ABSTRACT
WHIM syndrome is a primary autosomal dominant immuno deficiency due to CXCR4 mutations characterized by mucocutaneous warts, hypogammaglobulinemia, recurrent bacterial infections and myelokathesis. Treatment consists in prophylactic antibiotics, immunoglobulin replacement and granulocyte or granulocyte/monocyte colony stimulating factors. We present the case of a 21 year old woman who showed leukopenia at 10 months of age and one year later multiple infections with hypogammaglobulinemia requiring intravenous immunoglobulin. During follow up she developed chronic neutropenia. A bone marrow aspiration showed increased myeloid series with predominance of immature elements. On the basis of infections, low levels of IgG, IgA, IgM and lymphopenia with absent memory B cells, a diagnosis of common variable immunodeficiency was made. She started intravenous immunoglobulin replacement and prophylactic antibiotics. At age 20, small warts in hands that progressed to forearms, knees, abdomen and face were recorded. CXCR4 gene sequencing was done detecting a heterozygous p.Arg334STOP mutation, confirming WHIM syndrome. This disease is infrequent and difficult to diagnose.
Subject(s)
Immunologic Deficiency Syndromes/diagnosis , Immunologic Deficiency Syndromes/genetics , Mutation/genetics , Receptors, CXCR4/genetics , Warts/diagnosis , Warts/genetics , Adult , Delayed Diagnosis , Female , Humans , Primary Immunodeficiency Diseases , Young AdultABSTRACT
X-linked agammaglobulinemia (XLA) is characterized by absent or severely reduced B cells, low or undetectable immunoglobulin levels and clinically by extracellular bacterial infections which mainly compromise the respiratory tract as well as recurrent diarrheas. The mainstay of treatment is gammaglobulin replacement therapy, which allows most patients to reach adulthood with high quality of life. We analyzed the clinical features of 14 patients over 18 years of age with XLA diagnosis that received treatment in our unit from the year 2003, the date the first patient was derived, until 2015. The average age at which patients were referred was 20.4 years old; age at the last consult was 25.5. The average follow-up time was 59.8 months. Previously to being diagnosed all patients had suffered infections, most frequently respiratory. After diagnosis all were started on intravenous gammaglobulin replacement treatment and in spite of infections being reduced in severity and frequency, there were cases of severe disease with long term sequelae. At the beginning of our follow-up 35.7% presented impaired respiratory function with only one case being severe. In no cases during this period did the respiratory function worsen, nor were there severe clinical complications. Three patients were switched to subcutaneous immunoglobulin treatment with good tolerance. The number of XLA cases is increasing, as most reach the second decade of life without serious complications and remain free of severe infectious disease and further impairment of their respiratory functions with the treatment.
Subject(s)
Agammaglobulinemia/complications , Agammaglobulinemia/drug therapy , Disease Progression , Genetic Diseases, X-Linked/complications , Genetic Diseases, X-Linked/drug therapy , Immunoglobulins, Intravenous/administration & dosage , gamma-Globulins/administration & dosage , Administration, Cutaneous , Administration, Intravenous , Adult , Follow-Up Studies , Humans , Male , Quality of Life , Respiratory Tract Infections/etiology , Retrospective Studies , Young AdultABSTRACT
El síndrome WHIM es una inmunodeficiencia primaria de herencia autosómica dominante, debida a mutaciones en el gen CXCR4, que se caracteriza por verrugas cutáneo-mucosas, hipogammaglobulinemia, infecciones bacterianas recurrentes y mielocatesis. El tratamiento se basa en el uso de antibióticos profilácticos, gammaglobulina en dosis sustitutiva y factores estimulantes de colonias de granulocitos o de granulocitos y macrófagos, en forma crónica. Presentamos el caso de una mujer de 21 años que comenzó a los 10 meses de edad con leucopenia y al siguiente año múltiples infecciones con hipogammaglobulinemia requiriendo gammaglobulina endovenosa durante los episodios. Evolucionó con neutropenia crónica. Una punción aspiración de médula ósea mostró la serie mieloide aumentada con ligero predominio de elementos inmaduros. El cuadro fue interpretado como inmunodeficiencia común variable debido a la asociación de múltiples cuadros infecciosos, niveles disminuidos de IgG, IgM e IgA y linfopenia con disminución de linfocitos B de memoria, por lo que comenzó tratamiento sustitutivo con gammaglobulina endovenosa más antibióticos profilácticos. A los 20 años se registraron pequeñas verrugas en manos que progresaron hacia antebrazos, abdomen, cara y rodillas. Se realizaron estudios moleculares para la búsqueda de mutaciones en el gen CXCR4 donde se detectó la mutación p.Arg334STOP en estado heterocigota confirmando el diagnóstico de síndrome WHIM, que es una inmunodeficiencia infrecuente y de difícil diagnóstico.
WHIM syndrome is a primary autosomal dominant immuno deficiency due to CXCR4 mutations characterized by mucocutaneous warts, hypogammaglobulinemia, recurrent bacterial infections and myelokathesis. Treatment consists in prophylactic antibiotics, immunoglobulin replacement and granulocyte or granulocyte/monocyte colony stimulating factors. We present the case of a 21 year old woman who showed leukopenia at 10 months of age and one year later multiple infections with hypogammaglobulinemia requiring intravenous immunoglobulin. During follow up she developed chronic neutropenia. A bone marrow aspiration showed increased myeloid series with predominance of immature elements. On the basis of infections, low levels of IgG, IgA, IgM and lymphopenia with absent memory B cells, a diagnosis of common variable immunodeficiency was made. She started intravenous immunoglobulin replacement and prophylactic antibiotics. At age 20, small warts in hands that progressed to forearms, knees, abdomen and face were recorded. CXCR4 gene sequencing was done detecting a heterozygous p.Arg334STOP mutation, confirming WHIM syndrome. This disease is infrequent and difficult to diagnose.
Subject(s)
Humans , Female , Adult , Young Adult , Warts/diagnosis , Warts/genetics , Receptors, CXCR4/genetics , Immunologic Deficiency Syndromes/diagnosis , Immunologic Deficiency Syndromes/genetics , Mutation/genetics , Delayed Diagnosis , Primary Immunodeficiency DiseasesABSTRACT
La agammaglobulinemia ligada al cromosoma X (XLA) se caracteriza por la ausencia o reducción significativa de linfocitos B, niveles bajos o indetectables de inmunoglobulinas y, clínicamente, por infecciones principalmente respiratorias por bacterias capsuladas extracelulares y diarrea recurrente. El tratamiento de reemplazo con gammaglobulina ha permitido a la mayor parte de los enfermos llegar a adultos con una buena calidad de vida. Analizamos las características clínicas de 14 pacientes mayores de 18 años con diagnóstico de XLA asistidos en nuestra Unidad desde 2003, fecha en que fue derivado el primer paciente, hasta 2015. La edad promedio en el momento de la derivación fue de 20.4 años, en el momento de la última consulta de 25.5. El tiempo promedio de seguimiento fue de 59.8 meses. Previo al diagnóstico todos habían presentado infecciones, las más frecuentes fueron las respiratorias. Posteriormente al diagnóstico todos iniciaron tratamiento de reemplazo con gammaglobulina endovenosa, y a pesar de que las infecciones disminuyeron en frecuencia y gravedad, en este período se presentaron enfermedades con secuelas graves. Al comenzar el seguimiento en nuestra Unidad, 35.7% presentaban deterioro de la función respiratoria, solo grave en un paciente. Durante el seguimiento ninguno presentó deterioro de la función respiratoria ni complicaciones clínicas importantes. Tres pasaron a gammaglobulina subcutánea con buena tolerancia. El número de adultos con XLA es cada vez mayor, la mayoría llegan a la segunda década de la vida sin complicaciones graves y bajo tratamiento se mantienen libres de enfermedades infecciosas graves y de progresión de sus secuelas pulmonares.
X-linked agammaglobulinemia (XLA) is characterized by absent or severely reduced B cells, low or undetectable immunoglobulin levels and clinically by extracellular bacterial infections which mainly compromise the respiratory tract as well as recurrent diarrheas. The mainstay of treatment is gammaglobulin replacement therapy, which allows most patients to reach adulthood with high quality of life. We analyzed the clinical features of 14 patients over 18 years of age with XLA diagnosis that received treatment in our unit from the year 2003, the date the first patient was derived, until 2015. The average age at which patients were referred was 20.4 years old; age at the last consult was 25.5. The average follow-up time was 59.8 months. Previously to being diagnosed all patients had suffered infections, most frequently respiratory. After diagnosis all were started on intravenous gammaglobulin replacement treatment and in spite of infections being reduced in severity and frequency, there were cases of severe disease with long term sequelae. At the beginning of our follow-up 35.7% presented impaired respiratory function with only one case being severe. In no cases during this period did the respiratory function worsen, nor were there severe clinical complications. Three patients were switched to subcutaneous immunoglobulin treatment with good tolerance. The number of XLA cases is increasing, as most reach the second decade of life without serious complications and remain free of severe infectious disease and further impairment of their respiratory functions with the treatment.
Subject(s)
Humans , Male , Adult , Young Adult , Immunoglobulins, Intravenous/administration & dosage , Disease Progression , Agammaglobulinemia/complications , Agammaglobulinemia/drug therapy , Genetic Diseases, X-Linked/complications , Genetic Diseases, X-Linked/drug therapy , Quality of Life , Respiratory Tract Infections/etiology , Administration, Cutaneous , gamma-Globulins/administration & dosage , Retrospective Studies , Follow-Up Studies , Administration, IntravenousABSTRACT
Introducción. El síndrome de activación macrofágica (SAM) es una grave complicación de ciertas enfermedades reumáticas, especialmente la artritisidiopática juvenil sistémica (AIJS). El objetivo deeste trabajo es describir las manifestaciones clínicas y bioquímicas de pacientes con AIJS que desarrollaron SAM, así como su respuesta a diferentes esquemas terapéuticos.Población, material y métodos. Estudio observacional y restrospectivo de un grupo de niños con diagnóstico de AIJS que desarrollaron un SAM entre1993 y 2007. El diagnóstico de SAM se realizó sobre la base de elementos clínicos, bioquímicos y,en algunos casos, histopatológicos.Resultados. Se incluyeron 17 pacientes (14 niñas).La edad de los niños varió entre 1 y 16 años (mediana10 años). El SAM se desarrolló en el primer año de evolución de AIJS en 10 niños (en 6 fue la manifestacióninicial). Sus principales características fueron:fiebre continua (100%), hepatomegalia (100%),esplenomegalia (76%), erupción cutánea (59%),adenomegalias (53%), hemorragias (53%), compromisodel sistema nervioso central (SNC) (41%),edemas (29%); enzimas hepáticas elevadas (94%),plaquetopenia (76%), eritro sedimentación normal (76%), hipertrigliceridemia (71%), coagulopatía65%), leucopenia (59%), hipofibrinogenemia (47%);se halló hemofagocitosis en 9 de 13 (69%) pacientes biopsiados. El tratamiento incluyó corticosteroides en altas dosis en 17 (100%) casos, inmunosupresoresen 6 (35%). Doce (71%) pacientes remitieron y 529%) fallecieron en fallo multisistémico. Conclusiones. El SAM es un síndrome de variable gravedad que ocasiona morbimortalidad significativa.La presencia de fiebre continua, hepatosplenomegalia,coagulopatía, compromiso del SNC,citopenias hemáticas y normalización de la eritro sedimentaciónen un niño con AIJS deben despertar lasospecha diagnóstica, aun sin evidencia de hemofagocitosis.
Introduction. Macrophage activation syndrome is a severe complication of certain rheumatic diseases, mainly systemic juvenile idiopathic arthritis (SJIA).The objective of this presentation is to describe the clinical and biochemical features of patients with SJIA who developed MAS, and their response to different therapeutic regimes. Population, materials and methods. Retrospective, observational analysis of children with a diagnosis of SJIA who developed MAS between 1993 and 2007. Diagnosis of MAS was formulated based upon clinical, biochemical and, in some cases, histopathological evidence. Results. Seventeen children (14 girls) were included. Age varied between 1 and 16 years (median 10 years). MAS developed during the first year of AIJS course in 10 children (it was the presenting manifestation in 6). Its main features were: continuous fever (100%), hepatomegaly (100%), splenomegaly (76%), cutaneous rash (59%), lymphadenopathy (53%), hemorrhage (53%), CNS involvement (41%), edema (29%); elevated liver enzimes (94%), thrombocytopenia (76%), normal sedimentation rate (76%), hypertriglyceridemia (71%), coagulopathy (65%), leukopenia (59%), hypofibrinogenemia (47%); hemofagocytosis was found in 9 out of 13 (69%) patients who underwent biopsy. High-dose corticosteroids were prescribed in 17 cases and immunosupressants in 6. Twelve patients remitted and 5 died due to multiorgan failure. Conclusions. MAS is a syndrome of variable severity that may cause significant morbimortality. Presence of continuous fever, hepatosplenomegaly, coagulopathy, CNS involvement, cytopenias and normal sedimentation rate in a child with AIJS should prompt diagnosis, even without evidence of hemophagocytosis. Immunosuppressive therapy was effective in the majority of the studied patients.