HLA-B*58: 01 carrier status of Hmong in Minnesota: first in Hmong genotyping for prevalence of this biomarker of risk for severe cutaneous adverse reactions caused by allopurinol.

Allopurinol, a common medication to treat gout, is associated with severe cutaneous adverse reactions, and the occurrence is highly predicted by an individual's HLA-B*58:01 carrier status. Guidelines endorse preemptive testing in select Asian populations before initiating allopurinol. The Hmong, an Asian subpopulation originally from China who now live dispersed around the world, have a 2.5-fold higher risk of gout when compared to non-Hmong in Minnesota. Given the concern for severe cutaneous adverse reactions when prescribing allopurinol, we quantified the carrier status of HLA-B*58:01 in Hmong from two independent cohorts in Minnesota. Using a community-based participatory research approach, HLA-B*58:01 carrier status was determined in 49 US-born Hmong without a history of gout or allopurinol use. Further, 47 Hmong patients undergoing clinical evaluation to receive gout pharmacotherapy were also tested. The frequency of HLA-B*58:01 positive carrier status in these two cohorts were compared to published data from a Han Chinese (n = 2910) and a Korean cohort (n = 485) using a Fisher's exact test with a Bonferroni-corrected P-value <0.025 for significance. With one uninterpretable result, we identified two out of 95 people (2.1%) who carried HLA-B*58:01. This 2.1% incidence in these Hmong adults is notably lower than Han Chinese (19.6%, P < 0.0001) and Korean (12.2%, P = 0.0016) populations. Though commonly understood to be of Chinese descent, the lower prevalence within the Hmong underscores the risk of generalizing genotypic findings from Chinese to Asian subpopulations. We suggest no change to the current guidelines recommending which populations should be tested for HLA-B*58:01 before allopurinol use until further validation.

Pancreatic panniculitis in active systemic lupus erythematosus.

This report documents the case of a 64-year-old African-American female with new end-stage renal disease (ESRD), diagnosed with systemic lupus erythematosus (SLE) on renal biopsy and serologies including a positive ANA (>1:2560), positive anti-Sm antibodies, low titer anti-RNP antibodies, high titer anti-Ro antibodies, anti-dsDNA antibodies, lupus anticoagulant, and hypocomplementemia. She was also noted to have tender nodules on the bilateral shins. Excisional biopsy of one of the nodules showed marked fat necrosis with "ghost cells" and patchy basophilic granular debris consistent with pancreatic panniculitis. Further examination for pancreatic pathology showed an elevated lipase of 585 U/L (reference range 8-78 U/L) and amylase of 214 U/L (reference range 25-125 U/L). However, computed tomography imaging showed no evidence of pancreatitis or pancreatic tumors. This is very similar to another case recently reported in the literature. Similarities of these two cases (African-American females with lupus nephritis on dialysis) may represent a particular subset of SLE patients at increased risk for pancreatic panniculitis.

Nivolumab induced remitting seronegative symmetrical synovitis with pitting edema in a patient with melanoma: a case report.

BACKGROUND: Novel immune checkpoint inhibitors have been often utilized for different types of malignancies as salvage therapy with varying success. One obstacle to immune checkpoint inhibitor use is the higher incidence of immune-mediated side effects that can prompt discontinuation of therapy. Remitting seronegative symmetrical synovitis with pitting edema has been described with immune checkpoint inhibitors only once previously. We report a case of a patient who developed remitting seronegative symmetrical synovitis with pitting edema related to immune checkpoint inhibitor therapy and stress that these symptoms can be managed without cessation of immune checkpoint inhibitor therapy. CASE PRESENTATION: We present a 70-year-old white man who presented with 4 months of progressive inflammatory arthritis with pitting edema. He had been started on nivolumab therapy for his metastatic melanoma with excellent response prior to symptom onset. The symptoms started in his knees and subsequently involved both hands and feet. On evaluation, he was wheelchair bound and completely dependent for all activities of daily living. Evaluation revealed negative serological testing and plain film imaging. Ultrasound demonstrated diffuse flexor tenosynovitis and soft tissue swelling, and a diagnosis of remitting seronegative symmetrical synovitis with pitting edema was made. He was treated with orally administered corticosteroids (0.5 mg/kg per day) which improved his symptoms significantly and allowed him to regain prior independent functioning. His corticosteroids were tapered (0.15 mg/kg per day) but not discontinued and his nivolumab treatment was not interrupted. In follow up he continued to have stable control of his melanoma as well as his remitting seronegative symmetrical synovitis with pitting edema. CONCLUSIONS: In conclusion we present the first case of nivolumab-induced remitting seronegative symmetrical synovitis with pitting edema that is controlled by maintenance low-dose orally administered corticosteroids allowing for continuation of nivolumab therapy. Clinicians who encounter mild-to-moderate immune checkpoint inhibitor immune-mediated adverse effects can consider maintaining immune checkpoint inhibitor therapy with concomitant low-dose corticosteroids rather than abrupt cessation of the immune checkpoint inhibitor.

A case report of autoimmune necrotizing myositis presenting as dysphagia and neck swelling.

BACKGROUND: Severe dysphagia may occur in the immune mediated necrotizing myopathies (IMNM). Neck swelling and severe dysphagia as the initial symptoms upon presentation has not been previously described. CASE PRESENTATION: A 55-year-old male with a 4 week history of neck swelling, fatigue, dysphagia, myalgias, night sweats, and cough was admitted for an elevated CK. He underwent extensive infectious and inflammatory evaluation including neck imaging and muscle biopsy. Neck CT and MRI showed inflammation throughout his strap muscles, retropharyngeal soft tissues and deltoids. Infectious work up was negative. Deltoid muscle biopsy demonstrated evidence of IMNM. Lab tests revealed anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies confirming the diagnosis of HMGCR IMNM. CONCLUSIONS: HMGCR IMNM is a rare and incompletely understood disease process. Awareness of HMGCR IMNM could potentially lead to earlier diagnosis, treatment and improved clinical outcomes as disease progression can be rapid and severe.

Opportunistic computed tomography screening shows a high incidence of osteoporosis in ankylosing spondylitis patients with acute vertebral fractures.

Advanced ankylosing spondylitis is associated with reductions in bone mineral density (BMD), contributing to pain and predisposing to fractures. Quantifying this reduction is complicated because overgrowth of bone and loss of trabecular bone occur concurrently. Traditional methods such as dual-energy X-ray absorptiometry struggle to generate accurate estimates of BMD in these patients. The aim of this study was to evaluate the utility of computed tomography (CT) attenuation in generating estimates of BMD in patients with severe AS who had sustained vertebral fractures. Patients with severe AS and bridging syndesmophytes who presented, with acute fractures of the spine, were reviewed to assess whether they had a CT scan in the 6 mo before or after injury that included an image of the L1 vertebra; if it did, the scans were selected for analysis. A total of 17 patients were evaluated. Using a CT attenuation threshold of 135 HU balanced for sensitivity and specificity, 14 of 17 (82%) patients were osteoporotic. Using a CT attenuation threshold for higher sensitivity (160 HU), 15 of 17 (88%) patients were osteoporotic. Even using the L1 CT attenuation threshold of 110 HU for higher specificity, 14 of 17 (82%) patients were osteoporotic. CT attenuation demonstrates that a high proportion of AS patients who sustain fractures have osteoporosis. This overcomes some of the difficulties that have been encountered with the use of dual-energy X-ray absorptiometry in this group of patients. This simple and accessible method saves on time, cost, and exposure to radiation and can help in the planning of a patient's management.

Listeria rhomboencephalitis in a patient on a tumor necrosis factor α inhibitor (etanercept).

We describe a case of an 87-year-old woman with rheumatoid arthritis on etanercept who developed subacute encephalopathy. Magnetic resonance imaging and blood cultures led to the diagnosis of Listeria monocytogenes rhomboencephalitis, which proved to be fatal. Postmortem examination of the brain revealed abscesses with extensive necrosis. Gram stain showed small gram-positive rods in the necrotic tissue and the wall lining the abscesses. While rhomboencephalitis is a rare entity, and clinical recognition may be hampered by immunosuppression such as in this case, early blood cultures, lumbar puncture, and empiric treatment with ampicillin should be initiated in all patients with suspected rhomboencephalitis if suggested by imaging and by a clinical concern for infection.

Chronic kidney disease is an independent predictor of pocket hematoma after pacemaker and defibrillator implantation.

INTRODUCTION: The aim of this investigation was to determine additional predisposing factors of pocket hematoma formation in patients undergoing anti-arrhythmic device surgery. METHODS: Initially, we performed a retrospective chart review of 459 patients on warfarin therapy who underwent anti-arrhythmic device surgery (pacemaker or defibrillator implantation, generator replacement, or lead revision) between April 2004 and September 2008 to determine whether continuation of anticoagulation or cessation of anticoagulation, with or without bridging therapy, was the preferred approach. In those patients who developed pocket hematoma, we then analyzed factors that might predispose to hematoma formation. RESULTS: The incidence of pocket hematoma in the entire group was 2.2% (n = 10). Forty-eight percent of the patient group was on continued warfarin (n = 220), 27% on bridging therapy with intravenous heparin or subcutaneous enoxaparin (n = 123) and 66% were on antiplatelet therapy (aspirin or clopidegrol or both; n = 303) at the time of device implantation. Twelve percent of the patients had chronic kidney disease (n = 55). In multivariate regression analysis, after adjusting for anticoagulation and antiplatelet agents, chronic kidney disease was found to be a significant risk factor for pocket hematoma formation after ICD and pacemaker placement. An increase of 1.0 mg/dl in creatinine levels was associated with a nearly twofold increase in hematoma formation (OR, 1.99; 95% CI, 1.22-3.21; p = 0.03). CONCLUSION: Chronic kidney disease is a significant risk factor for pocket hematoma formation after pacemaker and ICD placement, independent of anticoagulation and antiplatelet agents.

Gout in the Hmong in the United States.

OBJECTIVE: To compare characteristics of gout in Hmong patients versus whites, and examine if Hmong ethnicity is associated with risk of tophaceous gout. METHODS: A retrospective chart review of Hmong and White patients with gout in a large health care system (Health Partners) in St. Paul, Minnesota, from January 2001 to March 2008, to compare clinical characteristics and risk factors for gout. Multivariable-adjusted hierarchical logistic regressions examined the association of Hmong ethnicity with risk of tophaceous gout, adjusting for age, sex, hypertension, diuretic use, and kidney function. RESULTS: The analytic dataset consisted of 89 Hmong patients and 84 White controls, all of whom had ethnicity confirmed, an International Classification of Diseases, ninth revision code for gout and had at least 2 physician-documented diagnoses of gout. The Hmong group was younger (58.3 vs. 66.3 years, P = 0.04), had an earlier onset of symptoms (37.4 vs. 55.0 years, P < 0.001) and higher mean serum uric acid levels during follow-up (9.1 vs. 7.6 mg/dL, P < or = 0.001). Hmong had higher rates of tophaceous gout (31.5% vs. 10.7%, P = 0.001), including hand tophi (21.3% vs. 3.6%, P < 0.001). In multivariable analyses that adjusted for age, sex, hypertension, diuretic, use, and kidney function, Hmong ethnicity was significantly associated with risk of tophaceous gout, with odds ratio 4.3 (95% confidence interval: 1.5, 12.2). CONCLUSION: Hmong patients have an earlier onset of gout symptoms. Hmong race is an independent risk factor for tophaceous gout. Future studies need to examine whether genetic or other comorbid factors predict this higher risk of more severe gout in Hmong.

Acute crystal-induced arthritis following arthroplasty.

Septic arthritis at the site of previous arthroplasty is a serious medical problem with high morbidity and mortality. Even with careful physical examination and laboratory evaluation, the diagnosis of septic arthritis may be difficult to confirm and many patients undergo operative procedures for presumed infection. In patients with previous arthroplasty, a synovial fluid white blood cell count of > 2500-3000/mm3 in the presence of an elevated erythrocyte sedimentation rate and C-reactive protein has been reported to indicate infection with a high degree of sensitivity and specificity. However, crystal-induced disease (gout, pseudogout) may present with the extact same clinical manifestations, physical examination, and laboratory results as infection. Yet crystal-induced disease is only rarely recognized in patients with previous arthroplasty. We report two cases of acute crystal disease in patients with previous arthroplasty that mimicked infection. Review of the few additional case reports extent suggests that crystal-induced disease may occur more frequently than heretofore recognized. We therefore propose that the evaluation of acute arthritis in a patient with previous arthroplasty include systematic evaluation for crystal disease, as patients may present with septic arthritis, crystal disease, or both.

Continuing warfarin therapy is superior to interrupting warfarin with or without bridging anticoagulation therapy in patients undergoing pacemaker and defibrillator implantation.

BACKGROUND: Current guidelines recommend stopping oral anticoagulation and starting bridging anticoagulation with intravenous heparin or subcutaneous enoxaparin when implanting a pacemaker or defibrillator in patients at moderate or high risk for thromboembolic events. A limited body of literature suggests that device surgery without cessation of oral anticoagulation may be feasible. OBJECTIVE: The purpose of this study was to evaluate the safety of device surgery in orally anticoagulated patients without interrupting warfarin therapy. METHODS: We performed a retrospective study of 459 consecutive patients on chronic warfarin therapy who underwent device surgery from April 2004 to September 2008. Warfarin was continued in 222 patients during the perioperative period. Warfarin was temporarily held and bridging therapy administered in 123 patients. Warfarin was temporarily held without bridging therapy in 114 patients. RESULTS: There were no significant differences with regard to age, sex, or risk factors for thromboembolism in the three groups. Patients who continued taking warfarin had a lower incidence of pocket hematoma (P = .004) and a shorter hospital stay (P <.0001) than did patients in the bridging group. Holding warfarin without bridging is associated with a higher incidence of transient ischemic attacks (P = .01). CONCLUSION: Temporarily interrupting anticoagulation is associated with increased thromboembolic events, whereas cessation of warfarin with bridging anticoagulation is associated with a higher rate of pocket hematoma and a longer hospital stay. Continuing warfarin with a therapeutic international normalized ratio appears to be a safe and cost-effective approach when implanting a pacemaker or defibrillator in patients with moderate to high thromboembolic risk.

Working memory capacity is decreased in sleep-deprived internal medicine residents.

BACKGROUND: Concerns about medical errors due to sleep deprivation during residency training led the Accreditation Council for Graduate Medical Education to mandate reductions in work schedules. Although call rotations with extended shifts continue, effects on resident sleep-wake times and working memory capacity (WMC) have not been investigated. OBJECTIVES: The objective of this study was to measure effects of call rotations on sleep-wake times and WMC in internal medicine residents. METHODS: During 2 months of an internal medicine training program adhering to ACGME work-hour restrictions (between April 2006 and June 2007), residents completed daily WMC tests, wore actigraphy watches, and logged their sleep hours. This observational study was conducted during a call month requiring 30-hour call rotations every fourth night, whereas the noncall month, which allowed sleep/wake cycle freedom, was used as the control. MAIN OUTCOME MEASURES: Sleep hours per night and WMC testing. RESULTS: Thirty-nine residents completing the study had less sleep per night during their call month (6.4 vs 7.3 h per night noncall, p < 0.001) and sleep per night varied from 3.7 to 10.1 hours. Call rotation caused greater self-assessed sleepiness and reduced WMC recall scores (-2.6/test, p < 0.05), and more math errors occurred when on call (+1.07/test, p < 0.04). Full recovery of WMC did not occur until the fourth day after call. On-call rotation on the first month had a confounding detrimental effect on WMC. CONCLUSION: A month of call rotations reduced overall sleep per night; sleep hours per night were variable, and WMC was adversely affected. Decreased WMC could explain impaired judgment during sleep deprivation, although clinical error rates were not evaluated.

Necrotizing granulomatous vasculitis associated with cocaine use.

Cocaine abuse may be associated with a destructive nasal and pharyngeal process felt to be due to ischemia secondary to vasoconstriction. This report is the first to document a necrotizing granulomatous vasculitis associated with nasal destruction and an oronasal fistula in a chronic cocaine user. Cocaine is an environmental insult that may play a role in triggering cerebral and non-cerebral vasculitis including a necrotizing granulomatous vasculitis of the respiratory tract.