OBJECTIVE: To evaluate the efficacy of rituximab (RTX)-containing therapy as first-line as well as rescue treatment for giant cell hepatitis with autoimmune hemolytic anemia (GCH-AHA).
METHODS: This retrospective study recruited patients diagnosed with GCH-AHA and treated with conventional immunosuppressor regimens consisting of prednisone or RTX-containing regimes consisting of RTX and prednisone, with or without another immunosuppressor. The primary outcomes were the complete remission (CR) rate and time-period required for CR. The secondary outcomes included relapses and adverse events.
RESULTS: Twenty patients (8 females and 12 males; age range 1-26 months), 15 receiving conventional regimens and 5 receiving RTX-containing regimens, were included. The CR rates were 73.3 % (11/15) and 100 % (5/5) in the conventional and RTX-containing groups, respectively. The time-period required for CR was significantly shorter in the RTX-containing group than in the conventional group (6 (3-8) versus 14 (5-25) months, P = 0.015). Relapses occurred in 30.8 % (4/13) of patients in the conventional group; all achieved CR after adding RTX. Relapses occurred in 40.0 % (2/5) of patients in the RTX-containing group; both achieved CR after adding intravenous immune globulins or tacrolimus. Transient low immunoglobulin and infections were recorded in both groups. Treatment withdrawal was achieved in 73.3 % (11/15) and 60.0 % (3/5) of patients receiving conventional and RTX-containing regimens after 36 (2-101) and 22 (4-41) months, respectively. Two patients in conventional group died of disease progression and infection.
CONCLUSIONS: RTX-containing first-line therapy achieves CR of GCH-AHA more quickly than the conventional therapy. RTX is efficacious when added to rescue therapy.

Thrombocytopenia with concomitant anemia is a serious condition with a high mortality risk. Destruction of platelets, i.e., thrombocytopenia, can be secondary to either auto-antibodies (immune-mediated) or mechanical destruction (non-immune-mediated). The Coombs test is a widespread tool to differentiate between the two categories, resulting in different specific treatment approaches for each diagnosis. A peripheral blood smear can also help make the diagnosis; for instance, in cases of mechanical destruction such as thrombotic thrombocytopenic purpura (TTP), the red blood cell (RBC) shape looks fragmented, forming schistocytes. In rare instances, TTP can present with both schistocytes and a positive Coombs test, challenging the diagnosis of TTP. TTP is a hematological emergency requiring appropriate anticipation and the initiation of treatment prior to the confirmatory ADAMTS-13 test results. Mild forms of TTP can be managed with glucocorticoids and therapeutic plasma exchange. Refractory cases need more aggressive additional treatment with caplacizumab and rituximab. Caplacizumab is an expensive medication that is usually reserved for use after confirmation of a TTP diagnosis. The advantage of caplacizumab lies in its targeted mechanism of action against the A1 domain of the von Willebrand multimers that are normally destructed by the ADAMTS-13 enzyme. Here, we present a young female patient with confirmed TTP, and the initial diagnosis was challenged by the presence of antibodies with the Coombs test. Very little research has studied this rare instance and the appropriate treatment. Our case will save many future lives, as clinicians should be more aggressive in treating refractory TTP with a positive Coombs test.

UNASSIGNED: Immunoglobulin A vasculitis (IgAV) is a rare condition that most commonly presents during childhood. Patients with adult-onset IgAV are more likely to exhibit severe symptoms at presentation with worse renal outcomes. Pulmonary manifestations of adult-onset IgAV have been described rarely in the literature and often indicate higher morbidity and mortality. Given the rarity of alveolar hemorrhage in IgAV, the literature describing the clinical entity and offering management recommendations is insufficient.
UNASSIGNED: We describe a patient with known adult-onset IgAV who presented with one month of abdominal pain, bloody stools, new skin lesions, and progressive shortness of breath. She developed rapidly worsening hypoxic respiratory failure associated with a hemoglobin drop and diffuse pulmonary infiltrates on imaging. Bronchoscopy demonstrated progressively hemorrhagic effluent on bronchoalveolar lavage (BAL) consistent with a diagnosis of diffuse alveolar hemorrhage (DAH). She developed acute renal failure requiring the initiation of emergent renal replacement therapy. Given concomitant DAH and acute renal failure, methylprednisolone and rituximab (RTX) therapy were initiated. With this treatment regimen, she exhibited marked improvement in respiratory function and complete renal recovery.
UNASSIGNED: This case highlights the importance of considering DAH as a rare and life-threatening pulmonary manifestation of adult-onset IgAV. Our case demonstrates the novel and successful use of RTX in combination with steroids to treat a patient with adult-onset IgAV presenting with concomitant DAH and renal failure.

Pemphigus foliaceus (PF) is an autoimmune blistering disease limited to the superficial skin without mucosal involvement. It is clinically, histologically, and immunopathologically distinct from pemphigus vulgaris (PV). As data on pediatric PF is often merged with data on both pediatric and adult PV patients, isolating clinical outcomes in pediatric PF is not always possible. Therefore, the authors of this review analyzed clinical outcomes following therapy in pediatric PF patients only. A search of databases resulted in 33 pediatric patients with PF. In total, 19 (57.6%) patients were treated with conventional immunosuppressive therapies (CISTs), which consisted of systemic corticosteroids and multiple immunosuppressive agents (ISAs). Further, 14 (42.4%) patients were treated with biologic agents, predominantly rituximab (RTX). The mean age of those treated with biologics was 12.8 years (range = 0.88-18 years) compared to 8.9 years (range = 0.92-15 years) of those treated with CIST (p = 0.01). Treatment with biologics was initiated significantly longer after the diagnosis of PF when compared to patients treated with CIST (p = 0.003). RTX was used in all patients who received biologic therapy. Two (6%) patients also received intravenous immunoglobulin. When clinical outcomes were compared between CIST and biologic therapy, rates of clinical remission, partial remission, and relapse, were not statistically significantly different between groups. When RTX was used, rates of relapse and adverse events were higher in those treated with the lymphoma protocol (375 mg/m2 once weekly for four weeks) compared to those treated with the rheumatoid arthritis protocol (two doses of 1,000 mg two weeks apart) (p < 0.0001). The incidence of adverse events was statistically significantly higher in patients treated with CIST when compared to RTX (p = 0.003). These included both physical and psychological changes. The infection rate after treatment with RTX was 7.1%. These outcomes occurred during a follow-up of 12.5 months (range = 1-36 months) in the CIST group and 20.5 months (range = 6-67 months) in the biologic therapy group. The difference in the follow-up period was not statistically significant. The literature suggests that biologics are superior to CIST in treating pemphigus patients. The results of this review suggest similar responses to therapy in pediatric PF patients treated with biologics compared to CIST. This may have been due to a limited duration of follow-up and a lack of detailed treatment outcomes in pediatric PF patients. The data in this review strongly suggests that specific treatment protocols need to be developed and implemented for pediatric PF patients. These patients are at a critical phase in life where PF therapy can influence or affect physical growth, hormonal changes, psychosocial development, and essential education.

UNASSIGNED: Rituximab (RTX) showed good efficacy and safety for patients with myasthenia gravis. However, the percentage of peripheral CD20+ B cell may be absent for years after low dose of RTX treatment. Persistent hypogammaglobulinemia and opportunistic infection may occur in patients under treatment of RTX with thymoma relapse.
UNASSIGNED: We report a case of refractory myasthenia gravis. After two doses of 100 mg rituximab, the patient developed transient neutropenia. The peripheral blood CD20+ B cell percentage was 0 more than 3 years. Eighteen months later, the patient\'s symptoms relapsed with thymoma recurred. She had persistent hypogammaglobulinemia and multiple opportunistic infections.
UNASSIGNED: In MG patient under B cell depletion therapy had thymoma relapse, Good\'s syndrome may induce prolonged B cell depletion, hypogammaglobulinemia and opportunistic infections.

Minimal change disease (MCD) is a major cause of nephrotic syndrome (NS) in children and a minority of adults. The higher tendency to relapse put patients at risk for prolonged exposure to steroids and other immunosuppressive agents. B cell depletion with rituximab (RTX) may be beneficial to the treatment and prevention of frequently relapsing MCD. Therefore, this study aimed to verify the therapeutic/preventive effects of low-dose RTX on the relapse in adult with MCD.
A total of 33 adult patients were selected for the study, including 22 patients with relapsing MCD in relapse treatment group who were treated with low-dose RTX (200 mg per week × 4 following by 200 mg every 6 months) and 11 patients in relapse prevention group with complete remission (CR) after steroid therapy were treated with RTX (200 mg ×1 every 6 months) for preventing the relapse of MCD.
Of the 22 patients with MCD in relapse treatment group, there were 21 cases (95.45%) of remission [2 (9.09%) partial remission (PR), 19 (86.36%) CR], 1 (4.56%) no remission (NR) and 20 (90.90%) relapse-free. The Median duration of sustained remission was 16.3 months (3, 23.5 months, inter quartile range (IQR)). 11 patients in the relapse prevention group during a follow-up of 12 months (9-31 months) had no relapse. The average dose of prednisone in two groups after RTX treatment was significantly lower than before treatment.
The results of this study suggested low-dose RTX can significantly reduce relapse rate and steroid dose in adults with MCD with fewer side effects. Low-dose RTX regimens may be beneficial for the treatment of relapsing MCD in adults and may be the preferred regimen for patients at high risk for the development of adverse events from corticosteroids.

UNASSIGNED: Pemphigus is a group of auto-immune blistering disorders, characterised clinically by mucocutaneous blisters and erosions and histopathologically by intra-epidermal acantholysis. It was traditionally associated with high morbidity and mortality. The use of rituximab has brought upon a new dawn in the treatment of pemphigus.
UNASSIGNED: A retrospective analysis to ascertain the efficacy, tolerance, adverse effect profile, remission, and relapse with the use of rituximab.
UNASSIGNED: A retrospective analysis of all diagnosed pemphigus patients who received rituximab therapy over a period of 3 years was performed. The patient\'s baseline characteristics, disease duration, clinical presentations, mucosal involvement, disease-severity assessment, and adverse events with rituximab were noted. The outcomes were evaluated based on the definitions of the disease-outcome parameters as early and late endpoints.
UNASSIGNED: Of the 17 pemphigus patients, there were 14 females (82.4%) and three males (17.6%) with a mean age of 35.9 ± 16.5 years (range: 9-65 years). Pemphigus vulgaris (PV) was the predominant type in 11 (64.7%) patients. After rituximab infusion, the 17 patients attained the end of consolidation phase (ECP) within 15 days to 3 months, and the mean duration was 1.24 months. The complete remission (CR on/off) ranged from 0.5 to 35 months, and the mean duration of remission was 21.7 months. Within a median time of 4.2 months, almost 80% patients achieved CR on therapy. Nine (53%) patients were in CR without any therapy till the end of the study period, and eight (47%) were in remission while on minimal therapy.
UNASSIGNED: Rituximab is an efficacious therapeutic agent for pemphigus and is better tolerated and safer to all the previous medications used in the treatment.

UNASSIGNED: Durable vaccine-mediated immunity relies on the generation of long-lived plasma cells and memory B cells (MBCs), differentiating upon germinal center (GC) reactions. SARS-CoV-2 mRNA vaccination induces a strong GC response in healthy volunteers (HC), but limited data is available about response longevity upon rituximab treatment.
UNASSIGNED: We evaluated humoral and cellular responses upon 3rd vaccination in seven patients with rheumatoid arthritis (RA) who initially mounted anti-spike SARS-CoV-2 IgG antibodies after primary 2x vaccination and got re-exposed to rituximab (RTX) 1-2 months after the second vaccination. Ten patients with RA on other therapies and ten HC represented the control groups. As control for known long-lived induced immunity, we analyzed humoral and cellular tetanus toxoid (TT) immune responses in steady-state.
UNASSIGNED: After 3rd vaccination, 5/7 seroconverted RTX patients revealed lower anti-SARS-CoV-2 IgG levels but similar neutralizing capacity compared with HC. Antibody levels after 3rd vaccination correlated with values after 2nd vaccination. Despite significant reduction of circulating total and antigen-specific B cells in RTX re-exposed patients, we observed the induction of IgG+ MBCs upon 3rd vaccination. Notably, only RTX treated patients revealed a high amount of IgA+ MBCs before and IgA+ plasmablasts after 3rd vaccination. IgA+ B cells were not part of the steady state TT+ B cell pool. TNF-secretion and generation of effector memory CD4 spike-specific T cells were significantly boosted upon 3rd vaccination.
UNASSIGNED: On the basis of pre-existing affinity matured MBCs within primary immunisation, RTX re-exposed patients revealed a persistent but atypical GC immune response accompanied by boosted spike-specific memory CD4 T cells upon SARS-CoV-2 recall vaccination.

BACKGROUND: The adverse events (AEs) of rituximab (RTX) for neuromyelitis optica spectrum disorder (NMOSD) are incompletely understood.
OBJECTIVE: To collate information on the reported the AEs of RTX in NMOSD and assess the quality of evidence.
METHODS: PubMed, EMBASE, Web of Science, Cochrane Library, Wanfang Data, CBM, CNKI, VIP, clinicaltrials.gov, and so on were searched for studies with control groups as well as for case series that had assessed the RTX-associated AEs. The incidence of AEs and the comparison of AE risks among different therapies were pooled. The GRADE was developed for evidence quality.
RESULTS: A total of 3566 records were identified. Finally, 36 studies (4 RCTs, 6 crochet studies, 2 NRCTs, and 24 case series), including 1542 patients (1299 females and 139 males), were included for final analyses. Rates of patients with any AEs, any serious AEs (SAEs), infusion-related AEs, any infection, respiratory infection, urinary infection, and death were 28.57%, 5.66%, 27.01%, 17.36%, 4.76%, 4.76%, and 0.17%, respectively. The results from subgroup analysis showed that AE rates were most likely not associated with covariates such as duration of illness and study designs. Very low-quality evidence suggested that the risk ratios (RR) of any AEs (0.84, 95% CI = 00.42-1.69, p = 0.62) and any infections (1.24 95% CI = 0.18-8.61) of RTX were similar to that of azathioprine, and the RR of any AEs of RXT was akin to that of mycophenolate mofetil (0.66, 95% CI = 0.32-1.35 p = 0.26). Evidence of low to high quality showed the lower RR of RTX in other AEs, but not in infusion-related AEs. Strategies to handle AEs focused on symptomatic treatments.
CONCLUSIONS: RTX is mostly safer than other immunosuppressants in NMOSD: the incidence of RTX-associated AEs was not high, and when present, the AEs were usually mild or moderate and could be well controlled. Given its efficacy and safety, RTX could be recommended as a first-line treatment for NMOSD.

BACKGROUND: The main aim of this study was to determine some simple but meaningful parameters that indicate immunochemotherapy-related interstitial lung disease (ILD) early in B-cell lymphoma and provide direction to hematologists.
METHODS: The clinical and laboratory characteristics, the treatments and outcomes of 21 B-cell lymphoma patients with ILD who underwent rituximab (RTX) -based immunochemotherapy were collected and retrospectively analyzed.
RESULTS: More cycles of immunochemotherapy and higher cumulative doses of RTX and doxorubicin hydrochloride liposome conferred a high risk of ILD. Compared to the baseline, patients had a significantly lower white blood cell count (WBC), absolute lymphocyte count (ALC), and albumin level (4.95×109 vs. 6.32×109, 0.71×109 vs. 1.61×109, 34.1 vs. 40.4 g/L; P<0.05), and higher C-reactive protein (CRP), alpha-hydroxybutyrate dehydrogenase (α-HBDH), and lactate dehydrogenase (LDH) (15.36 vs. 7.00 mg/L, 293.0 vs. 163.1 U/L, 361.8 vs. 231.1 U/L; P<0.05) levels at ILD onset. Further, a positive correlation was found between early glucocorticosteroid intervention and the good prognostication of ILD. In addition, an analysis of the prognoses of 2 cases of patients with pneumocystis pneumonia (PCP) infection indicated that after 3 cycles of treatment, patients, especially unfit patients or those who have received ILD glucocorticoid treatment, may need to receive trimethoprim/sulfamethoxazole (TMP/SMX) to prevent PCP.
CONCLUSIONS: There was a relationship between variations of blood parameters and the occurrence of ILD which might serve as a warning for B-cell lymphoma patients with immunochemotherapy-related ILD.