Debashish Danda

Supplementation of 1,25 dihydroxy vitamin D3 in patients with treatment naive early rheumatoid arthritis: a randomised controlled trial.

Aim:  1,25 dihydroxy vitamin D3 has immunomodulatory functions in rheumatoid arthritis (RA) and is an anti‐osteoporotic agent. No studies exist to assess its pain‐relieving action in RA.

Rapid control of disease activity by tocilizumab in 10 ‘difficult-to-treat’ cases of Takayasu arteritis

To assess outcome of 10 ‘difficult to treat’ patients with Takayasu arteritis (TA) treated with tocilizumab.

Analysis of the WISP3 gene in Indian families with progressive pseudorheumatoid dysplasia.

Progressive pseudorheumatoid dysplasia (PPD) is a progressive skeletal syndrome characterized by stiffness, swelling and pain in multiple joints with associated osteoporosis in affected patients. Radiographically, the predominant features resemble a spondyloepiphyseal dysplasia. Mutations in the WISP3 gene are known to cause this autosomal recessive condition. To date, only a limited number of studies have looked into the spectrum of mutations causing PPD. We report on clinical features and WISP3 mutations in a large series of Indian patients with this rare skeletal dysplasia. Families with at least one member showing clinical and radiologic features of PPD were recruited for the study. Symptoms, signs and radiographic findings were documented in 35 patients from 25 unrelated families. Swelling of small joints of hands and contractures are the most common presenting features. Mutation analysis was carried out by bidirectional sequencing of the WISP3 gene in all 35 patients. We summarize the clinical features of 35 patients with PPD and report on 11 different homozygous mutations and one instance of compound heterozygosity. Eight (c.233G>A, c.340T>C, c.348C>A, c.433T>C, c.682T>C, c.802T>G, c.947_951delAATTT, and c.1010G>A) are novel mutations and three (c.156C>A, c.248G>A, and c.739_740delTG) have been reported previously. One missense mutation (c.1010G>A; p.Cys337Tyr) appears to be the most common in our population being seen in 10 unrelated families. This is the largest cohort of patients with PPD in the literature and the first report from India on mutation analysis of WISP3. We also review all the mutations reported in WISP3 till date.

Ocular manifestations of Takayasu arteritis: a cross-sectional study.

Purpose: To detail the spectrum of eye manifestations in Takayasu arteritis and factors predisposing to its development. Methods: In this cross-sectional study, 61 patients with proven Takayasu arteritis who were identified during a 16-month period were evaluated for disease- and treatment-related eye manifestations. A fundus fluorescein angiography examination was performed where indicated and with the patients consent. Results: The mean (±standard deviation) duration of illness before ophthalmic evaluation was 55 ± 69 months. Decreased vision was the most common ocular symptom (30%). Thirty-five patients underwent fundus fluorescein angiography examination. Takayasu retinopathy was seen in 9 (15%), ocular ischemic syndrome in 4 (7%), and hypertensive retinopathy in 10 (16%) patients. The most common treatment-related ocular complication was steroid-induced cataract (23%). Other manifestations included iris neovascularization (n = 3), anterior ischemic optic neuropathy (n = 2), steroid-induced glaucoma (n = 1), neovascular glaucoma (n = 1), and uveitis (n = 1). Those manifesting Takayasu retinopathy and ocular ischemic syndrome had significantly (P < 0.05) lower blood pressure in both upper limbs compared with patients not manifesting ischemic retinopathy. A significant (P < 0.03) proportion of patients with Takayasu retinopathy and ocular ischemic syndrome had a nonrecordable right upper limb blood pressure. Conclusion: Disease- and treatment-related ocular complications are not infrequent in Takayasu arteritis. Arteritis involving the aortic arch and its branches favors the development of ischemic ocular complications.

MYCOPHENOLATE MOFETIL IN NEUROPSYCHIATRIC SYSTEMIC LUPUS ERYTHEMATOSUS

Neuropsychiatric abnormalities frequently occur in patients with systemic lupus erythematosus, affecting as many as 14-75% of people with this disease. High-dose steroid with or without anticoagulation is the mainstay of treatment in neuropsychiatric systemic lupus erythematosus (NPSLE). Use of mycophenolate as a steroid sparing drug may be a potential alternative agent in the therapy of NPLE, but lack of randomized trials and cost prohibit its widespread use. Its safety profile is higher than that of cyclophosphamide and azathioprine. We report a successfully treated case of neuropsychiatric systemic lupus erythematosus, presenting as psychosis, whose long-term remission was maintained on treatment with mycophenolate mofetil.

Does the buck stop with the bugs?: an overview of microbial dysbiosis in rheumatoid arthritis

The human body is an environmental niche which is home to diverse co‐habiting microbes collectively referred as the human microbiome. Recent years have seen the in‐depth characterization of the human microbiome and associations with diseases. Linking of the composition or number of the human microbiota with diseases and traits date back to the original work of Elie Metchnikoff. Recent advances in genomic technologies have opened up finer details and dynamics of this new science with higher precision. Microbe‐rheumatoid arthritis connection, largely related to the gut and oral microbiomes, has showed up as a result – apart from several other earlier, well‐studied candidate autoimmune diseases. Although evidence favouring roles of specific microbial species, including Porphyromonas, Prevotella and Leptotricha, has become clearer, mechanistic insights still continue to be enigmatic. Manipulating the microbes by traditional dietary modifications, probiotics, and antibiotics and by currently employed disease‐modifying agents seems to modulate the disease process and its progression. In the present review, we appraise the existing information as well as the gaps in knowledge in this challenging field. We also discuss the future directions for potential clinical applications, including prevention and management of rheumatoid arthritis using microbial modifications.

The matrix protein Fibulin-5 is at the interface of tissue stiffness and inflammation in fibrosis.

Fibrosis is a pervasive disease in which the excessive deposition of extracellular matrix (ECM) compromises tissue function. Although the underlying mechanisms are mostly unknown, matrix stiffness is increasingly appreciated as a contributor to fibrosis rather than merely a manifestation of the disease. Here we show that the loss of Fibulin-5, an elastic fibre component, not only decreases tissue stiffness, but also diminishes the inflammatory response and abrogates the fibrotic phenotype in a mouse model of cutaneous fibrosis. Increasing matrix stiffness raises the inflammatory response above a threshold level, independent of TGF-β, to stimulate further ECM secretion from fibroblasts and advance the progression of fibrosis. These results suggest that Fibulin-5 may be a therapeutic target to short-circuit this profibrotic feedback loop.

Influence of geolocation and ethnicity on the phenotypic expression of primary Sjögren's syndrome at diagnosis in 8310 patients : a cross-sectional study from the Big Data Sjögren Project Consortium

Objectives To analyse the influence of geolocation and ethnicity on the clinical presentation of primary Sjögrens syndrome (SjS) at diagnosis. Methods The Big Data Sjögren Project Consortium is an international, multicentre registry designed in 2014. By January 2016, 20 centres from five continents were participating. Multivariable logistic regression analyses were performed. Results We included 7748 women (93%) and 562 men (7%), with a mean age at diagnosis of primary SjS of 53 years. Ethnicity data were available for 7884 patients (95%): 6174 patients (78%) were white, 1066 patients (14%) were Asian, 393 patients (5%) were Hispanic, 104 patients (1%) were black/African-American and 147 patients (2%) were of other ethnicities. SjS was diagnosed a mean of 7 years earlier in black/African-American compared with white patients; the female-to-male ratio was highest in Asian patients (27:1) and lowest in black/African-American patients (7:1); the prevalence of sicca symptoms was lowest in Asian patients; a higher frequency of positive salivary biopsy was found in Hispanic and white patients. A north-south gradient was found with respect to a lower frequency of ocular involvement in northern countries for dry eyes and abnormal ocular tests in Europe (OR 0.46 and 0.44, respectively) and Asia (OR 0.18 and 0.49, respectively) compared with southern countries. Higher frequencies of antinuclear antibodies (ANAs) were reported in northern countries in America (OR=1.48) and Asia (OR=3.80) while, in Europe, northern countries had lowest frequencies of ANAs (OR=0.67) and Ro/La (OR=0.69). Conclusions This study provides the first evidence of a strong influence of geolocation and ethnicity on the phenotype of primary SjS at diagnosis.

Childhood-onset Takayasu arteritis: an update.

Childhood‐onset Takayasu arteritis (c‐TA) is a distinct subset affecting a wide age group, ranging from young infants to adolescents and it differs from adult TA in many aspects. There is scarcity of data on c‐TA worldwide. The disease is classified using the European League Against Rheumatism/Pediatric Rheumatology International Trials Organization/Pediatric Rheumatology European Society criteria. The non‐specific nature of presenting complaints and lack of appropriate biomarkers delay the early diagnosis of this illness and many children present with complications, which become irreversible once they set in. One of the largest cohorts of 40 children with c‐TA from our center reports hypertension as the commonest presenting feature. Systemic symptoms like headache, fever and weight loss are also described. Assessment of disease in c‐TA is done by correlating clinical features with raised inflammatory markers. Advanced imaging plays an important role in diagnosis. In c‐TA, the role of magnetic resonance angiography is advocated, taking into consideration the enormous amount of radiation exposure with other modalities. Complications of c‐TA include cardiovascular, pulmonary, neurological and those arising secondary to long‐term steroid and immunosuppression therapy.

A descriptive analysis of 14 cases of progressive-psuedorheumatoid-arthropathy of childhood from south India: Review of literature in comparison with Juvenile Idiopathic Arthritis

BACKGROUND Progressive-psuedorheumatoid-arthropathy of childhood (PPAC) is an autosomal recessive single gene skeletal dysplasia involving joints. The gene attributed to its cause is WNT1-inducible-signaling pathway protein3 (WISP3). OBJECTIVE To study the clinical and radiographic presentation of PPAC in Indian patients and to compare with described features of PPAC and Juvenile Idiopathic Arthritis (JIA) from published literature. METHODS All cases (n = 14) of PPAC seen in the Rheumatology and Clinical Genetics outpatient clinic between 2008 and 2011 with classical, clinical, and radiological features were studied. The demographic and clinical data were obtained from medical records of the outpatient visits. RESULTS Slight female preponderance (57%) and history of consanguinity in parents (43%) was observed in this group. The median age at onset was 4.5 years (range from birth to 9 years of age). Early presentation below the age of 3 years was seen in 3/14 patients (21%) in this group. The growth of all the patients fell below the 3rd percentile for the age. Historically, hip joint involvement was the most common presenting feature; however, elbow, wrist, knees, feet, spine, shoulder joints and small joints, namely proximal interphalangeal (PIP), distal interphalangeal (DIP), metacarpophalangeal (MCP), metatarsophalangeal joints (MTP), and interphalangeal joints (IP) of the feet, were also involved, either clinically or radiologically in varying proportions. Platyspondyly was noted in all. Molecular analysis of the WISP3 gene identified mutations in all the 5 individuals in whom it was done. CONCLUSION This descriptive case series of PPAC from India reports distinctly differentiating clinical, radiological, and molecular markers in contrast with classically described features of JIA, its mimic. Early presentation (age of onset below 3 years) with involvement of interphalangeal joints seen in three patients (21%) was a unique finding, with missense WISP3 gene mutations in all of them. Timely diagnosis of this entity can spare the patient from unnecessary investigations and toxic medications.