Clinical and Laboratory Features in Anti-NF155 Autoimmune Nodopathy

Background and ObjectivesTo study the clinical and laboratory features of antineurofascin-155 (NF155)–positive autoimmune nodopathy (AN).MethodsPatients with anti-NF155 antibodies detected on routine immunologic testing were included. Clinical characteristics, treatment response, and functional scales (modified Rankin Scale [mRS] and Inflammatory Rasch-built Overall Disability Scale [I-RODS]) were retrospectively collected at baseline and at the follow-up. Autoantibody and neurofilament light (NfL) chain levels were analyzed at baseline and at the follow-up.ResultsForty NF155+ patients with AN were included. Mean age at onset was 42.4 years. Patients presented with a progressive (75%), sensory motor (87.5%), and symmetric distal-predominant weakness in upper (97.2%) and lower extremities (94.5%), with tremor and ataxia (75%). Patients received a median of 3 (2–4) different treatments in 46 months of median follow-up. Response to IV immunoglobulin (86.8%) or steroids (72.2%) was poor in most patients, whereas 77.3% responded to rituximab. HLA-DRB1*15 was detected in 91.3% of patients. IgG4 anti-NF155 antibodies were predominant in all patients; anti-NF155 titers correlated with mRS within the same patient (r = 0.41, p = 0.004). Serum NfL (sNfL) levels were higher in anti-NF155+ AN than in healthy controls (36.47 vs 7.56 pg/mL, p < 0.001) and correlated with anti-NF155 titers (r = 0.43, p = 0.001), with I-RODS at baseline (r = −0.88, p < 0.001) and with maximum I-RODS achieved (r = −0.58, p = 0.01). Anti-NF155 titers and sNfL levels decreased in all rituximab-treated patients.DiscussionAnti-NF155 AN presents a distinct clinical profile and good response to rituximab. Autoantibody titers and sNfL are useful to monitor disease status in these patients. The use of untagged-NF155 plasmids minimizes the detection of false anti-NF155+ cases.Classification of EvidenceThis study provides Class IV evidence that anti-NF155 antibodies associate with a specific phenotype and response to rituximab.

COVID-19 vaccine-induced immune thrombotic thrombocytopenia: A review of the potential mechanisms and proposed management

With over 600 million coronavirus (COVID-19) vaccine doses administered globally, adverse events are constantly monitored. Recently however, reports of thrombosis and thrombocytopenia following vaccination with the ChAdOx1 nCoV-19 vaccine have emerged. This paper aims to review the available literature and guidelines pertaining to vaccine-induced immune thrombotic thrombocytopenia (VITT) and the proposed guidelines, while offering a potential approach that unifies the available evidence. While the risk of VITT remains extremely low and the benefits outweigh the risks, experimental studies are needed to clarify the pathophysiology behind VITT and possibly decrease the risk of thrombosis and other adverse events occurring. However, treatment should not be delayed in suspected cases, and IV immunoglobulin and non-heparin anticoagulation should be initiated.

Hemophagocytic Lymphohistiocytosis in Children

Objective of the Paper: To present a clinical case of a 2.5-year girl hospitalised with severe pneumonia with associated hemophagocytic lymphohistiocytosis (HLH). Key Points. HLH is a syndrome, the clinical representation of which is a system sepsis-like inflammatory reaction; in the majority of cases, this condition is hardly diagnosed by paediatricians. Associated pancytopenia and hyperferritinaemia are of diagnostic importance. Here we present a clinical case of a 2.5-year girl who was hospitalised with severe pneumonia and associated HLH. As there is no common approach to the management of HLH, we summoned a board of doctors and decided to start steroid therapy (dexamethasone) and IV immunoglobulin (Octagam), and if there was no effect from therapy within a week, cytostatic agents would be added. The therapy was initiated promptly after macrophages had been found in bone marrow smear. Clinical and paraclinic improvements were noted on day 5, so aggressive immunosuppresion was not initiated. In a month there were no signs of organ dysfunction; the values normalised, and the child was discharged from the inpatient clinic. Conclusion. HLH is associated with high mortality, therefore, early diagnosis and therapy are critical. The specificity of this case is that we managed to promptly diagnose the condition, initiated treatment and achieved complete remission without aggressive immunosuppresion. Keywords: hemophagocytic lymphohistiocytosis, macrophages, pancytopenia.

Monoclonal gammopathies of clinical significance

“Monoclonal gammopathy of clinical significance” (MGCS) is the term used to describe nonmalignant monoclonal gammopathies causing important disease. MGCS is the differential diagnosis for any patient presenting with what appears to be a monoclonal gammopathy of undetermined significance but is also experiencing other unexplained symptoms. Broadly, these conditions can be separated into symptoms and signs referable to the nerves, the kidneys, and the skin. The first step in making these diagnoses is to consider them. With a particular condition in mind, the next step is to order those tests that can help confirm or dismiss a particular diagnosis. Nearly all of the renal and dermatologic conditions are diagnosed by renal and skin biopsies, respectively. The importance of a highly competent renal pathologist and dermatopathologist cannot be underestimated. Biopsy is less specific for the neuropathic conditions. Because several of the MGCSs are syndromes, recognizing other manifestations is also key. Treatment recommendations for many of these conditions are anecdotal because of their rarity, but for several of the conditions, IV immunoglobulin, rituximab, and plasma cell–directed therapy are the best options.

Eastern equine encephalitis and use of IV immunoglobulin therapy and high-dose steroids

ObjectiveTo determine the clinical presentation and patient outcomes after treatment with IV immunoglobulin (IVIG), high-dose steroids, or standard of care alone in Eastern equine encephalitis (EEE), a mosquito-borne viral infection with significant neurologic morbidity and mortality.MethodsA retrospective observational study of patients admitted to 2 tertiary academic medical centers in Boston, Massachusetts, with EEE from 2005 to 2019.ResultsOf 17 patients (median [IQR] age, 63 [36–70] years; 10 (59%) male, and 16 (94%) White race), 17 patients had fever (100%), 15 had encephalopathy (88%), and 12 had headache (71%). Eleven of 14 patients with CSF cell count differential had a neutrophil predominance (mean = 60.6% of white blood cells) with an elevated protein level (median [IQR], 100 mg/dL [75–145]). Affected neuroanatomic regions included the basal ganglia (n = 9/17), thalamus (n = 7/17), and mesial temporal lobe (n = 7/17). A total of 11 patients (65%) received IVIG; 8 (47%) received steroids. Of the patients who received IVIG, increased time from hospital admission to IVIG administration correlated with worse long-term disability as assessed by the modified Rankin Scale (mRS) (r = 0.72, p = 0.02); steroid use was not associated with the mRS score. The mortality was 12%.ConclusionsClinicians should suspect EEE in immunocompetent patients with early subcortical neuroimaging abnormalities and CSF neutrophilic predominance. This study suggests a lower mortality than previously reported, but a high morbidity rate in EEE. IVIG as an adjunctive to standard of care may be considered early during hospitalization.

Bickerstaff brainstem encephalitis with or without anti-GQ1b antibody

ObjectiveTo clarify the differences in clinical characteristics between anti-GQ1b antibody-positive and antibody-negative Bickerstaff brainstem encephalitis (BBE).MethodsWe compared 73 anti-GQ1b antibody-positive BBE cases with 10 antibody-negative cases. Their clinical information and sera were collected from various hospitals throughout Japan between 2014 and 2017. The anti-GQ1b antibody was examined in each serum sample by ELISA.ResultsWe identified the distinctive findings of anti-GQ1b antibody-positive BBE compared with the antibody-negative cases: (1) upper respiratory infection and sensory disturbance were more common, (2) the cell count or protein concentration was lower in the CSF, (3) the abnormal findings on brain MRI were less, and (4) the consciousness disturbance disappeared earlier. Furthermore, IV immunoglobulin (IVIG) was more frequently administered to the anti-GQ1b antibody-positive cases of BBE compared with the antibody-negative cases.ConclusionsBBE with anti-GQ1b antibody has homogeneous features. IVIG is the treatment used prevalently for BBE with anti-GQ1b antibody in Japan.