Mixed Connective Tissue Disease Research Articles

Синдром Шарпа: от базисной противовоспалительной терапии к генно-инженерным биологическим препаратам

This article presents a clinical case of a patient with a mixed connective tissue disease. The clinical picture in the debut was polymorphic, the patient had arthritis, skin lesions, general inflammation, myopathy, Raynaud’s syndrome, dysphagia, angio-neurotic edema. The immunological panel reflected the presence of antibodies characteristic of autoimmune diseases (antinuclear antibodies, antibodies to ribonucleoprotein, antimitochondrial antibodies, antibodies to cytoplasmic antigen SS-B). Glucocorticosteroids (GCS), immunosuppressive drugs (metatrexate, sulfasalazine, hydroxychloroquine, azathioprine) were used as starting therapy, but the disease progressed. Pulse therapy of GCS and plasmapheresis did not give a positive result. We used Rituximab, because the pathogenesis of the disease was characterized by the activation of B-cells. Currently, two infusions have been performed, positive dynamics has been noted. Thus, the therapy of mixed connective tissue disease creates many diagnostic and therapeutic problems in clinical practice.

Очаговые образования в легких у ревматологических больных

Focal pulmonary masses in patients suffering from rheumatological diseases cause difficulties in conducting differential diagnosis with neoplastic and infectious processes, primarily with tuberculosis. In many cases, these masses are asymptomatic, being an accidental finding during routine examinations. Focal pulmonary masses can cause various comorbidities, such as hemoptysis and pneumothorax. In rheumatic diseases, the frequency of such masses ranges from 1 to 30%, as well as their incorrect diagnosis commonly leads to a wrong therapy choice. The article presents two clinical cases concerning the detection of focal pulmonary masses, which were observed during the visit to a rheumatologist: in patients with rheumatoid arthritis and with mixed connective tissue disease. Both cases are illustrated with follow-up computer tomography data. The presented clinical cases demonstrate various manifestations that a radiotherapist may encounter in this patient cohort: nodular masses, cavitation, infiltration, etc. Only a combination of clinical, anamnestic and laboratory data, along with X-ray data, allows to establish the correct diagnosis, commonly with case follow-up of the patient. KEYWORDS: focal pulmonary masses, rheumatoid arthritis, lung damage, rheumatoid nodules, tuberculosis, systemic connective tissue diseases. FOR CITATION: Teplyakova O.V., Shai S.E., Yakovleva Yu.V., Leshchenko I.V., Sarapulova A.V., Kolmakova O.V. Focal pulmonary masses in patients with rheumatological pathologies. Russian Medical Inquiry. 2023;7(7):467–471 (in Russ.). DOI: 10.32364/2587-6821-2023-7-7-10.

Dermoscopy of Crusted Scabies: Revisiting the New and Old Signs.

Dear Editor, Scabies is a common ectoparasitosis in India caused by the eight-legged mite, Sarcoptes scabiei var. hominis. Crusted scabies occurs predominantly in immunosuppressed individuals and presents with diffuse hyperkeratotic scales, crusts, or even erythroderma. It is highly contagious because crusted scabies patient may harbor millions of mites on their body in contrast to 10–12 mites found in classical scabies.[1] It may often be misdiagnosed due to the absence of typical nocturnal pruritus and atypical clinical presentations. Dermoscopy is extremely useful in the diagnosis of this uncommon variant of the common parasitosis. We present a case of crusted scabies showing the classical and newly described dermoscopic signs. A 38-year-old female, case of mixed connective tissue disease, on treatment with daily prednisolone (10 mg) along with azathioprine 100 mg and admitted to the medical ward due to cirrhosis and ascites, presented with skin rash of 1 month duration. On clinical examination, generalized erythematous rash with scaly papules and crusting was seen along with multiple dry crusted hyperkeratotic plaques (showing wet sand appearance) predominantly over the bony prominences, trunk, limbs, and scalp [Figure 1].Figure 1: (a) multiple dry crusted hyperkeratotic plaques with erythematous scaly papules and crusting. (b) scaly crusted plaque involving the scalp. (c) “wet sandpaper” appearance of crusted plaquesDermoscopic examination showed numerous burrows in a “noodle-like pattern” with multiple brownish triangular structures (delta glider sign) [Figure 2a]. These burrows showed the “gray-edged line sign”, which is a gray-brownish line on the outer edges of the burrow (Figure 2b) and wake sign [Figure 3]. Potassium hydroxide (KOH) mount of scales revealed numerous scabies mites and eggs [Figure 4]. On histopathology, hyperkeratosis, parakeratosis, acanthosis, and scabies mites in the stratum corneum were seen [Figure 5]. The patient was advised topical application of 5% permethrin cream every third day for 2 weeks along with oral ivermectin 12 mg to be taken on day 1, 2, and 8.Figure 2: Dermoscopy showing (a) “noodle-like pattern” consisting of accumulation of several curvilinear burrows displaying the “gray-edged line sign” [blue arrowhead (in fig b also)]. (Heine delta NC1, polarized, 10×) (b) brown-colored triangular structure (yellow arrow) that simulates a delta glider trailed by the jet contrail (inset). (Dinolite Videodermoscope polarized non-contact 50x)Figure 3: Wake sign—the burrow (black lines) and the wake-shaped scale (dashed line) together presenting a Y-shaped lesion. (Higher magnification Dinolite Videodermoscope polarized non-contact 50×)Figure 4: Potassium hydroxide mount showing numerous mites (red arrows), eggs (blue arrowhead), and scybala (yellow circles)Figure 5: Multiple scabies mites (black arrow) in stratum corneum (H & E 10x)Burrows are the pathognomonic lesions of scabies; however, they are difficult to be seen on naked eyes, especially in brown skin and in patients with excoriations. Various eponymous dermoscopic signs of scabies include “Delta sign”/“hang glider sign”/“triangle sign” (brownish triangular structures in the shape of hang glider) corresponding to the head and anterior legs of the mite and “Jetliner with contrail sign” (where the mite body appears translucent and air-filled burrow resembles a jetliner with contrail).[2] “Noodle pattern” or “millipede-like structure” (showing numerous burrows) as seen in our case is a characteristic dermoscopy sign of crusted scabies.[3] “Gray-edged line sign” on dermoscopy is a recently described sign where the dark line is often seen on the outer wall of the curved burrow and is supposed to form mainly due to the melanin containing fecal material of the mite, which gets deposited on the outer wall by the tail end of the mite as it crosses the curved burrow.[4] “Wake sign” is described as a pattern of scale reminiscent of the “wake” left on the water surface by a moving object.[5] All the dermoscopic signs were seen in our case. Thus dermoscopy is an extremely useful, rapid, and noninvasive in vivo tool for the diagnosis of crusted scabies. This case is interesting as the dermoscopic signs of noodle pattern and gray-edged line sign have not been previously described in Indian patients. Declaration of patients consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

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.

Severe Raynaud in a young female with Mixed Connective Tissue Disorder (MCTD)

Raynaud phenomenon is clinically manifested by sharply demarcated colour changes of the skin of the digits due to abnormal vasoconstriction of digital arteries and cutaneous arterioles. Raynaud can be primary or secondary. Here we present a young female patient who presented with Raynaud, inflammatory type of small joint pain and proximal muscle weakness. She was diagnosed to have mixed connective tissue disease after extensive evaluation.

CLINICAL SPECTRUM AND IMMUNOLOGICAL PROFILE OF PATIENTS WITH MIXED CONNECTIVE TISSUE DISEASE PRESENTING IN A TERTIARY CARE HOSPITAL

This study investigated the clinical spectrum and immunological profile of mixed connective tissue disease (MCTD) patients in a tertiary care hospital in Pakistan. This study was conducted in the Department of Rheumatology at Fatima Memorial Hospital in Lahore for six months from March to August 2021. A clinical diagnosis was made based on the Kasukawa criteria. In this study, 45 patients who fulfilled the MCTD criteria were enrolled. Their clinical presentation and laboratory findings were studied, and disease characteristics and demographics were recorded using a self-designed proforma. The analysis of the collected data was done using SPSS version 25.0. Of 45 patients, 42 were females, and 3 were males, with a mean age of 33. The most common clinical features studied were Raynaud phenomenon (found in 36 (80%) patients), sclerodactyly (in 12 (26.7%) patients), digital ulcers (in 12 (26.7%) patients), puffy hands (in 14 (31.1%) patients), skin tightness (in 21 (46.7%) patients), oral ulcers (in 8 (29.6%) patients), rash over face (in 13(28.9%) patients), rash over other areas than face (in 16 (35.6%) patients), calcinosis (in 2(4.4%) patients), diffuse hair loss (in 10(37%) patients), arthritis (in 21(46.7%) patients), proximal muscle weakness (in 9 (20%) patients), dryness of eyes and mouth (in 13 (48.1%) patients), and esophageal dysmotility (in 9 (20%) patients). Pulmonary HTN was found in 5(11.1%) patients, ILD with NSIP pattern in 7(13.7%) patients, and UIP pattern on HRCT chest was found in 2(4.4%) patients. Several antibodies were found in patients, including U1RNP in 24(53.3%) patients, ANA in 33(73.3%) patients, AntiScl 70 in 9(20%) patients, Anti-centromere in 2(4.4%) patients, Anti jo1 in 1(3.7%) patient, Anti-dsDNA in 14(31.1%) patients, LAC in 1(3.7%) patient, ACL in 1(3.7%) patient, Anti Ro in 14 (31.1%) patients, and Anti La in 2 (7.4%) patients. S/CPK was raised in 10(22.2%) patients. MCTD is an immune-mediated disorder affecting multiple systemic organs with shared features of three autoimmune disorders: scleroderma, systemic lupus erythematosus (SLE), and polymyositis. Sometimes, it can convert to a full autoimmune rheumatological condition, so if it is treated early, future complications can be prevented. Autoimmune rheumatological condition, so if it is treated early, future complications can be prevented.

A Case of Mixed Connective Tissue Disorder in a Young Female

We present a case of Mixed connective tissue disorder presented in our institute. Mixed connective tissue disease (MCTD), a rare entity in rheumatology.

Population-based prevalence and incidence estimates of mixed connective tissue disease from the Manhattan Lupus Surveillance Program.

Epidemiological data for MCTD are limited. Leveraging data from the Manhattan Lupus Surveillance Program (MLSP), a racially/ethnically diverse population-based registry of cases with SLE and related diseases including MCTD, we provide estimates of the prevalence and incidence of MCTD. MLSP cases were identified from rheumatologists, hospitals and population databases using a variety of International Classification of Diseases, Ninth Revision codes. MCTD was defined as one of the following: fulfilment of our modified Alarcon-Segovia and Kahn criteria, which required a positive RNP antibody and the presence of synovitis, myositis and RP; a diagnosis of MCTD and no other diagnosis of another CTD; and a diagnosis of MCTD regardless of another CTD diagnosis. Overall, 258 (7.7%) cases met a definition of MCTD. Using our modified Alarcon-Segovia and Kahn criteria for MCTD, the age-adjusted prevalence was 1.28 (95% CI 0.72, 2.09) per 100 000. Using our definition of a diagnosis of MCTD and no other diagnosis of another CTD yielded an age-adjusted prevalence and incidence of MCTD of 2.98 (95% CI 2.10, 4.11) per 100 000 and 0.39 (95% CI 0.22, 0.64) per 100 000, respectively. The age-adjusted prevalence and incidence were highest using a diagnosis of MCTD regardless of other CTD diagnoses and were 16.22 (95% CI 14.00, 18.43) per 100 000 and 1.90 (95% CI 1.49, 2.39) per 100 000, respectively. The MLSP provided estimates for the prevalence and incidence of MCTD in a diverse population. The variation in estimates using different case definitions is reflective of the challenge of defining MCTD in epidemiologic studies.

Delphi-Based Consensus on Interstitial Lung Disease Screening in Patients with Connective Tissue Diseases (Croatian National-Based Study).

The aim of this study was to develop a Croatian Delphi-based expert consensus for screening interstitial lung disease (ILD) associated with connective tissue disease (CTD). A systematic literature review was conducted on risk factors for the development of ILD, prevalence and incidence of ILD, diagnostic and screening methods for ILD, and prognosis of ILD in idiopathic inflammatory myopathy (IIM), mixed connective tissue disease (MCTD), primary Sjögren's syndrome (pSS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc) were performed. Based on the evidence found, experts developed questionnaires for screening and monitoring ILD in each CTD, which were provided via an online survey. Following the electronic survey, two screening algorithms were developed based on the consensus opinions. The detection strategy for ILD included high-resolution computed tomography (HRCT) in addition to pulmonary function testing for IIM, MCTD, and SSc. and pulmonary function testing for newly diagnosed pSS, RA and SLE. However, in patients with identified risk factors for ILD HRCT, these tests should also be performed. A screening strategy for early identification of patients with various CTD-ILD was first developed by a multidisciplinary team of rheumatologists, pulmonologists, and radiologists to identify early CTD patients at risk of ILD, a severe extra-articular manifestation of CTD.

Complicated Neurotrophic Corneal Ulcer in a Patient with Multiple Autoimmune Disorders

Neurotrophic keratitis is a rare degenerative corneal disease caused by impairment of trigeminal nerve innervation. This can lead to profound vision loss from corneal epithelial breakdown, ulceration, and in severe cases, perforation. This case report describes a 60-year-old male patient with multiple autoimmune diseases including Sjogren’s syndrome, Raynaud’s disorder, mixed connective tissue disorder, and Graves’ disease who presented with a complaint of blurred vision in his left eye due to a corneal ulcer. A careful analysis of the patient’s case history was crucial to arriving at the final diagnosis of a neurotrophic corneal ulcer. Although treated aggressively with topical antibiotics, artificial tears, and vitamin C, the corneal ulcer perforated 10 days later. Optometrists who choose to manage neurotrophic keratitis should be familiar with the potential complications and know when referral is needed. CE Notification This article is available as a COPE accredited CE course. You may take this course for 1-hour credit. Read the article and take the qualifying test to earn your credit. Click here to Enroll (https://www.crojournal.com/complicated-neurotrophic-corneal-ulcer-in-a-patient-with-multiple-autoimmune-disorders) Please check COPE course expiry date prior to enrollment. The COPE course test must be taken before the course expiry date.

ANA-specific antibodies, ANA patterns, anti-ds-DNA results, and clinical diagnosis: a laboratory and clinical audit.

The diagnosis of systemic autoimmune diseases (SAID) is challenging, due to overlapping features with other non-immune disorders. Anti-nuclear antibodies (ANA)/anti-cellular antibodies are the sensitive screening tests but anti-double-stranded-deoxyribonucleic acid-antibody (anti-ds-DNA) and ANA-specific antibodies are specific for SAID. We aimed to look at ANA-specific antibodies in our patients and correlated them with ANA patterns, anti-ds-DNA, and clinical diagnosis for proper interpretation and better patient management cost-effectively. A retrospective data analysis of 641 patients was done (1st of February 2019 to 31st of July 2021) who were tested for ANA-specific antibodies at the Immunology Department of Indus Hospital and Health Network. ANA and anti-ds-DNA results and clinical diagnosis were also analyzed for ANA-specific antibody-positive patients. Descriptive data were presented in mean ± standard deviation and frequency percentages whereas inferential data were analyzed with a chi-square test for association between ANA-specific antibodies status, ANA, anti-ds-DNA, and clinical features. ANA-specific antibodies test revealed positivity for at least one autoantibody in 245 (38.2%) patients. Of these, ANA was tested in 206 patients reactive for ANA-specific antibodies and found positive in 195 (95%) as compared to negative (< 0.001). Speckled and homogenous were predominant ANA patterns in ANA-specific antibody-positives (56% and 42% respectively). Multiple ANA patterns were found in 18 patients most commonly with systemic lupus erythematosus (SLE) and mixed connective tissue disorder (MCTD). Anti-SSA were the most common ANA-specific antibodies (50%) and were mostly found in sera with speckled (61/97) and homogenous (38/97) patterns and associated mostly with SLE (48%) and Sjogren's syndrome (86%). Among ANA-negative patients, anti-SSA were the most common antibodies (n = 5). Anti-ds-DNA was found in 66% of SLE patients along with another ANA-specific antibody. This study showed that testing for ANA-specific antibodies cannot be gated on ANA patterns. Also, there is a redundancy of these antibodies with various clinical diagnoses. Moreover, they are useful in making a diagnosis in ANA-negative patients as well with clinical suspicion.

Esophageal Stricture Recalcitrant to Repeated Dilation in Complex Rheumatological Disease

We report a case of severe refractory esophageal strictures in the setting of rheumatological disease found to be secondary to isolated esophageal autoimmune bullous disease. She had a history of Sjogren syndrome and esophageal strictures with many previous dilations. After rheumatological workup, she was diagnosed with mixed connective tissue disease. Biopsy showed complement and immunoglobulin G deposition in the basement membrane consistent with bullous lupus or bullous pemphigoid. She had no cutaneous bullae and was diagnosed with isolated esophageal bullous disease. She required multiple dilatations over several months of treatment and was started on mycophenolate mofetil with clinical improvement.

Increased Nuchal Translucency Without Aneuploidy in a Fetus: Abnormal Postnatal Radiograph and a Novel Mutation.

Increased Nuchal Translucency Without Aneuploidy in a Fetus: Abnormal Postnatal Radiograph and a Novel Mutation.

Pulmonary hypertension in connective tissue diseases: epidemiology, pathogenesis, and treatment.

Pulmonary hypertension (PH) is a clinical condition characterized by increased pulmonary arterial pressure arising from a heterogeneous range of diseases that has a deteriorating effect on the quality of life and may cause early mortality if left untreated. Connective tissue disorders (CTD)-associated PH is the second most common cause of pulmonary arterial hypertension (PAH), after the idiopathic form, categorized as group I. Systemic scleroderma (SSc) accounts for 75% of CTD-associated PH cases. Although SSc ranks first place for CTD-associated PH, SSc is followed by systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD), having a lesser frequency of PH occurrence, while it occurs as a rare complication in cases with rheumatoid arthritis (RA) and inflammatory myositis. PH may also occur during non-SSc CTDs and even other rheumatic diseases, including Behcet's disease and adult-onset Still's disease, albeit to a lesser extent. The prognosis of CTD-associated PH is worse than the other forms of PH. Although, as in idiopathic pulmonary arterial hypertension (IPAH), the mechanism of CTD-related PH is associated with an increase in vasoconstrictors like endothelin-1 and a decrease in vasodilators like prostacyclin and nitric oxide production, inflammation, and autoimmune mechanisms also play a role in the development and progression of PH. This may lead to the involvement of more than one mechanism in CTD-associated PH. Knowing which mechanism is dominant is very important in determining the treatment option. This review will primarily focus on the epidemiology, risk factors, and prognosis of PH that develops during rheumatic diseases; the pathogenesis and treatment will be briefly mentioned in light of the newly published guidelines. Key Points • Pulmonary arterial hypertension (PAH) associated with connective tissue disease (CTD) in Western countries is the second most common type of PAH after idiopathic PAH (IPAH). • CTD-PH can be seen most often in systemic scleroderma (SSc), less in systemic lupus erythematosus (SLE), mixed CTD (MCTD), and rarely in other CTDs. • While current guidelines recommend annual transthoracic echocardiography as a screening test for asymptomatic SSc patients, screening for PH is not advised in the absence of symptoms suggestive of PH in other CTDs. • CTD-PH treatment can be divided into specific vasodilator PH treatments and immunosuppressive therapy. Current treatment guidelines recommend the same treatment algorithm for patients with CTD-associated PH as for patients with IPAH. Several case series have shown the beneficial effect of immunosuppressive agents in patients with SLE-PH and MCTD-PH.

Adherence with mycophenolate mofetil in patients with autoimmune inflammatory rheumatic diseases in coventry: Signs of progress but challenges remain.

The study investigated adherence with MMF treatment among patients attending rheumatology clinics at University Hospitals Coventry and Warwickshire NHS Trust (UHCW) with Autoimmune inflammatory rheumatic diseases (AIIRDs). This retrospective study collated hospital pharmacy data in patients who requested the prescription for MMF between January 2015 and December 2018. Clinical data were obtained from paper and electronic notes. Data were analysed using Microsoft Excel. Ethical approval was obtained through Coventry University. We recruited 144 patients into this study with age range from 18 to 91years, including 100 females and 44 males. There were 112 White patients, 22 of South Asian origin, 3 East Asian and 4 black patients. SLE (56), scleroderma (18), mixed connective tissue disease (15), myositis (13), vasculitis (13) were the commonest diagnoses. Overall adherence with Mycophenolate mofetil was 62%. The adherence rates were below 80% for all age groups with ∼60% of patients having adherence levels of >60%. Poor adherence with MMF correlated with 3-fold increase in risk of flares compared to good adherence (p=0.002). We also found a significant difference between Asian patients (mean adherence 47%) and White patients (mean adherence 65%, p<0.001). Adherence with MMF has improved considerably compared to historical studies, although these remain suboptimal. Certain population groups such as young adults, elderly and Asian patients continue to have lower adherence and higher risk of flares. Strategies are needed to improve adherence levels overall and specifically in the high-risk groups to reduce risk of flares and organ damage.

Rituximab versus intravenous cyclophosphamide in patients with connective tissue disease-associated interstitial lung disease in the UK (RECITAL): a double-blind, double-dummy, randomised, controlled, phase 2b trial

Rituximab is often used as rescue therapy in interstitial lung disease (ILD) associated with connective tissue disease (CTD), but has not been studied in clinical trials. This study aimed to assess whether rituximab is superior to cyclophosphamide as a treatment for severe or progressive CTD associated ILD. We conducted a randomised, double-blind, double-dummy, phase 2b trial to assess the superiority of rituximab compared with cyclophosphamide. Patients aged 18-80 years with severe or progressive ILD related to scleroderma, idiopathic inflammatory myositis, or mixed CTD, recruited across 11 specialist ILD or rheumatology centres in the UK, were randomly assigned (1:1) to receive rituximab (1000 mg at weeks 0 and 2 intravenously) or cyclophosphamide (600 mg/m2 body surface area every 4 weeks intravenously for six doses). The primary endpoint was rate of change in forced vital capacity (FVC) at 24 weeks compared with baseline, analysed using a mixed-effects model with random intercepts, adjusted for baseline FVC and CTD type. Prespecified secondary endpoints reported in this Article were change in FVC at 48 weeks versus baseline; changes from baseline in 6 min walk distance, diffusing capacity of the lung for carbon monoxide (DLCO), physician-assessed global disease activity (GDA) score, and quality-of-life scores on the St George's Respiratory Questionnaire (SGRQ), King's Brief Interstitial Lung Disease (KBILD) questionnaire, and European Quality of Life Five-Dimension (EQ-5D) questionnaire at 24 and 48 weeks; overall survival, progression-free survival, and time to treatment failure; and corticosteroid use. All endpoints were analysed in the modified intention-to-treat population, which comprised all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov (NCT01862926). Between Dec 1, 2014, and March 31, 2020, we screened 145 participants, of whom 101 participants were randomly allocated: 50 (50%) to receive cyclophosphamide and 51 (50%) to receive rituximab. 48 (96%) participants in the cyclophosphamide group and 49 (96%) in the rituximab group received at least one dose of treatment and were included in analyses; 43 (86%) participants in the cyclophosphamide group and 42 (82%) participants in the rituximab group completed 24 weeks of treatment and follow-up. At 24 weeks, FVC was improved from baseline in both the cyclophosphamide group (unadjusted mean increase 99 mL [SD 329]) and the rituximab group (97 mL [234]); in the adjusted mixed-effects model, the difference in the primary endpoint at 24 weeks was -40 mL (95% CI -153 to 74; p=0·49) between the rituximab group and the cyclophosphamide group. KBILD quality-of-life scores were improved at 24 weeks by a mean 9·4 points (SD 20·8) in the cyclophosphamide group and 8·8 points (17·0) in the rituximab group. No significant differences in secondary endpoints were identified between the treatment groups, with the exception of change in GDA score at week 48, which favoured cyclophosphamide (difference 0·90 [95% CI 0·11 to 1·68]). Improvements in lung function and respiratory-related quality-of-life measures were observed in both treatment groups. Lower corticosteroid exposure over 48 weeks of follow-up was recorded in the rituximab group. Two (4%) of 48 participants who received cyclophosphamide and three (6%) of 49 who received rituximab died during the study, all due to complications of CTD or ILD. Overall survival, progression-free survival, and time to treatment failure did not significantly differ between the two groups. All participants reported at least one adverse event during the study. Numerically fewer adverse events were reported by participants receiving rituximab (445 events) than those receiving cyclophosphamide (646 events). Gastrointestinal and respiratory disorders were the most commonly reported adverse events in both groups. There were 62 serious adverse events of which 33 occurred in the cyclophosphamide group and 29 in the rituximab group. Rituximab was not superior to cyclophosphamide to treat patients with CTD-ILD, although participants in both treatment groups had increased FVC at 24 weeks, in addition to clinically important improvements in patient-reported quality of life. Rituximab was associated with fewer adverse events. Rituximab should be considered as a therapeutic alternative to cyclophosphamide in individuals with CTD-ILD requiring intravenous therapy. Efficacy and Mechanism Evaluation Programme (Medical Research Council and National Institute for Health Research, UK).

Heart and Lung Transplant for Mixed Connective Tissue Disease: A Case Report and Implications for Pretransplant Testing

We present a case of end-stage lung disease secondary to mixed connective tissue disease (MCTD) with concomitant myocarditis found on explant at time of transplant. The patient is a 37-year-old man who was first diagnosed with interstitial lung disease secondary to MCTD at 30 years of age. He underwent en bloc heart-lung transplant for progressive decline in left ventricular ejection fraction and severe pulmonary fibrosis despite immunosuppression with hydroxychloroquine, mycophenolate, and azathioprine. Cardiac MRI failed to demonstrate findings suggestive of myocarditis; however, explant demonstrated significant lymphocytic infiltrate with myocyte damage and areas of fibrosis with myocyte hypertrophy. In patients presenting with unexplained systolic dysfunction in the setting of MCTD, fluorodeoxyglucose-positron emission tomography may be a screening tool and if myocardial inflammation is noted, there may be a role for increased immunosuppression. While this strategy was not employed in our patient, his improvement in left ventricular ejection fraction while on mycophenolate mofetil as compared with HCQ and explant histology suggests a process that may have been further responsive to escalation of immunosuppression.

Abstract 15140: Post-Myocardial Infarction Ventricular Septal Defect in a Patient With Mixed Connective Tissue Disorder

Mixed connective tissue disorder (MCTD) is associated with a broad range of cardiovascular abnormalities, including coronary artery disease (CAD). It has been proposed that chronic systemic inflammation plays a key role in the development of atherosclerotic disease. A 66-year-old female with a history of MCTD and hypertension presented with mild dyspnea and pleuritic chest pain after one week of persistent flu-like symptoms. Her blood pressure was 108/77 mmHg, pulse 92 bpm, saturating 98% on room air. She was comfortable and denied other risk factors such as diabetes, hyperlipidemia, or prior smoking history. On exam she was found to have a soft holosystolic murmur across her precordium. EKG showed sinus rhythm with small Q waves and ST elevation in V1-V6. She was taken for cardiac catheterization which revealed a thrombotic occlusion in the proximal left anterior descending artery (LAD) and a severe lesion in the left circumflex artery. She underwent angioplasty with one drug eluted stent placed to LAD. Left ventriculography revealed a VSD near the apex, and transthoracic echocardiogram showed a 7.6 mm muscular VSD with left to right shunt, ejection fraction of 35% and hypokinesis of the anterior wall. She became hypotensive and required vasopressors prior to coronary artery bypass grafting and primary closure of her apical VSD. Intraoperatively, a 2 cm VSD with 5 cm of necrotic surrounding tissue was noted. Post-operative complications included asystolic cardiac arrest, marked cardiogenic shock and multiorgan failure to which she ultimately succumbed. Post-myocardial infarction VSD is a rare complication of MI occurring in approximately 0.2% of cases. However, patients with MCTD can develop atypical symptoms, resulting in delayed presentation and therefore higher risk of mechanical complications. We highlight the importance of a thorough physical exam and high suspicion for mechanical complications in these patients even when hemodynamically stable.

Mixed connective tissue disease and severe renal disease - an apparent misconception?

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A REFRACTORY CASE OF HYPOCOMPLEMENTEMIC URTICARIAL VASCULITIS

<h3>Introduction</h3> Hypocomplementemic Urticarial Vasculitis (HUV) is a rare small vessel vasculitis. Patients present to allergy clinic with recurrent urticarial lesions. Proposed diagnostic criteria include 2 major criteria: recurrent urticarial lesions and hypocomplementemia, with at least 2 minor criteria: dermal biopsy showing leukocytoclastic vasculitis, arthralgias/arthritis, organ involvement, or elevated anti-C1q antibodies. We describe here the clinical presentation and therapeutic management of a refractory case of HUV. <h3>Case Description</h3> A 28-year-old female presented with a 2-year history of inflammatory arthritis and recurrent hives. Workup revealed hypocomplementemia: C3: 60, C4:10, decreased serum C1q<3.6, elevated anti-C1q antibody (102) and negative autoimmune markers. Cutaneous biopsy showed IgG/C3 at the basement membrane. She had been diagnosed with HUV and treated without benefit with different medications regimens including prednisone, hydroxychloroquine, colchicine, and dapsone all discontinued due to adverse effects/ineffectiveness. Patient was then tried on Methotrexate and Cyclosporine with limited benefit and later on Mycophenolate and omalizumab with minimal improvement. Over time, she developed pulmonary capillaritis, pericarditis, and episcleritis. She progressively developed a multi-organ, complex syndrome all of which was attributed to HUVS. After multiple failed therapies and poor control of urticaria multi-disciplinary decision was made to start Rituximab. <h3>Discussion</h3> Suspicion of HUVS should increase when hives do not respond to therapy, last>24 hours, and leave hyperpigmentation upon resolution. Differential diagnosis includes Muckle-Wells syndrome (hearing loss), Cogan syndrome (progressive hearing/vision loss), Sharp syndrome (positive U1-RNP antibodies), and SLE (positive ANA, normal levels of C1 esterase inhibitor). The case describes an aggressive form of HUV and highlights refractory disease with escalating therapies.