[COVID-19 in adults with antibody deficiencies]. / COVID-19 en adultos con inmunodeficiencias humorales.

COVID-19, caused by SARS-CoV-2, emerged in late 2019 in Wuhan, China. Its clinical course is variable, as well as the mortality rate, which is higher among people over 65 years of age and persons with underlying conditions. Immunodeficiencies are potential risk factors for severe forms of COVID-19. Furthermore, patients with immunodeficiencies often undergo non-infectious complications, which could bear additional risk. So far, few reports of patients with COVID-19 and humoral immunodeficiencies have been published. Considering the importance of the study of this new viral disease and its potential health impact on patients with immunodeficiency disorders, we present six cases of COVID-19 in patients with impaired humoral immunity. Three were women and three were men. The average age was 48.5 years (range 20-67). Four had been diagnosed with primary antibody deficiency: three had common variable immunodeficiency and one had X-linked agammaglobulinemia. The other two patients had secondary hypogammaglobulinemia, one was associated with thymoma (Good's syndrome), and the other was associated with rituximab treatment. The evolution was favorable in all except the patient with Good's syndrome, who presented a marked decline in clinical status before contracting COVID-19.

La enfermedad COVID-19, causada por el virus SARS-CoV-2, surgió a fines de 2019 en Wuhan, China. La evolución clínica es variable, así como la tasa de mortalidad, que es mayor en pacientes mayores de 65 años y en quienes padecen enfermedades subyacentes. Las inmunodeficiencias son potenciales factores de riesgo para formas graves de COVID-19. Los pacientes con inmunodeficiencias tienen además mayor frecuencia de complicaciones no infecciosas, que podrían representar un riesgo adicional. Hasta el momento existen escasas publicaciones sobre asociación COVID-19 e inmunodeficiencias humorales. Considerando la importancia del estudio de esta nueva enfermedad viral y de su potencial repercusión en la salud de los pacientes con inmunodeficiencias presentamos seis casos de COVID-19 en adultos con déficit de anticuerpos (tres mujeres y tres varones, edad promedio 48.5 años, rango 20-67). Cuatro tenían inmunodeficiencias primarias: inmunodeficiencia común variable (n: 3) y agammaglobulinemia ligada al cromosoma X (n: 1). Los otro dos tenían hipogammaglobulinemia secundaria, en un caso asociada a timoma (síndrome de Good), y en el otro a tratamiento con rituximab. La evolución fue favorable en todos menos en el paciente con síndrome de Good, quien presentaba un marcado deterioro del estado general antes de contraer COVID-19.

COVID-19 en adultos con inmunodeficiencias humorales / COVID-19 in adults with antibody deficiencies

Resumen La enfermedad COVID-19, causada por el virus SARS-CoV-2, surgió a fines de 2019 en Wuhan, China. La evolución clínica es variable, así como la tasa de mortalidad, que es mayor en pacientes mayores de 65 años y en quienes padecen enfermedades subyacentes. Las inmunodeficiencias son potenciales factores de riesgo para formas graves de COVID-19. Los pacientes con inmunodeficiencias tienen además mayor frecuencia de complicaciones no infecciosas, que podrían representar un riesgo adicional. Hasta el momento existen escasas publicaciones sobre asociación COVID-19 e inmunodeficiencias humorales. Considerando la importancia del estudio de esta nueva enfermedad viral y de su potencial repercusión en la salud de los pacien tes con inmunodeficiencias presentamos seis casos de COVID-19 en adultos con déficit de anticuerpos (tres mujeres y tres varones, edad promedio 48.5 años, rango 20-67). Cuatro tenían inmunodeficiencias primarias: inmunodeficiencia común variable (n: 3) y agammaglobulinemia ligada al cromosoma X (n: 1). Los otro dos tenían hipogammaglobulinemia secundaria, en un caso asociada a timoma (síndrome de Good), y en el otro a tratamiento con rituximab. La evolución fue favorable en todos menos en el paciente con síndrome de Good, quien presentaba un marcado deterioro del estado general antes de contraer COVID-19.

Abstract COVID-19, caused by SARS-CoV-2, emerged in late 2019 in Wuhan, China. Its clinical course is variable, as well as the mortality rate, which is higher among people over 65 years of age and persons with underlying conditions. Immunodeficiencies are po tential risk factors for severe forms of COVID-19. Furthermore, patients with immunodeficiencies often undergo non-infectious complications, which could bear additional risk. So far, few reports of patients with COVID-19 and humoral immunodeficiencies have been published. Considering the importance of the study of this new viral disease and its potential health impact on patients with immunodeficiency disorders, we present six cases of COVID-19 in patients with impaired humoral immunity. Three were women and three were men. The average age was 48.5 years (range 20-67). Four had been diagnosed with primary antibody deficiency: three had common variable immunodeficiency and one had X-linked agammaglobulinemia. The other two patients had secondary hypogammaglobulinemia, one was associated with thymoma (Good's syndrome), and the other was associated with rituximab treatment. The evolution was favorable in all except the patient with Good's syndrome, who pre sented a marked decline in clinical status before contracting COVID-19.

[Recalcitrant cicatrizing conjunctivitis. Treatment of nine patients with rituximab]. / Conjuntivitis cicatrizal recalcitrante. Tratamiento de nueve pacientes con rituximab.

Cicatrizing conjunctivitis is the final consequence of several diseases. The most severe among them are cicatricial pemphigoid and chronic Stevens-Johnson syndrome. Systemic immunosuppressive drugs and steroids are usually an effective approach to these diseases. However, a few patients follow a recalcitrant course unremitting to usual therapy. We describe the treatment with rituximab of seven patients with cicatricial pemphigoid and two with chronic Stevens-Johnson syndrome. Eight of them also received gammaglobulin and all achieved clinical remission. Three relapsed and required two or three new courses of rituximab with good control of disease activity. Rituximab proved to be an efficacious drug for chronic recalcitrant cicatrizing conjunctivitis.

La conjuntivitis cicatrizal es la consecuencia de distintas enfermedades oculares. Entre ellas, las más graves son el penfigoide cicatrizal y el síndrome de Stevens-Johnson crónico. El tratamiento de estas enfermedades con corticoides e inmunosupresores es habitualmente exitoso, pero unos pocos pacientes siguen un curso recalcitrante. En los últimos años se introdujo el uso de rituximab, asociado o no a gammaglobulina endovenosa, en forma abierta, para el control de la inflamación conjuntival. Describimos aquí el tratamiento de siete pacientes con penfigoide y dos con Stevens-Johnson recalcitrante, con rituximab. Ocho recibieron también gammaglobulina y todos alcanzaron la remisión de la actividad. Tres recayeron y recibieron dos o tres nuevos cursos de la medicación con mejoría sintomática. El rituximab probó ser una droga efectiva para el tratamiento de la conjuntivitis cicatrizal crónica recalcitrante.

Conjuntivitis cicatrizal recalcitrante: Tratamiento de nueve pacientes con rituximab / Recalcitrant cicatrizing conjunctivitis. Treatment of nine patients with rituximab

La conjuntivitis cicatrizal es la consecuencia de distintas enfermedades oculares. Entre ellas, las más graves son el penfigoide cicatrizal y el síndrome de Stevens-Johnson crónico. El tratamiento de estas enfermedades con corticoides e inmunosupresores es habitualmente exitoso, pero unos pocos pacientes siguen un curso recalcitrante. En los últimos años se introdujo el uso de rituximab, asociado o no a gammaglobulina endovenosa, en forma abierta, para el control de la inflamación conjuntival. Describimos aquí el tratamiento de siete pacientes con penfigoide y dos con Stevens-Johnson recalcitrante, con rituximab. Ocho recibieron también gammaglobulina y todos alcanzaron la remisión de la actividad. Tres recayeron y recibieron dos o tres nuevos cursos de la medicación con mejoría sintomática. El rituximab probó ser una droga efectiva para el tratamiento de la conjuntivitis cicatrizal crónica recalcitrante.

Cicatrizing conjunctivitis is the final consequence of several diseases. The most severe among them are cicatricial pemphigoid and chronic Stevens-Johnson syndrome. Systemic immunosuppressive drugs and steroids are usually an effective approach to these diseases. However, a few patients follow a recalcitrant course unremitting to usual therapy. We describe the treatment with rituximab of seven patients with cicatricial pemphigoid and two with chronic Stevens-Johnson syndrome. Eight of them also received gammaglobulin and all achieved clinical remission. Three relapsed and required two or three new courses of rituximab with good control of disease activity. Rituximab proved to be an efficacious drug for chronic recalcitrant cicatrizing conjunctivitis.

[Anaphylaxis and allergic reactions during surgery and medical procedures]. / Anafilaxias y reacciones alérgicas durante cirugías y procedimientos médicos.

Anaphylaxis during anesthesia is an unpredictable, severe, and rare reaction. It has an incidence of 1/10 000 to 1/20 000 surgeries. In most series, the responsible drugs include neuromuscular blocking agents, latex, or antibiotics. The frequency and etiology of systemic allergic reactions in other medical procedures are largely unknown. The identification of responsible drugs of anaphylaxis is a complex task, requiring testing of all medications and substances used during surgery. We describe our experience in a retrospective study of 15 patients. Ten subjects developed anaphylaxis during surgery, two in endoscopic studies and one in a trans-vaginal ultrasound. The remaining two subjects, one in a trans-vaginal ultrasound and another during a dental procedure had a systemic allergic reaction. We studied all patients with all medications administered during the procedures, including latex and detergents and disinfectants. Three surgeries had to be suspended at induction of anesthesia, five were stopped incomplete and two were completed. Both patients that presented a reaction during endoscopy required intensive care unit admission and the rest were observed in a Hospital. The responsible drugs during surgery anaphylaxis were neuromuscular blocking agents, latex, patent blue, and ranitidine. Ortho-phthalaldehyde (OPA) was identified during endoscopic studies; latex was responsible in transvaginal ultrasounds; and amoxicillin in the dental procedure. The aim of the present article is to review our experience studying allergic systemic reactions and anaphylaxis during general anesthesia and medical procedures, emphasizing the severity of these reactions and the need for causative drug identification.

Anafilaxias y reacciones alérgicas durante cirugías y procedimientos médicos / Anaphylaxis and allergic reactions during surgery and medical procedures

Las reacciones anafilácticas intraoperatorias son impredecibles, infrecuentes y pueden poner en riesgo al paciente. Tienen una incidencia de 1/10 000 a 1/20 000 produciéndose en la mayoría de los casos por bloqueantes musculares, látex y antibióticos. No hay estadística de las reacciones alérgicas sistémicas durante otros procedimientos médicos. El estudio diagnóstico posterior a una reacción es complejo debiendo incluir toda la medicación utilizada en el procedimiento. En este estudio retrospectivo describimos 15 pacientes, de los cuales 10 tuvieron reacciones anafilácticas en un procedimiento quirúrgico, 2 en endoscopías y 1 en una ecografía transvaginal. Los dos pacientes restantes presentaron una reacción alérgica sistémica durante una ecografía transvaginal y un procedimiento odontológico. Estudiamos los pacientes con toda la medicación utilizada, incluimos látex y, eventualmente, los detergentes y desinfectantes, de haber sido empleados. Tres de las 10 cirugías no pudieron realizarse por desarrollarse la reacción durante la inducción anestésica, en cinco casos debieron interrumpirse y solo en dos se terminaron. Las reacciones posteriores a endoscopías fueron severas, requiriendo internación en terapia intensiva; las reacciones en ecografías transvaginales y procedimientos odontológicos fueron asistidas en emergencias. Los agentes causales en las cirugías incluyeron bloqueantes musculares, látex, cefalosporina, azul patente y ranitidina; en endoscopías el agente causal fue el orto-ftalaldehído (OPA), en las ecografías transvaginales el látex y en el procedimiento odontológico la amoxicilina. El objetivo de este artículo es describir la etiología de las reacciones alérgicas sistémicas y anafilácticas intraoperatorias y en procedimientos médicos, recalcando su gravedad y la necesidad de su identificación.

Anaphylaxis during anesthesia is an unpredictable, severe, and rare reaction. It has an incidence of 1/10 000 to 1/20 000 surgeries. In most series, the responsible drugs include neuromuscular blocking agents, latex, or antibiotics. The frequency and etiology of systemic allergic reactions in other medical procedures are largely unknown. The identification of responsible drugs of anaphylaxis is a complex task, requiring testing of all medications and substances used during surgery. We describe our experience in a retrospective study of 15 patients. Ten subjects developed anaphylaxis during surgery, two in endoscopic studies and one in a trans-vaginal ultrasound. The remaining two subjects, one in a trans-vaginal ultrasound and another during a dental procedure had a systemic allergic reaction. We studied all patients with all medications administered during the procedures, including latex and detergents and disinfectants. Three surgeries had to be suspended at induction of anesthesia, five were stopped incomplete and two were completed. Both patients that presented a reaction during endoscopy required intensive care unit admission and the rest were observed in a Hospital. The responsible drugs during surgery anaphylaxis were neuromuscular blocking agents, latex, patent blue, and ranitidine. Ortho-phthalaldehyde (OPA) was identified during endoscopic studies; latex was responsible in transvaginal ultrasounds; and amoxicillin in the dental procedure. The aim of the present article is to review our experience studying allergic systemic reactions and anaphylaxis during general anesthesia and medical procedures, emphasizing the severity of these reactions and the need for causative drug identification.

[Rituximab and hypogammaglobulinemia]. / Rituximab e hipogammaglobulinemia.

Rituximab, a chimeric monoclonal antibody against CD20, induces the depletion of B lymphocytes. It is used for the treatment of lymphoproliferative and autoimmune diseases. Antibody immunodeficiency associated to RTX treatment is a new motif for consultation to our service. We decided to study those patients that having been treated with RTX, consulted for hypogammaglobulinemia or recurrent infections between November 2010 and December 2014. We evaluated eight patients, seven female and one male. The average follow up time was 19.3±18.8 months, range 1 to 54, median 13. Three had a normal electrophoretic proteinogram before receiving RTX, three had hypogammaglobulinemia and in two data was not available. None of them had a quantitative determination of immunoglobulins before receiving RTX. Four received RTX as a treatment of non Hodking lymphoma, two as a treatment of chronic lymphocytic leukemia, one for immune thrombocytopenic purpura and other for microscopic polyangiitis. Six were diagnosed with hypogammaglobulinemia and one with combined IgM, IgA and IgG2 deficiency. Five presented infections, four of them with good response to intravenous immunoglobulin. RTX related antibody deficiency consultations are increasing. It is important to determine the immunoglobulin levels previously to RTX use in order to establish an etiologic relationship with RTX and a quick diagnosis of antibody deficiency. The substitutive treatment with gammaglobulin seems to be useful in patients with severe or recurrent infections.

Rituximab e hipogammaglobulinemia / Rituximab and hypogammaglobulinemia

El rituximab (RTX), un anticuerpo quimérico anti-CD20 que induce la depleción de linfocitos B, es utilizado para el tratamiento de enfermedades linfoproliferativas y autoinmunes. La inmunodeficiencia humoral relacionada al tratamiento con RTX comenzó a ser un motivo de derivación a nuestro Servicio, por lo que decidimos analizar a los pacientes con el antecedente de haber sido tratados con RTX que consultaron por hipogammaglobulinemia o infecciones recurrentes desde noviembre de 2010 hasta diciembre de 2014. Evaluamos a ocho pacientes, siete mujeres y un varón. El tiempo promedio de seguimiento fue de 19.3 ± 18.8 meses, rango 1 a 54, con una mediana de 13. Tres tenían proteinogramas normales previo a la administración de RTX, tres hipogammaglobulinemia, y de dos no hay datos. A ninguno se le realizó una determinación cuantitativa de inmunoglobulinas previa al tratamiento. Cuatro recibieron RTX por linfoma B no Hodgkin, dos por leucemia linfocítica crónica, uno por púrpura trombocitopénica autoinmune y otro por poliangeítis microscópica. A seis se les diagnosticó hipogammaglobulinemia y a uno deficiencia de IgM, IgA e IgG2. Cinco presentaron infecciones, cuatro con buena respuesta al tratamiento de reemplazo con gammaglobulina. La inmunodeficiencia humoral relacionada a RTX es una causa de consulta cada vez más frecuente. Resulta fundamental disponer de los niveles de inmunoglobulinas previo al inicio de su administración para poder establecer una relación etiológica y durante el seguimiento, para disminuir el retraso diagnóstico. El tratamiento con gammaglobulina en dosis sustitutivas parece ser de utilidad en pacientes con infecciones graves o recurrentes.

Rituximab, a chimeric monoclonal antibody against CD20, induces the depletion of B lymphocytes. It is used for the treatment of lymphoproliferative and autoimmune diseases. Antibody immunodeficiency associated to RTX treatment is a new motif for consultation to our service. We decided to study those patients that having been treated with RTX, consulted for hypogammaglobulinemia or recurrent infections between November 2010 and December 2014. We evaluated eight patients, seven female and one male. The average follow up time was 19.3 ± 18.8 months, range 1 to 54, median 13. Three had a normal electrophoretic proteinogram before receiving RTX, three had hypogammaglobulinemia and in two data was not available. None of them had a quantitative determination of immunoglobulins before receiving RTX. Four received RTX as a treatment of non Hodking lymphoma, two as a treatment of chronic lymphocytic leukemia, one for immune thrombocytopenic purpura and other for microscopic polyangiitis. Six were diagnosed with hypogammaglobulinemia and one with combined IgM, IgA and IgG2 deficiency. Five presented infections, four of them with good response to intravenous immunoglobulin. RTX related antibody deficiency consultations are increasing. It is important to determine the immunoglobulin levels previously to RTX use in order to establish an etiologic relationship with RTX and a quick diagnosis of antibody deficiency. The substitutive treatment with gammaglobulin seems to be useful in patients with severe or recurrent infections.