Lupus Nephritis Outcomes after Stopping Immunosuppression.

Background/Objectives: Immunosuppression (IS) is a standard therapy for lupus nephritis (LN). Data on the outcomes of patients with LN after the discontinuation of immunosuppression remain uncertain. This study aimed to evaluate the outcomes and results of patients with lupus nephritis (LN) who ceased immunosuppressive (IS) therapy. Methods: Records were obtained on the clinical and laboratory features of LN patients who were treated at our Lupus Unit. They included median values and ranges for various numerical variables such as patient age, disease duration, and treatment duration. Categorical variables such as gender, LN class, IS treatment type, and patient outcomes, which were categorized as either "stable" or "flare experienced", were presented as percentages and frequencies. A flare in LN was characterized by a two-fold increase in serum creatinine levels and a rise in proteinuria following the cessation of IS medication. Results: Outcomes were assessed for 45 patients with LN who ceased IS therapy after achieving remission. The patients' median age was 55 years (29-78). The median duration of treatment was 4 years (0.5-14). The LN histology distribution was class V = 24.4%, class IV = 17.8 %, class III = 17.8%, class III + IV = 15.6%, class III + V = 6.7%, class IV + V = 2.2%, and class II + IV and II = 2.2%. At the discontinuation of IS treatment, creatinine levels were elevated in 9/45 (20%) patients. Furthermore, 28.9% of patients relapsed after IS treatment discontinuation. Patients with anti-Smith antibodies (anti-Sm) were observed to have a higher occurrence of relapses, with six patients experiencing flare compared to four patients who remained stable (p = 0.03). Five (38.5%) of the patients with flares had high creatinine levels after IS discontinuation. Conclusions: Most of our patients maintained clinical remission and stable levels of LN parameters after IS treatment discontinuation. Those with a high serum creatinine level, ongoing proteinuria, depleted complement levels, and the presence of anti-Sm antibodies were more likely to experience flares after the discontinuation of IS therapy.

Long-Term Effectiveness of Benralizumab in Eosinophilic Granulomatosis With Polyangiitis.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a multisystemic disease characterized by eosinophilic tissue inflammation. Benralizumab, an anti-IL-5 receptor (anti-IL-5R) monoclonal antibody, induces rapid depletion of eosinophils; its longer-term effect in EGPA is unknown. OBJECTIVE: To assess the real-world effectiveness and clinical remission rates of anti-IL-5R therapy in EGPA. METHODS: We performed a retrospective cohort analysis of patients with EGPA, who commenced treatment with benralizumab. Clinical remission, assessed at 1 year and 2 years after the initiation of benralizumab, was defined as an absence of active vasculitis (Birmingham Vasculitis Activity Score of 0) and an oral corticosteroid (OCS) dose of ≤4 mg/d of prednisolone. "Super-responders" were defined as patients in remission and free of any significant relapses (asthma or extrapulmonary) over the preceding 12 months. The corticosteroid-sparing capacity of benralizumab, patient-reported outcome measures, and characteristics associated with clinical remission and super-responder status were also analyzed. RESULTS: A total of 70 patients completed at least 1 year of treatment with benralizumab, of whom 53 completed 2 years. Of 70 patients, 47 (67.1%) met the definition for clinical remission at 1 year, with a similar proportion in remission at 2 years. Excluding asthma-related relapses, 61 of 70 (87.1%) patients were relapse free at 1 year, and of the 53 who completed 2 years, 45 (84.9%) were relapse free. A total of 67.9% of patients no longer needed any OCS for disease control. No significant difference was seen between antineutrophilic cytoplasmic antibody (ANCA)-positive and ANCA-negative subgroups. CONCLUSIONS: In this real-world setting of patients with EGPA, treatment with benralizumab was well tolerated and resulted in corticosteroid-free clinical remission for the majority of patients.

Lupus enteritis: a narrative review.

Lupus enteritis (LE) is a rare manifestation of systemic lupus erythematosus. The pathophysiology of LE has not been fully elucidated, although inflammatory and thrombotic processes are likely important factors. The underlying pathophysiological mechanisms may depend on which portion of the intestine is affected. Over half of the patients with LE also present with renal or haematological complications. The diagnosis of LE is based on clinical, histopathological and imaging findings; abdominal computed tomography (CT) is the gold standard in diagnosis. Abdominal CT can also identify factors that predict complications and could potentially guide pharmacological and nutritional management. Timely identification and prompt treatment initiation are paramount to avoid life and organ threatening complications. Glucocorticoids are often the first-line treatment. Additional therapy including immunosuppressive therapy is utilised on a case-by-case basis as there are no clinical trials to define the optimal therapeutic approach. Surgical intervention may be needed especially if there is bowel perforation or peritonitis. In general, the prognosis of LE is good.

Reversible Cerebral Vasoconstriction Syndrome and Raynaud's Phenomenon: Is There a Link between the Pathogeneses of Their Underlying Complex Etiology? A Case Report and Literature Review.

Reversible cerebral vasoconstriction syndrome (RCVS) typically manifests as a sudden, severe thunderclap headache due to narrowing of the cerebral arteries. Symptoms usually resolve within three months. An imbalance in cerebral vascular tone, an abnormal endothelial function, and a decreased autoregulation of cerebral blood flow are thought to be involved in the pathogenesis of RCVS. However, the precise origin of this condition is not yet fully understood. Symptoms of Raynaud's phenomenon (RP) include vasospasm of arterioles of the digits. The pathophysiology of RP includes interactions between the endothelium, smooth muscle, and autonomic and sensory neurons that innervate arteries to help maintain vasomotor homeostasis. RP may occur before the clinical manifestation of a rheumatic condition. RCVS is rare in patients with autoimmune rheumatic disease. We describe a 54-year-old female who had a history of Raynaud's phenomenon affecting her fingers and toes since the age of 12 years. The patient was diagnosed with RCVS in 2012. She described RCVS precipitants, including the regular use of cannabis, cocaine, and amphetamine and tobacco smoking. In 2021, she presented with oral ulcers, intermittent swallowing difficulties, and Raynaud's phenomenon. Clinical examination revealed early sclerodactyly, and abnormal nail-fold capillaroscopy showed multiple giant capillaries, dilated capillary loops, and areas of capillary hemorrhage with capillary drop-out. The investigation revealed positive ANA, strongly positive SRP antibodies, and Ro60 antibodies. Our case report indicates that there may be a correlation between RCVS and Raynaud's phenomenon, and a potential connection between RCVS and autoimmune rheumatic diseases. Hence, physicians must be aware of the red flags and subtle differences in neurological abnormalities, such as headaches, in patients with autoimmune rheumatic diseases who have an inactive clinical status to improve patient care and outcomes.

Transverse myelitis associated with systemic lupus erythematosus (SLE-TM): A review article.

Systemic lupus erythematosus-related transverse myelitis (SLE-TM) is a rare but serious complication of SLE, which may result in significant morbidity. Its incidence is estimated between 0.5% and 1% of all SLE patients but may be the presenting feature in 30%-60% of these patients. Unfortunately, due to lack of high-quality studies, data regarding this condition remains limited. Its pathogenesis remains largely unknown and clinical presentation is variable. There are still no set guidelines regarding diagnosis, management, or monitoring and the role of autoantibodies remains controversial. In this review, we aim to summarize the available data regarding the epidemiology, pathogenesis, clinical features, management, and prognosis of this rare disease.

Relapsing polychondritis - A single Centre study in the United Kingdom.

INTRODUCTION AND OBJECTIVES: Relapsing Polychondritis (RP) is a rare immune mediated inflammatory disorder that may result in damage and destruction of cartilaginous tissues. PATIENTS AND METHODS: We retrospectively analysed patients with a clinical diagnosis of RP. Patients were investigated using pulmonary function tests, dynamic high-resolution CT scans, bronchoscopy, laryngoscopy and/or PET-CT scans along with autoimmune serology. Patients had other specialist reviews when indicated. RESULTS: We identified 68 patients with a diagnosis of RP, 55 (81%) were Caucasian, 8 (12%) Afro Caribbean, 4 (6%) Asian and 1 patient had Mixed Ethnicity. Twenty-nine (43%) had pulmonary involvement and in 16, pulmonary involvement was the initial presentation. The mean age at onset was 44 years (range 17-74). There was a mean diagnostic delay of 55 weeks. Sixty-six (97%) patients received a combination of oral Prednisolone and disease modifying anti-rheumatic drugs. Twelve of 19 (63%) received biologics, with an initial good response, and 10 remain on treatment. Eleven patients with respiratory collapse required CPAP to maintain airway patency. Twelve (18%) patients died due to RP and 9 had respiratory complications. Two patients developed myelodysplasia and one had lung carcinoma. In a multivariate regression analysis, the prognostic variables were ethnicity, nasal chondritis, laryngotracheal stricture and elevated serum creatinine. CONCLUSION: RP is a rare autoimmune condition often associated with significant delays in diagnosis and initiation of treatment. Pulmonary involvement in RP may cause significant morbidity and mortality due to organ damage. Disease modifying anti rheumatic drugs and biologics should be considered early in the disease course to minimise adverse effects of long-term corticosteroid therapy and organ damage.

Development of an algorithm for IgG4-related disease management.

OBJECTIVES: IgG4-related disease (IgG4-RD) is a rare fibro-inflammatory condition affecting multiple organs lacking standardized management. In this article, we review the evidence available to provide European expert-based statements on the management of IgG4-RD which were integrated in a final algorithm. METHODS: A panel of nine European experts in IgG4-RD from different specialties was asked to elaborate a set of consensus statements through a Delphi exercise. Three rounds of survey were taken. Consensus was reached when ≥75% of the responders agreed with a statement. RESULTS: Thirty-one statements on induction treatment, maintenance treatment, non-pharmacological treatment, and general considerations were assessed. Patients should be treated promptly in situations when there is an immediate organ threatened, or when organ damage is anticipated. Glucocorticoids (GC) are considered the first line of treatment and should be progressively tapered. Maintenance treatment is recommended for patients with high disease activity or with risk factors for relapse. Rituximab is effective for induction and maintenance of remission, but its use can be limited by economics. Low dose GC with or without GC-sparing agents can be used for maintenance therapy. Stenting or surgery should be ancillary to pharmacological treatment. Follow up should be based on physical examination, blood works, and imaging studies. Furthermore, it should be tailored on individual patient clinical history. 18-fluorodeoxyglucose positron emission tomography/computerized tomography may provide additional information over other imaging modalities. CONCLUSIONS: These new statements and algorithm reached a high degree of agreement and may help guiding the clinical management of IgG4-RD.

Proton pump inhibitor induced subacute cutaneous lupus erythematosus: Clinical characteristics and outcomes.

BACKGROUND: There is a growing literature reporting the association between proton pump inhibitor (PPI) use and subacute cutaneous lupus erythematosus (SCLE). AIMS: To compare the clinical characteristics of a cohort of patients with PPI-induced SCLE, their clinical course and treatment with a control group of primary SCLE patients not exposed to PPI. METHODS: We conducted a matched case-control study in a tertiary referral setting at the Louise Coote Lupus Unit. There were 64 SCLE patients: 36 with PPI-induced SCLE and 28 patients with primary SCLE. RESULTS: Twenty-six patients (72%) had pre-existing SLE in the PPI-induced SCLE group. Lower limb skin lesions were significantly more prevalent in the PPI group (p < 0.0001). The prevalence of anti-Ro and anti-Ro-52 antibodies was numerically higher in the PPI group (64% and 60%), respectively, compared with 46% and 42% in the primary SCLE group. Peripheral blood eosinophils were normal in all patients in the PPI group. Thirteen patients underwent skin biopsy in the PPI group and 12 had histology in keeping with SCLE. The median time to presentation was 8 months with a median resolution period of 6 weeks. PPIs were stopped in 34 patients, while 2 patients continued treatment for other clinical indications. Twelve patients received concurrent oral corticosteroids. Two patients had severe SCLE in the form of Toxic Epidermal Necrolysis requiring critical care admission and were managed with corticosteroids, IV immunoglobulin and/or belimumab. CONCLUSION: Lower limb involvement is a pointer to PPI-induced SCLE which is likely a class effect with all PPI.

Two subsets of human marginal zone B cells resolved by global analysis of lymphoid tissues and blood.

B cells generate antibodies that are essential for immune protection, but their subgroups are poorly defined. Here, we perform undirected deep profiling of B cells in matched human lymphoid tissues from deceased transplant organ donors and blood. In addition to identifying unanticipated features of tissue-based B cell differentiation, we resolve two subsets of marginal zone B (MZB) cells differing in cell surface and transcriptomic profiles, clonal relationships to other subsets, enrichment of genes in the NOTCH pathway, distribution bias within splenic marginal zone microenvironment, and immunoglobulin repertoire diversity and hypermutation frequency. Each subset is present in spleen, gut-associated lymphoid tissue, mesenteric lymph nodes, and blood. MZB cells and the lineage from which they are derived are depleted in lupus nephritis. Here, we show that this depletion is of only one MZB subset. The other remains unchanged as a proportion of total B cells compared with health. Thus, it is important to factor MZB cell heterogeneity into studies of human B cell responses and pathology.

The role of cardiovascular magnetic resonance in the evaluation of acute myocarditis and inflammatory cardiomyopathies in clinical practice - a comprehensive review.

Inflammatory cardiomyopathy (I-CMP) is defined as myocarditis in association with cardiac dysfunction and/or ventricular remodelling. It is characterized by inflammatory cell infiltration into the myocardium and has heterogeneous infectious and non-infectious aetiologies. A complex interplay of genetic, autoimmune, and environmental factors contributes to the substantial risk of deteriorating cardiac function, acute heart failure, and arrhythmia as well as chronic dilated cardiomyopathy and its sequelae. Multi-parametric cardiovascular magnetic resonance (CMR) imaging is sensitive to many tissue changes that occur during myocardial inflammation, regardless of its aetiology. In this review, we summarize the various aetiologies of I-CMP and illustrate how CMR contributes to non-invasive diagnosis.

Defective STAT5 Activation and Aberrant Expression of BCL6 in Naive CD4 T Cells Enhances Follicular Th Cell-like Differentiation in Patients with Granulomatosis with Polyangiitis.

Granulomatosis with polyangiitis (GPA) is a potentially fatal small vessel vasculitis of unknown etiology, characterized by anti-neutrophil cytoplasmic autoantibodies, chronic inflammation, and granulomatous tissue damage. T cell dysregulation, comprising decreased regulatory T cell function and increased circulating effector memory follicular Th cells (TFH), is strongly associated with disease pathogenesis, but the mechanisms driving these observations are unknown. We undertook transcriptomic and functional analysis of naive CD4 T cells from patients with GPA to identify underlying functional defects that could manifest in the pathogenic profiles observed in GPA. Gene expression studies revealed a dysregulation of the IL-2 receptor ß/JAK-STAT signaling pathway and higher expression of BCL6 and BCL6-regulated genes in GPA naive CD4 T cells. IL-2-induced STAT5 activation in GPA naive CD4 T cells was decreased, whereas STAT3 activation by IL-6 and IL-2 was unperturbed. Consistently, BCL6 expression was sustained following T cell activation of GPA naive CD4 T cells and in vitro TFH differentiation of these cells resulted in significant increases in the production TFH-related cytokines IL-21 and IL-6. Thus, naive CD4 T cells are dysregulated in patients with GPA, resulting from an imbalance in signaling equilibrium and transcriptional changes that drives the skewed pathogenic CD4 effector immune response in GPA.

Abdominal arterial lesions associated with antiphospholipid antibodies: a comparative cross-sectional magnetic resonance angiography study.

OBJECTIVE: Case reports and small case series suggest that stenotic lesions of the renal, coeliac and mesenteric arteries may occur in the antiphospholipid syndrome (APS) resulting in clinical consequences such as hypertension and abdominal angina. The objective was to determine the prevalence of stenotic lesions in arteries arising from the middle aorta in patients with antiphospholipid antibodies (aPL) compared with healthy, hypertensive and atherosclerotic controls. METHODS: In a cross-sectional comparative radiological study using magnetic resonance angiography (MRA), we assessed five groups of subjects for the prevalence of stenotic lesions in arteries arising from the middle aorta: APS/aPL positive, healthy renal donors, patients with hypertension, patients with atherosclerosis defined radiologically and patients with systemic lupus erythematosus and vasculitis who were negative for aPL. All subjects underwent MRA in suspended respiration and images were assessed by two senior radiologists blinded to the clinical details. RESULTS: In the atherosclerosis group, vascular stenotic lesions were more prevalent (71%) than in any other group (P ≤0.000002). The prevalence of all stenotic lesions in aPL positive patients (33%) was significantly higher than in the renal donors (18%) and hypertensive patients (19%) (P ≤0.009). Renal artery stenosis was significantly more prevalent in aPL positive patients than in renal donors (P ≤0.0006) but similar to the prevalence in hypertensive patients. Coeliac and/or mesenteric lesions were significantly more common in aPL positive patients vs hypertensive patients (P ≤0.001). Stenoses did not correlate with traditional risk factors. CONCLUSION: Arterial stenotic lesions in arteries arising from the middle aorta were highly prevalent in atherosclerotic subjects and were more common in aPL-positive patients than in hypertensive patients and healthy renal donors.

ANCA-associated vasculitis can present with episodic attacks of joint pain consistent with palindromic rheumatism.

A 64-year-old man with a 2-year history of palindromic rheumatoid arthritis, presented with recurrent flares of arthritis, weight loss, new onset Raynaud's phenomenon and one previous episode of small-volume haemoptysis. Investigations, including renal biopsy, revealed antineutrophil cytoplasmic antibodies-mediated vasculitis. This case highlights the need to consider vasculitis in patients in whom there is an atypical history of arthritis.

Human marginal zone B cell development from early T2 progenitors.

B cells emerge from the bone marrow as transitional (TS) B cells that differentiate through T1, T2, and T3 stages to become naive B cells. We have identified a bifurcation of human B cell maturation from the T1 stage forming IgMhi and IgMlo developmental trajectories. IgMhi T2 cells have higher expression of α4ß7 integrin and lower expression of IL-4 receptor (IL4R) compared with the IgMlo branch and are selectively recruited into gut-associated lymphoid tissue. IgMhi T2 cells also share transcriptomic features with marginal zone B cells (MZBs). Lineage progression from T1 cells to MZBs via an IgMhi trajectory is identified by pseudotime analysis of scRNA-sequencing data. Reduced frequency of IgMhi gut-homing T2 cells is observed in severe SLE and is associated with reduction of MZBs and their putative IgMhi precursors. The collapse of the gut-associated MZB maturational axis in severe SLE affirms its existence in health.

Physician-patient interaction and medication adherence in lupus nephritis.

OBJECTIVE: The quality of physician-patient interaction can have a significant impact on medication adherence. Little is known about this relationship in patients with lupus nephritis. METHODS: A cross-sectional, quantitative study. Data collected included demographics, current medication, systemic lupus erythematosus disease activity index, medication adherence, beliefs about medicines, shared decision-making, patient-doctor depth of relationship, patient-doctor quality of relationship, interpersonal trust in a physician and illness perceptions. RESULTS: Ninety-eight patients with lupus nephritis completed the questionnaires. Logistic regression indicated that medication adherence was significantly predicted by (a) interpersonal trust in a physician (B = 0.85, Wald 3.94, 95% confidence interval (CI) 1.01, 5.44; P = 0.05); (b) timeline cyclical (B = -0.89, Wald 4.95, 95% CI 0.19, 0.90; P < 0.05) and beliefs about the necessity of medicines (B = 0.75, Wald 4.14, 95% CI 1.03, 4.38; P < 0.05). Mediation analysis showed that beliefs about the necessity of medicines significantly mediated the relationship between trust and medication adherence when adjusted for age (B = 0.48, 95% CI 0.06, 1.08; P < 0.01). A further mediation analysis showed that patient-doctor depth of relationship (B = 0.05, 95% CI 0.01, 0.09; P < 0.001), shared decision-making (B = 0.07, 95% CI 0.01, 0.13; P < 0.001) and patient-doctor quality of relationship (B = 0.08, 95% CI 0.01, 0.16; P < 0.001) significantly mediated the relationship between illness coherence and interpersonal trust in a physician. CONCLUSION: The findings highlighted two key elements: (a) the importance of trust in relation to medication adherence; and (b) a good understanding of patients' illness is linked to a better relationship with their doctor and greater participation in shared decision-making which is associated with increased trust. Tailored psycho-educational interventions could contribute to improving the patient-doctor relationship quality, trust and increased shared decision-making, which, in turn, might improve medication adherence in patients with lupus nephritis.

An update on the management of antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by recurrent venous or arterial thrombosis with or without pregnancy morbidity in the presence of persistent antiphospholipid (aPL) autoantibodies. Anticoagulation has, until now, formed the cornerstone of treatment but a significant proportion of patients continue to experience thrombosis and pregnancy morbidity despite this treatment. Thrombosis is the most common cause of mortality and accounts for two fifths of deaths. Direct oral anticoagulant drugs represent an attractive alternative to conventional vitamin K antagonist drugs but emerging evidence suggests these may not be suitable for high-risk patients with thrombotic APS. Laboratory studies and case reports of the successful use of different classes of drugs in APS is increasing our understanding of the other pathophysiological mechanisms which may contribute to the high morbidity of APS. This review summarizes current accepted anticoagulant treatment for APS and examines other potential drugs such as immunomodulating agents, statins and novel agents such as sirolimus and defibrotide.