Central Nervous System (CNS) T-Cell Lymphoma as the Presenting Manifestation of Late-Onset Combined Immunodeficiency.

Late-onset combined immunodeficiency (LOCID), considered now a subset of common variable immunodeficiency (CVID) disorders, is characterized by a predominantly T-cell immune defect. LOCID has a distinct phenotype from CVID with a greater risk of lymphoproliferative complications. As compared to the CVID cohort, LOCID patients also have increased rates of splenomegaly and granulomatous disease. We report a case of central nervous system (CNS) T-cell lymphoma in a 67-year-old male as the presenting manifestation of LOCID. The patient achieved a complete response to therapy after 4 cycles of MATRix (methotrexate, cytarabine, and thiotepa) and 2 cycles of ICE (etoposide, carboplatin, and ifosfamide) chemotherapy followed by CNS-directed autologous stem cell transplantation. Intravenous immunoglobulin replacement was commenced to address the underlying immunodeficiency. Pulmonary lesions consistent with a diagnosis of granulomatous and lymphocytic interstitial lung disease (GLILD) were identified as a second noninfectious complication of LOCID. The pulmonary lesions resolved after chemotherapy and immunoglobulin replacement. The patient remains well with no evidence of disease recurrence now more than 18 months after completion of therapy. This is the first reported case of T-cell lymphoma in an adult patient with LOCID. Further study is needed to elucidate the mechanisms of transformation of B- or T-cells to lymphoproliferation in primary immunodeficiency patients as well as research to inform evidence-based therapeutic strategies for this challenging cohort of patients.

Subsequent COVID-19 Prophylaxis in COVID-19 Associated Glomerulopathies.

Successful vaccination has been the decisive factor in the overall decline of SARS-CoV2 infection related morbidity and mortality. However, global effects of the COVID-19 pandemic are ongoing, with reports of glomerular disease occurring in relation to both infection and vaccination. A particular rise in anti-GBM disease has been identified. Information is still emerging regarding the optimal management of such cases. We reviewed anti-GBM antibody detection rates at our test center over the past 5 years. We followed three patients with biopsy confirmed glomerular disease temporally related to COVID-19 vaccination. Each patient proceeded to receive subsequent COVID-19 vaccination as per immunologist recommendations. Further assessment included COVID-19 antibody testing in each case. A three-fold increase in significant anti-GBM antibody results noted at our center was associated with COVID infection in 10% of cases, and COVID vaccination in 25% of cases. We demonstrated that subsequent vaccination did not appear to lead to adverse effects including relapse in our three cases of COVID-19 vaccine-associated GN. We also identified positive COVID-19 antibody levels in two out of three cases, despite immunosuppression. We report a rise in anti-GBM antibody disease incidence. Our small study suggests that COVID-19 antibody testing can help determine COVID prophylaxis requirements, and subsequent vaccination with an alternative vaccine type appears safe.

A retrospective review of immunology patients with primary and/or secondary immunodeficiency, demonstrating the benefits of the rapid transitioning from intravenous immunoglobulin to subcutaneous immunoglobulin at the onset of the COVID-19 pandemic.

Forty-four of 50 immunology patients with primary or secondary immunodeficiency receiving intravenous immunoglobulin at a hospital in New South Wales, Australia, were rapidly enrolled in the subcutaneous immunoglobulin (SCIg) programme at the onset of the 2020 COVID-19 pandemic. Health and economic outcomes demonstrated that SCIg provides clinical efficacy as evidenced by the number of infections and maintenance of IgG levels, and also facilitates cost reduction in immunoglobulin maintenance programmes.

Case series: Immune checkpoint inhibitor-induced transverse myelitis.

Introduction: Increasing implementation of the highly efficacious immune checkpoint inhibitors (ICIs) has raised awareness of their various complications in the form of immune-related adverse events (irAEs). Transverse myelitis following ICIs is thought to be a rare but serious neurologic irAE and knowledge is limited about this distinct clinical entity. Cases: We describe four patients across three tertiary centers in Australia with ICI-induced transverse myelitis. Three patients had a diagnosis of stage III-IV melanoma treated with nivolumab and one patient had stage IV non-small cell lung cancer treated with pembrolizumab. All patients had longitudinally extensive transverse myelitis on magnetic resonance imaging (MRI) spine and clinical presentation was accompanied by inflammatory cerebrospinal fluid (CSF) findings. Half of our cohort had received spinal radiotherapy, with the areas of transverse myelitis extending beyond the level of previous radiation field. Inflammatory changes on neuroimaging did not extend to the brain parenchyma or caudal nerve roots, except for one case involving the conus medullaris. All patients received high dose glucocorticoids as first-line therapy, however the majority relapsed or had a refractory state (3/4) despite this, requiring escalation of their immunomodulation, with either induction intravenous immunoglobulin (IVIg) or plasmapheresis. Patients in our cohort who relapsed had a poorer outcome with more severe disability and reduced functional independence following resolution of their myelitis. Two patients had no progression of their malignancy and two patients had malignancy progression. Of the three patients who survived, two had resolution of their neurological symptoms and one remained symptomatic. Conclusion: We propose that prompt intensive immunomodulation is favored for patients with ICI-transverse myelitis in an attempt to reduce associated significant morbidity and mortality. Furthermore, there is a significant risk of relapse following cessation of immunomodulatory therapy. We suggest one treatment approach of IVMP and induction IVIg for all patients presenting with ICI-induced transverse myelitis based on such findings. With the increasing use of ICIs across oncology, further studies are required to explore this neurological phenomenon in greater detail to help establish management consensus guidelines.

Phenotyping variants of tumefactive demyelinating lesions according to clinical and radiological features-A case series.

Background: Tumefactive demyelinating lesions (TDLs) are defined as lesions >2 cm on MRI of the brain. They are identified in a range of demyelinating diseases including massive demyelination due to Marburg's acute MS, Schilder's Disease, Balo's concentric sclerosis, and Tumefactive MS. Apart from the rare demyelinating variants which are often diagnosed histologically, there are no detailed data to phenotype TDLs. Methods: We describe the clinical and radiological features of four similar patients with very large TDLs (>4 cm), that are not consistent with the rare demyelinating variants and may represent a distinct phenotype. Results: All patients presented with hemiplegia and apraxia. The mean age at onset was 37 years with an equal sex distribution. All patients were diagnosed with Tumefactive demyelination based on MRI and CSF analysis, precluding the need for brain biopsy. All responded to potent immunotherapy (including high dose corticosteroids, plasma exchange, rituximab, and/or cyclophosphamide). The mean lag from diagnosis to treatment was 1 day. The median EDSS at presentation was six and recovery to a median EDSS of two occurred over 6 months. Conclusion: We propose that Tumefactive lesions larger than 4 cm are termed "Giant demyelinating lesions" (GDLs) not only on the basis of size, but a rapid and fulminant demyelinating presentation leading to acute, severe neurological disability that is, nonetheless, responsive to immunotherapy. Further clinical studies are required to ratify this proposed phenotype, establish the immunological profile and best treatment for such patients.

Follow-up of penicillin allergy labels 1 year after successful penicillin delabeling.

BACKGROUND: Penicillin allergy delabeling confers many benefits, including reduced patient morbidity and mortality and improved health economics. Reports suggest that both patients and clinicians often remain hesitant to take and prescribe penicillins, respectively, after penicillin delabeling. However, follow-up of an individual's penicillin allergy label and incorporation of this into relevant health care records after delabeling have not been well studied in the Australian population. OBJECTIVE: To evaluate the status of penicillin allergy labels in the community 1 year after penicillin delabeling at a tertiary hospital in Australia. METHODS: A cross-sectional study was performed using follow-up interviews with patients and community primary care providers after 1 year from the date of patients' penicillin delabeling at a tertiary hospital in New South Wales, Australia. The main outcome measures that were evaluated included patient willingness to accept penicillin for future infections, patient self-reported receipt of penicillin-based antibiotics after delabeling, accuracy of penicillin allergy labels in the records of the primary care provider, and prescription of penicillin-based antibiotics by the general practitioner. RESULTS: A total of 86 patients were included in this study. The percentage of patients with a correct penicillin allergy status at 1-year follow-up was 94% in the hospital electronic medical record but only 37% in primary care records. At 1-year follow-up, 14% of delabeled patients continued to reject penicillin prescriptions. CONCLUSION: Better strategies are required to increase patient confidence in receiving penicillins after penicillin delabeling and to ensure that penicillin allergy labels are translated into the medical records at the primary care level.

Medical treatment of polymeric cerebral granulomatous reactions following endovascular procedures.

BACKGROUND: Endovascular procedures are standard of care for an increasing range of cerebrovascular diseases. Many endovascular devices contain plastic and are coated with a hydrophilic polymer which has been rarely described to embolize, resulting in distal granulomatous inflammatory lesions within the vascular territory. METHODS: We reviewed three cases of cerebral granulomatous reactions that occurred after endovascular intervention for internal carotid aneurysms. The patient procedure details, presentation, relevant investigations, and treatment course are described. We also provide a literature review on endovascular granulomatous reactions. RESULTS: These three cases represent the largest biopsy proven series of cerebral granulomatosis following endovascular intervention. We highlight the variable clinical presentation, with two of the three cases having an unusually delayed onset of up to 4 years following the intervention. We show the characteristic histological findings of granulomatous lesions with foreign body material consistent with a type IV reaction, radiological abnormalities of enhancing lesions within the vascular territory of the intervention, and the requirement of prolonged immunosuppression for maintenance of clinical remission, with two of the three patients requiring a corticosteroid sparing agent. In comparison with the available literature, in addition to hydrophilic gel polymer, we discuss that plastic from the lining of the envoy catheter may be a source of embolic material. We also discuss the recommendations of the Food and Drug Administration and the implementation of novel biomaterials for the prevention of these reactions in the future. CONCLUSIONS: There is a need for increased awareness of this severe complication of cerebral endovascular procedures and further longitudinal studies of its prevalence, optimal management and preventative measures.

The Successful Use of Infliximab in a Relapsing Case of Susac's Syndrome.

Susac's syndrome is a rare and debilitating disease characterized by the triad of encephalopathy, branch retinal artery occlusions, and sensorineural hearing loss. All manifestations may not be clinically apparent at presentation resulting in delayed diagnosis. Early recognition of the syndrome may prevent disease sequelae such as permanent cognitive, visual, and hearing loss. We present such a case of Susac's syndrome that was also refractory to conventionally prescribed combination of immunosuppressive treatments including high-dose potent corticosteroids, intravenous cyclophosphamide, methotrexate, plasma exchange, rituximab, and mycophenolate. His disease was stabilized with infliximab in combination with a tapering course of low-dose prednisone. After 2 years of remission with TNF treatment, consideration is being given to ceasing therapy. He has the sequelae of bilateral sensorineural hearing loss but no visual impairment or cognitive deficits on follow-up with neuropsychometric testing. This is the first case report to our knowledge of the successful use of infliximab for a patient with Susac's syndrome that was necessary following treatment with cyclophosphamide and then rituximab.