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Patients with joint-hypermobility and joint-hypermobility spectrum disorders (HSD), including hypermobile Ehlers-Danlos Syndromes (EDS) present numerous co-morbid concerns, and multidisciplinary care has been recommended. The complexity of these patient's needs and increased demand for medical services have resulted in long delays for diagnosis and treatment and exhausted extant clinical resources. Strategies must be considered to ensure patient needs are met in a timely fashion. This opinion piece discusses several potential models of care for joint-hypermobility disorders, several ways in which primary providers can be involved, and argues that primary providers should be an essential and integrated part of the management of these patients, in collaboration with multidisciplinary teams and pediatric subspecialists. We review several strategies and educational opportunities that may better incorporate primary providers into the care and management of these patients, and we also discuss some of the limitations and barriers that need to be addressed to improve provision of care. This includes establishing primary care physicians as the medical home, providing initial diagnostic and treatment referrals while connecting patients with specialty care, and collaboration and coordination with multi-disciplinary teams for more complex needs. Several barriers exist that may hamper these efforts, including a lack of available specialty trainings for providers interested in providing care to patients with EDS and HSD, a lack of expertly derived consensus guidelines, and limited time resources in extant primary care practices. Also, primary providers should have an active voice in the future for the further consideration and development of these presented strategies.
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Down syndrome (DS) is one of the most common chromosomal conditions that results in intellectual disability. Children with DS have many different inflammatory and noninflammatory conditions that can affect joint mobility leading to arthralgia and altered joint range of motion (ROM), and it is important to have normal reference values for comparison to determine the degree of impairment. The objective of this study was to establish normative joint ROM values, using a standardized measurement approach, for upper and lower joints of healthy children of both genders with DS. This study evaluated joint ROM in healthy males and females with DS who had no previous musculoskeletal pathology. Younger males have more ROM than females at the same age and both genders lose ROM with age but continue to have increased ROM in the ankles compared to children without DS. This study establishes optimal estimates of joint ROM in children with DS, and this information should be helpful to clinicians when assessment requires evaluation of joint ROM to know if evaluation falls within the normal ROM. This reference should be helpful to track joint disease progression over time or as part of a musculoskeletal screen for abnormal joint ROM in children with DS.
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Síndrome de Down , Niño , Humanos , Masculino , Femenino , Rango del Movimiento ArticularRESUMEN
Introduction: After diagnosis of Ehlers Danlos Syndrome (EDS), it is unclear what information patients and parents need and understand about EDS. The objective of this study is to characterize patient and parent knowledge and concerns about EDS after a diagnosis of EDS is made to determine patient and parent concerns and identify barriers that cause discomfort with the diagnosis. Methods: A convenience sample of patient and parent dyads were recruited after new diagnosis of EDS. Patients and parents completed questionnaires that assessed knowledge, comfort, and barriers of EDS before and after diagnosis, EDS education materials accessed, and additional clinical needs and concerns. Results: Seventy-two dyads completed the survey. Conclusion: Many respondents actively seek information on the diagnosis and management of EDS. Parents and patients look for information about EDS differently. Parents have more concerns after diagnosis and both want well-constructed, empirically supported educational materials delivered via multiple modalities, which makes clinical guidelines more essential.
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Background: Patients with rheumatic diseases are at a high risk of invasive pneumococcal disease due to immunosuppression. We conducted a quality improvement project, and the first aim was to increase the percentage of patients with systemic lupus erythematosus and mixed connective tissue disease that is up to date on pneumococcal vaccinations from 9.6% to 80% within one year. Subsequently, the second aim was to increase the percentage of patients on immunosuppression with systemic lupus erythematosus, mixed connective tissue disease, juvenile dermatomyositis and systemic vasculitis that is up to date on pneumococcal vaccinations from 62.6% to 80% within one year. Methods: Two process measures were up-to-date vaccination status on (1) 13-valent pneumococcal conjugated vaccine (PCV13) and (2) 23-valent pneumococcal polysaccharide vaccine (PPSV23). Our outcome measure was being fully up to date on both pneumococcal vaccinations. Interventions included an immunization algorithm, reporting of eligible patients, education, reminders, and pre-visit planning. Results: There were shifts in the centerline for all quality measures in both phases of this project. The combined pneumococcal vaccination rate for Phase 1 increased from 9.6% to 91.1%, and this centerline was sustained. Pneumococcal vaccination rates also significantly increased for Phase 2: 68.8% to 93.4% for PCV13, 65.2% to 88.5% for PPSV23, and 62.6% to 86.5% for the combined pneumococcal vaccination rate. Conclusions: Quality improvement methodology significantly increased and sustained pneumococcal vaccination rates in our high-risk, immunosuppressed patients. We continue to prioritize this important initiative to mitigate the risk of invasive pneumococcal disease.
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BACKGROUND: After introducing IL-1/IL-6 inhibitors, some patients with Still and Still-like disease developed unusual, often fatal, pulmonary disease. This complication was associated with scoring as DReSS (drug reaction with eosinophilia and systemic symptoms) implicating these inhibitors, although DReSS can be difficult to recognize in the setting of systemic inflammatory disease. OBJECTIVE: To facilitate recognition of IL-1/IL-6 inhibitor-DReSS in systemic inflammatory illnesses (Still/Still-like) by looking at timing and reaction-associated features. We evaluated outcomes of stopping or not stopping IL-1/IL-6 inhibitors after DReSS reaction began. METHODS: In an international study collaborating primarily with pediatric specialists, we characterized features of 89 drug-reaction cases versus 773 drug-exposed controls and compared outcomes of 52 cases stopping IL-1/IL-6 inhibitors with 37 cases not stopping these drugs. RESULTS: Before the reaction began, drug-reaction cases and controls were clinically comparable, except for younger disease-onset age for reaction cases with preexisting cardiothoracic comorbidities. After the reaction began, increased rates of pulmonary complications and macrophage activation syndrome differentiated drug-reaction cases from drug-tolerant controls (P = 4.7 × 10-35 and P = 1.1 × 10-24, respectively). The initial DReSS feature was typically reported 2 to 8 weeks after initiating IL-1/IL-6 inhibition. In drug-reaction cases stopping versus not stopping IL-1/IL-6-inhibitor treatment, reaction-related features were indistinguishable, including pulmonary complication rates (75% [39 of 52] vs 76% [28 of 37]). Those stopping subsequently required fewer medications for treatment of systemic inflammation, had decreased rates of macrophage activation syndrome, and improved survival (P = .005, multivariate regression). Resolution of pulmonary complications occurred in 67% (26 of 39) of drug-reaction cases who stopped and in none who continued inhibitors. CONCLUSIONS: In systemic inflammatory illnesses, recognition of IL-1/IL-6-inhibitor-associated reactions followed by avoidance of IL-1/IL-6 inhibitors significantly improved outcomes.
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BACKGROUND: Text messaging is a widespread, cost-effective method for communicating. It is widely used by both parents and teens. The study objective was to survey teens and their parents to assess the capability and willingness of teens to receive healthcare-related text messages from their physician. SUBJECTS AND METHODS: Parents and teens (12-17 years old) at an adolescent clinic were asked to complete surveys. Surveys were available in hard copy or electronically (via Survey Monkey) using computer kiosks in the waiting room. Approval was received from two local Institutional Review Boards. RESULTS: Of the 93 pairs who began the survey, 47 pairs (51%) qualified and completed both the teen and parent surveys. Over 85% of teens were willing to receive texts from their doctor. Teens were most interested in appointment reminders (81%), immunization reminders (53%), and general test results (for example, strep [53%]). Parents' willingness to allow teens to receive text messages directly varied by content. Many parents preferred to also receive a copy of any text message sent to their teen. CONCLUSIONS: Both parents and teens endorse using text messages for appointment reminders. Parents appear willing for their teens to receive some health information directly. Future research should evaluate the efficacy of using text messages for communication with teens to improve care and utilization of services for adolescents.
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Consentimiento Paterno , Sistemas Recordatorios , Envío de Mensajes de Texto , Adolescente , Adulto , Niño , Femenino , Humanos , Kansas , Masculino , Encuestas y CuestionariosRESUMEN
Objectives: Ehlers-Danlos Syndromes (EDS) are a family of heritable connective tissue diseases. Primary practitioners are capable of diagnosing and managing EDS; however, few are knowledgeable and comfortable enough to see patients with EDS, resulting in delays in diagnosis and care. This study explores the barriers physicians experience with diagnosing, managing, and caring for patients with EDS, and potential resolutions to those barriers. Methods: As part of a larger online study, providers (n = 107) in the United States were asked to specify "What information would improve (their) comfort" in diagnosing, caring for, and managing EDS via open-ended questions. Results: Providers reported wanting clinical practice guidelines, in formats that were easily accessible and usable, information on their roles in the management of EDS, the best ways to coordinate with specialty care, and available specialty consultation. Conclusions: Providers overall are willing to diagnose and treat EDS; however, additional supports and training are needed.
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Ehlers-Danlos Syndromes (EDS) is a group of connective tissue disorders often encountered within rheumatology clinics and is associated with several overlapping symptoms, which may require attention from other medical subspecialities. Barriers exist to implementing multidisciplinary care for EDS, including a lack of knowledge, comfort, and time managing EDS. In the absence of multidisciplinary care, patients are often forced to self-coordinate care. This can lead to gaps in care and a lack of clarity of medical ownership over the patient's care. Integrated multidisciplinary clinics are sorely needed, but the development and implementation of such clinics is limited by resources and personnel. As such, the development of a multidisciplinary clinic can be daunting and may serve to discourage providers with competencies in EDS from attempting to develop this service. In this editorial, we share our experiences in developing a multidisciplinary clinic for EDS at a moderately-sized children's hospital, relying on several core disciplines with established EDS clinical loads (ie, rheumatology, cardiology, genetics, and psychology). We discuss considerations for the expansion of this service, pitfalls, and barriers throughout the development of the clinic, and our rationale underlying our process-related decisions. Development of a greater number of multidisciplinary EDS clinics, even in the potential absence of larger institutional support, is both possible and imperative for improving EDS care globally.
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OBJECTIVE: To determine the utility and acceptability for depression and anxiety screening of adolescents and young adults (AYA) with childhood-onset systemic lupus erythematosus (cSLE) in the pediatric rheumatology setting. METHODS: AYA with cSLE, ages 12-21 years, from 8 collaborating sites, were consecutively screened for depression and anxiety with the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder 7-item scale (GAD-7). Demographic and disease characteristics were collected, as well as patient-reported outcome measures using the Patient Reported Outcomes Measurement Information System (PROMIS) pediatric profile-25. Acceptability of screening was assessed with postscreening surveys completed by AYA and parents. Chi-square and Wilcoxon rank sum tests examined the relationship between patient characteristics and history of previous screening. Spearman correlations examined relationships between screening scores, PROMIS domains, and other disease factors. RESULTS: Among 106 AYA screened, 64 (60%) had been previously screened, 25 (24%) by general pediatricians. Thirty-two (30%) AYA screened positive, including 24% for depression, 17% for anxiety, and 14% for suicidal ideation. Depression and anxiety symptom severity were highly correlated with increased PROMIS domain scores for fatigue and pain interference and moderately correlated with increased pain severity, decreased mobility, and decreased peer relationships. Eighty-six percent of AYA and 95% of parents expressed comfort with screening in the pediatric rheumatology setting. CONCLUSION: Depression, anxiety, and suicidal ideation are common among AYA with cSLE, and symptoms are correlated with important patient-reported outcomes. Mental health screening in the pediatric rheumatology setting was highly acceptable among AYA with cSLE and their parents.
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Depresión , Lupus Eritematoso Sistémico , Humanos , Niño , Adolescente , Adulto Joven , Adulto , Depresión/diagnóstico , Calidad de Vida , Ansiedad/diagnóstico , Ansiedad/etiología , Lupus Eritematoso Sistémico/diagnóstico , Trastornos de Ansiedad , Medición de Resultados Informados por el Paciente , DolorRESUMEN
Down syndrome (DS) results from a trisomy of chromosome 21, which causes immune dysregulation that leads to hyperactivation of interferon and Janus kinase (JAK) signaling. This results in complex medical abnormalities in the immune system and an increase in autoimmune and autoinflammatory conditions such as down syndrome-associated arthritis (DA). DA is an aggressive, destructive, inflammatory arthritis that is easily misdiagnosed and difficult to treat. Treatment commonly includes immunosuppressive therapy, but these are often associated with adverse effects and ineffectiveness. This case report outlines a 6-year-old male with DA that was successfully treated with the JAK inhibitor tofacitinib. Due to the aggressive nature of DA and poor response to many immunosuppressive therapies, this case report was created to increase awareness of JAK inhibition as an effective, well-tolerated treatment for DA.
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Down syndrome (DS) is one of the most common birth defects in the United States, the most common genomic disorder of intellectual disability, and results from trisomy 21. This chromosome disorder causes an extensive, heterogenous phenotype that results in a broad presentation of symptoms that includes atlantoaxial instability, congenital heart defects, muscle hypotonia, hypothyroidism, hematologic disorders, recurrent infections, and autoimmune diseases. The autoimmune diseases are caused by immune system dysregulation that results in increased pro-inflammatory cytokines, along with other innate and adaptive immune system dysregulation. This is the likely cause of the increased risk of inflammatory arthritis or Down syndrome-associated arthritis (DA) seen in individuals with DS. Most individuals with DA present with polyarticular (five or more joints with arthritis at presentation of disease), rheumatoid factor and anti-nuclear antibody negative disease that is aggressive with bone and joint damage at presentation. There is notable delay in diagnosis of DA as there are no formal guidelines on screening or monitoring for inflammatory arthritis in individuals with DS. Once diagnosed, and despite aggressive therapy with disease modifying antirheumatic drugs, disease burden is high for those with DA. Therapy can also be challenging for those with DA as many require second and third-line disease modifying therapies. Many also struggle with medication toxicity and ineffectiveness that further causes challenges with management and outcomes. The purpose of this current review is to provide an up-to-date summary of the literature related to DA in children and adolescents with focus on presentation, diagnosis, and management considerations, along with current barriers that inhibit optimal care.
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BACKGROUND: Ehlers-Danlos syndrome (EDS) represents a family of heritable connective tissue disorders with overlapping phenotypic features, frequently including joint hypermobility, tissue fragility, and skin hyperextensibility. Comorbid symptoms are common for patients with EDS and include multiple body systems marked by neurologic, cardiovascular, gastrointestinal, musculoskeletal issues, chronic pain, headaches, and anxiety and depression. The many comorbidities lead to high disease burden, which requires greater healthcare utilization. METHODS: This survey of families examines healthcare utilization, of adults and minors, through evaluation of subspecialty care appointments across many healthcare systems in one region. RESULTS: There were 155 adults and 83 minors with a diagnosis of EDS with a total of 693 unique visits across 27 different specialties at over 20 different hospitals or clinics in the surveyed area. Cardiology, neurology, and gastroenterology were the most utilized subspecialties for adults, while rheumatology, cardiology, and neurology were most utilized by minors. Many respondents (67%) reported their medical care needs are not being met, and 87% reported interest in a multidisciplinary clinic for EDS with the most interest in pain management, physical and occupational therapy, and rheumatology. CONCLUSION: Understanding healthcare utilization and needs of those with EDS can provide the foundation for improved care for those with EDS through a coordinated multidisciplinary care model.
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Enfermedades del Tejido Conjuntivo , Síndrome de Ehlers-Danlos , Inestabilidad de la Articulación , Anomalías Cutáneas , Adulto , Humanos , Síndrome de Ehlers-Danlos/epidemiología , Síndrome de Ehlers-Danlos/terapia , Síndrome de Ehlers-Danlos/diagnóstico , Inestabilidad de la Articulación/diagnóstico , Encuestas y CuestionariosRESUMEN
Objectives: Ehlers-Danlos Syndrome represents a family of heritable connective tissue disorders that include joint hypermobility, tissue fragility, and skin hyperextensibility. Ehlers-Danlos Syndrome presents with clinical sequela across multiple body systems that require multidisciplinary care. Little is known about adolescents with Ehlers-Danlos Syndrome who are transgender and gender diverse. To date, there have been no reports of transgender and gender diverse youth in pediatric patients with Ehlers-Danlos Syndrome. The objective of this study was to characterize transgender and gender diverse adolescents with Ehlers-Danlos Syndrome seen in a pediatric multidisciplinary specialty clinic. Methods: A retrospective chart review was performed and it was found that 28 patients were seen in the Ehlers-Danlos Syndrome multidisciplinary clinic were reported being transgender and gender diverse. Chart review included analysis of all documents in the electronic medical record, including demographic data, gender identity, chosen pronouns, specialty care previously received for Ehlers-Danlos Syndrome, symptoms and conditions related to it, and medications. Results: Of the 166 total adolescents seen in the pediatric multidisciplinary Ehlers-Danlos Syndrome clinic during the study period, 17% reported gender dysphoria. The average age at Ehlers-Danlos Syndrome diagnosis was 13.5 years (range 8-17 years). Most (61%) reported their gender identity as transgender, followed by nonbinary (14%). Most had preferred male (he/him) pronouns (47%), followed by nonbinary (they/them) pronouns (39%). The vast majority reported fatigue (75%), musculoskeletal issues (96%), psychiatric issues (86%), cardiac issues (71%), gastrointestinal issues (68%), and neurologic issues (79%). Conclusions: Here we report the first cohort of transgender and gender diverse adolescents in the Ehlers-Danlos syndrome population and show an association between the two. This report increases awareness for providers who care for patients with Ehlers-Danlos Syndrome. As care for those with Ehlers-Danlos Syndrome is often complex and multidisciplinary, providers should adopt practices of gender-affirming medical care that contribute to improved care and outcomes.
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Systemic juvenile idiopathic arthritis (sJIA) is a chronic, inflammatory disease of childhood, which is characterized by the combination of arthritis, serositis, daily, high-spiking fevers, and evanescent macular rash and can present with the life-threatening complication of macrophage activation syndrome (MAS). Children with Down syndrome (DS) have complex medical challenges related to abnormalities in their immune system, which can cause a broad spectrum of disease manifestations, which can occur atypically. Children with DS are at increased risk for arthritis and interstitial lung disease (ILD) associated with sJIA that has high mortality. This case report outlines an atypical presentation of sJIA in a 21-month-old male with DS in which fever was not part of the initial presentation of sJIA and then later developed MAS and ILD. Due to broad spectrum of disease and atypical presentation in children with DS, this case report was created to increase awareness of atypical presentations of rheumatic disease in children with DS.
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OBJECTIVE: Down syndrome-associated arthritis (DA) is underrecognized, and current therapies used for juvenile idiopathic arthritis (JIA) appear to be poorly tolerated and less effective in patients with DA. The objective of this study was to characterize clinical manifestations and therapeutic preferences in DA compared to JIA, using the new Childhood Arthritis and Rheumatology Research Alliance (nCARRA) registry. METHODS: In a case-control study, between July 2015 and March 2019, patients with a diagnosis of JIA and Down syndrome (DS) were identified and matched by age, sex, and JIA subtype to patients who have JIA without DS. Collected data included demographic characteristics, disease characteristics, laboratory results, treatment exposure, and outcome measures. RESULTS: A total of 36 children with DA and 165 with JIA were identified. Most patients presented with polyarticular rheumatoid factor-negative disease. At entry into the nCARRA registry, there were minimal differences between the groups, and at the last visit there were significant differences (P < 0.05) for multiple outcome measures. Patients with DA and those with JIA had similar therapeutic exposure to disease-modifying antirheumatic drugs (DMARDs) and biologics, but those with DA had more DMARD-related adverse events (93% versus 25%) and biologic therapy ineffectiveness (60% versus 17%). CONCLUSION: There was little difference between patients with DA and those with JIA at baseline, and similar therapy was implemented for those in the nCARRA registry; however, at the last visit, the patients with DA had greater disease burden. Additionally, there were more DMARD-related adverse events and biologic ineffectiveness for those patients with DA. More research is needed to determine differences in pathophysiology and optimal therapeutic approaches.
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Artritis Juvenil/tratamiento farmacológico , Artritis Juvenil/patología , Síndrome de Down/complicaciones , Adolescente , Antirreumáticos/uso terapéutico , Estudios de Casos y Controles , Niño , Preescolar , Estudios de Cohortes , Costo de Enfermedad , Femenino , Humanos , Lactante , Masculino , Sistema de Registros , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
BACKGROUND: Inflammatory arthritis in children with Down syndrome (DS) was first described in 1984 and is now termed Down syndrome-associated arthritis (DA). Studies have shown that DA is under-recognized with a 19-month average delay in diagnosis. Additionally, most patients present with polyarticular, rheumatoid factor (RF) and anti-nuclear antibody (ANA) negative disease. Current therapies for juvenile idiopathic arthritis (JIA) have been used, but appear to be poorly tolerated, more toxic and less effective in patients with DA. There is currently no standardized approach to the assessment or management of DA. The objective of this study was to describe provider perspectives toward diagnostic and treatment approach of DA, to provide baseline information upon which to design future studies. METHODS: An electronic survey, organized into sections regarding individual practices of assessment and treatment approach of DA, was sent to the Pediatric Rheumatology electronic list-serv. Survey responses were voluntary and results were analyzed by descriptive statistics. RESULTS: Of 90 survey responses received, 89 were included in the analysis (one was a duplicate response). The respondents were mostly pediatric rheumatologist (94%), with greater than 10 years of experience (55%). The majority (64%) currently see 1-3 patients with DA. Most view DA as the same disease as JIA (73%), and the majority (63%) use a combination of history, exam and imaging to diagnose DA. The most ordered diagnostic tests are CBC (97%) and ESR (96%). The most used treatments include NSAIDs (94%) and methotrexate (91%) followed by anti-TNF agents (90%). Methotrexate is most administered by subcutaneous route (84%) at a dose of 15 mg/m2 (56%). Oral corticosteroids were only used in 19% of the patients with DA. CONCLUSION: This is the first study to evaluate provider perspectives towards the diagnostic and treatment approach of DA. Most pediatric rheumatologists feel that DA and JIA are synonymous, and similar approaches to diagnosis are employed, utilizing history, physical exam, laboratory tests, and imaging modalities. DA is treated similarly to JIA with initiation of NSAIDs, disease-modifying anti-rheumatic drugs and biologic therapy. More research is needed to determine optimal screening and therapeutic approach specific to DA.
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Artritis Juvenil , Síndrome de Down/complicaciones , Administración del Tratamiento Farmacológico/estadística & datos numéricos , Reumatólogos , Antiinflamatorios no Esteroideos/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Juvenil/diagnóstico , Artritis Juvenil/etiología , Artritis Juvenil/terapia , Actitud del Personal de Salud , Terapia Biológica/métodos , Niño , Femenino , Humanos , Masculino , Manejo de Atención al Paciente/métodos , Manejo de Atención al Paciente/normas , Pautas de la Práctica en Medicina/estadística & datos numéricos , Encuestas y CuestionariosRESUMEN
BACKGROUND: Arthropathy of Down syndrome (DA) is largely under-recognized, with an average 2-year delay in diagnosis. Most patients present with polyarthritis, and treatment has historically been challenging. OBJECTIVES: Our objective was to investigate the clinical features and treatment of DA in the largest cohort reported to date. METHODS: In a retrospective chart review at two tertiary care hospitals, International Classification of Diseases, ninth revision, clinical modification (ICD-9-CM) codes for Down syndrome (DS) and juvenile idiopathic arthritis (JIA), between 1 January 1995 and 31 December 2015, were identified and charts reviewed. RESULTS: In total, 43 patients were identified, with an average (± standard deviation [SD]) follow-up period of 6 ± 4.4 years. The average age of symptom onset was 7.4 ± 3.9 years, with a mean delay of 19 ± 17 months from symptom onset to diagnosis. At diagnosis, 77% of patients had morning stiffness and 72% had abnormal laboratory values; there was an average of 15 ± 13 active joints (range 1-56). Treatment approaches varied, and there was a significant decrease in joints with active arthritis (p < 0.001), with 25% and 39% having at least one change in disease-modifying antirheumatic drug (DMARD) and biologic therapy, respectively. DMARD therapy was discontinued in 60% because of side effects, and 39% had inadequate response to first-line biologic therapy. CONCLUSIONS: DA remains under-recognized, with delays in diagnosis and extensive musculoskeletal symptoms at presentation. While DA can improve with current therapy for JIA (corticosteroids, DMARDs, biologics), barriers include medication toxicity, intolerance, and ineffectiveness. Earlier diagnosis through improved screening and more targeted treatment may allow for earlier disease control and better outcomes.
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Artritis Juvenil/diagnóstico , Síndrome de Down/diagnóstico , Antirreumáticos/uso terapéutico , Artritis Juvenil/tratamiento farmacológico , Productos Biológicos/uso terapéutico , Niño , Preescolar , Estudios de Cohortes , Síndrome de Down/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Estudios Retrospectivos , Centros de Atención Terciaria , Resultado del TratamientoRESUMEN
OBJECTIVE: To evaluate a safe, noninvasive magnetic resonance imaging (MRI) method to measure regional blood-brain barrier integrity and investigate its relationship with neurocognitive function and regional gray matter volume in juvenile-onset systemic lupus erythematosus (SLE). METHODS: In this cross-sectional, case-control study, capillary permeability was measured as a marker of blood-brain barrier integrity in juvenile SLE patients and matched healthy controls, using a combination of arterial spin labeling and diffusion-weighted brain MRI. Regional gray matter volume was measured by voxel-based morphometry. Correlation analysis was done to investigate the relationship between regional capillary permeability and regional gray matter volume. Formal neurocognitive testing was completed (measuring attention, visuoconstructional ability, working memory, and psychomotor speed), and scores were regressed against regional blood-brain barrier integrity among juvenile SLE patients. RESULTS: Formal cognitive testing confirmed normal cognitive ability in all juvenile SLE subjects (n = 11) included in the analysis. Regional capillary permeability was negatively associated (P = 0.026) with neurocognitive performance concerning psychomotor speed in the juvenile SLE cohort. Compared with controls (n = 11), juvenile SLE patients had significantly greater capillary permeability involving Brodmann's areas 19, 28, 36, and 37 and caudate structures (P < 0.05 for all). CONCLUSION: There is imaging evidence of increased regional capillary permeability in juvenile SLE patients with normal cognitive performance using a novel noninvasive MRI technique. These blood-brain barrier outcomes appear consistent with functional neuronal network alterations and gray matter volume loss previously observed in juvenile SLE patients with overt neurocognitive deficits, supporting the notion that blood-brain barrier integrity loss precedes the loss of cognitive ability in juvenile SLE. Longitudinal studies are needed to confirm the findings of this pilot study.
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Barrera Hematoencefálica/patología , Lupus Eritematoso Sistémico/diagnóstico por imagen , Lupus Eritematoso Sistémico/patología , Permeabilidad Capilar , Estudios de Casos y Controles , Estudios Transversales , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Imagen por Resonancia Magnética , Masculino , Proyectos Piloto , Adulto JovenRESUMEN
OBJECTIVE: To validate the pediatric Patient-Reported Outcomes Measurement Information System short forms (PROMIS-SFs) in childhood-onset systemic lupus erythematosus (SLE) in a clinical setting. METHODS: At 3 study visits, childhood-onset SLE patients completed the PROMIS-SFs (anger, anxiety, depressive symptoms, fatigue, physical function-mobility, physical function-upper extremity, pain interference, and peer relationships) using the PROMIS assessment center, and health-related quality of life (HRQoL) legacy measures (Pediatric Quality of Life Inventory, Childhood Health Assessment Questionnaire, Simple Measure of Impact of Lupus Erythematosus in Youngsters [SMILEY], and visual analog scales [VAS] of pain and well-being). Physicians rated childhood-onset SLE activity on a VAS and completed the Systemic Lupus Erythematosus Disease Activity Index 2000. Using a global rating scale of change (GRC) between study visits, physicians rated change of childhood-onset SLE activity (GRC-MD1: better/same/worse) and change of patient overall health (GRC-MD2: better/same/worse). Questionnaire scores were compared in support of validity and responsiveness to change (external standards: GRC-MD1, GRC-MD2). RESULTS: In this population-based cohort (n = 100) with a mean age of 15.8 years (range 10-20 years), the PROMIS-SFs were completed in less than 5 minutes in a clinical setting. The PROMIS-SF scores correlated at least moderately (Pearson's r ≥ 0.5) with those of legacy HRQoL measures, except for the SMILEY. Measures of childhood-onset SLE activity did not correlate with the PROMIS-SFs. Responsiveness to change of the PROMIS-SFs was supported by path, mixed-model, and correlation analyses. CONCLUSION: To assess HRQoL in childhood-onset SLE, the PROMIS-SFs demonstrated feasibility, internal consistency, construct validity, and responsiveness to change in a clinical setting.