Post Hematopoietic Cell Transplantation Maintenance Therapy with Low-Dose Azacitidine in a Pediatric Population with High-Risk Myeloid Malignancies.

Efgartigimod versus standard of care in new-Onset AChR subtype generalized myasthenia gravis: A prospective cohort study.

Tacrolimus is the maintenance immunosuppression of choice in pediatric liver transplant (LT) recipients. However, in selective cases, sirolimus is used as an alternative immunosuppressive treatment. We aimed to review a single centre's experience of using sirolimus as an alternative to tacrolimus in pediatric LT recipients. Single centre retrospective study of pediatric LT recipients who were started on sirolimus as an alternative immunosuppressant to tacrolimus. Children (< 16 years) who were started on sirolimus between May 2000 and May 2024 were included in the study. A total of 19 children were started on sirolimus following LT and followed up for a median of 4 years (range 0.4-12.8). Post-transplant lymphoproliferative disorder (PTLD) was the most common reason for tacrolimus discontinuation and conversion to sirolimus (n = 14), followed by tacrolimus-related adverse effects (n = 4) and disease recurrence (n = 1). There were no cases of PTLD recurrence or biopsy-confirmed rejection whilst on sirolimus. Proteinuria and hyperlipidaemia were the most common sirolimus side effects observed. Eighteen children remain on sirolimus to date, and none required discontinuation from side effects. In those with PTLD, 4 episodes of rejection occurred between the period of tacrolimus discontinuation and starting sirolimus (median immunosuppression-free time of 5 months), with one child requiring regrafting due to chronic rejection. The experience from our centre demonstrates sirolimus to be a safe and effective alternative to tacrolimus in a selected population of pediatric LT recipients. Further research with a larger sample size is required to confirm these findings and evaluate the long-term safety of sirolimus in this population.

ITPR1 autoantibody-associated autoimmunity as a cause of newly emerging cognitive decline mimicking Alzheimer's disease: Case report and brief review of the literature.

BACKGROUND Type II cryoglobulinemic vasculitis is a systemic syndrome that usually develops in the background of chronic HCV infection. Cases of non-hepatitis C (HCV)-related type II cryoglobulinemic vasculitis pose diagnostic and therapeutic challenges in patients with pre-existing hematologic and rheumatic conditions. CASE REPORT We present the case of an 82-year-old woman with a history of skin-limited hypocomplementemic urticarial vasculitis (HUV), monoclonal gammopathy of unknown significance (MGUS), and monoclonal B-cell lymphocytosis (MBL), with new-onset pericarditis, pleuritis, worsening rash, and acute kidney injury. Skin and renal biopsies confirmed a diagnosis of type II (mixed) cryoglobulinemic vasculitis. After an extensive infectious disease workup and an in-depth investigation on our patient's MGUS and MBL, none of the classic causative factors for non-infectious mixed-type cryoglobulinemia were identified. Ultimately, she was started on immunosuppressive treatment, despite which she experienced rapidly progressive disease with pulmonary involvement. Utilizing this case as a basis, we examine the challenges of treating non-HCV-related cryoglobulinemia in patients with complex medical histories. CONCLUSIONS We report a case of mixed cryoglobulinemia in the absence of infection and the presence of 2 premalignant hematologic disorders. Moreover, this case emphasizes the importance of conducting biopsies to differentiate between vasculitis syndromes with overlapping phenotypes, illustrates the diagnostic challenges of recognizing cryoglobulinemia in a timely fashion in patients with pre-existing hematologic and autoimmune comorbidities, and highlights the need for better prognostic and diagnostic methods.

Background. Common variable immunodeficiency (CVID) is the most frequent clinically symptomatic primary immunodeficiency; its clinical spectrum is highly variable, ranging from isolated recurrent infections to autoimmune (AID) and inflammatory rheumatic diseases (IRD), which may even be the unique manifestation at disease onset [1]. CVID is mainly a polygenic disease, even if recent studies employing whole-genome and exome sequencing analysis have highlighted that 15–30% may display a monogenic origin [2]. Aim of the study is to describe our CVID patients (pts) cohort, highlighting AID and IRD, and to describe genetic variants possibly linked to immunodeficiency and autoimmunity and therapeutic implications. Methods. This is a monocentric observational retrospective study considering CVID pts followed since 1985 to 2024. Diagnosis was made according to European Society for Immunodeficiency criteria [3]. A next generation sequencing (NGS) analysis of genes potentially linked to hypo-agammaglobulinemia and to antibody deficiency was executed when considered clinically appropriate. Results. Eighty-three pts with a CVID diagnosis were included. CVID total cohort description and comparisons between CVID pts with and without AID are reported in Table 1. Autoimmune cytopenia was the most common autoimmune manifestation occurring in 22.9% of the pts, with immune thrombocytopenia being the most prevalent. Immunosuppressive treatment was necessary in 89.5% of the pts affected by autoimmune cytopenia; in 5 cases, due to refractory cytopenia, rituximab was employed, achieving persistent remission in 4 pts. A diagnosis of IRD was made in 12 pts; 75.0% suffered from inflammatory arthritis. In one pt with Adenosine Deaminase 2 deficiency, genetic analysis aided in employing a target therapy leading remission of the IRD (Table 2). Genetic analysis for variants potentially leading to CVID had been performed in 37.3% of pts; analysis resulted positive in 41.9% of the tested. Genetic variants potentially linked to inborn errors of immunity (IEI) were found in more than half of pts with AID, much more frequently than in other CVID pts (56.5% vs 0.0%; p:0.010). The identified genetic variants are reported in Table 3. Conclusions CVID can be complicated by a wide spectrum of clinical pictures, including AID and IRD, being in our cohort inflammatory arthritis in most of the cases, categorized as a form of Spondyloarthritis in about two thirds. Notably, CVID pts affected by AID and IRD showed a higher frequency of genetic variants potentially leading to IEI; in one case genetic testing aided in orienting IS treatment, leading to remission of the IRD. Nowadays genetic analysis has still limited implications in influencing treatments in CVID, but in the future it might help in targeting precise mechanisms in patients with AID and IRD.

One-stop early noninvasive evaluation of renal allograft rejection and fibrosis: microstructural mapping via time-dependent diffusion MRI

A 38-year-old lady was referred to Cardiology for exertional dyspnoea. Medical history included Granulomatosis with polyangiitis (GPA) in remission after immunosuppressive treatment, End stage renal failure from GPA with renal transplant complicated by allograft nephropathy requiring re-initiation of haemodialysis, Hypertension. Transthoracic echocardiography showed dilated right ventricle with impaired function, preserved left ventricular systolic function, severe tricuspid regurgitation and high echocardiographic probability of pulmonary hypertension (PH). Computed tomography pulmonary angiogram showed no pulmonary embolism. Left and right heart catheterisation demonstrated minor coronary artery disease, pre-capillary PH, no step-up to suggest shunting, no features of chronic thromboembolic disease. Cardiac magnetic resonance was arranged to exclude Arrhythmogenic Right Ventricular Cardiomyopathy, after counselling on the risk of nephrogenic systemic fibrosis, which showed features of cardiac amyloidosis (CA). Cardiac Pyrophosphate scan returned negative for transthyretin (ATTR) CA. Serum myeloma panel demonstrated IgA/Lambda monoclonal gammopathy (anuric). Bone marrow aspiration and fat pad biopsy were unyielding. Endomyocardial biopsy showed characteristic congophilia and apple-green birefringence. Further tissue typing at Mayo Clinic demonstrated light chain (AL) lambda type amyloid deposition. Haematology commenced her on systemic chemotherapy. Cardiac amyloidosis is a form of restrictive cardiomyopathy from deposition of insoluble amyloid. In AL-CA, circulating free light chains exert an additional cytotoxic effect. It is unusual for cardiac amyloidosis to present with isolated RV failure, thus a high index of suspicion is required. Additionally, persistence in diagnostic evaluation with imaging and/or histology is key. With counselling, ESRF should not preclude gadolinium-based contrast imaging. Pursuance of histology is critical to initiate appropriate chemotherapy.

Total hip arthroplasty (THA) significantly enhances patients' quality of life. In the field of haematologic healthcare, hip replacement surgery is particularly relevant for those with conditions such as leukaemia, lymphoma, and myeloma. These patients often undergo extensive treatments, including chemotherapy and corticosteroids, which can lead to bone-related complications like avascular necrosis of the femoral head (ANFH). This systematic review explores the relationship between haematologic diseases and bone pathologies requiring THA. Data were collected from observational retrospective studies on hip arthroplasty in patients with haematologic disorder. Independent reviewers searched the literature, extracting relevant data according to PRISMA guidelines. We analysed 820 papers and included 10 observational studies in the review. Demographics, pathology, treatment, clinical outcomes, complications, survivorship, and follow-up were analysed. The study included a total of 363 patients and 401 hips. The mean age of the patients was 39.5 years. The mean follow-up was 5 years. In the examined studies, most patients were diagnosed with acute lymphoid leukemia (5 out of 11 studies). Avascular necrosis of the femoral head was consistently recognised as the significant etiology for THA. All patients had received corticosteroid therapy in the past, and additional therapies included chemotherapy, radiation, and stem cell transplantation. The median period before surgery was 2.05 years. There were 29 complications that required surgical revision. Aseptic loosening was the cause of 41.95% revisions, impingement and instability for 22.58%, infection for 19.35%, and fracture for 9.67%. Minor causes include sinking and a fractured ceramic liner. THA is a safe and valuable procedure in patients with an ANFH history of haematological diseases and immunosuppressive treatments. Although THA presents higher complication rates in these patients compared to the general population, it has demonstrated satisfactory success rates.

A 10-year-old boy developed progressive tremor, insomnia, and autonomic dysfunction after an upper respiratory tract infection. Initial workup, including brain MRI, CSF analysis, and antibody screening, was unremarkable. By the third month of illness, brain MRI revealed multiple hyperintensities on fluid-attenuated inversion recovery sequences. Empiric immunotherapy led to partial clinical and radiologic improvement. However, neurologic deterioration continued despite subsequent immunosuppressive treatment, and follow-up imaging demonstrated progressive cerebral atrophy. 18F-fluorodeoxyglucose PET revealed marked bilateral thalamic hypometabolism, providing a pivotal clue that redirected the diagnostic approach. Definitive diagnosis was ultimately established through targeted genetic analysis. This case underscores the importance of maintaining a broad differential diagnosis in pediatric patients presenting with progressive neurologic decline, even in the context of transient inflammatory or immune-appearing features. It also highlights the diagnostic value of genetic testing when conventional investigations are inconclusive.

To validate the applicability of the new histological criteria for autoimmune hepatitis (AIH) proposed by the International AIH Pathology Group (IAIH-PG) among Chinese patients with AIH and drug-induced liver injury (DILI). The gold standard for diagnosis relied on clinical response: discontinuing treatment without relapse supported DILI, while relapse or ongoing immunosuppressive treatment confirmed AIH. This two-centre retrospective cohort study included inpatients with DILI or AIH from January 2002 to March 2023. Cases that underwent liver biopsy were selected according to inclusion and exclusion criteria. The diagnostic performance of the criteria was assessed by an area under the receiver operating characteristic curve (AUROC). Out of 69 patients: AIH (41, 59%) and DILI (28, 41%). The accuracy, sensitivity and specificity of the new histological criteria for likely and possible AIH were 70%, 98% and 29%, respectively, with an AUROC of 0.8236 [95% confidence interval (CI): 0.7533-0.8938]. For likely AIH, the accuracy, sensitivity and specificity were 73%, 61% and 89%, respectively, with an AUROC of 0.9177 [95% CI: 0.8757-0.9596]. Moreover, for possible AIH, significant differences were found in serum alanine aminotransferase levels [178.4 (87.0, 435.0) versus 536.5 (206.9, 930.4) U/L] and antinuclear antibody (ANA) ≥1:160 [10 (67%) versus 1 (6%)], as well as in lobular lymphoplasmacytic infiltrate [15 (100%) versus 12 (71%)] and more than mild inflammation [13 (87%)versus 6 (35%)] between AIH and DILI (all Pvalues were <0.05). The new histological criteria exhibit good diagnostic efficacy in distinguishing AIH from DILI in China, with high AUROC. Key discriminators include low aminotransferase, ANA ≥1:160, lobular lymphoplasmacytic infiltrate and more than mild inflammation, which may further improve diagnostic accuracy for AIH.

Giant cell myocarditis is a rare cardiac disorder that can lead to rapid deterioration and poor outcomes. It presents with a wide array of symptoms, including heart failure, ventricular arrhythmias, or atrioventricular block. Its features overlap with other inflammatory cardiac conditions, particularly cardiac sarcoidosis, which can lead to diagnostic challenges. Diagnostic modalities, including cardiac magnetic resonance and positron emission tomography, can detect myocardial inflammation but are not diagnostic. Endomyocardial biopsy remains a gold standard, showing a diffuse inflammatory infiltrate with multinucleated giant cells and extensive myocyte necrosis. Management involves prompt initiation of immunosuppressive treatment, as well as management of the cardiac complications when indicated. Despite treatment, mechanical circulatory support or cardiac transplantation is required in numerous patients, and recurrence in the allograft has been noted. In this review, we discuss the clinical presentation, diagnostic strategy, differential diagnosis with sarcoidosis, and modern treatment options for giant cell myocarditis, emphasizing early diagnosis and newer therapies.

Giant cell myocarditis is a rare, rapidly progressive, potentially lethal disease caused by a T-cell-mediated inflammation of the myocardium. Rapid, early diagnosis is complicated by the diverse clinical picture (acute coronary syndrome, heart failure, arrhythmia episodes). Our 52-year-old female patient has no significant medical history; she had an upper respiratory tract infection prior to admission. She presented to the ER with chest pain and dyspnea. ECG showed anterior ST-elevation. Urgent coronary angiography showed an intact coronary system. Initially, she was hemodynamically stable, and echocardiography showed a mildly reduced EF. During a short observation period, her condition rapidly progressed, she became hypotonic, and due to third-degree AV block and significant pausa, temporary PM implantation was performed. She was admitted to our clinic due to suspected progressive myocarditis. Her condition stabilized with dual circulatory support. Due to continuous PM requirement, performing cardiac MRI was not possible. Cardiac biopsy confirmed giant cell myocarditis. We started high-dose IV steroid therapy. As a result, left ventricular function improved and necroenzyme levels decreased. According to the latest literature recommendations, her steroid treatment was supplemented with mycophenolate mofetil and tacrolimus, which gradually improved the EF and AV conduction, eliminated the need for a pacemaker, we removed the iPM, and stopped the inotropes and vasopressors. Extensive bacteriological, viral serological and immunological tests did not confirm active infection or immunological abnormalities. Cardiac MRI showed good left and right ventricular ejection fractions and late non-ischemic contrast enhancement. She was discharged after 2 weeks of treatment in a stable clinical condition, with the use of complex immunosuppressive therapy. She receives regular follow-up in the heart transplantation department of our clinic. With immunosuppressive treatment, she is symptom-free, EF 60%, and has no arrhythmia or conduction disorders. Our patient's case draws attention to the fact that in case of suspected myocarditis, myocardial biopsy and rapid diagnosis can be life-saving. It is rare that with combined immunosuppressive therapy and regular follow-up over a period of 1 year, the patient remained symptom-free, had good cardiac function, and was able to avoid possible heart transplantation and implantation of a circulatory support device.

Background: Libman-Sacks endocarditis (LSE) is a rare, non-infective form of endocarditis, often associated with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). It is characterized by sterile, verrucous vegetations that typically affect the mitral and aortic valves. While mitral regurgitation and aortic regurgitation are more frequently reported, severe aortic stenosis (AS) as the primary manifestation of LSE is exceedingly rare, with a reported prevalence of only 1.1% among affected patients. Even more unusual is its presentation as the first sign of undiagnosed SLE in a male patient, given the strong female predominance of the disease, with a female-to-male ratio of approximately 8:1. Case: A previously healthy 37-year-old male, presented with severe chest pain. A Transthoracic echocardiogram (TTE) revealed severe aortic stenosis (Figure1), with vegetations on the right coronary cusp (RCC) and non-coronary cusp (NCC) of the aortic valve. His left ventricular ejection fraction was reported as normal, and minimal pericardial effusion was also detected. Infective endocarditis and pericarditis were suspected and he was started on analgesics and colchicine. Empirical antibiotic treatment was initiated, and blood cultures were collected. Transesophageal echo revealed vegetation on the RCC and NCC of the aortic valve, confirming endocarditis (Figure2). His blood cultures returned with negative results, and an autoimmune workup was consistent with the diagnosis of SLE and APS (Table1). A diagnosis of Libman-Sacks endocarditis was suspected as the underlying cause of the valvular disease. He was started on prednisolone, enoxaparin, hydroxychloroquine, warfarin, and aspirin. On follow-up six months later, TEE and TTE showed no significant change in the severity of his AS, nor the vegetation. Therefore, an aortic valve replacement was planned. Discussion: This is a rare case of a male patient with no prior symptoms who presented with LSE as the first manifestation of SLE and APS. It involved severe aortic stenosis, a less common outcome, as LSE typically causes regurgitation. Diagnosis was challenging due to the atypical presentation and initial suspicion of infection. Despite immunosuppressive treatment, the stenosis persisted, necessitating eventual aortic valve replacement. Early diagnosis and management of SLE and APS are crucial to reduce the risk of thromboembolic complications and potentially prevent irreversible organ damage.

Efficacy of daratumumab in treatment of relapsed and/or refractory warm autoimmune hemolytic anemia in children

Safety and preliminary efficacy of anti-CD19 CAR T cells zorpocabtagene-autoleucel in systemic autoimmune diseases: Final analysis of the castle trial

Post-transplant cyclophosphamide-based graft-verses-host disease (GVHD) prophylaxis is associated with a low incidence of fibrotic chronic GVHD after allogeneic hematopoietic cell transplantation across diverse donor types

Infectious uveitis is characterized by inflammation triggered by microorganisms in the uveal tissues of the eye and constitutes a significant risk factor for cataract formation, both due to the chronic course of the disease itself and the widespread use of corticosteroids in treatment. This review comprehensively evaluates current approaches and treatment strategies related to the planning, implementation, and follow-up processes of cataract surgery in uveitis caused by viral, bacterial, and parasitic infections. Uveitis-associated cataracts are frequently posterior subcapsular, and a minimum three-month inactive period and eradication of active infection before surgery are essential prerequisites. In the preoperative period, alongside microorganism-specific treatments, inflammation control should be ensured through perioperative steroid prophylaxis. For example, in uveitis caused by herpes viruses, antiviral prophylaxis is recommended to reduce surgery-induced recurrence risk; in bacterial etiologies such as tuberculosis or syphilis, microbial treatment and serological control before surgery are mandatory. In cataract surgery, phacoemulsification is preferred; management of pupillary synechiae and selection of intraocular lenses (especially hydrophobic acrylic monofocal IOLs) directly influence surgical success. In the postoperative period, continuation of agent-specific prophylactic treatment is critically important since surgical stress and immunosuppressive treatments may trigger reactivation of the infection. The most common postoperative complications include recurrence of uveitis, cystoid macular edema, posterior capsule opacification, and glaucoma. Literature reports indicate that with appropriate management, 70–90% of uveitis patients achieve visual acuity of 20/40 or better. However, if permanent anatomical impairments such as macular scarring or optic nerve damage exist, the visual benefit of surgery may be limited. Therefore, the surgical decision should be made through a multidisciplinary approach, patient education, and management of realistic expectations. In conclusion, cataract surgery in patients with infectious uveitis can be challenging but may serve as an effective component of visual rehabilitation with careful preoperative planning, appropriate intraoperative techniques, and rigorous postoperative monitoring.

Incidence of Endophthalmitis after Cataract Surgery in the Setting of Uveitis and Immunosuppressive Therapy within the IRIS® Registry.

Abstract Introduction Dermatomyositis (DM) is an idiopathic inflammatory myopathy (IIM) characterised by skin rash and muscle weakness, and can be linked with interstitial lung disease (ILD). A severe, often amyopathic subtype is associated with the presence of anti-MDA5 antibodies and is linked to rapidly progressive ILD. Without early recognition and aggressive immunosuppression, anti-MDA5 dermatomyositis can lead to acute respiratory failure, irreversible lung damage and high mortality. This condition emphasises the importance of multidisciplinary care and prompt management of ILD. Case description A 74-year-old female seen by dermatology for a squamous cell carcinoma excision was noted to have a rash on her fingers, chest and back. She has been unwell with dry cough, shortness of breath, morning stiffness in her hands and feet, muscle stiffness with no weakness and significantly reduced exercise tolerance. She suffered from sicca symptoms and reported weight loss and dysphagia to solids. Apart from hypertension, she is fit and has never smoked. Admission investigations showed mildly elevated CRP and d-dimer and normal creatinine kinase (CK). Chest x-ray (CXR) showed bilateral reticular changes and lower zone patchy opacification. Initial observations were stable; however, later required one litre of oxygen. On examination, she had Gottron’s papules on her hands, Gottron’s sign on her left knee and elbows and V-neck and shawl signs. MMT8 was 150/150. She was started on prednisolone 40 mg. Following a high-resolution CT chest showing probable non-specific interstitial pneumonia (NSIP) and organising pneumonia, she was pulsed with intravenous (IV) methylprednisolone (500 mg x3). Despite steroids, her oxygen requirement increased, requiring high-flow nasal oxygen at 50L/ minute with desaturation on minimal exertion. Repeat CXR showed worsening bilateral infiltration. She was urgently transferred to a tertiary centre for IV cyclophosphamide and was commenced on tacrolimus. Atypical pneumonia screen was positive for Pneumocystis Jirovecii, though she was on prophylactic co-trimoxazole. The extended myositis panel was later positive for MDA5 and equivocal for NXP2. Connective tissue disease screen was positive for anti-Ro 52. She made a remarkable recovery following induction therapy and was successfully weaned off oxygen. She completed four cycles of cyclophosphamide and is being assessed for maintenance therapy. She can now walk an hour and even manage a short run for the bus. Malignancy screening picked up an incidental benign infratemporal fossa nerve sheath tumour, and the multidisciplinary team advised surveillance. Discussion This case highlights the importance of early recognition and multidisciplinary management of dermatomyositis, especially the MDA5 subtype, which is closely associated with rapidly progressive ILD. Input from specialities such as dermatology, respiratory, rheumatology and tertiary centres if treatment is not readily available at a district general hospital, is crucial. This patient presented with classic dermatological stigmata of DM and later developed systemic features, including ILD with NSIP and organising pneumonia. Her rapid deterioration despite high-dose steroids highlights the seriousness of this condition and the need for intense treatment to control the disease. This case also serves as a reminder that even subtle dermatological signs in a seemingly stable patient may be early features of serious systemic disease requiring urgent management. The prompt admission of this patient meant that she was in a safe environment to receive specialist care when her condition rapidly deteriorated. Dermatomyositis can be associated with malignancy; however, anti-MDA5 is classified as an intermediate risk factor, whereby patients with two or more intermediate risk factors are classified as being at moderate risk of developing IIM-associated cancer. Patients with a moderate risk, such as in our case, should undergo both basic and enhanced cancer screening. Although an incidental nerve sheath tumour was picked up in this case, she had no other malignancy identified. Key learning points MDA5 dermatomyositis commonly presents as an amyopathic myopathy with normal neurological examination and CK level. It is therefore important not to dismiss the diagnosis if other clinical signs, such as the characteristic rash, are present to ensure a timely diagnosis, particularly as the myositis panel is not usually available immediately. This patient initially presented to dermatology for an unrelated condition, but was noted to have the characteristic rash of dermatomyositis, highlighting the importance of a thorough clinical examination if there is a clinical concern. This patient developed rapidly progressive respiratory failure despite initial steroid treatment, highlighting the aggressive nature of MDA5-associated ILD. Prompt recognition of this is crucial in ensuring appropriate referrals are completed urgently and immunosuppressive treatment is escalated. Having good working relationships with tertiary centres is critical to providing good patient care. Immunocompromised patients are at risk of developing opportunistic infections such as Pneumocystis Jirovecii; hence, patients being treated with intense immunosuppressive therapy are commenced on prophylactic co-trimoxazole +/- acyclovir. In summary, this case highlights the need for high clinical suspicion, thorough investigation, and early aggressive therapy in anti-MDA5 dermatomyositis with ILD. A multidisciplinary team approach is essential to optimise outcomes in this potentially life-threatening condition.