Inflammatory colitis associated with Teriflunomide.

Teriflunomide is an oral disease modifying therapy for relapsing-remitting multiple sclerosis (RRMS). Gastrointestinal (GI) side effects occurred in 15-17.9% of patients in the clinical trials and usually were mild and self-limiting. Few cases of inflammatory colitis related to teriflunomide and leflunomide, a prodrug which converts to teriflunomide and is used in the treatment of rheumatoid arthritis, have been reported but no clinical data is available except for a single case of lymphocytic colitis. We here report a 49-year-old man with RRMS who developed severe diarrhea and weight loss six months after starting teriflunomide and eventually was found to have multiple ulcers and inflammatory changes consistent with Crohn's disease. After stopping teriflunomide and chelation therapy, he was started on immunotherapy for Crohn's given the highly inflammatory degree of GI symptoms and histology findings.

Delayed immune-related events (DIRE) after discontinuation of immunotherapy: diagnostic hazard of autoimmunity at a distance.

BACKGROUND: The risk of delayed autoimmunity occurring months or years after discontinuation of immunotherapy is frequently asserted in the literature. However, specific cases were rarely described until 2018, when a wave of reports surfaced. With expanding I-O indications in the adjuvant/neoadjuvant curative setting, growing numbers of patients will receive limited courses of immunotherapy before entering routine surveillance. In this context, under-recognition of DIRE could pose a growing clinical hazard. METHODS: The aim of this study was to characterize DIRE through identification of existing reports of delayed post-treatment irAE in cancer patients treated with immunotherapy. We performed a PubMed literature review from 2008 through 2018 to determine the median data safety reporting window from existing I-O clinical trials, which we then applied to define the DIRE cutoff, and collated all qualifying reports over the same time span. DIRE was defined as new immune-related adverse events (irAE) manifesting ≥90 days after discontinuation of immunotherapy. RESULTS: Median duration of I-O clinical trials data safety reporting was 90 days (82% ≤ 90 days). DIRE cutoff was thus set as ≥90 days post-immunotherapy. We identified 23 qualifying cases; 21 by literature review and 2 from our institution. Median off-treatment interval to DIRE was 6 months (range: 3 to 28). Median cumulative immunotherapy exposure was 4 doses (range: 3 to 42). Involvement included endocrine, neurologic, GI, pulmonary, cardiac, rheumatologic and dermatologic irAE. CONCLUSIONS: As immunotherapy indications expand into the curative setting, often with brief exposure and potentially sequenced with multimodality treatments, it will be necessary to recognize an emerging diagnostic complex, which we have termed delayed immune-related events (DIRE). Clinical vigilance has the potential to reduce morbidity from diagnostic delay, as irAE are generally manageable with prompt initiation of treatment - or from misdiagnosis - as misattribution can lead to unnecessary or harmful interventions as we describe. DIRE should therefore figure prominently in the differential diagnosis of patients presenting with illnesses of unclear etiology, irrespective of intervening treatments or interval post-immunotherapy, both of which can confound diagnosis. Increased recognition will rest on delineation of DIRE as a clinical diagnostic entity.

Acute myocardial infarction associated with initial alemtuzumab infusion cycle in relapsing-remitting multiple sclerosis.

Alemtuzumab is an anti-CD52 monoclonal antibody used for the treatment of lymphoproliferative disorders and relapsing-remitting multiple sclerosis. We report a 30-year-old woman with relapsing-remitting multiple sclerosis who developed a type 2 non-ST elevated myocardial infarction (NSTEMI) during her first alemtuzumab infusion cycle. While acute coronary syndrome has been described with alemtuzumab in the treatment of lymphoma, alemtuzumab-associated cardiac ischemia in multiple sclerosis is uncommon and can occur in patients without cardiovascular risk factors.

Daclizumab: Mechanisms of Action, Therapeutic Efficacy, Adverse Events and Its Uncovering the Potential Role of Innate Immune System Recruitment as a Treatment Strategy for Relapsing Multiple Sclerosis.

Daclizumab (DAC) is a humanized, monoclonal antibody that blocks CD25, a critical element of the high-affinity interleukin-2 receptor (IL-2R). DAC HYP blockade of CD25 inhibits effector T cell activation, regulatory T cell expansion and survival, and activation-induced T-cell apoptosis. Because CD25 blockade reduces IL-2 consumption by effector T cells, it increases IL-2 bioavailability allowing for greater interaction with the intermediate-affinity IL-2R, and therefore drives the expansion of CD56bright natural killer (NK) cells. Furthermore, there appears to be a direct correlation between CD56bright NK cell expansion and DAC HYP efficacy in reducing relapses and MRI evidence of disease activity in patients with RMS in phase II and phase III double-blind, placebo- and active comparator-controlled trials. Therapeutic efficacy was maintained during open-label extension studies. However, treatment was associated with an increased risk of rare adverse events, including cutaneous inflammation, autoimmune hepatitis, central nervous system Drug Reaction with Eosinophilia Systemic Symptoms (DRESS) syndrome, and autoimmune Glial Fibrillary Acidic Protein (GFAP) alpha immunoglobulin-associated encephalitis. As a result, DAC HYP was removed from clinical use in 2018. The lingering importance of DAC is that its use led to a deeper understanding of the underappreciated role of innate immunity in the potential treatment of autoimmune disease.

Acute progressive paraplegia in heroin-associated myelopathy.

As the opioid epidemic continues, understanding manifestations of abuse, including heroin-associated myelopathy remains essential. Here we describe a young man with a past medical history significant for polysubstance abuse who developed acute-onset, rapidly progressive myelopathy after resumption of intravenous heroin use. He had significant spinal cord involvement with findings suggestive of heroin-associated myelopathy. The salient features of this case include diffusion imaging of the spine and spinal angiography supporting a possible vasculopathy as the pathophysiologic mechanism underlying heroin-associated myelopathy. Additionally, CSF studies showed the transition from a neutrophilic pleocytosis to a lymphocytic pleocytosis suggesting an inflammatory component.

Jaw Dystonia and Reversible Basal Ganglia Changes as an Initial Presentation of Systemic Lupus Erythematosus.

Dystonia as a manifestation of neuropsychiatric lupus erythematosus (NPSLE) is uncommon. We report a 25-year-old woman who experienced progressive confusion, reduced speech, and difficulty opening her mouth approximately 2 weeks after development of a facial rash. Brain imaging showed bilateral, symmetric signal abnormalities within the basal ganglia and subcortical white matter. Despite treatment with high-dose steroids, she continued to have difficulty speaking with evidence of jaw dystonia on examination. Jaw dystonia rapidly improved with the initiation of levodopa. Repeat evaluation 3 months later exhibited the absence of jaw dystonia and near resolution of the imaging abnormalities. Our patient demonstrated a unique presentation with jaw dystonia refractory to traditional treatment for NPSLE. Such a presentation likely represents a severe variant of NPSLE requiring both immunosuppressive and symptomatic therapies.

Calcaneal quantitative ultrasound compared with hip and femoral neck dual-energy x-ray absorptiometry in people with a spinal cord injury.

OBJECTIVE: To evaluate the sensitivity and specificity of calcaneal quantitative ultrasound (QUS) measurements for identifying osteoporosis determined by dual-energy x-ray absorptiometry (DXA) at the hip in a spinal cord injury (SCI) population. DESIGN: Cross-sectional retrospective review of data collected in the bone health registry of persons with a disability. SETTING: Inpatients and outpatients at a single acute rehabilitation hospital. PARTICIPANTS: A convenience sample of 66 participants, both inpatients and outpatients, with a spinal cord injury. METHODS: Calcaneal T scores were determined by ultrasound, and bone density of the lumbar spine, total hip, and femoral neck were determined by DXA. MAIN OUTCOME MEASUREMENTS: Right and left calcaneal QUS T scores and right and left hip and femoral neck DXA T scores. RESULTS: Right and left hip DXA T scores were strongly associated with corresponding right and left calcaneal QUS T scores (right: r = .72, P < .001; left: r = .70, P < .001). Similar associations were found when we evaluated femoral neck T scores and calcaneal QUS T scores. Receiver operating characteristic analysis for evaluating QUS to identify DXA-defined osteoporosis demonstrated an area under the curve of 0.81 for all participants (acute and chronic injury) and 0.68 for those with a chronic SCI. CONCLUSIONS: A strong association exists between calcaneal QUS T scores and bone density T scores at the hip measured by DXA. QUS may have a place in the screening of people with SCI 1 year or more after their injury to evaluate their bone status.