Impact of Immunomodulatory Therapy on COVID-19 Vaccine Response in Patients with Autoimmune Inflammatory Rheumatic Diseases.

Coronavirus disease 2019 (COVID-19) vaccination is essential for patients with autoimmune inflammatory rheumatic diseases (AIIRD) to reduce the risk of morbidity and mortality associated with serious COVID-19 infection. With endemicity, waning of vaccine- and infection-acquired immunity, and development of SARS-CoV-2 variants, the need for additional doses of vaccines against serious illness in high-risk immunocompromised persons remains imperative. This review examines how immunomodulatory therapies affect vaccine-induced immune response in patients with AIIRD. Glucocorticoids, methotrexate, azathioprine, calcineurin inhibitors, mycophenolate mofetil, tumor necrosis factor inhibitors, and abatacept have been shown to variably attenuate both humoral and cellular immune responses to vaccination. Janus kinase inhibitors reduce humoral immune response. In contrast, sulfasalazine, leflunomide, belimumab, interleukin (IL)-17, IL-12/23, IL-6, and IL-1 inhibitors appear favorable, with mild or no impact on vaccine response. Although rituximab is known to profoundly diminish humoral immune response, cellular immunity is relatively preserved. Administering a third and subsequent vaccine dose or temporally coordinating the dosing of immunomodulatory drugs may improve vaccine effectiveness. Further research is needed to personalise vaccination strategies for AIIRD patients, considering their specific immunomodulatory treatments.

Autoimmune manifestations of CTLA-4 haploinsufficiency in two patients of Southeast Asian ethnicity.

We report 2 patients who first developed cutaneous manifestations, followed by autoimmune phenomena, infections, and hypogammaglobulinemia. They were initially diagnosed with common variable immunodeficiency; however, the diagnosis was revised to cytotoxic T-lymphocyte antigen 4 haploinsufficiency after genetic and functional testing.

Autoimmune Rheumatic Disease Flares with Myocarditis Following COVID-19 mRNA Vaccination: A Case-Based Review.

Since the introduction of coronavirus disease 2019 (COVID-19) messenger ribonucleic acid (mRNA) vaccines, there have been multiple reports of post-vaccination myocarditis (mainly affecting young healthy males). We report on four patients with active autoimmune rheumatic diseases (ARDs) and probable or confirmed myocarditis following COVID-19 mRNA vaccination managed at a tertiary hospital in Singapore; we reviewed the literature on post-COVID-19 mRNA vaccination-related myocarditis and ARD flares. Three patients had existing ARD flares (two had systemic lupus erythematosus (SLE), one had eosinophilic granulomatosis polyangiitis (EGPA)), and one had new-onset EGPA. All patients recovered well after receiving immunosuppressants comprising high-dose glucocorticoids, cyclophosphamide, and rituximab. Thus far, only one case of active SLE with myocarditis has been reported post-COVID-19 mRNA vaccination in the literature. In contrast to isolated post-COVID-19 mRNA vaccination myocarditis, our older-aged patients had myocarditis associated with ARD flares post-COVID-19 vaccination (that occurred after one dose of an mRNA vaccine), associated with other features of ARD flares, and required increased immunosuppression to achieve myocarditis resolution. This case series serves to highlight the differences in clinical and therapeutic aspects in ARD patients, heighten the vigilance of rheumatologists for this development, and encourage the adoption of risk reduction strategies in this vulnerable population.

Atypical presentation of Good syndrome: acute hepatitis from hepatitis B virus reactivation.

Good syndrome (GS) is a primary immunodeficiency (PID) that presents in middle aged to older adults with features of thymoma, hypogammaglobulinemia, CD4 T lymphopenia, inverted CD4/CD8+ ratio, and impaired T-cell mitogen proliferative responses. We present a patient, a 62-year-old female, who first presented with disease manifestation of acute hepatitis from hepatitis B virus (HBV) reactivation, which was subsequently complicated by recurrent hospitalizations for recurrent pneumonia and concomitant Helicobacter pylori and cytomegalovirus enteritis. She was later found to have thymoma and hypogammaglobulinemia and was diagnosed with GS. Although the well-known importance of T cell is in directing B-cell responses in the immunopathology of thymoma, low levels of natural killer and CD4+ γδ T cells may also be the cause of both low immune surveillance of tumor development and weak clearance of viral infection. Hence, the temporal sequence of opportunistic infections following HBV reactivation and thymoma discovery may reflect a loss of immune surveillance as the first manifestation of PID.

Enterovirus-related rhombencephalitis and myelitis in the third trimester of pregnancy: A case report highlighting clinico-radiological findings at diagnosis and follow-up.

Rhombencephalitis (RE) refers to inflammatory diseases involving the brainstem and cerebellum. Although RE is a rare entity, it is associated with high morbidity and mortality. The management of such patients is often challenging in terms of identifying the etiology and defining prognosis. Infections, autoimmune and paraneoplastic conditions are commonly implicated. Patients with RE often present with a biphasic illness with an initial flu-like syndrome followed by brainstem dysfunction. CSF pleocytosis, abnormal brain MRI findings, isolation of organism or molecular (PCR/antigen) detection in CSF/blood cultures/stool samples and nasal/rectal swabs help in arriving at a definitive or probable diagnosis. Prompt aggressive treatment with antibacterial and antiviral drugs and/or immunoglobulins along with supportive therapy is crucial for avoiding a poor outcome. We present a case report of a 28-year old female patient who developed RE and myelitis in the third trimester of pregnancy. We aim to highlight the highly suggestive radiological findings which corroborated with the clinical diagnosis of enterovirus infection. The patient's radiological follow-up and neurological sequalae are also described. To the best of our knowledge, ours is the first report which describes the MRI features of this clinical scenario in the third trimester of pregnancy, and also the subsequent clinico-radiological follow up.