Background: The positivity of anti-RNP autoantibodies as biological criteria for the diagnosis of mixed connective tissue disease (MCTD) has recently divided the rheumatology community. Autoantigenicity of the U1-snRNP complex tends to generate multiple autoantibodies against RNP-A, -C and -70 KDa or Sm proteins. The aim of this study is to identify the most informative autoantibodies in clinical practice, in particular, to contribute to differential diagnosis between MCTD and systemic lupus erythematosus (SLE). Methods: Sera from 74 patients positive for anti-RNP autoantibodies were selected over a period of one year of laboratory practice. Autoantibodies directed against extractable nuclear antigen, RNP proteins (A, C, 70 KDa) and 40 kDa fragments of RNP-70 KDa were investigated by using quantitative fluoroenzymatic assay and Western blot analysis. Results: Among the 74 patients, 40 patients were diagnosed with SLE, 20 with MCTD, six with another autoimmune disease, three with SARS-CoV-2 infection, three with cancer and two were healthy. No preferential clinical association of IgG or IgM autoantibodies directed against each of the RNP proteins was found between SLE and MCTD. In contrast, the proportion of autoantibodies directed against the RNP component within the U1-snRNP complex showed a significantly higher RNP index in patients with MCTD than in those with SLE (p = 0.011), with good performance (sensitivity: 69.2%, specificity: 88.9%). Conclusions: The analysis of the proportion of the different autoantibodies directed against the U1-snRNP complex is more informative than the analysis of each autoantibody separately. A follow-up of patients could be informative about the interest of the RNP index as a predictor of disease evolution.

Drug-induced immune thrombocytopenia is an adverse reaction marked by accelerated destruction of blood platelets. In cancer therapy, thrombocytopenia has many other causes including bone marrow suppression induced by chemotherapeutic agents, infection, and progression of cancer; drug-induced thrombocytopenia can easily be misdiagnosed or overlooked. Here, we present a case of an ovarian cancer patient with a history of mixed connective tissue disease who underwent surgery followed by treatment with paclitaxel, cisplatin, and bevacizumab. The patient developed acute isolated thrombocytopenia after the sixth cycle. Serum antiplatelet antibody testing revealed antibodies against glycoprotein IIb. After we analyzed the whole therapeutic process of this patient, drug-induced immune thrombocytopenia was assumed, and bevacizumab was conjectured as the most probable drug. Thrombocytopenia was ultimately successfully managed using recombinant human thrombopoietin, prednisone, and recombinant human interleukin-11. We provide a summary of existing literature on immune thrombocytopenia induced by bevacizumab and discuss related mechanisms and triggers for drug-induced immune thrombocytopenia. The present case underscores the potential of bevacizumab to induce immune-mediated thrombocytopenia, emphasizing the need for heightened vigilance towards autoimmune diseases or an autoimmune-activated state as plausible triggers for rare drug-induced immune thrombocytopenia in cancer therapy.

Overlapping autoimmune disorders are used to describe the coexistence of more than one autoimmune disease in the same patient. Mixed connective tissue disease (MCTD) and anti-synthetase syndrome (ASS) are autoimmune diseases that manifest with pulmonary involvement, presenting as persistent dyspnea. The coexistence of both conditions in the same patient is extremely rare. We herein report a case of a 44-year-old female who was diagnosed with MCTD with features of ASS (anti-Jo-1 antibody) in the setting of rheumatoid arthritis (anti-cyclic citrullinated peptide (anti-CCP) antibody), which shows temporary breathing improvement following treatment with corticosteroid and mycophenolate mofetil. However, after the completion of mycophenolate mofetil, she was found to be anti-Jo-1 antibody negative and anti-CCP antibody positive. Our case emphasizes the need to recognize overlapping autoimmune conditions in patients with complex clinical features and presentations with the immediate application of a comprehensive diagnostic approach and tailored treatment strategies. Early diagnosis and aggressive treatment are crucial for achieving remission and preventing organ damage.

UNASSIGNED: To investigate the clinical features, severity and prognosis of interstitial lung disease (ILD) in patients with mixed connective tissue disease (MCTD).
UNASSIGNED: We performed a retrospective study on clinical data of MCTD patients admitted to China-Japan Friendship Hospital between October 2012 and October 2022. Data including long-term follow-up were retrieved from medical records. We compared MCTD patients with and without ILD in terms of clinical features, laboratory and imaging findings, severity and treatment response.
UNASSIGNED: A total of 59 patients were included, with a mean age of 46 years, among which 91.5% (n = 54) were females. Symptoms of pulmonary involvement were present in 44 patients (74.6%, 95% CI: 62.3-84.9%). Based on lung high-resolution computed tomography (HRCT), ILD was diagnosed in 39 (66.1%) patients, among which 31 (79.5%) showed nonspecific interstitial pneumonia (NSIP) as the radiological pattern, 21 (53.9%) showed a reticulation pattern, while 24 (61.5%) showed ground glass opacity (GGO). Eight (13.6%) patients had pulmonary arterial hypertension (PAH), and 7 (11.9%) had pleural effusions. Based on pulmonary function tests (PFTs), 27 patients were divided into the mild 13 (48.1%) and moderate 14 (51.9%) groups. Multivariate analysis showed that gastroesophageal reflux (GER; OR=5.28, p=0.010) and cough (OR=4.61, p=0.043) were the predictive factors for ILD. With a median follow-up of 50 months, the mortality rate was 2.38%.
UNASSIGNED: ILD is common in MCTD patients, with NSIP as the common imaging pattern. Patients with GER and cough are relevant factors in the development of ILD. The majority of MCTD patients with ILD are mild to moderate in severity.

Diagnostic accuracy is of the utmost importance, both in the clinical setting and for research purposes. Mixed connective tissue disease (MCTD), rheumatoid arthritis (RA), Sjogren\'s syndrome (SS), and overlap syndrome (OS) frequently exhibit symptoms that mimic those of other conditions. Unfortunately, there is no singular definitive test for diagnosing these connective tissue diseases (CTDs), necessitating the reliance on expert opinions. Further complicating the matter, these diseases have overlapping clinical and serological features, and some individuals with one autoimmune disease may develop additional autoimmune disorders, either concurrently or at a later stage of their ailment. Autoimmune diseases (ADs) may manifest as a single AD or, concurrently with other ADs, a condition named polyautoimmunity (polyA). Polyautoimmunity refers to the presence of numerous autoimmune disorders in a single patient. Multiple autoimmune syndrome (MAS) is a condition that occurs when three or more autoimmune illnesses coexist. Moreover, the coexistence of two or more ADs with classification criteria is named \"overt polyA,\" whereas the presence of autoantibodies not related to the index AD, without criteria fulfillment, is termed \"latent polyA.\" Furthermore, both conditions can exist simultaneously within an individual patient. This case report\'s findings underscore that patients exhibiting both latent and overt polyautoimmunity tend to group, exhibiting distinct clinical and immunological characteristics. Additionally, CTDs not only have overlapping features amongst their various subclasses but also tend to mimic other conditions due to an underlying chronic inflammatory state. This case study also attempts to highlight the diagnostic dilemmas faced in such situations.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) has been extensively studied in various causes of pulmonary hypertension (PH), but its utility as a noninvasive marker remains highly debated. The objective of our study was to assess FeNO levels in patients with idiopathic pulmonary arterial hypertension (IPAH) and mixed connective tissue disease complicating pulmonary hypertension (MCTD-PH), and to correlate them with respiratory functional data, disease severity, and cardiopulmonary function.
METHODS: We collected data from 54 patients diagnosed with IPAH and 78 patients diagnosed with MCTD-PH at the Shanghai Pulmonary Hospital Affiliated to Tongji University. Our data collection included measurements of brain natriuretic peptide (pro-BNP), cardiopulmonary exercise test (CPET), pulmonary function test (PFT), impulse oscillometry (IOS), and FeNO levels. Additionally, we assessed World Health Organization functional class (WHO-FC) of each patient.
RESULTS: (1) The fractional exhaled concentration of nitric oxide was notably higher in patients with IPAH compared to those with MCTD-PH. Furthermore, within the IPAH group, FeNO levels were found to be lower in cases of severe IPAH compared to mild IPAH (P = 0.024); (2) In severe pulmonary hypertension as per the WHO-FC classification, FeNO levels in IPAH exhibited negative correlations with FEV1/FVC (Forced Expiratory Velocity at one second /Forced Vital Capacity), MEF50% (Maximum Expiratory Flow at 50%), MEF25%, and MMEF75/25% (Maximum Mid-expiratory Flow between 75% and 25%), while in severe MCTD-PH, FeNO levels were negatively correlated with R20% (Resistance at 20 Hz); (3) ROC (Receiving operator characteristic curve) analysis indicated that the optimal cutoff value of FeNO for diagnosing severe IPAH was 23ppb; (4) While FeNO levels tend to be negatively correlated with peakPETO2(peak end-tidal partial pressure for oxygen) in severe IPAH, in mild IPAH they had a positive correlation to peakO2/Heart rate (HR). An interesting find was observed in cases of severe MCTD-PH, where FeNO levels were negatively correlated with HR and respiratory exchange ratio (RER), while positively correlated with O2/HR throughout the cardiopulmonary exercise test.
CONCLUSIONS: FeNO levels serve as a non-invasive measure of IPAH severity. Although FeNO levels may not assess the severity of MCTD-PH, their significant makes them a valuable tool when assessing severe MCTD-PH.

A 50-year-old female patient presenting with joint pains, Raynaud\'s phenomenon, epistaxis, and telangiectasias was posed with a diagnostic conundrum, i.e., whether to accept the diagnosis of mixed connective tissue disease (MCTD), for which she fulfilled all the criteria, or test for another probable disease, namely hereditary hemorrhagic telangiectasia (HHT), even though only some clinical features were present and all diagnostic criteria were not satisfied. Taking the patient\'s onset of epistaxis as an important clue, the patient was counseled for genetic testing for HHT, which was positive. Treatment for both MCTD and HHT is underway, and appropriate surveillance is planned for the patient.

BACKGROUND: Data on real-world clinical practice and outcomes of patients with pulmonary arterial hypertension associated with connective tissue disease (CTD-PAH) are scarce. The OPUS/OrPHeUS studies enrolled patients newly initiating macitentan, including those with CTD-PAH. This analysis describes patient characteristics, treatment patterns, outcomes, and safety profiles of patients with CTD-PAH newly initiating macitentan in the US using the OPUS/OrPHeUS combined dataset.
METHODS: OPUS was a prospective, US, multicenter, long-term, observational drug registry (April 2014-June 2020). OrPHeUS was a retrospective, US, multicenter medical chart review (October 2013-March 2017). The characteristics, treatment patterns, safety, and outcomes during macitentan treatment of patients with CTD-PAH and its subgroups systemic sclerosis (SSc-PAH), systemic lupus erythematosus (SLE-PAH), and mixed CTD (MCTD-PAH) were descriptively compared to patients with idiopathic/heritable PAH (I/HPAH).
RESULTS: The combined OPUS/OrPHeUS population included 2498 patients with I/HPAH and 1192 patients with CTD-PAH (708 SSc-PAH; 159 SLE-PAH; 124 MCTD-PAH, and 201 other CTD-PAH etiologies). At macitentan initiation for patients with I/HPAH and CTD-PAH, respectively: 61.2 and 69.3% were in World Health Organization functional class (WHO FC) III/IV; median 6-min walk distance was 289 and 279 m; and 58.1 and 65.2% received macitentan as combination therapy. During follow-up, for patients with I/HPAH and CTD-PAH, respectively: median duration of macitentan exposure observed was 14.0 and 15.8 months; 79.0 and 83.0% experienced an adverse event; Kaplan-Meier estimates (95% confidence limits [CL]) of patients free from all-cause hospitalization at 1 year were 60.3% (58.1, 62.4) and 59.3% (56.1, 62.3); and Kaplan-Meier estimates (95% CL) of survival at 1 year were 90.5% (89.1, 91.7) and 90.6% (88.6, 92.3).
CONCLUSIONS: Macitentan was used in clinical practice in patients with CTD-PAH and its subgroups, including as combination therapy. The safety and tolerability profile of macitentan in patients with CTD-PAH was comparable to that of patients with I/HPAH.
BACKGROUND: OPsumit® Users Registry (OPUS): NCT02126943; Opsumit® Historical Users cohort (OrPHeUS): NCT03197688; www.
RESULTS: gov Graphical abstract available for this article.

UNASSIGNED: Mixed connective tissue disease (MCTD) is characterized by high titres of distinct antibodies: U1 ribonucleoprotein with variable clinical features seen in rheumatoid arthritis, systemic lupus erythematosus, scleroderma, polymyositis, and dermatomyositis. Limited case reports revealed the association between MCTD and cancer, like lymphoma, lung cancers, and others.
UNASSIGNED: A 22-year-old female presented with enlargement of the abdomen and oedema of the lower extremities, gradually started 25 days The patient had been diagnosed to have rheumatoid arthritis. She was treated with 7.5 mg/week MTX for 6 months. Physical examination revealed: pallor, lower limb oedema, with synovitis and deformities of hands. The laboratory tests showed anaemia, elevated levels of creatine phosphokinase ESR, positivity of antinuclear antibody, anti-ds DNA, and antinuclear ribonucleoprotein. Urinary protein excretion was 1625 mg/24 h. Chest X-ray showed bilateral pleural effusion. Echocardiography revealed pericardial effusion Thoracic-abdominal and pelvic tomography showed a heterogeneous mass with a diameter of 5 × 6 cm at the expense of the right ovary. The mass was removed surgically, and a biopsy was taken, and was compatible with ovarian high-grade serous adenocarcinoma. A course of solumedrol 1 g/IV/3 days was applied, and then continue with 60 mg/day oral predlone. Later on discharge, she was taken 25 mg/day predlone, and methotrexate 10 mg.
UNASSIGNED: Our case showed that the patient had no risk factors for developing ovary cancer. On the contrary, our patient was a young, non-smoker, without any previous treatment before the RA diagnosis was taken, and finally, she had 3 children with full-term pregnancy, and well health. This case highlights the importance of maintaining a high index of suspicion for malignancy in MCTD patients. However, further investigation on the role of the immune system in the development of ovarian cancer in women with autoimmune diseases including MCTD remains necessary.

BACKGROUND: Overlap autoimmune syndromes (OAS) and mixed connective tissue disease (MCTD) are rare in children. We performed a retrospective, longitudinal and descriptive study of Afro-Caribbean patients from the French West Indies followed for MCTD and OAS to describe their characteristics and outcomes during childhood.
METHODS: Retrospective study from January 2000 to 2023. Listings of patients were obtained from multiple sources: computerized hospital archives and national hospital-based surveillance system, registry of pediatricians and adult specialists in internal medicine and the national registry for rare diseases. MCTD was defined according to Kasukawa\'s criteria. OAS was defined as overlapping features of systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and dermatomyositis/autoimmune myositis (DM/AM).
RESULTS: Sixteen patients were included over a 23-year period (10 MCTD and 6 OAS). The incidence was 0.23 per 100,000 children-years. The mean age at diagnosis was 11.9 years old (2.4-17) with median follow up of 7.9 years (2.1-19.6). SLE phenotype was present in the highest, followed by SSc and DM/AM. Patients had an average of three flares during childhood (1-7). A quarter (25%) had symptomatic pulmonary arterial hypertension (PAH). Ninety-four percent received steroids during follow-up and 88% required a corticosteroid-sparing therapy. Three patients (19%) developed SLE after more than 10y of follow-up. There were no death and no chronic organ failure.
CONCLUSIONS: This is the largest pediatric cohort of MCTD and OAS in Afro-descendant patients treated in a country with a high standard of care. The clinical evolution did not differ between MCTD and OAS. The main complication was PAH, more frequent in our cohort.