Aims
To elucidate the diagnostic value of sarcoplasmic expression of myxovirus resistance protein A (MxA) for dermatomyositis (DM) specifically analysing different DM subforms, and to test the ...superiority of MxA to other markers.
Methods
Immunohistochemistry for MxA and retinoic acid‐inducible gene I (RIG‐I) was performed on skeletal muscle samples and compared with the item presence of perifascicular atrophy (PFA) in 57 DM patients with anti‐Mi‐2 (n = 6), ‐transcription intermediary factor 1 gamma (n = 10), ‐nuclear matrix protein 2 (n = 13), ‐melanoma differentiation‐associated gene 5 (MDA5) (n = 10) or ‐small ubiquitin‐like modifier activating enzyme (n = 1) autoantibodies and with no detectable autoantibody (n = 17). Among the patients, nine suffered from cancer and 22 were juvenile‐onset type. Disease controls included antisynthetase syndrome (ASS)‐associated myositis (n = 30), immune‐mediated necrotizing myopathy (n = 9) and inclusion body myositis (n = 5).
Results
Sarcoplasmic MxA expression featured 77% sensitivity and 100% specificity for overall DM patients, while RIG‐I staining and PFA reached respectively 14% and 59% sensitivity and 100% and 86% specificity. In any subset of DM, sarcoplasmic MxA expression showed higher sensitivity than RIG‐I and PFA. Some anti‐MDA5 antibody‐positive DM samples distinctively showed a scattered staining pattern of MxA. No ASS samples had sarcoplasmic MxA expression even though six patients had DM skin rash.
Conclusions
Sarcoplasmic MxA expression is more sensitive than PFA and RIG‐I expression for a pathological diagnosis of DM, regardless of the autoantibody‐related subgroup. In light of its high sensitivity and specificity, it may be considered a pathological hallmark of DM per se. Also, lack of MxA expression in ASS supports the idea that ASS is a distinct entity from DM.
L’association de mouvements anormaux avec une atteinte du nerf périphérique doit faire évoquer un certain nombre de diagnostics, guidés par les résultats de l’ENMG.
Décrire les différentes situations ...cliniques associant mouvements anormaux et neuropathie périphérique.
Revue de la littérature et cas cliniques.
Les tremblements sont les plus représentés. D’origine cérébelleuse et associés à une neuropathie d’aggravation progressive, ils font rechercher une étiologie génétique, qu’il s’agisse du groupe des ataxies spino-cérébelleuses, du syndrome de pré-mutation à l’X-fragile, des maladies mitochondriales ou des leucodystrophies métaboliques. D’installation aiguë, associés à une ganglionopathie, ils sont d’abord d’origine paranéoplasique. Ils sont fréquemment représentés dans les atteintes purement périphériques. Les deux grandes causes de neuropathie démyélinisante associée à un tremblement sont d’une part les maladies de Charcot Marie Tooth et d’autre part les polyradiculoneuropathies inflammatoires démyélinisantes chroniques et surtout la neuropathie démyélinisante sensitivomotrice associée à des anticorps anti-MAG. Il n’est pas toujours facile de les différentier mais dans la seconde, les ralentissements des VCM sont plus marqués en distalité (ILT<0,25). L’existence d’un tremblement n’est pas obligatoirement synonyme d’une atteinte sensitive. Ainsi, les patients atteints d’amyotrophie spinale ou de maladie de Kennedy présentent-ils souvent un tremblement intentionnel. Plus exceptionnellement une chorée, une dystonie ou encore des clonies, font découvrir une atteinte du nerf périphérique. C’est parfois le cas dans la neuroacanthocytose et aussi dans la maladie de Creutzfeld Jacob.
Différentes situations cliniques associent mouvements anormaux et neuropathie, dont nous avons décrit les particularités électrophysiologiques des plus fréquentes.
As more young female patients with cancer survive their primary disease, concerns about reproductive health related to primary therapy gain relevance. Cancer therapy can often affect reproductive ...organs, leading to impaired pubertal development, hormonal regulation, fertility, and sexual function, affecting quality of life.
The Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancer (COG-LTFU Guidelines) are evidence-based recommendations for screening and management of late effects of therapeutic exposures. The guidelines are updated every 2 years by a multidisciplinary panel based on current literature review and expert consensus.
This review summarizes the current task force recommendations for the assessment and management of female reproductive complications after treatment for childhood, adolescent, and young adult cancers. Experimental pretreatment as well as post-treatment fertility preservation strategies, including barriers and ethical considerations, which are not included in the COG-LTFU Guidelines, are also discussed.
Ongoing research will continue to inform COG-LTFU Guideline recommendations for follow-up care of female survivors of childhood cancer to improve their health and quality of life.
Objective
To provide evidence‐based recommendations on the use of vaccinations in children and adults with rheumatic and musculoskeletal diseases (RMDs).
Methods
This guideline follows American ...College of Rheumatology (ACR) policy guiding management of conflicts of interest and disclosures and the ACR guideline development process, which includes the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. It also adheres to the Appraisal of Guidelines for Research and Evaluation (AGREE) criteria. A core leadership team consisting of adult and pediatric rheumatologists and a guideline methodologist drafted clinical population, intervention, comparator, outcomes (PICO) questions. A review team performed a systematic literature review for the PICO questions, graded the quality of evidence, and produced an evidence report. An expert Voting Panel reviewed the evidence and formulated recommendations. The panel included adult and pediatric rheumatology providers, infectious diseases specialists, and patient representatives. Consensus required ≥70% agreement on both the direction and strength of each recommendation.
Results
This guideline includes expanded indications for some vaccines in patients with RMDs, as well as guidance on whether to hold immunosuppressive medications or delay vaccination to maximize vaccine immunogenicity and efficacy. Safe approaches to the use of live attenuated vaccines in patients taking immunosuppressive medications are also addressed. Most recommendations are conditional and had low quality of supporting evidence.
Conclusion
Application of these recommendations should consider patients’ individual risk for vaccine‐preventable illness and for disease flares, particularly if immunosuppressive medications are held for vaccination. Shared decision‐making with patients is encouraged in clinical settings.
Diffuse large B-cell lymphoma (DLBCL) presents as a limited-stage disease in 25% to 30% of patients, with better overall survival (OS) than that for advanced-stage disease but with continuous relapse ...regardless of treatment approach. The preferred treatment is abbreviated rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and radiation therapy. On the basis of promising results of positron emission tomography (PET)-directed treatment approaches, we designed a National Clinical Trials Network (NCTN) study to improve outcomes and decrease toxicity.
Patients with nonbulky (< 10 cm) stage I/II untreated DLBCL received 3 cycles of standard R-CHOP therapy and underwent a centrally reviewed interim PET/computed tomography scan (iPET). Those with a negative iPET proceeded with 1 additional cycle of R-CHOP, whereas those with a positive iPET received involved field radiation therapy followed by ibritumomab tiuxetan radioimmunotherapy.
Of 158 patients enrolled, 132 were eligible and 128 underwent iPET, which was positive in 14 (11%) of the patients. With a median follow-up of 4.92 years (range, 1.1-7.7 years), only 6 patients progressed and 3 died as a result of lymphoma. Eleven patients died as a result of nonlymphoma causes at a median age of 80 years. The 5-year progression-free survival estimate was 87% (95% CI, 79% to 92%) and the OS estimate was 89% (95% CI, 82% to 94%), with iPET-positive and iPET-negative patients having similar outcomes.
To our knowledge, S1001 is the largest prospective study in the United States of limited-stage DLBCL in the rituximab era, with the best NCTN results in this disease subset. With PET-directed therapy, 89% of the patients with a negative iPET received R-CHOP × 4, and only 11% had a positive iPET and required radiation, with both groups having excellent outcomes. The trial establishes R-CHOP × 4 alone as the new standard approach to limited-stage disease for the absolute majority of patients.
Background and purpose
Charcot–Marie–Tooth disease type 1 (CMT1) is a group of autosomal dominantly inherited demyelinating sensorimotor neuropathies. Symptoms usually start in the first to second ...decade and include distal muscle weakness and wasting, sensory disturbances and foot deformities. The most frequent cause is a duplication of PMP22 whilst point mutations in PMP22 and other genes are rare causes. Recently, FBLN5 mutations have been reported in CMT1 families.
Methods
Individuals with FBLN5‐associated CMT1 were compiled from clinical and research genetic testing laboratories. Clinical data were extracted from medical records or obtained during patients’ visits at our centres or primary care sites.
Results
Nineteen CMT1 families containing 38 carriers of three different FBLN5 missense variants were identified and a mutational hotspot at c.1117C>T (p.Arg373Cys) was confirmed. Compared to patients with the common PMP22 duplication, individuals with FBLN5 variants had a later age of diagnosis (third to fifth decade) and less severely reduced motor median nerve conduction velocities (around 31 m/s). The most frequent clinical presentations were prominent sensory disturbances and painful sensations, often as initial symptom and pronounced in the upper limbs, contrasting with rather mild to moderate motor deficits.
Conclusions
Our study confirms the relevance of FBLN5 mutations in CMT1. It is proposed to include FBLN5 in the genetic work‐up of individuals suspected with CMT1, particularly when diagnosis is established beyond the first and second decade and comparably moderate motor deficits contrast with early and marked sensory involvement. FBLN5‐associated CMT1 has a recognizable clinical phenotype and should be referred to as CMT1H according to the current classification scheme.
Background and purpose
To describe a large series of patients with α, β, and γ sarcoglycanopathies (LGMD‐R3, R4, and R5) and study phenotypic correlations and disease progression.
Methods
A ...multicentric retrospective study in four centers in the Paris area collecting neuromuscular, respiratory, cardiac, histologic, and genetic data. The primary outcome of progression was age of loss of ambulation (LoA); disease severity was established according to LoA before or after 18 years of age. Time‐to‐event analysis was performed.
Results
One hundred patients (54 γ‐SG; 41 α‐SG; 5 β‐SG) from 80 families were included. The γ‐SG patients had earlier disease onset than α‐SG patients (5.5 vs. 8 years; p = 0.022) and β‐SG patients (24.4 years). Axial muscle weakness and joint contractures were frequent and exercise intolerance was observed. At mean follow‐up of 22.9 years, 65.3% of patients were wheelchair‐bound (66.7% α‐SG, 67.3% γ‐SG, 40% β‐SG). Dilated cardiomyopathy occurred in all sarcoglycanopathy subtypes, especially in γ‐SG patients (p = 0.01). Thirty patients were ventilated and six died. Absent sarcoglycan protein expression on muscle biopsy and younger age at onset were associated with earlier time to LoA (p = 0.021 and p = 0.002). Age at onset was an independent predictor of both severity and time to LoA (p = 0.0004 and p = 0.009). The α‐SG patients showed genetic heterogeneity, whereas >90% of γ‐SG patients carried the homozygous c.525delT frameshift variant. Five new mutations were identified.
Conclusions
This large multicentric series delineates the clinical spectrum of patients with sarcoglycanopathies. Age at disease onset is an independent predictor of severity of disease and LoA, and should be taken into account in future clinical trials.
This large multicentric Parisian series delineates the clinical spectrum of patients with sarcoglycanopathies. Age at disease onset and absence of sarcoglycan expression on muscle biopsy are predictors of severity of disease and loss of ambulation, and should be taken into account in future clinical trials.
Objective
To provide evidence‐based recommendations on the use of vaccinations in children and adults with rheumatic and musculoskeletal diseases (RMDs).
Methods
This guideline follows American ...College of Rheumatology (ACR) policy guiding management of conflicts of interest and disclosures and the ACR guideline development process, which includes the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. It also adheres to the Appraisal of Guidelines for Research and Evaluation (AGREE) criteria. A core leadership team consisting of adult and pediatric rheumatologists and a guideline methodologist drafted clinical population, intervention, comparator, outcomes (PICO) questions. A review team performed a systematic literature review for the PICO questions, graded the quality of evidence, and produced an evidence report. An expert Voting Panel reviewed the evidence and formulated recommendations. The panel included adult and pediatric rheumatology providers, infectious diseases specialists, and patient representatives. Consensus required ≥70% agreement on both the direction and strength of each recommendation.
Results
This guideline includes expanded indications for some vaccines in patients with RMDs, as well as guidance on whether to hold immunosuppressive medications or delay vaccination to maximize vaccine immunogenicity and efficacy. Safe approaches to the use of live attenuated vaccines in patients taking immunosuppressive medications are also addressed. Most recommendations are conditional and had low quality of supporting evidence.
Conclusion
Application of these recommendations should consider patients’ individual risk for vaccine‐preventable illness and for disease flares, particularly if immunosuppressive medications are held for vaccination. Shared decision‐making with patients is encouraged in clinical settings.
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