Neuroendocrine tumor in a child with common variable immunodeficiency / Tumor neuroendócrino em criança com imunodeficiência comum variável

ABSTRACT Objective: To report a case of a child with primary immunodeficiency who at eight years developed digestive symptoms, culminating with the diagnosis of a neuroendocrine tumor at ten years of age. Case description: One-year-old boy began to present recurrent pneumonias in different pulmonary lobes. At four years of age, an immunological investigation showed a decrease in IgG and IgA serum levels. After the exclusion of other causes of hypogammaglobinemia, he was diagnosed with a Common Variable Immunodeficiency and started to receive monthly replacement of human immunoglobulin. The patient evolved well, but at 8 years of age began with epigastrium pain and, at 10 years, chronic persistent diarrhea and weight loss. After investigation, a neuroendocrine tumor was diagnosed, which had a rapid progressive evolution to death. Comments: Medical literature has highlighted the presence of gastric tumors in adults with Common Variable Immunodeficiency, emphasizing the importance of early diagnosis and the investigation of digestive neoplasms. Up to now there is no description of neuroendocrine tumor in pediatric patients with Common Variable Immunodeficiency. We believe that the hypothesis of digestive neoplasm is important in children with Common Variable Immunodeficiency and with clinical manifestations similar to the case described here in the attempt to improve the prognosis for pediatric patients.

RESUMO Objetivo: Relatar um caso de criança portadora de imunodeficiência primária que, aos oito anos, desenvolveu sintomas digestivos, culminando com o diagnóstico de tumor neuroendócrino aos dez anos de idade. Descrição do caso: Menino, com um ano de idade, começou a apresentar pneumonias de repetição em diferentes lobos pulmonares. Aos quatro anos, a investigação imunológica mostrou diminuição dos níveis séricos de IgG e IgA. Após exclusão de outras causas de hipogamaglobulinemia, teve diagnóstico de imunodeficiência comum variável, passando a receber reposição mensal de imunoglobulina humana. Evoluiu bem, porém, aos oito anos, começou com epigastralgia e, aos dez anos, diarreia crônica persistente e perda de peso. O quadro culminou com o diagnóstico de tumor neuroendócrino intestinal, de rápida progressão, com óbito do paciente. Comentários: A literatura tem chamado a atenção para tumores gástricos em adultos com imunodeficiência comum variável, alertando para a importância do diagnóstico precoce e da pesquisa de neoplasias digestivas. Até o momento, não há descrição de tumor neuroendócrino em pacientes pediátricos portadores de imunodeficiência comum variável. Acredita-se ser importante a hipótese de neoplasia digestiva diante de crianças com imunodeficiência comum variável e com manifestações clínicas semelhantes ao caso descrito, na tentativa de melhorar o prognóstico para pacientes pediátricos.

Successful treatment of enteropathy associated with common variable immunodeficiency

No abstract available.

Inmunodeficiencia común variable: Epidemiología y manifestaciones clínicas en 69 pacientes / Common variable immunodeficiency: Epidemiology and clinical manifestations in 69 patients

La inmunodeficiencia común variable (IDCV) se caracteriza por una alteración en la producción de anticuerpos y una mayor susceptibilidad a infecciones por bacterias extracelulares capsuladas, principalmente del tracto respiratorio. Analizamos las características clínicas de 69 pacientes, evaluados en un período de 10 años en tres centros de la ciudad de Buenos Aires. Al inicio del estudio se encontraban en seguimiento 14 pacientes y al finalizar 60; la mayoría fueron derivados por infecciones o hipogammaglobulinemia, y casi la mitad con diagnóstico establecido de inmunodeficiencia. Sesenta y cinco (94.2%) pacientes presentaron infecciones por gérmenes capsulados, cuatro (6.1%) sepsis y dos tuberculosis. La edad promedio de comienzo de los síntomas infecciosos fue de 18.1 años, la edad promedio al momento del diagnóstico fue de 29.6 años y el retraso diagnóstico de 11.9 años. En 41 (59.4%) pacientes se registró el antecedente de diarreas recurrentes o crónicas. En 22 (31.9%) se diagnosticaron 13 enfermedades autoinmunes, siendo las más frecuentes las hematológicas y el hipotiroidismo. Ocho pacientes tuvieron linfoproliferación policlonal histológica, cuatro (5.8%) como enfermedad granulomatosa de hígado, laringe y piel, y cuatro como neumonía intersticial linfoidea (NIL). Diecinueve (27.5%) pacientes presentaron esplenomegalia y 23/57 (40.3%) imágenes sugestivas de procesos granulomatosos o linfocíticos en la TAC de tórax (incluidos los 4 con NIL). Tres (4.3%) pacientes desarrollaron linfoma B, cuatro (5.8%) adenocarcinoma de estómago y uno cáncer de mama. El estudio tuvo una mediana de seguimiento de 54 meses, rango 1-353 y durante el período del mismo murieron cuatro pacientes (5.8%).

Common variable immunodeficiency (CVID) is characterized by an impaired antibody production and an increased susceptibility to recurrent infections of the respiratory tract, mainly by extracellular encapsulated bacteria. We analyzed the clinical characteristics of 69 patients evaluated over a period of 10 years at three centers in the city of Buenos Aires. At the onset of the study 14 patients were on follow up, and at its end the number of patients reached to 60. Most of them consulted for infection or hypogammaglobulinemia and nearly half had an established diagnosis of immunodeficiency. Sixty-five (94.2%) patients had infections by encapsulated bacteria, four (6.1%) sepsis and two tuberculosis. The average age of onset of infectious symptoms was 18.1 years; the average age at diagnosis was 29.6 years and the delay to diagnosis 11.9 years. Forty one (59.4%) patients reported a history of recurrent or chronic diarrhea. In 22 (31.9%) 13 autoimmune diseases were diagnosed, being the most frequent the hematological disorders and hypothyroidism. Eight patients had histological polyclonal lymphoproliferation, four (5.8%) with granulomatous disease affecting the liver, the larynx and/or the skin; and four as lymphoid interstitial pneumonitis (LIP). Nineteen (27.5%) patients had splenomegaly and 23/57 (40.3%) images suggestive of lymphocytic or granulomatous processes (including the 4 with LIP) in the chest CT. Three (4.3%) patients developed B cell lymphoma, four (5.8%) stomach adenocarcinoma and one breast cancer. The study had a median follow-up of 54 months, range 1-353 and four patients (5.8%) died during the follow up.

Inmunodeficiencia variable común: afectación digestiva de un trastorno sistémico / [Common variable immunodeficiency: digestive involvement of a systemic disease].

Common variable immunodeficiency is characterized by a primary deficiency in antibody production that is clinically manifested by respiratory recurrent infections and gastrointestinal diseases (infectious, inflammatory and neoplastic). Above 50

of the patients have diarrhea and 10

develop idiopathic malabsorption and weight loss. We present the case of a 34-year-old woman submitted to our service for chronic diarrhea, abdominal pain and bloating and history of recurrent respiratory infections since childhood. The laboratory assessment showed severe hypoproteinemia and confirmed low IgG, IgA and IgM levels. Upper gastrointestinal endoscopy and videocapsule endoscopy showed a nodular duodenum with multiple polypoid-like formations all through the small bowel. Histology confirmed chronic duodenitis and Giardia lamblia infection. With the diagnosis of common variable immunodeficiency, monthly intravenous gammaglobulin infusion was initiated and metronidazole was indicated for Giardia lamblia infection achieving excellent clinical and laboratory response.

Common variable immunodeficiency and isosporiasis: first report case / Imunodeficiência comum variável e isosporíase: primeiro relato de caso

We report a severe case of diarrhea in a 62-year-old female HIV-negative patient from whom Giardia lamblia and Isospora belli were isolated. Because unusual and opportunistic infections should be considered as criteria for further analysis of immunological status, laboratory investigations led to a diagnosis of common variable immunodeficiency (CVID). This is the first reported case of isosporiasis in a patient with CVID and illustrates the importance of being aware of a possible link, particularly in relation to primary immunodeficiency.

Trata-se de relato de caso de uma paciente de 62 anos, sexo feminino, HIV negativo apresentando um quadro grave de diarréia, sendo isolados Giardia lamblia e Isospora belli. Infecções incomuns e oportunistas devem ser consideradas como um sinal para alerta para que se analise o sistema imunológico. O diagnóstico de imunodeficiência de comum variável foi realizado após investigação. Este é o primeiro caso relatado de isosporíase em pacientes com imunodeficiência comum variável e mostra a importância de estar alerta tambem em relação a imunodeficiências primárias.

Membranous Nephropathy in a 13-Year-Old Boy with Common Variable Immunodeficiency

Various forms of hypogammaglobulinemia can occur in patients with autoimmune diseases and vice versa. We report a 13-yr-old boy with membranous nephropathy and common variable immunodeficiency. He presented with the nephrotic syndrome, pneumonia with bronchiectasis, and profound hypogammaglobulinemia. Renal biopsy showed diffusely thickened glomerular capillary walls with 'spikes' suggesting a membranous nephropathy. Secondary causes were ruled out by laboratory studies; however, heavy proteinuria persisted with steroid therapy. Cyclosporine and intravenous immunoglobulin were added, and the patient was discharged with decreased proteinuria. Hypogammaglobulinemia may have a deleterious impact on the immune dysregulation in some patients with membranous nephropathy.

Nocardiosis in a patient with common variable immunodeficiency.

We report a case of nocardiosis in a 42, years male with common variable immunodeficiency syndrome (CVID). He presented with arthritis, subcutaneous abscess and pleural effusion. Diagnosis of CVID was made during this presentation. Serum IgG, IgA and IgM levels were markedly decreased. Nocardia asteroides was cultured from pleural fluid. He was successfully treated with intravenous immunoglobulin and cotrimoxazole.

Rheumatologic manifestations in patients with selected primary immunodeficiencies evaluated at the University Hospital

OBJECTIVE: To characterize an IgA deficient and common variable immunodeficiency (CVI) group of patients in terms of the presence of rheumatologic manifestations. BACKGROUND: Although the molecular basis of some of the primary immunodeficiencies has been elucidated, it has not been possible to explain why in most cases these conditions are often associated with autoimmune manifestations, besides infections. The concomitant inability to fight infections adequately (immunodeficiency) and an inordinate reaction of the immune system to self components (autoimmunity) has been a perplexing situation. METHODS: The clinical and immunological profile of 71 patients fulfilling the diagnostic criteria of selective IgA deficiency (n=38) and common variable immunodeficiency (n=33) were evaluated for concurrent rheumatologic manifestations after a thorough medical history, physical examination and pertinent immunological parameters. RESULTS: The most common autoimmune conditions identified in patients with selective IgA deficiency were Crohn's disease and systemic lupus erythematosus (SLE); while immune thrombocytopenic purpura and Crohn's disease were the most common disorders associated to CVI. Anti-IgA antibodies were only found in 26.6(95C.I. 10.1-51.4) of patients with selective IgA deficiency but were present in all patients with that condition and SLE. Fifty per cent patients with CVI and ITP exhibited ANA positivity. CONCLUSIONS: The IgA-deficient group of patients in this study showed a higher prevalence of autoimmune conditions and greater positivity for ANA as compared to patients with CVI. In contrast to other reports with around 44positivity of anti-IgA antibodies in selective IgA patients these were only present in 263of patients with that disorder in this study. The high prevalence of antinuclear antibodies not associated with any clinical autoimmune condition in the IgA-deficient patients in this study will need to be further explored to ascertain why IgA-deficient patients may be at an increased risk of autoimmunity. Inflammatory bowel disease (Crohn's disease and ulcerative colitis) constituted the most common clinical autoimmune manifestations in both groups of patients studied. ITP was the commonest organ-specific autoimmune condition identified in the CVI group, as reported in previous publications. The limited number of patients studied does not allow a reliable estimate of the prevalence of SLE in the IgA-deficient population analyzed.

Association of Secondary Amyloidosis with Common Variable Immune Deficiency and Tuberculosis

This paper describes the first case of common variable immunodeficiency (CVID) and AA amyloidosis. A recently treated tuberculosis, and chronic inflammation induced by frequent respiratory tract infections, were thought to be responsible for the amyloidosis. No other reason for this condition could be detected. Although T cell dysfunction in some CVID patients has been reported, pulmonary tuberculosis is quite rare with this condition. Bacterial or viral agents or evidence in favour of intestinal tuberculosis, which would explain this patient's recurrent diarrhea, were not found. In this case, the response of the attacks of diarrhea to metranidazole and the histologic observation of extensive intestinal amyloid deposition, which is known to decrease intestinal motility, made us conclude that the diarrhea was associated with bacterial overgrowth. In this report, we discuss the association of CVID and tuberculosis to secondary amyloidosis and recurrent diarrhea.

Recurrent meningitis in association with common variable immune deficiency.

Recurrent meningitis in children is unusual and usually associated with a predisposing factor like immune-deficiency disorder or cranio-spinal defect. We report a case of recurrent meningitis in association with Common Variable Immune deficiency.

A case of recurrent pneumonias.

A description is given of the case of a young boy who presented with repeated episodes of pneumonias since childhood. In addition, he had episodes of intermittent diarrhoeas. His investigative work-up revealed a deficiency of serum immunoglobulins, that is, hypogammaglobulinaemia. The profile was suggestive of common variable immunodeficiency. Because of the relative rarity of this disease, it is often missed leading to significant morbidity. Treatment consists of immunoglobulin replacement therapy and management of recurrent infections with appropriate drugs.

Effect of IVIG on the hair regrowth in a common variable immune deficiency patient with alopecia universalis.

Common variable immune deficiency (CVID) is associated with a variety of autoimmune diseases. Alopecia universalis (AU), believed to have an autoimmune basis, has been found in 1.6% of patients with CVID. Intravenous immunoglobulin (IVIG) therapy is used in various immunodeficiency disorders including CVID, and benefit has been shown in the therapy of autoimmune diseases. We report a patient with CVID and AU treated with IVIG who experienced significant hair regrowth. An 8-year-old girl with CVID and AU was treated with IVIG 400 mg/kg every 4 weeks. Since her second dose of IVIG, regrowth of eyelashes, eyebrows, body and scalp hair was observed in this patient. At present, about 1 year treat-meant of IVIG, significant hair regrowth is noted with 5-6 cm of scalp hair. We believe that IVIG may be beneficial in the treatment of AU, at least in patients with CVID.

Manifestaciones articulares en inmunodeficiencias primarias / Articular manifestations in primary immunodeficiencies

Las inmunodeficiencias primarias constituyen entidades clínicas que, aun cuando se presentan esporádicamente en la práctica diaria, suelen acompañarse de gran morbilidad y mortalidad si no se efectúan un diagnóstico y un tratamiento oportunos. Algunas de estas inmunodeficiencias pueden iniciar su sintomatología con manifestaciones articulares que semejan un proceso reumatológico. De las numerosas inmunodeficiencias primarias descritas hasta la fecha, la hipogamaglobulinemia común variable es la entidad que con más frecuencia se asocia con estas manifestaciones. La enfermedad se caracteriza por una deficiencia severa en la producción de anticuerpos, lo que conduce a infecciones bacterianas recurrentes. En tanto, ciertas condiciones predisponentes para algunas enfermedades reumatológicas, tales como Lupus eritematoso Diseminado, Vasculitis, Nefropatía y otras. El conocimiento de estas condiciones inmunológicas reviste una gran importancia en la patogenia y manejo de las enfermedades reumatológicas

Hipogamaglobulinemia común, variable del adulto: a propósito de un caso clínico / Common variable hypogammaglobulinemia of the adult: apropos of a case

La Hipogamaglobulinemia común variable del adulto es una afección poco frecuente. Sus manifestaciones clínicas son similares a los de la hipogamaglobulinemia congénita, destacándose la presencia de bronquiectasias adquiridas por infecciones respiratorias reiteradas. El hallazgo de otras anomalías inmunitarias, en particular, alteraciones cuanti y cualitativas de los linfocitos T, ponen en la pista del diagnóstico de esta afección. A propósito de este caso, se repasan las causas más frecuentes de bronquiectasias en el adulto, su metodología de estudio y su relación con alteraciones del sistema inmune. Se señala además el hallazgo de mutaciones vinculadas con la mucovisidosis como una interrogante en la interpretación patogénica de todo el cuadro

Bronquiectasia como forma de presentación de inmunodeficiencia común variable / Bronchiectasis as a common variable immunodeficiency

Se presentan 2 pacientes con bronquiectasia en los cuales se demostró inmunodefiencia común variable (IDCV). Ambos pacientes fueron tratados con gammaglobulina con buena respuesta. Consideramos que el estudio de pacientes con bronquiectasias debe investigarse la IDCV