The Coexisting Neuromyelitis Optica Spectrum Disorder and Systemic Lupus Erythematosus: A Therapeutic Challenge.

Neuromyelitis Optica (NMO), or Devic's disease, is an immune-mediated, usually relapsing, central nervous system (CNS) demyelination disorder associated with optic neuritis and transverse myelitis. It is characterised by the presence of longitudinally extensive transverse myelitis (LETM) and antibodies against water channel aquaporin-4 (AQP4-immunoglobulin G [IgG]). The term NMO spectrum disorder (NMOSD) includes patients with limited forms of NMO who are at risk of recurrence. Often patients with NMO or NMOSD have an associated systemic autoimmune disease, most commonly systemic lupus erythematosus (SLE) or Sjogren syndrome (SS) or a related profile of non-organ-specific autoantibodies. The intriguing aspect of coexisting NMOSD and SLE is whether they are independent diseases that can coexist with each other or the serological findings specific to both diseases in a patient is a non-specific finding of no prognostic or therapeutic concern. We have presented two cases of NMOSD coexisting with SLE and based upon the existing evidence in the literature we present that the two conditions are independent of each other, and, at times, it can throw a therapeutic challenge to any clinician.

The prevalence of osteoporosis and its association with serum testosterone and serum vitamin D in the elderly male population: A cross-sectional study.

Background: Male osteoporosis is under-diagnosed and poorly studied. With the ageing population, osteoporotic fracture in men is an emerging health problem. The aim of this study was to study the prevalence of osteoporosis and its association with serum testosterone and serum vitamin D in elderly men (>60 years old) attending the outpatient department (OPD). Methods: An observational cross-sectional study was performed in elderly men (>60 years old) attending OPD of a tertiary care hospital of Western Maharashtra between April 2017 and June 2019. Patients with rheumatological disorders, history of vertebral/femoral fractures, chronic kidney disease, chronic liver disease, thyroid disorders and alcohol dependence were excluded. Data were analysed using the chi-square test and descriptive statistics. Results: In total, 408 male patients were included. The mean age was 68.33 years. Osteoporosis was seen in 39.5% of patients (161/408) with a T score of ≤2.5. Osteopenia was noted in 48.3% of patients (197/408). T and Z scores had significant correlation (p = <0.001). Only 12% of elderly men had normal bone mineral density score. Serum testosterone, chronic obstructive pulmonary disease (COPD) and benign prostatic hypertrophy (BPH) were significantly associated with male osteoporosis with a p-value of 0.019, 0.016 and 0.010, respectively. Vitamin D levels, type 2 diabetes mellitus, hypertension and coronary artery disease did not show any significant association with male osteoporosis. Conclusion: Osteoporosis was noted in 39.5% of the elderly men. In addition, decreased testosterone, COPD and BPH were significantly associated with male osteoporosis. It is important to screen elderly men to diagnose osteoporosis early and prevent osteoporotic fractures.

The diagnostic utility of rheumatoid factor and anticitrullinated protein antibody for rheumatoid arthritis in the Indian population.

Background: There is lack of Indian data on diagnostic utility of rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) for diagnosis of rheumatoid arthritis (RA) and prevalence of these antibodies in patients with RA and the healthy population. The study was aimed to assess the diagnostic utility and prevalence of RF and ACPA at different titers in the Indian scenario. Method: All the patients of RA fulfilling the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) 2010 classification criteria and age and gender-matched healthy controls were included in the study. RF and ACPA were measured by nephelometry and the enzyme-linked immunosorbent assay (ELISA) method, respectively. Result: Of 803 patients (291 men and 512 women) included, the RF was positive in 566 (70.5%) study patients. The ACPA was positive in 527 (71.7%) patients of 735 of them. Among 408 healthy controls, 45 (11%) were RF positive and 19 (4.7%) were ACPA positive.At the positive cutoff level, the RF had a specificity of 87.6% (95% confidence interval [CI] = 84.4-90.8; positive likelihood ratio [LR+] 5.7). Specificity at 2 and 3 times above the upper limit of normal (ULN) increased to 96.2% (95% CI = 94.3-98.1; LR+ 15.7) and 97.1% (95% CI = 95.5-98.7; LR+ 17.1), respectively.The specificity of ACPA at the positive cutoff level was 94.4% (95% CI = 92.2-96.6; LR+ 12.7), which increased to 98% (95% CI = 96.6-99.4), at 2xULN level. The likelihood ratio for ACPA at all cutoff levels measured was more than 10. Conclusion: The sensitivity and specificity of RF and ACPA in our study population are comparable with those of other studies. ACPA at lower titers may have sufficient diagnostic utility for RA in an appropriate clinical setting.

Serum interleukin-6 in seropositive rheumatoid arthritis and response to tocilizumab: An observational study.

OBJECTIVE: There is no clinically useful biomarker as a predictor of response to any class of biological disease-modifying antirheumatic drugs (bDMARD). Serum interleukin-6 (IL-6) has a major role in the pathogenesis of rheumatoid arthritis (RA) and its serum level in patients of RA may predict response to treatment with IL-6 receptor (IL-6R) antagonist tocilizumab. METHODS: Biological DMARD naïve patients of seropositive RA, fulfilling American College of Rheumatology/European League Against Rheumatism classification criteria 2010, were treated with 06 doses of tocilizumab (8mg/kg) at monthly interval. Baseline and post-treatment serum IL-6 levels were measured and correlated with response to treatment measured by disease activity score-28 joints erythrocyte sedimentation rate (DAS28 ESR) after treatment. RESULTS: The study included 34 patients and 26 (70%) of them achieved DAS-28 remission (DAS28 ESR < 2.6). The baseline serum IL-6 did not correlate with post-treatment DAS28 ESR (R -0.197, P = .264). Though, statistically not significant (P = .085) more patients with comparatively lower baseline serum IL-6 attained DAS28 remission (16 out of 17, P = .085). There was an increase in the serum IL-6 level (median 40.5pg/ml [IQR 130.2] to 72.6pg/ml [IQR 162.5]) after tocilizumab treatment and the change in IL-6 level also did not correlate with post-treatment DAS28 ESR (R -0.240, P = .172). CONCLUSION: Higher number of patients with comparatively lower serum IL-6 level attained DAS28 remission in this study; however, it was not statistically significant. It requires further evaluation in larger studies to make any conclusion on the role of serum IL-6 as a predictor of response to tocilizumab in seropositive RA.

Assessment of ideal serum dilution for screening of antinuclear antibodies by an indirect immunofluorescence method in diagnosis of autoimmune disorders.

BACKGROUND: Time and cost constraints lead to majority of clinical laboratories deviating away from an ideal practice of checking for antinuclear antibodies (ANAs) by indirect immunofluorescence (IIF) at multiple dilutions. Usage of screening dilution of 1:40 recommended by most manufacturers of commercial ANA kits results in numerous false positive-tests and misdiagnosis of connective tissue disorders (CTDs). We sought to study the ideal screening dilution for ANA by IIF for a diagnosis of ANA-related CTDs. METHODS: Serum samples of patients with ANA-related conditions (n = 233) and healthy controls (n = 154) were evaluated by IIF using Immuno Concepts Hep-2000 ® ANA kits at dilutions from 1:40 to 1:640. Accuracy for diagnosis of CTDs for each serum dilution was assessed by receiver operating curve (ROC) analysis. RESULTS: Antinuclear antibodies (ANA) positivity was observed in 19.5%, 10.4%, 4.55%, 0.65%, and 0% of healthy controls at dilutions of 1:40, 1:80, 1:160, 1:320, and 1:640, respectively. ANA positivity at 1:40 dilution was observed among 26.4% cases with mimics of CTDs. Prevalence of ANA positivity in ANA-related CTDs was 97.3%, 96.4%, 89.3%, 83.9%, and 71.4% at dilutions of 1:40, 1:80, 1:160, 1:320, and 1:640, respectively. ROC analysis revealed best test performance for distinction between healthy and ANA-related CTD populations at a serum dilution of 1 in 80. CONCLUSIONS: Antinuclear antibodies (ANA) positivity at low titers (1:40) is highly prevalent in healthy population (19.5%) as well as amongst mimics of CTD (26.4%). Our study suggests a higher screening dilution of 1:80 for ANA by IIF for diagnosis of CTD maybe better. Combination of 1:80 and 1:160 dilutions provides optimum sensitivity and specificity for diagnosis of ANA-related disorders.

Nailfold capillaroscopy in psoriasis.

BACKGROUND: Psoriasis a chronic inflammatory skin disease manifests with microcirculatory changes within skin which may precede skin manifestations, correlate with their severity, joint involvement and resolve with treatment. Nailfold capillaroscopy (NFC) is used in rheumatology for connective tissue disorder assessment and is assuming significance in psoriasis. The aim was to study the nailfold capillaroscopic findings in patients with psoriasis. METHODS: A cross-sectional observational study was carried out at a skin center of a tertiary care hospital from January 2016 to June 2017. Selected cases underwent NFC using a portable color capillaroscope with an attached computer with software to analyze the nailfold capillaries for morphological parameters and abnormalities. Independent-samples t test and chi-square test was used to analyze the relationships between variables. RESULTS: Mean capillary loop density in 96% of study population was subnormal (<9 capillaries/mm), mean arterial limb diameter 11.37 ± 2.434µ; mean venous limb diameter 15.89 ± 3.131µ, top of the loop diameter 14.41 ± 4.373µ and length of the loop was 152.51 ± 57.21µ. Only 3 had length of loop >300µ. Bizarre morphology was seen in 15.5% of capillaries (p value < 0.001). Crossed loops/tortuous capillaries were seen in 17.3% of patients (p value < 0.001). Ramified capillaries were seen in 9.1% of patients with psoriasis (p value < 0.001). Other abnormalities observed were hemorrhage, avascular areas and subpapillary plexus. Widespread disease and psoriatic arthritis (18.2%) had irregular and haphazard distribution of capillaries (p value < 0.001). Analysis of Psoriasis Area Severity Index score, age of the patient and NFC did not reveal any statistically significant relationship. CONCLUSIONS: Nailfold capillaroscopy (NFC), a non invasive imaging technique for microcirculation evaluation can serve to prognosticate and follow up patirents with psoriasis as a simple and highly reproducible tool. Nailfold capillaroscopy is a simple and an easy method to study the microvascular abnormalities in psoriasis. Findings correlate with disease severity. It can be used for follow-up as a predictor of disease worsening or response to treatment.

Stem cell transplant in systemic sclerosis: An Indian experience.

AIM: To prospectively evaluate long term outcomes in a cohort of patients with Systemic sclerosis treated with Hematopoietic stem cell transplant (HSCT). METHOD: This is a prospective observational study of four SSc patients who underwent HSCT at a tertiary care center in India between 2008-2012. The selection criteria included young individuals with rapidly progressive disease and at least one major organ involvement. We used granulocyte colony-stimulating factor for peripheral blood stem cell mobilization, pre-transplant conditioning with fludarabine, cyclophosphamide and rabbit anti-thymocyte globulin followed by re-infusion of autologous stem cells as per standard institute protocol. RESULTS: A total of four patients (one male and three females) underwent autologous HSCT for SSc. Patients had heterogeneous disease manifestations including severe Raynaud's phenomenon with vasculopathic ulcers, gastrointestinal problems and mild interstitial lung disease (ILD). Patients were followed up for a mean duration of 7 years. There was significant sustained improvement in skin score, vasculopathy and gastrointestinal manifestations. Interstitial lung disease did not show any deterioration. The quality of life indices showed remarkable improvement in all subjects. No complications related to transplant were noted. CONCLUSION: In absence of an effective pharmacotherapy for SSc, autologous HSCT has a huge potential in management of cutaneous and internal organ manifestations.

Proteomic analysis of human osteoarthritis synovial fluid.

BACKGROUND: Osteoarthritis is a chronic musculoskeletal disorder characterized mainly by progressive degradation of the hyaline cartilage. Patients with osteoarthritis often postpone seeking medical help, which results in the diagnosis being made at an advanced stage of cartilage destruction. Sustained efforts are needed to identify specific markers that might help in early diagnosis, monitoring disease progression and in improving therapeutic outcomes. We employed a multipronged proteomic approach, which included multiple fractionation strategies followed by high resolution mass spectrometry analysis to explore the proteome of synovial fluid obtained from osteoarthritis patients. In addition to the total proteome, we also enriched glycoproteins from synovial fluid using lectin affinity chromatography. RESULTS: We identified 677 proteins from synovial fluid of patients with osteoarthritis of which 545 proteins have not been previously reported. These novel proteins included ADAM-like decysin 1 (ADAMDEC1), alanyl (membrane) aminopeptidase (ANPEP), CD84, fibulin 1 (FBLN1), matrix remodelling associated 5 (MXRA5), secreted phosphoprotein 2 (SPP2) and spondin 2 (SPON2). We identified 300 proteins using lectin affinity chromatography, including the glycoproteins afamin (AFM), attractin (ATRN), fibrillin 1 (FBN1), transferrin (TF), tissue inhibitor of metalloproteinase 1 (TIMP1) and vasorin (VSN). Gene ontology analysis confirmed that a majority of the identified proteins were extracellular and are mostly involved in cell communication and signaling. We also confirmed the expression of ANPEP, dickkopf WNT signaling pathway inhibitor 3 (DKK3) and osteoglycin (OGN) by multiple reaction monitoring (MRM) analysis of osteoarthritis synovial fluid samples. CONCLUSIONS: We present an in-depth analysis of the synovial fluid proteome from patients with osteoarthritis. We believe that the catalog of proteins generated in this study will further enhance our knowledge regarding the pathophysiology of osteoarthritis and should assist in identifying better biomarkers for early diagnosis.

Clinical profile of benign joint hypermobility syndrome from a tertiary care military hospital in India.

BACKGROUND AND AIMS: Joint hypermobility when associated with symptoms in the absence of systemic rheumatologic disease is termed as benign joint hypermobility syndrome (BJHS). BJHS is often an under-recognised and a poorly managed entity. Indian studies on BJHS are very few and none have been carried out in any of the service rheumatology centres. Hence this retrospective study was carried out at a tertiary medical institute of the Indian Army to assess the varied clinical profile of BJHS. METHODS: All patients consecutively diagnosed as BJHS at the rheumatology clinic of the Army Hospital (Research and Referral) Delhi from May 2010 to May 2011 were included in the study. Their age, sex, presenting features, clinical profile, laboratory and radiological parameters were studied. RESULTS: The mean age of these patients was 30 ± 5.71 years with a median duration of symptoms of 42 (06-120) months. There were 45 males and 39 females (male : female = 1.15 : 1.00). The median Beighton's score in these patients was 6/9 (range 4-9). Most of our patients were military personnel (43/84), and all had knee joint pain with evidence of degenerative changes in 19 and synovitis in two patients. Eleven patients including nine military personnel had evidence of soft tissue rheumatism with associated fibromyalgia in four and anxiety disorder in one. Out of 18 patients with a Beighton's score of ≥ 7, nine had incidental findings of lateral head tilt on frontal observation. There was evidence of carpal tunnel syndrome in a patient with wrist synovitis and one patient had associated skin laxity without features of Ehlers-Danlos syndrome. CONCLUSION: BJHS is often under-recognized in clinical practice and is usually missed because of a lack of awareness. A high index of clinical suspicion to diagnose this entity is essential due to its associated morbidities, especially among those exposed to strenuous physical activities.

Nailfold capillaroscopy by digital microscope in an Indian population with systemic sclerosis.

AIM: Nailfold capillaroscopy (NFC) is a simple, non-invasive method with exceptional predictive value for the analysis of microvascular abnormalities, especially in systemic sclerosis (SSc) but remains underutilized due to cost factors of the nailfold videocapillaroscope, lack of expertise and availability issues. The aim of this study was to establish the utility of an inexpensive digital microscope to study NFC changes in SSc in correlation with disease subsets and extent of skin involvement. METHODS: Twenty-two diffuse cutaneous SSc (DSS), 20 limited cutaneous SSc (LSS) patients and 42 controls were evaluated with NFC using a digital microscope at 30× and 100× magnification. Digital micrographs were used to study qualitative and quantitative changes in microvasculature. RESULTS: The capillary density was significantly less in all cases of SSc as compared to controls (5.3 ± 1.4 vs. 8.7 ± 1.2; P < 0.00001). Disorganized architecture was much more prevalent in DSS versus LSS (86.4%vs. 25%). The vascular deletion score (VDS) was significantly higher in DSS as compared to LSS (P < 0.0001). Scleroderma pattern (SP) was seen in 18 (81.9%) and 15 (75%) of patients with DSS and LSS, respectively. Only 4% of normal subjects showed non-specific pattern and none showed SP. The mean modified Rodnan skin score (MRSS) was positively correlated with vascular deletion score (r = 0.572; P < 0.001) and negatively with capillary density (r = -0.8; P < 0.001). CONCLUSION: Nailfold capillaroscopy changes in SSc are related to disease subset and MRSS. NFC with digital microscope is a simplified, inexpensive, outpatient procedure with results comparable to previous studies.

Bone mineral density in young males with ankylosing spondylitis.

OBJECTIVE: To assess bone mineral density (BMD) abnormalities in young Indian males with ankylosing spondylitis (AS) and factors influencing this. METHODS: Eighty AS male subjects were compared with 160 age/sex matched controls for BMD of lumbar spine and proximal femur. AS subjects were evaluated and followed up every 3 months for disease activity. BMD was estimated at spine and proximal femur using the dual-energy X-ray absorptiometry (DXA) technique. RESULTS: All subjects were males with mean age of 32.9 ± 8.3 years and mean duration of disease was 8.1 ± 5.8 years. AS subjects had significantly lower BMD at the spine and femur as compared with controls (both P < 0.001). Using WHO standards, osteoporosis (OP) in spine and femur neck was seen in 28.75% (controls: 1.84%, P < 0.001) and 11.54% (controls: 1.23%, P < 0.001), respectively. No statistically significant difference in prevalence of OP was seen with disease duration, C-reactive protein levels and disease activity indices (all P > 0.05). Syndesmophytes were seen in 22.5% (n = 18) of AS subjects. There was no significant difference between BMD values at spine in AS subjects with or without syndesmophytes (0.91 + 0.16 g/cm(2) vs. 0.90 + 0.14 g/cm(2), P = 0.79). CONCLUSION: OP is a significant complication in AS even in young males with early disease, and more prevalent in the spine compared to femur. In our study, BMD was not influenced by disease activity indices, inflammatory markers or total disease duration. Spinal BMD is the most sensitive site for defining OP in AS.

Intramedullary fat necrosis, polyarthritis and panniculitis with pancreatic tumor: a case report.

Acute polyarthritis can occur in non-rheumatic systemic illnesses, presenting a diagnostic dilemma. We present an extremely rare case presenting as acute polyarthritis, panniculitis and medullary fat necrosis with underlying pancreatic pathology. This case report describes a young woman presenting with panniculits, pancreatic tumour, polyarthritis and intra-osseus fat necrosis with a fatal outcome. The medical fraternity needs to be aware of this potentially fatal albeit rare musculoskeletal complication secondary to a pancreatic pathology.