Exploratory clinical subgroup clustering in systemic sclerosis: Results from the Indian Progressive Systemic Sclerosis Registry.

Objective: To conduct an exploratory cluster analysis of systemic sclerosis patients from the baseline data of the Indian systemic sclerosis registry. Methods: Patients satisfying American College of Rheumatology-European League Against Rheumatism classification criteria for systemic sclerosis were included. The clusters formed using clinical and immunological parameters were compared. Results: Of the 564 systemic sclerosis registry participants, 404 patients were included. We derived four clusters of which three were anti-topoisomerase I predominant and one was anti-centromere antibody 2 dominant. Cluster 1 (n-82 (20.3%)) had diffuse cutaneous systemic sclerosis patients with the most severe skin disease, anti-topoisomerase I positivity, males, younger age of onset and high prevalence of musculoskeletal, vasculopathic and gastrointestinal features. Cluster 2 (n-141 (34.9%)) was also diffuse cutaneous systemic sclerosis and anti-topoisomerase I predominant but with less severe skin phenotype than cluster 1 and a lesser prevalence of musculoskeletal, vasculopathic and gastrointestinal features. Cluster 3 (n-119 (29.5%)) had limited cutaneous systemic sclerosis patients with anti-topoisomerase I positivity along with other antibodies. The proximal muscle weakness was higher and digital pitting scars were lower, while other organ involvement was similar between clusters 2 and 3. Cluster 4 (n-62 (15.30%)) was the least severe group with limited cutaneous systemic sclerosis and anti-centromere antibody predominance. Age of onset was higher with low musculoskeletal disease and a higher presence of upper gastrointestinal features. The prevalence of interstitial lung disease was similar in the three anti-topoisomerase I predominant clusters. Conclusion: With exploratory cluster analysis, we confirmed the possibility of subclassification of systemic sclerosis along a spectrum based on clinical and immunological characteristics. We also corroborated the presence of anti-topoisomerase I in limited cutaneous systemic sclerosis and the association of interstitial lung disease with anti-topoisomerase I.

Microscopic Polyangiitis with Pulmonary-renal Involvement in a Patient with Polyarticular Juvenile Idiopathic Arthritis: A Case Report.

The association of polyarticular juvenile idiopathic arthritis (p-JIA) and microscopic polyangiitis (MPA) is extremely rare. Very few case reports described the coexistence of these two diseases to date. Here we report a 26-year-old female, a diagnosed patient of rheumatoid factor positive p-JIA for 15 years who developed MPA with renal and pulmonary involvement at the age of 26 years. She was successfully treated with intravenous corticosteroid and injection rituximab. This case report is unique as an association between MPA and p-JIA is very rare.

Recurrent macrophage activation syndrome as the initial manifestation of paediatric systemic lupus erythematosus.

Introduction: Macrophage Activation Syndrome (MAS) is a rare but potentially fatal complication in rheumatic diseases. Here, we report the case of a 14-year-old girl with MAS as the primary manifestation of Systemic Lupus Erythematosus (SLE). She had three episodes of MAS during the course of her treatment. This case is unique as recurrent MAS in pediatric SLE is rare.Methods: Demographic, clinical, laboratory features and outcomes of our patient was noted. We also reviewed the two reported cases of recurrent MAS in pediatric SLE. Literature review was performed on PubMed search forum. Search items included Macrophage activation syndrome, pediatric systemic lupus erythematosus, recurrent MAS.Conclusion: The diagnosis and management of MAS are challenging as it can simulate an infectious complication or can be the exacerbation of the underlying disease. Early detection and prompt treatment can reduce morbidity in these patients.

Evaluation of Subclinical Hand Joint Synovitis by Ultrasonography in Patients with Psoriatic Arthritis and Cutaneous Psoriasis: A Case-Control Study.

Objectives: To find the frequency of subclinical hand joint synovitis (SS) in patients with psoriatic arthritis (PsA) and cutaneous psoriasis (PsC) compared to healthy controls (HC), and correlation of SS with disease activity. Methods: PsA patients (n= 52), without any past/current history of hand joint arthritis, PsC patients (n= 48), and 45 HC were recruited. Grey-scale and power Doppler Ultrasonography of bilateral hand joints were performed. The proportions of hand joints with SS were estimated in each group. A wrist-ray score was devised. Correlations were obtained between the number of joints with SS and disease activity parameters. Results: Higher proportion of PsA patients (55.8%) had SS than PsC (29.2%, p= 0.007), and HC (22.2%, p=0.001). Proportion of joints with SS was higher in PsA patients (5.38%) compared to PsC (2.92%, [p=0.0008]), and HC (1.11%, [p=0.0007]). Compared to HC, PsA patients had significantly higher bilateral ray 3 (p=0.002 and 0.01 for left and right ray 3, respectively), and right ray 4 involvement (p=0.037) and PsC patients had higher left ray 3 involvement (p=0.03). Wrist-ray score above 2.5 could distinguish patients of PsC with significant subclinical synovitis compared to controls (area under curve: 0.857, 95% confidence interval: 0.71-1.00). There was a significant correlation of SS with ESR in PsA group (p-value: 0.044), and with CRP in PsC group (p-value: 0.003), but not with other disease activity indices. Conclusion: SS was noted in approximately half of PsA and 1/3rd of PsC patients. Both PsA and PsC patients had a significantly higher number of hand joint SS than HC. Ray pattern of hand joint SS could be present in both PsA and PsC.

Clinical and psychosocioeconomic impact of COVID-19 pandemic on patients of the Indian Progressive Systemic Sclerosis Registry (IPSSR).

OBJECTIVES: The aim was to determine the impact of the coronavirus disease 2019 (COVID-19) pandemic on access to health care among patients with scleroderma and to analyse the economic and psychosocial impacts and the infection prevention measures taken by them during the pandemic. METHODS: A 25-item questionnaire designed to assess the components of the objectives was tele-administered between October 2020 and January 2021 to the patients enrolled in the Indian Progressive Systemic Sclerosis Registry. RESULTS: Of the 428 patients in the registry, 336 took part in the study. A scheduled outpatient visit was missed by 310 (92.3%) patients, and 75 (22.3%) skipped prescription drugs. During the pandemic, 75 (22.3%) had a family member lose a job. Financial difficulties were reported by 155 (46.1%), with 116 (34.5%) patients having to spend an additional INR 4000 (2000-10 000) [USD 54.9 (27.0-137.4)] to continue treatment. Although 35 patients (10.4%) had at least one symptom suggestive of COVID-19, infection was confirmed in only 4. None of them needed hospitalization or had adverse outcomes. Worsening of scleroderma was seen in 133 (39.6%) individuals, with 15 (4.5%) requiring hospitalization. Most (96%) of the patients were aware of infection prevention measures, and 91 (27.1%) had taken unproven prophylactic medications. CONCLUSION: Individuals with scleroderma in India have been affected during the pandemic owing to closure of hospital services, lack of transport, loss of jobs and the additional financial burden. Health-care providers should continue to educate patients to stay on their medications and encourage them to be vaccinated for COVID-19.

High-resolution ultrasonography in carpal tunnel syndrome: role of ancillary criteria in diagnosis and response to steroid injection.

OBJECTIVES: (1) Development and validation of a composite ultrasound score (cUSS) for the diagnosis of carpal tunnel syndrome (CTS). (2) To predict treatment response after local corticosteroid injection. METHODS: Wrists of CTS patients and controls were evaluated with high-resolution ultrasound and cross-sectional area of median nerve at carpal tunnel inlet (CSAp) and outlet (CSAd) and bowing of flexor retinaculum (FRB), flexor tenosynovitis, and intraneural vascularity and echogenicity changes were noted. Patients were prospectively followed after ultrasound-guided corticosteroid injection. RESULTS: We studied 479 wrists of 141 patients and 99 controls. Optimal cut-offs for diagnosing CTS were 9.5 mm2 and 10.5 mm2, respectively, for CSAp and CSAd. A cUSS consisting of the following parameters was developed: age, CSAp, CSAd, FRB, and flexor tenosynovitis and echogenicity changes. External validation of cUSS yielded sensitivity, specificity, and diagnostic accuracy of 91.7%, 87.1%, and 89.8%, respectively. Treatment responses from 88 injections (median duration of follow-up of 6 months) were available with satisfactory initial responses in 69.32% (61/88) and relapses in 30.86% (25/81). Median time to relapse was 2 months. Initial response was predicted by FRB (odds ratio (OR): 5.43, 95% confidence interval (CI): 1.45-20.3, p = 0.012). Relapse was predicted by age (hazard ratio (HR) 1.168, 95% CI: 1.076-1.268, p = 0.0002), male gender (HR: 8.1.02, 95% CI: 2.394-27.422, p = 0.0007), FRB, (HR: 46.982, 95% CI: 5.048-437.293, p = 0.0008), and higher body mass index (HR: 0.238, 95% CI: 0.064-0.892, p = 0.0332). CONCLUSIONS: The developed cUSS has a diagnostic accuracy of 88% for diagnosing CTS. Ultrasound parameters could predict both initial treatment response and relapse. KEY POINTS: • Anatomical ultrasound parameters in addition to nerve cross-sectional area is important for diagnosis of CTS. • A composite US score for diagnosis of CTS was developed with accuracy 88.6%. • Bowing of flexor retinaculum predicts short and long term response to local steroid injection.

Rituximab in the treatment of systemic sclerosis-related interstitial lung disease: a systematic review and meta-analysis.

OBJECTIVES: To assess the effect of rituximab (RTX) on the lung function parameters in SSc interstitial lung disease (SSc-ILD) patients. METHODS: PubMed and Embase were searched to identify studies on SSc-ILD treated with RTX, confined to a predefined inclusion and exclusion criteria. A systematic review and meta-analysis were performed on the included studies on changes in forced vital capacity (FVC) and diffusion capacity of carbon monoxide (DLCO) from baseline to 6 and 12 months of follow-up. RESULTS: A total of 20 studies (2 randomized controlled trials, 6 prospective studies, 5 retrospective studies and 7 conference abstracts) were included (n = 575). RTX improved FVC from baseline by 4.49% (95% CI 0.25, 8.73) at 6 months and by 7.03% (95% CI 4.37, 9.7) at 12 months. Similarly, RTX improved DLCO by 3.47% (95% CI 0.99, 5.96) at 6 months and 4.08% (95% CI 1.51, 6.65) at 12 months. In the two studies comparing RTX with other immunosuppressants, improvement of FVC by 6 months in the RTX group was 1.03% (95% CI 0.11, 1.94) greater than controls. At the 12 month follow-up, RTX treatment was similar to controls in terms of both FVC and DLCO. Patients treated with RTX had a lower chance of developing infections compared with controls [odds ratio 0.256 (95% CI 0.104, 0.626), I2 = 0%, P = 0.47). CONCLUSIONS: Treatment with RTX in SSc-ILD was associated with a significant improvement of both FVC and DLCO during the first year of treatment. RTX use was associated with lower infectious adverse events.

Quality of life among female patients with systemic lupus erythematosus in remission.

The objective is to assess quality-of-life (QoL) parameters among Indian female systemic lupus erythematosus (SLE) patients with durable remission. Indian female SLE patients in remission determined by the European consensus criteria and age-matched female control participants were included in the study. All included participants underwent measurements of QoL [Medical Outcomes Study Short-Form-12 (SF12)], Fatigue Severity Scale, and structured interview with a clinical psychologist. The population comprised of 126 female SLE patients [median age: 27.5 years [interquartile range (IQR): 11]; median disease duration: 36 months (IQR 26)] and 110 female controls [median age 30 years (IQR 9)]. Clinical remission was seen in 65.9% (83/126) and complete remission in 34.1% (43/126). Significant fatigue was present in 18.3% (23/126). Both SF-12 physical component summary (PCS) and mental component summary (MCS) were similar between SLE patients and controls [median PCS: 50.3 (IQR: 16.2) vs. 48.6 (IQR: 11.6); median MCS: 57.2 (IQR: 4.8) vs. 57.9 (IQR: 7.6)]. In generalised linear modelling, PCS was associated with fatigue [odd's ratio (OR) 0.012, 95% confidence interval (CI) 0.006-0.025, p < 0.001], disease duration ≥ 5 years (OR 23.16, 95% CI 1.548-346.58, p = 0.023), and complete remission (OR 33.16, 95% CI 4.43-248.15, p = 0.001); MCS with fatigue (OR 0.53, 95% CI 0.34-0.84, p = 0.007) and absence of depression (OR 3.65, 95% CI 1.07-12.44, p = 0.038). Patients with SLE in remission report significant fatigue in 18.3% of subjects. Both PCS and MCS scores are similar to healthy controls. Better PCS was associated with less fatigue, longer disease duration, and complete remission. Better MCS was associated with less fatigue and absence of depression.

Cutting Edge: Dysregulated Endocannabinoid-Rheostat for Plasmacytoid Dendritic Cell Activation in a Systemic Lupus Endophenotype.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease, characterized by loss of tolerance toward self nuclear Ags. Systemic induction of type I IFNs plays a pivotal role in SLE, a major source of type I IFNs being the plasmacytoid dendritic cells (pDCs). Several genes have been linked with susceptibility to SLE in genome-wide association studies. We aimed at exploring the role of one such gene, α/ß-hydrolase domain-containing 6 (ABHD6), in regulation of IFN-α induction in SLE patients. We discovered a regulatory role of ABHD6 in human pDCs through modulating the local abundance of its substrate, the endocannabinoid 2-arachidonyl glycerol (2-AG), and elucidated a hitherto unknown cannabinoid receptor 2 (CB2)-mediated regulatory role of 2-AG on IFN-α induction by pDCs. We also identified an ABHD6High SLE endophenotype wherein reduced local abundance of 2-AG relieves the CB2-mediated steady-state resistive tuning on IFN-α induction by pDCs, thereby contributing to SLE pathogenesis.

Steroid-free remission in lupus: myth or reality; an observational study from a tertiary referral centre.

OBJECTIVE: Whether maintaining steroid-free remission is feasible in Indian patients with systemic lupus erythematosus (SLE). METHODS: In 148 patients with SLE including 78 lupus nephritis (LN) previously put into remission, steroid therapy was gradually tapered off. RESULTS: Patients received glucocorticoids for median 1855 days (interquartile range (IQR) 901-2834) before discontinuing. Median duration of follow-up was 539 days (IQR 266.25-840.75). Flare occurred in 31 patients (20.9%; 95% confidence interval (CI) 15.17-28.19, renal flare in 12.16% (18/148, 95% CI 7.83-18.41)). Most of the flares occurred in the first year of follow-up (41.9%, 13/31). Overall 93.5% (29/31) of flares occurred in those who received ≤ 8 years of glucocorticoids, compared to 6.5% (2/31) of flares in others (p = 0.009). Median flare-free survival was 611 days (95% CI 518-704). Multivariate Cox regression identified the following predictors of flare-free survival: duration of disease (hazard ratio (HR) 0.89, 95% CI 0.84-0.94, p < 0.001), duration of glucocorticoid before discontinuing (HR 1.000086, 95% CI 1.000047-1.00012, p < 0.001) and second immunosuppressive (HR 1.89, 95% CI 1.251-2.87, p = 0.003). Additional risk factors of a renal flare-free survival among patients with LN were initial dose of glucocorticoids (HR 0.97, 95% CI 0.94-0.99, p = 0.005) and presence of haemolytic anaemia (HR 2.43, 95% CI 1.067-5.54, p = 0.035). CONCLUSIONS: About 20% patients undergo exacerbation of disease activity after glucocorticoid withdrawal. Treatment for ≥ 8 years before discontinuing and an additional immunosuppressive agent improve the chance of flare-free survival.

Cyclophosphamide Versus Mycophenolate Versus Rituximab in Lupus Nephritis Remission Induction: A Historical Head-to-Head Comparative Study.

OBJECTIVE: We report comparative efficacy between high-dose cyclophosphamide (HDCyC), low-dose cyclophosphamide (LDCyC), mycophenolate mofetil (MMF) and rituximab in patients with lupus nephritis (LN). METHODS: We analyzed comparative efficacy of 4 induction regimens of biopsy-proven LN: LDCyC: 500 mg fortnightly, HDCyC: 750 to 1200 mg monthly, MMF: 1.5 to 3 g/d, and rituximab. Outcomes of 4 groups were analyzed at the sixth month. RESULTS: Among a total 222 patients, 26 received LDCyC (3-g total dose), 113 received HDCyC (mean, 5.1-g total dose), 61 received MMF (mean, 2.2 g/d), and 22 received rituximab (mean, 1.9-g total dose). Relapsing/refractory LN was 11 in HDCyC, 1 in LDCyC, 10 in MMF, and 14 in the rituximab group. Overall 16.2% had no improvement of proteinuria, 18% had partial response, and 65.8% (146/222) had complete response. Renal response (RR) was higher in HDCyC (90.3%) and rituximab (90.9%) groups compared with LDCyC (73%) and MMF (72%) groups. Rituximab was effective in relapsing disease (100% RR). Infection was highest with the HDCyC, followed by LDCyC and rituximab (p = 0.15), whereas the MMF group had a higher incidence of gastrointestinal adverse effects (p < 0.001). The following predictors of RR were identified: rituximab (odds ratio [OR], 20.4; 95% confidence interval [CI], 1.9-215.7; p = 0.012), renal Baseline Systemic Lupus Erythematosus Disease Activity Index at baseline (OR, 0.86; 95% CI, 0.75-0.99; p = 0.034), and duration of disease (OR, 0.98; 95% CI, 0.97-0.99; p = 0.009). CONCLUSIONS: High-dose cyclophosphamide and rituximab were the most effective therapeutic strategies in patients with LN, especially in the Indian context. Rituximab was highly effective in relapsing disease.

Assessment of nail unit structures by ultrasound in patients with psoriatic arthritis and their correlations with disease activity indices: a case-control study.

Ultrasound (USG) of nail was performed to assess, (1) morphological alterations of nail plates in psoriatic arthritis (PsA) patients, (2) differences of nail unit parameters [nail bed thickness (NBT), nail matrix thickness (NMT) and nail plate distance (NPD)] in PsA patients from healthy controls (3) correlation of nail unit parameters with PsA disease activity indices. Total of 895 fingernails (448 nails of 45 PsA patients and 447 of 45 controls) were evaluated by USG. Psoriasis Area and Severity Index (PASI), Disease Activity in Psoriatic Arthritis (DAPSA), and Nail Psoriasis Severity Index (NAPSI) were calculated in PsA patients. Nail unit parameters were compared between two study groups. Correlation study was done between nail unit parameters and disease activity indices. All PsA patients showed ultrasound evidence of nail plate changes (87.95% of the total fingernails and 75.34% of the clinically normal nails). Loosening of the ventral nail plate border was most common (51.79%). Mean NBT (PsA: 0.19 ± 0.035 cm, control: 0.17 ± 0.018 cm, p = 0.003) and mean NMT (PsA: 0.32 ± 0.041 cm, control: 0.28 ± 0.031 cm, p = < 0.0001) were significantly increased in the PsA patients. Moderately positive correlation was observed between NAPSI score and mean NMT (Spearman r = 0.411, 95% confidence interval: 0.125-0.634, p = 0.005). USG evidence of nail plate alterations was frequent among PsA patients, even in clinically normal nails. Increased mean nail bed and matrix thickness were noted in PsA patients. Mean NMT had a moderately positive correlation with NAPSI score.

Intravenous cyclophosphamide vs rituximab for the treatment of early diffuse scleroderma lung disease: open label, randomized, controlled trial.

Objectives: SSc is characterized by fibrotic changes in the skin and lung, and the mainstay of treatment has been CYC. B cell involvement suggests that rituximab (RTX) may also be of therapeutic benefit. The aim of the study was to compare the efficacy and safety of RTX compared with CYC in retarding the progression of interstitial lung disease and skin manifestations of primary SSc. Methods: We randomly assigned 60 patients of dcSSc, age 18-60 years with skin and lung involvement, to monthly pulses of CYC 500 mg/m2 or RTX 1000 mg × 2 doses at 0, 15 days. Primary outcomes were forced vital capacity (FVC) percent predicted at 6 months. Secondary outcomes were: absolute change in litres (FVC-l) at 6 months; modified Rodnan skin scores at 6 months, 6-min walk test, Medsgers score and new onset or worsening of existing pulmonary hypertension by echocardiographic criteria. Results: The FVC [%mean (s.d.)] in the RTX group improved from 61.30 (11.28) to 67.52 (13.59), while in the CYC group it declined from 59.25 (12.96) to 58.06 (11.23) at 6 months (P = 0.003). The change of FVC was 1.51 (0.45) l to 1.65 (0.47) l in the RTX group, compared with 1.42 (0.49) to 1.42 (0.46) l in the CYC group. The mRSS changed from 21.77 (9.86) to 12.10 (10.14) in the RTX group and 23.83 (9.28) to 18.33 (7.69) in the CYC group after 6 months. Serious adverse events were more common in the CYC group. Conclusion: RTX is a safe and effective alternative to CYC in the primary therapy of skin and lung manifestations of scleroderma. Trial registration: Clinical Trials Registry - India, www.ctri.nic.in, CTRI/2017/07/009152.

Synovial IL-9 facilitates neutrophil survival, function and differentiation of Th17 cells in rheumatoid arthritis.

BACKGROUND: Role of Th9 cells and interleukin-9 (IL-9) in human autoimmune diseases such as psoriasis and ulcerative colitis has been explored only very recently. However, their involvement in human rheumatoid arthritis (RA) is not conclusive. Pathogenesis of RA is complex and involves various T cell subsets and neutrophils. Here, we aimed at understanding the impact of IL-9 on infiltrating immune cells and their eventual role in synovial inflammation in RA. METHODS: In vitro stimulation of T cells was performed by engagement of anti-CD3 and anti-CD28 monoclonal antibodies. Flow cytometry was employed for measuring intracellular cytokine, RORγt in T cells, evaluating apoptosis of neutrophils. ELISA was used for measuring soluble cytokine, Western blot analysis and confocal microscopy were used for STAT3 phosphorylation and nuclear translocation. RESULTS: We demonstrated synovial enrichment of Th9 cells and their positive correlation with disease activity (DAS28-ESR) in RA. Synovial IL-9 prolonged the survival of neutrophils, increased their matrix metalloprotienase-9 production and facilitated Th17 cell differentiation evidenced by induction of transcription factor RORγt and STAT3 phosphorylation. IL-9 also augmented the function of IFN-γ + and TNF-α + synovial T cells. CONCLUSIONS: We provide evidences for critical role of IL-9 in disease pathogenesis and propose that targeting IL-9 may be an effective strategy to ameliorate synovial inflammation in RA. Inhibiting IL-9 may have wider impact on the production of pathogenic cytokines involved in autoimmune diseases including RA and may offer better control over the disease.

Menstrual and Gonadal Function Alterations in Women with Systemic Lupus Erythematosus.

PURPOSE: Systemic lupus erythematosus (SLE) is an autoimmune disorder and may affect the reproductive health status of the women. Objective is to analyze the types, incidence of various menstrual disturbances in these women, to identify risk factors and to assess the gonadal function. METHODS: The prospective cohort study was conducted in the SLE clinic of the Rheumatology Department of IPGMEandR, Kolkata from April 2010 to April 2011. Out of 152 females attending clinic, 110 patients fulfilling criteria were included in the study. RESULTS: Mean age of the study population was 27.25±3.4 years. Sixty six cases had menstrual abnormalities (12.72% amenorrhea, 44.45% oligomenorrhea, 2.7% premature ovarian failure, 10.9% menorrhogia). When comparative analysis of demographic, hormonal, ovarian Doppler and therapeutic variables of normal and abnormal cycles was carried out, following parameters were significantly more related to patients with abnormal cycle ; SLEDAI score (12.48±5.53 vs 8.69±4.9; p=0.00), disease duration (6.46±3.08 vs 4.3±1.36; p< 0.05), TSH (7.73±8.64 vs 3.07±2.06; p=0.00.), LH (6.55±4.38 vs 4.56±3.29; p=0.02), a high normal prolactin (12.57±7.75 vs 8.73±3.07; p=0.02), peak systolic velocity (6.53±2.17 vs 9.12±2.1; p=0.00), end-diastolic volume (4.21±2.9 vs 9.35±2.32; p=0.00) and cumulative dose of steroid (24.02±41.44 vs 9.32±9.96; p=0.01).Cyclophosphamide with cumulative dose ≥10 gm was related to amenorrhea and affected gonadal function. Gonadal insufficiency was evident in 33.63% and 2.72% had ovarian failure. CONCLUSIONS: Reduced menstruation is a major health concern in women with SLE as it is frequent and can result in depressed and failed gonadal function later. Doppler study of ovaries is a novel way of depiction of gonadal status in these women. Certain risk factors and revolving treatment part can be preventable.

Cutaneous manifestations of mixed connective tissue disease: study from a tertiary care hospital in eastern India.

CONTEXT: Mixed connective tissue disorder is an uncommon disease. Some scientists are reluctant to recognize it as a separate entity. Some others have defined this ailment. Cutaneous features of this condition are unique. Researchers from India have described these features to relate to those described in the studies from other parts of the globe. AIMS: This study aims to delineate the skin manifestations of clearly defined mixed connective tissue disease (MCTD) patients, to compare them with those established as overlap syndrome, and to relate them with studies from other parts of the globe. SETTINGS AND DESIGN: Successive patients who fulfilled the specific criteria for MCTD presenting in the skin outpatient department of a tertiary care hospital in eastern India were clinically examined from 2009 for 3 years. MATERIALS AND METHODS: The number of participants was 23 and the dermatological features of these were compared with 22 patients with overlap syndrome. The antibody to uridine-rich U1 ribonucleoprotein was measured for all patients. STATISTICAL ANALYSIS USED: SPSS (Version 17) and MedCalc (Version 11.6). RESULTS: THE MALE: Female ratio among the MCTD patients was 1:6.67 and that of the overlap syndrome was 1:10. Twenty patients of the MCTD group presented with synovitis as against only seven in the overlap group. Raynaud's phenomenon was present in some of the subjects. Puffy fingers were rare in our study. Facial numbness was reported by four of those suffering from MCTD. Antinuclear antibody (ANA) was essentially of a speckled pattern in this disease. CONCLUSIONS: Cutaneous indicators of MCTD are distinct from overlap syndrome. Knowledge of these manifestations prevalent in a region may lead to early diagnosis of the disease.