Consensus Diagnostic Criteria Research Articles

Cricopharyngeus muscle dysfunction: a poorly defined disorder from diagnosis to treatment.

Cricopharyngeus muscle dysfunction (CPMD) is a common clinical occurrence with very few clear diagnostic criteria and multiple pathways for treatment. Incidence of CPMD is not known, but some data suggest around 25% of people with dysphagia experience some degree of CPMD, which negatively impacts swallowing safety and efficiency. Workup and treatment of CPMD can require multidisciplinary collaboration across laryngologists, speech-language pathologists with training in dysphagia management, and gastroenterologists. The purpose of this paper is to review what is known about CPMD and identify areas of future research in CPMD diagnosis and treatment. An overview of CPMD, relative treatments and disorders, and a discussion of future areas of research needed to improve clinical care of CPMD. Details regarding historical background, pathophysiology and treatment practiced for CPMD are included. In summary, CPMD is a poorly defined disease due to a lack of understanding of its pathophysiology and the lack of consensus diagnostic criteria. Well-designed, prospective clinical trials are necessary to develop a better understanding of clinical incidence of CPMD, impact of the disorder on oropharyngeal swallowing, and how to approach treatment of the disorder surgically or in conjunction with therapy directed by a specialized speech-language pathologist.

Culturally adapted cognitive assessment tool for Indigenous communities in Brazil: Content, construct, and criterion validity.

Initial dementia prevalence estimates have revealed a significant burden of the disease in Indigenous communities in Amazonas, Brazil. However, the need for culturally adapted cognitive tools poses a critical challenge when assessing cognitive performance in these communities. This study addressed this issue by culturally adapting and providing validity indicators for the Brazilian Indigenous Cognitive Assessment (BRICA) tool in Manaus, Brazil's urban multiethnic Indigenous community. Using a three-stage process and a stakeholder-engaged approach, the BRICA tool was culturally adapted in an urban multiethnic Indigenous community from Manaus, Brazil. The content validity index (CVI) examined inter-rater concordance between experts, while criterion and concurrent validity were performed using diagnostic consensus criteria in 141 Indigenous participants aged ≥ 50 years. Findings showed evidence of content validity in terms of equivalence aspects (scale CVI [S-CVI] 0.93) and relevance ratings (S-CVI 0.85) between expert panels. The identified cut-off score of ≤ 33/39 on the BRICA demonstrated a sensitivity of 94.4%, specificity of 99.2%, positive predictive value of 94.4%, and negative predictive value of 99.2% for dementia diagnosis. Using a stakeholder-engaged approach, we culturally adapted the BRICA tool for a Brazilian urban multiethnic Indigenous community. This comprehensive adaptation process resulted in favorable indicators of content, construct, and criteria validity for the BRICA tool. By addressing the existing bias in cognitive assessment within Indigenous communities, the BRICA tool represents a noteworthy breakthrough. Its implementation exhibits potential for improving the early detection and management of dementia among Indigenous groups. Culturally sensitive tools are essential to assess cognition in Indigenous populations.An expert panel and stakeholders' perspectives were incorporated to design the Brazilian Indigenous Cognitive Assessment (BRICA) tool.A cognitive screening tool was adapted and validated using a stakeholder approach.BRICA is the first culturally sensitive cognitive tool for urban Brazilian Indigenous individuals.

Exploring Blood Cell Count-Derived Ratios as Practical Diagnostic Tools for Scabies in Vulnerable Populations.

Scabies is a neglected tropical disease and represents a considerable global burden. Although consensus diagnostic criteria for scabies have been recently published, diagnosing scabies infestation remains challenging in clinical practice. We investigated the diagnostic utility of complete blood cell count (CBC) and CBC-derived ratios obtained at diagnosis in a set of 167 patients who are Vietnamese with confirmed scabies. These parameters were compared with those of patients with dermatophytosis (N = 800) and urticaria (N = 2023), two diseases frequent in Vietnam, which can present with similar skin manifestations to scabies and tend to pose a diagnostic challenge in vulnerable populations. Our analysis revealed that white blood cell, monocyte, and eosinophil counts were significantly higher among patients with scabies than the other two diseases. Similarly, the monocyte-to-lymphocyte ratio (MLR) and eosinophil-to-lymphocyte ratio (ELR) were significantly higher among patients with scabies. The optimal cut-off values to distinguish scabies from dermatophytosis and urticaria were 0.094 for ELR (sensitivity: 74.85%, specificity: 70.7%) and 0.295 for MLR (sensitivity: 52.69%, specificity: 73.54%). CBC, ELR, and MLR are low-cost and easily calculated parameters that may be helpful for the diagnosis of scabies.

Quantitative brain 18F-FDG PET/CT analysis in seronegative autoimmune encephalitis.

Brain 18F-FDG PET/CT is a useful diagnostic in evaluating patients with suspected autoimmune encephalitis (AE). Specific patterns of brain dysmetabolism have been reported in anti-NMDAR and anti-LGI1 AE, and the degree of dysmetabolism may correlate with clinical functional status.18FDG-PET/CT abnormalities have not yet been described in seronegative AE. We conducted a cross-sectional analysis of brain18FDG-PET/CT data in people with seronegative AE treated at the Johns Hopkins Hospital. Utilizing NeuroQ™ software, the Z-scores of 47 brain regions were calculated relative to healthy controls, then visually and statistically compared for probable and possible AE per clinical consensus diagnostic criteria to previous data from anti-NMDAR and anti-LGI1 cohorts. Eight probable seronegative AE and nine possible seronegative AE were identified. The group only differed in frequency of abnormal brain MRI, which was seen in all of the probable seronegative AE patients. Both seronegative groups had similar overall patterns of brain dysmetabolism. A common pattern of frontal lobe hypometabolism and medial temporal lobe hypermetabolism was observed in patients with probable and possible seronegative AE, as well as anti-NMDAR and anti-LGI1 AE as part of their respective characteristic patterns of dysmetabolism. Four patients had multiple brain18FDG-PET/CT scans, with changes in number and severity of abnormal brain regions mirroring clinical status. A18FDG-PET/CT pattern of frontal lobe hypometabolism and medial temporal lobe hypermetabolism could represent a common potential biomarker of AE, which along with additional clinical data may facilitate earlier diagnosis and treatment.

Primary lateral sclerosis: application and validation of the 2020 consensus diagnostic criteria in an expert opinion-based PLS cohort

BackgroundValidation of the 2020 consensus criteria for primary lateral sclerosis (PLS) is essential for their use in clinical practice and future trials.MethodsIn a large cohort of patients diagnosed with PLS...

Neuromyelitis Optica Spectrum Disorder (NMOSD) or Chronic-Relapsing Inflammatory Optic Neuropathy (CRION)?: A Challenge in Diagnosis and Treatment

Abstract
 Introduction : Neuromyelitis optica spectrum disorder (NMOSD) is a chronic inflammatory, immune-mediated central nervous system disease targeting the AQP4-water channel membrane protein of the optic nerve and the spinal cord. This case report aims to present a case of seroconverting NMOSD which was initially diagnosed as chronic relapsing inflammatory optic neuropathy (CRION).
 Case Illustration : 15-year-old female with recurrent, steroid-dependent optic neuritis of the LE. During the first attack, brain MRI showed optic nerve inflammation with normal brain findings. Initial test for AQP4-IgG, MOG-Ab and ANA profile were negative. The diagnosis of CRION was made. Treatment with corticosteroid and immunosuppressant agent was maintained for one year. After treatment cessation, however, LE optic neuritis recurred with bilateral lower limb weakness. Spinal MRI showed signs of longitudinal extensive transverse myelitis. Re-testing for AQP4-IgG showed positive result. Diagnosis of NMOSD was made, and the patient was treated with high-dose intravenous corticosteroid followed by oral dose, and immunosuppressant. Final visual acuity of the LE was 1.0, with minimal residual visual field defect and good motor function.
 Discussion : During the initial attack, the patient did not meet the 2015 NMOSD international consensus diagnostic criteria. The AQP4-IgG was negative and no other corresponding signs and symptoms. The criteria was met one year after: optic neuritis, LETM and positive seroconversion of AQP4-IgG.
 Conclusion : Diagnosing NMOSD is at times challenging especially during initial attack. Retesting of the AQP4- IgG is at times necessary in seronegative patients, especially in children showing ADEM-like event with optic neuritis and LETM to achieve diagnosis and proper treatment strategy.

Food Protein Induced Enterocolitis Syndrome in an Allergy Department: Adherence to International Consensus Diagnostic Criteria

Food Protein Induced Enterocolitis Syndrome in an Allergy Department: Adherence to International Consensus Diagnostic Criteria

Examining the New Consensus Criteria for Traumatic Encephalopathy Syndrome in Community-Dwelling Older Adults.

In 2021, an expert panel of clinician-scientists published the first consensus research diagnostic criteria for traumatic encephalopathy syndrome (TES), a clinical condition thought to be associated with chronic traumatic encephalopathy neuropathological change. This study evaluated the TES criteria in older adults and assessed associations between TES criteria and a history of repetitive head impacts. This cross-sectional, survey-based study examined the symptoms of TES, previous repetitive head impacts, and a variety of current health difficulties. To meet symptom criteria for TES, participants had to report progressive changes with memory, executive functioning, and/or neurobehavioral dysregulation. To meet the criterion for substantial exposure to repetitive head impacts via contact sports, participants reported at least 5 years of contact sport exposure (with 2+ years in high school or beyond). A sample of 507 older adults (mean age = 70.0 years, 65% women) completed the survey and 26.2% endorsed having one or more of the progressive core clinical features of TES. Those who had a significant history of contact sport exposure were not significantly more likely to meet TES criteria compared with those who did not (31.3% vs. 25.3%, p = 0.46). In a binary logistic regression predicting TES status, current depression or anxiety (odds ratio [OR] = 12.55; 95% confidence interval [CI] = 4.43-35.51), history of psychiatric disorders (OR = 2.07, 95% CI = 1.22-3.49), male sex (OR = 1.87), and sleep problems (OR = 1.71, 95% CI = 1.01-2.91) were associated with meeting TES criteria. The sport exposure criterion, age, and current pain were not significantly associated with TES status (ps > 0.05). A significant minority of participants with no history of neurotrauma endorsed symptoms consistent with TES (22.0% of men and 19.8% of women). Nearly 80% of neurotrauma naïve participants with clinically significant anxiety/depression met criteria for TES. In summary, approximately one in four older adults met the symptom criteria for TES, many of whom had no history of repetitive neurotrauma. Mental health problems and sleep issues were associated with TES, whereas having a history of repetitive head impacts in contact sports was not. These data suggest that the new consensus diagnostic criteria for TES may have low specificity and may carry a higher risk of misdiagnosing those with other physical and mental health conditions as having TES.

Musical experience influences socio-emotional functioning in behavioural variant frontotemporal dementia.

On phenotypic and neuroanatomical grounds, music exposure might potentially affect the clinical expression of behavioural variant frontotemporal dementia (bvFTD). However, this has not been clarified. 14 consecutive patients with bvFTD fulfilling consensus diagnostic criteria were recruited via a specialist cognitive clinic. Earlier life musical experience, current musical listening habits and general socio-emotional behaviours were scored using a bespoke semi-quantitative musical survey and standardised functional scales, completed with the assistance of patients' primary caregivers. Associations of musical scores with behavioural scales were assessed using a linear regression model adjusted for age, sex, educational attainment and level of executive and general cognitive impairment. Greater earlier life musical experience was associated with significantly lower Cambridge Behavioural Inventory (Revised) scores (β ± SE = -17.2 ± 5.2; p = 0.01) and higher Modified Interpersonal Reactivity Index (MIRI) perspective-taking scores (β ± SE = 2.8 ± 1.1; p = 0.03), after adjusting for general cognitive ability. Number of hours each week currently spent listening to music was associated with higher MIRI empathic concern (β ± SE = 0.7 ± 0.21; p = 0.015) and MIRI total scores (β ± SE = 1.1 ± 0.34; p = 0.014). Musical experience in earlier life and potentially ongoing regular music listening may ameliorate socio-emotional functioning in bvFTD. Future work in larger cohorts is required to substantiate the robustness of this association, establish its mechanism and evaluate its clinical potential.

A missense variant in MYOF is associated with ARVC and sudden cardiac death

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is rare autosomal dominant genetic disorder that leads to severe arrhythmia and sudden cardiac death. Although previous studies in clinical, pathological and genetics of ARVC established consensus diagnostic criteria and expanded the spectrum of pathogenic genes, there is still a proportion of patients with unclear causative factors.Here, whole-exome sequencing was employed to investigate the genetic etiology of a 15-year-old sudden cardiac death female caused by ARVC. A novel variant of MYOF (NM_013451.3: c.4723G > C: p.D1575H) was identified, which is a member of the Ferlin family of proteins is associated with cardiomyopathy. And the bioinformatics analysis predicted the pathogenicity of this variant. We report the first variant of MYOF in ARVC, which imply a vital role of MYOF in cardiomyopathy.

Restless Sleep Disorder as a New Primary Sleep Disorder in Children and Adolescents

Restless sleep is a frequent complaint clinically and often associated with specific sleep or medical conditions. Recently, restless sleep disorder (RSD) has been identified as a new pediatric sleep disorder with core features of restless sleep and frequent large muscle movements during sleep, which are not explained by other conditions. Based on the medical literature and expert clinical experience, the task force developed a consensus diagnostic criteria for RSD and scoring large muscle group movements in children aged 6–18 years. Eight essential criteria of RSD include a complaint of restless sleep, observed large body movements during sleep, video-polysomnographic documentation of ≥5 large body movements/hour, occurrence at least thrice weekly for at least 3 months, clinically significant impairment, and differentiation from other conditions that may secondarily cause restless sleep. There is evidence to support a pathophysiology based on iron deficiency, sleep instability, and increased sympathetic activation, and treatment options include oral or intravenous iron supplementation. This review describes the key features of RSD, potential pathophysiology, and current treatment options to help diagnose patients with RSD, which has been overlooked.

Energy and nutrient intake by people with and without sarcopenia diagnosed by the European Working Group on Sarcopenia in Older People: a systematic review and meta-analysis.

There is growing evidence that insufficient dietary intake is associated with sarcopenia. In this systematic review and meta-analysis, the energy and nutrient intakes by people with and without sarcopenia were compared using only the European Working Group on Sarcopenia in Older People 2010 (EWGSOP1) and 2019 (EWGSOP2) consensus diagnostic criteria. Only observational studies that compared energy and nutrient intake from food alone by individuals with and without sarcopenia were included. Studies were searched in the following databases: Embase, PubMed, Scopus, Web of Science, Lilacs, Ovid, and Scopus. The review followed the PRISMA checklist and submitted the protocol to PROSPERO. Data were extracted by 2 authors independently. The methodological quality of the studies was assessed using the Newcastle-Ottawa scale. A total of 8648 articles were identified and 12 were selected. Among individuals with sarcopenia, lower intakes of energy and some nutrients, mainly with antioxidant properties, were observed compared with those without sarcopenia. Meta-analyses showed that individuals with sarcopenia consume fewer calories/day than individuals without sarcopenia (n = 10 studies; standardized mean difference (SMD) -0.15; 95% confidence interval: -0.29, -0.01) diagnosed by EWGSOP1 and EWGSOP2. Individuals with sarcopenia consume less omega-3, folate, magnesium, phosphorus, selenium, zinc, and vitamins C, D, and E when compared with those without sarcopenia. The results of the present study suggest that insufficient intake of energy and nutrients with antioxidant potential may be associated with sarcopenia. PROSPERO registration no. CRD 42020195698.

Delimiting MOGAD as a disease entity using translational imaging.

The first formal consensus diagnostic criteria for myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) were recently proposed. Yet, the distinction of MOGAD-defining characteristics from characteristics of its important differential diagnoses such as multiple sclerosis (MS) and aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorder (NMOSD) is still obstructed. In preclinical research, MOG antibody-based animal models were used for decades to derive knowledge about MS. In clinical research, people with MOGAD have been combined into cohorts with other diagnoses. Thus, it remains unclear to which extent the generated knowledge is specifically applicable to MOGAD. Translational research can contribute to identifying MOGAD characteristic features by establishing imaging methods and outcome parameters on proven pathophysiological grounds. This article reviews suitable animal models for translational MOGAD research and the current state and prospect of translational imaging in MOGAD.

What's in a Name? Chronic Vestibular Migraine or Persistent Postural Perceptual Dizziness?

Current consensus diagnostic criteria for vestibular migraine (VM) describes this as an episodic disorder. However, a minority of patients report prolonged (>72 h duration) or even persistent VM symptoms, prompting whether a chronic variant of vestibular migraine (CVM) should be introduced to the current classification and how best to define it. Here we summarize current evidence of such a potential chronic variant of VM and critically review proposed definitions for CVM. Potential approaches to establish a diagnostic framework for CVM include (a) following the distinction between episodic and chronic migraine headaches, namely, frequent and/or prolonged episodes of VM (but not persistent vertigo or dizziness) in the context of chronic migraine headaches or (b) daily dizzy spells over more than 6 months that responded well to prophylactic anti-migraine therapy. A key challenge when defining diagnostic criteria for CVM is how to distinguish it from other chronic vestibular syndromes such as motion sickness, persistent postural-perceptual dizziness (PPPD), and mal de débarquement syndrome. Indeed, more than 50% of patients with PPPD and up to 46% with mal de débarquement syndrome fulfil diagnostic criteria for episodic migraine headaches, suggesting these disorders may all lie along a spectrum. We propose that when VM becomes persistent, it is best classified as PPPD but that VM and PPPD are not mutually exclusive, such that patients with PPPD need not have features of VM, and the triggering event for persistent dizziness may be independent of migraine. However, further research is needed to better characterize the spectrum of clinical phenotypes in patients with chronic dizziness, migraine headaches and anxiety, to define whether a chronic variant of VM sufficiently differs from current persistent dizziness definitions.

Global birth prevalence of Robin sequence in live-born infants: a systematic review and meta-analysis.

Robin sequence (RS), a congenital disorder of jaw maldevelopment and glossoptosis, poses a substantial healthcare burden and has long-term health implications if airway obstruction is suboptimally treated. This study describes the global birth prevalence of RS and investigates whether prevalence estimates differ by geographical location, ethnicity or study data source (registry versus non-registry data). The protocol was prospectively registered with PROSPERO.Databases were searched using keywords and subject terms for "Robin sequence", "epidemiology", "incidence" and "birth prevalence". Meta-analysis was performed fitting random effects models with arcsine transformation.From 34 eligible studies (n=2722 RS cases), pooled birth prevalence was 9.5 per 100 000 live births (95% CI 7.1-12.1) with statistical heterogeneity. One third of studies provided a case definition for RS and numerous definitions were used. A total of 22 countries were represented, predominantly from European populations (53% of studies). There was a trend towards higher birth prevalence in European populations and lower prevalence from registry-based studies. Only two studies reported ethnicity.This study indicates that RS occurs globally. To investigate geographical differences in prevalence, additional studies from non-European populations and reporting of ethnicity are needed. Heterogeneity of estimates may be due to variable diagnostic criteria and ascertainment methods. Recently published consensus diagnostic criteria may reduce heterogeneity among future studies.

Prospective Clinical and Biomarker Validation of the ASTCT Consensus Definition for Transplant-Associated Thrombotic Microangiopathy (TA-TMA)

Introduction: Transplantation-associated thrombotic microangiography (TA-TMA) is a disorder that causes severe complications post-hematopoietic cell transplantation (HCT). Diagnosing TA-TMA is challenging due to non-standardized criteria. The American Society for Transplantation and Cellular Therapy (ASTCT) has proposed new consensus diagnostic criteria for standard risk (ASTCT-SR) and high risk (ASTCT-HR) but their correlation with older criteria based on microangiopathic hemolytic anemia (MAHA) or diagnostic complement biomarkers used in previous TA-TMA studies, such as levels of the terminal complement activation product sC5b-9 and the alternative complement pathway activation product Factor Ba, is unknown. Using data and samples from an ongoing prospective pediatric cohort study, we compared the two definitions and their associations with biomarkers. Methods: Patients aged 0 to 18 years who underwent first allogeneic HCT 2021-2023 at Texas Children's Hospital were included in the clinical and biomarker study. Those who did not have at least 100-day post-HCT event-free follow-up were excluded. Two different definitions for TA-TMA were applied. Clinical TMA (cTMA) was diagnosed if a patient 1) met 4/4 concurrent criteria of MAHA (schistocytosis, thrombocytopenia, anemia, and elevated lactate dehydrogenase (LDH)) at least twice in 14 days and 2) clinically adjudicated to exclude known mimics or alternative causes of TMA. In contrast, ASTCT-HR TMA was diagnosed if a patient 1) met 4/7 non-concurrent criteria (schistocytosis, thrombocytopenia, anemia, elevated LDH, elevated blood pressure, elevated urinary protein excretion, and elevated sC5b9) at least twice in 14 days and 2) had evidence of LDH >2x normal, proteinuria ≥1 mg/mg, elevated sC5b9, acute graft-versus-host disease, active bacterial/viral infection, or end-organ damage. Cumulative incidence of TA-TMA was assessed by the competing risk method. Overall survival was compared by the Kaplan Meier estimator and log-rank test. Biomarker levels for samples collected at day 15 (+/- 14 days) were compared using the t-test. Results: A total of 32 patients met the inclusion criteria. The median age was 5.7 years (range 1.1-18.8) and most were White (68.8%) and Hispanic (56.2%). Malignant disease was the indication for HCT in 50% of patients. While the classic MAHA-based cTMA definition had an incidence of 12.7%, the newly proposed ASTCT-HR definition doubled it to 28.5% by day-100 (Figure 1). In contrast to patients with concordant TA-TMA diagnosis (+/+) who had significantly worse post-transplant survival (p=0.0047) compared with those with concordant non-TMA (-/-), those reclassified as TA-TMA by the new definition only (-/+) had an unexpectedly good prognosis (100% survival at day 100) despite the lack of TMA-directed therapy. Longitudinal biomarker analysis was conducted on 29 patients. The highest average plasma levels of sC5b-9 and Ba during the first 100 days were observed in patients meeting both cTMA and ASTCT-HR criteria (+/+). When focused on early biomarkers measured around day 15, sC5b-9 (P=0.041) and Ba (P=0.004) were significantly elevated in the doubly positive TMA group (+/+) vs. non-TMA group (-/-) (Figure 2). We did not observe significant differences for ASTCT-HR singly positive (-/+) vs. non-TMA group (-/-). Conclusions: In the current prospective clinical and biomarker study, the recently proposed ASTCT-HR definition was more sensitive but less prognostic than the traditional cTMA definition for TA-TMA. Patients who solely met the ASTCT-HR diagnostic criteria but not the cTMA criteria had benign complement biomarker profiles and excellent survival prognosis without TMA-directed therapy. While clinicians need to be vigilant for this infrequent yet potentially severe complications, it is crucial that diagnostic criteria accurately identify affected patients given the expense and potential complications of treatment. We recommend ongoing validations of the new consensus diagnostic criteria from other prospective cohort studies with larger sample sizes and extended follow-up.

The Clinical Picture of Castleman Disease: A Systemic Review and Meta-Analysis of Almost 2000 Patients

Background: Castleman disease (CD) encompasses a spectrum of rare disorders with characteristic histopathological features, including unicentric (UCD), idiopathic multicentric (iMCD) and cases that are associated with the human herpesvirus 8 (HHV8+ MCD). As treatment options for each type of CD vary, it is important to be able to distinguish their clinical presentation from their subtypes and determine the correct diagnosis. To our knowledge, there are no major review articles summarising the clinical features of different CD subtypes. The aim of this study was to describe and compare the clinical presentation of different CD subtypes reported in the literature. Methods: We performed a systematic review of publications reporting ≥5 cases of CD between 1995 and 2021, following the PRISMA guidelines. Publications were cross-checked by study location, data collection period and investigators to identify duplicated patients. Where a patient may have been included in >1 study, the publication with the fewest patients or least symptom data was excluded. For each subtype of CD within each study, we extracted data on demographics, clinical symptoms and laboratory parameters as stated in the international consensus diagnostic criteria for iMCD. We estimated the mean percentage of patients meeting each diagnostic criterion for each CD subtype using meta-analyses conducted with random-effects logistic regression models. Results: We analysed 32 studies with 1998 patients from 16 countries, including 559 UCD, 1023 iMCD and 416 HHV8+ MCD cases. There was a predominance of males not only in HHV8+ MCD (88.5% males) but also in iMCD (59.1% males). Patients with UCD tended to be younger than patients with iMCD and HHV8+ MCD. Most patients with iMCD (91.8%) and UCD (84.7%) were of Asian ethnicity. Only 58 patients (6.4%) with iMCD were White. In contrast, almost all patients with HHV8+ MCD (93.7%) were White or Black/African American. Many symptoms and laboratory abnormalities occurred at similar rates in patients with iMCD and HHV8+ MCD (Table 1). There were no significant differences in laboratory findings between patients with iMCD and HHV8+ MCD. However, compared with patients with HHV8+ MCD, patients with iMCD had significantly lower rates of constitutional symptoms (46.6% vs 98.6%, p=0.038) and splenomegaly (48.2% vs 89.2%, p=0.031). In contrast, renal dysfunction seemed to appear more commonly in iMCD (36.9% vs 17.4%, not statistically significant). Patients with UCD had significantly lower rates of laboratory abnormalities vs those with iMCD and HHV8+ MCD (p<0.05 for all parameters listed in Table 1). Except for cutaneous findings, patients with UCD had significantly lower rates of symptoms than patients with either iMCD or HHV8+ MCD (p<0.05 for all non-cutaneous parameters in Table 1). However, elevated C-reactive protein (CRP), anaemia and hypergammaglobulinaemia occurred in almost 20% of patients with UCD and pulmonary findings were observed in 15.3% of cases. We identified five additional publications including 88 paediatric patients with UCD. Paediatric patients with UCD had more signs of systemic inflammation than adult UCD patients. Elevated CRP was reported in 45.1% (95% CI 20.9-71.8, n=50) of paediatric UCD patients (vs 19.7% of adults [95% CI 11.2-30.9]). Constitutional symptoms were reported in 44.4% (95% CI 21.5-69.2, n=18) of patients - significantly higher than the rate reported in adult patients with UCD (4.5%, 95% CI 1.6-12.3; p=0.0005). Conclusions: This systematic review complements the diagnosis and management guidelines for iMCD and UCD and provides a detailed description of the clinical presentation of HHV8+ MCD. We found several distinct differences between iMCD and HHV8+ MCD, probably reflecting the heterogeneity of the underlying pathomechanisms and/or different comorbidity burdens of these CD subtypes. We confirmed that systemic symptoms may be present in up to 20% of patients with UCD. Whether these cases represent a distinct entity and whether intermediate CD cases require systemic therapy beyond surgery remains to be elucidated.

Real-world clinical management of individuals with Rett syndrome: a physician survey

BackgroundRett syndrome (RTT) is a severe neurodevelopmental disorder. Management strategies are heterogeneous with no clear definition of success. This study describes physician decision-making regarding diagnosis, therapeutic goals, and management strategies to better understand RTT clinical management in the US.MethodsThis study was conducted among practicing physicians, specifically neurologists and pediatricians in the US with experience treating ≥2 individuals with RTT, including ≥1 individuals within the past two years. In-depth interviews with five physicians informed survey development. A cross-sectional survey was then conducted among 100 physicians.ResultsNeurologists had treated more individuals with RTT (median: 12 vs. 5, p < 0.001) than pediatricians throughout their career and were more likely to report being “very comfortable” managing RTT (31 vs. 4%, p < 0.001). Among physicians with experience diagnosing RTT (93%), most evaluated symptoms (91%) or used genetic testing (86%) for RTT diagnoses; neurologists used the 2010 consensus diagnostic criteria more than pediatricians (54 vs. 29%; p = 0.012). Improving the quality of life (QOL) of individuals with RTT was the most important therapeutic goal among physicians, followed by improving caregivers’ QOL. Most physicians used clinical practice guidelines to monitor the progress of individuals with RTT, although neurologists relied more on clinical scales than pediatricians. Among all physicians, the most commonly treated symptoms included behavioral issues, epilepsy/seizures, and feeding issues. Management strategies varied by symptom, with referral to appropriate specialists being common across symptoms. A large proportion of physicians (37%) identified the lack of novel therapies and reliance on symptom-specific management as an unmet need.ConclusionAlthough most physicians had experience and were comfortable diagnosing and treating individuals with RTT, better education and support among pediatricians is warranted. Additionally, novel treatments that target multiple symptoms associated with RTT could reduce the burden and improve the QOL of individuals with RTT and their caregivers.

IgG4-related uveitis. A French cohort and literature review

IntroductionIgG4-related disease (IgG4-RD) is a fibro-inflammatory disorder that can affect almost any organ. IgG4-related ophthalmic disease is a protean condition involving the orbit and ocular adnexa. Although a few cases of uveitis have been reported, the exact pattern of IgG4-related intraocular manifestations remains unclear. Here, we report on a nationwide French multicenter cohort of patients with IgG4-RD and uveitis and conducted a literature review. MethodsPatients with uveitis and a concomitant definite diagnosis of IgG4-RD (Revised Comprehensive Diagnostic criteria, American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-RD, International Consensus Diagnostic Criteria for auto-immune pancreatitis, or diagnostic criteria for IgG4-related hypophysitis), were screened from our national IgG4-RD and systemic fibrosis database. Concomitantly, we conducted a PubMed literature review and selected cases of definite IgG4-RD with uveitis. ResultsWe reported on 16 patients (8 from our database and 8 from the literature) and a total of 30 episodes of uveitis. Uveitis cases represented 3 % of total IgG4-RD patients in the national database on IgG4-RD and systemic fibrosis. Uveitis was inaugural in IgG4-RD in 4/16 cases (25 %) (appearing before any other IgG4-related symptom, at a median of 9 months), occurred concurrently to other IgG4-related symptoms in 9/16 cases (56 %) (at a median of 15 months before IgG4-RD diagnosis), and appeared during follow up in 3/16 patients (19 %) (at a median of 57 months after first IgG4-related symptoms). When uveitis occurred during follow up, it was associated with IgG4-RD manifestations in other organs in 6/9 patients (67 %). Uveitis was bilateral in 8/16 cases (50 %) and granulomatous in 5/10 cases (50 %). It was anterior in 8/13 (62 %), intermediate in 3/13 (23 %), and global (panuveitis) in 4/13 patients (31 %). Median serum IgG4 at diagnosis was 3.2 g/L. Median follow up time was of 6 years, during which 8/16 patients (50 %) experienced at least one relapse of uveitis. Treatment data was available for 29/30 uveitis flares. Steroids were used in 28/29 episodes of uveitis (97 %), leading to remission of uveitis in 16/28 cases (57 %). Methotrexate and rituximab (in combination with systemic steroids) were administered as second- or third-line therapy in 6/29 (21 %) and 5/29 (17 %) episodes of uveitis, respectively, and led to remission of uveitis in 4/6 cases (67 %) and 4/5 cases (80 %), respectively. One third of uveitides required at least two different lines of treatment for remission induction (mainly a combination of both systemic steroids and methotrexate or rituximab). Discussion and conclusionsUveitis may be one of the initial symptoms of IgG4-RD, and IgG4-RD should be considered in the diagnostic workup of uveitis. Its early onset in IgG4-RD may help with early diagnosis and treatment of the disease. Steroid monotherapy may be sufficient to treat IgG4-related uveitis, yet relapses were frequent (50 %) and ultimately a third of patients required at least two lines of treatment. Hence, steroid-sparing agents can be considered at early stages of the disease, particularly for patients with a high risk of relapse or steroid-related complications.

Abstract 17846: Successful Treatment of Recurrent Pericarditis With Rilonacept in the Setting Of ATRA/ATO Use in Acute Promyelocytic Leukemia

Case Presentation: A 40-year-old female was admitted for a 4-day history of recurrent left-sided pleuritic chest pain. Physical examination was pertinent for tachycardia and presence of a pericardial friction rub. Past medical history included recently diagnosed Acute Promyelocytic Leukemia undergoing active chemotherapy. Complete blood count showed leukopenia. Brain natriuretic peptide was slightly elevated at 241 pg/mL. Electrocardiogram demonstrated sinus tachycardia with diffuse ST-segment elevation and PR-segment depression (Figure 1. A). Echocardiogram showed normal biventricular function with a small posterior and lateral pericardial effusion and small pericardial effusion adjacent to the right ventricle (Figure 1. B). Cardiac magnetic resonance (CMR) imaging showed a moderate circumferential pericardial effusion and increased pericardial signal on T2 STIR imaging and late gadolinium enhancement (LGE) (Figure 1. C, D). Given the constellation of symptoms and findings, the patient was diagnosed with acute pericarditis secondary to differentiation syndrome (DS) suspected to be due to her underlying malignancy and anti-cancer treatments. She was started on aspirin and colchicine. Steroids and rilonacept were later added for incomplete treatment response. On follow-up, she was doing well. Repeat CMR demonstrated mild to moderate pericardial delayed enhancement with no edema and no pericardial effusion (Figure 1. E,F). Discussion: The presentation of DS can vary, and consensus diagnostic criteria are lacking. Cases of myopericarditis with concurrent pericardial effusions have been reported in the setting of patients undergoing chemotherapeutic treatment with differentiating agents. Management is complicated and requires multi-disciplinary care. Our case illustrates that rilonacept may be considered as an alternative to corticosteroids in the treatment of recurrent pericarditis in a patient with a hematologic malignancy.