Multicentric Reticulohistiocytosis (Mrh): A Case Report On A Rare Destructive Arthritis.

Multicentric Reticulohistiocytosis is a rare disorder of unknown aetiology which affects skin and joints predominantly. There are no specific laboratory investigations for diagnosis. Diagnosis can be made clinically and on a histopathological basis. There is no consensus on treatment. We report a case from Pakistan with classical presentation who did well on methotrexate and low dose steroids. Prompt diagnosis and early treatment may save from significant disability.

Interactions of Chitosan-coated Green Synthesized Silver Nanoparticles using Mentha spicata and Standard Antibiotics against Bacterial Pathogens.

BACKGROUND: Infectious diseases are caused by various multidrug-resistant pathogenic bacteria and in recent scenarios, nanoparticles have been used as innovative antimicrobial agents. AIMS: This current research aimed to evaluate the bactericidal effect of chitosan-coated green synthesized silver nanoparticles using aqueous extract of Mentha spicata (MSaqu) against bacterial pathogens, i.e., Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Serratia marcescens, Staphylococcus aureus, and Streptococcus pyogenes. METHODS: Synthesis and characterization of silver nanoparticles (MSAgNPs) were carried out via atomic absorption spectrometer and Fourier-transform infrared spectroscopy. Agar well and agar disc diffusion methods were used to assess the antibacterial and synergistic effect of chitosanmediated biogenic silver nanoparticles and standard antibiotics. Three types of interactions, i.e., antagonistic (↓), synergistic (↑), and additive (¥) were observed. RESULTS: Synergistic effect was recorded against Pseudomonas aeruginosa (8.5±0.25 mm↑), Serratia marcescens (19.0±1.0 mm↑), and Klebsiela pneumonia (8.5±0.25 mm↑), an additive effect was exhibited by Escherichia coli (9.0±0.0 mm¥), Streptococcus pyogenes (10.0±0.0 mm¥), and Staphylococcus aureus (7.5±0.25 mm↓) and they showed antagonistic effects when chitosan-coated silver nanoparticles (CLMSAgNPs) were applied compared to chitosan, MSaqu, and MSAgNPs. Interesting antibacterial results were recorded when chitosan-coated Mentha spicata extract and silver nanoparticles were applied along with antibiotics. The synergistic effects of chitosan-coated silver nanoparticles (CLMSAgNPs) + K were recorded against E. coli (14.5±0.25 mm). The synergistic effects of chitosan-coated silver nanoparticles (CLMSAgNPs) + AML were recorded against E. coli (5.5±0.0 mm), S. pyogenes (10.0±0.0 mm), K. pneumonia (5.5±0.0 mm), and S. aureus (4.0±0.0 mm). The synergistic effects of chitosan-coated silver nanoparticles (CLMSAgNPs) + NOR were recorded against E. coli (16.0±0.0 mm), P. aeruginosa (19.0±0.0 mm), S. marcescens (19.5±0.25 mm), S. pyogenes (11.5.0±0.25 mm), K. pneumonia (23.0±0.0 mm), and S. aureus (8.5±0.25 mm). CONCLUSION: Current findings concluded that chitosan-coated biogenic silver nanoparticles have potential bactericidal effects against infectious pathogens and could be used as forthcoming antibacterial agents.

A common missense variant rs874881 of PADI4 gene and rheumatoid arthritis: Genetic association study and in-silico analysis.

The peptidylarginine-deiminase 4 (PADI4) is involved in the post-translational catalytic conversion of arginine into citrulline. The autoantibodies including anti-citrullinated protein antibodies (ACPAs) produced in response to hypercitrullinated proteins are a hallmark of rheumatoid arthritis (RA) autoimmunity. Therefore, the role of a missense variant rs874881 (Gly112Ala) of PADI4 in RA susceptibility was analyzed, along with in-silico analysis of structural and functional impacts of this substitution. We did a case-control association study and in-silico analysis. For the case-control study, confirmed RA cases and healthy controls were recruited. Genotyping for rs874881 (n = 750) was performed through polymerase chain reaction-restriction fragment length polymorphism. Multivariate logistic regression analysis was employed to determine association. The in-silico analysis was carried out through HOPE, VarMap, MutationAssessor, MutPred2, SIFT, PolyPhen, CADD, REVEL and MetaLR. In the case-control study, the rs874881 exhibited a strong association with increased RA susceptibility (G vs C odds ratio = 3.85, 95 % confidence interval = 2.81-5.27). Interaction analysis revealed significant interaction of genotype with smoking and gender (p < 0.05). Significant results (p < 0.05) were also obtained in stratified analysis by presence/absence of comorbidities and radiographic damage. According to in-silico pathogenicity prediction analysis, this Gly112Ala substitution does not exert a major effect on protein structure and function including its enzymatic activity. We report a significant association of PADI4 rs874881 with overall RA susceptibility. To our knowledge, this is the first study to do the interaction and stratified analyses on the PADI4 rs874881 in RA. Similar detailed studies should also be performed in other populations.

Not Another Case Of Juvenile Idiopathic Arthritis: Congenital Insensitivity To Pain Presenting With Joint Problems.

Congenital insensitivity to pain with anhidrosis (CIPA) is a rare condition with protean manifestations. Occasionally, these diseases may present with musculoskeletal problems. Here we report a case of young child who presented with joint problems in our clinic. Since the child had a number of musculoskeletal manifestations her diagnosis was difficult and delayed. She was given supportive treatment and a team of doctors from different specialties was involved in her management.

Association Of Tumour Necrosis Factor-Alpha -308 G/A Promoter Polymorphism With Susceptibility And Disease Profile Of Rheumatoid Arthritis.

BACKGROUND: Single nucleotide polymorphism underlying the auto-immune process governing the pathologic manifestations of rheumatoid arthritis has been the focus of study for quite a while. TNF-alpha -308 G/A promoter polymorphism have been reported to be responsible for a number of manifestations of rheumatoid arthritis. METHODS: This case-control study was conducted at the department of Rheumatology at Pakistan Institute of Medical Sciences Islamabad from 9th May to 9th August 2019 with a focus to determine the Association of tumour necrosis factor-alpha -308 G/A promoter polymorphism with susceptibility and disease profile of rheumatoid arthritis. One hundred and fifty cases with diagnosed rheumatoid arthritis and 150 age and gender matched controls were enrolled in the study. Their genotyping was done for tumour necrosis factor-alpha - 308 G/A promoter polymorphism. RESULTS: The genotypic analysis showed that GG genotype was the most common genotype found in 118 cases (78.66%) followed by GA (18.66%) and AA genotype (2.6%) p=0.0096 in both cases and controls. Overall, G allele was more common than A in both cases and controls pointing towards the preponderance of G genotype in our population. (p=0.003). However, the GA genotype and A allelotype was more common among cases with rheumatoid arthritis (p <0.05). No significant association of G/A polymorphism with smoking and gender, however, within gender, males had a significantly more expression of the GA genotype and A allelotype (p <0.05). CONCLUSIONS: There is a significantly more expression of the GA genotype and the A allelotype of the TNF-alpha -308 G/A promoter gene in rheumatoid arthritis patients in our population. Similarly, more males, compared to females have increased expression of the GA genotype as well as the A allelotype.

Prevalence of Depression in Patients with Juvenile Idiopathic Arthritis Presenting at a Tertiary Care Hospital.

Background and objective Juvenile idiopathic arthritis (JIA) is an idiopathic autoimmune rheumatic disorder in children. JIA has been associated with depression and has a negative psychological impact on patients' quality of life. The aim of the study is to determine the prevalence of depression in patients with JIA presenting at a tertiary care hospital in Islamabad, Pakistan. Materials and methods This cross-sectional study, conducted at the Department of Rheumatology, Pakistan Institute of Medical Sciences, Islamabad, Pakistan, included 100 children aged >6 years who had been diagnosed with JIA according to the 2004 revised International League of Associations for Rheumatology classification. Physical disability was measured using the Childhood Health Assessment Questionnaire disability index (CHAQ-DI), whereas depression was assessed by measuring their Center for Epidemiological Studies Depression Scale for Children (CES-DC) scores. Results were analyzed using IBM SPSS Statistics for Windows, Version 20.0. (Armonk, NY: IBM Corp.), with p-values ≤ 0.05 considered statistically significant. Results The 100 patients included 54 male patients (mean age, 16.3 ± 4.9 years) and 46 female patients (mean age, 18.6 ± 5.1 years). CES-DC scores showed that 72 patients with JIA had significant depression. Of these 72 patients, 50 (69.4%) had mild, 21 (29.2%) had moderate, and one (1.4%) had severe disability according to CHAQ-DI criteria. Age was the only effect modifier significantly associated with significant depression in patients with JIA (P < 0.05). Conclusion A cross sectional survey was carried out to find prevalence of depression in children with JIA. Physical disability and depression were measured using standardized tools. The percentage of significant depression among children with JIA is very high in our local population and was significantly associated with disease severity. Our findings emphasize the need to initiate early and prompt measures to prevent depression and reduce overall morbidity in patients with JIA.

The Role of the Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as Markers of Disease Activity in Ankylosing Spondylitis.

Background Ankylosing spondylitis (AS) is a chronic rheumatological condition affecting sacroiliac joint and spine and occurs more often in younger patients than in the elderly population. Objective The purpose of the study was to determine the association of the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) with the disease activity of AS. Methodology This case-control study was conducted in the rheumatology department at the Pakistan Institute of Medical Sciences (PIMS) hospital in Islamabad from September 2018 to July 2019. The study consisted of two groups of 59 patients per group. We assessed a full blood count with erythrocyte sedimentation rate (ESR) for each participant using the PIMS hospital laboratory. NLR and PLR were calculated. Results The mean age of the participants in the control group and the cases group was the same (32 ± 4 years). The control group NLR was 1.30 ± 0.16, the PLR was 94.98 ± 17.96, and the ESR was 16.88 ± 3.76 mm/hour. For the cases group, the NLR was 3.08 ± 0.91, the PLR was 171.50 ± 38.06, and the ESR was 29.30 ± 9.20 mm/hour. There was a significant increase in cases for NLR, PLR, and ESR as compared to control samples (p<0.05). The mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of participants with active diseases was 5.91±1.28. In the same group, the mean ESR was 27.65 ± 9.07 mm/hour, the NLR was 3.46 ± 0.80, and the PLR was 184.39 ± 36.13. For those in the inactive disease group, the mean BASDAI score was 2.84 ± 0.46, the ESR was 33.42 ± 8.48 mm/hour, the NLR was 2.17 ± 0.37, and the PLR was 139.71 ± 26.05. NLR and PLR were significantly higher in the active disease group (p<0.05). Conclusion NLR and PLR are good markers of inflammation in AS patients, and higher values indicate more active disease activity.