Mixed Connective Tissue Disease Research Articles

Novel genetic and molecular pathways in pulmonary arterial hypertension associated with connective tissue disease

Abstract Introduction PAH is a severe complication of CTD, with remarkable morbidity and mortality. SSc is most commonly associated with PAH, but it can be present in other CTD. Despite major advances in PAH therapy, survival in CTD-PAH remains poor. Furthermore, the molecular and genetic basis of PAH in CTD are not well established. Purpose This study aimed to screen for genetic defects in a cohort of patients with CTD-PAH. Methods Since November 2011, genetic testing is offered to all patients with idiopathic, hereditable and associated forms of PAH, and PVOD included in a national registry of PAH. A PAH-specific panel of 35 genes was designed. Results During enrolling, 79 patients were recruited: 59 SSc, 11 SLE and 9 other. 69 female, mean age 55,6±1,9 years, mean PVR 8,6±0,5 WU and mean DLCO 47,5±2%. Disease-associated variants were observed in 9 patients: 4 pathogenic/likely pathogenic in 4 different genes (TBX4, ABCC8, KCNA5 and GDF2/BMP9) and 5 VUS in 4 genes (ABCC8, NOTCH3, TOPBP1 and CTCFL). Clinical characteristics of patients with pathogenic/likely pathogenic variants and variant analyses are shown in Tables 1 and 2. Patient 1 is a Caucasian female with mixed CTD, diagnosed with PAH at 58 years of age. She has a frameshift pathogenic variant in TBX4. Pulmonary function test (PFT) ruled out interstitial lung disease (ILD), but a reduction in DLCO was observed (61% of predicted). Two patients carry variants in ABCC8. Patient 2 is a Caucasian female with SSc, diagnosed with PAH at 27 years of age. She carries a splicing variant in ABCC8, classified as likely pathogenic. Her mother was diagnosed with PAH associated with a repaired ASD at 61 years of age. In the genetic testing, no variants were observed in PAH genes. DLCO was 71% of predicted, without signs of ILD. Patient 3 is a Caucasian male, with clinical suspicion of PVOD associated with SSc and HIV infection. PAH was diagnosed at 57 years of age. He presented a missense variant in ABCC8, located in a gating regulatory region, and classified as VUS. Her sister was also diagnosed with PVOD associated with SSc at 48 years of age. No blood or tissue samples are available. In patient 3, DLCO was 22% of predicted value. CT scan showed the typical triad of PVOD. Patient 4 is a Latin American female with SLE, diagnosed with PAH at 25 years of age. She presented a pathogenic nonsense variant in GDF2/BMP9. Patient 5 is a Caucasian female with SSc, diagnosed with PAH at 70 years of age. She presented a pathogenic variant in KCNA5. Patients 6–9 have SSc-PAH and carry VUS in NOTCH1, CTCFL, CTCFL and TOPBP1, respectively. Conclusions We demonstrate the practical diagnostic utility of genetic testing with a panel in CTD-PAH. The discovery of rare variants in these patients forces us to take a comprehensive approach and accurate genetic counseling. Further research is still necessary to confirm these findings and help to provide a personalized medicine approach to these patients. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This project was founded by project “Bases Genético Moleculares de la Medicina de Precisiόn en la Hipertensiόn Arterial Pulmonar”. Funder: Instituto Carlos III. Ministerio de Economía y Competitividad.

S473 High Prevalence of Esophageal Motility Disorders in Patients With Rheumatic Diseases

Introduction: While esophageal motor dysfunction is known to be associated with systemic sclerosis, the prevalence of esophageal dysmotility in other rheumatic conditions is not well known. The aim of this study was to examine the prevalence of esophageal motility disorders in rheumatic diseases. Methods: In this retrospective cohort study, adults with a diagnosis of a rheumatic disease [rheumatoid arthritis (RA), Sjogren’s syndrome, systemic sclerosis (SS), systemic lupus erythematous (SLE), mixed connective tissue disease (MCTD), idiopathic Raynaud’s phenomenon, and other], who underwent high-resolution esophageal manometry (HREM) were included. Demographics, clinical characteristics, rheumatic diseases and associated therapies, HREM findings, motility disorders per Chicago classification (CCv3.0) criteria and swallow characteristics, were extracted from the medical record. We analyzed the data using descriptive statistics to assess the prevalence and types of esophageal motor disorders amongst patients with known rheumatic conditions. Results: Of 118 patients, 80% were women, and 73% were white (Table). The most common esophageal symptoms were dysphagia (88%), heartburn (81%), and regurgitation (41%). Rheumatic diseases included RA (38%), Raynaud’s (30%), Sjogren’s (22%), SS (19%) and MCTD (11%). On HREM, 53% had an esophageal motility disorder per Chicago classification. Of note, 38% of the sample with a normal barium swallow had an esophageal dysmotility disorder on HREM. Esophageal hypocontractility (including ineffective esophageal motility, absent contractility, and fragmented peristalsis) was diagnosed in 29 patients (25%), achalasia and/or esophagogastric junction outflow obstruction were found in 25 (21%), and esophageal hypercontractility (including diffuse esophageal spasm and jackhammer esophagus) in 8 (7%). These esophageal disorders were found amongst rheumatic diseases including SLE, RA, Sjogren’s, SS, MCTD, psoriatic arthritis and Raynaud’s (Figure). Conclusion: Esophageal motor disorders were found in more than half of patients with rheumatic diseases who underwent HREM, even though many patients previously had a normal barium swallow. HREM should be considered in patients with rheumatic conditions who present with esophageal symptoms.Figure 1.: Disorders of Esophageal Motility by Rheumatologic DiseaseTable 1.: Patient Characteristics and Manometry Findings

NO RHEUM FOR AIR: MIXED CONNECTIVE TISSUE DISEASE PRESENTING AS INTERSTITIAL LUNG FIBROSIS IN A YOUNG WOMAN

TOPIC: Pulmonary Manifestations of Systemic Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Interstitial Lung Disease(ILD) is a serious complication of Mixed Connective Tissue Disorder(MTCD) associated with high morbidity and mortality. We describe an unusual case of a young patient presenting with advanced fibrosis at the time of initial diagnosis of MTCD. CASE PRESENTATION: A 39 year old female presented with dyspnea and dry cough of four months duration that progressively worsened requiring assistance for daily activities. She had associated weight loss, night sweats, diffuse arthralgia without any swelling and right hand stiffening. She denied any fevers, oral/nasal ulcers, vision changes, recent travel, tick bites, skin rash, smoking, household mold or pets. Physical examination revealed bibasilar crackles and mild dusky appearance of fingers. Laboratory investigations showed a normal blood count, elevated d-dimer and inflammatory markers. High Resolution Computerized Tomography(HRCT) Scan of the chest showed diffuse ground glass opacities, subpleural reticulation/scarring, traction bronchiectasis with multiple areas of honeycombing as well as extensive mediastinal lymphadenopathy. The serological panel was significant for high titers of Anti-Nuclear Antibodies(ANA) 1:1280 speckled pattern with low complement C3/C4 level, Rheumatoid Factor(RF) 138, Immunoglobulin G(IgG) 5000, anti-SSA and anti-ribonucleoprotein antibodies 133 and 148 respectively, elevated aldolase and creatinine kinase. Infectious workup was negative. The diffusely positive serology and lymphadenopathy was concerning for lymphoma. However, the excisional lymph node biopsy was negative for malignancy and showed changes consistent with autoimmune etiology. She was diagnosed with MTCD with features of lupus, sjogrens, rheumatoid arthritis, myositis presenting as ILD. Treatment with steroids and hydroxychloroquine was initiated with improvement in her respiratory symptoms. DISCUSSION: ILD in patients with MTCD ranges from being asymptomatic to advanced fibrosis with a high mortality rate.Typically, intial pulmonary function testing shows reduced diffusion capacity which progresses to restrictive pattern in the later stages along with HRCT changes. Our patient, although young, had rapid progression of pulmonary symptoms and was found to have advanced scarring on initial presentation. The diffusely positive serology can overlap with lymphoma and biopsy of lymph node/lung can give definite diagnosis. Since screening guidelines for MTCD-ILD are not clearly established any clinical symptoms should prompt further investigations. Treatment especially steroids during the acute inflammatory phase with ground glass opacities has good prognosis whereas the response is poor once signs of fibrosis develop. CONCLUSIONS: Advanced fibrosis ILD is an uncommon presentation of MTCD in a young patient. Early diagnosis and prompt initiation of therapy especially during the acute phase can prevent further progression of disease. REFERENCE #1: Narula N, Narula T, Mira-Avendano I, Wang B, Abril A. Interstitial lung disease in patients with mixed connective tissue disease: pilot study on predictors of lung involvement. Clin Exp Rheumatol. 2018 Jul-Aug;36(4):648-651. Epub 2018 May 8. PMID: 29745875 REFERENCE #2: Taha R, Feteih M. Pulmonary Manifestations of Connective Tissue Diseases. Skills in Rheumatology. 2020 Aug 29:139–75. doi: 10.1007/978-981-15-8323-0_7. PMCID: PMC7784640.? DISCLOSURES: No relevant relationships by Sana Hyder, source=Web Response No relevant relationships by Evan Nadler, source=Web Response No relevant relationships by Nikola Perosevic, source=Web Response No relevant relationships by Evan Wasserman, source=Web Response

A Case of ANCA-Associated Vasculitis (AAV) in Mixed Connective Tissue Disease (MCTD) Manifesting as Pulmonary Renal Syndrome

A Case of ANCA-Associated Vasculitis (AAV) in Mixed Connective Tissue Disease (MCTD) Manifesting as Pulmonary Renal Syndrome

Rituximab for Membranous Nephropathy in a Patient with Sjögren Syndrome and Mixed-Connective Tissue Disease

Rituximab for Membranous Nephropathy in a Patient with Sjögren Syndrome and Mixed-Connective Tissue Disease

LIGHT CHAIN DEPOSITION DISEASE: WHAT?

TOPIC: Diffuse Lung Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Pulmonary light chain deposition disease (PLDD) is an exceptionally rare diagnosis characterized by the deposition of nonamyloid light chains leading to progressive dyspnea and airflow obstruction. Cystic PLDD demonstrates extensive, bilateral thin-walled cysts. Pathologically, deposition of amorphous eosinophilic material surrounded by giant cell reaction that does not react Congo-Red staining is noted. Lung transplantation can be curative. CASE PRESENTATION: A 38-year-old female with past medical history of mixed connective tissue disease with lupus-like features, and long-term tobacco use was seen in the pulmonology office for worsening dyspnea on exertion and dry cough. CT-Chest showed bilateral and multiple thin-walled cysts. Pulmonary function tests were unremarkable. VEGF-D, Alpha-1-antitrypsin genotype, and HIV were unremarkable. A left upper lobe video assisted thorascopic lung biopsy was performed. Pathology was consistent with pulmonary light chain deposition disease associated with giant cell reaction and patchy lymphocytic infiltrates, without evidence of lymphoproliferative disease. There were amyloid-like nodules that did not react with Congo-Red, and staining for Pulmonary Langerhans Histiocytosis was negative.Further work-up revealed normal cell counts, kidney function, and a normal SPEP and UPEP. Free light chains and Kappa/Lambda ratio were slightly elevated. Bone marrow biopsy, FISH analysis, and karyotype were performed to rule-out a clonal process. These studies were unremarkable. She was referred to a transplant center. DISCUSSION: Light chain deposition disease is a result of monoclonal immunoglobulin deposits, and typically involves the renal, hepatic, and cardiac systems. Isolated pulmonary involvement (PLDD) is exceptionally rare, and is only a recently noted phenomenon. Cystic-predominant PLDD is characterized by extensive, bilaterally thin-walled and progressively expanding cysts that are similar in appearance to lymphangioleiomyomatosis (LAM). Clinically, PLDD is characterized by progressive dyspnea that correlates with worsening obstructive disease on PFT's. Free light chains and the Kappa/Lambda ratio are often elevated without other lab abnormalities. Surgical biopsy should be obtained, particularly if the patient has a tobacco history, as differentiating PLDD from Pulmonary Langerhans is crucial. Pathologically, PLDD is similar to amyloidosis, with amorphous eosinophilic material in cystic walls that stains positive on hematoxylin and eosin. The amorphous material is usually surrounded by giant cell reactions, and material can also be noted in airways and blood vessels. However, there is no reaction in Conge-Red staining. Treatment for PLDD is limited to lung transplantation. CONCLUSIONS: Cystic lung disease often requires surgical biopsy, particularly if rheumatologic or hematologic comorbidities are present. REFERENCE #1: Colombat M, Caudroy S, Lagonotte E, et al. Pathomechanisms of cyst formation in pulmonary light chain deposition disease. Eur Respir J 2008;32:1399-403. 10.1183/09031936.00132007 REFERENCE #2: Khawaja et al. Shedding Light on Cystic Lung Disease. The Expert Clinician. 2019. DISCLOSURES: No relevant relationships by Kaitlyn Musco, source=Web Response No relevant relationships by Dylan Soller, source=Web Response No relevant relationships by Richard Strobel, source=Web Response

S3675 Azithromycin-Induced Acute Liver Injury

Introduction: Idiosyncratic drug-induced liver injury (DILI) is a subtype of drug-induced liver injury that is typically variable in presentation and independent of medication dose or duration. A great number of commonly used medications and herbal supplements have been associated with idiosyncratic drug-induced liver injury. DILI is of clinical significance due to the potential for progression to chronic liver disease or acute liver failure, and may be caused by drugs not commonly associated with liver injury. Case Description/Methods: A 60 year old female was admitted after presenting with sore throat, fever, cough, diarrhea, rash and generalized malaise for 4 days prior to admission. Her past medical history was significant for mixed connective tissue disease, rheumatoid arthritis, and a remote history of alcohol abuse. She was on day two of an outpatient Azithromycin course prescribed for community acquired pneumonia. Physical exam showed diffuse, blanching, maculopapular rash along chest wall and dorsum of her upper extremities. Hepatic panel showed AST 64, ALT 42, Total bilirubin 1.1, and alkaline phosphatase of 68. Liver chemistries peaked during admission to AST 607, ALT 936, Total Bilirubin 20.8, ALP 739. MRCP demonstrated gallbladder adenomyomatosis and multiple simple hepatic cysts. Azithromycin was discontinued, and patient was started on N-acetylcysteine infusion. Workup for viral hepatitis was negative, as were EBV, CMV, HSV and HIV serologies. Immunologic workup showed positive ANA with chromatin of 6.5, SMRNP >8, and RNP of 8. AMA and ASMA were < 1:20. Given rising liver chemistries and history of autoimmune disease, a liver biopsy was obtained and revealed mild chronic hepatitis with minimal periportal activity, moderate bile duct injury with marked cholestasis, pseudoxanthomatous degeneration, and mild anisonucleosis consistent with DILI. Liver chemistries began improving on day 11 of admission. Patient’s maculopapular rash was largely cleared prior to discharge. Discussion: Azithromycin is recognized as a common agent in DILI. In this case, Azithromycin was recognized early as a potential cause of the patient’s worsening liver chemistries. Cessation of the offending agent will resolve most cases of DILI. This case demonstrates how a commonly prescribed medication may cause DILI with risk of progression to acute liver failure. Medications not typically associated with hepatic injury should be assessed when considering DILI.Figure 1.: Portal area with reactive atypia in bile ducts consistent with cholestasis. Mixed inflammatory infiltrate surrounding portal area.

Detection of microvascular changes in systemic sclerosis and other rheumatic diseases.

Morphological and functional analysis of the microcirculation are objective outcome measures that are recommended for use in the presence of clinical signs of altered peripheral blood flow (such as Raynaud phenomenon), which can occur in systemic sclerosis (SSc) and other autoimmune rheumatic diseases. Several advanced non-invasive tools are available for monitoring the microcirculation, including nailfold videocapillaroscopy, which is the best-studied and most commonly used method for distinguishing and quantifying microvascular morphological alterations in SSc. Nailfold videocapillaroscopy can also be used alongside laser Doppler techniques to assist in the early diagnosis and follow-up of patients with dermatomyositis or mixed connective tissue disease. Power Doppler ultrasonography, which has been used for many years to evaluate the vascularity of synovial tissue in rheumatoid arthritis, is another promising tool for the analysis of skin and nailbed capillary perfusion in other autoimmune rheumatic diseases. Other emerging methods include raster-scanning optoacoustic mesoscopy, which offers non-invasive high-resolution 3D visualization of capillaries and has been tested in psoriatic arthritis and SSc. The principle functions and operative characteristics of several non-invasive tools for analysing microvascular changes are outlined in this Review, and the clinical roles of validated or tested imaging methods are discussed for autoimmune rheumatic diseases.

Factors Associated With Variation in Pediatric Systemic Lupus Erythematosus Care Delivery.

ObjectivePatients with pediatric systemic lupus erythematosus (pSLE) and mixed connective tissue disease (MCTD) receive only a fraction of recommended care. Using published quality indicators and guidelines, we developed a 13‐item pediatric lupus care index (p‐LuCI) to quantify the proportion of recommended clinical evaluations and comorbidity prevention interventions completed and the timeliness of follow‐up. Our objective was to assess baseline index performance and identify sources of p‐LuCI variation.MethodsWe performed a cross‐sectional study in patients with pSLE or MCTD and analyzed the performance of individual p‐LuCI process metrics and calculated the overall p‐LuCI score. We identified factors associated with the p‐LuCI using multivariable linear regression with clustering by provider.ResultsFor 110 patients (99 with pSLE and 11 with MCTD), the median p‐LuCI was 65.2% (interquartile range: 9.1‐92.3%). Component performance ranged from 27.3% (on‐time scheduling) to 95.4% (steroid‐sparing treatment). Patients with p‐LuCI scores above the median had higher scores across all 13 components. Higher p‐LuCI scores were independently associated with disease‐modifying antirheumatic drug use (β = 14.3 [95% confidence interval (CI), 1.5‐27.2]), nephritis (β = 10.4 [95% CI, 5.1‐15.8]), higher provider pSLE/MCTD volume (β = 3.1 [95% CI, 1.9‐4.2] per patient), assignment to rheumatology fellow trainee (β = 36.3 [95% CI, 17.3‐55.2]), and disease duration of less than 1 year (β = 12.6 [95% CI, 0.7‐24.5]). Differences by race, ethnicity, and/or insurance were not observed.ConclusionUsing an index of recommended pSLE care metrics, we identified significant variation in performance by disease, treatment, and provider characteristics. The p‐LuCI may be useful to assess care quality at the patient, provider, and practice levels and to identify areas in need of greater standardization.

A rare variant of chronic inflammatory demyelinating polyneuropathy with autonomic dysfunction

A young hypothyroid female with history of chronic inflammatory small joint arthralgias presenting with distal sensory motor symptoms of 8 weeks duration and prominent disturbances of bladder sensations was found to have symmetric motor and distal large fibre sensory loss and blunting of perineal sensations. On evaluation was found to have a normal nerve conduction study at presentation and imaging showing hypertrophic and enhancing cervical and lumbosacral nerve roots with a positive marker of mixed connective tissue disorder on ANA profile, fitting into a diagnosis of Chronic Immune Sensorimotor Polyradiculopathy in the background of a connective tissue disorder.

Elevated IgG Antibody to Aluminum Bound to Human Serum Albumin in Patients with Crohn’s, Celiac and Alzheimer’s Disease

Aluminum is in our water and food, and is used as an adjuvant in vaccines. About 40% of the ingested dose accumulates within the intestinal mucosa, making the gut the main target of inflammation and autoimmunity; about 1% accumulates in the skeletal system and brain, inducing the cross-linking of amyloid-β-42 peptide and the formation of amyloid aggregates associated with Alzheimer’s disease. To examine whether the accumulation of aluminum in the gut and brain tissues results in neoantigen formation, we bound aluminum compounds to human serum albumin. We used ELISA to measure IgG antibody in 94 different sera from healthy controls and 47 sera from each group of patients: anti-Saccharomyces cerevisiae antibody-positive (Crohn’s), and positive for deamidated α-gliadin and transglutaminase-2 IgA antibodies (celiac disease), autoimmune disorders associated with intestinal tissue antigens. Because earlier studies have shown that aluminum exposure is linked to Alzheimer’s disease etiology, and high aluminum content is detected in Alzheimer’s patients’ brain tissue, we also measured aluminum antibody in the blood of these patients. Additionally, we measured aluminum antibody in the sera of mixed connective tissue disease patients who were positive for antinuclear antibodies, and used them as disease controls. We found significant IgG antibody elevation against all three aluminum compounds in the sera of patients with Crohn’s, celiac and Alzheimer’s disease, but not in patients with mixed connective tissue disease. We concluded that aluminum ingestion and absorption from the GI tract and brain may contribute to Crohn’s, celiac and Alzheimer’s disease, but not to mixed connective tissue disease.

Poster Presentations

Background: The workload at rheumatology clinics have been growing relentlessly and an audit on new referrals helps to identify referral behavior of primary care doctors and improvement can be done by providing further training. Objective: To audit on new referral cases to rheumatology clinic during Covid-19 pandemic 2020 and to identify new cases with misdiagnosis for future training purpose. Methods: This was a retrospective study. The electronic medical records of all new referral to rheumatology clinic Hospital Sultan Ismail from 1 st January 2020 to 28 th February 2021 were reviewed. The variety of new cases, reason of referral and final diagnoses were identified and analyzed. Results: There were total of 462 new cases referred throughout the 14 months during Covid-19 pandemic. Majority of them are diagnosed to have rheumatoid arthritis (RA, 115/462) followed by systemic lupus erythematosus (SLE, 93/462), psoriatic arthritis (PSA,82/462), gout (26/462), osteoarthritis (23/462), soft tissue rheumatism (14/462), systemic sclerosis (SSc, 11/462), fibromyalgia (8/462), ankylosing spondylitis (AS, 8/462), sjogren syndrome (8/462), vasculitis (7/462), mixed connective tissue disease (MCTD, 7/462) and miscellaneous (23/462). 17 out of the new cases were diagnosed as unlikely rheumatic diseases. There were 20 pending cases awaiting final diagnosis. 96 of the referrals were identified as misdiagnosis with the highest as nodal osteoarthritis (18/96) followed by unlikely rheumatic disease (17/96), soft tissue rheumatism (14/96), RA (12/96), PSA (9/96), gout (4/96), sjogren syndrome (4/96), fibromyalgia (3/96), SLE (3/96), polymyositis (2/96), AS (2/96) and others (8/96 : DISH, hypermobility syndrome, RS3PE syndrome, degenerative disc disease, idiopathic uveitis, graft versus host disease, JIA, MCTD and traumatic arthritis). Conclusion: Nodal osteoarthritis and soft tissue rheumatism can be great mimicker for inflammatory arthritis and if wrongly diagnosed will induce unnessary anxiety or wrong treatment. More training are needed to improve clinical skills amongst primary care doctors.

Impact of a new coronavirus infection on the clinical course of immunoinflammatory rheumatic diseases

BACKGROUND: The COVID-19 pandemic poses a particular threat to patients suffering from immunoinflammatory rheumatic diseases. New coronavirus infection has been found to be accompanied by the development of a wide range of extrapulmonary clinical and laboratory manifestations, which are characteristic of a number of immunoinflammatory rheumatic diseases.&#x0D; AIM: To evaluate the features of the clinical course of immunoinflammatory rheumatic diseases in patients who underwent new coronavirus infection.&#x0D; MATERIALS AND METHODS: The clinical course of immunoinflammatory rheumatic diseases was analyzed in 324 patients who underwent new coronavirus infection from March 2020 to February 2021 and were treated at the Clinical Rheumatology Hospital No. 25, Saint Petersburg, for exacerbation of the underlying disease.&#x0D; RESULTS: Analysis showed that the risk factors for severe new coronavirus infection in patients with immunoinflammatory rheumatic diseases were: age over 60, comorbidities, use of prednisolone in a dose greater than 12,5 mg, and ESR values 40 mm/hour before the development of new coronavirus infection. There was no effect of immunosuppressive and biological therapy on the severity of the course of viral infection. There was no effect of immunosuppressive therapy and biological therapy on the severity of the course of viral infection in patients with immunoinflammatory rheumatic diseases. The development of the postinfectious syndrome was observed in 1/4 of patients, which was characterized by the formation of postinfectious arthritis in 3,6% of patients, transformation of undifferentiated arthritis into various rheumatic diseases in 49% of patients (more often into early rheumatoid arthritis), as well as exacerbation of the underlying disease in 83,4% of patients with an advanced stage of rheumatoid arthritis. In patients with mixed connective tissue disease, there was a significant increase in immunologic activity due to antinuclear factor (up to a maximum of 1:163 840). Clinical cases of the development of arthritis associated with viral infection and the debut of rheumatoid arthritis after an new coronavirus infection are presented.&#x0D; CONCLUSIONS: New coronavirus infection in the cohort of patients with immunoinflammatory rheumatic diseases observed in the Clinical Rheumatology Hospital No. 25, Saint Petersburg, proceeded in the variant of medium severity in half of patients, initiated the development of lung lesions in 68,6% of patients, arthritis associated with viral infection in 3,6% of patients, immunoinflammatory rheumatic diseases which transformed from undifferentiated arthritis in 49% of cases and exacerbation of the main disease in an overwhelming number of patients. Patients with immunoinflammatory rheumatic diseases have a high risk of adverse outcome of new coronavirus infection, especially in cases of unstable course of the disease or exacerbation of this group of diseases.

Nailfold capillaroscopy in systemic diseases: short overview for internal medicine.

Nailfold capillaroscopy (NFC) is now one of the main imaging tools in systemic sclerosis and imposed over time as an easy, non-invasive method for the nailfold microvascular bed assessment. In qualitative NFC normal pattern is characterized by homogeneous, parallel fashion arrangement of the last capillaries row as well as by capillaries with hairpin or non-specific variations like tortuous and/ or crossing shape. Nailfold capillaroscopy is strongly recommended for evaluation of all patients with Raynaud phenomenon. Appearance of giant capillaries is chronologically the first relevant finding for scleroderma spectrum disorders development (systemic sclerosis, dermatomyositis, undifferentiated and mixed connective tissue disease). Collapses of the giant loops generate microhemorrhages and further capillary loss with subsequent hypoxia, and neoangiogenesis seen as ramified/ bushy capillaries. Nailfold capillaroscopy is indicated especially in systemic sclerosis, being also included in the classification criteria. Based on these major NFC pathologic findings (giant capillaries, microhemorrhages, avascularity and neoangiogenesis), three evolutive stages were described in systemic sclerosis, namely the early, active, and late scleroderma pattern. In other connective tissue diseases than those scleroderma-related, like systemic lupus erythematosus, psoriatic arthritis, or antiphospholipid syndrome, the interest for capillaroscopy is growing, but the attempts of defining specific characteristics failed until now. Besides qualitative NFC, semiquantitative and quantitative capillaroscopic assessments were proposed for more accurate evaluation. Lately, automated systems are under development. There is still need of more studies to sustain the nailfold capillaroscopy validity as diagnostic and prognostic test.

Clinical profile of cutaneous manifestations of connective tissue diseases in North-East India

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Connective tissue diseases (CTDs) are a heterogeneous group of autoimmune disorders having overlapping clinical features. Skin is often involved and it may be the earliest sign of the disease. This study highlighted the various cutaneous manifestations of common CTDs.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; A hospital-based cross-sectional study was carried out for a period of two years in 83 patients with CTDs in dermatology OPD, RIMS, Imphal. Detailed history taking, examination and relevant serological tests were performed.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; The mean age was 39.78±17.29 years with female to male ratio of 4.5:1. Majority of the patients had lupus erythematosus (LE) (N=45) followed by systemic sclerosis (SSc) (N=25), rheumatoid arthritis (RA) (N=6), mixed connective tissue disease (MCTD) (N=4) and morphea (N=3). The most common presentation was raised skin lesions (45.8%) followed by Raynaud’s phenomenon (36.1%), photosensitivity (27.7%), skin tightness (26.5%) and joint pain (19.3%). Among LE patients, chronic cutaneous lupus erythematosus (CCLE) was the commonest variant and localised discoid lupus erythematosus (DLE) (22.9%) was the commonest presentation followed by malar rash and annular subacute lupus erythematosus (SCLE). Skin induration, microstomia and sclerodactyly were seen in most patients of SSc. Antinuclear antibodies were positive in 89.1% of patients. Anti-dsDNA and anti-Sm antibodies were positive in 62.2% and 33.3% of LE patients, anti-Scl 70 antibody was positive in 68% of SSc patients.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; CTDs are rare but potentially life-threatening. Proper understanding of the spectrum of cutaneous manifestations of CTDs is therefore necessary for early diagnosis and efficient management.&lt;/p&gt;

Relationship between type of skin lesions and nailfold capillaroscopy pattern in mixed connective tissue disease

IntroductionMixed connective tissue disease (MCTD) is a rare disease with clinical picture consisted of multiple organ manifestations, including skin changes resembling systemic lupus erythematosus (SLE), systemic sclerosis (SSc), or dermatomyositis (DM). On the background of these manifestations are microvascular changes — alteration of endothelial function and impairment of endothelial progenitor cell. Nailfold capillaroscopy (NFC) is a simple, non-invasive technique for investigating microvascular involvement in rheumatic diseases.ObjectivesTo describe the relationship between type of skin lesions and NFC pattern in MCTD patients.MethodsWe analyzed the clinical picture and NFC patterns in 79 patients with MCTD. The NFC changes were classified into Normal, “Early,” “Active,” and “Late” scleroderma-like patterns (SD-like pattern) based on Cutolo classification.In all patients, subjective and physical examinations were carried out, specifically the occurrence of skin lesions in the course of MCTD was assessed (systemic sclerosis-like (Ssc-like), systemic lupus erythematosus-like (SLE-like), dermatomysitis-like (DM-like)).ResultsSkin changes were present in 64 (81%) patients, involving 43 (54%) SLE-like, 48 (61%) SSc-like, and 4 (5.1%) DM-like. NFC changes were observed in a total of 55 (69.6 %) patients with predominance of the “Early” pattern — 41 (51.9 %) patients. According to skin change phenotypes, NFC changes were observed in 31 (72%) patients with SLE-like and in 32 (66.7%) patients with SSc-like skin phenotypes. The “early” pattern predominated in both group.ConclusionsWe did not find any correlation between NFC pattern and the type skin changes.Key Points• The study did not show a correlation between the presence and absence of skin lesions and NFC pattern.• Scleroderma-like patterns were found in over 60% of patients with mixed connective tissue disease.• The “early” pattern is dominant regardless of the occurrence or absence of skin lesions in patients with MCTD.• Skin lesions, regardless of their type (SLE or SSc), do not correlate with type of lesion found in the NFC examination.

26441 Palisaded and neutrophilic granulomatous dermatitis in a child

Palisaded and neutrophilic granulomatous dermatitis (PNGD) is a rare entity that occurs in conjunction with autoimmune diseases as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), juvenile idiopathic arthritis, sarcoidosis, and mixed connective tissue disease. Autoimmune diseases in pediatric patients can be challenging to diagnose. We present the first pediatric case of PNGD associated with SLE. A 10-year-old girl with a history of atopic dermatitis, asthma, and a family history of SLE and RA presented to the ED with palpable purpura of the lower extremities and arthralgias and was diagnosed clinically with Henoch- Schoenlein purpura.

Interpretation of Anti-Nuclear Antibody Tests

Anti-nuclear antibodies (ANAs) are autoantibodies against nuclear substances or other cellular components. ANA tests are used in the diagnostic process to screen patients with suspected rheumatic or autoimmune diseases. ANA-associated diseases are characterized by a high titer of antinuclear antibodies and include systemic lupus erythematosus, systemic sclerosis, and mixed connective tissue diseases. ANA test results must be cautiously interpreted as they can be positive not only in infections and oncological diseases but also for the healthy general population. The ANA test mainly uses the indirect immunofluorescence test, and the results are expressed in terms of the final titer and pattern. The ANA test can increase diagnostic value when used in conjunction with the evaluation of disease-related clinical symptoms.

Connective Tissue Disease Associated Myocarditis on Computed Tomography Coronary Angiogram

A 27-year-old lady presented to the emergency department with an acute episode of chest pain, on the background of a 6-year history of poorly controlled mixed connective tissue disease manifested by gastro-oesophageal reflux disease, digital ulceration, Raynaud’s phenomenon and interstitial lung disease (forced vital capacity 42% and diffusion capacity for carbon monoxide 27% of predicted). There were no preceding infective symptoms or fevers. Electrocardiogram demonstrated isolated non-dynamic q waves in aVL.

Suitability for e-health of non-pharmacological interventions in connective tissue diseases: scoping review with a descriptive analysis

ObjectiveNon-pharmacological interventions support patients with connective tissue diseases to better cope with and self-manage their diseases. This study aimed to map existing evidence on non-pharmacological interventions in patients with systemic...