[Mixed connective tissue disease and its management]. / La connectivite mixte et sa prise en charge.

Mixed connective tissue disease (MCTD) is a rare autoimmune condition. Since its first description 50 years ago, its mere existence has been debated, given that it shares features of other autoimmune diseases, such as systemic lupus erythematosus (SLE), systemic sclerosis, inflammatory myopathy, rheumatoid arthritis and Sjogren's syndrome. Also, while antibodies to U1-RNP are essential for the diagnosis of MCTD, these antibodies may be expressed in other circumstances, such as in case of SLE. Nevertheless, the patient fulfilling criteria for MCTD needs specific management. In this review, we describe the clinical features and the potential complications of this complex disease, often wrongly disregarded as benign. We will also emphasize the recommended follow-up exams and address treatment, which is currently lacking formal recommendations.

La connectivite mixte (mixed connective tissue disease (MCTD)) est une maladie auto-immune rare. Dès sa description il y a cinquante ans, l'existence propre de la MCTD est débattue, car les limites avec d'autres maladies, comme le lupus érythémateux systémique (LES), la sclérodermie, les myopathies inflammatoires, la polyarthrite rhumatoïde et le syndrome de Sjögren, sont floues. Les anticorps anti-U1-RNP obligatoires au diagnostic de MCTD sont également exprimés dans d'autres circonstances, comme le LES. Quoi qu'il en soit, le patient présentant des critères de MCTD nécessite une prise en charge spécifique. Nous présentons ici les signes cliniques et complications potentielles d'une maladie longtemps estimée à tort comme d'évolution bénigne. Nous abordons aussi les examens de suivi recommandés et la thérapeutique, qui reste à ce jour mal définie.

Fractional exhaled nitric oxide in idiopathic pulmonary arterial hypertension and mixed connective tissue disease complicating pulmonary hypertension.

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

Nailfold capillaroscopy abnormalities and pulmonary hypertension in mixed connective tissue disease and systemic sclerosis patients.

OBJECTIVE: Pulmonary arterial hypertension (PAH) represents an important vascular complication of mixed connective tissue disease (MCTD) and systemic sclerosis (SSc). Microvascular involvement in these diseases can be investigated by means of nailfold capillaroscopy (NFC). Microvascular involvement detected in the nailfold bed is the mirror of the microvascular damage occurring in the entire body, further indicating the involvement of the target organs. The aim of this study was to evaluate the microvascular involvement in MCTD patients with or without PAH, compared to that found in SSc patients with or without PAH. PATIENTS AND METHODS: This cross-sectional study was performed in the Department of Internal Medicine and Department of Rheumatology, Timișoara, Romania, during the time period between January 2017 and December 2022, on a group of 26 patients with MCTD and 26 SSc patients. Antinuclear antibodies, anti-U1-RNP, anti-Scl 70, anti-centromere, anti-cardiolipin antibodies (aCL) (IgM, IgG), anti-ß2-glycoprotein I (aß2GPI) (IgM, IgG) antibodies, and lupus anticoagulant (LAC) were determined in both the groups. PAH was evaluated through cardiac ultrasonography, determining the sPAP (systolic pulmonary artery pressure). Nailfold capillaroscopy was performed using a USB Digital Microscope and 2.0-megapixel digital camera recording capillaries density, giant capillaries, enlarged capillaries, capillaries hemorrhages, avascular areas, ramified/bushy capillaries scores. Data were recorded and presented as mean ± standard deviation. Statistical analyses were performed using the Student's t-test, ANOVA test, and Pearson's correlation. Differences were considered statistically significant if p-value < 0.05. RESULTS: Among the MCTD patients, PAH was identified in 12 patients (46.15%), while among the SSc patients PAH was identified in 14 patients (53.84%). Development of PAH in MCTD patients was associated with lower capillaries density (p-value < 0.00001), higher scores of giant capillaries, ramified/bushy capillaries, and capillary hemorrhages (p-value < 0.00001, for each of them). Anti-U1-RNP, aCL, aß2GPI antibodies and LAC were also found to be involved in PAH-associated MCTD development. Unlike MCTD patients, SSc patients with PAH presented with lower capillaries density and ramified/bushy capillaries scores (p-value < 0.05). CONCLUSIONS: The MCTD patients who presented significant NFC abnormalities (especially active and late scleroderma-like capillaroscopic pattern) are prone to PAH development. Capillary density reduction is the most important factor associated with the occurrence of PAH. Differences in NFC findings (especially capillary density and ramified/bushy capillaries) were detected among patients with MCTD and SSc having PAH.

Pulmonary hypertension in connective tissue diseases: What every CTD specialist should know - but is afraid to ask!

Pulmonary hypertension (PH) is a possible complication of connective tissue diseases (CTDs), especially systemic sclerosis (SSc), systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD). It is defined by an elevation of the mean pulmonary arterial pressure above 20mmHg documented during a right heart catheterization (RHC). Due to their multiorgan involvement, CTDs can induce PH by several mechanisms, that are sometimes intricated: pulmonary vasculopathy (group 1) affecting arterioles (pulmonary arterial hypertension, PAH) and possibly venules (pulmonary veno-occlusive-like disease), left-heart disease (group 2), chronic lung disease (group 3) and/or chronic thromboembolic PH (group 4). PH suspicion is often raised by clinical manifestations (dyspnea, fatigue), echocardiographic data (increased peak tricuspid regurgitation velocity), isolated decrease in DLCO in pulmonary function tests, and/or unexplained elevation of BNP/NT-proBNP. Its formal diagnosis always requires a hemodynamic confirmation by RHC. Strategies for PH screening and RHC referral have been extensively investigated for SSc-PAH but data are lacking in other CTDs. Therapeutic management of PH depends of the underlying mechanism(s): PAH-approved therapies in group 1 PH (with possible use of immunosuppressants, especially in case of SLE or MCTD); management of an underlying left-heart disease in group 2 PH; management of an underlying chronic lung disease in group 3 PH; anticoagulation, pulmonary endartectomy, PAH-approved therapies and/or balloon pulmonary angioplasty in group 4 PH. Regular follow-up is mandatory in all CTD-PH patients.

Mixed connective tissue disease-myositis overlap syndrome presenting as an allergic disease process to the emergency department: A case report.

BACKGROUND: The "allergy epidemic" of the Western World, has led to an overwhelming number of emergency department presentations with allergic rhinitis, allergic conjunctivitis, atopic eczema, and asthma. Careful consideration should be given to screening for the typical signs and symptoms of Mixed connective tissue disease (MCTD) in patients presenting to the ED with what appears to be a simple allergic process. MCTD is a rare systemic rheumatic disease characterized by high levels of anti-U1RNP antibodies and various clinical signs and symptoms. The pathophysiology of MCTD is poorly understood. An association between allergen-mediated processes and MCTD has been reported in recent literature. Our case report involves a 40 year old African American female with initial outpatient presentation suggestive of atopic disease, with progressive worsening of symptoms while receiving allergen immunotherapy. The patient presented to the emergency department with bilateral leg cramping. The patient was found to have a CPK of 7000 unresponsive to fluids. The patient was evaluated by the Allergy and Rheumatology services. The patient was ultimately diagnosed with MCTD-Myositis Overlap Syndrome and started on steroids and IVIG with improvement in symptoms. While MCTD is not a diagnosis readily made in the ED, early identification and treatment of the disease is critical for prevention of long term complications.

Anti-SMN autoantibodies in mixed connective tissue disease are associated with a severe systemic sclerosis phenotype.

OBJECTIVES: The survival of motor neuron (SMN) complex has an essential role in the assembly of small nuclear ribonucleoproteins (RNP). Recent reports have described autoantibodies (aAbs) to the SMN complex as novel biomarkers in anti-U1RNP+ myositis patients. The aim of this study was to compare phenotypic features of anti-U1RNP+ mixed connective tissue disease (MCTD) patients with and without anti-SMN aAbs. METHODS: A retrospective MCTD cohort was studied. Addressable laser bead immunoassay was used to detect specific anti-SMN aAbs with <300 mean fluorescence intensity (MFI) as normal reference range, 300-999 MFI as low-titre and ≥1000 MFI as high-titre positivity. Comparison of clinical features between anti-SMN+ and anti-SMN- subgroups used two-tailed Fisher's exact test, and logistic regression analyses. RESULTS: Sixty-six patients were included. Median age at MCTD diagnosis was 40.6 years, and duration of follow-up was 12 years. Based on the highest available titre, 39 (59%) were anti-SMN+: 10 (26%) had low titre and 29 (74%) had high titre. Anti-SMN+ patients had a higher frequency of fingertip pitting scars (anti-SMN+ 23% vs anti-SMN- 4%, p=0.04), lower gastrointestinal (GI) involvement (26% vs 4%, p=0.04), and myocarditis (16% vs 0%, p=0.04). The combined outcome of pitting scars and/or lower GI involvement and/or myositis and/or myocarditis was highest among high-titre anti-SMN+ patients: adjusted OR 7.79 (2.33 to 30.45, p=0.002). CONCLUSIONS: Anti-SMN aAbs were present in 59% of our MCTD cohort. Their presence, especially at high-titres, was associated with a severe systemic sclerosis (scleroderma) phenotype including myositis, myocarditis and lower GI involvement.

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

OBJECTIVE: We aimed to compare two matched populations of patients with MTCD with and without associated ILD and to identify predictive factors for ILD progression and severity. METHODS: This international multicenter retrospective study (14 tertiary hospitals), included MCTD patients who fulfilled at least one historical MCTD classification criteria. ILD was defined by the presence of typical chest high-resolution computed tomography (HRCT) abnormalities. Factors associated with ILD were assessed at baseline. Long-term progressive ILD was assessed in MCTD-ILD patients with multiple forced vital capacity (FVC) measurements. RESULTS: 300 patients with MCTD were included. Mean age at diagnosis was 39.7 ± 15.4 years and 191 (63.7%) were women. Mean follow-up was 7.8 ± 5.5 years. At baseline, we identified several factors associated with ILD presence: older age (p = 0.01), skin thickening (p = 0.03), upper gastro-intestinal (GI) symptoms (p<0.001), FVC <80% (p<0.0001), diffusing capacity for carbon monoxide <80% (p<0.0001), anti-topoisomerase antibodies (p = 0.01), SSA/Ro antibodies (p = 0.02), cryoglobulinemia (p = 0.04) and elevated C-reactive protein (p<0.001). Patients with MTCD-ILD were more likely to be treated with synthetic immunosuppressant agents (p<0.001) in particular mycophenolate mofetil (p = 0.03). Digital ulcers (DU) were identified as a risk factor for FVC decline >10%. During follow-up mortality was higher in the MTCD-ILD group (p<0.001). CONCLUSION: In this large international cohort of patients with MTCD, we identified different factors associated with ILD. Our findings also provide evidence that MCTD-ILD patients have increased mortality and that DU are associated with progressive lung disease.

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

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

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

OBJECTIVE: Nailfold videocapillaroscopy (NVC) allows the detection of microvascular damage in autoimmune connective tissue diseases (CTDs). The prevalence of the morphological capillary findings was retrospectively evaluated in a wide cohort of patients with Raynaud's phenomenon secondary to a CTD at the time of the first single NVC, independently from their current treatment, autoantibody profile and comorbidities. METHODS: One-thousand-one-hundred-eighty-one patients affected by CTDs were included from 2001 to 2021. The considered CTDs were systemic sclerosis (SSc), undifferentiated connective tissue disease (UCTD), mixed connective tissue disease (MCTD), dermatomyositis (DM), systemic lupus erythematosus, Sjögren's syndrome and primary antiphospholipid syndrome (aPS). The capillaroscopic parameters were distinguished between scleroderma patterns and non-scleroderma patterns. RESULTS: Giant capillaries were significantly more frequent in SSc, DM and MCTD than in other CTDs (respectively, in 73%, 73% and 61% of patients, p<0.001 when comparing each rate vs the other CTDs). The mean capillary count was significantly lower in SSc, DM and MCTD (respectively, 7.04±0.18 vs 6.5±0.75 vs 7.7±2 capillaries/linear mm) compared with the other CTDs (p<0.001 for each rate vs the other CTDs). The non-specific abnormalities of capillary morphology were significantly more frequent in SSc, MCTD and aPS (respectively, in 48%, 41% and 36% of cases, all p<0.001 vs each other CTDs). CONCLUSION: This large size sample of patients with CTDs, collected over 20 years of analysis, confirms the highest prevalence of specific capillaroscopic alterations in patients with SSc, DM and MCTD, when compared with other CTDs.

FROSTED BRANCH ANGIITIS ASSOCIATED WITH MIXED CONNECTIVE TISSUE DISEASE.

PURPOSE: To present a case of frosted branch angiitis associated with an exacerbation of mixed connective tissue disease (MCTD). METHODS: Single case report. RESULTS: A 31-year-old woman presented with a flare of her long-standing MCTD after a change in her immunosuppressive medications. She developed blurred vision and floaters first in the left eye but eventually in both eyes. Fundoscopy showed patchy perivascular sheathing of tertiary branch venules surrounded by retinal hemorrhages characterized as frosted branch angiitis. The patient's MCTD symptoms and retinal vasculitis improved with continued immunosuppressive therapy. At 1-month follow-up, her visual acuity had improved to 20/20 bilaterally with complete resolution on fundoscopy. CONCLUSION: To the authors' knowledge, this is the first report of frosted branch angiitis seen in association with MCTD. The improvement in the patient's visual acuity and fundoscopic findings in this case supports the role of immunosuppressive therapy to treat secondary frosted branch angiitis associated with an autoimmune condition such as MCTD. However, it is recommended that a comprehensive medical workup is performed to exclude an infective cause, particularly in immunocompromised patients.

In-depth characterization of pulmonary arterial hypertension in mixed connective tissue disease: a French national multicentre study.

OBJECTIVE: Pulmonary arterial hypertension (PAH) is a leading cause of death in MCTD. We aimed to describe PAH in well-characterized MCTD patients. METHODS: MCTD patients enrolled in the French Pulmonary Hypertension Registry with a PAH diagnosis confirmed by right heart catheterization were included in the study and compared with matched controls: MCTD patients without PAH, SLE patients with PAH and SSc patients with PAH. Survival rates were estimated by the Kaplan-Meier method and risk factors for PAH in MCTD patients and risk factors for mortality in MCTD-PAH were sought using multivariate analyses. RESULTS: Thirty-six patients with MCTD-PAH were included in the study. Comparison with MCTD patients without PAH and multivariate analysis revealed that pericarditis, polyarthritis, thrombocytopenia, interstitial lung disease (ILD) and anti-Sm antibodies were independent predictive factors of PAH/PH in MCTD. Estimated survival rates at 1, 5 and 10 years following PAH diagnosis were 83%, 67% and 56%, respectively. MCTD-PAH presentation and survival did not differ from SLE-PAH and SSc-PAH. Multivariate analysis revealed that tobacco exposure was an independent factor predictive of mortality in MCTD-PAH. CONCLUSION: PAH is a rare and severe complication of MCTD associated with a 56% 10-year survival. We identified ILD, pericarditis, thrombocytopenia and anti-Sm antibodies as risk factors for PAH in MCTD and tobacco exposure as a predictor of mortality in MCTD-PAH.

Anti-MDA5 antibody dermatomyositis-associated rapidly progressive interstitial lung disease patient complicated with mixed connective tissue disease: A case report.

Anti-MDA5 antibody dermatomyositis (DM) is a special type of myositis, which can potentially cause rapidly progressive interstitial lung disease (RP-ILD). Mixed connective tissue disease (MCTD) is a complex disease with different characteristics of autoimmune connective tissue disease, associated with ILD. Both are rare diseases, and few patients with both diseases have been reported. A 71-year-old woman complained of palpitations, with a 2 months history of rash around her hands, extensor surface of right elbow, and the nape of her neck. Subsequently, the patient had acute exacerbation of dyspnea and tachypnea. Anti-Ro52, U1 RNP and MDA5 antibodies were positive; the presenting evidence was suggestive of anti-MDA5+ DM-RP-ILD complicated with MCTD. Our patient deteriorated rapidly and had a fatal outcome, despite "triple therapy" for RP-ILD. This case illustrates that patients with coexisting anti-MDA5+ DM and MCTD have the former's typical clinical manifestations, and may develop ILD quickly rather than slowly as in MCTD, especially with the coexistence of anti-Ro52 antibodies.

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.

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.

Clinical characteristics and outcomes of digital gangrene in connective tissue disorders: a longitudinal single-centre experience from Jodhpur, India.

Epidemiology, clinical presentation, and outcomes for digital gangrene in connective tissue disorders (CTD) remain underreported from tropical countries like India. In this series, we aimed to explore the clinical profile and outcomes of patients who presented with digital gangrene and a diagnosis of CTD. Hospital-based longitudinal observational study. Patients with digital gangrene and underlying diagnosis of CTD presenting to our tertiary-care centre in Jodhpur, India between1st January 2018 and 31st June 2021 were included. Clinical outcomes including mortality, limb outcomes, functional status and other systemic involvement were assessed. Of the 312 patients registered in the rheumatology clinic during this period, 22 (7%) patients were found to satisfy the inclusion criteria. Mean age was 46 years and 90% were females. The most common underlying diagnosis was Mixed connective tissue disorder (MCTD). Digital gangrene was the presenting symptom in 13 (60%) patients. Half of the patients received only corticosteroids as immunosuppression. Two died due to systemic complications. Complete resolution occurred in 17 (85%), autoamputation in 3, and infection requiring surgical drainage in one patient. All surviving patients reported good functional limb outcome on 6 months follow-up. MCTD is an important cause of digital gangrene in rheumatology practice. In patients presenting with digital gangrene, an active search for an underlying CTD is imperative, as this could result in timely initiation of appropriate limb-saving therapy. Corticosteroids alone with rapid tapering may be an appropriate option to consider in the initial management of digital gangrene in CTD. Key Points • Mixed connective tissue disorder is an important cause of digital gangrene in rheumatology practice in western India. • In patients presenting with digital gangrene, an active search for an underlying connective tissue disorder is imperative, as this could result in timely initiation of appropriate therapy and can prove limb saving. • Corticosteroids alone with rapid tapering may be an appropriate option to consider in the initial management of digital gangrene in connective tissue disorders.