Inmunodeficiencia variable común y déficit selectivo de inmunoglobulina A en pacientes celiacos / Common variable immunodeficiency and selective IgA deficiency in celiac disease patients

La enfermedad celíaca (EC) es una de las enfermedades autoinmunes gastrointestinales que con más frecuencia se asocia a inmunodeficiencias primarias (IDP) como el déficit selectivo de IgA y la inmunodeficiencia variable común (IDVC). A propósito del vínculo entre IDP y celiaquía, se presentan dos pacientes femeninas diagnosticadas como celíacas con formas de presentación diferentes y compromiso inmunonutricional variable. Las bajas concentraciones de inmunoglobulina G (IgG) y la ausencia de IgA fueron los principales hallazgos humorales registrados, no se evidenció compromiso de células B y T, de acuerdo a la cuantificación de subpoblaciones linfoides por citometria de flujo. La intervención nutricional e inmunológica permitió la remisión de las manifestaciones clínicas y la evolución satisfactoria en ambos casos(AU)

Celiac disease (CD) is an autoimmune gastrointestinal disease very often associated with Primary Immunodeficiencies (PID) as selective IgA deficiency and variable immunodeficiency common. About the link between celiac disease IDP, two female patients diagnosed as celiac patients with different forms of presentation and varying commitment immunonutritional presented. Low levels of immunoglobulin G (IgG) and absence of immunoglobulin A (IgA) were the main humoral findings recorded, no commitment of B and T cells, according to the quantification of lymphoid subpopulations by flow cytometry. Nutritional and immunological intervention allowed remission of clinical manifestations and satisfactory outcome in both cases(AU)

Disseminated bronchiectasis in an adult with common variable immunodeficiency / Bronquiectasias diseminada en un adulto con inmunodeficiencia común variable

Primary immunodeficiencies (PID) are traditionally considered childhood diseases; however, adults account for 35% of all patients with PID. Antibody deficiencies, especially Common Variable Immunodeficiency (CVID), which have their peak incidence in adulthood, require a high suspicion index. Even though the estimated frequency of CVID is not high (1:25,000), high rates of under diagnosis and under reporting are very likely. The delay in diagnosis increases the morbidity and mortality; therefore, adult physicians should be able to suspect, identify and initiate management of individuals with PID. Here we report the case of a 37 year-old man presenting to the emergency room with dyspnea, fever and cough; he developed respiratory failure requiring mechanical ventilation. He complained of recurring pneumonia associated with widespread bronchiectasis since he was 18 years old. Serum immunoglobulins quantification showed severe hypogammaglobulinemia (total IgG <140 mg/dL; total IgA, 2.9 mg/dL; and total IgM <5 mg/dL). Treatment with Human Intravenous Immunoglobulin (IVIG) 10% was started, and with antibiotic treatment for severe pneumonia (during 14 days) was also prescribed. His clinical evolution has been favorable after one year follow-up. Common Variable Immunodeficiency (CVID) diagnosis was made.

Las inmunodeficiencias primarias (IDP) son patologías que tradicionalmente se consideran de la niñez sin embargo los adultos representan el 35% del total de pacientes con IDP. Las deficiencias de anticuerpos, en especial la Inmunodeficiencia Común Variable (IDCV) tienen su pico de incidencia en la edad adulta, requiere un alto índice de sospecha y si bien su frecuencia estimada no es alta (1:25,000), es muy posible que el subregistro y subdiagnóstico si lo sean. El retraso en el diagnóstico aumenta la morbi-mortalidad razón por la cual los médicos de adultos deben estar en capacidad de sospechar, identificar e iniciar el manejo de las personas con IPD. Presentamos el caso de un hombre de 37 años de edad atendido en la sala de urgencias con disnea, fiebre y tos, desarrolla falla respiratoria requiriendo ventilación mecánica. Refería neumonías a repetición desde los 18 años de edad asociadas con bronquiectasias generalizadas. La cuantificación de inmunoglobulinas séricas evidenció hipogammaglobulinemia severa (IgG total <140 mg/dL, IgA total 2.9 mg/dL, IgM total <5 mg/dL), se inició inmunoglobulina humana endovenosa (IGIV) al 10%, y recibió tratamiento antibiótico por 14 dias para neumonía severa, su evolución clínica ha sido favorable hasta ahora (un año de seguimiento), se estableció el diagnostico de Inmunodeficiencia Común Variable (IDCV).

Inmunodeficiencia común variable: caracterización clínica e inmunológica de pacientes e identificación de subgrupos homogéneos con base en la tipificación de subpoblaciones de linfocitos B / Common variable immunodeficiency: Clinical and immunological characterization of patients and homogeneous subgroup definition by means of B lymphocyte subpopulation typing

Introducción. La inmunodeficiencia común variable es un síndrome heterogéneo caracterizado por infecciones recurrentes, hipogammaglobulinemia y producción deficiente de anticuerpos específicos. Las anormalidades en subpoblaciones de linfocitos en sangre periférica, particularmente de linfocitos B, permiten la clasificación de los pacientes en grupos homogéneos. Objetivo. Caracterizar clínica e inmunológicamente los linfocitos B y tipificar sus subpoblaciones en doce pacientes colombianos con inmunodeficiencia común variable, para clasificarlos en grupos homogéneos. Materiales y métodos. Se revisaron las historias clínicas de los pacientes y se evaluaron las inmunoglobulinas séricas, la proliferación de linfocitos y la hipersensibilidad retardada, así como las subpoblaciones de linfocitos y de linfocitos B mediante citometría de flujo. Resultados. Todos los pacientes presentaron infecciones respiratorias o gastrointestinales recurrentes y, algunos, infecciones en otros sistemas. Además, todos presentaban disminución de la IgG, en tanto que la IgA y la IgM fueron bajas en nueve y diez pacientes, respectivamente. En todos hubo disminución de la proliferación de linfocitos inducida por mitógenos, pero fue normal frente a antígenos específicos. La tipificación de subpoblaciones reveló valores elevados de linfocitos T en tres pacientes; siete presentaron disminución en la relación CD4+/CD8+ y, cuatro, linfocitos NK bajos. El conteo de linfocitos B fue normal en once pacientes, ocho de los cuales presentaron linfocitos B de memoria bajos, en tanto que cuatro presentaron aumento de linfocitos B de transición o de linfocitos B CD21 low . Conclusión. La tipificación de subpoblaciones de linfocitos solo permitió asignar a 11 de los pacientes a grupos homogéneos según los esquemas de clasificación internacionales, lo que indica la necesidad de agregar más criterios hasta lograr una clasificación ideal. Este estudio permitirá establecer mejores seguimientos médicos para pacientes con inmunodeficiencia común variable en grupos con alto riesgo de desarrollar complicaciones clínicas.

Introduction: Common variable immunodeficiency is a heterogeneous syndrome characterized by recurrent infections, hypogammaglobulinemia and defective production of specific antibodies. Abnormalities in peripheral blood lymphocyte subpopulations, in particular of B lymphocytes, allow the classification of patients into homogeneous groups. Objective: To perform a clinical and immunological characterization and to evaluate lymphocyte subpopulations of twelve Colombian patients with common variable immunodeficiency in order to define homogeneous groups. Materials and methods: We reviewed medical records and evaluated serum immunoglobulins (Ig), lymphoproliferation, delayed hypersensitivity and used flow cytometry to quantify peripheral blood total lymphocyte and B cell populations. Results: All patients had recurrent respiratory and/or gastrointestinal infections, while some also had infections affecting other systems. All patients had abnormally low serum IgG levels, while IgA and IgM levels were reduced in nine and ten patients, respectively. Lymphoproliferation to mitogen was lower in patients than in healthy controls but lymphoproliferation to specific antigen was normal in all. Flow cytometry revealed high numbers of T cells in three patients, while seven had a low CD4+/CD8+ ratio and four had reduced NK cells . Eleven patients had normal B cell counts, and eight of them also showed decreased memory B lymphocytes, and four had increased transitional or CD21 low B lymphocytes. Conclusion: Lymphocyte typing allowed assigning all but one patient to homogeneous groups according to international classification schemes, indicating the necessity of including more criteria until an ideal classification is achieved. This study will lead to a better medical monitoring of common variable immunodeficiency patients in groups at high risk of developing clinical complications.

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.

Linfadenite granulomatosa em paciente renal crônica em hemodiálise e hipogamaglobulinemias: relato de caso / Granulomatous lymphadenitis in a patient on chronic hemodialysis and hypogammaglobulinemia: a case report

Imunodeficiência comum variável (IDCV) é a síndrome de imunodeficiência primária mais frequente em adultos1. É uma desordem imunológica caracterizada por defeito na síntese de anticorpos, infecções recorrentes, mais notavelmente no trato respiratório, fenômenos autoimunes e câncer2. Relata-se caso de paciente de 61 anos com história prévia de hepatite B e suspeita de tuberculose ganglionar e pleural, admitida com quadro de emagrecimento, febre, astenia, ascite e oligúria acentuada, iniciando tratamento dialítico com diagnóstico de doença renal crônica terminal secundária à nefroesclerose hipertensiva. Apresentava cirrose hepática, anemia grave não responsiva ao tratamento com eritropoetina, ascite refratária e desnutrição. A contagem de leucócitos encontrava-se dentro dos valores de referência. Ao longo do tratamento dialítico, apresentou linfadenomegalia cervical, supraclavicular e axilar direita, com linfonodos móveis, fibroelásticos, doloridos e alguns supurativos. Biopsia excisional de lesão cutânea cervical demonstrou dermoepidermite, fistulizada com granuloma e necrose de etiologia indeterminada, com PPD não reator (< 1 mm) e pesquisa de fungos e BAAR negativa. Ainda apresentou infecções recorrentes de cateter duplo lúmen para hemodiálise e artrite séptica, tendo seu quadro clínico agravado e evoluindo para óbito por choque séptico. Durante a maior parte da evolução do quadro, o diagnóstico mais provável assumido foi de tuberculose. A imunodeficiência comum variável foi diagnóstico questionado apenas após a morte da paciente. É muito importante que se pense em diversas afecções frente a quadros clínicos com tantos sinais e de etiologia indeterminada, como o da paciente, para que não se incorra num tratamento ineficiente e errôneo.

Common Variable Immunodeficiency Syndrome (CVIS) is the most frequent syndrome of primary immunodeficiency. It is an immunologic disorder characterized by a defect in antibodies synthesis, recurrent infections, especially in the respiratory tract, auto- immune manifestations and cancer. We describe a case of a 61-year-old patient with a previous history of hepatitis B and a suspicion of pleural and lymph node tuberculosis who was admitted showing weight loss, fever, weakness, ascites and oliguria. Dialytic treatment has been initiated and chronic terminal renal disease due to hypertensive nephrosclerosis was diagnosed. She had hepatic cirrhosis, severe anemia non-responsive to erythropoietin treatment, refractory ascites and and she was malnourished. The white blood cell count was normal. During the dialytic treatment, the patient presented cervical, supraclavicular and right axilla lymphadenosis. The lymph nodes were mobile, fibroelastic, painpful and some of them suppurative. Biopsy of the cutaneal cervical lesion showed dermoepidermitis fistulized with granuloma and necrosis of undetermined etiology, nonreactor PPD and negative findings for fungus as well as for alcohol-acid resistant bacilli. She also had recurrent infections of the hemodialysis central catheter and septic arthritis. Her clinical status deteriorated and she died from septic shock. For a long time during the treatment, it was hypothesized the patient had been affected by tuberculosis. The CVIS was inquired as a possible diagnostic just after the patientïs death. Facing uncommon diseases as well as unusual clinical presentations still remain a challenge for the clinician and should always be considered in unexpected clinical evolution in patients on chronic renal replacement therapy.

Gastrointestinal and hepatic manifesatations of primary immune deficiency diseases

Primary immune deficiency disease [PIDs] are a heterogeneous group of inherited diseases characterized by variable genetic immune defects, conferring susceptibility to recurrent infections. They have a vast array of manifestations some of which involve the gastrointestinal and hepatobiliary systems. These complications can be the consequence of five different factors, namely, infection, autoimmune process, unregulated inflammation, malignancies and complications of therapeutic intervention. They may precede the PID diagnosis and, once developed, they pose high risk of morbidity. Untrained clinicians may treat these manifestations only at the level of their presentation, leaving the PIDs dangerously undiagnosed. In fact, early diagnosis of PIDs and accompanied gastrointestinal and hepatic complications clearly require appropriate treatment, and in- turn lead to an improved quality of life for the patient. To improve the awareness of gastoenterologists and related health care providers about these diseases, we have reviewed herein the complications of different PIDs focusing on gastrointestinal and hepatic manifestation

Registro argentino de inmunodeficiencias primarias. Segundo informe / The Argentinean Registry of primary inmunodeficiencies. Second report

Las inmunodeficiencias primarias son un grupo de enfermedades poco frecuentes, habitualmente diagnosticada sen la edad pediátrica, que comprometen el desarrollo y las funciones del sistema inmunitario.En 1994 se constituyó el Grupo de Inmunología Pediátricade la Sociedad Argentina de Pediatría que sepropuso, entre otros objetivos, mantener un Registrode las inmunodeficiencias primarias, cuyo primer informe se publicó en 2001: comprendía los 652 casos diagnosticados en Argentina entre 1984 y 1999.Este segundo informe analiza la evolución del Registro,la progresión experimentada en las áreas mayoresde diagnóstico y el aporte de la biología molecular,que ha permitido identificar numerosos genes implicado sen la etiología de las inmunodeficiencias primarias.El registro incluye 1.319 pacientes a diciembrede 2005; 918 (69,5%) deficiencias humorales, 192(14,5%) asociadas a otros defectos, 80 (6%) asociadasa defectos del fagocito, 58 (4,3%) defectos del fagocito,52 (3,94%) defectos celulares y 19 (1,4%) defectos del complemento. Las patologías más diagnosticadas fueron la deficiencia de IgA (42%), la inmunodeficiencia común variable (10%) y la agammaglobulinemialigada al sexo (8%). El síndrome de DiGeorgey la ataxia-telangiectasia (5% c/u) fueron los trastornosmás frecuentes. Se confirmaron diagnósticos porbiología molecular en 184 pacientes de todo el país entre 1995 y 2005.El número de casos anuales se incrementó en general,sin embargo, documentamos subregistro osubdiagnóstico en la mayor parte de las provinciascon excepción de Buenos Aires y Santa Fe. Esto muestra la necesidad de elaborar un proyecto más eficiente de difusión y educación para su detección temprana en el futuro.Con el análisis de los datos volcados al Registro, del país, reiterando el interés que representa mantener un registro actualizado de las inmunodeficiencias primarias, a través de su participación mediante la comunicación de nuevos casos.

Polarized light microscopy of hair shafts aids in the differential diagnosis of Chédiak-Higashi and Griscelli-Prunieras syndromes

OBJETIVO: Estudar e comparar o aspecto dos cabelos de portadores das síndromes de Chédiak-Higashi e Griscelli-Prunieras, tanto na microscopia óptica convencional quanto com luz polarizada. MÉTODO: Cabelos de dois doentes portadores da síndrome de Chédiak-Higashi e de dois portadores da síndrome de Griscelli-Prunieras foram obtidos e estudados tanto à microscopia convencional quanto com luz polarizada. RESULTADOS: Na microscopia óptica convencional, os cabelos dos doentes portadores da síndrome de Chédiak-Higashi mostraram grânulos de melanina regulares, com distribuição homogênea e de maior tamanho em comparação aos presentes no cabelo normal. À microscopia de luz polarizada notou-se aspecto brilhante e refringência policromática. Diferentemente, os cabelos dos doentes portadores da síndrome de Griscelli-Prunieras apresentaram à microscopia convencional, grânulos de melanina irregulares e maiores do que os presentes no cabelo normal e os presentes nos cabelos dos doentes portadores da síndrome de Chédiak-Higashi, preferencialmente próximos à medula das hastes pilosas. À microscopia de luz polarizada apresentaram aspecto monotonamente esbranquiçado. CONCLUSÃO: O exame dos cabelos pela microscopia convencional nas síndromes de Chédiak-Higashi e Griscelli-Prunieras revela diferenças sutis no reconhecimento dessas doenças. No presente trabalho apresentamos evidência de que o exame das hastes pilosas com microscopia de luz polarizada - não descrito previamente - contribui na diferenciação de ambas doenças sugerindo que esse seja um método diagnóstico útil na distinção entre as síndromes de Chédiak-Higashi e Griscelli Prunieras, especialmente nos casos em que estudos moleculares mais sofisticados não estejam disponíveis.

Griscelli syndrome - a case report.

Griscelli syndrome is a rare autosomal recessive disorder characterized by partial albinism with variable immunodeficiency. Silvery gray hair with large, clumped melanosomes on microscopy of hair shafts are diagnostic. The commonest complication leading to mortality includes lymphohistiocytic proliferation in various organs, including the brain. We present a child with classic clinical features and confirmatory findings of clumped melanosomes on microscopy of hair shaft.

Inmunodeficiencia idiopática de comienzo tardío. Una rareza clínica / Idiopathic late-onset immunodeficiency. A rare clinical entity

Se presenta un paciente de 66 años con un síndrome de inmunodeficiencia común variable (IDCV) con frecuentes uinfecciones respiratorias bajas y favoraable evolución con inmunoglobulinas endovenosas. Los posibles mecanismos fisiopatológicos en el desarrollo de este síndrome son analizados con el aporte de la literatura. Se remarca la infrecuente presentación de la IDCV en un paciente de edad avanzada

Hipogamaglobulinemia congénita como sustrato favorecedor de infecciones respiratorias recurrentes y bronquiectasias / Congenital hypogammaglobulinemia as a predisposing substrate of recurrent respiratory infections and bronchiectasis

Se describe el caso de un paciente con una historia de infecciones recurrentes del tracto respiratorio alto y bajo desde la niñez. Se encontró como sustrato favorecedor una hipogamaglobulinemia congénita, probablemente del tipo inmunodeficiencia variable común. Esta enfermedad condiciona una predisposición de la pared del árbol bronquial a la infección o a la colonización, lo que a largo plazo determina las alteraciones estructurales permanentes (bronquiectasias) como se dio en este caso. El tratamiento se basa en medidas higiénico dietéticas, administración de gamaglobulinas, inmunización y antibióticos en los cuadros infecciosos. La evolución dependerá de la respuesta y adhesión al tratamiento, así como de la aparición de complicaciones derivadas de las bronquiectasias y de la hipogamaglobulinemia en sí misma

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

Common variable immunodeficiency (CVID) in northern India.

Fourteen patients with common variable immunodeficiency (CVID) were studied. The common clinical manifestations were recurrent sore throat, sinusitis, respiratory infections, diarrhea, and malnutrition. All had low IgG, with normal cell-mediated immunity. Treatment with immunoglobulin and/or plasma was effective in most of them. There were no severe adverse events with the therapy.

Common variable immunodeficiency: a clinical and laboratory evaluation of l5 cases

The clinical and laboratory data for 15 patients with common variable immunodeficiency (CVI) (5 females and 10 males aged 3 years and 6 months to 40 years at first examination) were evaluated. The age of onset of infectious signs and symptoms ranged from 6 months to 35 years. Recurrent pulmonary infections predominated (86.6%), followed by chronic diarrhea (46.6%). Aproximately 60% of the patients with pulmonary complaints presented chronic sequelae (bronchiectasis). Two developed a polymyositis-like picture. No neoplasms were observed. All patients presented immunoglobulin levels below 300mg/dl and absence of globulin levels below 300mg/dl and absence of antibody responses to poliovirus and to hemagglutinin. Two patients were negative when tested for autoimmunity. Cell immunity tested by the limphoproliferative response in the presence of phytohemagglutinin was normal in 11 patients and depressed in 4. A decrease in the helper T population and inversion of the OKT4/8 ratio occured in 13. Cimetidine treatment (1200mg/day) applied to 5 patients for 4 weeks did not produce any clinical or laboratory improvement. Gamma globulin is the treatment of choice for these patients