Initiation Of Immunosuppressive Therapy Research Articles

Serological Profiles of Hepatitis B Virus in Patients With Crohn's Disease Undergoing Anti-Tumor Necrosis Factor Alpha (TNFα) Therapy at Ibn Sina University Hospital, Rabat.

Introduction Anti-tumor necrosis factor alpha (TNFα) therapies have revolutionized the management of Crohn's disease (CD). However, they increase the risk of viral reactivation, particularly hepatitis B virus (HBV). This study aims to define the HBV serological profiles of patients with CD who are candidates for biological therapy, identifying profiles at potential risk for reactivation or exacerbation following immunosuppressive treatment. Materials and methods This descriptive retrospective study included patients with CD, aged over 16 years, who were candidates for anti-TNFα treatment at Ibn Sina University Hospital Center (UHC) in Rabat, Morocco, from January 2015 to March 2023. The serological profiles of patients, including hepatitis B surface antigen (HBsAg), hepatitis B surface antibodies, and total hepatitis B core antibodies (HBcAb), were determined using microparticle chemiluminescence immunoassay with the ARCHITECT i2000sr or Alinity (Abbott Diagnostics, Chicago, Illinois, United States) automated systems at the Central Virology Laboratory (CVL) of Ibn Sina UHC Rabat. HBV DNA quantification was performed using the m2000 Abbott Diagnostic or GeneXpert system. Results Out of 249 patients with CD who were candidates for biological therapy, 131 (52.6%) received anti-TNFα treatment, including 39 (29.8%) with adalimumab and 92 (70.2%) with infliximab. The median age was 41 years, and the male-to-female ratio was 0.52. The overall HBV screening rate before starting biological therapy was 68.7%. HBV screening was conducted for 90 patients at the CVL, where serological marker analysis categorized five distinct profiles. A majority of patients (65, 72.2%) had negative serological profiles for HBV, while 10 (11.1%) were immunized via vaccination. Profiles at risk of viral reactivation or worsening following immunosuppressive therapy included 12 (13.3%) patients immunized by contact, two (2.3%) with isolated HBcAb, and one (1.1%) with active viral hepatitis (positive HBsAg and HBcAb), who was initiated on tenofovir 300 mg before starting combination therapy. No cases of primary infection or viral B reactivation were observed during the study. Conclusions In our study, 15 patients (16.7%) exhibited a potential risk of viral reactivation or worsening of HBV following the initiation of immunosuppressive therapy. The authors recommend precise patient selection, thorough pretreatment evaluation, and regular follow-up during therapy to minimize adverse events associated with anti-TNFα treatment. Additionally, a prophylactic or preemptive strategy should be considered. The risk of late reactivation after discontinuation of biological therapy should also be carefully monitored.

Long-Term Outcome of Eltrombopag With First-Line Immunosuppressive Therapy for Newly Diagnosed Severe Aplastic Anemia.

To investigate whether the addition of eltrombopag (EPAG) to rabbit anti-thymocyte globulin (ATG)-based immunosuppressive therapy (IST) for newly diagnosed severe aplastic anemia (SAA) improves outcomes and affects the cumulative incidence of clonal evolution (CE), we conducted a multicenter retrospective analysis. Data were collected from 101 patients, aged 15 - 65 years, undergoing initial IST. No significant imbalance in age, sex, or severity was observed between the EPAG (n = 20) and non-EPAG (n = 81) groups. The median duration of EPAG administration in EPAG group was 16.1 months (range: 0.6 - 41.1 months). Six months after the initiation of IST, the complete response (CR) rate significantly improved in the EPAG group (P < 0.01). The cumulative incidence of allogeneic stem cell transplantation (allo-SCT) at 2 years and the 2-year overall survival (OS) were not significantly different between the two groups (allo-SCT, P = 0.31; OS, P = 0.64). Grade 3-4 adverse events in the EPAG group and the cumulative incidence of CE (P = 0.96) showed no increase. In summary, IST showed significantly better initial efficacy in the EPAG group. Although the addition of EPAG did not reduce the need for allo-SCT, no increase was observed in the incidence of CE with long-term EPAG use.

A case of vesiculobullous dermatomyositis with anti-NXP-2 antibody without malignancy.

Vesiculobullous dermatomyositis (VD) is a rare manifestation of dermatomyositis (DM) and has been suggested to be associated with malignancy. Although the myositis-specific autoantibodies are associated with distinct clinical presentations of DM, those associated with VD remain unclear. Here, we present the case of a 54-year-old man with VD who tested positive for antinuclear matrix protein 2 (NXP-2) antibodies, one of the DM-specific autoantibodies. Serological and histopathological findings did not support autoimmune blistering disease. Physical and histological findings suggested that the severe oedema in combination with the interface dermatitis of DM contributed to blister formation. Although a systemic examination was performed, no evidence of malignancy was found. Following initiation of immunosuppressive therapy, the patient showed significant improvement in both skin lesions and myositis. This case represents the first report of anti-NXP-2-positive VD without malignancy or autoimmune blistering disease. Subcutaneous oedema, a characteristic feature of anti-NXP-2-positive DM, could be related to the formation of VD.

Temporal evolution of primary angiitis of the central nervous system (PACNS) on MRI following immunosuppressant treatment

PurposeTo systematically analyse the time course of vessel wall enhancement and associated stenosis in patients with primary angiitis of the central nervous system (PACNS) following immunosuppressive therapy.Material and methodsTwo neuroradiologists retrospectively analysed MRIs of patients with PACNS seen at the Bern University Hospital and the St. Gallen Cantonal Hospital between 2015 and 2020. MRIs were examined for the presence of vessel wall enhancement, length of vessel wall enhancement (mm), circumferential extent of enhancement (degree) and degree of stenosis (%). Descriptive statistics and measurements of interobserver reliability were obtained. To investigate the temporal profiles of the variables following the commencement of immunosuppressant treatment, four series of Bayesian generalised multi-level models were generated.ResultsA total of 23 patients with 43 affected vessels identified from 209 MRI exams were evaluated (mean follow-up: 715 days, standard deviation ± 487 days), leading to a complete dataset of 402 entries. Vessel wall enhancement and circumferential extent of enhancement decreased for approximately 1 year after the initiation of immunosuppressant therapy. Changes were more pronounced in younger patients. Disappearance of vessel wall enhancement (in at least one vessel) was seen in about half of patients after a median of 172 days interquartile range 113–244, minimum 54 days, maximum 627 days.ConclusionsThis study evaluated the typical time course of vessel wall enhancement in patients with PACNS. Our results could be a useful reference for radiologists and clinicians interpreting follow-up imaging in patients with PACNS.Critical relevance statementRoutine clinical exams can be interpreted with more confidence when radiologists are aware of the typical temporal evolution of vessel wall enhancement in patients with primary angiitis of the central nervous system after initiation of immunosuppressive therapy.Key PointsFew data exist for vessel wall imaging of primary angiitis of the central nervous system.Following immunosuppressant therapy, vessel wall enhancement decreases for approximately one year.These results may serve as a reference for radiologists performing follow-up imaging.Graphical

Immunosuppressive therapy in elderly patients with neuromyelitis optica spectrum disorder: a retrospective multicentre study

BackgroundThe risk–benefit relationship of immunosuppressive therapies (ISTs) for elderly patients with neuromyelitis optica spectrum disorder (NMOSD) is not well established. This study aimed to investigate the safety and efficacy of...

EOSINOPHILIC MYOPERICARDITIS: A CASE SERIES

Abstract Background Eosinophilic myocarditis is characterized by acute myocardial inflammation due to eosinophilic tissue infiltration. Methods Diagnosis was based on laboratory tests, Echo and CMR; EMB was performed in uncertain cases. Treatment was performed according to the etiology of EM. All patients underwent regular follow–up at our Center. Results This study includes 9 patients (89% Caucasian, 78% women, mean age 48.2±13.6 years), admitted in our Center from February 2021 to November 2023. 66.67% cases occurred in the setting of eosinophilic granulomatosis with polyangiitis, 11% was secondary to B–cell lymphoblastic leukemia, and 22% were labelled as idiopathic EM. All patients presented with high eosinophil count (6133±4893/mcL), elevated CRP (57±66 mg/L) and hs–troponin I (3610±5166 ng/L) levels, and 67% cases NT–proBNP (10751±4038 ng/L) was elevated. 67% patients presented with dyspnea, 56% with chest pain, and 56% with fever. On ECG, sinus tachycardia, low QRS voltages and ST segment depression with negative T–waves were common. Thickening of the myocardial walls with reduction of GLS was seen in all cases; in 44% cases, the EF was below 50%; 56% cases had mild pericardial effusion. 1 patient had intraventricular thrombi at CMR, another one had bilateral pulmonary embolism. On CMR, all patients had areas of hypokinesia, myocardial edema, and myo–pericardial late gadolinium enhancement. EMB was performed in 5 cases, confirming the presence of intramyocardial eosinophilic infiltrates. 7 patients required CICU, and 1 needed inotrope (dobutamine) use. The patient with ALL was treated with combined chemotherapy. The other EM cases were treated with immunosuppressive therapy consisting of corticosteroids and either cyclophosphamide or rituximab or mepolizumab. All patients received cardioprotective therapy with BBs and ACE–inhibitors; in patients with pericardial involvement, colchicine was administered. All patients showed rapid clinical improvement following immunosuppressive therapy initiation, with prompt reduction of circulating eosinophils and hs–troponin I values and normalization of the ejection fraction. On CMR imaging, edema disappeared at follow–up, with LGE replacement in one case. All patients were alive and in good conditions at the last follow–up. Conclusions EM is an underdiagnosed life–threatening disease. A careful assessment of the etiology, as prompt therapy, is mandatory to achieve clinical amelioration and good mid–term prognosis.

Undiagnosed HIV in Patients on Immunosuppressive Medications Presenting with HIV-Associated Kidney Disease.

Approximately 158,500 adults and adolescents in the United States live with undiagnosed human immunodeficiency virus (HIV). Missed or delayed diagnoses adversely affect disease management and outcomes. This is particularly salient for patients receiving immunosuppressive and immunomodulatory therapy for the management of chronic inflammatory conditions, in which additional immunosuppression may increase the risk and severity of opportunistic infections. Despite this risk, comprehensive HIV testing before the initiation of immunosuppressive therapy is not yet the norm. We describe a case series containing the narratives of three patients recently treated with immunosuppressive agents, who presented with signs concerning for HIV-associated kidney diseases and who were found to have undiagnosed HIV later in the treatment course, which, unfortunately, resulted in poor outcomes. Screening for HIV or related illnesses, such as viral hepatitis or mycobacterial co-infections including tuberculosis, is essential before initiating biologic immunosuppression.

Should Histoplasmosis be Screened for Before Initiation of Tumour Necrosis Factor Alpha Inhibitors?

Histoplasmosis is associated with ANCA positivity.Despite the negative investigations for histoplasmosis and criteria for GPA being met, patients should be closely monitored for possible clinical worsening after the initiation of immunosuppressive therapy, especially TNF-alpha inhibitors.Current guidelines are not recommending routine screening or pre-emptive therapy for histoplasmosis before initiation of TNF-alpha inhibitors.

Increased incidence of seronegative autoimmune hepatitis in children during SARS-CoV-2 pandemia period.

Seronegative autoimmune hepatitis in children is a rare but potentially severe disease, sometimes requiring liver transplantation. This type of hepatitis may be associated with various immunological and hematological disorders, ranging from isolated lymphopenia to aplastic anemia. Precise pathophysiological mechanisms are still unknown, but the role of viruses cannot be excluded, either as directly pathogenic or as triggers, responsible for an inappropriate immune stimulation. Having the impression of an increasing number of seronegative autoimmune hepatitis since the beginning of SARS-CoV-2 pandemia period, we hypothesized that SARS-CoV-2 virus could be an infectious trigger. We conducted a retrospective, observational, descriptive study about children with seronegative autoimmune hepatitis, in a tertiary care center, between 2010 and 2022. Thirty-two patients were included. The overall incidence of seronegative autoimmune hepatitis increased 3.3-fold in 2020-2022, during the SARS-CoV-2 pandemia period (16 patients in 2.8 years) compared with 2010-2019 the pre pandemia period (16 patients in 9 years). Patients' clinical and biochemical liver characteristics did not differ between the two periods. Hematological damages were less severe during the pandemia period. Immunological studies revealed a dysregulated immune response. The initiation of immunosuppressive therapy (corticosteroids ± cyclosporine) was earlier during the pandemia period than before. In cases of undetermined acute hepatitis, an immune-mediated origin should be considered, prompting a liver biopsy. If the histological aspect points to an immune origin, immunosuppressive treatment should be instituted even though autoimmune hepatitis antibodies are negative. Close hematological monitoring must be performed in all cases. The 3.3-fold increase of cases during the SARS-CoV-2 pandemia will need to be further analyzed to better understand the underlying immunological mechanisms, and to prove its potential involvement.

A Preliminary Report of Clinical Study on Immunosuppressive Therapy Combined with Avatrombopag As the First-Line Treatment for Severe Aplastic Anaemia in Elderly Patients

Objective The objective is to evaluate the early hematologic response (HR) rate and safety of immunosuppressive therapy (IST) combined with avatrombopag as the first-line treatment for severe/very sever aplastic anaemia(V/SAA) in elderly patients. Methods Prospective，multi-center, single-arm, clinical research. IST treatment regimen: pig anti-human lymphocyte globulin (ALG-p, Wuhan Institute of Biological Products Co., Ltd. China) 20 mg/kg/d for five days and cyclosporin A (CsA) 3 mg/kg/d with adjusted concentration of 150-250 ng/mL, and oral avatrombopag 40 mg/d from the first day of IST initiation up to six months. The patients' treatment responses were evaluated and the major adverse events were collected. Results Ten patients have been enrolled in the study at our centre from June 2022 to October 2022.Among 10 patients, six had SAA and four had VSAA; male: female = 1:1, median age of 68 (60-82) years, and median time from diagnosis to treatment of 44 (20-480) days. The patients' treatment responses were evaluated after initiation of IST, at 3 months: 7 HR [1 complete response (CR), 3 good partial response (GPR), 3 partial response (PR), and 3 no response (NR)]; and at 6 months: 8 HR (1 CR, 5 GPR, 2 PR) and 2 deaths due to infection. The median time of red-cell transfusion independence was 60 (3-168) days in HR patients and that of platelets was 60 (16-153) days. No relapse and clonal evolution occurred within six months. Major adverse events within three months were infection in five cases, electrolyte disturbance in five cases, and cardiac insufficiency in three cases. Liver function abnormalities occurred in two cases, both of which showed elevated alanine aminotransferase up to 174 μ/L and 208.7 μ/L on day 8 and 20 of IST treatment, respectively. Two of the five infected patients had sepsis caused by Enterobacter cloacae. Except for infection, the remaining adverse events were of grade I-II. All the adverse events were effectively controlled. Table 1 summarises the characteristics and clinical status of patients before and after the treatment. Conclusion This preliminary study of IST combined with avatrombopag for the treatment of elderly patients with V/SAA showed the potential of the combination to improve haematologic response rate and quality in elderly patients with AA, and it is well tolerated as well. Keywords: immunosuppressive therapy, severe aplastic anaemia, avatrombopag, elderly

Appropriateness of Immunosuppression and Blood Product Utilization in Acquired Hemophilia A: A Multicentre Provincial Practice Audit

Introduction: Acquired hemophilia A (AHA) is a life-threatening bleeding disorder associated with significant morbidity and mortality. Despite publication of international consensus guidelines, quality of care and guideline adherence have not been examined. While some jurisdictions have reference centres for AHA management, in Canadian provinces outside of Quebec, AHA is managed in both hemophilia treatment centres (HTCs) and community hospitals. We performed a multicentre practice audit in a Canadian province to assess use of immunosuppressive therapy (IST), blood product utilization, and evaluate treatment burden and outcomes. Methods: We included adults diagnosed with AHA (January 2000-December 2021) in Alberta, Canada, and examined the following quality of care indicators: delayed IST initiation from diagnosis, corticosteroid use alone in high-risk AHA (FVIII &amp;lt;0.01 IU/ml or FVIII inhibitor &amp;gt;20 BU/ml), cyclophosphamide use in low-risk patients (FVIII ≥0.01 IU/ml and inhibitor ≤20 BU/ml), prolonged cyclophosphamide use (&amp;gt;6 weeks), and inappropriate use of plasma, intravenous immunoglobulin (IVIG) and hemostatic products. Outcome measures included response, length of stay (LOS) and 30-day readmission. We evaluated treatment burden including frailty syndromes, increased level of care and hospitalization for treatment-related adverse events. Results: Of the 38 patients diagnosed with AHA, 25 (66%) were female, the median age was 74 years (IQR 61-81), and median Charlson comorbidity index was 5 (IQR 3-7). Cardiovascular comorbidities were common, including venous thromboembolism (5; 13%), atrial fibrillation (5; 13%), and myocardial infarction (4; 11%). Fifteen (39%) had ≥1 frailty syndromes, including functional dependence (6; 16%), dementia (6; 16%), falls/fractures (5; 13%), and depression/anxiety (3; 8%). Five (13%) patients required higher levels of care (long term care placement) following discharge. Twenty-one (55%) patients had high-risk disease and 17 (45%) had low-risk. In those with low-risk disease, 11 (29%) had inhibitor titres 5-20 BU/ml and 6 (16%) had inhibitors &amp;lt;5 BU/ml. Despite diagnostic delays ≥7 days from bleeding in 15 (39%), most received prompt initiation of IST (median 0 days [IQR 0-3] from diagnosis). First-line IST included: prednisone (38; 100%), cyclophosphamide (23; 61%), and rituximab (13; 34%). IVIG was prescribed in 5 (13%), out of keeping with guideline recommendations. We observed very high rates of first-line cyclophosphamide use in low risk AHA (11/17; 65%), including 4/6 with inhibitor titres &amp;lt;5 BU/ml (Table 1). First-line cyclophosphamide was also used in 3 reproductive-aged women. Prolonged courses of cyclophosphamide &amp;gt;6 weeks and &amp;gt;6 months were used in 21/23 (91%) and 7/23 (30%) patients, respectively. Two high-risk patients did not receive cyclophosphamide or rituximab-containing therapy. Of the 58 episodes of bleeding events, 41 (71%) were ISTH major bleeds. Fifteen (26%) bleeding events did not receive hemostatic therapy, whereas 27 (47%), 19 (33%), and 3 (5%) were treated with recombinant factor VIIa, activated prothrombin complex concentrates, and porcine FVIII, respectively. Dosing of bypassing agents was in keeping with guidelines. DDAVP and human FVIII were inappropriately used in 3/58 (5%) and 1 (2%) bleeding episodes, respectively. Most patients (24; 63%) received red cell transfusions with a median of 2 (IQR 0-7) units each. Five (13%) patients received a total of 18 units of plasma. Clinical responses included: complete remission (CR) in 30 (79%), partial remission in 3 (8%), and unevaluable due to early deaths in 5 (13%). All 5 patients who relapsed (13%) achieved second CR. The median LOS was 38 days (IQR 19-57) across 95 hospitalizations. The 30-day readmission rate was 24%. Reasons for admission included bleeding (50/95; 53%), infections (14/95; 15%), and other treatment side-effects (13/95; 14%). Conclusion: In this provincial cohort of AHA patients with high comorbidity and frailty, we identified gaps in quality of care including overuse of cyclophosphamide in patients with low-titre inhibitors, prolonged duration of cyclophosphamide, and inappropriate use of IVIG and plasma. Aggressive cytotoxic therapy predisposes patients to unnecessary risks of infections and malignancies. Our findings highlight the need for centralization of care in specialized centres and education initiatives.

Abstract 12715: Can 18F-Fluorodeoxyglucose Uptake Stratify the Risk of the Patients With Cardiac Sarcoidosis After Initiation of Immunosuppressive Therapy?

Introduction: While 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is well-established for diagnosing cardiac sarcoidosis (CS) initially, its potential as a risk stratification tool for patients receiving immunosuppressive therapy remains controversial. Hypothesis: We aim to assess the prognostic value of FDG-PET in CS patients after 12 months of corticosteroid treatment. Methods: Our study consists of a retrospective review of clinical data and patient outcomes of stable CS cases that underwent FDG-PET following 12 months of corticosteroid treatment initiation. We excluded patients in the previous six months who had a heart failure hospitalization, sustained ventricular tachycardia (SVT) or ventricular fibrillation (VF), recent pacemaker implantation or upgrade, changes in corticosteroid dosage, or newly introduced additional immunosuppressive therapy. Major adverse cardiac events (MACE) include a composite of cardiac death, onset of SVT/VF, appropriate implantable cardioverter-defibrillator intervention, heart failure hospitalization, and cardiac functional deterioration. Results: Among the 72 analyzed patients, 35 exhibited cardiac accumulation in FDG-PET scans. Over an average of 49 (22-76) months, 19 patients experienced MACE. The occurrence of MACE was higher in the reduced left ventricle ejection fraction (LVEF) group (&lt;50%) than in the preserved LVEF group (≥50%) (51.5% vs. 5.1%, Log rank p &lt;0.001). Similarly, MACE was more common in the SVT/VF (+) group as compared to the SVT/VF (-) group (50.0% vs. 23.4%, Log rank p =0.041). However, the presence of cardiac accumulation in FDG-PET showed no significant correlation (Log rank p =0.718). Conclusions: The presence of residual cardiac accumulation after initiation of immunosuppressive therapy was not associated with the prognosis of the patients with CS. Established predictors, such as reduced LVEF and the occurrence of SVT/VF, remain integral in predicting MACE.

Abstract 16715: Rare or Disregarded; A Case of Autoimmune Myopathy

Introduction: Statin-induced myopathy can present with symptoms ranging from mild myalgia to significant muscle weakness. This case report highlights how statin-induced autoimmune myopathy often goes undiagnosed. Case Presentation: We present a 69 year old male with a past medical history of coronary artery disease who presented with myalgia and progressive proximal muscle weakness for 2 months. On admission, creatinine kinase (CK) level was noted to be elevated at 8323 u/L. Atorvastatin was held on admission and the patient received intravenous (IV) fluid as treatment for presumed rhabdomyolysis. Although CK was trending down, the patient did not show any significant improvement in muscle weakness or myalgia. At this point, myositis was suspected, so a myositis panel including anti-HMG Co-A Reductase antibody was ordered and the patient was started on IV steroids. Anti-HMG Co-A Reductase antibody was positive and the rest of myopathy workup was negative; meanwhile, the patient's muscle weakness significantly improved. The patient was discharged on a methylprednisolone with close outpatient rheumatology follow-up. Discussion: Drug-induced rhabdomyolysis is one of many causes of myalgia. It is crucial to review a patient’s medication list and discontinue any possible medications that are possible offenders. Statin-induced myopathy should also be suspected when typical treatment for rhabdomyolysis is failing. Statin induced autoimmune myopathy is associated with muscle weakness, elevated CK and a positive anti-HMG Co-A Reductase antibody, which requires discontinuation of Statin and initiation of immunosuppressive therapy. Conclusions: This case report highlights the importance of early identification and management of statin-induced autoimmune myopathy as a possible differential diagnosis in patients with muscle weakness, elevated CK levels while on statin therapy who do not respond to IV fluid alone.

Effectiveness of rituximab versus oral immunosuppressive therapies in neuromyelitis optica spectrum disorder in a racially diverse cohort of subjects: A single-center retrospective study.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune, inflammatory disorder characterized by severe relapses and high level of disability. In clinical trials of NMOSD, Black patients are under-represented, < 12%, compared to a relatively high prevalence of NMSOD in this population, 10/100,000. Despite the higher prevalence of NMOSD in Black and Asian patients, there is limited knowledge of the effectiveness of disease modifying treatments across racially diverse groups. To assess the effectiveness of rituximab and oral immunosuppressive agents in a cohort of NMOSD patients, the majority of whom are Black, in a real-world, clinical setting. A single-center retrospective study was conducted at the University of Chicago Medical Center. (1) diagnosis according to the 2015 International Panel for NMO Diagnosis (IPND) Criteria, (2) positive anti-aquaporin-4 antibodies on ELISA or cell-based tests, (3) initiation of immunosuppressant therapy within 5 years of disease onset, (4) first-line treatment with rituximab, mycophenolate (MMF), or azathioprine (AZA). Patients with negative anti-AQP4 titers were excluded. Kaplan-Meier survival analysis was used to estimate proportion of relapse-free patients following initiation of first line immunosuppressive therapy. A Cox proportional hazards regression model assessed the association of risk of relapsing with first-line immunosuppressive treatments with and without adjustments of pre-specified factors (age at disease onset, duration of disease, sex, race, CNS location of relapse). 7 of 29 patients (24%) receiving rituximab experienced a relapse within the first 3 years of treatment vs. 13 of 23 patients (57%) receiving either AZA or MMF. Within the first 6 months of treatment, 2 (6.9%) patients treated with rituximab experienced a relapse vs. 7 (30.4%) patients treated with either MMF or AZA. In the 29 patients treated with rituximab, the 1-year and 3-year proportion of relapse-free patients was 88.8% and 70.9%. For the 23 patients treated with either AZA or MMF, the 1-year and 3-year proportion of relapse-free patients was 69.5% and 38.7%. In the univariate analysis, the risk of relapse was significantly higher in patients treated with AZA or MMF compared to those treated with rituximab (hazard ratio [HR] of 2.48 [0.99 - 6.21]; p=0.046). In this real-world study involving a majority of Black NMOSD patients, rituximab was relatively more effective in preventing relapses within 3 years of therapy initiation than AZA and MMF. Rituximab remains an effective option for treating NMOSD, especially when there are delays in treatment due to access and economic issues associated with newer treatments.

Eosinophilic myocarditis: comprehensive update on pathophysiology, diagnosis, prognosis and management.

Hypereosinophilic syndromes are a group of disorders secondary to the accumulation of eosinophils leading to the injury of one or more organs. Among them, eosinophilic myocarditis (EM) is a rare form of inflammatory cardiomyopathy characterized by eosinophilic infiltration into myocardial tissue and subsequent release of substances with cell membrane damage and cell destruction. The degree of infiltration is thought to depend on the underlying condition, as well as the degree and duration of eosinophil exposure and ranges from mild localized disease to diffuse multifocal infiltrates associated with myocardial necrosis, thrombotic complications and endomyocardial fibrosis. The main causes of EM are hypersensitivity reactions, eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndrome variants, infections and cancer. Clinical presentation can be variable, ranging from asymptomatic forms to life-threatening conditions, to chronic heart failure due to progression to chronic restrictive cardiomyopathy. Marked eosinophilia in peripheral blood, elevated serum eosinophilic cationic protein concentration and multimodality imaging may suggest the etiology of EM, but in most cases an endomyocardial biopsy must be performed to establish a definitive diagnosis. Systemic treatment varies greatly depending on the underlying cause, however the evidence of an eosinophilic infiltrate allows initiation of immunosuppressive therapy, which is the mainstay of treatment in idiopathic and in most forms of EM. Patients with helminthic infection benefit from anti-parasitic therapy, those with myeloid clone often need a tyrosine kinase inhibitor, while anticoagulant therapy should be undertaken in case of possible thrombotic complications.

A case of hyperhemolysis syndrome in sickle cell disease and concomitant COVID-19

BackgroundHyperhemolysis syndrome (HHS) is an uncommon transfusion reaction described in several hematologic disorders, including sickle cell disease (SCD). HHS is characterized by a decline in hemoglobin (Hb) values below pre-transfusion levels following transfusion of red blood cells (RBCs), coupled with laboratory markers consistent with hemolysis. The proposed pathophysiologic mechanisms underlying HHS include increased phosphatidylserine expression, macrophage activation, and complement dysregulation. Many pathophysiologic mechanisms thought to contribute to HHS have been similarly described in cases of severe COVID-19. Case reportA 28-year-old male with a history of HbSS presented with shortness of breath, right-sided chest pain, and a two-day history of fever. Polymerase chain reaction (PCR) detected SARS-CoV-2 infection with the omicron variant. The patient required an RBC transfusion (pre-transfusion hemoglobin [Hb]5.8 g/dL) with an immediate post-transfusion Hb of 6.3 g/dL. However, Hb rapidly declined to 1.7 g/dL, and lactate dehydrogenase (LDH) rose to 8701 u/L. The absolute reticulocyte count of 538 × 109/L correspondingly fell to 29 × 109/L. Despite additional RBC transfusions and initiation of immunosuppressive therapy, he expired on Day 9(D9). ConclusionGiven the similarities in their proposed pathophysiology, patients with SCD and concomitant SARS-CoV-2 infection may be predisposed to developing HHS.

Serum IgG4 level during initial treatment as a predictor of relapse in IgG4-related disease.

We aimed to investigate the predictors of relapse in immunoglobulin G4-related disease (IgG4-RD), focusing on the serum IgG4 levels during initial treatment. We retrospectively recruited 57 patients with IgG4-RD who were treated with immunosuppressants and elevated serum IgG4 levels in a tertiary hospital between January 2011 and December 2020. They were followed up for ≥ 6 months after initiation of immunosuppressive therapy. Clinical and laboratory findings including serum IgG4 levels (reference value: 6-121 mg/dL) were compared between relapsed (n = 13) and non-relapsed (n = 44) groups. Multivariate Cox regression analysis was used to assess the predictors for relapse. We performed a Kaplan-Meier analysis with a log-rank test to evaluate the cumulative relapse rate for two years. Median serum IgG4 levels at baseline were 321 mg/dL in the relapsed group and 299 mg/dL in the non-relapsed group. Serum IgG4 levels were normalized after six months in five (38.5%) relapsed and 28 (63.6%) non-relapsed patients. In multivariate Cox regression analysis, the normalization of serum IgG4 levels at six months was associated with a lower risk of relapse, with a hazard ratio of 0.232 (p = 0.019). Central nervous system involvement was associated with the relapse, with a hazard ratio of 21.130 (p = 0.015). The cumulative relapse rate for two years was lower in the normal serum IgG4 group at six months than in the elevated serum IgG4 group at six months (p = 0.027). Our study suggests that normalization of serum IgG4 levels during immunosuppressive treatment for IgG4-RD independently predicts relapse-free outcomes. Thus, monitoring serum IgG4 levels might be used as a marker of prognosis.

Fragmented QRS on 12-lead electrocardiogram predicts long-term prognosis in patients with cardiac sarcoidosis.

Fragmented QRS (fQRS) on a 12-lead electrocardiogram is a known marker of fatal arrhythmias or cardiac adverse events in ischemic and non-ischemic cardiomyopathy patients. Nonetheless, the association between fQRS and clinical outcomes in patients with cardiac sarcoidosis (CS) remains unclear. Herein, we investigated whether fQRS is associated with long-term clinical outcomes in CS patients. A total of 78 patients who received immunosuppressive therapy (IST) for clinically diagnosed CS were retrospectively examined. Patients were classified into two groups according to the presence (n = 19) or absence (n = 59) of fQRS on electrocardiogram before IST. The primary outcome was the composite event of all-cause death, ventricular tachyarrhythmias (VTs), and hospitalization for heart failure. Results of late gadolinium enhancement on cardiac magnetic resonance imaging were also analyzed. During a median follow-up period of 3.7years (interquartile range: 1.6-6.2years), the primary outcome occurred more frequently in patients with fQRS than in those without (47% vs. 13%, log-rank p = 0.002). Multivariable Cox regression analyses showed that fQRS was an independent determinant of the primary outcome. The incidence of VTs, within 12months of IST initiation, was comparable between the two groups; however, late-onset VTs, defined as those occurring ≥ 12months after IST initiation, occurred more frequently in the fQRS group (21% vs. 2%, log-rank p = 0.002). The scar zone and scar border zone were greater in patients with fQRS than in those without it. In conclusion, our analysis suggests that fQRS is an independent predictor of adverse events, particularly late-onset VTs, in patients with CS.

Dysfunctional high-density lipoprotein in chronic inflammatory rheumatic diseases.

The mechanism explaining low cholesterol concentrations in chronic inflammatory rheumatic disease (CIRD) is incompletely understood. We hypothesized that chronic inflammation impairs the functionality of high-density lipoprotein (HDL), for example, by oxidative processes. Assessment of oxidized HDL (HDLox), a marker of dysfunctional HDL, in newly diagnosed patients with CIRD before and after initiation of immunosuppressive therapy and comparison of HDLox values of patients with CIRD to non-CIRD controls. Prospective observational trial. The study was conducted on 44 newly diagnosed CIRD patients, who were initiated on immunosuppressive therapy (baseline). A total of 136 patients without CIRD served as control. Lipid profiles including HDLox levels and C-reactive protein (CRP) were measured in both groups at baseline. In CIRD patients, measurements were repeated 12 weeks after baseline. Validated outcome tools for disease activity and function were assessed at baseline and 12 weeks. A total of 33 (75%) patients with rheumatoid arthritis, 7(16%) with axial spondyloarthritis, and 4 (9%) with systemic lupus erythematosus were included. Groups were comparable for age and BMI. CIRD patients had higher HDLox concentrations (1.57 versus 0.78, p = 0.02) and tended to have lower low-density lipoprotein cholesterol, HDL cholesterol, and cholesterol concentrations compared to controls. HDLox (1.57 versus 1.4, p = 0.26) and CRP levels (2.1 versus 0.7 mg/dl, p < 0.01) decreased in CIRD patients from baseline to follow-up. CIRD is associated with an impairment of the anti-inflammatory properties of HDL as reflected by an increase in HDLox concentrations. This effect may contribute to the increased cardiovascular risk in chronic inflammatory diseases.

Renal-limited systemic lupus erythematosus: Avoiding delay in diagnosis

Abstract Nephrotic syndrome (NS) and glomerulonephritis (GN) are disorders of varied etiologies. Systemic lupus erythematosus (SLE) is one of the multisystemic diseases causing NS and GN. SLE is often suspected whenever NS/GN is associated with extrarenal manifestations. However, it presents solely as NS or GN without extrarenal features in a handful of cases. This affects the prognosis adversely as negligent delay in diagnosis of SLE and initiation of immunosuppressive therapy is associated with poorer response. We present a series of five women who presented solely with renal manifestations. The diagnosis of SLE was delayed, as the women did not have any extrarenal features. We started immunosuppressive therapy after a diagnosis of lupus nephritis was made in retrospect after a kidney biopsy. This case series highlights the importance of performing serology tests for SLE in all young female patients who present with NS/GN to avoid delay in diagnosis.