Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome.

Camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP) is a rare autosomal recessive disease caused by mutation in proteoglycan 4 (PRG4) gene on chromosome 1q25-q31. We faced a dilemma and delay in diagnosis in two sisters. The elder sister had pericardial effusion with constrictive pericarditis, underwent pericardiectomy and received empirical treatment for suspected tuberculosis. After 2 years, she developed bilateral knee swelling with restriction of movement. At the same time, her younger sister also presented with bilateral knee swelling which aroused the suspicion of genetic disease. The whole-genome sequencing revealed homozygous PRG4 mutation suggestive of CACP syndrome.

Bevacizumab-induced immune thrombocytopenia in an ovarian cancer patient with mixed connective tissue disease: case report and literature review.

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.

Association between anti-SSA autoantibodies and conduction disturbances in heart failure.

BACKGROUND: Conduction disturbances play an important role in the occurrence and development of heart failure (HF). Studies suggest autoantibodies may attack the conduction system. However, whether autoantibodies are associated with conduction disturbances in patients with HF is unclear. OBJECTIVE: The purpose of this study was to assess whether anti-SSA, anti-Ro/Sjögren syndrome-related antigen A antibodies known for congenital atrioventricular block (AVB), is associated with conduction disturbances in patients with HF. METHODS: This retrospective observational study used data from patients with HF who were admitted to Beijing Anzhen Hospital between January 2018 and June 2022. Patients who were tested for anti-SSA and had undergone electrocardiographic examination during hospitalization were included. Conduction disturbances, including AVB, bundle branch block (BBB), and intraventricular conduction delay, were confirmed by a cardiologist blinded to anti-SSA status. Univariate and multivariable logistic regression analyses were performed to assess the association between anti-SSA and conduction disturbances. RESULTS: A total of 766 patients were included in this study, of whom 70 (9.1%) were anti-SSA positive. Subjects who were anti-SSA positive showed a higher prevalence of AVB (20% vs 10.6%) and BBB (27.3 % vs 10.9 %), including both left BBB and right BBB (all P <.05). After adjusting for known risk factors, anti-SSA was independently associated with AVB (odds ratio [OR] 2.42; 95% confidence interval [CI] 1.18-5.43; P = .03) and BBB (OR 3.15; 95% CI 1.68-5.89; P <.001). CONCLUSION: Anti-SSA is independently associated with AVB and BBB in patients with HF. Further study of the role of autoantibodies in the development of conduction abnormalities in patients with HF to generate possible targeted treatments is required.

A Case of Overlapping Autoimmune Syndrome.

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.

Drug-Induced Undifferentiated Connective Tissue Disease in a Two-Year-Old Girl: A Manifestation of Factitious Disorder Imposed on Another (FDIA).

Factitious disorder imposed on another (FDIA), formerly known as Munchausen syndrome by proxy (MSBP), constitutes a form of child abuse wherein a caregiver fabricates or induces illness in a person under their care or supervision. Here, we present a case of a two-year-old girl with signs and symptoms suggestive of undifferentiated connective tissue disease (UCTD) and probable autoinflammatory disease, which was a manifestation of FDIA. The patient manifested recurrent febrile episodes and presented with hepatosplenomegaly, elevated inflammatory markers, and mesangial proliferative glomerulonephritis. Regardless of extensive medical interventions, including corticosteroids and immunosuppressive therapy, the patient's condition failed to improve until the caregiver was isolated from the patient. Upon questioning, the caregiver admitted to having administered pyrogenal, an immunomodulator, to induce symptoms. This case highlights the challenges and difficulties of diagnosing and managing FDIA-associated illnesses, drawing attention to the importance of considering this diagnosis in cases of unexplained or recurrent fever in children.

Connective tissue disease-associated lung disease in children.

Connective tissue diseases are a heterogeneous group of autoimmune diseases that can affect a variety of organ systems. Lung parenchymal involvement is an important contributor to morbidity and mortality in children with connective tissue disease. Connective tissue disease-associated lung disease in children often manifests as one of several radiologic-pathologic patterns of disease, with certain patterns having a propensity to occur in association with certain connective tissue diseases. In this article, key clinical, histopathologic, and computed tomography (CT) features of typical patterns of connective tissue disease-associated lung disease in children are reviewed, with an emphasis on radiologic-pathologic correlation, to improve recognition of these patterns of lung disease at CT and to empower the pediatric radiologist to more fully contribute to the care of pediatric patients with these conditions.

An explainable machine learning-based model to predict intensive care unit admission among patients with community-acquired pneumonia and connective tissue disease.

BACKGROUND: There is no individualized prediction model for intensive care unit (ICU) admission on patients with community-acquired pneumonia (CAP) and connective tissue disease (CTD) so far. In this study, we aimed to establish a machine learning-based model for predicting the need for ICU admission among those patients. METHODS: This was a retrospective study on patients admitted into a University Hospital in China between November 2008 and November 2021. Patients were included if they were diagnosed with CAP and CTD during admission and hospitalization. Data related to demographics, CTD types, comorbidities, vital signs and laboratory results during the first 24 h of hospitalization were collected. The baseline variables were screened to identify potential predictors via three methods, including univariate analysis, least absolute shrinkage and selection operator (Lasso) regression and Boruta algorithm. Nine supervised machine learning algorithms were used to build prediction models. We evaluated the performances of differentiation, calibration, and clinical utility of all models to determine the optimal model. The Shapley Additive Explanations (SHAP) and Local Interpretable Model-Agnostic Explanations (LIME) techniques were performed to interpret the optimal model. RESULTS: The included patients were randomly divided into the training set (1070 patients) and the testing set (459 patients) at a ratio of 70:30. The intersection results of three feature selection approaches yielded 16 predictors. The eXtreme gradient boosting (XGBoost) model achieved the highest area under the receiver operating characteristic curve (AUC) (0.941) and accuracy (0.913) among various models. The calibration curve and decision curve analysis (DCA) both suggested that the XGBoost model outperformed other models. The SHAP summary plots illustrated the top 6 features with the greatest importance, including higher N-terminal pro-B-type natriuretic peptide (NT-proBNP) and C-reactive protein (CRP), lower level of CD4 + T cell, lymphocyte and serum sodium, and positive serum (1,3)-ß-D-glucan test (G test). CONCLUSION: We successfully developed, evaluated and explained a machine learning-based model for predicting ICU admission in patients with CAP and CTD. The XGBoost model could be clinical referenced after external validation and improvement.

Nintedanib combined with immunosuppressive agents improves forced vital capacity in connective tissue disease-associated PF-ILD: a single-center study.

BACKGROUND: In 2020, Nintedanib (NTB), a tyrosine kinase inhibitor, was the first drug approved worldwide for treating progressive fibrosing interstitial lung disease (PF-ILD). This study evaluated the efficacy and safety of NTB in Japanese patients with CTD-associated PF-ILD in a real-world setting, as there are few reports on this topic. We also evaluated the efficacy and safety of combination therapy with NTB and immunosuppressive agents (IS). METHODS: CTD-associated PF-ILD patients receiving NTB at our institution were included in this retrospective study. To evaluate the efficacy and safety of NTB, we investigated changes in forced vital capacity (FVC) (%), diffusing capacity for carbon monoxide (DLCO) (%), monthly change in FVC (%/month), serum Krebs von den Lungen-6 (KL-6) levels (U/mL) before and after NTB treatment, and adverse events (AEs) during NTB treatment. Moreover, to evaluate the efficacy of the NTB + IS combination therapy, we divided the patients into two groups: one received only NTB (NTB group), and the other received both NTB and IS (NTB + IS group) following the diagnosis of CTD-associated PF-ILD. We analyzed the differences in the changes of these variables between the two groups. RESULTS: Twenty-six patients with CTD-associated PF-ILD were included. After NTB treatment, there were no significant deteriorations in FVC (%) and DLCO (%), while the monthly change in FVC (%/month) significantly increased (p < 0.001). The changes in FVC (%) and the monthly change in FVC (%/month) were significantly greater in the NTB + IS group than in the NTB group. Following NTB treatment, the mean serum KL-6 levels significantly decreased (p < 0.001). AEs associated with NTB in this study were similar to those in previous clinical trials, and there was no significant difference in the incidence of AEs between the two groups. CONCLUSIONS: This study demonstrates that NTB is an effective medication for slowing the progression of CTD-associated PF-ILD in real-world settings. NTB + IS combination therapy for CTD-associated PF-ILD may be more effective than NTB alone in slowing the progression of CTD-associated PF-ILD.

Serum S1P level in interstitial lung disease (ILD) is a potential biomarker reflecting the severity of pulmonary function.

BACKGROUND: sphingosine-1-phosphate (S1P), a naturally occurring sphingolipid, has been involved in pulmonary interstitial remodeling signaling. However, no study has examined its clinical merits for interstitial lung disease (ILD). This study aimed to investigate the serum level of S1P in ILD patients and its clinical correlation with the severity of disease in the two main types of ILDs: the IPF and the CTD-ILD patients. METHODS: This retrospective observational pilot study included 67 ILD patients and 26 healthy controls. These patients were stratified into the IPF group (35) and the CTD-ILD group (32). The severity of ILD was evaluated through pulmonary function indicators and the length of hospital stay. RESULTS: Serum S1P level was statistically higher in ILD patients than in health control (p = 0.002), while the Serum S1P levels in CTD-ILD and IPF patients were comparable. Serum S1P level further showed statistically negative correlation with pulmonary function indexes (TLC% pred, FVC% pred and FEV1% pred) and positive correlation with length of hospital stay (r = -0.38, p = 0.04; r = -0.41, p = 0.02, r = -0.37, p = 0.04; r = 0.42, p = 0.02, respectively) in CTD-ILD patients, although serum S1P level was not significantly correlated with inflammatory indexes. The IPF patients failed to exhibit a significant correlation of serum S1P level with pulmonary function and length of hospital stay. CONCLUSIONS: Serum S1P level might be a clinically useful biomarker in evaluating the severity of CTD-ILD patients rather than IPF patients.

Case report: "Fur stole and turtleneck" and "halter-back" signs: an expanded wardrobe for dermatomyositis.

A diagnosis of dermatomyositis requires recognition of distinct patterns of skin disease in combination with, and sometimes without, muscle weakness. Often, a striking contrast between involved and uninvolved areas is observed. Familiar patterns include eyelid and midfacial eruptions, Gottron papules/sign, and upper back (shawl sign), central chest (V/open collar sign), and lateral thigh (holster sign) involvement. More recently, new specific antibody/phenotype-associated patterns have been reported. We describe a case series of two distinct patterns of skin involvement in six adult patients with both classical and amyopathic dermatomyositis. Three had paraneoplastic disease. All had intermediate to richly pigmented skin; five were of Afro-Caribbean and one was of Asian-Caribbean descent. Four were men, and two were women. Ages ranged from 41 to 89 years. All patients had concomitant hallmark signs (facial, hand, and/or trunk signs). Three were amyopathic. The first pattern involved a sharply demarcated, horizontally oriented hyperpigmented patch/thin plaque across the shoulders and upper chest, extending up the anterior neck. The second was the combination of the classical upper back shawl distribution with distinct mid-back sparing and diffuse involvement of the lower back. Named patterns help with the recognition of skin rashes in dermatomyositis. Based on the current lexicon describing items of apparel, we liken the first pattern to a "fur stole and turtleneck" sign and the latter to a "halter-back" or "reflected-shawl" sign. Biopsies revealed hyperkeratosis and interface dermatitis, often with epidermal atrophy, compatible with dermatomyositis. These patterns perhaps represent the coalescence of already well-described signs, photo-exacerbation, koebnerization, mechanical stretch, and other currently unclear factors contributing to patterning in dermatomyositis. Pattern distribution recognition is particularly valuable in individuals with richly pigmented skin who may lack typical violaceous erythema. The distinct demarcation led to the initial misdiagnosis of allergic contact dermatitis or other exogenous dermatitis in most of our patients. Further work involves evaluation of antibody phenotype and internal involvement associations. Limitations include lack of specific antibody panels and longitudinal follow-up data.

Diagnostic yield of flexible bronchoscopy for immunocompromised patients with lung infiltrates: A single-center, retrospective study.

BACKGROUND: Pulmonary complications are associated with mortality in immunocompromised patients. The usefulness of bronchoscopy has been reported. However, clinical factors and procedures that influence diagnostic yield are still not established. MATERIALS AND METHODS: We retrospectively analyzed 115 bronchoscopies performed on 108 immunocompromised patients, defined as those who take corticosteroids and/or immunosuppressants. We evaluated clinical factors, sampling procedures, final diagnosis, and severe complications of bronchoscopy. RESULTS: The clinical diagnosis was obtained in 51 patients (44%). Of those, 33 cases were diagnosed as infectious diseases and 18 as non-infectious diseases. Nine out of 115 cases (7.8%) initiated new immunosuppressive treatment for an underlying disorder based on the negative microbiological results obtained with bronchoscopy. Collagen vascular disease was the most common underlying disorders (62 patients, 54%). Bronchoscopy was useful regardless of whether the patient was immunosuppressed to treat collagen vascular disease (P = 0.47). Performing transbronchial biopsy correlated with better diagnostic yield of bronchoscopy (54.7% vs 35.5%, P = 0.049). Other clinical factors, such as radiological findings, respiratory failure or antibiotic use at the time of bronchoscopy did not significantly influence diagnostic yield. Respiratory failure requiring intubation after bronchoscopy occurred only in one case (0.9%). CONCLUSIONS: Our study implied the transbronchial biopsy may be a useful procedure for reaching a diagnosis in immunocompromised patients with pulmonary infiltrates. In addition, our data suggest the usefulness of bronchoscopy for immunocompromised patients due to the treatment of collagen vascular disease as well as other underlying disorders.

Impressive resolution of refractory hypertrophic discoid lupus erythematosus with anifrolumab.

Hypertrophic discoid lupus erythematosus is a rare variant of chronic cutaneous lupus erythematosus and is often challenging to treat. A male in his early 60s presented with diffuse erythematous, crusty, pruritic plaques on his upper and lower extremities, face, upper back, dorsal aspect of the hands and chest. He also described prolonged morning stiffness, swelling of his fingers and wrists, oral sores and Raynaud's phenomenon. He was positive for antinuclear antibody and anti-SSA antibody and had low C3 and C4 proteins. The skin biopsy was consistent with hypertrophic discoid lupus erythematosus. He was diagnosed with systemic lupus erythematosus. Skin lesions were refractory to treatment with topical corticosteroids, topical acitretin, hydroxychloroquine, azathioprine or mycophenolate. Anifrolumab infusions were initiated with a near-complete resolution of cutaneous symptoms within 3 months.

Morphoea presenting histopathologically as mycosis fungoides: an illustrative series of four cases.

AIMS: There have been exceptional reports of morphoea presenting with epidermal changes overlapping histopathologically with cutaneous T cell lymphoma of the mycosis fungoides type (MF). This phenomenon gives rise to an ambiguous clinicopathological scenario in which distinguishing these conditions may be challenging. The aim of this study is to characterise the clinical, histopathological and molecular findings of this phenomenon through a case series. METHODS AND RESULTS: Four patients with classical clinical presentation of morphoea but unusual histopathology displaying typical findings of morphoea, together with intra-epidermal CD8 positive lymphocytes indistinguishable from MF, were identified. The clinical phenotypes of morphoea were varied, and they all presented early in the active phase of the disease. They all exhibited intra-epidermal lymphocytes with tagging and cytological atypia. Pautrier-like microabscesses were also seen. Using molecular analysis, two cases showed clonal TCR gene rearrangement. Follow-up of all cases has been consistent with classical morphoea. CONCLUSION: Early morphoea can seldom present with atypical clonal intra-epidermal lymphocytes indistinguishable from MF. The fact that these changes can occur in several different clinical subtypes of morphoea raises the possibility that this could be a pattern of inflammation in early disease more common than currently appreciated.

Imaging of Pulmonary Manifestations of Connective Tissue Disease.

The majority of connective tissue diseases (CTDs) are multisystem disorders that are often heterogeneous in their presentation and do not have a single laboratory, histologic, or radiologic feature that is defined as the gold standard to support a specific diagnosis. Given this challenging situation, the diagnosis of CTD is a process that requires the synthesis of multidisciplinary data which may include patient clinical symptoms, serologic evaluation, laboratory testing, and imaging. Pulmonary manifestations of connective tissue disease include interstitial lung disease as well as multicompartmental manifestations. These CT imaging patterns and features of specific diseases will be discussed in this article.

Connective Tissue Disease Associated Interstitial Lung Disease.

Connective tissue disease associated interstitial lung disease (CTD-ILD) is a heterogenous collection of conditions with a diverse spectrum of interstitial lung disease (ILD) manifestations. Currently, clinical practice of lung-directed immunosuppression in CTD-ILD is supported by several randomized, placebo-controlled trials (RCTs) in patients with scleroderma and several observational, retrospective studies in other autoimmune conditions. However, given the harm of immunosuppression in idiopathic pulmonary fibrosis, there is an urgent need for RCTs of immunosuppression and antifibrotic agents in fibrotic CTD-ILD populations as well as the study of intervention in patients with subclinical CTD-ILD.

Pulmonary Hypertension Associated with Connective Tissue Disease.

Pulmonary hypertension (PH), a syndrome characterized by elevated pulmonary pressures, commonly complicates connective tissue disease (CTD) and is associated with increased morbidity and mortality. The incidence of PH varies widely between CTDs; patients with systemic sclerosis are most likely to develop PH. Several different types of PH can present in CTD, including PH related to left heart disease and respiratory disease. Importantly, CTD patients are at risk for developing pulmonary arterial hypertension, a rare form of PH that is associated with high morbidity and mortality. Future therapies targeting pulmonary vascular remodeling may improve outcomes for patients with this devastating disease.

Clinically Relevant Biomarkers in Connective Tissue Disease-Associated Interstitial Lung Disease.

Interstitial lung disease (ILD) complicates connective tissue disease (CTD) with variable incidence and is a leading cause of death in these patients. To improve CTD-ILD outcomes, early recognition and management of ILD is critical. Blood-based and radiologic biomarkers that assist in the diagnosis CTD-ILD have long been studied. Recent studies, including -omic investigations, have also begun to identify biomarkers that may help prognosticate such patients. This review provides an overview of clinically relevant biomarkers in patients with CTD-ILD, highlighting recent advances to assist in the diagnosis and prognostication of CTD-ILD.