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INTRODUCTION: Mixed connective tissue disease (MCTD) is a rare entity in children. There is a paucity of studies on juvenile-onset MCTD (jMCTD) worldwide especially from Southeast Asia. OBJECTIVES: To describe clinical and laboratory features of jMCTD diagnosed at pediatric rheumatology centers across India. METHODS: A predesigned detailed case proforma in an excel format was prepared and was sent to all the Pediatric Rheumatology centers in India. Eleven centers provided the clinical and laboratory data of their jMCTD patients, which was then compiled and analyzed in detail. RESULTS: Thirty-one jMCTD patients from 11 centers were included in the study. Our cohort had 27 females and four male patients over 12 months (August 2021 to July 2022). The median age at presentation was 12 years (range 5-18 years) and the median duration of symptoms was 24 months at diagnosis (range 2-96 months). The common features included arthritis (90%), malar rash (70.9%), and Raynaud's phenomenon (70.9%). At a mean follow-up of 43 months (range 1-168 months), 45% of them were in remission. There were two deaths reported, due to macrophage activation syndrome and sepsis respectively. CONCLUSION: We present the largest multicenter experience on jMCTD from the Indian subcontinent. The study's findings serve as a crucial stepping stone toward unraveling the complexities of jMCTD and improving patient care and management strategies.
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Doença Mista do Tecido Conjuntivo , Humanos , Criança , Masculino , Feminino , Doença Mista do Tecido Conjuntivo/diagnóstico , Doença Mista do Tecido Conjuntivo/terapia , Doença Mista do Tecido Conjuntivo/epidemiologia , Índia/epidemiologia , Adolescente , Pré-Escolar , Resultado do Tratamento , Idade de Início , Imunossupressores/uso terapêutico , Antirreumáticos/uso terapêutico , Estudos Retrospectivos , Fatores de Tempo , Indução de RemissãoRESUMO
Idiopathic intracranial hypertension (IIH) is a diagnosis of exclusion characterized by features of raised intracranial pressure (ICP) in the absence of brain parenchymal lesion, vascular malformations, hydrocephalus, or central nervous system (CNS) infection. Commonly used other terms for this entity include benign intracranial hypertension (BIH) or pseudotumor cerebri. Few case reports of systemic lupus erythematosus (SLE) presenting as IIH are available in the literature. We report a 12-year-old girl presented with chronic holocranial headache and occasional episodes of projectile vomiting for the last 6 months and then developed blurring of vision for the last month. She fulfilled the criteria for IIH. Subsequent evaluation revealed a diagnosis of SLE. The occurrence of IIH in SLE is not coincidental and is reported in 1%-5.4% of patients with SLE. Though corticosteroids have not been widely used in IIH, underlying SLE warranted administering corticosteroids with subsequent complete resolution of IIH. Pediatricians, neurologists, intensivists, and ophthalmologists should consider SLE as a differential diagnosis in children presenting with IIH.
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Lúpus Eritematoso Sistêmico , Pseudotumor Cerebral , Humanos , Feminino , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Criança , Pseudotumor Cerebral/diagnóstico , Pseudotumor Cerebral/etiologia , Diagnóstico Diferencial , Cefaleia/etiologia , Hipertensão Intracraniana/etiologia , Hipertensão Intracraniana/diagnósticoRESUMO
INTRODUCTION: X-linked lymphoproliferative syndrome (XLP) is a rare primary immune deficiency. Two types of XLP have been described: XLP-1 and XLP-2. METHODS: We found 7 patients with XLP (3 had XLP-1 and 4 had XLP-2) after reviewing the data from Pediatric Immunodeficiency Clinic from 1997 to 2021. RESULTS: Mean age at diagnosis was 3.8 years, and mean delay in diagnosis was 2.6 years. Five patients had recurrent episodes of infections. Four patients developed at least one episode of hemophagocytic lymphohistiocytosis (HLH) (2 with XLP-1 and 2 with XLP-2). Of these, 2 had recurrent HLH (both with XLP-2). Epstein-Barr virus (EBV) infection was detected in 2 (1 with XLP-1 and 1 with XLP-2). Both these patients had HLH. One child with XLP-2 had inflammatory bowel disease. Hypogammaglobulinemia was seen in 3 (2 with XLP-1 and 1 with XLP-2). Genetic analysis showed previously reported variants in 5, while 2 had novel variants (one in exon 7 of XIAP gene [c.1370dup p.Asn457Lysfs Ter16] and other had splice site variant in intron 1 of SH2D1A gene [c.138-2_138-1insG]). Episodes of HLH were managed with intravenous immunoglobulin (IVIg), methylprednisolone, oral prednisolone, cyclosporine, and rituximab. Inflammatory bowel disease was managed using oral prednisolone and azathioprine. One patient underwent haploidentical hematopoietic stem cell transplantation. One child with XLP-2 and WAS died because of fulminant pneumonia. DISCUSSION/CONCLUSIONS: XLP should be considered as a strong possibility in any patient with features of HLH, repeated infections with hypogammaglobulinemia, persistent EBV infection, and early-onset IBD.
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Agamaglobulinemia , Infecções por Vírus Epstein-Barr , Doenças Inflamatórias Intestinais , Linfo-Histiocitose Hemofagocítica , Transtornos Linfoproliferativos , Criança , Humanos , Agamaglobulinemia/diagnóstico , Agamaglobulinemia/genética , Agamaglobulinemia/terapia , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4/genética , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/genética , Transtornos Linfoproliferativos/terapia , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/genética , Linfo-Histiocitose Hemofagocítica/terapia , PrednisolonaRESUMO
Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. The International League of Associations for Rheumatology (ILAR) has defined JIA as "arthritis of unknown etiology persisting for ≥6 wk with an onset at <16 y of age, after excluding other causes of joint inflammation". Synovial inflammation is the result of a complex interplay of aberrant immune systems (both adaptive and innate) in a genetically susceptible individual, with possible external stimuli/triggers. Diagnosis of JIA essentially remains clinical, and laboratory investigations usually help to assess the severity of disease activity. Few investigations like antinuclear antibodies (ANA), human leukocyte antigen (HLA)-B27, and rheumatoid factor (RF) help to categorize or prognosticate a child with JIA. Timely use of effective therapeutic interventions including biological has shown good long-term outcomes of JIA.
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BACKGROUND: Juvenile localized scleroderma (JLS) or morphoea, a rare chronic autoimmune disease predominantly affects skin, subcutaneous tissue and occasionally the adjacent muscle, fascia and bone. We report the largest single-centre cohort of patients with JLS from India. METHODS: Patients who were diagnosed to have JLS were enrolled from the Paediatric Dermatology Clinic and the Paediatric Rheumatology Clinic of a tertiary care referral hospital in India. Collected data included details of the clinical profile, laboratory investigations and management. RESULTS: We analysed 84 patients with Juvenile localized scleroderma. Median age of disease onset was 5 years, and median age at diagnosis was 8 years. Commonest subtype was linear scleroderma (57 patients, 67.7%) followed by plaque morphoea and generalized morphoea. Fourteen patients (16.6%) were noted to have extracutaneous manifestations (ECMs). These included arthritis in eight (33.3%), brain parenchymal abnormalities in four (4.7%) and pulmonary involvement in two (8.3%) patients. Antinuclear antibody (ANA) was positive in eight/25 patients (32%; diffuse and speckled pattern in four patients each). One amongst these also had elevated anti-dsDNA titres. Positive ANA was found to have no association with ECMs (p 1.000). Patients were treated using methotrexate (61 patients; 72.6%), dexamethasone oral mini-pulse (OMP; 35 patients; 41.6%), calcipotriol (39 patients; 46.4%), topical corticosteroids (32 patients; 38%) and topical tacrolimus (three patients; 3.7%). Using linear regression analysis, administration of dexamethasone OMP and calcipotriol was found to be a predictor of good treatment response (p 0.034 and 0.019, respectively). CONCLUSION: Early use of systemic corticosteroids along with methotrexate may be more beneficial than methotrexate therapy alone.
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Metotrexato , Esclerodermia Localizada , Criança , Humanos , Pré-Escolar , Metotrexato/uso terapêutico , Esclerodermia Localizada/complicações , Glucocorticoides/uso terapêutico , Índia , Doenças Raras/complicações , Doenças Raras/tratamento farmacológico , Dexametasona/uso terapêuticoRESUMO
Inborn errors of immunity (IEIs) are a group of heterogeneous disorders characterized by a broad clinical spectrum of recurrent infections and immune dysregulation including autoimmunity and lymphoproliferation (LP). LP in the context of IEI may be the presenting feature of underlying immune disorder or may develop during the disease course. However, the correct diagnosis of LP in IEI as benign or malignant often poses a diagnostic dilemma due to the non-specific clinical features and overlapping morphological and immunophenotypic features which make it difficult to treat. There are morphological clues to LP associated with certain IEIs. A combination of ancillary techniques including EBV-associated markers, flow cytometry, and molecular assays may prove useful in establishing a correct diagnosis in an appropriate clinical setting. The present review attempts to provide comprehensive insight into benign and malignant LP, especially the pathogenesis, histological clues, diagnostic strategies, and treatment options in patients with IEIs.
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Autoimunidade , Doenças do Sistema Imunitário , Progressão da Doença , HumanosRESUMO
Ghosal hematodiaphyseal dysplasia (GHDD) is a rare, autosomal recessive condition characterised by diaphyseal dysplasia of long bones with defective haematopoiesis. We describe 2 such cases with clinical and radiological evidence of GHDD. Molecular analysis revealed novel variants in TBXAS1 gene in both of them. Suspicion and confirmation of this entity is crucial in cases of refractory anemia with bony deformities, as the clinical manifestations in this entity are usually well responsive to corticosteroids.
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Anemia Refratária , Osteocondrodisplasias , Anemia Refratária/diagnóstico por imagem , Anemia Refratária/genética , Osso e Ossos , Criança , Humanos , Osteocondrodisplasias/diagnóstico por imagem , Osteocondrodisplasias/genética , RadiografiaRESUMO
Objectives: We aimed to evaluate shoulder joint by magnetic resonance imaging (MRI) using the Juvenile Arthritis Magnetic Resonance Imaging Scoring (JAMRIS) system in children with juvenile idiopathic arthritis (JIA) and to compare clinical, laboratory parameters and disease activity scores with MRI parameters. Patients and methods: A total of 32 shoulder joints of 20 patients (16 males, 4 females; mean age: 8.9±3.5 years; range, 2.5 to 14 years) with a known diagnosis of JIA and a clinical suspicion of shoulder joint involvement and underwent MRI were included. Reliability was determined by inter- and intra-observer correlation coefficients. Correlation of the clinical and laboratory parameters with JAMRIS scores was done using the non-parametric tests. Sensitivity of clinical examination to detect shoulder joint arthritis was also determined. Results: Of the 32 joints, 27 joints in 17 patients showed MRI changes. Seven joints in five patients fulfilled the definition of clinical arthritis, all revealed MRI changes. In 25 joints without clinical arthritis, early and late MRI changes were seen in 19 (67%) and 12 (48%) joints, respectively. The inter- and intra-observer correlation coefficients for JAMRIS system were excellent. No correlation was found between MRI parameters, clinical, laboratory, and disease activity scores. The sensitivity of clinical examination to detect shoulder joint arthritis was 25.9%. Conclusion: The JAMRIS system is reliable and reproducible to determine shoulder joint inflammation in JIA. Detection of shoulder joint arthritis by clinical examination has a poor sensitivity.
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Aim: To assess distress, insomnia, and psychosocial impact of SARS-CoV-2 outbreak on children with SLE and their caregivers. Methods: Patients with pSLE undergoing treatment in the Department of Pediatrics, PGIMER, Chandigarh, and their caregivers were enrolled. Questionnaires were sent to eligible patients and their parents through email or WhatsApp and telephonic interviews were conducted. Self-designed SLE-COVID-19 stress questionnaire; Peritraumatic Distress Inventory; Insomnia Severity Index, Positive and Negative Affect Schedule were used. Ethical approval was sought from Institutes Ethics Committee (IEC/2020/000583). Results: Telephonic connection was possible with 80 families (160 participants). Telephonic contact was possible with 80 families (160 participants); off these 61 children with pSLE (78.2%) and 55 caregivers (70.5%) responded to the questionnaire. Among participants, 23% patients, and 21.8% caregivers were severely stressed about SARS-CoV-2 infection; 78.7% patients and 80% caregivers had heard about hydroxychloroquine (HCQ) being used for the treatment of COVID-19; 52.7% caregivers exhibited moderate concern about shortage of HCQ; and 52.5% patients, and 43.6% caregivers were worried about side effects of HCQ. We found that 20 (32.8%) patients and 18 (32.7%) caregivers experienced significant distress. Majority of participants reported sleep disturbances. High positive affect scores were seen in 40 (65.5%) patients and 43 (78.2%) caregivers, low positive affect scores were noted in 21 (34.5%) patients and 12 (21.8%) caregivers. Conclusion: Patients with pSLE and their caregivers are at risk of psychosocial problems during the COVID-19 pandemic. Psychological interventions can be very helpful.
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Wiskott-Aldrich syndrome (WAS) is an uncommon X-linked combined-immunodeficiency disorder characterized by a triad of thrombocytopenia, eczema, and immunodeficiency. Patients with WAS are also predisposed to autoimmunity and malignancy. Autoimmune manifestations have been reported in 26%-72% of patients with WAS. Autoimmunity is an independent predictor of poor prognosis and predisposes to malignancy. Development of autoimmunity is also an early pointer of the need for hematopoietic stem-cell transplantation. In this manuscript, we have collated the published data and present a narrative review on autoimmune manifestations in WAS. A summary of currently proposed immunopathogenic mechanisms and genetic variants associated with development of autoimmunity in WAS is also included.
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Artrite Juvenil , Síndrome de Ativação Macrofágica , Artrite Juvenil/complicações , Artrite Juvenil/tratamento farmacológico , Ciclosporina , Frequência Cardíaca , Humanos , Síndrome de Ativação Macrofágica/tratamento farmacológico , Síndrome de Ativação Macrofágica/etiologia , MetilprednisolonaRESUMO
Background: Wiskott Aldrich syndrome (WAS) is characterized by bleeding manifestations, recurrent infections, eczema, autoimmunity, and malignancy. Over the last decade, improved awareness and better in-house diagnostic facilities at several centers in India has resulted in increased recognition of WAS. This study reports collated data across major primary immunodeficiency diseases (PID) centers in India that are involved in care of children with WAS and highlights the varied clinical presentations, genetic profile, and outcomes of patients in India. Methods: Request to share data was sent to multiple centers in India that are involved in care and management of patients with PID. Six centers provided requisite data that were compiled and analyzed. Results: In this multi-institutional cohort, clinical details of 108 patients who had a provisional diagnosis of WAS were received. Of these, 95 patients with 'definite WAS' were included Fourteen patients were classified as XLT and 81 patients as WAS. Median age at onset of symptoms of patients was 3 months (IQR 1.6, 6.0 months) and median age at diagnosis was 12 months (IQR 6,48 months). Clinical profile included bleeding episodes (92.6%), infections (84.2%), eczema (78.9%), various autoimmune manifestations (40%), and malignancy (2.1%). DNA analysis revealed 47 variants in 67 cases. Nonsense and missense variants were the most common (28.4% each), followed by small deletions (19.4%), and splice site defects (16.4%). We also report 24 novel variants, most of these being frameshift and nonsense mutations resulting in premature termination of protein synthesis. Prophylactic intravenous immunoglobulin (IVIg) was initiated in 52 patients (54.7%). Hematopoietic stem cell transplantation (HSCT) was carried out in 25 patients (26.3%). Of those transplanted, disease-free survival was seen in 15 patients (60%). Transplant related mortality was 36%. Outcome details were available for 89 patients. Of these, 37% had died till the time of this analysis. Median duration of follow-up was 36 months (range 2 weeks- 12 years; IQR 16.2 months- 70 months). Conclusions: We report the first nationwide cohort of patients with WAS from India. Bleeding episodes and infections are common manifestations. Mortality continues to be high as curative therapy is not accessible to most of our patients.
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Países em Desenvolvimento , Mutação , Proteína da Síndrome de Wiskott-Aldrich/genética , Síndrome de Wiskott-Aldrich/genética , Fatores Etários , Pré-Escolar , Intervalo Livre de Doença , Feminino , Predisposição Genética para Doença , Transplante de Células-Tronco Hematopoéticas , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Índia , Lactente , Masculino , Fenótipo , Medição de Risco , Fatores de Risco , Fatores de Tempo , Síndrome de Wiskott-Aldrich/diagnóstico , Síndrome de Wiskott-Aldrich/imunologia , Síndrome de Wiskott-Aldrich/terapiaRESUMO
A spectrum of dermatologic manifestations has been reported in multisystem inflammatory syndrome in children associated with SARS-CoV-2 infection. We report 2 patients with multisystem inflammatory syndrome in children and severe cardiovascular dysfunction who developed acral gangrene. Both responded well to therapy and recovered in the follow-up.
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COVID-19/patologia , Gangrena/virologia , Síndrome de Resposta Inflamatória Sistêmica/patologia , COVID-19/diagnóstico por imagem , COVID-19/fisiopatologia , COVID-19/virologia , Criança , Família , Gangrena/diagnóstico por imagem , Gangrena/patologia , Gangrena/fisiopatologia , Humanos , Masculino , SARS-CoV-2/isolamento & purificação , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico por imagem , Síndrome de Resposta Inflamatória Sistêmica/fisiopatologia , Síndrome de Resposta Inflamatória Sistêmica/virologiaAssuntos
COVID-19/diagnóstico , Síndrome Congênita de Insuficiência da Medula Óssea/diagnóstico , Elastase de Leucócito/genética , Mutação/genética , Neutropenia/congênito , SARS-CoV-2/fisiologia , Febre , Humanos , Lactente , Masculino , Neutropenia/diagnóstico , Insuficiência Respiratória , Úlcera , Eliminação de Partículas ViraisRESUMO
Cold agglutinin disease (CAD) is extremely rare in children. We report an 8-year-old boy who presented with gangrene of right foot with hypertension and absent lower limb pulses. Blood peripheral smear evidence of autoagglutination and falsely elevated red blood cell indices were suggestive of CAD and on subsequent investigations he was found to have high titres of cold agglutinin antibodies. He also had evidence of pneumonia on chest X-ray and serology for mycoplasma was positive. Computed tomography angiography showed multifocal thrombotic occlusion in bilateral popliteal arteries. He was effectively managed using antimicrobials, warm clothing, aspirin, anticoagulation and corticosteroids. He remains clinically well on follow-up and had no recurrence. CAD presenting with peripheral gangrene is extremely unusual. A careful look at peripheral blood smear gives an initial diagnostic clue. CAD triggered by infection is often self-limiting and requires supportive care.
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Anemia Hemolítica Autoimune/complicações , Anemia Hemolítica Autoimune/etiologia , Gangrena/complicações , Infecções por Mycoplasma/complicações , Infecções por Mycoplasma/microbiologia , Trombose/diagnóstico , Trombose/etiologia , Testes de Aglutinação , Anemia Hemolítica Autoimune/diagnóstico , Antibacterianos/uso terapêutico , Anticoagulantes/uso terapêutico , Biomarcadores , Criança , Crioglobulinas/imunologia , Pé/patologia , Gangrena/diagnóstico , Gangrena/tratamento farmacológico , Gangrena/etiologia , Humanos , Masculino , Infecções por Mycoplasma/tratamento farmacológico , Radiografia Torácica , Trombose/terapia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Background: Chronic granulomatous disease (CGD) is an inherited defect in phagocytic respiratory burst that results in severe and life-threatening infections in affected children. Single center studies from India have shown that proportion of autosomal recessive (AR) CGD is more than that reported from the West. Further, affected patients have high mortality rates due to late referrals and difficulties in accessing appropriate treatment. However, there is lack of multicentric collaborative data on CGD from India. Objective: To describe infection patterns, immunological, and molecular features of CGD from multiple centers in India. Methods: A detailed proforma that included clinical and laboratory details was prepared and sent to multiple centers in India that are involved in the care and management of patients with inborn errors of immunity. Twelve centers have provided data which were later pooled together and analyzed. Results: Of the 236 patients analyzed in our study, X-linked and AR-CGD was seen in 77 and 97, respectively. Male female ratio was 172:64. Median age at onset of symptoms and diagnosis was 8 and 24 months, respectively. Common infections documented include pneumonia (71.6%), lymphadenitis (31.6%), skin and subcutaneous abscess (23.7%), blood-stream infection (13.6%), osteomyelitis (8.6%), liver abscess (7.2%), lung abscess (2.9%), meningoencephalitis (2.5%), splenic abscess (1.7%), and brain abscess (0.9%). Forty-four patients (18.6%) had evidence of mycobacterial infection. Results of molecular assay were available for 141 patients (59.7%)-CYBB (44.7%) gene defect was most common, followed by NCF1 (31.9%), NCF2 (14.9%), and CYBA (8.5%). While CYBA variants were documented only in Southern and Western parts of India, a common dinucleotide deletion in NCF2 (c.835_836delAC) was noted only in North Indian population. Of the 174 patients with available outcome data, 67 (38.5%) had expired. Hematopoietic stem cell transplantation was carried out in 23 patients, and 12 are doing well on follow-up. Conclusions: In India, proportion of patients with AR-CGD is higher as compared to Western cohorts, though regional differences in types of AR-CGD exist. Clinical profile and mortality rates are similar in both X-linked and AR-CGD. However, this may be a reflection of the fact that milder forms of AR-CGD are probably being missed.