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The Journal of International Medical... Jun 2024This report presents a case involving a woman aged >65 years who had been diagnosed with marginal zone lymphoma 3 years prior. The patient was hospitalized with enlarged... (Review)
Review
Brentuximab vedotin therapy followed by autologous peripheral stem cell transplantation as a viable treatment option for an older adult with transformed lymphoma: a case report and literature review.
This report presents a case involving a woman aged >65 years who had been diagnosed with marginal zone lymphoma 3 years prior. The patient was hospitalized with enlarged inguinal lymph nodes, and pathological examination revealed that the lymphoma had transformed into diffuse large B-cell lymphoma. After two cycles of brentuximab vedotin in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (BV-R-CHP) chemotherapy, the patient achieved complete remission. This treatment was followed by autologous hematopoietic stem cell transplantation and lenalidomide maintenance therapy. At the last follow-up, the patient had been in continuous remission for 24 months. This case study suggests that the utilization of BV and R-CHP in conjunction can result in rapid remission, and it can be followed by autologous hematopoietic stem cell transplantation and maintenance therapy with lenalidomide. This treatment approach exhibits potential as a viable option for older individuals with transformed lymphoma.
Topics: Humans; Female; Brentuximab Vedotin; Aged; Transplantation, Autologous; Antineoplastic Combined Chemotherapy Protocols; Lymphoma, Large B-Cell, Diffuse; Doxorubicin; Peripheral Blood Stem Cell Transplantation; Rituximab; Prednisone; Cyclophosphamide; Lenalidomide; Lymphoma, B-Cell, Marginal Zone; Combined Modality Therapy
PubMed: 38869106
DOI: 10.1177/03000605241258597 -
Cureus May 2024Immune checkpoint inhibitors (ICIs) are a form of immunotherapy increasingly utilized in cancer therapies. While offering promise in malignancy treatment, ICIs,...
Immune checkpoint inhibitors (ICIs) are a form of immunotherapy increasingly utilized in cancer therapies. While offering promise in malignancy treatment, ICIs, including atezolizumab, can elicit immune-related adverse events (irAEs) such as cardiotoxicity. We present the case of a 67-year-old male with stage IV metastatic small-cell lung cancer undergoing carboplatin, etoposide, and atezolizumab therapy, who developed pericardial tamponade two months into treatment. Initially presenting with hypoxia on day three of his third treatment cycle, he was admitted due to multifocal pneumonia and subsequently diagnosed with pericardial tamponade stemming from a sizable pericardial effusion. Pericardiocentesis was performed, effectively resolving the tamponade. Infectious etiology was ruled out. Notably, there was no associated myocarditis, as evidenced by negative cardiac markers and magnetic resonance imaging (MRI) findings, and cytologic analysis of the pericardial fluid did not reveal malignant cells, indicating an isolated immunologic etiology for the pericardial effusion. Following successful management, including oxygen support and a prednisone taper, chemotherapy without immunotherapy was resumed after a one-week delay. This rare case underscores the significance of promptly utilizing multimodality imaging with timely cardiology intervention, a prompt pericardial fluid analysis in diagnosing cardiac irAEs, and management leading to improved patient outcomes.
PubMed: 38868282
DOI: 10.7759/cureus.60184 -
Cureus May 2024Background Immunosuppressants are administered in various combinations to prevent immune-induced transplant rejection in patients with liver transplant, as each...
Background Immunosuppressants are administered in various combinations to prevent immune-induced transplant rejection in patients with liver transplant, as each immunosuppressant acts on different cellular sites. However, the use of multiple immunosuppressants also increases the risk for adverse events. Therefore, it is desirable to reduce the types of immunosuppressants administered without increasing the incidence of transplant rejection. The effectiveness of prednisone avoidance has been suggested, although this was not based on statistical significance in many instances. To definitively establish the effectiveness of prednisone avoidance, a statistically significant difference from a prednisone-use group should be demonstrated. Additionally, the effectiveness of prednisone avoidance might vary depending on the combination of other immunosuppressants administered. It has therefore been considered necessary to investigate, for various immunosuppressant combinations, the administration patterns in which prednisone avoidance is effective. Objectives This study aimed to investigate the effectiveness of prednisone avoidance in patients with liver transplant and discuss the results based on statistically significant differences. Methods Data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) were obtained. In studying immunosuppressant combinations, it was essential to control for confounding. Thus, the immunosuppressant combinations, excluding prednisone, were kept the same in the two groups being compared (prednisone-use and prednisone-avoidance groups). The large sample from FAERS allowed for those various immunosuppressant combinations to be compared. Comparisons of transplant rejection in the prednisone-use and prednisone-avoidance groups used the reporting odds ratio (ROR) and the adjusted ROR (aROR), which controlled for differences in patient background. Results With the prednisone-use groups being set as the reference, ROR and aROR were calculated for the prednisone-avoidance groups. Various immunosuppressant combinations were evaluated, and in four patterns - (1) the combination of prednisone and tacrolimus, (2) the combination of prednisone, cyclosporine, and tacrolimus, (3) the combination of prednisone, tacrolimus, and basiliximab, and (4) the combination of prednisone and everolimus) - both the ROR and the aROR for transplant rejection in the prednisone-avoidance group were significantly <1.000. Conclusions This study identified effective immunosuppressant combinations for prednisone avoidance that were not associated with increased transplant rejection. The evidence supporting the effectiveness of prednisone avoidance is strengthened when combined with results from previous studies.
PubMed: 38868240
DOI: 10.7759/cureus.60193 -
Clinical Case Reports Jun 2024This case signifies the importance of recognizing DIAIH within the context of antibiotic therapy, especially in older adults and even shortly after common drug exposures...
KEY CLINICAL MESSAGE
This case signifies the importance of recognizing DIAIH within the context of antibiotic therapy, especially in older adults and even shortly after common drug exposures for treating UTI.
ABSTRACT
Various drugs can induce immune-mediated liver damage and in rare instances may lead to autoimmune hepatitis. Here we report an 84-year-old woman who developed autoimmune hepatitis less than 3 weeks after treatment for urinary tract infection with the antibiotic nitrofurantoin. She presented with jaundice, right upper quadrant abdominal pain, nausea, and vomiting. In the absence of a history of an autoimmune disorder or elevated liver enzymes in the past; elevated liver enzymes after a short course of Nitrofurantoin and the presence of smooth muscle antibodies strongly suggested autoimmune hepatitis, which was confirmed through biopsy sample analysis. The patient scored 7 points on the Naranjo adverse reaction probability scale. The patient's rapid recovery within 1 month of prednisone therapy supports the association of liver damage with nitrofurantoin use.
PubMed: 38868111
DOI: 10.1002/ccr3.9050 -
Child's Nervous System : ChNS :... Jun 2024Tuberculous meningitis (TBM) causes significant morbidity and mortality in young children. Early treatment can be initiated with magnetic resonance (MR) imaging... (Review)
Review
PURPOSE
Tuberculous meningitis (TBM) causes significant morbidity and mortality in young children. Early treatment can be initiated with magnetic resonance (MR) imaging diagnosis. We present MR-detectable miliary meningeal TB in two patients. CASE 1: A 9-year-old girl developed fevers, cough, lethargy, and seizures. Brain MRI demonstrated multiple, small, T2-dark, rim-enhancing lesions, associated with cranial nerve and leptomeningeal enhancement. CSF showed pleocytosis, low glucose, and high protein. Chest CT showed mediastinal lymphadenopathy, multiple small interstitial lung nodules, and a splenic hypo enhancing lesion. Serial bronchoalveolar lavage studies were Xpert MTB/RIF and acid-fast negative. Endobronchial US-guided biopsy of a subcarinal lymph node was positive for Xpert MTB PCR. She was started on a 4-drug treatment for TBM and dexamethasone. Contact tracing revealed a remote positive contact with pulmonary tuberculosis. CASE 2: A 17-year-old female with Crohn's disease on adalimumab developed refractory ear infections despite multiple courses of antibiotics. She underwent myringotomy, with negative aerobic ear fluid culture. Brain MRI, obtained due to persistent otorrhea, showed multiple, small, round, T2-dark lesions. CSF studies were normal. CT chest, abdomen, and pelvis to assess for disseminated disease showed left upper lobe tree-in-bud nodules, hypoattenuating splenic lesions and a left obturator internus abscess with adjacent osteomyelitis. She underwent CT-guided aspiration of the obturator muscle collection, bronchoscopy with bronchoalveolar lavage, biopsy of two preexisting chronic skin lesions, and ear fluid aspiration. QuantiFERON Gold was positive. Ear fluid was Xpert MTB/RIF assay and acid-fast stain positive. Cultures from the ear fluid, skin tissue, muscle tissue, and alveolar lavage showed growth of acid-fast bacilli. She was started on 4-drug therapy and prednisone.
CONCLUSION
Our cases highlight that TBM in many cases remains a diagnostic dilemma - both our patients presented in a prolonged atypical manner. The term miliary TB not only refers to a pattern of interstitial nodules on chest radiographs but also indicates the hematogenous spread of the disease and concurrent pulmonary and extrapulmonary involvement with high risk of TB meningitis. We promote the use of the term miliary meningeal TB - in both cases, the neuroimaging diagnosis of TB preceded both chest imaging and laboratory confirmation of the disease. Miliary meningeal nodules on MRI may have characteristic T2 low signal and may be more conspicuous in children and immunocompromised individuals where background basal meningeal enhancement is less prominent.
PubMed: 38867108
DOI: 10.1007/s00381-024-06480-y -
Hepatology (Baltimore, Md.) Jun 2024While avoidance of long-term corticosteroids is a common objective in the management of autoimmune hepatitis (AIH), prolonged immunosuppression is usually required to...
BACKGROUND AIMS
While avoidance of long-term corticosteroids is a common objective in the management of autoimmune hepatitis (AIH), prolonged immunosuppression is usually required to prevent disease progression. This study investigates the patient and provider factors associated with treatment patterns in U.S. patients with AIH.
APPROACH RESULTS
A retrospective cohort of adults with incident and prevalent AIH was identified from Optum's de-identified Clinformatics® Data Mart Database. All patients were followed for at least 2 years, with exposures assessed during the first year and treatment patterns during the second. Patient and provider factors associated with corticosteroid-sparing monotherapy and cumulative prednisone use were identified using multivariable logistic and linear regression, respectively.The cohort was 81.2% female, 66.3% White, 11.3% Black, 11.2% Hispanic and with median age 61 years. Among 2,203 patients with ≥1 AIH prescription fill, 83.1% received a single regimen for >6 months of the observation year, which included 52.2% azathioprine monotherapy, 16.9% azathioprine/prednisone and 13.3% prednisone monotherapy. Budesonide use was uncommon (2.1% combination, 1.9% monotherapy). Hispanic ethnicity (aOR 0.56; p=0.006), cirrhosis (aOR 0.73; p=0.019), osteoporosis (aOR 0.54; p=0.001) and top quintile of provider AIH experience (aOR 0.66; p=0.005) were independently associated with lower use of corticosteroid-sparing monotherapy. Cumulative prednisone use was greater with diabetes (+441 mg/year; p=0.004), osteoporosis (+749 mg/year; p<0.001) and highly experienced providers (+556 mg/year; p<0.001).
CONCLUSIONS
Long-term prednisone therapy remains common, and unexpectedly higher among patients with comorbidities potentially aggravated by corticosteroids. The greater use of corticosteroid-based therapy with highly experienced providers may reflect more treatment-refractory disease.
PubMed: 38865589
DOI: 10.1097/HEP.0000000000000961 -
Ocular Immunology and Inflammation Jun 2024To provide a comprehensive overview of the diagnostic and therapeutic journey of a pediatric patient with persistent sarcoid-associated panuveitis over a 10-year period,...
PURPOSE
To provide a comprehensive overview of the diagnostic and therapeutic journey of a pediatric patient with persistent sarcoid-associated panuveitis over a 10-year period, who ultimately developed bilateral macular subretinal fibrosis and visual loss.
METHODS
Retrospective case report.
RESULTS
The patient was diagnosed with sarcoidosis after undergoing a transbronchial biopsy. She was followed up because of granulomatous panuveitis, multifocal choroiditis, and papillitis bilaterally. She maintained a stable condition, and visual acuity was 0.3 RE and 0.5 LE. Immunomodulatory therapy included prednisone, methotrexate, and adalimumab. The patient was lost to follow-up for 20 months because of the COVID-19 pandemic. She was represented with active uveitis and was not responding to TNF-ɑ inhibitors (adalimumab and infliximab). Ultimately, the patient's intraocular inflammation was successfully controlled by using intravitreal steroids (Triamcinolone and Fluocinolone acetonide implant). However, the visual outcome was guarded because of bilateral subretinal fibrosis.
CONCLUSION
10% of patients with sarcoidosis-associated uveitis risk blindness in one eye. The index case progressed to sight-robbing bilateral subretinal fibrosis, a rare complication of ocular sarcoidosis despite a combination of conventional and biologic anti-inflammatory therapies. There is a pressing need to develop new treatment agents for refractory non-infectious uveitis.
PubMed: 38865486
DOI: 10.1080/09273948.2024.2363481 -
JAMA Dermatology Jun 2024VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly defined genetic disease with an estimated prevalence of 1 in 4269 men older than 50...
IMPORTANCE
VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly defined genetic disease with an estimated prevalence of 1 in 4269 men older than 50 years and is marked by systemic inflammation, progressive bone marrow failure, and inflammatory cutaneous manifestations.
OBJECTIVE
To define the spectrum of cutaneous manifestations in VEXAS syndrome and the association of these findings with clinical, genetic, and histological features.
DESIGN, SETTING, AND PARTICIPANTS
This observational cohort study included data from 112 patients who were diagnosed with VEXAS-defining genetic variants in UBA1 between 2019 and 2023. Data were collected from medical record review or from patients with VEXAS directly evaluated at the National Institutes of Health in Bethesda, Maryland.
MAIN OUTCOMES AND MEASURES
To define the spectrum of cutaneous manifestations in VEXAS in association with genetic, histological, and other clinical findings. A secondary outcome was cutaneous response to treatment in VEXAS.
RESULTS
Among the 112 patients (median [range] age, 69 [39-79] years; 111 [99%] male), skin involvement was common (93 [83%]), and the most frequent presenting feature of disease (68 [61%]). Of 64 histopathologic reports available from 60 patients, predominant skin histopathologic findings were leukocytoclastic vasculitis (23 [36%]), neutrophilic dermatosis (22 [34%]), and perivascular dermatitis (19 [30%]). Distinct pathogenic genetic variants were associated with specific cutaneous manifestations. The p.Met41Leu variant was most frequently associated with neutrophilic dermal infiltrates (14 of 17 patients [82%]), often resembling histiocytoid Sweet syndrome. In contrast, the p.Met41Val variant was associated with vasculitic lesions (11 of 20 patients [55%]) with a mixed leukocytic infiltrate (17 of 20 patients [85%]). Oral prednisone improved skin manifestations in 67 of 73 patients (92%). Patients with VEXAS treated with anakinra frequently developed severe injection-site reactions (12 of 16 [75%]), including ulceration (2 of 12 [17%]) and abscess formation (1 of 12 [8%]).
CONCLUSIONS AND RELEVANCE
Results of this cohort study show that skin manifestations are a common and early manifestation of VEXAS syndrome. Genetic evaluation for VEXAS should be considered in older male patients with cutaneous vasculitis, neutrophilic dermatoses, or chondritis. Awareness of VEXAS among dermatologists is critical to facilitate early diagnosis.
PubMed: 38865133
DOI: 10.1001/jamadermatol.2024.1657 -
Cureus May 2024The Coronavirus disease of 2019 (COVID-19) pandemic undoubtedly ranks among the most health-impacting pandemics throughout medical history. Although the COVID-19 global...
INTRODUCTION
The Coronavirus disease of 2019 (COVID-19) pandemic undoubtedly ranks among the most health-impacting pandemics throughout medical history. Although the COVID-19 global public health emergency has ended, lessons need to be learned to be more ready to face similar pandemics in the future. Few studies in Saudi Arabia discuss the impact of the COVID-19 pandemic on autoimmune rheumatic disease (AIRD) patients. Thus, this study was conducted to elaborate on the effects of the COVID-19 pandemic on AIRD patients and rheumatology practices in Saudi Arabia. Methods: This observational cross-sectional study was conducted among patients aged over 14 with AIRD using a pre-designed validated survey questionnaire. Data were collected from AIRD patients who were following up between November 2021 to April 2022 at the Rheumatology Clinic of King Fahad General Hospital in Madinah City, Saudi Arabia. This center was chosen as being the main hospital in the city following patients of AIRD.
RESULTS
A total of 324 patients were included in our study, with the majority (n=264, 81.5%) being females. The mean age was 44.42±14.4 years. Clinical data revealed that 115 (35.5%) of our patients experienced mild COVID-19 infection, 19 (5.9%) suffered from respiratory insufficiency, and seven (2.2%) required admission to the intensive care unit (ICU). Non-compliance to medication was recorded at 25.2%. There were 115 (35.5%) patients who had an AIRD flare that was significantly higher among those who were not adherent to the medications (p<0.001). Disease flare was also significantly seen among patients who were not on prednisone or were on low doses of prednisone (p<0.001). The majority (n=33, 97.1%) of the 34 infected patients who had an AIRD flare had their flare-up at the same time as their COVID-19 infection (p<0.001). COVID-19 vaccination rate was 87.7% (n=284). The most common reason for non-vaccination in 40 (12.3%) patients was the patients' concern about disease flare-ups by the vaccine or interference of the vaccine with their medication (n=16, 4.9%).
CONCLUSION
Our study showed a 35.5% (n=115) COVID-19 infection rate. The majority of our AIRD patients sustained minor infections that did not require hospitalization or ICU admission. The majority of the patients who underwent a severe COVID-19 infection course were not on prednisolone or were on low-dose prednisone. Due to COVID-19 restrictions and drug shortages, one in four patients (25.3%) stopped taking their medications and was significantly found to have a high prevalence of underlying AIRD flare. Despite the high vaccination rate, disease flare was the biggest concern for those who were not immunized. Although the COVID-19 pandemic has ended, doctors should be aware of risk factors associated with severe AIRD outcomes that should be balanced based on the infection severity, underlying disease flares, and patient-centered education about medication adherence and vaccination.
PubMed: 38864060
DOI: 10.7759/cureus.60128 -
Doklady. Biochemistry and Biophysics Jun 2024Rituximab (RTX) has been used for the treatment of systemic sclerosis (SSс) for a long time and has shown good efficacy for skin fibrosis and interstitial lung disease...
Rituximab (RTX) has been used for the treatment of systemic sclerosis (SSс) for a long time and has shown good efficacy for skin fibrosis and interstitial lung disease (ILD). However, data on tolerability and long-term adverse events (AEs) during RTX therapy in SSc are insufficient. The objective of this study was to assess the tolerability and safety of RTX in patients with SSс in a long-term prospective follow-up. Our open-label prospective study included 151 SSс patients who received at least one RTX infusion. The mean age of the patients was 47.9 ± 13.4 years; the majority of them were women (83%). The mean disease duration was 6.4 ± 5.8 years. The mean follow-up period after the first RTX infusion was 5.6 ± 2.6 years (845.6 patient-years (PY)). All patients received RTX in addition to ongoing therapy with prednisone and/or immunosuppressants. AEs were assessed and recorded by a doctor in the hospital immediately after RTX infusion and then by patient's reported outcome during the observation period. All causes of death were considered, regardless of treatment. A total of 85 AEs (56%) were registered, the overall incidence of AEs was 10/100 PY (95% confidence interval (CI) 8-12). The highest frequency of all AEs was observed in the first 2-6 months after the first course of RTX, however, these were mainly mild and moderate AEs (71%). The most frequent AEs were infections, they were observed in 40% of cases, with no serious opportunistic infections reported. The overall incidence of all infections was 7.1/100 PY (95% CI 5.5-9), serious infections-1.5/100 PY (95% CI 0.9-2.6). Infusion reactions occurred in 8% of patients. Other AEs were noted in 3% (0.6/100 PY, 95% CI 0.3-1.4). The overall incidence of serious AEs was 18%-3.2/100 PY (95% CI 2.2-4.6). There was a significant decrease of the immunoglobulin G (Ig G) during follow-up; however, its average values remained within normal limits. There were 17 deaths (11%) (2/100 PY, 95% CI 1.3-3.2). In most cases, patients died from the progression of the major organ failure, which arose before RTX treatment. In our study, the safety profile of RTX in SSс was assessed as favorable. It was similar to the AE profile in other autoimmune diseases treated with RTX. With an increase in the cumulative dose of RTX, no increase in AEs was observed. The mortality is comparable to the other severe autoimmune diseases in observational studies. Monitoring of IgG may be useful for patients with SSс on RTX therapy for early detection of the risk of developing infectious complications. RTX could be considered as a relatively safe drug for the complex therapy of SSс when standard therapy is ineffective or impossible.
PubMed: 38861145
DOI: 10.1134/S1607672924700856