Treatment of Severe Japanese Encephalitis Complicated With Hashimoto’s Thyroiditis and Guillain-Barré Syndrome With Protein A Immunoadsorption: A Case Report

A severely comatose female patient was diagnosed with Japanese encephalitis (JE). Her condition was complicated by Hashimoto’s thyroiditis (HT) and Guillain-Barré syndrome (GBS). After antiviral, glucocorticoid, and immunoglobulin treatment, the patient’s consciousness was restored, and she could breathe spontaneously. Following this, new-onset, primarily demyelinating GBS developed, which progressed to demyelination combined with axonal injury. The patient was switched to protein A immunoadsorption (PAIA) therapy, and her Hughes score decreased rapidly, from 4 to 1 after 6 months. This patient is the first to receive PAIA combined with an antiviral-glucocorticoid-immunoglobulin regimen to treat encephalitis, meningitis, HT, and GBS caused by JE infection, thereby reflecting the importance of clinical application of PAIA in the treatment of immunological complications of JE.

A Multi‑Center, Open‑Label, Single‑Arm Trial to Evaluate the Efficacy, Pharmacokinetics, and Safety and Tolerability of IGSC 20% in Subjects with Primary Immunodeficiency

Purpose The purpose of this phase 3 study was to evaluate the efficacy, pharmacokinetics (PK), and safety of Immune Globulin Subcutaneous (Human), 20% Caprylate/Chromatography Purified (IGSC 20%) in patients with primary immunodeficiency (PI). Methods Immunoglobulin treatment-experienced subjects with PI received 52 weeks of IGSC 20% given weekly at the same dose as the subject’s previous IgG regimen (DAF 1:1); the minimum dose was 100 mg/kg/week. The primary endpoint was serious bacterial infections (SBIs [null vs alternative hypothesis: SBI rate per person per year ≥ 1 vs < 1]). IgG subclasses and specific pathogen antibody levels were also measured. Results Sixty-one subjects (19 children [≤ 12 years], 10 adolescents [> 12–16 years], and 32 adults) were enrolled. The rate of SBIs per person per year was 0.017. The 1-sided 99% upper confidence limit was 0.036 (< 1), and the null hypothesis was rejected. The rate of hospitalization due to infection per person per year was 0.017 (2-sided 95% confidence interval: 0.008–0.033) overall. The mean trough total IgG concentrations were comparable to the previous IgG replacement regimen. The average of the individual mean trough ratios (IGSC 20%:previous regimen) was 1.078 (range: 0.83–1.54). The average steady-state mean trough IgG concentrations were 947.64 and 891.37 mg/dL, respectively. Seven subjects had serious treatment-emergent adverse events (TEAEs); none was drug-related. The rate of all TEAEs, including local infusion site reactions, during 3045 IGSC 20% infusions was 0.135. Most TEAEs were mild or moderate. Conclusions IGSC 20% demonstrated efficacy and good safety and tolerability in subjects with PI.

Evaluation of Intravenous Immunoglobulin G treatment in Outpatients Rheumatology Practice

Objective: Intravenous immunoglobulin is an alternative therapeutic agent that can be used off-label in many autoimmune rheumatological diseases. The aim of this study is to evaluate the autoimmune rheumatological diseases characteristics in which intravenous immunoglobulin therapy is used and the efficacy and safety of this therapy. Methods and Methods: We performed a retrospective review of 133 patients with autoimmune rheumatological disease who received at least 1 course of intravenous immunoglobulin treatment at Hacettepe University Rheumatology Outpatient Clinic between January 2013 and December 2020. The autoimmune rheumatological disease demographic and clinical features, organ involvements, treatment phases (primary-secondary or infection), treatment responses and adverse effects were evaluated. Results: A total of 79% (n=105) patients were female and the mean±SD age was 45.5±16.9 years. The most common underlying rheumatic diseases were systemic lupus erythematosus (35%, n=47) and dermatomyositis/polymyositis (35%, n=47). Intravenous immunoglobulin therapy was most commonly used for resistant/relapsed myositis and haematological involvement. The median (IQR) intravenous immunoglobulin treatment course was 6.5 (13) and the duration of intravenous immunoglobulin treatment was 10.8 (24) months. Although it is used as second-line therapy in 77% of patients, complete clinical response was observed in 32% and partial response in 47%. There was a significant reduction in the median (IQR) steroid doses (methylprednisolone or equivalent dose) patients received from baseline after intravenous immunoglobulin treatment [30 (33) vs 8 (12), p<0.0001]. It was observed that the use of conventional disease-modifying antirheumatic drugs decreased after intravenous immunoglobulin treatment and the use of rituximab increased. Adverse effects associated with intravenous immunoglobulin treatment (10%) and discontinuation (4%) were found to be very low. Conclusion: Intravenous immunoglobulin treatment was commonly given in systemic lupus erythematosus and dermatomyositis/polymyositis patients because of hematological involvement and resistant/relapsed myositis in our study, respectively. Although it is mainly the second-line treatment, two-thirds of the patients achieved a complete/partial response. Side effects and related discontinuation due to intravenous immunoglobulin treatment are very few.

Correlations between Electrophysiological Parameters, Lymphocyte Distribution and Cytokine Levels in Patients with Chronic Demyelinating Inflammatory Polyneuropathy

The goal of this study was to analyse, in relation to electrophysiological results, the distribution of lymphocyte subpopulations and the level of cytokines in patients with the typical form of chronic demyelinating inflammatory polyneuropathy (CIDP) before immunoglobulin treatment. The study group consisted of 60 patients (52 men, eight women), with a mean age 64.8 ± 11.2, who fulfilled the diagnostic criteria for the typical variant of CIDP, with (23 patients) and without (37 patients) diabetes mellitus. We analysed the results of the neurophysiological tests, and correlated them with the leukocyte subpopulations, and cytokine levels. In CIDP patients, IL-6, IL-2, IL-4 and TNF-α levels were significantly increased compared to the control group. Fifty patients had decreased levels of T CD8+ lymphocytes, and 51 patients had increased levels of CD4+ lymphocytes. An increased CD4+/CD8+ ratio was also found. Negative correlations were observed mainly between compound muscle action potential (CMAP) amplitudes and cytokine levels. The study enabled the conclusion that electrophysiological parameters in CIDP patients are closely related to the autoimmune process, but without any clear differences between patients with and without diabetes mellitus. Correlations found in the study indicated that axonal degeneration might be independent of the demyelinating process and might be caused by direct inflammatory infiltration.

Duration and temporal dispersion measurements in CIDP subjects from the Polyneuropathy And Treatment with Hizentra (PATH) study

Introduction: Distal compound muscle action potential (dCMAP) duration and temporal dispersion (TD) are electrophysiological hallmarks of demyelination and important for the diagnosis of CIDP. While the impact of CIDP treatment on other nerve conduction parameters has been examined, the effects on dCMAP and TD remain unexplored. The aim of the study was to examine the impact of withdrawal of immunoglobulin treatment on dCMAP duration and TD, and also the influence of the measurement technique on dCMAP duration and TD. Methods: Nerve conduction studies were analyzed from the PATH (Polyneuropathy And Treatment with Hizentra) study which randomized patients with CIDP to two doses of IgPro 20 and placebo. Distal CMAP duration and TD were obtained by two methods of measurements (D1 and D2, TD1 and TD2) from the median and peroneal nerves. Results: The dCMAP and TD were obtained from 389 tracings. While the two methods of measurement showed differences in D1 and D2 with D2 longer than D1 in all the three groups, there was no difference between the TD1 and TD2. There was no difference at baseline in dCMAP duration or TD among the three groups. At the end of treatment, patients in the placebo arm had no worsening of dCMAP and TD compared to baseline or the treated groups. Conclusion: dCMAP duration and TD did not show a difference between treated and placebo groups, and may be less sensitive measures than other nerve conduction parameters when evaluating changes in treatment. The method of dCMAP duration measurement does not affect TD as long as a consistent method is followed.

Endocarditis Caused by Candida parapsilosis Presenting With Severe Thrombocytopenia in a Patient With Tetralogy of Fallot

Infective endocarditis (IE) occurs more frequently in individuals living with congenital heart disease, often with high morbidity and mortality. Although gram-positive bacterial infections commonly cause IE, prosthetic valves are a known risk factor for fungal IE. We report a case of prosthetic pulmonary valve Candida parapsilosis IE in a 58-year-old male with repaired tetralogy of Fallot. He presented with fatigue, petechiae, and hematochezia. He had severe thrombocytopenia from idiopathic/immune thrombocytopenia purpura, which resolved with steroids and immunoglobulin. Treatment with antifungals as well as a surgical pulmonary valve replacement resulted in recovery without relapse at greater than a year.

Posterior reversible encephalopathy syndrome following Miller-Fisher syndrome

A 71-year-old woman presented to the emergency room with dysphonia, diplopia, dysphagia and generalised weakness since that day. Neurological examination revealed eye adduction limitation, ptosis, hypoactive reflexes and gait ataxia. Blood and cerebrospinal fluid analysis and brain CT were normal. Electromyography revealed a sensory axonal polyneuropathy. She was diagnosed with Miller-Fisher syndrome (MFS) and started on intravenous immunoglobulin. Two days after intravenous immunoglobulin treatment was completed, she developed a sustained hypertensive profile and presented a generalised tonic-clonic seizure. Brain MRI was suggestive of posterior reversible encephalopathy syndrome (PRES) and supportive treatment was implemented with progressive improvement. PRES may be a possible complication of MFS not only due to autonomic and inflammatory dysfunctions, but also as a consequence of its treatment. Patients with MFS should be maintained under close surveillance, especially in the first days and preferably in intermediate care units.