Mixed Connective Tissue Disease Research Articles

Unclassifiable interstitial lung disease and autoimmunity: Towards IPAF in children?

Interstitial pneumonia with autoimmune features (IPAF) has been defined for adults with interstitial lung disease (ILD) and autoimmunity who do not meet the criteria for a specific connective tissue disease (CTD). We aimed to determine whether IPAF criteria could apply to children. We retrospectively studied patients with ILD and autoimmunity followed at Necker Hospital between 2008 and 2019. Children were classified according to specific CTD and IPAF criteria. The epidemiology and course of the disease were studied according to the final diagnosis. Among 27 patients, 6 fulfilled the criteria for IPAF and represented 4.5% of all patients with ILD during the study period. Other diagnoses included juvenile dermatomyositis (30%), overlap syndromes (19%), systemic lupus erythematosus (15%), systemic sclerosis (7%), mixed CTD (4%), and rheumatoid arthritis (4%). IPAF patients were more frequently boys versus CTD-ILD patients (67% vs. 14%, p = .02). Two patients had severe respiratory distress that led to death for one of them. The course was favorable for the others, with a good response to steroids. The course tended to be more favorable for IPAF patients than for those with CTD-ILD (0% lung fibrosis in the IPAF group vs. 43% in the CTD-ILD group, p = .07). We confirmed the existence of IPAF in children. Its prevalence was lower than in adults but comparable to that found for other pediatric series. Boys were more highly represented than in CTD-ILD. The course was favorable for most cases. Larger and more prospective studies are needed to confirm these results.

Gastrointestinal bezoars. Review of the literature and report of a rare case of pumpkin seed rectal impaction.

In science, bezoar is a mass of hair or undigested vegetable matter, found in a human or animal's intestines, similar to a hairball. Usually, it is found trapped in every part of the gastrointestinal system and must be distinguished by pseudobezoar which is an indigestive object voluntarily introduced into the digestive tract. The term Bezoar is from Arabic bāzahr, "bezoar" or ultimately from Middle Persian p'tzhl pādzahr, "antidote, bezoar"ægagropile o egagropile It should be a universal antidote that works against any poison, and could neutralize any poison. Otherwise, the name could derive from a kind of Turkish goat whose name is just bezoar. Authors report a case of fecal impaction by pumpkin seeds bezoar with abdominal pain: a difficulty to void with subsequent rectal inflammation and hemorrhoid enlargement was observed. The patient underwent a successful manual disimpaction. Guidelines do not require IRB approval Authors examined the literature about occlusion from bezoar The most common causes of occlusion from bezoar are: a previous gastric surgery such as a gastric band (for weight loss) or gastric bypass, a reduced stomach acid (hypochlorhydria) or decreased stomach size, a delayed gastric emptying, typically due to diabetes, autoimmune disorders, or mixed connective tissue disease. Seed bezoars are usually found in the rectum of patients without predisposing factors, causing constipation and pain. Rectal impaction is common after ingestion of seeds while a true occlusion is rare. Although several cases of phytobezoars composed of various types of seeds are reported in literature, bezoars of pumpkin seeds have rarely been reported.

The phenotype of mixed connective tissue disease patients having associated interstitial lung disease

ObjectiveWe aimed to compare two matched populations of patients with MTCD with and without associated ILD and to identify predictive factors for ILD progression and severity. MethodsThis international multicenter retrospective study (14 tertiary hospitals), included MCTD patients who fulfilled at least one historical MCTD classification criteria. ILD was defined by the presence of typical chest high-resolution computed tomography (HRCT) abnormalities. Factors associated with ILD were assessed at baseline. Long-term progressive ILD was assessed in MCTD-ILD patients with multiple forced vital capacity (FVC) measurements. Results300 patients with MCTD were included. Mean age at diagnosis was 39.7 ± 15.4 years and 191 (63.7%) were women. Mean follow-up was 7.8 ± 5.5 years. At baseline, we identified several factors associated with ILD presence: older age (p = 0.01), skin thickening (p = 0.03), upper gastro-intestinal (GI) symptoms (p<0.001), FVC <80% (p<0.0001), diffusing capacity for carbon monoxide <80% (p<0.0001), anti-topoisomerase antibodies (p = 0.01), SSA/Ro antibodies (p = 0.02), cryoglobulinemia (p = 0.04) and elevated C-reactive protein (p<0.001). Patients with MTCD-ILD were more likely to be treated with synthetic immunosuppressant agents (p<0.001) in particular mycophenolate mofetil (p = 0.03). Digital ulcers (DU) were identified as a risk factor for FVC decline >10%. During follow-up mortality was higher in the MTCD-ILD group (p<0.001). ConclusionIn this large international cohort of patients with MTCD, we identified different factors associated with ILD. Our findings also provide evidence that MCTD-ILD patients have increased mortality and that DU are associated with progressive lung disease.

Insights into the cellular basis of skin inflammation in systemic autoimmune rheumatic diseases from single-cell technologies.

Cutaneous inflammation is a common feature of several systemic autoimmune rheumatic diseases (SARDs) including systemic lupus erythematosus (SLE), undifferentiated connective tissue disease (UCTD), mixed connective tissue disease (MCTD) and dermatomyositis (DM) but is less common in other SARDs such as primary Sjögren's syndrome (pSS). It is important to understand whether the pathophysiological processes underlying skin inflammation are different or shared between SARDs to develop targeted therapies. This review will discuss commonalities and differences between inflammatory skin disease in SARDs focusing on histopathology and describe newer insights obtained from single-cell technologies.

Association of red cell distribution width with pulmonary arterial hypertension in patients with mixed connective tissue disease

BackgroundPulmonary arterial hypertension (PAH) is a severe complication of mixed connective tissue disease (MCTD) and contributes to increased morbidity and mortality. Still, the demographic characteristics and risk factors of PAH in MCTD remain poorly understood. This study explored risk factors for PAH development in MCTD.MethodsData from patients with MCTD and PAH hospitalized from May 2009 to December 2022 in a single center were collected and compared with patients with MCTD without PAH. The variables were analyzed by logistic regression to identify the factors associated with PAH in patients with MCTD. The receiver-operating characteristic (ROC) curve was used to assess the diagnostic value of the identified factors.ResultsFinally, 119 patients with MCTD were included; 46 had PAH. The mean age at PAH onset and diagnosis was 38.9 ± 13.4 and 39.9 ± 13.7 years, respectively. The median pulmonary arterial systolic pressure (PASP) was 67.0 mmHg. The median brain natriuretic peptide (BNP) level was 180.0 pg/ml at PAH diagnosis. Red cell distribution width (RDW) (OR: 2.128; 95% confidence interval: 1.497–3.026; P < 0.001) was associated with PAH in patients with MCTD. There was a positive correlation between RDW and PASP (r = 0.716, P < 0.001). At a cutoff of 15.2%, RDW had the best sensitivity (80.4%) and specificity (82.2%) for PAH.ConclusionRDW may serve as a sensitive index to predict PAH in patients with MCTD.

E58 The rheumatologic masquerader: a case report on SLE-dermatomyositis-systemic scleroderma overlap syndrome

Abstract Introduction Juvenile dermatomyositis is an autoimmune connective tissue disorder characterized by idiopathic inflammatory myopathy primarily affecting the skin and muscles(1, 2). It may occur alone or in overlap syndromes usually with systemic scleroderma, systemic lupus erythematosus (SLE) and mixed connective tissue disease(3, 4). There is need to further describe and characterize cases encountered in different set ups. Objective To describe a case of dermatomyositis-scleroderma overlap in an African male adolescent. Methods We carried out a retrospective chart review to ascertain clinical features and management strategies. Results We present a case of a 17- year old African male patient who presented with a diagnosis of systemic lupus erythematosus made at a peripheral facility in February 2021, and started on azathioprine 50 mg daily, hydroxychloroquine 200 mg daily and prednisolone 5 mg twice daily. He presented on 30th November 2022 with a 2-year history of bilateral elbow, knee, ankle pain and swelling with an 8-month history of bilateral proximal upper and lower limb muscle weakness. Review of systems revealed alopecia, occasional fever and hyperpigmentation over his proximal interphalangeal and metacarpophalangeal joints that has since evolved to hypopigmentation. Positive examination findings included fine sparse hair, heliotrope rash, Gottron's papule, salt and pepper skin rash, hardening of the skin over the arm and thighs with a rodnan score 3/3 over the phalanges, nodular non tender lesions in the abdominal subcutaneous tissue and dactylitis with fixed flexion deformities of both elbows. He had bilateral flexion contractures of both elbows and knees with dactylitic fingers. Laboratory investigations showed an elevated CRP 94 mg/l, elevated lactate dehydrogenase 458 U/l, elevated creatine kinase 492U/l, positive antinuclear antibodies (1:640 titres) with a nuclear coarse and large speckled pattern, positive double stranded DNA antibodies and weak positive anti SM, anti RNP and PCNA antibodies. Myositis panel was positive for MDA5 and OJ. Pelvic MRI showed features of proximal inflammatory myositis. The childhood myositis assessment scale revealed a score of 25/52. ECHO and chest radiograph were normal. Pulmonary function test showed a low FEV 1 and FVC in keeping with a restrictive lung picture. Gastroenterology review revealed gastritis with no other stigmata of autoimmune disease. Management has consisted of monthly therapy with intravenous immunoglobulin. Azathioprine therapy was switched with mycophenolate mofetil 1 gram twelve hourly. He was advised on sunscreen protection. Physiotherapy and occupational therapy has been ongoing. Three months of follow up has led to the resolution of the flexion knee contractures, improved functionality in activities of daily living and a rodnan score of 2/3 over the phalanges. Conclusion SLE-juvenile dermatomyositis and systemic scleroderma can occur as an overlap syndrome and a definitive diagnosis remains elusive to many clinicians. A thorough history and comprehensive physical examination remains key to establishing a correct diagnosis. Early patient referral to paediatric rheumatologist for prompt appropriate treatment can avert debilitating morbidity and mortality.

Can Artificial Intelligence help a clinical laboratory to draw useful information from limited data sets? Application to mixed connective tissue disease

&lt;p&gt;Diagnosis is a key step of patient management. During decades, refined decision algorithms and numerical scores based on conventional statistical methods were elaborated to ensure optimal reliability. Recently, a number of machine learning tools were developed and applied to process more and more extensive data sets, including up to millions of items and yielding sophisticated classification models. While this approach met with impressive efficiency in some cases, practical limitations stem from the high number of parameters that may be required by a model, resulting in increased cost and delay of decision making. Also, information relative to the specificity of local recruitment may be lost, hampering any simplification of universal models. Here, we explored the capacity of currently available artificial intelligence tools to classify patients found in a single health center on the basis of a limited number of parameters. As a model, the discrimination between systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD) on the basis of thirteen biological parameters was studied with eight widely used classifiers (including logistic regression, support vector machine, nearest neighbor classifier, random forests and neural networks). A retrospective study including 44 patients (34 SLE, 10 MCTD) was conducted in Marseilles hospital organization. The best area under ROC curve yielded on test sets with classifiers using all 13 parameters was 0.83 ± 0.03 standard error and 0.86 ± 0.02 SE with 5 selected parameters. It is concluded that classification efficiency may be significantly improved by a knowledge-based selection of discriminating parameters.&lt;/p&gt;

Extramural hematoma after esophageal stricture dilatation in mixed connective tissue disease.

Extramural hematoma after esophageal stricture dilatation in mixed connective tissue disease.

Pulmonary Hypertension in Autoimmune Diseases – A Review of New Concepts in Screening, Diagnosis and Therapeutic Management

Pulmonary hypertension (PH) has gained more and more attention in the last years given the increased mortality and morbidity rate and in particular pulmonary arterial hypertension associated with autoimmune diseases (a specific subgroup of PH), entities with an increasing incidence and prevalence globally. Among these, systemic sclerosis is of particular interest, being the most common among connective tissue diseases (CTDs) with PH as a major complication. Other CTDs such as mixed connective tissue disease (MCTD), systemic lupus erythematosus (SLE), primary Sjogren's syndrome, and dermatomyositis may also develop PH as a complication of these severe and complex conditions, which can have a major impact on prognosis and quality of life. PH has also been reported in rheumatoid arthritis and ankylosing spondylitis but further studies are necessary. Several studies have shown that the 3-year survival rate for patients with systemic sclerosis-associated with pulmonary hypertension (SSc-PH) is between 31% and 52%, while the 5-year survival rate is below &lt;50%. Therefore, an early and accurate diagnosis as well as subsequent management of PH in these conditions is mandatory, since survival remains suboptimal despite treatment advances. The aim of this article is to provide an overview of different autoimmune diseases associated with PH and to provide an easy reference source on current best practices.

Discovery of the TLR7/8 Antagonist MHV370 for Treatment of Systemic Autoimmune Diseases.

Toll-like receptor (TLR) 7 and TLR8 are endosomal sensors of the innate immune system that are activated by GU-rich single stranded RNA (ssRNA). Multiple genetic and functional lines of evidence link chronic activation of TLR7/8 to the pathogenesis of systemic autoimmune diseases (sAID) such as Sjögren's syndrome (SjS) and systemic lupus erythematosus (SLE). This makes targeting TLR7/8-induced inflammation with small-molecule inhibitors an attractive approach for the treatment of patients suffering from systemic autoimmune diseases. Here, we describe how structure-based optimization of compound 2 resulted in the discovery of 34 (MHV370, (S)-N-(4-((5-(1,6-dimethyl-1H-pyrazolo[3,4-b]pyridin-4-yl)-3-methyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-1-yl)methyl)bicyclo[2.2.2]octan-1-yl)morpholine-3-carboxamide). Its in vivo activity allows for further profiling toward clinical trials in patients with autoimmune disorders, and a Phase 2 proof of concept study of MHV370 has been initiated, testing its safety and efficacy in patients with Sjögren's syndrome and mixed connective tissue disease.

Meningococcal ACWY conjugate vaccine immunogenicity in adolescents with primary or secondary immune deficiencies, a prospective observational cohort study

BackgroundImmunization with meningococcal ACWY conjugate vaccine induces protective antibodies against invasive meningococcal disease (IMD) caused by serogroups A, C, W and Y. We studied MenACWY-TT vaccine immunogenicity in adolescents with a heterogenous group of primary and secondary immune deficiency including patients with systemic lupus erythematosus, mixed connective tissue disease, vasculitis, uveitis, 22Q11 syndrome, sickle cell disease, and patients who underwent stem cell transplantation for bone marrow failure.FindingsWe enrolled 69 individuals aged 14–18 years diagnosed with a primary or secondary immune deficiency in a prospective observational cohort study. All patients received a single dose of MenACWY-TT vaccine during the catch-up campaign 2018-19 because of the IMD-W outbreak in the Netherlands. Capsular polysaccharide-specific (PS) IgG concentrations against MenACWY were measured before and 3–6, 12, and 24 months after vaccination. Overall, geometric mean concentrations (GMCs) of MenACWY-PS-specific IgG were lower in patients compared to data from healthy, aged-matched controls (n = 75) reaching significance at 12 months postvaccination for serogroup A and W (adjusted GMC ratios 0.26 [95% CI: 0.15–0.47] and 0.22 [95% CI: 0.10–0.49], respectively). No serious adverse events were reported by study participants.ConclusionsThe MenACWY conjugate vaccine was less immunogenic in adolescent patients with primary or secondary immunodeficiency compared to healthy controls, urging the need for further surveillance of these patients and supporting considerations for booster MenACWY conjugate vaccinations in these patient groups.

Microvascular damage in autoimmune connective tissue diseases: a capillaroscopic analysis from 20 years of experience in a EULAR training and research referral centre for imaging

ObjectiveNailfold videocapillaroscopy (NVC) allows the detection of microvascular damage in autoimmune connective tissue diseases (CTDs). The prevalence of the morphological capillary findings was retrospectively evaluated in a wide cohort of...

Towards Early Diagnosis of Mixed Connective Tissue Disease: Updated Perspectives.

Mixed Connective Tissue Disease (MCTD) is an autoimmune disease first described by Sharp et al in 1972, characterized by the presence of anti-Ribonucleoprotein antibodies directed against the U1 complex (anti-U1RNP). The condition shares clinical characteristics with Systemic Lupus Erythematosus, Rheumatoid Arthritis, and Systemic Sclerosis. Diagnosis is quite difficult due to its rarity, the lack of validated classification criteria, and its heterogeneous clinical presentation. While in the early stages its nuanced clinical features might lead to it being incorrectly classified as other Connective Tissue Diseases (CTDs) or even not recognized, in cases of longstanding disease its classification as a CTD is clear but challenging to discriminate from overlap syndromes. MCTD should be considered a distinct entity due to the presence of a specific genetic substrate and the presence of the high titer of a specific autoantibody, anti-U1RNP, present in all the commercial kits for Extractable Nuclear Antigens, and almost always associated with Antinuclear Antibody positivity with a coarse speckled pattern. Except for anti-U1RNP, no specific biomarkers are available to guide clinicians to a correct classification of MCTD, which is arrived at by the association of clinical, serological and instrumental evaluation. In the first stages, the disease is mainly characterized by Raynaud's phenomenon, inflammatory arthritis, puffy fingers, myalgia and/or myositis, and rarely, trigeminal neuropathy. Longstanding disease is generally associated with the development of Pulmonary Hypertension and Interstitial Lung Disease, which are the two main causes of mortality in MCTD. The aim of this review is to summarize current knowledge on the early recognition of MCTD.

Spectrum of high-resolution computed tomography pattern in lungs in patients with connective tissue disorders.

Connective tissue disease associated with interstitial lung disease, or CT-ILD, is a lung condition that affects a large number of patients with a connective tissue disease. Our aim in this study is to correlation between images of high-resolution computed tomography (HRCT) of different connective tissue diseases associated interstitial lung diseases (CTD-ILDs). We shall be aiming to investigate the feasibility of HRCT imaging and thereby avoid lung biopsy in such patients. Rheumatoid arthritis predominantly presented with usual interstitial pneumonia (UIP) (47.8%), followed by nonspecific interstitial pneumonia (NSIP) (30.4%). Mixed connective tissue disorder predominantly presented with NSIP and UIP (42.8%), followed by organizing pneumonia (OP) (14.2%). Systemic lupus erythematosus predominantly presented with UIP (38.8%), followed by NSIP (27.7%). Sjogren's syndrome predominantly presented with lymphocytic interstitial pneumonia (40%), followed by UIP (26.6%). Scleroderma predominantly presented with UIP (45.4%), followed by NSIP (36.4%). Sarcoidosis predominantly presented with UIP (75%), followed by NSIP (25%). Dermatomyositis predominantly presented with NSIP (50%), followed by UIP and OP each (25%). Both clinicians and radiologists should be aware of the expected evolution of HRCT changes in a variety of CT-ILDs.

Diagnostic dilemma: Multiple Autoimmune Syndrome versus incomplete Graham-Little-Piccardi-Lassueur Syndrome overlap mixed connective tissue disease

Objectives. We present a very rare case of incomplete Graham-Little-Piccardi-Lassueur syndrome (GLPLS) overlap with Mixed Connective Tissue Disease (MCTD) versus Multiple Autoimmune Syndrome (MAS). Case Presentation. A 53- year-old female with a long history of more than two years of patchy hair loss on scalp like “footprints in the snow”, partial loss of eyebrows' hair, face erythema, scaly atrophied red/brown patches on face, grouped follicular papules 2-3 mm in diameter with a pointed or hair-like horny spine extending approximately 1-2 mm around the tip of the follicle on lumbar area. The histopathological results from biopsies of scalp and lumbar areas confirmed the clinical diagnosis of cicatricial alopecia induced by lichen plan pilaris (LPP) and also presence of lichen spinulosus (LS) on lumbar area. The description provided by pathologist is however borderline regarding so called interface dermatosis like chronic cutaneous lupus erythematous (CCLE) or Pseudopelade of Brocq (PPB) as the end stage of CCLE or LPP. Blood tests showed both Antinuclear antibodies and U1-nRNP in high titers and the absence of anti-Sm, anti SS-A, anti SS-B and anti-dsDNA antibodies, and also peculiar antibody patterns of MCTD. Outcome. After thorough investigation, MCTD was proven by antibodies results. After one year of treatment a lot of clinical features dramatically responded under therapy. Conclusions. Clinical manifestations in the pathology with strictly cutaneous or systemic localization in conjunction or overlap with other autoimmune diseases (grouped in the MAS) represent a rare diagnostic in daily practice.

Is The Glycerol, Petroleum Jelly and Liquid Paraffin Mixture (Dexeryl®) an Adjunctive Therapy for Vitiligo of Autoimmune Origin? Toward a Novel Therapeutic Indication. About a Case

Introduction: Vitiligo, considered to have an autoimmune basis, is an acquired, non-contagious disorder characterized by progressive, patchy loss of pigmentation from skin, overlying hair, and oral mucosa. The treatment of vitiligo includes medicines or medicated skin creams, such as corticosteroids or a calcineurin inhibitor, phototherapy, Depigmentation, or removing color from dark areas, surgical techniques. The results from treatments can vary from one part of the body to another, and new patches may appear in the meantime Here, we report a case with complete remission of vitiligo of autoimmune origin under DMARDs and the glycerol, petroleum jelly and liquid paraffin mixture (dexeryl®), of which we hypothesize that the glycerol, petroleum jelly and liquid paraffin mixture (dexeryl®) would have played a role in rapid and complete vitiligo lesion regression. Clinical Observation: An 18-year-old Malian female presented to the internal medicine outpatient clinic with 3-months history of pruritic achromic skin patches. Concomitantly, this was associated with Gottron's papules, polyarthralgia with arthritis and exertional dyspnea for which the diagnosis of mixed connective tissue disease (MTCD) based on the EULAR/ACR 2019 criteria for systemic lupus erythematosus, EULAR/ACR 2010 criteria for rheumatoid arthritis with subcutaneous rheumatoid nodule, EULAR/ ACR 2013 criteria for systemic scleroderma, Bohan and Peter 1975 criteria for probable dermato-polymyositis and Kasukawa’s criteria 1988 for MTCD itself; and autoimmune hemolytic anemia (AHA) with positivity of the direct coombs test and the context of hemolysis were made. Vitiligo of autoimmune origin was considered because of the clinical context and the immunological disorder in this case. She was treated only with Disease-Modifying Anti-rheumatic Drugs (DMARDs) and glycerol, petroleum jelly and liquid paraffin mixture (dexeryl®). The vitiligo lesion had completely resolved on 1-year follow-up visit in our case without specific vitiligo treatment. Discussion: The glycerol, petroleum jelly and liquid paraffin mixture (dexeryl®) in our case was indicated for dry skin presentation. But we observed a rapid and complete vitiligo regression under this mixture associated with DMARDs. This is why, beside a controlled inflammation process by DMARDs, we suspected a role of glycerol, petroleum jelly and liquid paraffin mixture (dexeryl®) in melanocyte regeneration. Conclusion: This case would highlight a potential novel indication of glycerol, petroleum jelly and liquid paraffin mixtures (dexeryl®) in vitiligo of autoimmune origin. A clinical trial will be necessary to deeply appreciation this novel therapeutic property of glycerol, petroleum jelly and liquid paraffin mixtures (dexeryl®).

Doubtful Clinical Value of Subtyping Anti-U1-RNP Antibodies Regarding the RNP-70 kDa Antigen in Sera of Patients with Systemic Lupus Erythematosus.

The detection of antinuclear antibodies is central to the diagnosis and prognosis of systemic lupus erythematosus (SLE), primary Sjögren's syndrome (pSS) and mixed connective tissue disease (MCTD). Anti-U1-RNP and anti-RNP70 antibodies were assayed in the sera of patients with SLE (n = 114), pSS (n = 54) and MCTD (n = 12). In the SLE group, 34/114 (30%) were anti-U1-RNP positive, and 21/114 (18%) were both anti-RNP70 positive and anti-U1-RNP positive. In the MCTD group, 10/12 (83%) were anti-U1-RNP positive, and 9/12 (75%) were anti-RNP70 positive. Only one individual with pSS was antibody positive (for both anti-U1-RNP and anti-RNP70). All anti-RNP70-positive samples were also anti-U1-RNP positive. Anti-U1-RNP-positive subjects with SLE were younger (p < 0.0001); showed lower concentrations of complement protein 3 (p = 0.03); had lower eosinophil (p = 0.0005), lymphocyte (p = 0.006) and monocyte (p = 0.03) counts; and had accrued less organ damage (p = 0.006) than the anti-U1-RNP-negative SLE patients. However, we observed no significant clinical or laboratory parameter differences between the anti-U1-RNP-positive individuals with/without anti-RNP70 in the SLE group. In conclusion, anti-RNP70 antibodies are not exclusive to MCTD but are rarely detected in pSS and healthy individuals. In SLE, anti-U1-RNP antibodies are associated with a clinical phenotype that resembles MCTD, with hematologic involvement and less damage accrual. Based on our results, the clinical value of subtyping anti-RNP70 in anti-U1-RNP-positive sera appears to be of limited value.

IFIH1 and DDX58 gene variants in pediatric rheumatic diseases.

The IFIH1 gene codes the MDA5 protein and the DDX58 gene codes the RIG-I receptor. Both proteins are parts of the interferon (IFN) I signaling pathway and are responsible for antiviral defense and innate immune response. IFIH1 and DDX58 polymorphisms are associated with a spectrum of autoimmune diseases. Rare gain-of-function IFIH1 mutations have been found in Singleton-Merten and Aicardi-Goutières syndrome, while DDX58 mutation can cause atypical Singleton-Merten syndrome. To characterize children with pediatric rheumatic diseases (PRD) carrying DDX58 or IFIH1 variants. Clinical exome sequencing was performed on 92 children with different PRD. IFIH1 and DDX58 variants have been detected in 14 children. IFN-I score has been analyzed and the clinical characteristics of patients have been studied. A total of seven patients with systemic lupus erythematosus (SLE) (n = 2), myelodysplastic syndrome with SLE features at the onset of the disease (n = 1), mixed connective tissue disease (MCTD) (n = 1), undifferentiated systemic autoinflammatory disease (uSAID) (n = 3) have 5 different variants of the DDX58 gene. A common non-pathogenic variant p.D580E has been found in five children. A rare variant of uncertain significance (VUS) p.N354S was found in one patient with uSAID, a rare likely non-pathogenic variant p.E37K in one patient with uSAID, and a rare likely pathogenic variant p.Cys864fs in a patient with SLE. Elevated IFN-I score was detected in 6 of 7 patients with DDX58 variants. Seven patients had six different IFIH1 variants. They were presented with uSAID (n = 2), juvenile dermatomyositis (JDM) (n = 1), SLE-like disease (n = 1), Periodic fever with aphthous stomatitis, pharyngitis, and adenitis syndrome (n = 1), and systemic onset juvenile idiopathic arthritis (n = 1). Three patients have VUS p.E627X, one patient has benign variant p.I923V. Rare VUS p.R595H was detected in the JDM patient. Another rare VUS p.L679Ifs*2 and previously not reported variant p.V599Ffs*5 were detected in the patient with uSAID. One patient with uSAID has rare VUS p.T520A. All patients had elevated IFN-I scores. Rare compound-heterozygous IFIH1 variant (p.L679Ifs*2 and p.V599Ffs*5), heterozygous IFIH1 variant (p.T520A) and heterozygous DDX58 variant (p.Cys864fs) are probably disease causative for uSAID and SLE. The majority of patients with different DDX58 and IFI1 variants had hyperactivation of the IFN I signaling pathway.

Vertebromedullary hydatidosis: a case report.

This article presents the case of a 12-year-old child with no particular pathological antecedent, who presents a spinal cord compression syndrome evolving gradually for 2 weeks whose objective clinical examination found a 2/5 paraparesis with a sharp pyramidal syndrome and subxiphoid sensory level. Medullary MRI has objectified an aspect of hydatid cysts at the level of D8 D9 and D10 compressing the spinal cord. Management was surgical by decompression by laminectomy of stage D8, D9, and D10 under general anesthesia and put on albendazole, the diagnosis was confirmed by histopathological examination, the evolution was marked by a partial recovery of deficit. Clinical symptomatology is vague with a gradually inescapable movement towards spinal or root pressure.

Heterogeneity of echocardiographic variables in systemic lupus erythematosus among clinical subgroups according to non-cardiac organ involvement

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease. Cardiac involvement is rare but plays an important prognostic role. The degree of cardiac involvement according to SLE subsets defined by non-cardiac manifestations is unknown. The objective of this study was to identify differences in TTE parameters associated with different SLE subgroups. One hundred and eighty-one patients fulfilling the ACR/EULAR 2019 classification criteria for SLE and had a TTE were included in this cross-sectional study. We defined four subsets of SLE based on the predominant clinical manifestations. A multivariate multinomial regression analysis was performed to determine whether TTE parameters differ between the subsets. The first subset (n = 37) of patients showed features of mixed connective tissue disease (MCTD); the second subset (n = 76) had primarily cutaneous involvement; the third subset (n = 18) exhibited serositis and the last subset (n = 50) had severe disease with significant organ involvement, including renal involvement. Forty TTE parameters were assessed in each patient. Using a multivariate multinomial regression analysis, 3 parameters differed between groups: early diastolic tricuspid annular velocity (RV-E′, P < 0.0001), RV-S′ (RV-pulse DTI systolic peak wave, P = 0.0031), and RV end-diastole diameter (P = 0.0419). The degree of RV dysfunction was lowest in patients with primarily cutaneous involvement. Four distinct clinical subsets based on clinical manifestations differed in terms of TTE parameters of right heart function and diastolic dysfunction. This could help to tailor the cardiac follow-up required by the different clinical subsets of SLE.