Colchicine and/or Naltrexone for Hospitalized COVID-19 Patients Not Requiring High Levels of Ventilatory Support (COLTREXONE): A Prospective, Randomized, Open-Label Trial.

We assessed the efficacy and safety of colchicine and low-dose naltrexone (LDN), alone and in combination, in preventing progression to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this prospective, randomized, open-label trial, colchicine and LDN were compared to standard of care (SOC) in patients hospitalized with SARS-CoV-2 not requiring high levels of ventilatory support. Patients were randomly assigned to colchicine alone, LDN alone, colchicine/LDN in combination, or SOC. The primary outcome was time to disease recovery. Secondary outcomes included total time hospitalized, study enrollment, level of care, oxygen support, and adverse events.  One-hundred and thirty-seven patients were randomized (Nc = 34, Nc+ldn = 33, Nldn = 35, Nsoc = 35). Eighty-four patients (61%) achieved disease recovery by day 5. There was no significant difference in the proportion of patients who experienced the primary efficacy outcome among those who received colchicine, LDN, or between the four study arms.Patients receiving colchicine had a shorter length of enrollment but not a significant reduction in the length of stay. Diarrhea was the most common adverse reaction. In adults hospitalized with SARS-CoV-2 not requiring high-level ventilatory support, colchicine and LDN, alone and in combination, were not associated with significant reductions in progression to severe disease.

Continuous IV infusion of anakinra.

Objective: A review of the use of continuous IV infusion of anakinra; a description of the protocol for continuous IV infusion of anakinra in the treatment of cytokine storm developed over the past 4 years at a tertiary level academic medical center in the United States. Methods: We reviewed published reports of continuous IV infusion of anakinra in cytokine storm and summarize this method of treatment in other diseases. As well, over the past 4 years, continuous IV infusions of anakinra were administered at our tertiary level academic medical center in the United States (Regions Hospital, St. Paul, Minnesota) for approximately 400 patient days of treatment primarily for the cytokine storm associated with macrophage activation syndrome (MAS) in adults. This updated protocol is presented. While this a single center protocol, it may serve as an initial guide for further refinement of protocols in MAS and other conditions. Conclusion:Continuous IV infusion of anakinra has advantages over subcutaneous infusions and may be important in controlling severe life-threatening cytokine storm as seen in macrophage activation syndrome. This has the potential to be an important therapy for other syndromes including Cytokine Release Syndrome related to CAR T-cell therapy. Close collaboration between Rheumatology, Pharmacy and Nursing allows this treatment to be delivered rapidly and efficiently.

Unique Considerations for the Management of Gout in the Hmong Population: Examining Tertiary Encounters at a Large Regional Health Care System.

OBJECTIVE: To evaluate demographic characteristics, care encounters, comorbidities, and clinical differences in Hmong and non-Hmong patients with gout. METHODS: Using retrospective chart review, all inpatient encounters (Hmong versus non-Hmong) were reviewed from 2014 to 2017. Acute or chronic gout was the primary or secondary diagnosis for the encounter. RESULTS: Hmong gout patients were on average 11 years younger than non-Hmong patients, but after adjustment for age, sex, and type of encounter, they had similar rates of hypertension, diabetes mellitus, and heart disease. Hmong patients had significantly decreased renal function at the time of presentation; the odds ratio of chronic kidney disease for Hmong patients was 2.33 versus 1.48 for non-Hmong patients (P < 0.05), the mean creatinine level was 3.3 mg/dl versus 2.0 mg/dl (ß = 1.35, P < 0.001), and the glomerular filtration rate was 44.8 ml/minute versus 49.3 ml/minute (ß = -6.95, P < 0.001). Hmong gout patients were more likely to use emergency care versus elective or urgent care, they were less likely to be using medications for the treatment of gout prior to admission (32.3% versus 58.2%), and the length of hospital stay was increased (8.8 versus 5.2 days; P < 0.05). CONCLUSION: Hmong gout patients who had a tertiary care encounter were 11 years younger than non-Hmong patients with similar rates of comorbidities but had worse renal function despite the age differences. They were more likely to use emergency services, to be insured through Medicaid, and not to use preventive medications for gout prior to their encounter. Intensive efforts are needed in the Hmong population for culturally appropriate preventive care management of gout along with diabetes mellitus, hypertension, heart disease, and kidney disease.

A 56-Year-Old Woman with Recurrent Strokes: A Clear Case with a Therapeutic Dilemma.

A 56-year-old woman with a history of cerebral amyloid angiopathy (CAA) complicated by prior intracranial hemorrhage (ICH) was evaluated for an asymptomatic ischemic stroke discovered on screening brain MRI. On echocardiogram, she was found to have a mass on her mitral valve and strongly positive antiphospholipid antibodies. She was diagnosed with nonbacterial thrombotic (Libman-Sacks) endocarditis associated with the primary antiphospholipid syndrome (APS). The treatment decision was complicated by the history of CAA with ICH within the last year with very high risk for bleeding complications if on anticoagulation. A multidisciplinary decision was made to initiate a trial of warfarin for 3 months. She fared well and warfarin was continued. She has not had any further bleeding or ischemic events over the subsequent 1.5 years and remains on warfarin for her APS.

Continuous Intravenous Anakinra Infusion to Calm the Cytokine Storm in Macrophage Activation Syndrome.

OBJECTIVE: The objective of this study was to report the benefit of a therapeutic approach consisting of intravenous (IV) continuous anakinra (recombinant human interleukin-1 receptor antagonist) infusions in treating severely ill adult patients with secondary hemophagocytic lymphohistiocytosis or macrophage activation syndrome (MAS). METHODS: A retrospective chart review of five patients treated at Regions Hospital from 2016 to 2019 was conducted. Demographic, clinical, and laboratory characteristics and outcomes were recorded. RESULTS: Continuous IV anakinra infusions up to 2400 mg/d resulted in rapid serologic, then clinical response in 4 of 5 severely ill patients who were refractory to all other therapies, including subcutaneous anakinra. Subsequently, 3 of 5 patients have been maintained on anakinra or canakinumab, with no recurrence of MAS. CONCLUSION: Continuous infusion of IV anakinra may result in rapid serologic and subsequent clinical improvement in adult patients with MAS. This method for treating cytokine storm should be considered in the current COVID-19 pandemic in the subgroup of patients with severe disease who have a cytokine storm presentation.

Guidelines for treatment of Susac syndrome - An update.

Susac syndrome is an immune-mediated, pauci-inflammatory, ischemia-producing, occlusive microvascular endotheliopathy/basement membranopathy that affects the brain, retina, and inner ear. Treatment of Susac syndrome is particularly challenging. The organs involved can easily become irreversibly damaged, and the window of opportunity to protect them is often short. Optimal outcome requires rapid and complete disease suppression. Adding to the challenge is the absence of objective biomarkers of disease activity and the great variability in presentation, timing and extent of peak severity, duration of peak severity, and natural disease course. There have been no randomized controlled trials or prospective treatment studies. We offer treatment guidelines based on cumulative clinical experience and a large cohort of patients followed longitudinally in a comprehensive database project. These guidelines state our preferences but do allow flexibility and discuss other options. The guidelines also serve as an initial step in the planning of prospective treatment studies, future consensus-based recommendations, and future randomized controlled trials.

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.

Safety of retrievable inferior vena cava filters in patients with the antiphospholipid syndrome.

OBJECTIVE: Consideration for placement of an inferior cava filter arises in patients with APS where cessation of anticoagulation is necessary or thrombotic complications continue despite maximal anticoagulation. Permanent IVC filters are recommended to be avoided. We evaluated the safety of placement and removal of retrievable inferior vena cava filters in patients with APS. METHODS: Case series of 5 patients with APS and aPL antibodies who had placement and removal of retrievable IVC filter (because of contraindication to anticoagulation or ongoing thrombosis despite full anticoagulation) to assess for safety, presence of clots in the vena cava or on the filter while in the body, evidence of PE, or clot on the explanted filter. RESULTS: Insertion and removal, even while on anticoagulation, was safe. There was no evidence of clot in the vena cava, on the filter or pulmonary embolism in all cases. CONCLUSION: Where necessary, retrievable IVC filters may be safer in APS patients but should not be left in for long periods of time.

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.

Severe polyserositis induced by the 13-valent pneumococcal conjugate vaccine: a case report.

BACKGROUND: The United States Advisory Committee on Immunization Practices recommends administration of the 13-valent pneumococcal conjugate vaccine in series with the 23-valent pneumococcal polysaccharide vaccine for prevention of pneumonia in the elderly. Reports of autoimmune or auto-inflammatory diseases as a result of pneumococcal vaccination, especially pneumococcal conjugate vaccine, are extremely rare. CASE PRESENTATION: We present a case of severe serositis in a 75-year-old Caucasian woman complicated by pericardial and pleural effusions in the setting of recent 13-valent pneumococcal conjugate vaccine vaccination and no other obvious etiology. Our patient required steroid treatment, thoracentesis, chest tube, and pericardial window and subsequently recovered to her baseline. CONCLUSIONS: To the best of our knowledge, no such reaction to the 13-valent pneumococcal conjugate vaccine has previously been documented. Although the benefits of vaccination outweigh the risks, knowledge of this potential side effect can help clinicians in diagnosis and treatment of similar patients.

Lupus Gastrointestinal Tract Vasculopathy: Lupus "Enteritis" Involving the Entire Gastrointestinal Tract from Esophagus to Rectum.

Gastrointestinal symptoms are very common in systemic lupus erythematosus (SLE). Lupus "enteritis" is very responsive to treatment but can have devastating consequences if not detected. Most descriptions of enteritis involve the small and large bowel. This is the first report of lupus "enteritis" involving the entire gastrointestinal tract from the esophagus and stomach to the rectum. Lupus "enteritis" is another cause of upper gastrointestinal involvement in SLE (involving even the esophagus and stomach) in addition to involvement of the lower intestinal tract.

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.

Susac syndrome with prominent dermatological findings and a prompt response to intravenous immunoglobulin, steroids, and rituximab: a case report.

BACKGROUND: Susac syndrome (retinocochleocerebral vasculopathy) is an autoimmune endotheliopathy affecting the precapillary arterioles of the brain, retina, and inner ear. It presents with encephalopathy, branch retinal artery occlusions, and hearing loss. The condition is often under recognized because the clinical symptoms may present at different times and physicians may be unfamiliar with the syndrome. Peripheral findings would be helpful in early diagnosis. There are numerous treatment regimens proposed with varying effectiveness. CASE PRESENTATION: We report the case of a 22-year-old Caucasian man in whom there were prominent skin findings, including livedo reticularis and a micropapular eruption which responded promptly to treatment suggesting that skin involvement may facilitate earlier diagnosis. Rituximab has occasionally been used in more refractory disease. We observed a prompt response to the combination of intravenous immunoglobulin, corticosteroids, and rituximab instituted immediately after diagnosis. CONCLUSIONS: A careful search for dermatological manifestations may help with earlier diagnosis. Skin findings may be another marker of endothelial cell involvement. Early use of rituximab as part of the therapeutic regimen may be warranted.

Anakinra for the treatment of acute severe gout in critically ill patients.

OBJECTIVES: To report on the efficacy and safety of anakinra for treatment of acute gouty arthritis in medically complex, critically ill patients. METHODS: Retrospective chart review of 13 critically ill hospitalized patients treated with anakinra for 20 episodes of acute gouty arthritis between 2009 and 2014 at a single health plan and institution (HealthPartners Medical Group and Regions Hospital) in Saint Paul, Minnesota. Data was obtained on baseline characteristics, medical comorbidities, reason for hospitalization, prior gout treatment, reason for choosing anakinra over standard therapy, anakinra dosing, response to treatment, and adverse outcomes. RESULTS: A total of 10 patients were in the Intensive Care Unit, 1 was in the Burn Unit for extensive 3rd degree burns, 1 was critically ill with a new diagnosis of hemophagocytic lymphohistiocytosis, and 1 was critically ill in isolation with active disseminated multidrug-resistant tuberculosis. Of these patients, 85% had active infections and 92% had renal insufficiency. All patients had a significant response to anakinra treatment: 50% (10/20 episodes) within 24h, an additional 40% (8/20 episodes) by 48h, and the remaining 10% (2/20 episodes) by 72h. Anakinra was well tolerated with only 1 case of leukopenia and 1 possible infectious complication. CONCLUSIONS: Anakinra is a safe and efficacious treatment for acute gouty arthritis in medically complex, critically ill patients when standard treatment modalities cannot be used.

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.