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Abstract Cytokine storm syndromes such as hemophagocytic lymphohistiocytosis (HLH), Adult-onset Still’s disease (AOSD), and COVID-19 cytokine storm (CCS) are characterized by markedly elevated inflammatory cytokines. However clinical measurement of serum cytokines is not widely available. This study examined the clinical utility of C-reactive protein (CRP) and ferritin, two inexpensive and widely available inflammatory markers, for distinguishing HLH from AOSD and CCS. This single centre retrospective study included 44 secondary HLH patients, 14 AOSD patients, and 13 CCS patients. Baseline CRP and ferritin measured within 72 h of diagnosis and before administration of corticosteroids or other anti-inflammatory therapies were analyzed. The median CRP in HLH patients was lower than AOSD (71 mg/L vs. 172 mg/L, p 136 improves the specificity of HScore alone for HLH from 85.2 to 96.3%. Adding CRP 15,254 µg/L increases specificity for HLH from 88.9 to 100%. This study demonstrates that median CRP is lower in HLH than in AOSD and CCS, and median ferritin is lower in CCS than in HLH or AOSD. This study demonstrates the clinical utility of these widely available inflammatory markers for distinguishing between different cytokine storm syndromes.

Aggressive natural killer cell leukemia (ANKL) is a rare, aggressive hematologic malignancy which often presents as fulminant Epstein-Barr virus (EBV)- driven hemophagocytic lymphohistiocytosis (HLH). ANKL lacks a distinct immunologic and morphologic signature, making early diagnosis particularly challenging. Here we present a case of ANKL in a patient presenting with EBV-HLH. After poor treatment response to the HLH-2004 protocol (etoposide and dexamethasone), bone marrow biopsy demonstrated an atypical CD3-/CD56+ natural killer (NK) cell population with diminished CD7 expression consistent with EBV+ ANKL. Asparaginase-based chemotherapy was initiated but his disease progressed and he died from multiorgan failure. This case highlights the diagnostic challenges of ANKL given the lack of standardized diagnostic criteria, the importance of considering T/NK cell malignancies in the differential diagnosis of EBV-HLH, and adds to the literature on this rare disease.

Abstract Inborn errors of immunity (IEIs) are a group of conditions whereby parts of the immune system are missing or dysfunctional. Once thought to primarily be a pediatric disorder, it is now estimated that more than 50% of worldwide incident IEI cases are accounted for by adults. Delayed diagnosis, late symptom onset, and IEI phenocopies can all lead to adult-onset recognition of IEIs. Lack of awareness regarding the diversity of IEI manifestations in adults contributes to diagnostic and treatment delays. Prompt referral to immunology is critical so that patients can receive a precise molecular diagnosis and targeted therapy when available. This article serves as a primer on IEIs in adulthood, highlighting the pathophysiology, epidemiology and clinical features. We present clinical vignettes of three key IEIs to assist clinicians in building illness scripts on their presentations. We provide a framework for the laboratory evaluation of IEIs and their initial treatment, with the aim of improving recognition and management of these conditions.

Abstract We compared liquid chromatography tandem mass spectrometry (LC–MS/MS) against Binding Site immunonephelometry (BSIN) with regards to these methods’ abilities to diagnose IgG4-related disease (IgG4-RD). IgG subclasses were gathered from laboratory from December 2011 to December 2020. The IgG4-RD positive and negative patients were diagnosed according to the ACR/EULAR classification criteria by extensive chart review. Both methods’ results were compared in terms of test characteristics. For BSIN, there were 43 IgG4-RD positive cases and 174 disease negative cases, while for LC–MS/MS, there were 102 IgG4-RD positive cases and 562 disease negative cases. The majority of IgG4-RD patients by BSIN and LC–MS/MS had an elevated IgG4 level, 81% and 86%, respectively. For BSIN, the ROC curve, cut-off value of 1.25 g/L, had a sensitivity of 81% and a specificity of 84%. For LC–MS/MS, the ROC curve, cut-off value of 1.25 g/L, had a sensitivity of 86% and a specificity of 84%. The responder index score to IgG4 level r-correlation value for BSIN and LC–MS/MS was 0.5 and 0.6, respectively. In our center, LC–MS/MS and BSIN are equivalent test methods in IgG4-RD diagnosis. IgG4 level does correlate with disease activity by the responder index. LC–MS/MS is a valid and equally reliable alternative to BSIN in the diagnosis of IgG4-related disease.

Objectives Classroom-based learning such as academic half days (AHDs) are complementary to workplace learning in postgraduate medical education. This study examined three research questions: the purpose of AHDs, elements of an effective AHD, and factors that make AHD sustainable. Methods We conducted a case study of the AHD in a large Obstetrics and Gynecology residency program at the University of British Columbia. Residents were interviewed in 2013 ( n = 11) and 2018 ( n = 7) and the program administrator was interviewed in 2018. The themes in each research question were identified by modified inductive analysis. Results Residents expressed that the purposes of AHD included: providing organization and an overview for their knowledge acquisition; preparation for their Royal College specialty exam; and to provide a venue for peer support and mentorship. Elements of an effective AHD include the repetition of key concepts; formative assessments such as quizzes, a suitable balance of faculty input and resident active participation, and protection from clinical duty during AHD. Regarding the sustainability of AHD, themes included: addressing barriers to faculty participation, providing administrative support for logistical needs, and providing feedback to faculty. Conclusions This work provides important insights into the purpose, effectiveness, and sustainability of AHDs for those who design and implement classroom learning for residents.

Abstract Background Immunoglobulin G4-related disease (IgG4-RD) is a systemic lymphoproliferative disorder characterized by elevated serum IgG4 levels and tumefactive lesions that can involve nearly every organ system. Involvement of the prostate is rare but has been reported in limited cases. Case presentation A 28-year-old man of Asian descent with a history of sinusitis and priapism presented to hospital with rigors and voiding symptoms. He was diagnosed with IgG4-RD one month prior to presentation, following pathological analysis of a submandibular mass that demonstrated chronic sclerosing sialadenitis. On presentation, white blood cell count, C-reactive protein, and prostate serum antigen levels were all within normal limits. Examination was notable for a large, firm prostate, and a foley catheter was inserted. Contrast CT of the abdomen was unremarkable. Further workup revealed elevated serum IgG4 levels (9.22 g/L) and he was subsequently started on prednisone 35 mg daily. Imaging to screen for systemic IgG4-RD involvement demonstrated paravertebral soft tissue involvement and he was given rituximab 1000 mg IV × 2 doses. MRI revealed diffuse prostatitis. Five days after starting prednisone and one day after his first dose of rituximab, he successfully passed trial of void and was discharged home. Conclusions IgG4-related prostatitis is a rare and underrecognized manifestation of IgG4-RD. Our case highlights the need to consider IgG4-related prostatitis as an etiology of urinary obstruction in young individuals. Resolution of symptoms following treatment with steroids may be diagnostic of IgG4-related prostatitis, and may potentially avoid the need for invasive diagnostic procedures such as prostate biopsy.

Abstract Background Retroperitoneal fibrosis (RPF) is characterized by the proliferation of fibrous tissue in the retroperitoneum. The majority of RPF cases are due to idiopathic or IgG4-related disease. Recent studies on IgG4-related disease have shown rituximab to be an effective treatment. The current first-line treatment for idiopathic RPF (iRPF) is glucocorticoid therapy. Relapse rates vary widely in the literature, and DMARDs remain poorly studied. We sought to evaluate the efficacy of rituximab in idiopathic RPF by quantifying changes in iRPF diameter on imaging pre- and post-rituximab therapy and response by lab parameters in 10 iRPF patients. Methods We selected 10 patients diagnosed with iRPF and previously treated with rituximab (1000 mg) in two doses approximately 2 weeks apart. Pre- and post-therapy contrast enhanced cross-sectional abdomen and pelvis imaging were compared. In all patients, the thickest portion of the peri-aortic disease was measured in the axial and coronal planes. The presence of acute or long standing back pressure related renal findings were documented. Details of clinical visits including patient demographics and laboratory evaluations were collected pre- and post-therapy. Statistical analysis was performed using a Wilcoxon signed rank test. Results The RPF diameter around the aorta before and after therapy decreased from a mean of 15.9 ± 4.9 mm to 10.6 ± 6.1 mm, respectively (p

Purpose of the review: Immunoglobulin G4-related disease (IgG4-RD) is a systemic fibroinflammatory disorder affecting nearly all organs, including the kidney. Tubulointerstitial nephritis (IgG4-TIN) is the most common form of IgG4-related kidney disease (IgG4-RKD) and is the focus of this concise review. Objective: The study aims to describe when IgG4-TIN should be suspected and to summarize the diagnosis, treatment, and natural history of the disease. Sources of information: Ovid MEDLINE, Google Scholar, and PubMed were searched for full-text English language articles up to January 2016. References included in the manuscript were chosen at the authors' discretion based on their relevance to the subject of the review. Findings: IgG4-TIN should be considered in patients presenting with abnormal urinalysis, abnormal kidney function, renal lesions on imaging, and elevated IgG, IgE, or hypocomplementemia. Diagnosis of IgG4-TIN requires a combination of histologic features (plasma cell-enriched TIN with >10 IgG4+ plasma cells/hpf, +/– TBM immune complex deposits in many cases) and at least one of the following: – Characteristic radiologic findings (small peripheral low-attenuation cortical nodules, round or wedge-shaped lesions, or diffuse patchy involvement) – Elevated serum IgG4 level – Characteristic findings of IgG4-RD in other organs Other conditions such as lupus, vasculitis, diabetic nephropathy, and lymphoma must be excluded, as these can also present with IgG4+ plasma cells in the renal parenchyma. IgG4-TIN is generally responsive to steroids and B cell depletion with rituximab, but relapses are common and patients require close long-term follow-up. Limitations: Available data on IgG4-TIN are from retrospective observational studies. Implications: IgG4-TIN is a distinct and emerging subtype of interstitial nephritis. Nephrologists must be aware of this entity and how to definitively diagnose and treat it. Prospective studies and ideally multi-center clinical trials are needed to study the epidemiology, treatment, and natural history of this disease.