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.

Clinicoradiological profile of interstitial lung diseases at a tertiary care center in Northern India: An eight-year study.

BACKGROUND AND OBJECTIVES: Interstitial lung diseases (ILDs) are a varied group of disorders that have been clubbed together due to some common attributes. The data is abundant from the developed world. However, the developing countries have gradually amassed the knowledge of these disorders and epidemiological data is still missing. We aimed to profile the ILD patients at our center. METHODS: All ILD patients above the age of 14 years were included in the study. A detailed history, examination, exercise capacity assessment, pulmonary function test and relevant serological investigations were done. Tissue was obtained wherever possible. Diagnosis was made after discussion from concerned specialists. RESULTS: Among the total 884 subjects recruited, 54% were females with a mean age of 53 years. Most were residents of rural areas. Reticulations and traction bronchiectasis was seen in most subjects. Hypersensitivity pneumonitis was present in 35.9% and connective-tissue disease related ILD (CTD-ILD) in 30.9%. CONCLUSION: Most common ILDs at our center are hypersensitivity pneumonitis and CTD-ILD. Reticulations and traction bronchiectasis are the most common findings on HRCT thorax.

Neglected tropical rheumatic diseases.

The complexities of dealing with rheumatic diseases in tropical countries are diverse and likely due to limited health care infrastructure, lack of diagnostic and therapeutic facilities, impact of dominant prevailing diseases, and the challenges of differentiating from infectious and non-infectious disease mimics. Several tropical diseases present with musculoskeletal and rheumatic manifestations and often pose a diagnostic dilemma to rheumatologists. The diagnosis is often delayed or the disease is misdiagnosed, leading to poor patient outcomes. Endemic tropical diseases like tuberculosis and leprosy have myriad rheumatic presentations and remain important differentials to consider in patients with rheumatic manifestations. Infection with human immunodeficiency virus is a great masquerade and can mimic manifestations of multiple diseases. The role of viral infections in triggering and perpetuating autoimmunity is well known and chikungunya arthritis is a classic example of the same. This review highlights the rheumatic manifestations of tropical diseases and aims to create awareness among the caregivers. Key Points • It is crucial to be aware and identify infectious diseases presenting with rheumatic manifestations in the tropics. • Presentations akin to classic rheumatic syndromes such as rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus and vasculitis are common.

Clinical, radiologic and serologic profile of patients with interstitial pneumonia with autoimmune features: a cross-sectional study.

The current study aimed to characterize patients from a rheumatology referral center in north India, who satisfied the definition of interstitial pneumonia with autoimmune features (IPAF) as given by the American Thoracic Society and European Respiratory Society (ATS/ERS) consensus committee in 2015. Thirty-five adult patients aged 18 years and above, fulfilling the 2015 ATS/ERS criteria for IPAF were included in the study. The clinical and immunological profile, and radiologic findings on high-resolution computerized tomography thorax were noted. Antinuclear antibody (ANA) by indirect immunofluorescence at 1:320 titer and myositis-specific antibody (MSA) assays were performed. Non-parametric tests were used to compare variables between groups. The study cohort included predominantly female patients with a mean age of 50.6 ± 13 years and mean duration of disease of 38.8 ± 28.4 months. Majority of patients (49%) fulfilled the morphologic and serologic domains as per the IPAF consensus criteria and 31% patients had features in all three domains. Non-specific interstitial pneumonia was the most common pattern observed in 77% patients. Raynaud's phenomenon and inflammatory arthritis were the predominant autoimmune features. Pulmonary arterial hypertension was documented in 60% of patients on echocardiography. Positive ANA at 1:320 dilution was present in all 26 patients tested, whereas extractable nuclear antigen and MSA assays detected autoantibodies in 49% and 51% of patients respectively. IPAF predominantly affected females in the age group of 50 years and above, with varied autoimmune manifestations and autoantibody profile.

Estimates of Prevalence of Pulmonary Hypertension according to Different International Definitions.

Background: Pulmonary hypertension is a dreaded disease associated with considerable morbidity and mortality. The pulmonary hypertension developing due to chronic respiratory disease is a unique subset with symptoms often getting masqueraded by the underlying respiratory condition. The importance of early detection of this complication has been realized worldwide, and recently, the definition of pulmonary hypertension was revised to set the cutoff of mean pulmonary artery pressure (mPAP) at 20 mmHg instead of 25 mmHg at rest. In our study, we have tried to estimate the difference this new definition brings to the prevalence of pulmonary hypertension among interstitial lung disease patients at our centre. Methods: This was a cross-sectional study in which all the patients of ILDs (n = 239) attending the outdoor and indoor Department of Respiratory Medicine, King George's Medical University, India, for the duration of one year were subjected to transthoracic echocardiography along with measurement of serum pro-B-type natriuretic peptide (BNP) and troponin T values. The data were analyzed using the different definitions, and the prevalence was compared. Result: Incidence of pulmonary hypertension among ILD patients at mPAP cutoff ≥ 25 was 28.9%, while that at value ≥20 mmHg, incidence of pulmonary hypertension increased to 46.0%. An increment of 15-20% in incidence of pulmonary hypertension was observed among different types of ILD when cutoff of mPAP was changed. Conclusion: The new definition helps in a significant increase in the detection of pulmonary hypertension, which certainly helps in earlier detection and better management of patients.

Spectrum of interstitial lung diseases and their association with pulmonary hypertension.

Interstitial lung diseases (ILDs) are an intriguing group of pulmonary disorders, which still require the study of epidemiological, genetic, pathophysiological, clinical, and radiological parameters. Pulmonary hypertension (PH) is an underreported complication in interstitial lung diseases which is associated with worse outcome. In our study, we have reported the spectrum of ILDs and estimated the prevalence of pulmonary hypertension among these subjects at a tertiary care centre. A cross-sectional study was performed in which demographical, clinical, radiological, and histological data of subjects with ILD, attending the department of Respiratory Medicine in the University was collected from 1st September 2018 to 31st August 2019. Serological tests were done wherever indicated. Standard criteria along with multidisciplinary opinion were needed to arrive at the final diagnosis. All subjects were screened for pulmonary hypertension via 2-D echocardiography. Mean pulmonary artery pressure ≥20 mmHg was used to define PH. In the defined period, 239 subjects were enrolled (58% females, n=141; mean age 52.38±13.40 years). A tissue diagnosis was obtained in 34% cases.  The most common ILD was hypersensitivity pneumonitis (32.2%), followed by autoimmune-ILD (31.4%), idiopathic pulmonary fibrosis (IPF) (15.9%) and sarcoidosis (12.6%), non-IPF idiopathic interstitial pneumonitis (2.1%) and rest 21 (5.9%) subjects were diagnosed as other types of ILD.  Pulmonary hypertension was seen in 46.0% of subjects.

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.

Multidrug-resistant novel Nocardia neocaledoniensis brain abscess in sarcoidosis.

Central nervous system nocardiosis is a rare, life-threatening infection seen commonly in immunocompromised individuals. Nocardia neocaledoniensis is a novel species seldom causing infections in humans. We describe a patient of sarcoidosis on immunosuppression, who presented with altered sensorium due to a frontal lobe abscess secondary to N. neocaledoniensis infection. Despite appropriate and adequate antibiotic coverage, and timely surgical intervention, the patient succumbed to her illness on day 6 of hospitalisation. This case warrants the consideration of novel infections in patients on immunosuppression and the need for aggressive management.

Prevalence of liver fibrosis by Fibroscan in patients on long-term methotrexate therapy for rheumatoid arthritis.

INTRODUCTION: Data on the long-term use of methotrexate (MTX) causing liver fibrosis in patients with rheumatoid arthritis (RA) is sparse. Liver biopsy is the gold standard to assess fibrosis but is an invasive procedure. Transient elastography (TE) by Fibroscan is a noninvasive validated tool to detect and quantify liver fibrosis. The present study aimed to assess the prevalence of liver fibrosis by Fibroscan in patients with RA on long-term MTX therapy and its correlation with cumulative dose of MTX. METHODS: This cross-sectional study included adult patients (≥ 18 years age) of RA who had been on MTX for ≥ 3 years. The patients' records were reviewed, and the cumulative dose of MTX was calculated. Liver fibrosis was assessed by TE method, and the cutoff value of 7.1 kPa (kilopascal) was considered abnormal (liver fibrosis). Spearman's rank test was used to assess the correlation between the cumulative dose of MTX and Fibroscan score. RESULTS: Seventy-five patients were enrolled of which 69 were females (92%). The mean age was 47.2 ± 11.3 years. The mean body mass index and waist circumference were 24.8 ± 3.9 kg/m2 and 91.6 ± 9.9 cm, respectively. The median duration and cumulative dose of MTX were 336 weeks (interquartile range,144-912 weeks) and 6300 mg (interquartile range, 2400-22,000 mg), respectively. The mean liver stiffness was 5.22 ± 2.03 kPa. Twelve patients (16%) had Fibroscan score ≥ 7.1 kPa, of which 3 patients had severe liver stiffness (9.5 to 12.5 kPa) and one patient had liver stiffness in the range of cirrhosis (> 12.5 kPa). Fibroscan scores significantly correlated with cumulative dose of MTX (r= 0.30, p = 0.008). CONCLUSIONS: Long-term MTX therapy in RA was associated with increased liver stiffness on Fibroscan. Key Points • Fibroscan is a useful tool for monitoring MTX-induced liver fibrosis. • Liver fibrosis as evidenced by increased liver stiffness on Fibroscan is prevalent among patients on long-term MTX therapy for RA.

Prevalence of hydroxychloroquine retinopathy with long-term use in a cohort of Indian patients with rheumatic diseases.

The study aims to estimate the prevalence of hydroxychloroquine (HCQ) retinopathy in a cohort of Indian patients and analyse the associated factors. Adult patients with rheumatological disorders aged ≥ 18 years using HCQ for more than 5 years and/or having received a cumulative dose > 400 g were included. Demographic and clinical data were collected and all underwent ophthalmological tests which included Humphrey automated visual fields (AVF) and spectral domain optical coherence tomography (SD-OCT). The various clinical characteristics of the patients were compared. The study included 110 patients with a mean age of 43.5 ± 10.1 years and predominantly females. Eleven patients (10%) were diagnosed with definite HCQ retinopathy. The mean daily dose of HCQ (mg/kg of real body weight) was significantly different in the groups with and without retinopathy (5.7 ± 0.9 vs 5.1 ± 0.8, p = 0.04). Patients with retinopathy had significantly more colour vision abnormalities (odds of 16.9; confidence interval 4.1-69.1, p = 0.0001) and higher prevalence of both parafoveal and perifoveal thinning (p < 0.0001). Age, gender, duration of HCQ use, cumulative HCQ dose and body mass index were not found to be associated with retinopathy. Four out of 11 patients had abnormalities only on 30-2 protocol for AVF testing, two had abnormalities only on 10-2 protocol, whereas five patients had abnormalities on both protocols. SD-OCT abnormalities were present in all patients with retinopathy. Hydroxychloroquine retinopathy was prevalent in the study cohort and significantly associated with a higher daily dose of HCQ (mg/kg real body weight).

Staphylococcus-associated acute glomerulonephritis in a patient with dermatomyositis.

Staphylococcus-associated glomerulonephritis (SAGN) occurs as a complication of staphylococcal infection elsewhere in the body. Dermatomyositis (DM) can be associated with glomerulonephritis due to the disease per se. We report a case of a 40-year-old male patient with DM who presented with acute kidney injury, and was initially pulsed with methylprednisolone for 3 days, followed by dexamethasone equivalent to 1 mg/kg/day prednisolone. He was subsequently found to have SAGN on kidney biopsy along with staphylococcus bacteraemia and left knee septic arthritis. With proof of definitive infection, intravenous immunoglobulin 2 g/kg over 2 days was given and steroids were reduced. He was treated with intravenous vancomycin. With treatment, the general condition of the patient improved. On day 38, he developed infective endocarditis and died of congestive heart failure subsequently. Undiagnosed staphylococcal sepsis complicating a rheumatological disease course can lead to complications like SAGN, infective endocarditis and contribute to increased morbidity and mortality, as is exemplified by our case.