MSU crystal deposition was associated with increasing serum urate levels (OR adj 1.61 [95% CI 1.10–2.36] for each increase of 1 mg/dl).ConclusionAsymptomatic sons of patients with gout frequently have hyperuricemia and MSU crystal deposits. In this study MSU crystal deposits were present in participants with serum urate levels of ≥5 mg/dl. Evaluation of subjects without a family history of gout is needed to determine whether the threshold for MSU crystal deposition is also lower in the general population.

Association of Gout With Long-Term Cardiovascular Outcomes Among Patients With Obstructive Coronary Artery Disease.

BackgroundEpidemiological studies demonstrating a relationship between gout and cardiovascular disease are older and predate modern cardiovascular preventive therapy. We assessed the contemporary association between gout and cardiovascular disease in patients with obstructive coronary artery disease.Methods and ResultsData were from the Duke Databank for Cardiovascular Diseases, which followed up patients undergoing cardiac catheterization with obstructive coronary artery disease at Duke University Medical Center (1998–2013). We assessed the relationship between gout diagnosis at baseline or during follow‐up and the primary composite outcome of cardiovascular death, myocardial infarction, or stroke, adjusting for differences in baseline clinical factors. Secondary end points included cardiovascular death and all‐cause mortality. New, postbaseline, gout diagnosis was included as a time‐dependent covariate. Among 17 201 patients, 1406 (8.2%) had baseline gout and a high burden of cardiovascular risk factors, but high rates of optimal medical therapy. Over a median follow‐up of 6.4 years, gout diagnosis at time of catheterization was not associated with the primary outcome (hazard ratio [95% confidence interval], 1.05 [0.96–1.15]; P=0.31) or cardiovascular death (hazard ratio [95% confidence interval], 1.10 [0.99–1.22]; P=0.08), but was associated with increased all‐cause mortality (hazard ratio [95% confidence interval], 1.13 [1.05–1.23]; P=0.002). After including new, postbaseline, gout diagnosis, the instantaneous risk of the primary outcome was significantly associated with prior gout diagnosis (hazard ratio [95% confidence interval], 1.15 [1.07–1.25]; P=0.0004).ConclusionsA clinical history of gout is associated with worse outcomes in a contemporary population of patients with obstructive coronary artery disease. This increased risk exists despite high levels of optimal baseline cardiovascular disease medical therapy, suggesting that residual cardiovascular risk is not addressed by standard medical therapy.

Chemolysis of a Uric Acid Stone in a Horseshoe Kidney

Chemolysis of kidney stone is not unheard of. However, to our knowledge, there is no previous report of chemolysis of a kidney stone in a horseshoe kidney. We report the first ever case of chemolysis of a stone in a horseshoe kidney. As part of his visible haematuria workup 4 years ago, a 66-year-old gentleman with a history of gout was found to have a horseshoe kidney. In early 2017, he was seen in the urology clinic with some non-specific abdominal pain without a recent history of visible haematuria, lower urinary tract symptoms, and urinary tract infections. His CT KUB (computed tomography of kidneys, ureters and bladder), revealed a 1.3cm stone in his horseshoe kidney [Figure 1 and 2]. At the same time, his CT KUB has also picked up some retroperitoneal lymphadenopathy in the abdomen and pelvis which were suspicious of lymphoma. His serum uric acid level was noted to be normal. Subsequently, he underwent a laparoscopic right iliac lymph node biopsy which confirmed nodal marginal zone non-Hodgkin's B-cell lymphoma. He was reviewed by the haematology team and they decided to adopt a watch and wait approach to his disease with quarterly CT CAP (computed tomography of chest, abdomen and pelvis) scans. During this period of time, he had several gout attacks and he was started on allopurinol i.e. 100mg once a day. He also considerably increased his daily fluid intake. 6 months after his initial CT KUB, he was found to be completely stone free on his CT scan [Figure 3 and 4].

FR-10 BIFOCALS AND BLADDER OUTLET OBSTRUCTION: BENJAMIN FRANKLIN AND HIS FASCINATING UROLOGIC MORBIDITIES AND CONTRIBUTIONS TO OUR FIELD

You have accessJournal of UrologyHistory Forum1 Apr 2018FR-10 BIFOCALS AND BLADDER OUTLET OBSTRUCTION: BENJAMIN FRANKLIN AND HIS FASCINATING UROLOGIC MORBIDITIES AND CONTRIBUTIONS TO OUR FIELD Allison Glass and Marc Dall'Era Allison GlassAllison Glass More articles by this author and Marc Dall'EraMarc Dall'Era More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.3030AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Benjamin Franklin (1706-1790) is a well renowned 18th century American author, diplomat and scientist. As one the Founding Fathers of the United States, he also made contributions to the study of physics, electricity and medicine. In addition to the study and promotion of smallpox inoculation he was instrumental to the development of bifocal glasses. Benjamin Franklin may also be credited for advancing the field of urology. He suffered from bladder stones and is theorized to have had multiple physiologic risk factors for developing uric acid urolithiasis. We sought to further understand the role Benjamin Franklin played to the field of Urology. METHODS A comprehensive PubMed search was performed. We reviewed articles captures under search words "Benjamin Franklin," "medicine," "stone," and "urology." RESULTS Benjamin Franklin was credited for inventing the flexible urethral catheter. The idea came about after he was contacted by his older brother, who suffered from bladder stones and severe lower urinary tract symptoms. Franklin designed a flexible catheter which had been crafted by a silversmith. Franklin was documented to have history of gout and bladder stones. It is theorized that his urolithiasis was largely related to hyperuricemia. Unfortunately, no pathological specimens from Franklin's stones exist to confirm this theory. He is described as having multiple risk factors for uremia, including genetics, gender, diet, age (Finger and Hagemann, 2008). It is also proposed that psoriasis and exposure to lead may a have contributed to his stone disease. In addition to early American Colony culture, his occupation is also presumed to have resulted in cumulatively significant lead exposure and lead toxicity can compromise the kidney's ability to excrete urate. At the time, treatment for urolithiasis consisted of alkaline medicines including "Blackrie's solvent," a concoction that included soap lye. There is no evidence that Franklin used his own flexible catheter. Franklin's morbidity from gout - and possibly his bladder stones - reportedly may have compromised some his diplomatic obligations. Franklin had such debilitation from bladder stones, that he was reportedly bed-bound and opioid-dependent in the last year of his life. Detailed accounts of Franklin's suffering from his bladder stone are described in his letters to family and friends (Corner and Goodwin, 1953). CONCLUSIONS Benjamin Franklin's place in the history of science and medicine includes unique ties to the field of urology. He himself suffered from severe symptoms secondary to bladder stones. His development of urethral catheter and struggles with stone morbidity no doubt impacted both colonial and modern day urology. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e1244 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Allison Glass More articles by this author Marc Dall'Era More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Dyslipidemia, Alcohol Consumption, and Obesity as Main Factors Associated With Poor Control of Urate Levels in Patients Receiving Urate-Lowering Therapy.

In real life, in a substantial proportion of gouty patients receiving urate-lowering therapy (ULT), urate levels are not maintained below the target of 6.0 mg/dl. We aimed to search for factors associated with poor control of serum uric acid (UA) levels in a large population of patients with gout receiving ULT. This cross-sectional study involved adults with gout in primary care who were receiving ULT. Demographics, gout history, comorbidities, lifestyle, clinical factors, concomitant treatments, and laboratory data were compared in well-controlled gout (serum UA ≤6.0 mg/dl) versus poorly controlled gout (serum UA >6.0 mg/dl) on univariate and multivariate analyses. Among the 1,995 patients receiving ULT, only 445 (22.3%) had reached the target of 6.0 mg/dl serum UA. Such patients had a lower rate of gout flares within the previous year than patients without the target (mean ± SD 1.7 ± 1.4 versus 2.1 ± 1.4; P < 0.0001). The main factors associated with poor serum UA level control in multivariate analysis were low high-density lipoprotein cholesterol level (adjusted odds ratio [OR] 0.5 [95% confidence interval (95% CI) 0.26-0.96]; P = 0.04), high total cholesterol level (OR 1.83 [95% CI 1.29-2.60]; P = 0.0007), increased waist circumference (OR 1.55 [95% CI 1.11-2.13]; P = 0.008), and alcohol consumption (OR 1.52 [95% CI 1.15-2.00]; P = 0.003). Dyslipidemia, abdominal obesity, and alcohol consumption are the main factors associated with a poor response to ULT. Knowledge of these factors might help physicians identify cases of gout that may be less likely to achieve target urate level.

Hyper-Uricemia and Gouty Access in the Adult Population of the Southeast of Gabon: Biochemical Aspects.

Gout is caused by a chronic hyperuricemia whose complications are not currently well evaluated in Africa. The aim of this study was to determine the prevalence and risk factors of hyperuricemia and gout in 85 patients recruited. A total of 26 cases of hyperuricemia, i.e., 30.6% of the study population, with 12 cases of gout and seven cases of gouty access. In this population, hyperuricemia was proportional to age (p-value < 10−4, OR = 2.6), but it was more prevalent in men, 23.5% versus 7.1% for women (p-value = 0.0047). In addition, none of these women showed signs of a gouty affection. Consumption of alcohol (OR = 13) and nucleoprotein-rich foods, obesity (BMI 30 kg/m2; OR = 6), family history of gout (OR = 6.8), as well as diseases such as high blood pressure (associated with taking diuretics; OR = 1.7), renal insufficiency (OR = 4.4) and diabetes (p < 0.049) were the main factors of the diseases associated with gout and hyperuricemia in this population. The biochemical role of these factors may increase and/or decrease the processes of synthesis and/or elimination of uric acid by acting on metabolites involved in the regulation of urate production.

Stroke Mimic Caused by Acetazolamide.

ObjectivesTo describe a case of a stroke mimic caused by iatrogenic ataxia due to acetazolamide.Case descriptionAn 86-year-old man with a history of gout and glaucoma, presented to the emergency department with progressive confusion, dizziness, disequilibrium and slurred speech, 3 days after he had started acetazolamide following ocular surgery. Physical examination showed he was hypertensive and had dysarthria; it was not possible to observe his gait due to pain in the right foot presumed to be due to a gout crisis. A stroke was thought to be the cause of these neurological deficits so a head CT scan was performed but did not show any alterations. During a stay in the stroke unit the neurological deficits remained unchanged and so, after review of the history, neurological side effects due to acetazolamide were suspected and the drug was suspended. A head MRI was performed to rule out stroke and the patient gradually improved. In the meanwhile, the patient was observed by an ophthalmologist and repeat surgery was proposed because of increased intraocular pressure.ConclusionsNeurological deficits with a normal head CT scan in the emergency department pose many difficulties and require extensive knowledge of brain vascular anatomy and the differential diagnoses for stroke.LEARNING POINTSNot all focal neurological deficits are strokes.The need to diagnose stroke very quickly in order that effective treatment can be started can obscure the actual diagnosis so the differential diagnoses should always be carefully considered.Even though the sudden onset of focal neurological deficits suggests a stroke, a careful history should indicate the correct diagnosis.

Aspiration cytopathology of tophaceous gout: a report of 22 patients

Gout may manifest with crystal-induced arthropathy and/or soft tissue tophi. Demonstration of monosodium urate (MSU) crystals is necessary to establish the diagnosis. Despite the fact that alcohol is an ideal fixative to preserve MSU crystals, very few fine-needle aspiration (FNA) cases of gout have been published. A retrospective review was performed for FNA cases diagnosed as tophaceous gout. Samples included unstained smears or smears stained with Diff-Quik or Papanicolaou stain, and formalin-fixed paraffin-embedded cell block stained with hematoxylin and eosin (H&E). We identified 22 FNA cases involving 18 men and 4 women. Only 7 patients had a clinical history of gout and 5 were taking gout medication. At least 4 patients presented with a clinical diagnosis of rule out sarcoma. All had soft tissue masses from either upper (n = 5) or lower (n = 17) extremities. Extracellular polarizing needle-shaped crystals with negative birefringence were present and visible on unstained, Diff-Quik, or Papanicolaou-stained conventional smears as well as in H&E-stained cell blocks in all cases. Our study demonstrates that MSU crystals are readily detectable under polarization on direct smears with or without staining. FNA cytology can serve as an alternative to core needle biopsy or synovial biopsy in not only confirming a diagnosis of tophaceous gout, but also in eliminating a diagnosis of soft tissue sarcoma in those patients where clinical and/or radiologic features were concerning for malignancy.

Ultrasonographic assessment of joint pathology in type 2 diabetes and hyperuricemia: The Fremantle Diabetes Study Phase II

AimsThe prevalence and consequences (articular and extra-articular) of hyperuricemia in type 2 diabetes, especially when asymptomatic (ASH), are incompletely understood. The aim of this study was to use ultrasonography to assess pathology associated with monosodium urate deposition in the joints of well-characterized hyperuricemic patients with type 2 diabetes. MethodsA subset of 101 participants (mean age 70.4 years, 59.8% males, median diabetes duration 14.6 years) with hyperuricemia (fasting serum uric acid ≥0.42 mmol/L) from the community-based observational Fremantle Diabetes Study Phase II were assessed by ultrasound for signs of intra-articular urate deposition and inflammation in 14 joints at increased risk of involvement in patients with gout. ResultsMost participants had evidence of crystal deposition comprising aggregates (59.4%), tophi (19.8%) or a double contour sign (27.7%), and 37% had a power Doppler signal indicative of inflammation in at least one joint. There was no difference between the prevalence of these abnormalities in those with ASH (n = 60) versus participants with a history of gout (n = 41; P ≥ 0.15). There was no association between a history of ischemic heart disease (reported by 17.8% of participants) and either any abnormality on joint ultrasound or inflammatory changes assessed by power Doppler (P ≥ 0.41). ConclusionsJoint inflammation and/or urate deposition were present in the majority of community-based patients with type 2 diabetes and hyperuricemia regardless of whether there was a history of gout. Given the potential consequences of chronic inflammation for joint damage and extra-articular complications such as cardiovascular disease, these data have potential clinical implications.

Allopurinol-Induced Granulomatous Hepatitis

Introduction: Liver enzyme elevation is a common reason for referral to the Gastroenterologist. Drugs are one of the most common reasons for asymptomatic elevation of liver enzymes. We present here a case of granulomatous hepatitis (GH) secondary to long-term use of allopurinol.Figure: A low power showing the expanded portal tracts.Figure: a higher power showing the mixed nature of the inflammation (including lymphocytes, plasma cells, neutrophils and eosinophils).Case: An 83-year old male with a history of chronic gout and hypertension was evaluated for elevation of liver enzymes. He denies any complaints of abdominal pain, nausea, fever, chills, weight loss, night sweats or yellowness of skin. He denies any use of herbal medications. He was a heavy drinker in the past but now cut down his drinking to 2 beers a week. He was on Losartan, statins and allopurinol for years. No new medications reported. Physical examination was unremarkable. Labs showed AST 101 U/L, ALT 81 U/L, and ALP 645 U/L. Hepatitis panel, ANA and anti-smooth muscle antibody unremarkable. Ultrasound of the abdomen showed coarse liver texture concerning for parenchymal disease. Liver biopsy was done which showed mixed GH (Figure 1, 2 and 3). Given negative autoimmune and viral serologies, allopurinol-induced GH was suspected. His liver chemistries improved after stopping the allopurinol (Table 1).Figure: Well-formed epithelioid granuloma seen.Discussion: Hepatic Granulomas are associated with many systemic conditions including systemic infections, malignancy and autoimmune disorders. Many drugs have been associated with GH including allopurinol, diltiazem, amiodarone, and penicillin. The clinical manifestation of GH is variable. Fever is common in infectious causes like AIDS. Weight loss and night sweats are also common. Similar to our patient, some present with asymptomatic elevation of liver enzymes. Removal of the offending drug is the beneficial treatment. Corticosteroids are not generally recommended for drug-induced liver injury and the use is limited to severe cholestatic jaundice with no improvement after removal of drug or concomitant extrahepatic manifestation secondary to hypersensitivity to the drug. Serial follow-up of liver chemistries should be done to evaluate for improvement. Patients with signs and symptoms of hepatic failure should be referred to transplant center. Bilirubin levels > 2 times along with ALT > 3 times the upper normal limit following initiation of a drug is the indicator of a poor outcome and should be evaluated by a hepatologist. Prevention is the key and can be done by patient education, appropriate dosing and checking liver chemistries if liver dysfunction is suspected.

Fortuitous Splenic Rupture: An Unusual Presentation of Pancreatic Cancer

Early diagnosis of pancreatic ductal adenocarcinoma (PDAC) is difficult. Multifocal pancreatic masses are not common when it comes to PDAC. This especially holds true for cancer of the pancreatic body and tail that do not manifest with jaundice. We present a case of pancreatic cancer involving the head and tail A 52-year-old Caucasian male with past history of hypertension, gout and osteoarthritis presented to the hospital with acute left upper quadrant pain radiating to the back after sustaining a fall. Examination revealed severe tenderness to palpation of the left upper quadrant. Initial laboratory data showed hemoglobin of 10.4 g/dl, AST of 166 U/L, ALT of 352 U/L, ALP of 368 U/L and serum lipase level of 869 U/L. CT abdomen showed splenic laceration with hemoperitoneum. The patient was vigorously resuscitated, and subsequently underwent emergency laparotomy. Operative findings revealed splenic laceration with hemoperitoneum. Intraoperatively, the pancreatic tail was hard and abutted the mesocolon and omentum. Short gastric vessels were engorged suggestive of splenic vein thrombosis. Irregular masses were noticed in the head of the pancreas without involvement of superior mesenteric vasculature. Histopathology of the mass revealed PDAC. The patient underwent Whipple surgery with adjuvant FOLFIRINOX therapy. Post-operative pathology showed T3N1 disease with perineural and lymphovascular invasion. The patient is currently undergoing surveillance for recurrence. Splenic rupture is extremely rare presenting feature of pancreatic cancer. Only ten prior cases have been reported in literature. Most of those cases reported rupture of splenic artery aneurysm secondary to direct vascular invasion of PDAC. Cancer of the pancreatic tail can invade the splenic hilum causing splenic ischemia and vein occlusion which may culminate in splenic rupture. Another rare finding in our case was the multifocal nature of pancreatic cancer. Only around 50 cases have been reported so far as per our literature review. Most of the cases that have been reported in literature present as contiguous masses. Surgical removal is recommended in the absence of distant metastatic disease and local vascular invasion. Overall prognosis continues to remain grim for all stages.Figure: Splenic rupture is a rare presenting feature of pancreatic cancer. It can however present an opportunity for early stage discovery that may lead to improvement in prognosis by earlier initiation of treatment.

Asymptomatic hyperuricemia and coronary artery disease in elderly patients without comorbidities.

Because many subjects with hyperuricemia have comorbidities, it can be difficult to differentiate the role of hyperuricemia from that of other comorbidities of coronary artery disease (CAD). Subjects aged ≥ 65 years were enrolled in the study and were available at enrollment and at 5-year follow-up. Subjects were excluded if they were overweight or obese, hypertensive, diabetic, hyperlipidemic, had a pre-existing cardiovascular disease, a history of gout or hyperuricemia on medications, or chronic kidney disease as estimated by a glomerular filtration rate (eGFR) < 60 mL/min per 1.73 m2. We used Poisson regression to estimate the hazard ratio (HR) for incident CAD events between hyperuricemic (> 7 mg/dL in men and ≥ 6 mg/dL in women) and normouricemic subjects. A total of 2,142 subjects without comorbidities (mean age of 70.7 ± 5.9 years, 1,194 men) were followed for 57.4 ± 8.9 months. Hyperuricemia was associated with an increased cumulative incidence of incident CAD events (15.0% versus 8.8%, P < 0.001). After adjusting for confounding factors, hyperuricemia independently predicted the risk of incident CAD events (HR=1.71, 95% CI 1.26–2.34). In conclusion, asymptomatic hyperuricemia is a valuable biomarker for predicting the development of incident CAD events.

Functional non-synonymous variants of ABCG2 and gout risk.

Common dysfunctional variants of ATP binding cassette subfamily G member 2 (Junior blood group) (ABCG2), a high-capacity urate transporter gene, that result in decreased urate excretion are major causes of hyperuricemia and gout. In the present study, our objective was to determine the frequency and effect on gout of common and rare non-synonymous and other functional allelic variants in the ABCG2 gene. The main cohort recruited from the Czech Republic consisted of 145 gout patients; 115 normouricaemic controls were used for comparison. We amplified, directly sequenced and analysed 15 ABCG2 exons. The associations between genetic variants and clinical phenotype were analysed using the t-test, Fisher's exact test and a logistic and linear regression approach. Data from a New Zealand Polynesian sample set and the UK Biobank were included for the p.V12M analysis. In the ABCG2 gene, 18 intronic (one dysfunctional splicing) and 11 exonic variants were detected: 9 were non-synonymous (2 common, 7 rare including 1 novel), namely p.V12M, p.Q141K, p.R147W, p.T153M, p.F373C, p.T434M, p.S476P, p.D620N and p.K360del. The p.Q141K (rs2231142) variant had a significantly higher minor allele frequency (0.23) in the gout patients compared with the European-origin population (0.09) and was significantly more common among gout patients than among normouricaemic controls (odds ratio = 3.26, P < 0.0001). Patients with non-synonymous allelic variants had an earlier onset of gout (42 vs 48 years, P = 0.0143) and a greater likelihood of a familial history of gout (41% vs 27%, odds ratio = 1.96, P = 0.053). In a meta-analysis p.V12M exerted a protective effect from gout (P < 0.0001). Genetic variants of ABCG2, common and rare, increased the risk of gout. Non-synonymous allelic variants of ABCG2 had a significant effect on earlier onset of gout and the presence of a familial gout history. ABCG2 should thus be considered a common and significant risk factor for gout.

Allopurinol-Induced Granulomatous Hepatitis: A Case Report and Review of Literature

Liver enzyme elevation is a common reason for referral to a gastroenterologist. Drugs are one of the most common reasons for asymptomatic elevation of liver enzymes. We present here a case of granulomatous hepatitis (GH) secondary to long-term use of allopurinol. An 83-year-old male with a history of chronic gout and hypertension was evaluated for elevation of liver enzymes. He denies any complaints of abdominal pain, nausea, fever, chills, weight loss, night sweats, or yellowness of skin. He denies any use of herbal medications. He was on losartan and allopurinol for years. No new medications reported. Physical examination was unremarkable. Labs showed aspartate transaminase 101 U/L, alanine transaminase 81 U/L, and alkaline phosphatase 645 U/L. Ultrasound of the abdomen showed coarse liver texture. Liver biopsy was done that showed mixed GH. Given negative autoimmune and viral serologies, allopurinol-induced GH was suspected. Allopurinol was held, and repeat liver enzymes were checked in 3 months, which showed improvement in transaminase and alkaline phosphatase levels. This case highlights the importance of reviewing medications carefully when evaluating a patient with liver enzymes elevation, as stopping the offending drug can normalize the abnormalities in liver chemistries and can prevent subsequent expensive testing.

Asymptomatic Hyperuricemia Without Comorbidities Predicts Cardiometabolic Diseases: Five-Year Japanese Cohort Study.

Whether asymptomatic hyperuricemia in the absence of comorbidities increases the risk for cardiometabolic disorders and chronic kidney disease remains controversial. This study was conducted to clarify the association between asymptomatic hyperuricemia and cardiometabolic conditions. Subjects consisting of Japanese adults between 30 and 85 years of age were enrolled in the study at Center for Preventive Medicine, St Luke's International Hospital, Tokyo, and were available at enrollment (2004) and at 5-year follow-up (2009). Subjects were excluded if they were overweight or obese, hypertensive, diabetic, and dyslipidemic, had a history of gout or hyperuricemia on medications, or had chronic kidney disease as estimated glomerular filtration rate <60 mL/min per 1.73 m2 Linear and logistic regression analyses were used to examine the relationship between hyperuricemia and development of hypertension, diabetes mellitus, dyslipidemia, chronic kidney disease, and overweight/obesity (unadjusted and adjusted for age, sex, smoking, drinking habits, baseline estimated glomerular filtration rate, and body mass index). Five thousand eight hundred and ninety-nine subjects without comorbidities (mean age of 47±10 years, 1864 men) were followed for 5 years. Hyperuricemia (defined as >7 mg/dL in men and ≥6 mg/dL in women) was associated with increased cumulative incidence of hypertension (14.9% versus 6.1%; P<0.001), dyslipidemia (23.1% versus 15.5%; P<0.001), chronic kidney disease (19.0% versus 10.7%; P<0.001), and overweight/obesity (8.9% versus 3.0%; P<0.001), while diabetes mellitus (1.7% versus 0.9%; P=0.087) showed a trend but did not reach statistical significance. In conclusion, asymptomatic hyperuricemia carries a significant risk for developing cardiometabolic conditions in Japanese individual without comorbidities.

Gout mimicking spondyloarthritis: case report and literature review.

Gout is clinically characterized by episodes of monoarthritis, which not only typically affects the peripheral joints but also occasionally affect the axial joint, such as the sacroiliac joint (SIJ), and often mimics spondyloarthritis (SpA). Two cases of gout mimicking SpA are presented in the current paper. One patient was a 32-year-old man with a history of asymmetrical oligoarthritis of ankle and metatarsophalangeal joints (MTPJ). He had left gluteal pain for 2 weeks. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed the bone erosion of the left SIJ. T1-weighted MRI showed hypointense T1 and hyperintense T2 signals of the left SIJ. The other patient was a 24-year-old man with left back pain and hip pain for 4 months and intermittent fever for 3 months. He had a history of gout for 3 years. Both patients underwent CT-guided sacroiliac biopsy, and monosodium urate (MSU) crystals were shown by polarized microscopy. Gout can often mimic SpA and seldomly affects the SIJ. Thus, its correct diagnosis and adequate therapy can halt the development of such damaging complications.