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BMJ Case Reports Jun 2024A man in his 40s with end-stage kidney disease due to IgA nephropathy and receiving peritoneal dialysis presented with a 1-week history of breathlessness, cough and...
A man in his 40s with end-stage kidney disease due to IgA nephropathy and receiving peritoneal dialysis presented with a 1-week history of breathlessness, cough and nosebleeds. CT scan of the chest revealed ground glass changes while blood tests indicated elevated inflammatory markers and a negative vasculitis screen. This included negative ANCA and anti-GBM antibodies. Initial treatment for suspected atypical pneumonia with antibiotics yielded no clinical improvement.Over the course of the admission, his symptoms progressively worsened, leading to oxygen dependency with a FiO2 of 40% and episodes of haemoptysis. Suspicions of pulmonary vasculitis arose due to clinical deterioration, prompting consultation with a tertiary vasculitis centre. It was subsequently concluded that the clinical and radiological findings correlated with ANCA-negative pulmonary vasculitis or a rare case of IgA-associated pulmonary capillaritis. Treatment with methylprednisolone and rituximab led to significant improvement, allowing rapid oxygen withdrawal. The patient was discharged with a tapering prednisolone regimen.
Topics: Humans; Male; Antibodies, Antineutrophil Cytoplasmic; Adult; Rituximab; Vasculitis; Methylprednisolone; Diagnosis, Differential; Tomography, X-Ray Computed; Kidney Failure, Chronic; Lung Diseases; Immunoglobulin A
PubMed: 38901853
DOI: 10.1136/bcr-2023-258766 -
Bilateral Aggressive Mooren Ulcer in the Setting of Bilateral Pterygia and Pregnancy: A Unique Case.Cornea Jun 2024To report an unusual case of bilateral aggressive Mooren ulcer that occurred in the setting of bilateral pterygia and showed a relentless course during pregnancy.
PURPOSE
To report an unusual case of bilateral aggressive Mooren ulcer that occurred in the setting of bilateral pterygia and showed a relentless course during pregnancy.
METHODS
A 39-year-old woman of Black African ethnicity, 36-week pregnant, presented to the eye casualty with bilateral nasal corneal ulcer and associated melt around preexisting pterygia. A detailed workup including microbial evaluation, culture and sensitivity, polymerase chain reaction for herpes simplex virus, varicella zoster virus, and cytomegalovirus, inflammatory blood profile, autoimmune markers, and human leucocyte antigen (HLA) screening was undertaken. Treatment was initiated in a stepwise approach.
RESULTS
Infections and systemic autoimmune and rheumatologic conditions were ruled out. A diagnosis of bilateral Mooren ulcer was made by exclusion. The peripheral blood was positive for HLA DQ2. As the condition seemed refractory to medical management (topical steroids and intravenous pulse methylprednisolone followed by oral prednisolone and topical cyclosporine), urgent bilateral conjunctival resection with multilayered amniotic membrane transplantation was performed to reduce the inflammatory stimulus and keratolysis. Stabilization of the condition warranted the need for systemic immunosuppressive agents. Using a multidisciplinary approach, in liaison with Obstetricians and Rheumatologists, the patient was planned for an earlier elective Cesarean section and commencement of oral mycophenolate mofetil postpartum, which aided in successful control of the disease.
CONCLUSIONS
Mooren ulcer could follow an aggressive course during pregnancy, especially in the setting of preexisting pterygium. The complex hormonal and immunological changes during pregnancy and the delivery of inflammatory mediators directly onto the cornea by pterygium could contribute to the severity. A well-planned, stepwise, and multidisciplinary management is pivotal for the treatment of this condition.
PubMed: 38900823
DOI: 10.1097/ICO.0000000000003591 -
Journal of Virology Jun 2024Chronic hepatitis E mostly occurs in organ transplant recipients and can lead to rapid liver fibrosis and cirrhosis. Previous studies found that the development of...
Chronic hepatitis E mostly occurs in organ transplant recipients and can lead to rapid liver fibrosis and cirrhosis. Previous studies found that the development of chronic hepatitis E virus (HEV) infection is linked to the type of immunosuppressant used. Animal models are crucial for the study of pathogenesis of chronic hepatitis E. We previously established a stable chronic HEV infection rabbit model using cyclosporine A (CsA), a calcineurin inhibitor (CNI)-based immunosuppressant. However, the immunosuppression strategy and timing may be optimized, and how different types of immunosuppressants affect the establishment of chronic HEV infection in this model is still unknown. Here, we showed that chronic HEV infection can be established in 100% of rabbits when CsA treatment was started at HEV challenge or even 4 weeks after. Tacrolimus or prednisolone treatment alone also contributed to chronic HEV infection, resulting in 100% and 77.8% chronicity rates, respectively, while mycophenolate mofetil (MMF) only led to a 28.6% chronicity rate. Chronic HEV infection was accompanied with a persistent activation of innate immune response evidenced by transcriptome analysis. The suppressed adaptive immune response evidenced by low expression of genes related to cytotoxicity (like and ) and low anti-HEV seroconversion rates may play important roles in causing chronic HEV infection. By analyzing HEV antigen concentrations with different infection outcomes, we also found that HEV antigen levels could indicate chronic HEV infection development. This study optimized the immunosuppression strategies for establishing chronic HEV infection in rabbits and highlighted the potential association between the development of chronic HEV infection and immunosuppressants.IMPORTANCEOrgan transplant recipients are at high risk of chronic hepatitis E and generally receive a CNI-based immunosuppression regimen containing CNI (tacrolimus or CsA), MMF, and/or corticosteroids. Previously, we established stable chronic HEV infection in a rabbit model by using CsA before HEV challenge. In this study, we further optimized the immunosuppression strategies for establishing chronic HEV infection in rabbits. Chronic HEV infection can also be established when CsA treatment was started at the same time or even 4 weeks after HEV challenge, clearly indicating the risk of progression to chronic infection under these circumstances and the necessity of HEV screening for both the recipient and the donor preoperatively. CsA, tacrolimus, or prednisolone instead of MMF significantly contributed to chronic HEV infection. HEV antigen in acute infection phase indicates the development of chronic infection. Our results have important implications for understanding the potential association between chronic HEV infection and immunosuppressants.
PubMed: 38899900
DOI: 10.1128/jvi.00846-24 -
Muscle & Nerve Jun 2024Efgartigimod, a neonatal Fc-receptor inhibitor, has recently been approved as treatment for myasthenia gravis (MG). In this retrospective cohort study, we aimed to...
INTRODUCTION/AIMS
Efgartigimod, a neonatal Fc-receptor inhibitor, has recently been approved as treatment for myasthenia gravis (MG). In this retrospective cohort study, we aimed to systematically assess short- and long-term effectiveness of efgartigimod in patients with refractory MG.
METHODS
Sixteen patients with refractory autoimmune acetylcholine receptor MG were treated with efgartigimod. Data were collected from January 2021 to March 2023 on Myasthenia Gravis Activities of Daily Living (MG-ADL), Quantitative Myasthenia Gravis score (QMG), Myasthenia Gravis Composite score (MGC) and the 15-item revised version of the Myasthenia Gravis Quality of Life questionnaire (MG-QoL15r).
RESULTS
A favorable outcome was seen in 56% of patients at the last measurement. Out of 16 patients, 50% were an MG-ADL responder after the first treatment cycle. After 4 weeks, a clinically meaningful improvement compared to baseline was seen on the MG-ADL, QMG, and MGC. There was a statistically significant improvement on the MGQoL15r from baseline to week 4. The improvement was maintained until the last measurement for the MGC and the MGQoL15r. At the last visit, all patients had discontinued 4-weekly dosages, shifting to administration frequencies of 1, 2, or 3 weeks. Drug doses could be decreased for prednisolone (n = 7), azathioprine (n = 2), and intravenous immunoglobulin (n = 9). Frequency of plasma exchange was decreased in nine patients.
DISCUSSION
In patients with refractory MG, efgartigimod was effective for at least half of all patients. Patients required more frequent dosing compared to the ADAPT phase 3 trial. In 80% of the patients concurrent medication could be reduced or discontinued.
PubMed: 38899431
DOI: 10.1002/mus.28184 -
World Journal of Clinical Cases Jun 2024Angioimmunoblastic T-cell lymphoma (AITL) is a common subtype of peripheral T-cell lymphoma. Approximately half of patients with AITL may concurrently present with...
BACKGROUND
Angioimmunoblastic T-cell lymphoma (AITL) is a common subtype of peripheral T-cell lymphoma. Approximately half of patients with AITL may concurrently present with hypergammaglobulinemia. Increased numbers of plasma cells in the bone marrow are commonly observed at diagnosis. These tumors mimic plasma cell myelomas, hindering a conundrum of clinical diagnoses and potentially delaying appropriate treatment.
CASE SUMMARY
A 78-year-old woman experienced poor appetite, weight loss of 5 kg, fatigue 2 months before presentation, and shortness of breath 2 d before presentation, but no fever or night sweats. Physical examination revealed splenomegaly and many palpable masses over the bilateral axillary regions, approximately > 2 cm in size, with rubbery consistency and no tenderness. Blood tests revealed anemia and thrombocytopenia, lactate dehydrogenase level of 153 U/L, total protein level of 10.9 g/dL, albumin to globulin ratio of 0.2, and immunoglobulin G level more than the upper limit of 3000 mg/dL. The free kappa and lambda light chain concentrations were 451 and 614 mg/L, respectively. A pathological examination confirmed the diagnosis of AITL. The initial treatment was the cyclophosphamide, epirubicin, vincristine, and prednisolone regimen. Following this treatment, pleural effusion was controlled, and the patient was discharged in a stable condition and followed up in our outpatient department.
CONCLUSION
This report highlights the importance of differentiating reactive plasmacytosis from plasma cell myeloma in patients with hypergammaglobulinemia. A precise diagnosis of AITL requires a comprehensive evaluation, involving clinical, immunophenotypic, and histological findings conducted by a multidisciplinary team to ensure appropriate treatment.
PubMed: 38898855
DOI: 10.12998/wjcc.v12.i17.3226 -
Journal of Veterinary Internal Medicine Jun 2024Traditionally, 6-month courses of prednisolone are used to treat steroid-responsive meningitis-arteritis (SRMA), but this medication is associated with adverse effects...
BACKGROUND
Traditionally, 6-month courses of prednisolone are used to treat steroid-responsive meningitis-arteritis (SRMA), but this medication is associated with adverse effects that can lead to poor quality of life.
HYPOTHESIS/OBJECTIVES
Resolution of clinical signs and rate of relapse of SRMA would not be significantly different between a 6-month prednisolone protocol and a 6-week protocol.
ANIMALS
Forty-four hospital cases from multiple referral centers in the United Kingdom (2015-2019). Twenty of 44 were treated with the 6-month protocol and 24/44 with the 6-week protocol.
METHODS
Prospective, randomized trial with 12-month follow-up. The same prednisolone protocol reinitiated in the event of relapse. Analysis of relapses with binary logistic and Poisson regression modeling.
RESULTS
All cases responded to their treatment protocol. Relapses occurred in 6/20 (30%) of the 6-month protocol and 9/24 (38%) of the 6-week protocol. There was no statistical difference in the incidence risk of at least 1 relapse between the 2 groups (odds ratio = 1.40; 95% confidence interval [CI], 0.40-4.96, P = 0.60). Among the 15 dogs that relapsed, 10/15 (67%) relapsed once, 3/15 (20%) relapsed twice, and 2/15 (13%) relapsed 3 times. No statistical difference was detected in the incidence rate ratio (IRR) of total relapse events between the 2 groups (IRR = 1.46; 95% CI, 0.61-3.48; P = 0.40).
CONCLUSIONS AND CLINICAL IMPORTANCE
"Short" 6-week prednisolone protocols could be used to treat SRMA, thereby presumably reducing the duration and severity of prednisolone's adverse effects.
PubMed: 38895927
DOI: 10.1111/jvim.17130 -
Clinical, Cosmetic and Investigational... 2024Zoledronic acid is a bisphosphonate that can be administered intravenously and used to treat several bone disorders. It decreases bone resorption, thereby improving bone...
Zoledronic acid is a bisphosphonate that can be administered intravenously and used to treat several bone disorders. It decreases bone resorption, thereby improving bone mineral density (BMD) and reducing fractures. The Food and Drug Administration (FDA) has approved zoledronic acid for the prevention and treatment of osteoporosis in postmenopausal females and males and for other conditions. Zoledronic acid is generally well tolerated, with most side effects being musculoskeletal or gastrointestinal. Cutaneous side effects include maculopapular rash and other mild skin reactions. Rare severe skin rashes, such as toxic epidermal necrolysis, have been reported. Here, we report the case of a 64-year-old female with a medical history of breast cancer status post-radical mastectomy and chemotherapy presenting with delayed hypersensitivity reaction to a hyaluronic acid dermal filler two days after receiving zoledronic acid intravenously given to maintain bone density, symptoms completely resolved with oral prednisolone 20 mg once daily and cetirizine 10 mg. Cases of delayed inflammatory reaction to hyaluronic acid soft tissue filler have previously been reported in patients who have received vaccination or those with viral infections. However, to our knowledge, there have been no reports of delayed inflammatory reactions to facial hyaluronic acid injections after zoledronic acid administration.
PubMed: 38895606
DOI: 10.2147/CCID.S458750 -
Veterinary and Comparative Oncology Jun 2024Multiagent chemotherapy is considered the most effective treatment for canine high-grade lymphoma; however, due to cost and time requirements, single-agent protocols...
Multiagent chemotherapy is considered the most effective treatment for canine high-grade lymphoma; however, due to cost and time requirements, single-agent protocols have also been described. The aim of our study was to evaluate the outcome and prognostic factors of dogs affected by multicentric lymphoma treated with lomustine and prednisolone as first-line treatment. Cases of medium-large-cell multicentric lymphoma treated with lomustine and prednisolone were included in the study. Response to therapy, time to progression (TTP), median disease-free interval (MDFI) and median survival time (MST) were retrospectively described. Thirty cases were included. Eleven (36.67%) were T cell, 11 (36.67%) were B cell and 8 (26.66%) had unknown immunophenotype. The overall response rate (RR) was 87%, with 15 patients achieving CR (50%) and 11 patients PR (37%). The median TTP, MDFI and MST were 42, 63 and 90 days, respectively. The only factor significantly associated with MDFI and MST was the stage. Dogs with multicentric lymphoma treated with lomustine and prednisolone have lower RR, TTP, MDFI and MST compared with dogs receiving multiagent protocols. Based on the short-lasting response, this study confirms that this protocol might have minimal utility beyond palliation.
PubMed: 38890811
DOI: 10.1111/vco.12990 -
BMC Nephrology Jun 2024Sarcoidosis is a systemic disease that can affect multiple organs. While pulmonary sarcoidosis is most commonly observed, renal sarcoidosis occurs less frequently. We...
BACKGROUND
Sarcoidosis is a systemic disease that can affect multiple organs. While pulmonary sarcoidosis is most commonly observed, renal sarcoidosis occurs less frequently. We herein report a case of sarcoidosis with an exceptionally rare distribution including renal lesions.
CASE PRESENTATION
A 51-year-old Japanese female was referred because of bilateral parotid swelling and renal dysfunction. Computed tomography scan showed the swelling of bilateral kidneys, parotid glands, and uterus. Ga scintigraphy also showed remarkable accumulation in these organs. Renal biopsy and cytological evaluations of parotid gland and uterus were performed and she was diagnosed as sarcoidosis of these organs. Treatment was initiated with prednisolone 40 mg/day and then renal dysfunction subsequently improved. In addition, the swelling of parotid glands and uterus improved and Ga accumulation in each organ had disappeared.
CONCLUSION
This is a first case of renal sarcoidosis complicated by parotid glands and uterus lesions. Pathological findings and the reactivity observed in Ga scintigraphy indicated the presence of lesions in these organs.
Topics: Humans; Female; Middle Aged; Sarcoidosis; Kidney Diseases; Parotid Gland; Uterine Diseases; Prednisolone; Parotid Diseases; Radionuclide Imaging; Tomography, X-Ray Computed
PubMed: 38890580
DOI: 10.1186/s12882-024-03635-6 -
The Lancet. Haematology Jun 2024A standard of care and optimal duration of therapy have not been established for patients with multiply relapsed or refractory follicular lymphoma. The aim of this study...
BACKGROUND
A standard of care and optimal duration of therapy have not been established for patients with multiply relapsed or refractory follicular lymphoma. The aim of this study was to evaluate epcoritamab, a novel CD3 × CD20 bispecific antibody, in the third-line and later setting of follicular lymphoma.
METHODS
EPCORE NHL-1 is a multicohort, single-arm, phase 1-2 trial conducted at 88 sites across 15 countries. Here, we report the primary analysis of patients with relapsed or refractory follicular lymphoma in the phase 2 part of the trial, which included the pivotal (dose expansion) cohort and the cycle 1 optimisation cohort. Eligible patients were aged 18 years or older, had relapsed or refractory CD20 follicular lymphoma (grade 1-3A), an Eastern Cooperative Oncology Group performance status of up to 2, and had received at least two previous lines of therapy (including an anti-CD20 monoclonal antibody and an alkylating agent or lenalidomide). Patients were treated with subcutaneous epcoritamab 48 mg in 28-day cycles: weekly in cycles 1-3, biweekly in cycles 4-9, and every 4 weeks until disease progression or unacceptable toxicity. To mitigate the risk and severity of cytokine release syndrome, in the pivotal cohort, cycle 1 consisted of a step-up dosing regimen of a 0·16-mg priming dose on day 1 and a 0·80-mg intermediate dose on day 8, followed by subsequent 48-mg full doses and prophylactic prednisolone 100 mg; in the cycle 1 optimisation cohort, a second intermediate dose of 3 mg on day 15, adequate hydration, and prophylactic dexamethasone 15 mg were evaluated during cycle 1 to further reduce risk and severity of cytokine release syndrome. Primary endpoints were independently reviewed overall response rate for the pivotal cohort and the proportion of patients with grade 2 or worse and any-grade cytokine release syndrome for the cycle 1 optimisation cohort. Analyses were done in all enrolled patients who had received at least one dose of epcoritamab. This study is registered with ClinicalTrials.gov, NCT03625037, and is ongoing.
FINDINGS
Between June 19, 2020, and April 21, 2023, 128 patients (median age 65 years [IQR 55-72]; 49 [38%] female and 79 [62%] male) were enrolled and treated in the pivotal cohort (median follow-up 17·4 months [IQR 9·1-20·9]). The overall response rate was 82·0% (105 of 128 patients; 95% CI 74·3-88·3), with a complete response rate of 62·5% (80 of 128; 95% CI 53·5-70·9). The most common grade 3-4 treatment-emergent adverse event was neutropenia in 32 (25%) of 128 patients. Grade 1-2 cytokine release syndrome was reported in 83 (65%) of 128 patients; grade 3 cytokine release syndrome was reported in two (2%). Immune effector cell-associated neurotoxicity syndrome was reported in eight (6%) of 128 patients (five [4%] grade 1; three [2%] grade 2). Between Oct 25, 2022, and Jan 8, 2024, 86 patients (median age 64 years [55-71]; 37 [43%] female and 49 [57%] male) were enrolled and treated in the cycle 1 optimisation cohort. The incidence of cytokine release syndrome was 49% (42 of 86 patients; eight [9%] grade 2; none of grade 3 or worse), with no reported immune effector cell-associated neurotoxicity syndrome.
INTERPRETATION
Epcoritamab monotherapy showed clinically meaningful activity in patients with multiply relapsed or refractory follicular lymphoma, and had a manageable safety profile.
FUNDING
Genmab and AbbVie.
PubMed: 38889737
DOI: 10.1016/S2352-3026(24)00166-2