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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 -
European Heart Journal. Case Reports Apr 2024Atrial fibrillation is a common cardiac arrhythmia and often develops secondary to structural cardiac changes. Both the occurrence of atrial fibrillation and/or...
BACKGROUND
Atrial fibrillation is a common cardiac arrhythmia and often develops secondary to structural cardiac changes. Both the occurrence of atrial fibrillation and/or structural changes of the heart may lead to development of atrial cardiomyopathy and heart failure (HF). However, isolated atrial cardiomyopathy caused by focal atrial thickening is a rare condition, previously only described in case reports as a result of different aetiologies all linked to inflammation.
CASE SUMMARY
A patient with inflammatory-mediated atrial cardiomyopathy causing atrial fibrillation and acute decompensated HF presented as isolated left atrial wall thickening on transoesophageal echocardiography. The diagnosis was confirmed using multimodality imaging with transthoracic and transoesophageal echocardiography, cardiac magnetic resonance imaging, positron emissions tomography/computer tomography scanning and intracardiac echocardiography-guided endomyocardial biopsy. Despite no specific histological aetiology, the observed atrial cardiomyopathy might be associated with type 1 diabetes mellitus. The patient in the present case was successfully treated with prednisolone.
DISCUSSION
Diabetes mellitus is an important risk factor for developing atrial fibrillation and diabetic cardiomyopathy, due to reduced levels of anti-inflammatory and increased levels of proinflammatory cytokines causing cardiac inflammatory structural remodelling. The regression of the atrial thickening might be due to prednisolone's anti-inflammatory effects and thereby ability to suppress atrial remodelling and reduce the occurrence of atrial fibrillation. However, the effect of prednisolone might only affect the non-manifested inflammatory-mediated atrial remodelling. Due to the rare occurrence of isolated atrial cardiomyopathy a multiple imaging approach during the diagnostic process and follow-ups are essential to determine the aetiology and effect of the treatment.
PubMed: 38887777
DOI: 10.1093/ehjcr/ytae167 -
Clinical Case Reports Jun 2024The immunomodulatory effect of CMV makes coinfection with other microbes, like VZV possible and potentially deadlier in the post kidney transplant period. Treatment...
KEY CLINICAL MESSAGE
The immunomodulatory effect of CMV makes coinfection with other microbes, like VZV possible and potentially deadlier in the post kidney transplant period. Treatment should be started promptly. Both infections can be treated with Valganciclovir.
ABSTRACT
Infections are common complications in kidney transplant recipients owing to the lifelong immunosuppression. Cytomegalovirus (CMV) and Varicella Zoster Virus (VZV) infections are quite common in the posttransplant period. Coinfection with both however has been reported only once. The immunomodulatory effect of CMV makes their interaction with other organisms like VZV potentially sinister. This is a case of a young woman who developed coinfection with HZV and CMV in the first month following a live related kidney transplantation from her mother. Transplant surgery went well with good urine output, but serum creatinine did not fall below 1.7 mg/dL. Immunosuppression consisted of intravenous (IV), followed by oral prednisolone, Mycophenolate Sodium (MPS) and Tacrolimus. 25 days after an uneventful surgery, she developed fever, followed by pain and vesicular eruption on the forehead, typical of VZV infection, along with rising creatinine. CMV PCR yielded 300 copies/mL of DNA, which was undetectable in both donor and recipient pre-transplant. Total white blood cell count fell to 2 × 10/L. MPS was temporarily stopped. Treatment with Valgancyclovir led to resolution of fever, skin lesions and brought serum creatinine down to baseline over 2 weeks.
PubMed: 38887304
DOI: 10.1002/ccr3.9089 -
BMJ Case Reports Jun 2024Rheumatoid pleurisy is common in patients with rheumatoid arthritis, but distinguishing it from other diseases, such as heart failure and tuberculous pleurisy, is often...
Rheumatoid pleurisy is common in patients with rheumatoid arthritis, but distinguishing it from other diseases, such as heart failure and tuberculous pleurisy, is often difficult. A man in his 70s with stable rheumatoid arthritis presented with cardiac enlargement and bilateral pleural effusion on chest radiography. Pleural fluid studies showed lymphocytosis, adenosine deaminase level of 51.6 U/L and rheumatoid factor level of 2245.3 IU/mL, suggestive of rheumatoid pleurisy and tuberculous pleurisy. Thoracoscopy under local anaesthesia revealed erythema of the parietal pleura, small papillary projections and fibrin deposits. H&E-stained biopsy specimens showed inflammatory granulomas with strong lymphocytic infiltration and non-caseating granulomas. He was diagnosed with rheumatoid pleurisy. His symptoms improved with 30 mg of prednisolone. This study highlights that biopsy using thoracoscopy under local anaesthesia effectively diagnoses rheumatoid pleurisy, which may be challenging to diagnose.
Topics: Humans; Male; Thoracoscopy; Anesthesia, Local; Pleurisy; Aged; Biopsy; Thoracic Wall; Diagnosis, Differential; Arthritis, Rheumatoid; Prednisolone; Pleura
PubMed: 38885997
DOI: 10.1136/bcr-2024-260140