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.

Semi-quantitative thigh magnetic resonance imaging scores in assessing disease activity and determining long-term clinical outcome in idiopathic inflammatory myopathies: a causal mediation analysis.

OBJECTIVES: To evaluate the relationship of thigh MRI (t-MRI) with manual muscle testing-8 (MMT-8), muscle enzymes and autoantibodies. To determine the causal and mediating factors resulting in poor recovery of MMT-8 in inflammatory myositis (IIM). METHODS: This was a single-centre retrospective study in IIM patients. t-MRI was semi-quantitatively scored for muscle oedema, fascial oedema, muscle atrophy and fatty infiltration. Spearman correlation of t-MRI scores was done with muscle enzymes at baseline, and MMT-8 at baseline and on follow-up. Causal mediation analysis was performed with age, sex, symptom duration, autoantibodies, diabetes and BMI as independent variables, follow-up MMT-8 as dependent and t-MRI scores as mediating variables. RESULTS: Baseline evaluation was done on 59 and follow-up on 38 patients. Median follow-up of the cohort was 31 (10-57) months. Baseline MMT-8 negatively correlated with muscle oedema (r = -0755), fascial oedema (r = -0.443) and muscle atrophy (r = -0.343). Creatinine kinase (r = 0.422) and aspartate transaminase (r = 0.480) positively correlated with muscle oedema. Follow-up MMT-8 correlated negatively with baseline atrophy (r = -0.497) and fatty infiltration (r = -0.531). On follow-up, MMT-8 males had positive total effect (estimate (95%CI)) via atrophy [2.93 (0.44, 4.89)] and fatty infiltration [2.08 (0.54, 3.71)]. Antisynthetase antibody had a positive total effect via fatty infiltration [4.50 (0.37, 7.59)]. Age had a negative total effect via atrophy [-0.09 (0.19, -0.01)] and fatty infiltration [-0.07 (-0.15, -0.01)]. Disease duration had a negative total effect via fatty infiltration [-0.18 (-0.27, -0.02)]. CONCLUSION: Baseline fatty infiltration and muscle atrophy resulting from older age, female sex, longer disease duration and absent anti-synthetase antibodies, partly mediate muscle recovery in IIM.

Kidney histopathology in predicting flares following drug withdrawal in proliferative lupus nephritis in clinical remission.

Residual renal histopathological activity at clinical remission in Proliferative Lupus Nephritis (PLN) can predict renal flare upon immunosuppression withdrawal. Data on the role of histological renal remission in predicting extra-renal flares is lacking. We assessed renal histopathology prior to drug withdrawal and the occurrence of renal and extra-renal flares over 52 weeks after drug withdrawal in PLN patients in long-term clinical remission. This is a subgroup analysis of a non-inferiority, open-label randomized (1:1) controlled trial. Patients with biopsy-proven Class III/IV LN in the past (biopsy 1), on immunosuppressants (IS) ≥ 3 years, in clinical remission for ≥ 1 year, on stable prednisolone dose (≤ 7.5 mg/day) plus a maintenance IS and hydroxychloroquine (HCQ) were subjected to a repeat renal biopsy (biopsy 2). Individuals with biopsy 2 having activity index (AI) < 4/24 were randomised to either prednisolone or IS withdrawal. Primary end-point was the proportion experiencing a flare [SELENA-SLEDAI flare index (SFI)] at week 52. Twenty-eight eligible patients underwent biopsy 2 and randomized to prednisolone (n = 15) and IS (n = 13) withdrawal. At biopsy 1, 12 (43%) had class III, 15 (53.5%) had class IV, and 1 (3.5%) had class III + V. At biopsy 2, PLN persisted in 4 (14.2%) while 18 (64.2%) were in histological remission (AI = 0) with 6 (21.4%) in class II. Following drug withdrawal, 9/28 (32%) had flares especially musculoskeletal (55.5%), mucocutaneous (44.4%), and renal (33.3%). Among the four persistent PLN patients, one of the two (50%) with AI = 1 had extra-renal flare while both the two with AI = 2 (100%) had renal and extra-renal flares. In those with histological remission (biopsy 2), 6/18 (66.6%) experienced extra-renal flare of whom one also had renal flare. Upon drug withdrawal, renal histopathology findings with any activity index can predict renal flare while histological remission is not enough to predict extra-renal flare, thus making it an unsuitable marker for deep SLE remission.

Performance of Clinical and Biochemical Parameters in Identifying Renal Histopathology and Predictors of One-Year Renal Outcome in Lupus Nephritis-A Single Centre Study from India.

Objectives: To assess the performance of clinical and biochemical parameters in identifying renal histopathology. To assess the performance of a combination of demographic, clinical, serological and histopathological parameters in determining renal response at one year. Methods: Data of biopsy-proven (ISN/RPS­2003 criteria) Lupus Nephritis (LN) were extracted from the institute database. Demographic, clinical and biochemical parameters at the time of biopsy were noted, and their associations with histopathological class, activity and chronicity scores were evaluated. Follow-up data at one year were collected. Complete, partial or no response (CR, PR, NR) for renal outcomes at one year and the predictors of NR were assessed. Results: Out of the 333 renal biopsies, 240 (71.8%) were Class III/IV. More patients with Class III/IV LN had hypertension (52.1%) and low eGFR (p < 0.001). Among Class III/IV, AS correlated weakly with UPCR (r = 0.31, p < 0.01), eGFR (r = −0.172; p < 0.01) and CS with eGFR (r = −0.212; p < 0.01). The presence of either hypertension, UPCR > 0.5 g/day, active urinary sediments or serum creatinine >1.3 g/dL had a sensitivity of >96% and specificity of <9% in detecting proliferative LN, crescents, interstitial inflammation and chronicity. NR was higher in males (aOR:3.9, 95% CI:1.4−11.0, p < 0.001), those with abnormal baseline creatinine (aOR: 1.9, 95% CI: 1.1−3.2, p < 0.001), higher renal SLEDAI (p < 0.05), higher AS, CS (p < 0.001) and interstitial inflammation (p < 0.005). In the binary logistic regression, the combination of male sex, baseline creatinine, UPCR and CS performed best in predicting NR (AUC: 0.762; 95% CI: 0.684−0.840, p < 0.001). Conclusions: Clinical and biochemical parameters alone have a poor specificity in identifying renal histopathology. A combination of demographic, clinical and histopathology parameters can better predict renal outcomes at one year.

Effect of skin phototype on quantitative nailfold capillaroscopy.

Objectives: To determine the impact of Fitzpatrick scale-based skin phototype on visualization of capillary density using nailfold capillaroscopy in healthy Indian adults. Methods: In this cross-sectional study, healthy adults were examined for nailfold capillaroscopy findings utilizing a portable capillary microscope at 800× magnification. Photographs of two contiguous areas measuring 1 mm2 each of the distal row of capillaries were captured. Images were captured from the central area of all fingers except thumb in both hands. Capillary density and morphology of nailfold capillaroscopies were assessed by two blinded assessors. The nailfold capillaroscopy parameters were compared between the Standard Fitzpatrick scale-based skin phototypes. Results: A total of 118 healthy adults were enrolled in the study. Type III, IV, V, and VI skin phototypes were seen in 27 (22.90%), 32 (27.19%), 29 (24.58%), and 30 (25.42%) participants, respectively. All participants (100%) had normal nailfold capillaroscopy morphology and architecture. Zero capillaries were visible in 11 fingers among 5 patients (4.24%) and all of them had Type VI phototype. The median capillary density per mm was 5.19 (interquartile range = 4.37-6.75) with 90 (76.27%) participants having less than seven capillaries. The median average capillary density was significantly different (p-value < 0.0001) across Type III (8.13, interquartile range = 6.44-8.88), Type IV (5.67, interquartile range = 4.41-6.98), Type V (4.94, interquartile range = 4.19-5.38), and Type VI (4.53, interquartile range = 3.72-4.91) phototypes (p < 0.05). Conclusion: The number of capillaries visualized during nailfold capillaroscopy decreases as the skin pigmentation increases. There is a need to redefine the nailfold capillaroscopy density and avascularity by taking skin phototype as one of the determinants before labeling a nailfold capillaroscopy finding with less visualized capillaries as abnormal.

Performance of timed function tests as outcome measures in idiopathic inflammatory myopathy-results from a single-centre cohort.

OBJECTIVE: To evaluate performance of timed function tests (TFTs) in assessing muscle strength and endurance as determined by Manual Muscle Testing 8 (MMT-8) and Functional Index 2 (FI-2), respectively, in idiopathic inflammatory myopathies (IIM). METHODS: This cohort study included 42 IIM patients satisfying 2017 EULAR/ACR criteria. Patients were classified as active (n = 18) or inactive disease (n = 24) based on clinical status at baseline. MMT-8, FI-2, 30 s rise from chair test, 30 s 1 kg arm rise test and 2-min walking distance (2MWD) were administered at baseline, 3 months and 6 months. Pearson rank correlation analysis and receiver operating curves were performed to assess the performance of timed function tests. RESULTS: All patients were followed up at 3 months and 39 completed 6 months' follow-up. All the three TFTs had excellent convergent (r > 0.7, P < 0.05) and divergent validity (P < 0.05). Only 2MWD had moderate to strong correlation with ΔMMT-8 at 3 and 6 months among those with active disease (P = 0.001). All the TFTs correlated with ΔFI-2 in active disease but only Δ2MWD correlated with ΔFI-2 in inactive disease at 6 months (r = 0.506, P = 0.036). At a cut-off of 5% improvement in MMT-8, 2MWD had an area under the curve (AUC) of 0.868 with 95% sensitivity with 2% improvement at 3 months. To detect a 10% ΔMMT-8, Δ2MWD at a cut of 8% and 7% had an AUC of 0.909 and 0.893 with a sensitivity of 92% at 3 and 6 months, respectively (P < 0.05). CONCLUSION: 2MWD is a reliable indicator of muscle strength, endurance and treatment response. The 2MWD can be self-administered by patients, making it a potential patient-reported outcome measure.

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.

Tele-rheumatology for overcoming socioeconomic barriers to healthcare in resource constrained settings: lessons from COVID-19 pandemic.

OBJECTIVES: To assess acceptability of teleconsultation among the socioeconomically marginalized sections of patients with rheumatic and musculoskeletal diseases (RMDs), to identify the socioeconomic barriers in continuing rheumatology care during the COVID-19 crisis and to identify patients who could benefit by shifting to tele-rheumatology consultations. METHODS: This was a cross sectional analytical study done at a tertiary care teaching hospital in India including patients with RMDs who were not on biological diseases modifying agents. Assessment of disease status, socioeconomic status and economic impact of COVID-19 was done via tele-consultation. RESULTS: Out of the 680 patients satisfying inclusion criteria, 373 completed the study. The format was found easy by 334 (89.6%) of them and 284 (76.1%) considered tele-rheumatology better than in-person consultation. During the pre-COVID months, the median monthly per capita income of the families of our patients and cost of illness was Indian rupees (INR) 2000 (US$ 26) and INR 1685 (US$ 21.91), respectively. Families whose financial needs were met (OR = 0.38, 95% CI: 0.239, 0.598) or those with schooling upto at least secondary school (OR = 0.442, 95% CI: 0.260, 0.752) (P =0.002) were less likely to stop prescription drugs. In a hypothetical model, 289 (77.4%) could be successfully switched to tele-rheumatology follow-up. CONCLUSION: The acceptability of tele-rheumatology among socioeconomically marginalized patients with RMDs is good. During times of crisis, patients from poorer strata of society and lower educational background are likely to abruptly stop medications. Switching to a telemedicine-based hybrid model is likely to improve drug adherence with substantial savings on loss of pay and out of pocket expenditure.

Cultural adaptation, translation and validation of Cochin Hand Function Scale and evaluation of hand dysfunction in systemic sclerosis.

OBJECTIVES: Hand dysfunction causes significant reduction in quality of life in systemic sclerosis. We assessed the validity and reliability of the culturally adapted Indian version of Cochin Hand Function Scale (I-CHFS). We determined the factors contributing to hand dysfunction and its burden on quality of life. METHOD: I-CHFS was formulated by replacing five questions (questions 7, 9, 10, 14 and 15) in CHFS which were determined as unsuitable in an Indian setting. The instrument was assessed for acceptability, reliability, reproducibility and validity measures. A total of 87 patients were assessed for various demographic and disease parameters, hand disability and quality of life. RESULTS: The median I-CHFS score was 22(5-54) and 04 (0.5-17.5) among diffuse (dcSSc) and limited cutaneous systemic sclerosis (lcSSc). I-CHFS showed good reproducibility (interclass correlation coefficient = 0.92) and a strong correlation with I-HAQ (rs = 0.832), usual activities EQ-5D-5L (rs = 0.744), self-care EQ-5D-5L (rs = 0.734) and anxiety/depression EQ-5D-5L (rs = 0.729). It had moderate correlation with pain/discomfort EQ-5D-5L (rs = 0.661) and hand HAQ (rs = 0.576) and poor correlation with HAQ-DI (rs = 0.396) and modified Rodnan skin score (rs = 0.390). Finger to table distance, finger to palm distance in extension and limited hand modified Rodnan skin score were significantly associated with higher values of I-CHFS. CONCLUSIONS: Hand dysfunction in systemic sclerosis is substantial and contributes significantly to poor quality of life. The culturally adapted I-CHFS is a valid and reliable tool to assess it and correlated well with the overall disease burden. Key Points • Hand dysfunction is common among systemic sclerosis patients. • Hand dysfunction contributes to the poor quality of life and more disease burden. • Culturally adapted Cochin Hand function Scale helps assess hand dysfunction among Indian scleroderma patients.

Case control study: magnetic resonance spectroscopy of brain in HIV infected patients.

BACKGROUND: In vivo proton magnetic resonance spectroscopy ((1)H-MRS) studies on brain in HIV infected patients have shown significant alteration in neuro-biochemicals. METHODS: In this study, we measured the neuro-biochemical metabolites from the left frontal white matter (FWM) and left basal ganglia (BG) caudate head nucleus in 71 subjects that include 30 healthy controls, 20 asymptomatic HIV and 21 HIV patients with CNS lesion. Proton MR spectra were acquired at 3 T MRI system and the concentration (institutional units) of tNAA (N-acetylaspartate, NAA + N-acetylaspartylglutamate, NAAG), tCr (Creatine, Cr + phosphocreatine, PCr), choline containing compounds (tCho), glutamate + glutamine (Glx) and lipid and macromolecules at 0.9 ppm were determined using LC Model. RESULTS: In BG, the concentration of tNAA (6.71 ± 0.64) was decreased and in FWM, the concentration of Glx (20.4 ± 7.8), tCr (9.14 ± 3.04) and lipid and macromolecules at 0.9 ppm (8.69 ± 2.96) were increased in HIV patients with CNS lesion. In healthy controls, the concentration of tNAA in BG was 7.31 ± 0.47 and concentration of Glx, tCr and lipid and macromolecules in FWM were 15.0 ± 6.06, 6.95 ± 2.56, 5.59 ± 1.56, respectively. CONCLUSION: Reduced tNAA in BG suggests neuronal loss in HIV patients with CNS lesion while increased Glx in FWM may suggest excito-toxicity. In addition, increased levels of tCr in FWM of HIV patients were observed. The study indicates region specific metabolic changes in tNAA, tCr and Glx in brain of HIV infected patients.