Microscopic Polyangiitis with Pulmonary-renal Involvement in a Patient with Polyarticular Juvenile Idiopathic Arthritis: A Case Report.

The association of polyarticular juvenile idiopathic arthritis (p-JIA) and microscopic polyangiitis (MPA) is extremely rare. Very few case reports described the coexistence of these two diseases to date. Here we report a 26-year-old female, a diagnosed patient of rheumatoid factor positive p-JIA for 15 years who developed MPA with renal and pulmonary involvement at the age of 26 years. She was successfully treated with intravenous corticosteroid and injection rituximab. This case report is unique as an association between MPA and p-JIA is very rare.

Does post-COVID reactive arthritis exist? Experience of a tertiary care centre with a review of the literature.

BACKGROUND: Rheumatological manifestations following COVID-19 are various, including Reactive Arthritis (ReA), which is a form of asymmetric oligoarthritis mainly involving the lower limbs, with or without extra-articular features. The current case series describes the clinical profile and treatment outcome of 23 patients with post-COVID-19 ReA. METHODS: A retrospective, observational study of patients with post-COVID-19 arthritis over one year was conducted at a tertiary care centre in India. Patients (n=23) with either a positive polymerase chain reaction test for SARS-CoV2 or an anti-COVID-19 antibody test were included. Available demographic details, musculoskeletal symptoms, inflammatory markers, and treatment given were documented. RESULTS: Sixteen out of 23 patients were female. The mean age of the patients was 42.8 years. Nineteen patients had had symptomatic COVID-19 infection in the past. The duration between onset of COVID-19 symptoms and arthritis ranged from 5 to 52 days with a mean of 25.9 days. The knee was the most involved joint (16 out of 23 cases). Seven patients had inflammatory lower back pain and nine had enthesitis. Most patients were treated with non-steroidal anti-inflammatory drugs (NSAIDs) and steroids - either depot injection or a short oral course. Three patients required treatment with hydroxychloroquine and methotrexate which were eventually stopped. No relapse was reported in any of the patients. CONCLUSION: On combining our data with 21 other case reports of ReA, a lower limb predominant, oligoarticular, asymmetric pattern of arthritis was seen with a female preponderance. The mean number of joints involved was 2.8. Axial symptoms and enthesitis were often coexistent. Treatment with NSAIDs and intra-articular steroids was effective. However, whether COVID-19 was the definitive aetiology of the arthritis is yet to be proven.

Does post-COVID reactive arthritis exist? Experience of a tertiary care centre with a review of the literature / ¿Existe la artritis reactiva post-COVID?: experiencia de un centro de tercer nivel de atención con revisión de la literatura

Background: Rheumatological manifestations following COVID-19 are various, including Reactive Arthritis (ReA), which is a form of asymmetric oligoarthritis mainly involving the lower limbs, with or without extra-articular features. The current case series describes the clinical profile and treatment outcome of 23 patients with post-COVID-19 ReA. Methods: A retrospective, observational study of patients with post-COVID-19 arthritis over one year was conducted at a tertiary care centre in India. Patients (n=23) with either a positive polymerase chain reaction test for SARS-CoV2 or an anti-COVID-19 antibody test were included. Available demographic details, musculoskeletal symptoms, inflammatory markers, and treatment given were documented. Results: Sixteen out of 23 patients were female. The mean age of the patients was 42.8 years. Nineteen patients had had symptomatic COVID-19 infection in the past. The duration between onset of COVID-19 symptoms and arthritis ranged from 5 to 52 days with a mean of 25.9 days. The knee was the most involved joint (16 out of 23 cases). Seven patients had inflammatory lower back pain and nine had enthesitis. Most patients were treated with non-steroidal anti-inflammatory drugs (NSAIDs) and steroids – either depot injection or a short oral course. Three patients required treatment with hydroxychloroquine and methotrexate which were eventually stopped. No relapse was reported in any of the patients. Conclusion: On combining our data with 21 other case reports of ReA, a lower limb predominant, oligoarticular, asymmetric pattern of arthritis was seen with a female preponderance. The mean number of joints involved was 2.8. Axial symptoms and enthesitis were often coexistent. Treatment with NSAIDs and intra-articular steroids was effective. However, whether COVID-19 was the definitive aetiology of the arthritis is yet to be proven.(AU)

Antecedentes: Las manifestaciones reumatológicas posteriores al COVID-19 son diversas, entre ellas, la artritis reactiva, que es una forma de oligoartritis asimétrica que afecta principalmente a los miembros inferiores, con o sin características extraarticulares. La serie de casos actual describe el perfil clínico y el resultado del tratamiento de 23 pacientes con artritis reactiva posterior a COVID-19. Métodos: Se realizó un estudio observacional retrospectivo de pacientes con artritis post-COVID-19 durante un año en un centro de atención terciaria en India. Se incluyeron pacientes (n=23) con una prueba de reacción en cadena de la polimerasa positiva para SARS-CoV-2 o una prueba de anticuerpos anti-COVID-19. Se documentaron los detalles demográficos disponibles, los síntomas musculoesqueléticos, los marcadores inflamatorios y el tratamiento administrado. Resultados: Dieciséis de los 23 pacientes eran mujeres. La edad media de los pacientes fue de 42,8 años. Diecinueve pacientes habían tenido infección sintomática por COVID-19 en el pasado. La duración entre el inicio de los síntomas de COVID-19 y la artritis osciló entre 5 y 52 días, con una media de 25,9 días. La rodilla fue la articulación más comúnmente involucrada (16 de 23 casos). Siete pacientes tenían dolor lumbar inflamatorio y 9 tenían entesitis. La mayoría de los pacientes fueron tratados con medicamentos antiinflamatorios no esteroideos y esteroides, ya fuera una inyección de depósito o un ciclo oral corto. Tres pacientes requirieron tratamiento con hidroxicloroquina y metotrexato, que finalmente se suspendieron. No se reportaron recaídas en ninguno de los pacientes. Conclusión: Al combinar nuestros datos con otros 21 informes de casos de artritis reactiva, se observó un patrón de artritis oligoarticular asimétrico predominante en las extremidades inferiores con predominio femenino.(AU)

Refractory Takayasu arteritis with recurrent pyoderma gangrenosum: a therapeutic challenge with case-based review.

Takayasu arteritis (TA) is an uncommon chronic granulomatous large-vessel vasculitis affecting the aorta and its branches. Pyoderma gangrenosum (PG) is a chronic neutrophilic dermatosis characterized by rapidly developing painful ulcers. The association of PG with TA is relatively uncommon. We report a case of a 22-year-old lady with a history of recurrent pyoderma lesions for 4 months following which she developed right upper limb claudication. She underwent contrast-enhanced magnetic resonance angiography of the aorta and its branches and was initially diagnosed with type IIb TA. She was put on prednisolone and methotrexate but had a major relapse with new-onset lower limb claudication despite an appropriate course of immunosuppression. She was planned for tocilizumab infusion 8 mg/kg intravenous every 4 weeks. Following the first dose of tocilizumab, her vascular symptoms improved but she had a flare of PG. This was followed by another flare after the second dose. She was switched to tofacitinib which led to sustained remission of her TA activity and healing of her skin lesions, and the prednisolone dose could be reduced to 5 mg daily over the next 1 year. Various immunosuppressives were used to date for treating PG in TA. However, tofacitinib is being reported for the first time in literature for treating PG and controlling TA activity. The paradoxical flare of PG with tocilizumab is quite uncommon and is also reported in our case with literature review.

Effect of vasodilator and immunosuppressive therapy on the endothelial dysfunction in patients with systemic sclerosis.

A comparative analysis of flow-mediated vasodilation (FMD), vasoactive angiogenic, and fibrogenic mediators between treatment-naive and treated systemic sclerosis (SSc) patients is an unmet need. (1)To assess the FMD and different pathogenic mediators in SSc patients about endothelial dysfunction. (2) To assess the proportion of circulating endothelial cells (CECs) in treatment-naïve patients. SSc patients were grouped into treatment-naïve (Group-I, n = 24) on vasodilator (Group-II, n = 10), on vasodilator + immunosuppressive (Group-III, n = 22)]. Age-sex matched healthy controls (n = 20) were included. Endothelial dysfunction (ED) was measured radiologically using FMD. Serum levels of NO, ET1, NO/ET1, sVCAM, sICAM, TGF, IL-6, and VEGF, as well as gene expressions of eNOS, iNOS, ET-1, and TGF, were measured to assess the status of ED in various study groups. CEC was measured in Group-I and HC. CEC was used as a marker to identify a key regulator of ED in SSc. FMD was significantly decreased in all SSc patients through receiving treatment. Upregulation of serum NO and ET concentrations was noted post-treatment with an unaltered NO/ET1 ratio. NO was positively correlated with FMD (r = 0.6) and negatively with TGFß (r = - 0.5). ET-1 showed a negative correlation with TGFß (r = - 0.5) but no significant correlation with FMD. Circulating endothelial cell (CEC) was significantly higher in Group-I (3.2%) than HC (0.8%) (p = 0.002), and it showed a good correlation with NO (r = - 0.7, p = 0.0001) and NO/ET1 (r = - 0.6, p = 0.007). Persistent ED was observed in all SSc patients irrespective of treatment. Dysbalance in NO/ET1 ratio might be the considering factor for the underlying progression of ED. Based on our findings, it may be hypothesized that reduced NO may be a contributing factor in the pathogenesis of endothelial dysfunction in SSc.

Does post-COVID reactive arthritis exist? Experience of a tertiary care centre with a review of the literature.

Background: Rheumatological manifestations following COVID-19 are various, including Reactive Arthritis (ReA), which is a form of asymmetric oligoarthritis mainly involving the lower limbs, with or without extra-articular features. The current case series describes the clinical profile and treatment outcome of 23 patients with post-COVID-19 ReA. Methods: A retrospective, observational study of patients with post-COVID-19 arthritis over one year was conducted at a tertiary care centre in India. Patients (n = 23) with either a positive polymerase chain reaction test for SARS-CoV2 or an anti-COVID-19 antibody test were included. Available demographic details, musculoskeletal symptoms, inflammatory markers, and treatment given were documented. Results: Sixteen out of 23 patients were female. The mean age of the patients was 42.8 years. Nineteen patients had had symptomatic COVID-19 infection in the past. The duration between onset of COVID-19 symptoms and arthritis ranged from 5 to 52 days with a mean of 25.9 days. The knee was the most involved joint (16 out of 23 cases). Seven patients had inflammatory lower back pain and nine had enthesitis. Most patients were treated with non-steroidal anti-inflammatory drugs (NSAIDs) and steroids - either depot injection or a short oral course. Three patients required treatment with hydroxychloroquine and methotrexate which were eventually stopped. No relapse was reported in any of the patients. Conclusion: On combining our data with 21 other case reports of ReA, a lower limb predominant, oligoarticular, asymmetric pattern of arthritis was seen with a female preponderance. The mean number of joints involved was 2.8. Axial symptoms and enthesitis were often coexistent. Treatment with NSAIDs and intra-articular steroids was effective. However, whether COVID-19 was the definitive aetiology of the arthritis is yet to be proven.

Antecedentes: Las manifestaciones reumatológicas posteriores al COVID-19 son diversas, entre ellas, la artritis reactiva, que es una forma de oligoartritis asimétrica que afecta principalmente a los miembros inferiores, con o sin características extraarticulares. La serie de casos actual describe el perfil clínico y el resultado del tratamiento de 23 pacientes con artritis reactiva posterior a COVID-19. Métodos: Se realizó un estudio observacional retrospectivo de pacientes con artritis post-COVID-19 durante un año en un centro de atención terciaria en India. Se incluyeron pacientes (n = 23) con una prueba de reacción en cadena de la polimerasa positiva para SARS-CoV-2 o una prueba de anticuerpos anti-COVID-19. Se documentaron los detalles demográficos disponibles, los síntomas musculoesqueléticos, los marcadores inflamatorios y el tratamiento administrado. Resultados: Dieciséis de los 23 pacientes eran mujeres. La edad media de los pacientes fue de 42,8 años. Diecinueve pacientes habían tenido infección sintomática por COVID-19 en el pasado. La duración entre el inicio de los síntomas de COVID-19 y la artritis osciló entre 5 y 52 días, con una media de 25,9 días. La rodilla fue la articulación más comúnmente involucrada (16 de 23 casos). Siete pacientes tenían dolor lumbar inflamatorio y 9 tenían entesitis. La mayoría de los pacientes fueron tratados con medicamentos antiinflamatorios no esteroideos y esteroides, ya fuera una inyección de depósito o un ciclo oral corto. Tres pacientes requirieron tratamiento con hidroxicloroquina y metotrexato, que finalmente se suspendieron. No se reportaron recaídas en ninguno de los pacientes. Conclusión: Al combinar nuestros datos con otros 21 informes de casos de artritis reactiva, se observó un patrón de artritis oligoarticular asimétrico predominante en las extremidades inferiores con predominio femenino. El número medio de articulaciones afectadas fue de 2,8. A menudo coexistían síntomas axiales y entesitis. El tratamiento con antiinflamatorios no esteroideos y esteroides intraarticulares fue eficaz. Sin embargo, aún no se ha demostrado si el COVID-19 fue la etiología definitiva de la artritis.

Recurrent macrophage activation syndrome as the initial manifestation of paediatric systemic lupus erythematosus.

Introduction: Macrophage Activation Syndrome (MAS) is a rare but potentially fatal complication in rheumatic diseases. Here, we report the case of a 14-year-old girl with MAS as the primary manifestation of Systemic Lupus Erythematosus (SLE). She had three episodes of MAS during the course of her treatment. This case is unique as recurrent MAS in pediatric SLE is rare.Methods: Demographic, clinical, laboratory features and outcomes of our patient was noted. We also reviewed the two reported cases of recurrent MAS in pediatric SLE. Literature review was performed on PubMed search forum. Search items included Macrophage activation syndrome, pediatric systemic lupus erythematosus, recurrent MAS.Conclusion: The diagnosis and management of MAS are challenging as it can simulate an infectious complication or can be the exacerbation of the underlying disease. Early detection and prompt treatment can reduce morbidity in these patients.

Interleukin-17 as a predictor of subclinical synovitis in the remission state of rheumatoid arthritis.

OBJECTIVES: To compare the level of pro and anti-inflammatory cytokines, and angiogenic mediators between Rheumatoid arthritis (RA) patients with and without subclinical synovitis (SS) in remission state, to find the correlation of these mediators with Greyscale synovitis (GSS) and power Doppler (PD) scores, and to find the probable predictor/s of SS. METHODS: 52 RA patients in remission state were recruited and subdivided into with and without SS group by Ultrasonography (USG) of 14 joints. Total GSS and PD scoring was done. The serum levels of the pro/anti-inflammatory cytokines and angiogenic mediators were compared between groups, and correlation and regression analysis were done with GSS and PD scores. RESULT: 63.46% patients had USG evidence of SS. Patients with SS had significantly higher levels of pro-inflammatory and angiogenic mediators [matrix-metalloproteinase -3 (p = 0.0001), Tumour necrosis factor-α (p = 0.0001), Interleukin (IL)-6 (p = 0.001), IL-1b (p = 0.0001), IL-17 (p = 0.0005), IL-33 (p = 0.0003), Tie-2 (p = 0.0001), vascular endothelial growth factor (VEGF (p = 0.03)], and lower anti-inflammatory cytokines [IL-27 (p = 0.0003), IL-10(p = 0.0001)]. A strong positive correlation of GSS score was noted with IL-17(r = 0.7), IL-6 (r = 0.7), IL-1b (r = 0.7), and IL-33 (r = 0.6). Multiple linear regression model identified IL-17 and IL-6 as predictors of GSS score, and TNF-α and VEGF as predictors of PD score. IL-17 level > 249 picogram/millilitre (pg/ml) could predict the SS with high specificity (89.5%). CONCLUSION: Patients with SS in the remission state of RA showed altered expression of some of the pro/anti-inflammatory/angiogenic markers compared to those not having SS. IL-17, IL-6, VEGF, and TNF-α could be the predictors of USG synovial scores.

Two flares of Still's disease after two doses of the ChAdOx1 vaccine.

We report the case of an 18-year-old male with Still's disease for the last 3 years, in remission, who developed two flares of his disease after receiving two doses of the ChAdOX1 nCoV-19 vaccine. While the first flare was mild requiring steroid initiation and resolved rapidly, the second flare after the second dose was much severe, requiring pulse steroid and tocilizumab. We also review three reported cases of flares of Still's disease after COVID-19 vaccination. The temporal association of the flares with both vaccine doses strengthens the association between the vaccine administration and the flare. The proposed mechanism may be due to activation of the innate immune system by the vaccine adjuvants. This review serves to inform the medical community regarding a possible role of the vaccine in producing a systemic inflammatory response. Early detection and treatment can help reduce morbidity in these cases.

Evaluation of Subclinical Hand Joint Synovitis by Ultrasonography in Patients with Psoriatic Arthritis and Cutaneous Psoriasis: A Case-Control Study.

Objectives: To find the frequency of subclinical hand joint synovitis (SS) in patients with psoriatic arthritis (PsA) and cutaneous psoriasis (PsC) compared to healthy controls (HC), and correlation of SS with disease activity. Methods: PsA patients (n= 52), without any past/current history of hand joint arthritis, PsC patients (n= 48), and 45 HC were recruited. Grey-scale and power Doppler Ultrasonography of bilateral hand joints were performed. The proportions of hand joints with SS were estimated in each group. A wrist-ray score was devised. Correlations were obtained between the number of joints with SS and disease activity parameters. Results: Higher proportion of PsA patients (55.8%) had SS than PsC (29.2%, p= 0.007), and HC (22.2%, p=0.001). Proportion of joints with SS was higher in PsA patients (5.38%) compared to PsC (2.92%, [p=0.0008]), and HC (1.11%, [p=0.0007]). Compared to HC, PsA patients had significantly higher bilateral ray 3 (p=0.002 and 0.01 for left and right ray 3, respectively), and right ray 4 involvement (p=0.037) and PsC patients had higher left ray 3 involvement (p=0.03). Wrist-ray score above 2.5 could distinguish patients of PsC with significant subclinical synovitis compared to controls (area under curve: 0.857, 95% confidence interval: 0.71-1.00). There was a significant correlation of SS with ESR in PsA group (p-value: 0.044), and with CRP in PsC group (p-value: 0.003), but not with other disease activity indices. Conclusion: SS was noted in approximately half of PsA and 1/3rd of PsC patients. Both PsA and PsC patients had a significantly higher number of hand joint SS than HC. Ray pattern of hand joint SS could be present in both PsA and PsC.

Methotrexate and theaflavin-3, 3'-digallate synergistically restore the balance between apoptosis and autophagy in synovial fibroblast of RA: an ex vivo approach with cultured human RA FLS.

BACKGROUND: Imbalance between apoptosis and autophagy in fibroblast-like synoviocytes (FLS) is one of the pathogenic mechanisms responsible for their abnormal proliferation in rheumatoid arthritis (RA). Methotrexate (MTX) demonstrated limited efficacy in amending this imbalance in fluid-derived (fd)-FLS. The active compound of black tea Theaflavin 3,3'-digallate (TF3) may be effective in restoring apoptosis-autophagy imbalance in (fd)-FLS. The combined effect of MTX + TF3 upon the same is yet to be elucidated. OBJECTIVE: To evaluate the effect of MTX + TF3 on fd-FLS to induce apoptosis and inhibit autophagy through Endoplasmic Reticulum (ER) stress-mediated pathways. METHODS: FLS from synovial fluid of 11 RA and 10 osteoarthritis patients were cultured after treatment with MTX/TF3 or a combination of MTX (125 nM) and TF3(10 µM) and the following parameters were evaluated. C-reactive protein, cytokines (TNF-α, IL-6), angiogenic markers were quantified by ELISA. fd-FLS viability was determined by MTT assay and apoptosis by flow cytometry. ER stress markers were estimated by RT-PCR (IRE1A, spliced-XBP-1) and immunoblotting (Grp78, Hsp70, CHOP, HIF-1α). Immunoblot studies were done to evaluate apoptotic (Bcl-2, Bax, Caspases) and autophagic (Beclin1, LC3b, p62) proteins. RESULTS: MTX (IC25) and TF3 (IC50) both in single doses could down-regulate the levels of pro-inflammatory and angiogenic markers. Combinatorial treatment modulated autophagosomal proteins in fd-FLS and induced apoptosis by regulating ER stress response. CONCLUSION: Disruption in homeostasis between apoptosis and autophagy in fd-FLS might be an underlying phenomenon in the progression of pathophysiology in RA. Co-administration of MTX + TF3 successfully restored the homeostasis by inducing apoptosis.

Phenotypic characterization of circulating endothelial cells induced by inflammation and oxidative stress in ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic auto-immune disease, affecting the spine, sacroiliac, and sometimes peripheral joints. It is also involved with cardio-vascular risk factors due to accelerated atherosclerosis. Oxidative burst, systemic inflammation coupled with endothelial dysfunction (ED), resulting in reduced bioavailability of the vasodilator nitric oxide (NO) and an increased number of circulating endothelial cells (CECs) may correlate with disease activity and its sustenance. Hence, the study was aimed to detect and quantify CECs and assess the oxidative stress and inflammatory status in AS patients vis-à-vis healthy controls, as well as relate these parameters with AS disease activity and atherosclerotic markers in patients. Our study showed an increased frequency of endothelial cells in peripheral blood of AS patients in pro-inflammatory conditions. In AS patient population, they showed significant reduction of flow-mediated dilatation (%FMD) (p < 0.05), and increased soluble adhesion molecules such as sICAM-1 (p < 0.01) and sVCAM-1 (p < 0.05) compared to healthy controls. A marked increase in pro-inflammatory markers such as TNF-α (p < 0.01) and IL-1ß (p < 0.001) and reactive free radicals (p < 0.05) along with reduced serum nitrite in AS, provided a strong pro-inflammatory milieu which positively correlated with Bath ankylosing spondylitis disease activity and functional indices (BASDAI and BASFI). The observed significant upregulation in CECs (CD45-/CD31+/CD105+/CD144+) in patients compared to healthy controls positively correlated with disease activity and duration as well as with markers of oxidative stress. Thus, chronic inflammation and oxidative burst induce loss of NO bioavailability, leading to ED. This may cause the derangement of CECs that may be considered as a prognostic biomarker for ED.

Parotid swelling due to external carotid artery thrombus-a rare manifestation in antiphospholipid syndrome.

Vascular complications in forms of venous and arterial thrombi are common scenario in antiphospholipid syndrome with raised titer of antibodies. Here we describe an 18 years old female who was admitted with right parotid swelling due to external carotid artery thrombi within gland parenchyma in antiphospholipid syndrome, with past history of right lower leg arterial occlusion and digital gangrene.