Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 233
Filtrar
1.
Clin Rheumatol ; 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34606036

RESUMO

Pulmonary mucormycosis is rare in systemic lupus erythematosus. A 20-year-old lady with lupus nephritis and neuropsychiatric lupus was treated with injection methylprednisolone and cyclophosphamide. After few days, she developed fever, breathlessness, and hoarseness of voice. After neck and chest imaging, possibility of mucormycosis was considered which was later confirmed on microbiological test. Patient was treated with conventional amphotericin B. Literature review was done, and 8 patients with disseminated or pulmonary mucormycosis were identified with SLE. In patients with high index of suspicion, early imaging can help in diagnosis and early and aggressive management even with conventional amphotericin B can result in favorable outcome. Key Points • Pulmonary mucormycosis in systemic lupus erythematosus is rare. • Radiological investigation can guide towards diagnosis. • Early and aggressive treatment can lead to good outcome.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34626102

RESUMO

OBJECTIVE: We studied the rate of remission of lupus nephritis (LN) in an international cohort of 248 children and adolescents with biopsy proven LN. Five different definitions from scientific studies and the definitions recommended by the American College of Rheumatology and Kidney Disease Improving Global Outcomes (KDIGO) were used. METHODS: Anonymized clinical data in patients with biopsy proven LN class ≥ III (International Society of nephrology/Royal Pathology Society-ISN/RPS) diagnosed and treated in the last 10 years in 23 international centers from 10 countries were collected. We compared the rate of patients in complete and partial remission applying the different definitions. RESULTS: The mean age at diagnosis was 11 years and 4 month and 177 were females.The number of patients in complete and partial remission varied a lot between the different definitions. At 24 months, between 50% and 78.8% of the patients were in full remission as defined by the different criteria. The number of patients in partial remission was low, between 2.3% and 25%. No difference in achieved remission was found between boys and girls or between children and adolescents (P > 0.05). Patients with East Asian ethnicity reached remission more often than other ethnicities (P = 0.03-0.0008). Patients treated in high income countries showed a higher percentage of complete remission at 12 and 24 months (P = 0.002-0.000001). CONCLUSION: The rate of children and adolescents with LN achieving remission varied hugely with the definition used. Our results give important information for long awaited treatment studies in children and young people.

3.
Am J Gastroenterol ; 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34506335

RESUMO

INTRODUCTION: Relative adrenal insufficiency (RAI) is associated with poor outcome in adult cirrhotics. So far, pediatric studies are not available on the same. We aimed to prospectively study the presence and outcome of RAI in children with decompensated cirrhosis over 180 days. METHODS: Hemodynamically stable children with decompensated cirrhosis were sampled for serum basal cortisol and peak cortisol (after 30 minutes of 1-µg intravenous Synacthen) at day 1 and day 21. RAI was diagnosed as peak cortisol <500 nmol/L. Serum cytokines (interleukin-6 and tumor necrosis factor-α) and lipid profile were correlated with RAI. Cohort was followed up for outcomes over 180 days for complications and survival. With the identified risk factors, prognostic models were derived and compared with pediatric end-stage liver disease (PELD) and Child-Turcotte-Pugh scores. RESULTS: Prevalence of RAI was 54% at baseline and 61% at day 21 in the enrolled patients (n = 63, aged 128 ± 48 months, male 78%). No significant differences in cytokines and serum lipid levels were seen between RAI and normal adrenal function groups. Patients with RAI at baseline (D1-RAI) developed higher complications at follow-up as compared to the normal adrenal function group (53% vs 24%, P = 0.02). The PELD score (odds ratio 1.08, confidence interval 1.05-1.12, P < 0.01) and D1-RAI (odds ratio 3.19, confidence interval 1.32-7.73, P = 0.01) were independent predictors of follow-up complications. The PELD-delta cortisol model (area under the receiver operating curve 0.84, P < 0.001, 92% sensitivity; 60% specificity) predicted morbidity better than isolated PELD or Child-Turcotte-Pugh scores. DISCUSSION: RAI is a risk factor for development of complications in pediatric cirrhosis over short-term follow-up. The PELD-delta cortisol score is a promising prognostic model for predicting follow-up complications.

4.
Rheumatol Int ; 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34580753

RESUMO

Catatonia is a rare psychomotor syndrome characterized by stupor, posturing and echophenomena. It can be associated with schizophrenia, infections, drugs and autoimmune causes like anti N-methyl D-aspartate (NMDA) receptor encephalitis and systemic lupus erythematosus (SLE). Here we report two cases of systemic lupus erythematosus with catatonia, who improved with immunosuppressive treatment and review the cases described in the literature. The first case presented with fever, pancytopenia, toxic epidermal necrolysis (TEN)-like rash and later developed catatonia and macrophage activation syndrome (MAS). The second case presented with acute cutaneous lupus erythematosus (ACLE), fever, alopecia, polyarthralgias, nephritis, cytopenias along with catatonia. Successful management of this syndrome requires prompt recognition and treatment with immunosuppression as well as benzodiazepines with or without electroconvulsive therapy (ECT).

5.
PLoS One ; 16(8): e0255639, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34339423

RESUMO

This study was aimed at exploring whether latent tuberculosis infection (LTBI) contributes to the pathogenesis of immune-mediated inflammatory diseases in a TB endemic setting. We screened 198 rheumatoid arthritis (RA) patients with tuberculin skin test (TST) and studied 61 (median DAS28-ESR = 6.3) who were positive. Whole blood T cell proliferative responses to Mycobacterium tuberculosis (Mtb) membrane (MtM) antigens, including the latency-induced protein alpha crystallin (Acr), were determined by flow cytometry using Ki67 expression as the marker for nuclear proliferation. Serum antibody levels were determined by ELISA. Follow-up investigations (at 3-6, 9-12 and 15-18 months after baseline) were performed in 41 patients who were classified empirically as 'high' (HR-T/HR-B) or 'low' (LR-T/LR-B) responders based on their dynamic T cell or antibody responses. Significant correlations were seen between baseline T cell responses to MtM and Acr, and between IgG, IgA and IgM antibody responses to MtM. However, no correlation was seen between T and B cell responses. At all time points during the follow-up, T cell responses to both antigens (except for MtM at one point) were significantly higher in HR-T (n = 25) than LR-T (n = 16) patients. Levels of IgA and IgM (but not IgG) antibodies to MtM were also significantly higher in HR-B (n = 13) than LR-B (n = 28) at all time points. Importantly, HR-T patients exhibited significantly higher baseline and follow-up DAS28 scores than LR-T. Ten (of 61) patients had a history of TB and developed RA 6 years (median) after contracting TB. Three new TB cases (1 from TST-positive and 2 from TST-negative groups) emerged during the follow-up. Our results suggest that persistently elevated T cell responses to Mtb antigens may contribute to disease activity in RA.

7.
Arthritis Rheumatol ; 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34279063

RESUMO

OBJECTIVE: To develop a Standardized Steroid dosing Regimen (SSR) by physicians treating childhood-onset systemic lupus erythematosus (cSLE) complicated by lupus nephritis (LN), using consensus formation methodology. METHODS: Parameters influencing corticosteroid (CS) dosing were identified (Step-1). Data from children with proliferative LN were used to generate Patient Profiles (PP) (Step-2). Physicians rated change in activity of renal and extra-renal cSLE between two consecutive visits and proposed CS dosing (Step-3). Using PP ratings, the SSR was developed (Step-4) with refinements achieved in a physician focus group (Step-5). A second type of PP describing cSLE course for ≥4 months since kidney biopsy were rated to validate the SSR-recommended oral and intravenous CS-dosages (Step-6). PP adjudication was based on majority ratings for both renal and extra-renal disease courses, and consensus level was set at 80%. RESULTS: Degree of proteinuria, estimated glomerular filtration rate, change in renal and extra-renal disease activity, and time since kidney biopsy influenced CS dosing (Steps-1/2). Considering these parameters in 5,056 PP-ratings from 103 raters, and renal and extra-renal course definitions, CS-dosing rules of the SSR were developed (Steps-3-5). Validation of the SSR for up to 6 months post kidney biopsy was achieved with 1,838 PP-ratings from 60 raters who achieved consensus for oral and intravenous CS dosage as per the SSR (Step-6). CONCLUSION: The SSR represents an international consensus on CS dosing for use in patients with cSLE and proliferative LN. The SSR is anticipated to be used for clinical care and standardize CS-dosage during clinical trials.

8.
Rheumatol Int ; 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34191047

RESUMO

INTRODUCTION: There is paucity of data on tuberculosis in Indian patients with systemic lupus erythematosus (SLE). We retrospectively studied clinical features and outcome of tuberculosis in SLE. METHODS: Medical records of patients who developed tuberculosis simultaneous or after the diagnosis of SLE were retrospectively reviewed. All patients fulfilled 1997 ACR and/or SLICC 2012 classification criteria for SLE. A diagnosis of tuberculosis required bacteriological, histopathological or CT/MRI suggestive of tuberculosis and initiation of four drug antituberculous therapy. Baseline parameters were compared with the rest of cohort to identify predictors of tuberculosis. RESULTS: In our cohort of 1335 SLE patients, 48 (3.6%) developed tuberculosis. Incidence of tuberculosis was calculated to be 733 per 100,000 patient years and occurred after a mean disease duration of 3.0 ± 4.1 years. Extrapulmonary tuberculosis (n = 37) was commoner than pulmonary tuberculosis (n =11). Most common radiological pattern in pulmonary tuberculosis was miliary and musculoskeletal TB was most common extrapulmonary TB. A microbiological diagnosis was obtained in 52.1% patients. Male gender was associated with higher risk of tuberculosis [OR 3.30 (1.55-7.05)]. Mortality was 14.5% and all patients who died had either disseminated (n = 5) or central nervous system (CNS) tuberculosis (n = 2). CONCLUSION: Incidence of tuberculosis in SLE is higher than general population and is associated with different phenotype and higher mortality. Male gender was associated with increased risk of tuberculosis in SLE.

9.
Ann Rheum Dis ; 80(11): 1376-1384, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34112656

RESUMO

OBJECTIVES: There are no head-to-head trials of different dose escalation strategies of methotrexate (MTX) in RA. We compared the efficacy, safety and tolerability of 'usual' (5 mg every 4 weeks) versus 'fast' (5 mg every 2 weeks) escalation of oral MTX. METHODS: This multicentre, open-label (assessor blinded) RCT included patients 18-55 years of age having active RA with disease duration <5 years, and not on DMARDs. Patients were randomized 1:1 into usual or fast escalation groups, both groups starting MTX at 15 mg/week till a maximum of 25 mg/week. Primary outcome was EULAR good response at 16 weeks, secondary outcomes were ΔDAS28 and adverse effects (AE). Analyses were intention-to-treat. RESULTS: 178 patients with mean DAS28-CRP of 5.4(1.1) were randomized to usual (n=89) or fast escalation groups (n=89). At 16 weeks, there was no difference in good EULAR response in the usual (28.1%) or fast escalation (22.5%) groups (p=0.8). There was no difference in mean ΔDAS28-CRP at 8 weeks (-0.9, -0.8, p=0.72) or 16 weeks (-1.3, -1.3, p=0.98). Even at 24 weeks (extended follow-up), responses were similar. There were no inter-group differences in ΔHAQ, or MTX-polyglutamates 1-3 levels at 8 or 16 weeks. Gastrointestinal AE were higher in the fast escalation group over initial 8 weeks (27%, 40%, p=0.048), but not over 16 weeks. There was no difference in cytopenias, transaminitis, or drug discontinuation/dose reduction between the groups. No serious AE were seen. CONCLUSION: A faster MTX escalation strategy in RA was not more efficacious over 16-24 weeks, and did not significantly increase AE, except higher gastrointestinal AE initially. TRIAL REGISTRATION NUMBER: CTRI/2018/12/016549.

10.
Rheumatology (Oxford) ; 60(6): 3004-3011, 2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-34144605

RESUMO

OBJECTIVES: Peripheral SpA (pSpA) is comprised of ReA, PsA, enteritis-associated arthritis and undifferentiated pSpA (upSpA). ReA and upSpA share T cell oligotypes and metabolomics in serum and SF. We investigated HLA-B27 subtypes and cytokines in serum and SF that were compared between ReA and upSpA. METHODS: ReA and upSpA were compared in two cohorts. In cohort I (44 ReA and 56 upSpA), HLA-B27 subtyping was carried out. In cohort II (17 ReA and 21 upSpA), serum and SF cytokines were compared using a multiplex cytokine bead assay (27 cytokines). A total of 28 healthy controls with similar age and sex to cohort II were included for comparison of serum cytokine levels. RESULTS: In cohort I, HLA-B27 was positive in 81.8% (36/44) of ReA and 85.71% (48/56) of upSpA patients. HLA-B27 typing was successful in 70 patients (30 ReA and 40 uSpA). HLA-B*2705 was the most common, followed by HLA-B*2704 and HLA-B*2707. Frequencies were the same between ReA and upSpA. In cohort II, 14 cytokines were detectable in the serum of patients. The levels of eight cytokines were higher than in the controls. The cytokine levels of ReA and upSpA were similar. Sixteen cytokines were detectable in the SF of patients. There was no statistical difference in the levels between ReA and upSpA. The cytokine profiles in sera and SF were also similar among HLA-B27-positive and negative patients. CONCLUSION: ReA and upSpA have similar HLA-B27 subtype associations and similar cytokine profiles. They should be considered as a single entity during studies as well as clinical management.


Assuntos
Artrite Reativa/imunologia , Citocinas/imunologia , Antígeno HLA-B27/imunologia , Espondilartrite/imunologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
11.
Clin Rheumatol ; 40(11): 4619-4627, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34169374

RESUMO

BACKGROUND: The data on long-term outcome in enthesitis-related arthritis (ERA), the commonest category of JIA in India, is scant. Thus, we studied outcomes of ERA in a resource-constrained setting. METHODS: Patients with ERA (ILAR classification) (≥ 5 years of disease and ≥ 18 years) were included. Data on clinical features, Bath indices (BASMI, BASDAI, BASFI), ASDAS, and health assessment questionnaire-disability index (HAQ-DI) was collected. X-ray pelvis including hips was obtained and compared with baseline X-ray for progression of sacroiliitis and hip arthritis. Fulfillment of adult criteria of spondyloarthropathy (SpA) were also assessed. RESULTS: Seventy-three 73 patients (72 males) of median age 20 (18-23) years and disease duration 8 (5.5-11) years were recruited. There was delay in diagnosis of 4 (1.75-6) years. Thirty-nine (53%) had BASDAI ≥ 4 and 63 (91%) had ASDAS-CRP > 1.3. Two-third (60%) had functional disability (HAQ-DI ≥ 0.5). Poor outcome (BASDAI ≥ 4, ASDAS > 2.1, BASFI > 0.9, or HAQ-DI ≥ 0.5) was seen in three-fourths (n = 56.76%) of patients and was associated with hip involvement, HLA-B27 positivity, and fulfillment of axial ASAS criteria. Sixty-seven (91%) patients fulfilled axial ASAS criteria, while 71 (97%) fulfilled peripheral ASAS criteria. Overall, 81% had X-ray sacroiliitis and 37% had hip involvement. Nearly half (46.6%) and one-fourths (25%) of the patients had X-ray sacroiliitis and hip arthritis progression, respectively. Those with X-ray hip arthritis had longer delay in diagnosis (6 vs 3 years), higher Bath indices, ASDAS, and HAQ-DI. Hip arthritis correlated with radiological sacroiliitis (r = 0.301). Fulfillment of modified NY criteria was seen more often in patients with hip arthritis (95 vs 63%; p < 0.002). CONCLUSION: Most ERA patients had active disease in adulthood. Hip involvement, axial involvement, and HLA-B27 positivity were predictors of poor outcome. Key Points • Almost 90% of adults with ERA had active disease even after 8 years of disease. • Poor outcomes were seen in three-fourths of patients and hip involvement, presence of HLA B27, and axial involvement were the predictors of poor outcome.


Assuntos
Artrite Juvenil , Sacroileíte , Espondilartrite , Espondiloartropatias , Adulto , Artrite Juvenil/complicações , Criança , Antígeno HLA-B27 , Humanos , Masculino , Sacroileíte/complicações , Sacroileíte/diagnóstico por imagem , Adulto Jovem
12.
J Bodyw Mov Ther ; 26: 435-442, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33992280

RESUMO

INTRODUCTION: Shoulder adhesive capsulitis is a common pathology in middle aged population, physical therapy being the mainstay treatment for it. Various conventional treatment modalities have been proven to help in this condition. Instrument Assisted Soft Tissue Mobilization (IASTM) is a considerably new technique, which is being used widely for various sports related injuries for a faster recovery. This study proposes to evaluate the effect of IASTM as an added treatment for improving pain, range of motion and functional ability in patients with adhesive capsulitis. METHOD: 30 shoulders were randomly allocated into two groups- Group A (IASTM + conventional treatment) and Group B (conventional treatment). Treatment was given for 12 sessions, 3 sessions per week for 4 weeks. Participants were evaluated pre treatment, post 6th session and post 12th session. Outcome measures was Numerical Pain Rating Scale, Shoulder Pain And Disability Index, Shoulder Range of Motion, Apley's scratch test. RESULTS: Pain and Disability scale had shown improvement within the group only. However, in experimental group significant improvement was seen in active and passive mobility including functional performance. CONCLUSION: IASTM along with conventional protocol was able to improve mobility and function among adhesive capsulitis patients.


Assuntos
Bursite , Articulação do Ombro , Bursite/terapia , Humanos , Pessoa de Meia-Idade , Medição da Dor , Amplitude de Movimento Articular , Dor de Ombro , Resultado do Tratamento
13.
Front Immunol ; 12: 630691, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33815380

RESUMO

Background: Systemic autoinflammatory diseases (SAID) are rare inherited disorders involving genes regulating innate immune signaling and are characterized by periodic or chronic multi-systemic inflammation. Objective: To describe spectrum of clinical, immunological, molecular features, and outcomes of patients with SAID in India. Methods: Request to share data was sent to multiple centers in India that are involved in care and management of patients with Inborn Errors of Immunity. Six centers provided requisite data that were compiled and analyzed. Results: Data on 107 patients with SAID were collated-of these, 29 patients were excluded due to unavailability of complete information. Twelve patients (15%) had type 1 interferonopathies, 21 (26%) had diseases affecting inflammasomes, 30 patients (41%) had non-inflammasome related conditions and 1five patients (19%) had Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA). Type1 interferonopathies identified in the cohort included patients with Deficiency of Adenosine Deaminase 2 (DADA2) (six patients; five families); STING-associated vasculopathy infantile-onset (SAVI) (three patients, one family); Spondyloenchondro-dysplasia with Immune Dysregulation (SPENCD) (two patients). Diseases affecting inflammasomes include Mevalonate Kinase Deficiency (eight patients); Cryopyrin-Associated Periodic Syndromes (CAPS) (seven patients); NLR Family, Pyrin domain-containing 12 (NLRP12) (two patients); Familial Mediterranean fever (FMF) (two patients); Autoinflammation and PLCG2-associated antibody deficiency and immune dysregulation (APLAID) (two patients). TNF receptor-associated periodic syndrome (TRAPS) (three patients); A20 haploinsufficiency (four patients); Deficiency of Interleukin 1 Receptor Antagonist (DIRA) (two patients) were categorized as non-inflammasome related conditions. There were significant delays in diagnosis Corticosteroids and other immunosuppressive agents were used for treatment as anti-IL-1 drugs and other biological agents were and still are not available in India. Eight (16.3%) patients had so far succumbed to their illness. Conclusions: This is the first nationwide cohort of patients with SAID from India. Clinical manifestations were diverse. Overlapping of clinical features with other relatively common rheumatological disorders often resulted in delays in diagnosis. More nationwide efforts are needed to enhance awareness of SAID among health care professionals and there is an urgent need to make targeted immunotherapies universally available.


Assuntos
Doenças Hereditárias Autoinflamatórias/complicações , Feminino , Doenças Hereditárias Autoinflamatórias/diagnóstico , Doenças Hereditárias Autoinflamatórias/terapia , Humanos , Masculino
14.
Front Immunol ; 12: 631298, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33732252

RESUMO

Mendelian Susceptibility to Mycobacterial diseases (MSMD) are a group of innate immune defects with more than 17 genes and 32 clinical phenotypes identified. Defects in the IFN-γ mediated immunity lead to an increased susceptibility to intracellular pathogens like mycobacteria including attenuated Mycobacterium bovis-Bacillus Calmette-Guérin (BCG) vaccine strains and non-tuberculous environmental mycobacteria (NTM), Salmonella, fungi, parasites like Leishmania and some viruses, in otherwise healthy individuals. Mutations in the IL12RB1 gene are the commonest genetic defects identified. This retrospective study reports the clinical, immunological, and molecular characteristics of a cohort of 55 MSMD patients from 10 centers across India. Mycobacterial infection was confirmed by GeneXpert, Histopathology, and acid fast bacilli staining. Immunological workup included lymphocyte subset analysis, Nitro blue tetrazolium (NBT) test, immunoglobulin levels, and flow-cytometric evaluation of the IFN-γ mediated immunity. Genetic analysis was done by next generation sequencing (NGS). Disseminated BCG-osis was the commonest presenting manifestation (82%) with a median age of presentation of 6 months due to the practice of BCG vaccination at birth. This was followed by infection with Salmonella and non-typhi Salmonella (13%), Cytomegalovirus (CMV) (11%), Candida (7%), NTM (4%), and Histoplasma (2%). Thirty-six percent of patients in cohort were infected by more than one organism. This study is the largest cohort of MSMD patients reported from India to the best of our knowledge and we highlight the importance of work up for IL-12/IL-23/ISG15/IFN-γ circuit in all patients with BCG-osis and suspected MSMD irrespective of age.


Assuntos
Predisposição Genética para Doença/genética , Imunidade Inata/genética , Mutação , Infecções por Mycobacterium/genética , Infecções por Mycobacterium/imunologia , Adolescente , Adulto , Vacina BCG/imunologia , Criança , Pré-Escolar , Coinfecção/epidemiologia , Coinfecção/microbiologia , Feminino , Predisposição Genética para Doença/epidemiologia , Humanos , Índia/epidemiologia , Lactente , Recém-Nascido , Masculino , Infecções por Mycobacterium/epidemiologia , Infecções por Mycobacterium/microbiologia , Fenótipo , Receptores de Interleucina-12/genética , Receptores de Interleucina-12/imunologia , Estudos Retrospectivos , Adulto Jovem
15.
Front Immunol ; 12: 612583, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33746956

RESUMO

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of immune dysregulation characterized by hyperactivation of the immune system, excessive cytokine secretion and severe systemic inflammation. HLH is classified as familial (FHL) when associated with mutations in PRF1, UNC13D, STX11, and STXBP2 genes. There is limited information available about the clinical and mutational spectrum of FHL patients in Indian population. This study is a retrospective analysis of 101 molecularly characterized FHL patients over the last 10 years from 20 different referral centers in India. FHL2 and FHL3 together accounted for 84% of cases of FHL in our cohort. Patients belonging to different FHL subtypes were indistinguishable based on clinical and biochemical parameters. However, flow cytometry-based assays viz. perforin expression and degranulation assay were found to be specific and sensitive in diagnosis and classification of FHL patients. Molecular characterization of respective genes revealed 76 different disease-causing mutations including 39 (51%) novel mutations in PRF1, UNC13D, STX11, and STXBP2 genes. Overall, survival was poor (28%) irrespective of the age of onset or the type of mutation in our cohort. Altogether, this article sheds light on the current scenario of FHL in India. Our data reveal a wide genetic heterogeneity of FHL in the Indian population and confirms the poor prognosis of FHL. This study also emphasizes that though mutational analysis is important for diagnostic confirmation of FHL, flow cytometry based assays help significantly in rapid diagnosis and functional validation of novel variants identified.


Assuntos
Biomarcadores , Suscetibilidade a Doenças , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/etiologia , Fenótipo , Alelos , Criança , Pré-Escolar , Terapia Combinada , Biologia Computacional/métodos , Bases de Dados Genéticas , Gerenciamento Clínico , Suscetibilidade a Doenças/imunologia , Feminino , Predisposição Genética para Doença , Humanos , Índia , Lactente , Linfo-Histiocitose Hemofagocítica/metabolismo , Linfo-Histiocitose Hemofagocítica/terapia , Masculino , Mutação , Perforina/genética , Perforina/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Resultado do Tratamento
16.
Indian J Pediatr ; 88(8): 819-823, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33712926

RESUMO

Monogenic disorders causing systemic lupus erythematosus represent a small subset of cases. Type-1 interferonopathies, like spondyloenchondrodysplasia with immune dysregulation constitute an important functional category of monogenic lupus. Apart from autoimmune disorders, neurological and skeletal abnormalities are additional manifestations observed in this disorder. A young female presented with seizures due to acute hemorrhagic stroke secondary to malignant hypertension. On evaluating the cause for hypertension, there was evidence of glomerulonephritis and multiple autoantibodies positivity including dsDNA. A diagnosis of lupus was made based on clinical and laboratory findings. Kidney biopsy revealed mesangial proliferative glomerulonephritis with predominant IgA deposits favouring IgA nephropathy. Additional features in the form of short stature with vertebral abnormalities and bilateral basal ganglia calcification led to evaluation of Type-1 interferonopathies. Sanger sequencing identified a novel compound heterozygous variants c.550C>T (p.Q184*) in exon 3 and c.740T>G (p.L247R) in exon 4 of ACP5 gene. Parents were found to be carriers of the variants in ACP5 gene. Management included antihypertensive agents and symptomatic therapy. On follow-up, there was complete resolution of glomerulonephritis and normalization of blood pressure. This case report documents the classic phenotype comprising autoimmune, skeletal, and neurological abnormalities in spondyloenchondrodysplasia with immune dysregulation with a novel variant on Sanger sequencing in an Indian patient. This report also highlights the rare coexistence of IgA nephropathy in monogenic lupus.


Assuntos
Doenças Autoimunes , Glomerulonefrite por IGA , Síndromes de Imunodeficiência , Lúpus Eritematoso Sistêmico , Feminino , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/genética , Humanos , Osteocondrodisplasias
17.
Int J Rheum Dis ; 24(5): 654-662, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33780152

RESUMO

INTRODUCTION: The adenosine pathway is one of the ways through which methotrexate (MTX) ameliorates inflammation. We therefore explored an association of polymorphism of genes involved in adenosine and MTX metabolic pathways with response to MTX. METHODS: Association of polymorphism in 7 genes (rs2236225 [MTHFD1 1958G>A], rs17602729 [AMPD1 G>A], rs1127354 [ITPA C>A], rs1431131 [TGFBR2 A>T], rs2372536 [ATIC C>G], rs11188513 [ENTPD1 C>T] and rs5751876 [ADORA2A T>C]) with efficacy of MTX was studied in Indian rheumatoid arthritis (RA) patients. The patients, classified by European League Against Rheumatology (EULAR)/American College of Rheumatology (ACR) 2010 criteria, were DMARD (disease-modifying antirheumatic drug)-naïve, with Disease Activity Score (DAS28) >3.2. After 4 months of MTX monotherapy, patients were classified as responders (R) or non-responders (NR) based on EULAR response criteria. Genotyping was done by TaqMan 5' nuclease assay and association of gene polymorphisms with response to MTX was determined by Chi-squared test. RESULTS: Two hundred and twenty-six patients (86% female, median age 40 [interquartile range, IQR = 17.25] years), with disease duration of 24 (IQR = 38.25) months and DAS28-C-reactive protein score of 4.61 (IQR = 1.34) were enrolled. After therapy, 186 patients were classified as R and 40 as NR. GG genotype of ATIC (P = .01, odds ratio [OR] 2.56, 95% CI, 1.04-6.30) and CC genotype of ITPA (P = .009, OR 1.34, 95% CI 1.02-1.76) genes were found to be associated with the response. On binary logistic regression analysis, GG genotype of ATIC and CC of ITPA genes were independent predictors of the response. CONCLUSION: Polymorphisms of ATIC and ITPA genes alone or with clinical variables were associated with response to MTX therapy in Indian RA patients.

18.
Rheumatol Int ; 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33723658

RESUMO

Acute pancreatitis (AP) is a rare but life threatening manifestation of Systemic Lupus Erythematosus (SLE). The current study aims to study the clinical characteristics, severity, mortality, and outcome of SLE-related AP in Indian population. We retrospectively reviewed medical records of patients with SLE who had AP in the past. Data from 13 rheumatology centers across India were compiled. All patients satisfied SLICC criteria for SLE and ATLANTA criteria for AP. AP was classified in to mild, moderate and severe using revised Atlanta classification. Patients with known risk factors like gall stone and alcohol were excluded.Sixty-six patients (six, children) were studied. Majority of patients were females (82%). The median age of presentation was 24 (11-63) years and most patients (57.5%) presented within first year of diagnosis of lupus. AP occurred mostly in the setting of active lupus (89%). Active nephritis was seen in 39% while a fourth had CNS disease. Patients with severe AP had lower C3. Ascites and sepsis were most common local and systemic complications, respectively. Mortality was 17%. Hypocalcemia, presence of sepsis and shock predicted mortality. In the multivariate analysis, only presence of shock remained as independent predictor of death (OR 63.0, 95% CI: 5.2-760.3). Pancreatitis is an early manifestation of SLE and is associated with active disease. Significant mortality is seen particularly with severe pancreatitis.

19.
Lupus ; 30(6): 921-925, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33593161

RESUMO

INTRODUCTION: IL-36 is a new member of the IL-1 family with pro-inflammatory properties. Serum levels of IL-36 are elevated in patients with Systemic Lupus Erythematosus (SLE). However, no data is available on urinary levels of IL-36 in Lupus Nephritis (LN). In psoriasis expression of IL-36 is site specific and expressed in skin. Hence, we studied urinary levels of IL-36 cytokines in SLE patients. METHODS: A total of 196 patients with SLE [97 active LN patients (ALN), 42 inactive LN (ILN) and 57 active lupus patients with no renal involvement (ANR)] and 25 healthy subjects were recruited for the study after obtaining informed consent. Urinary and plasma IL-36α, IL-36γ and IL-36Ra levels were measured by ELISA. RESULTS: Out of 196 patients 178 were females. Urinary IL-36γ levels in SLE patients [0(14.3) pg/ml] were significantly higher than healthy controls [0(0) pg/ml, (P < 0.01)]. Patients with ALN [0(40.6) pg/ml] had significantly higher IL-36γ when compared to ANR [0(0) pg/ml] as well as ILN [0(0) pg/ml]. Urinary IL-36γ levels in ALN patients had a fair correlation with renal SLEDAI (r = 0.26, P = 0.004).The levels reduced significantly post 3 months in patients with ALN. No inverse relationship was noted between IL-36Ra and IL-36α/IL36γ levels. CONCLUSION: Urinary IL-36γ is produced locally in kidney, correlates with renal disease activity and reduces upon treatment, suggesting that it may have a role in pathogenesis of LN.

20.
Rheumatol Int ; 41(5): 887-894, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33433731

RESUMO

Systemic lupus erythematosus (SLE) cohorts across the world have allowed better understanding of SLE, including its bimodal mortality, and the impact of social factors and ethnicity on outcomes. The representation of patients from South Asia has been poor in the existing SLE cohorts across the world. Hence, we planned to initiate an inception cohort to understand the diversity of lupus in India. Indian SLE Inception cohort for REsearch (INSPIRE), planned over 5 years is a multi-centric cohort of adult and childhood lupus patients of Indian origin, fulfilling the SLICC-2012 classification criteria, with an aim to provide cross-sectional information on demography, ethnicity, socio-economic status, standard disease variables, quality of life, and prospective information on new events like hospitalization, infections, pregnancies, changes in disease activity, and damage. One of the other deliverables of this project is the establishment of a biorepository. The instruments to be used for each variable and outcome were finalized, and a web-enabled case report form was prepared to encompass SLEDAI, BILAG, SLICC damage scores, and Lupus quality-of-life index.Ten centers located in different geographic areas of India would enroll patients who are seen for the first time after the start of the study. In the first 8 months, 476 patients (63 children, 36 males) have been enrolled with a median disease duration of 10 (IQR 4-17) months and mucocutaneous features being the most prevalent clinical manifestations. INSPIRE is the first prospective Indian SLE cohort to study the diversity of Indian patients.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...