RESUMEN
Ataxia-telangiectasia (A-T) is a disease caused by mutations in the ATM gene (11q22.3-23.1) that induce neurodegeneration Sasihuseyinoglu AS et al. Pediatr Allergy Immunol Pulmonol 31(1):9-14, 2018, Teive HAG et al. Parkinsonism Relat Disord 46:3-8, 2018. Clinically, A-T is characterized by ataxia, mucocutaneous telangiectasia, immunodeficiency, and malignancy. Movement disorders have been the most described and well-studied symptoms of A-T. Other studies have reported visuospatial processing disorders, executive function disorders and emotional regulation disorders, which are clinical manifestations that characterize cerebellar cognitive affective syndrome (CCAS) Choy KR et al. Dev Dyn 247(1):33-46, 2018. To describe the neurocognitive and emotional state of pediatric patients with ataxia-telangiectasia and to discuss whether they have cerebellar cognitive affective syndrome. This observational, cross-sectional, and descriptive study included 9 patients with A-T from May 2019 to May 2021. A complete medical history was retrieved, and tests were applied to assess executive functions, visual-motor integration and abilities, language, psychological disorders, and ataxia. Six girls and 3 boys agreed to participate. The age range was 6 to 14 years. The participants included five schoolchildren and four teenagers. Eight patients presented impaired executive functioning. All patients showed some type of error in copying and tracing (distortion) in the performance of visual perceptual abilities. Emotional disorders such as anxiety and depression were observed in six patients. Eight patients presented with dyslalia and impairments in word articulation, all patients presented with ataxia, and seven patients used a wheelchair. All patients presented symptoms consistent with CCAS and had variable cognitive performance.
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Ataxia Telangiectasia , Ataxia Cerebelosa , Enfermedades Cerebelosas , Masculino , Femenino , Adolescente , Humanos , Niño , Ataxia Telangiectasia/complicaciones , Estudios Transversales , Ataxia Cerebelosa/genética , Cognición/fisiologíaRESUMEN
PURPOSE: We aimed to describe the clinical, immunological, and genetic features of patients with DOCK8 deficiency (DOCK8-Def) in a tertiary care center for children. METHODS: Retrospective chart review of patients' clinical, immunological, and genetic characteristics with DOCK8-Def. Genetic analysis was performed with targeted- or whole-exome sequencing; we also assessed DOCK8 protein expression and a lymphoproliferation assay and analyzed survival by the Kaplan-Meier method. RESULTS: We described 11 patients from 8 unrelated kindreds. The median age at symptoms' onset was 10 months (range 1-54 months). The median follow-up time was 53.4 months (4.8-118.8). All patients presented eczema and recurrent sinopulmonary and cutaneous infections. Besides those symptoms, the most frequent manifestations were bronchiectases (8/11), food allergies (6/11), and severe infections (6/11). Infrequent characteristics were detection of CMV in bronchial lavage, C. parvum-driven sclerosing cholangitis, Takayasu vasculitis, neurological syndromes, pulmonary tuberculosis, and lymphomatoid granulomatosis. CONCLUSION: DOCK8-Def has a broad spectrum of manifestations, including allergy, autoimmunity, inflammation, infection, and cancer. The hallmark of this inborn error of immunity is IEI-associated eczema with eosinophilia and increased IgE. Here, we report six new mutations causing human DOCK8 deficiency and symptoms previously unrecognized to occur in DOCK8-Def. Therefore, an early diagnosis of DOCK8-Def is essential to facilitate an adequate treatment such as HSCT.
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Eccema , Hipersensibilidad , Síndrome de Job , Niño , Humanos , Lactante , Preescolar , Estudios Retrospectivos , Síndrome de Job/genética , Eccema/epidemiología , Eccema/genética , Mutación , Factores de Intercambio de Guanina Nucleótido/genéticaRESUMEN
Juvenile idiopathic arthritis (JIA) is a heterogeneous group of arthritis of autoimmune aetiology. Systemic-onset juvenile idiopathic arthritis (soJIA) presents with fever, transient erythematous rash, hepatomegaly, splenomegaly, lymphadenopathy, and serositis. SoJIA presents multiple complications, and the most severe is the macrophage activation syndrome (MAS); the timely treatment of MAS must be established early and aggressively to avoid a fatal outcome. Therapeutic plasma exchange has anecdotally been used in refractory cases. A 66-month-old male with a 1-year illness characterized by evening-predominant, intermittent fever, adenomegalies, urticarial-like rash, arthralgia, and arthritis. Biochemical analysis revealed anaemia, leukocytosis, neutrophilia, hypertriglyceridemia, hyperferritinemia, and hypofibrinogenemia; bone marrow aspirate showed hemophagocytosis. He was diagnosed with SoJIA complicated with MAS. He received multiple treatments with IV human gammaglobulin, cyclosporine, dexamethasone, and tocilizumab without improvement. Plasma replacement treatment was performed. Afterwards, he presented significant improvement. After 3-year-follow-up, he remains in good general condition. We present a refractory case of soJIA complicated with MAS successfully treated with plasma exchange.
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Artritis Juvenil , Exantema , Linfohistiocitosis Hemofagocítica , Síndrome de Activación Macrofágica , Humanos , Masculino , Preescolar , Artritis Juvenil/complicaciones , Artritis Juvenil/terapia , Artritis Juvenil/diagnóstico , Síndrome de Activación Macrofágica/complicaciones , Síndrome de Activación Macrofágica/terapia , Intercambio Plasmático/efectos adversos , Linfohistiocitosis Hemofagocítica/complicacionesRESUMEN
Visual disturbances in Takayasu arteritis (TA) are common but tend to be late manifestations of the disease. However, its presence at diagnosis must alert TA to avoid sight disabilities. Herein, we present two children with TA that debuted with vision loss, and the results of the literature review displayed 58 subjects with vision loss before the diagnosis of TA. The world English literature was reviewed by searching the PubMed database of the National Library of Medicine for the terms "Takayasu Arteritis" and "Blindness" or "Amaurosis fugax", from 190 to 2021. Cases eligible must present vision loss before or at TA diagnosis. Our two patients who presented with amaurosis fulfilled the criteria for TA diagnosis. The first patient had a bilateral and transient visual loss, whereas the second had monocular and permanent amaurosis. Both patients were cursed with hypertension and demonstrated large vessel compromise; their clinical picture improved with corticosteroids and immunosuppressant therapy. We identified in the literature review sixteen patients with TA in case reports and 42 in case series, plus our two cases presented herein with monocular or bilateral vision loss at the time of diagnosis. Previous literature indicated that amaurosis represents a severely advanced disease. Herein, we reported two children with amaurosis as their pivotal symptom; they had significant head and neck vascular alterations, so prompt and aggressive treatment is needed to prevent disease progression and disability. Transient or permanent vision loss must alert the physician to include Takayasu arteritis in the differential diagnosis.
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Terapia de Inmunosupresión , Arteritis de Takayasu , Estados Unidos , Humanos , Niño , Ceguera/diagnóstico , Progresión de la Enfermedad , Arteritis de Takayasu/tratamiento farmacológico , Diagnóstico DiferencialRESUMEN
BACKGROUND: Leukocyte adhesion deficiency type 1 (LAD-1) is an inborn error of immunity characterized by a defect in leukocyte trafficking. METHODS: Patients with clinical suspicion of LAD-1 were referred to our institution. Complete blood count and flow cytometric analysis, to identify the expression of CD18, CD11b, and the lymphocyte population phenotyping, were performed, and statistical analysis was completed. RESULTS: We report clinical manifestations and immunological findings of six Mexican patients diagnosed with LAD-1. The diagnosis was based on typical clinical presentation, combined with laboratory demonstration of leukocytosis, and significant reduction or near absence of CD18 and its associated molecules CD11a, CD11b, and CD11c on leukocytes. We found atypical manifestations, not described in other countries, such as early-onset autoimmunity or infections caused by certain microorganisms. CONCLUSIONS: Patients with LAD-1 may present with atypical manifestations, making flow cytometry an indispensable tool to confirm the diagnosis. We present the first report of LAD-1 patients in a Latin American country.
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Antígenos CD18 , Síndrome de Deficiencia de Adhesión del Leucocito , Humanos , Antígenos CD18/metabolismo , México , Síndrome de Deficiencia de Adhesión del Leucocito/diagnóstico , LeucocitosRESUMEN
Multisystemic inflammatory syndrome in children is an inflammatory condition with multiorgan dysfunction that manifest late in the course of Severe acute respiratory syndrome coronavirus 2 infection. We present a 12-year-old boy with a history of fever, vomiting, diarrhoea, and abdominal pain. He developed shock with ventricular dysfunction and pericardial effusion. He was diagnosed with multisystemic inflammatory syndrome in children and treatment with intravenous immunoglobulins, corticosteroids, and tocilizumab proved to be ineffective. Eventually, the patient responded to cyclosporin-A treatment. Multisystemic inflammatory syndrome in children has been treated with immunoglobulins and glucocorticoids and in refractory cases biologics and cyclosporin-A have been used. Intravenous and oral cyclosporin-A seems to be a safe and effective alternative treatment for refractory multisystemic inflammatory syndrome in children patients.
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COVID-19 , Ciclosporina , Masculino , Humanos , Niño , Dolor Abdominal , Administración Intravenosa , Diarrea , SíndromeRESUMEN
BACKGROUND AND OBJECTIVES: Glucose-6-phosphate catalytic subunit 3 (G6PC3) deficiency is characterized by severe congenital neutropenia with recurrent pyogenic infections, a prominent superficial venous pattern and cardiovascular and urogenital malformations caused by an alteration of glucose homeostasis, with increased endoplasmic reticulum stress and cell apoptosis. METHODS: We reviewed our patients with G6PC3 deficiency diagnosed along the last decade in Mexico; we also searched the PubMed/Medline database for the terms ('G6PC3 deficiency' OR 'Dursun syndrome' OR 'Severe congenital neutropenia type 4'), and selected articles published in English from 2009 to 2020. RESULTS: We found 89 patients reported from at least 14 countries in 4 continents. We describe five new cases from Mexico. Of the 94 patients, 56% are male, 48% from Middle East countries and none of them had adverse reactions to live vaccines; all presented with at least 1 severe infection prior to age 2. Seventy-five per cent had syndromic features, mainly atrial septal defect in 55% and prominent superficial veins in 62%. CONCLUSIONS: With a total of 94 patients reported in the past decade, we delineate the most frequent laboratory and genetic features, their treatment and outcomes, and to expand the knowledge of syndromic and non-syndromic phenotypes in these patients.
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Glucosa-6-Fosfatasa , Neutropenia , Dominio Catalítico , Síndromes Congénitos de Insuficiencia de la Médula Ósea , Femenino , Glucosa-6-Fosfatasa/genética , Glucosa-6-Fosfatasa/metabolismo , Humanos , Masculino , Neutropenia/congénito , Neutropenia/genéticaRESUMEN
Mutations in recombinase activating genes 1 and 2 (RAG1/2) result in human severe combined immunodeficiency (SCID). The products of these genes are essential for V(D)J rearrangement of the antigen receptors during lymphocyte development. Mutations resulting in null-recombination activity in RAG1 or RAG2 are associated with the most severe clinical and immunological phenotypes, whereas patients with hypomorphic mutations may develop leaky SCID, including Omenn syndrome (OS). A group of previously unrecognized clinical phenotypes associated with granulomata and/or autoimmunity have been described as a consequence of hypomorphic mutations. Here, we present six patients from unrelated families with missense variants in RAG1 or RAG2. Phenotypes observed in these patients ranged from OS to severe mycobacterial infections and granulomatous disease. Moreover, we report the first evidence of two variants that had not been associated with immunodeficiency. This study represents the first case series of RAG1- or RAG2-deficient patients from Mexico and Latin America.
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Proteínas de Unión al ADN/deficiencia , Proteínas de Unión al ADN/genética , Proteínas de Homeodominio/genética , Mutación/genética , Mutación/inmunología , Proteínas Nucleares/deficiencia , Proteínas Nucleares/genética , Adolescente , Niño , Femenino , Humanos , Síndromes de Inmunodeficiencia/genética , Síndromes de Inmunodeficiencia/inmunología , Lactante , Linfocitos/inmunología , Masculino , México , FenotipoRESUMEN
INTRODUCTION: Patients with inborn errors of immunity (IEI) have a compromised or inappropriate immune response. Although they might be considered a high-risk group for severe SARS-CoV-2 infection, the reported impact of COVID-19 in these patients has been reassuring, while the differential susceptibility of distinct types of IEI remains unclear. OBJECTIVE: We aimed to describe the findings and outcomes of our known patients with IEI who were diagnosed with COVID-19. METHODS: In a retrospective study from March 2020 to February 2021, four centers in Mexico collected clinical, laboratory, and genetic data from pediatric and adult patients with known diagnoses of IEI who presented with COVID-19, based on compatible symptoms and positive SARS-CoV-2 testing or known household exposure. RESULTS: We report 31 patients with known IEI from Mexico who presented with SARS-CoV-2 infection. Seventy-four percent were male, 52% were pediatric, and 81% survived. Their ages ranged from 5 months to 56 years, with a median of 17 years. Sixty-five percent had predominant antibody deficiencies, 48% were hospitalized, and 26% required ICU. Pediatric patients had a higher hospital admission rate than adults. Inpatient mortality was 40%, and ICU mortality rate was 63%. Forty-eight percent developed pneumonia, while 36% had evidence of hyperinflammation (4 adults and 7 children). Predominant laboratory features were lymphopenia and thrombocytopenia, seen in 70 and 44% of patients, respectively. The serum D-dimer median value was 2.6 (0.5-20.6) µg/mL, and the median highest ferritin value was 1015 (32-10,303) ng/mL. Intravenous immunoglobulin was used in 80% of patients. Other treatments included macrolides (39%) and corticosteroids (29%). Six patients died from secondary infection or uncontrolled systemic inflammation. DISCUSSION: Although impaired immunity due to IEI may be a predisposing factor for severe COVID-19, most of our patients with IEI who acquired the SARS-CoV-2 infection developed a well-tolerated infection and survived, as have more than 80% of worldwide reported patients to date. An impaired immune or inflammatory response may be a predisposing factor for some and a protective factor for others. A systematic review of the literature could help identify those patients at risk of severe disease and complications. Healthcare-associated infections should be aggressively prevented.
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COVID-19/diagnóstico , Enfermedades de Inmunodeficiencia Primaria/diagnóstico , SARS-CoV-2/fisiología , Adolescente , Adulto , COVID-19/epidemiología , COVID-19/mortalidad , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , México/epidemiología , Persona de Mediana Edad , Enfermedades de Inmunodeficiencia Primaria/epidemiología , Enfermedades de Inmunodeficiencia Primaria/mortalidad , Estudios Retrospectivos , Riesgo , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Adulto JovenRESUMEN
Mucocutaneous eruptions associated with respiratory pathogens, specifically Mycoplasma pneumoniae (MP), has recently been described as a MIRM (MP-induced rash and mucositis). The term reactive infectious mucocutaneous eruption (RIME) has been proposed, since non-MP pathogens may also cause a similar rash and mucositis. We report two cases with clinical manifestations suggestive of MIRM/RIME, both with documented adenovirus infection.
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Exantema , Mucositis , Neumonía por Mycoplasma , Exantema/diagnóstico , Exantema/etiología , Humanos , Mucositis/diagnóstico , Mycoplasma pneumoniaeRESUMEN
BACKGROUND: Kawasaki disease (KD) is an acute systemic vasculitis that predominantly affects patients younger than 5 years. In the absence of an available, affordable diagnostic test, detailed clinical history and physical examination are still fundamental to make a diagnosis. METHODS: We present five representative cases with KD-like presentations: systemic onset juvenile idiopathic arthritis, mycoplasma-induced rash and mucositis, staphylococcal scalded skin syndrome, BCGosis, and the recently described multisystemic inflammatory syndrome in children (MIS-C) associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) virus. RESULTS: Rash, fever, and laboratory markers of inflammation can be present in several childhood diseases that may mimic KD. CONCLUSION: The term 'Kawasaki syndrome' instead of 'Kawasaki disease' may be more appropriate. Physicians should consider an alternative diagnosis that may mimic KD, particularly considering MIS-C during the present pandemic, as an aggressive diagnostic and therapeutic approach is needed.
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COVID-19 , Síndrome Mucocutáneo Linfonodular , Niño , Humanos , Síndrome Mucocutáneo Linfonodular/diagnóstico , ARN Viral , SARS-CoV-2 , Síndrome de Respuesta Inflamatoria SistémicaRESUMEN
Severe combined immunodeficiency (SCID) represents the most lethal form of primary immunodeficiency, with mortality rates of greater than 90% within the first year of life without treatment. Hematopoietic stem cell transplantation and gene therapy are the only curative treatments available, and the best-known prognostic factors for success are age at diagnosis, age at hematopoietic stem cell transplantation, and the comorbidities that develop in between. There are no evidence-based guidelines for standardized clinical care for patients with SCID during the time between diagnosis and definitive treatment, and we aim to generate a consensus management strategy on the supportive care of patients with SCID. First, we gathered available information about SCID diagnostic and therapeutic guidelines, then we developed a document including diagnostic and therapeutic interventions, and finally we submitted the interventions for expert consensus through a modified Delphi technique. Interventions are grouped in 10 topic domains, including 123 "agreed" and 38 "nonagreed" statements. This document intends to standardize supportive clinical care of patients with SCID from diagnosis to definitive treatment, reduce disease burden, and ultimately improve prognosis, particularly in countries where newborn screening for SCID is not universally available and delayed diagnosis is the rule. Our work intends to provide a tool not only for immunologists but also for primary care physicians and other specialists involved in the care of patients with SCID.
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Guías de Práctica Clínica como Asunto , Inmunodeficiencia Combinada Grave/diagnóstico , Inmunodeficiencia Combinada Grave/terapia , Consenso , Humanos , América LatinaRESUMEN
Kawasaki disease (KD) has features that appear supporting an infectious cause with a secondary deranged inflammatory/autoimmune response. The association of KD in adults with human immunodeficiency virus infection and the presence of KD in patients with immunodeficiency disorders support the infectious theory. We present four KD patients associated with immunodeficiencies: one with X-linked agammaglobulinemia, one with HIV infection, and two with leukemia; one of these patients also had Down syndrome. We did a literature search to find out all reported cases of immunodeficiency with KD in children. In immunodeficiency disorders, the inability of the immune system to eradicate the pathogens coupled to an exaggerated inflammatory response, especially in chronic granulomatous disease, may lead to the development of KD. The study of patients with immunodeficiencies complicated with KD may shed light into the etiopathogenesis of the disease.
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Agammaglobulinemia/inmunología , Enfermedades Genéticas Ligadas al Cromosoma X/inmunología , Infecciones por VIH/inmunología , Huésped Inmunocomprometido , Leucemia/inmunología , Síndrome Mucocutáneo Linfonodular/inmunología , Corticoesteroides/uso terapéutico , Agammaglobulinemia/complicaciones , Agammaglobulinemia/diagnóstico , Agammaglobulinemia/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Preescolar , Síndrome de Down/complicaciones , Enfermedades Genéticas Ligadas al Cromosoma X/complicaciones , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/tratamiento farmacológico , Infecciones por VIH/complicaciones , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Lactante , Leucemia/complicaciones , Leucemia/diagnóstico , Leucemia/tratamiento farmacológico , Masculino , Síndrome Mucocutáneo Linfonodular/diagnóstico , Síndrome Mucocutáneo Linfonodular/tratamiento farmacológico , Factores de Riesgo , Resultado del TratamientoAsunto(s)
Enfermedades Autoinmunes , Exantema , Niño , Humanos , Exantema/diagnóstico , Exantema/etiologíaRESUMEN
BACKGROUND: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by inborn errors of the phagocyte nicotinamide adenine dinucleotide phosphate oxidase complex. From the first year of life onward, most affected patients display multiple, severe, and recurrent infections caused by bacteria and fungi. Mycobacterial infections have also been reported in some patients. OBJECTIVE: Our objective was to assess the effect of mycobacterial disease in patients with CGD. METHODS: We analyzed retrospectively the clinical features of mycobacterial disease in 71 patients with CGD. Tuberculosis and BCG disease were diagnosed on the basis of microbiological, pathological, and/or clinical criteria. RESULTS: Thirty-one (44%) patients had tuberculosis, and 53 (75%) presented with adverse effects of BCG vaccination; 13 (18%) had both tuberculosis and BCG infections. None of these patients displayed clinical disease caused by environmental mycobacteria, Mycobacterium leprae, or Mycobacterium ulcerans. Most patients (76%) also had other pyogenic and fungal infections, but 24% presented solely with mycobacterial disease. Most patients presented a single localized episode of mycobacterial disease (37%), but recurrence (18%), disseminated disease (27%), and even death (18%) were also observed. One common feature in these patients was an early age at presentation for BCG disease. Mycobacterial disease was the first clinical manifestation of CGD in 60% of these patients. CONCLUSION: Mycobacterial disease is relatively common in patients with CGD living in countries in which tuberculosis is endemic, BCG vaccine is mandatory, or both. Adverse reactions to BCG and severe forms of tuberculosis should lead to a suspicion of CGD. BCG vaccine is contraindicated in patients with CGD.