Hemosiderosis pulmonar idiopática, caso clínico en México. Importancia de un diagnóstico y tratamiento oportuno / Idiopathic pulmonary hemosiderosis, clinical case in Mexico. The relevance of performed an early diagnosis and treatment

La hemosiderosis pulmonar idiopática (HPI) es una patología poco frecuente; su distribución geográfica, su incidencia y prevalencia se desconocen de manera exacta a nivel mundial. Tiene una fuerte asociación con condiciones autoinmunes y una adecuada respuesta al tratamiento inmunosupresor. A pesar de ser una patología grave, presenta una tasa de morbilidad y mortalidad mediana, siempre que se realice un diagnóstico y tratamiento precoz. Se presenta el caso clínico de una paciente femenina con diagnóstico de HPI quien cursó con la triada clásica de esta enfermedad: hemoptisis, anemia ferropénica e infiltrados pulmonares difusos. Se descartaron otras causas de hemorragia pulmonar difusa y se realizó el diagnóstico por biopsia pulmonar. Se trató con esteroides sistémicos e inhalados y azatioprina. Tras casi 2 años después del diagnóstico, estando sin tratamiento por 3 meses, presentó una exacerbación con hemorragia pulmonar masiva ocasionando el fallecimiento de la paciente.

Idiopathic pulmonary hemosiderosis (IPH) is a rare pathology; its geographic distribution, incidence and prevalence are not accurately known worldwide. It has a strong association with autoimmune conditions and has an adequate response to immunosuppressive treatment. Despite being a serious pathology, it has a medium morbidity and mortality rate, provided that early diagnosis and treatment is performed. We present the clinical case of a female patient diagnosed with IPH who presented with the classic triad of this disease: hemoptysis, iron deficiency anemia and diffuse pulmonary infiltrates. Other causes of diffuse pulmonary hemorrhage were ruled out and the diagnosis was made by lung biopsy. She was managed with systemic and inhaled steroids and azathioprine. After almost 2 years before the diagnosis, being without treatment for 3 month she had a massive pulmonary hemorrhage, causing the death of the patient.

Hemosiderosis pulmonar idiopática: seguimiento de pacientes durante 25 años (1995-2019) / Idiopathic pulmonary hemosiderosis: follow-up of patients for 25 years (1995-2019)

La hemosiderosis pulmonar idiopática (HPI) es una causa de hemorragia alveolar difusa. OBJETIVO: describir la evolución de niños con HPI en nuestra institución. Se realizó una revisión retrospectiva con protocolo de seguimiento. Se reclutaron 13 pacientes, 7 hombres. Procedentes de una zona agrícola (6/13). No todos presentaron la tríada diagnóstica completa: infiltrados algodonosos (9/13), anemia (11/13), hemoptisis (9/13). Todos evidenciaron un recuento de hemosiderófagos sobre 30% en el lavado broncoalveolar. Tomografía computada de tórax: normal (5/13), patrón intersticial (5/13), vidrio esmerilado (2/13) y fibrosis (1/13). Espirometría: normal (7/13), restrictiva (4/13), obstructiva (1/13) y no efectuada (1/13). Tratamiento durante la fase aguda: bolos de metilprednisolona (7/13) o prednisona (6/13) o hidrocortisona (1/13). En la fase de mantención se administró: prednisona (13/13) más un inmunosupresor, azathioprina (12/13), hidroxicloroquina (1/13), micofenolato (1/13), más budesonida MDI (13/13). Ocho pacientes detuvieron los sangrados. Dos pacientes fallecieron y hubo cinco embarazos de curso fisiológico en 3 adolescentes. Se observó: a) diferentes modalidades de presentación que retrasaron el diagnóstico; b) gran exposición a pesticidas; c) mejor pronóstico si el diagnóstico y el tratamiento eran precoces, también en niñas adolescentes; d) la mayoría detuvo los episodios de sangrado.

Idiopathic pulmonary hemosiderosis (IPH) is a cause of diffuse alveolar hemorrhage. OBJECTIVE: to describe the evolution of children with IPH in our institution. Retrospective monitoring with a follow-up protocol was carried out. 13 patients, seven males, were recruited. From an agricultural area (6/13). Not all of patients had the complete diagnostic triad: cotton infiltrates (9/13), anemia (11/13), hemoptysis (9/13). Hemosiderin-laden macrophages counting in the bronchoalveolar lavage fluid was over 30% in all the patients. Computed chest tomography was informed as normal (5/13), interstitial pattern (5/13), ground glass (2/13) and fibrosis (1/13). Spirometry: normal (7/13), restrictive (4/13), obstructive (1/13) and not performed (1/13). Treatment during the acute phase: bolus of methylprednisolone (7/13) or prednisone (6/13) or hydrocortisone (1/13). In the maintenance phase: prednisone (13/13) plus an immunosuppressant, azathioprine (12/13), hydroxychloroquine (1/13), mycophenolate (1/13), plus budesonide MDI (13/13). Eight patients stopped the bleeding episodes. Two patients died and there were five physiological pregnancies in 3 adolescents. It was observed:(a) different modes of IPH presentation that delayed its diagnosis; (b) large exposure to pesticides; (c) prognosis improved if diagnosis and treatment were early, also in adolescent girls; (d) most of the patients stopped the bleeding episodes.

Hemosiderosis pulmonar idiopática (HPI): presentación de un caso y revisión de la literatura / Idiopathic pulmonary hemosiderosis (IPH): a case report and review of the literature

We present the case-report of a one-month-old infant, admitted to the Emergency Department with hypovolemic shock secondary to pulmonary hemorrhage who required life-support measures, including vasoactive drugs and methylprednisolone pulses. She was discharged from the hospital after 13 days of evolution and then readmitted 5 days later for a new episode of hemoptysis with hemodynamic compromise. Fiberoptic bronchoscopy was performed 4 days after the first episode showed a normal anatomy, without active bleeding, with 20% of hemosiderophages in bronchoalveolar lavage. Diffuse infiltrates were found on the chest radiograph. Differents studies were performed for check-out infection, heart disease, immune disease, thrombophilia, celiac disease, swallowing disorder, vascular abnormalities and allergy to cow's milk protein were negative, which led to Idiopathic Pulmonary Hemosiderosis (IPH). It was managed with amino acid formula, daily oral prednisone until 6 months of age and then every other day, and permanent inhaled fluticasone. In subsequent controls, normal growth and development were found, with no recurrences up to the time of this report, at 1 year of age. The favorable evolution in this case is attributed to early diagnosis and timely treatment with systemic corticosteroids. A review of the topic of IPH in pediatrics is presented, and study and treatment algorithms are proposed.

Se presenta el caso de una lactante de un mes de edad, que se presentó en el Servicio de Urgencia con shock hipovolémico secundario a hemorragia pulmonar. Necesitó medidas de soporte vital, incluyendo drogas vasoactivas y pulsos de metilprednisolona. Egresó del hospital a los 13 días de evolución y reingresó 5 días después por nuevo episodio de hemoptisis con compromiso hemodinámico. La fibrobroncoscopía efectuada a los 4 días de evolución del primer episodio mostró una anatomía normal, sin sangrado activo, con 20% de hemosiderófagos en el lavado broncoalveolar. En la radiografía de tórax se encontró infiltrados difusos. Los estudios en busca de infección, cardiopatía, enfermedad inmunológica, trombofilia, enfermedad celíaca, trastorno de deglución, anomalías vasculares y alergia a la proteína de la leche de vaca resultaron negativos, por lo que se planteó una Hemosiderosis Pulmonar Idiopática (HPI). Se manejó con fórmula aminoacídica, prednisona oral diaria hasta los 6 meses de edad y después en días alternos y fluticasona inhalada permanente. En controles posteriores se constató crecimiento y desarrollo normal, sin recidivas hasta el momento de este reporte, con 1 año de edad. La evolución favorable en este caso se atribuye al diagnóstico precoz y tratamiento oportuno con corticoides sistémicos. Se presenta una revisión del tema de HPI en pediatría y se proponen algoritmos de estudio y tratamiento.

Evaluación de efectividad y seguridad de deferasirox en Hemosiderosis Transfusional / Evaluation of effectiveness and safety of deferasirox in Hemosiderosis Transfusional

Antecedentes: Descripción de la condición de salud de interés (indicación): El cuerpo humano no posee un mecanismo activo para la excreción de hierro, y sus niveles son controlados principalmente por su absorción en el intestino delgado. Fisiológicamente, la cantidad de hierro absorbido (1-2mg/dia) se pierde mediante exudados de la mucosa intestinal y piel, así como pequeñas cantidades a través de la orina y bilis. Los pacientes que cursan con anemias crónicas y que son dependientes de transfusiones sanguíneas, reciben un exceso de hierro con cada transfusión (cada unidad de glóbulos rojos contiene aproximadamente 250mg de hierro); este hierro es acumulado de forma gradual en diferentes tejidos, tales como corazón e hígado. Descripción de la tecnología: El deferasirox es un medicamento quelante, trifdentado que se une especialmente al hierro; es empleado en el tratamiento de la sobrecarga crónica de este metal en el organismo. Está disponible en comprimidos para administración por vía oral. Cuenta con registro sanitario en Colombia. Evaluación de efectividad y seguridad: En pacientes con diagnóstico de hemosiderosis transfusional ¿cuál es la efectividad y seguridad de deferasirox comparado con deferoxamina, en la reducción de depósitos de hierro hepático o cardíaco, niveles de ferritina sérica y mortalidad? La pregunta de investigación fue validada teniendo en cuenta las siguientes fuentes de información: registro sanitario INVIMA, Acuerdo 029 de 2011, guías de práctica clínica, revisiones sistemáticas y narrativas de la literatura, estudios de prevalencia/incidencia y carga de enfermedad, libros de texto, consulta con expertos temáticos, sociedades científicas y otros actores clave. Población: pacientes con diagnóstico de hemosiderosis transfusional. Tecnología de interés: Deferasirox. Conclusiones: Efectividad: Deferasirox es una alternativa terapéutica de administración oral, efectiva para el tratamiento de la hemosiderosis transfusional. No existen diferencias significativas en mortalidad entre deferasirox y deferoxamina. La efectividad de deferasirox puede ser similar a deferoxamina dependiendo de la dosis y proporción comparada; sin embargo, la satisfacción de los pacientes es mayor en el grupo de pacientes previamente tratados con deferoxamina, que recibieron posteriormente deferasirox, lo que puede llevar a una mejor adherencia al tratamiento. Seguridad: los eventos adversos más frecuentes se encuentran relacionados con síntomas gastrointestinales, sin diferencias estadísticamente significativas entre ambos agentes. Sin embargo, se demuestra una mayor probabilidad de presentar aumento en los niveles de creatinina sérica con deferasirox en comparación con deferoxamina.

Deferasirox: Oral, once daily iron chelator - An expert opinion.

Iron overload is a serious and potentially fatal condition that results from multiple blood transfusions required over a long period of time to treat certain types of anemias such as, that caused by β-thalassemia, sickle cell disease and myelodysplastic syndrome. Deferoxamine, which has been used since four decades as an iron chelator has limited efficacy due to its demanding therapeutic regimen, leading to poor compliance. Deferasirox, once daily oral iron chelator provides an effective alternative to Deferoxamine in the treatment of transfusional hemosiderosis. In this review, the role of Deferasirox as an ideal iron chelator has been discussed. Pubmed searches on Deferasirox were carried out for the same. Several studies demonstrated the safety and efficacy of Deferasirox in reducing iron burden in iron-overloaded patients with β-thalassemia, sickle cell anemia and myelodysplastic anemia. Thus, convenient, effective and tolerable chelation therapy with oral Deferasirox is likely to be a significant development in the treatment of transfusional iron overload, due to its ability to provide constant chelation coverage and the potential to improve compliance.

Advances in management of thalassemia.

Thalassemias represent the most common single-gene disorder causing a major public health problem in India. Thalassemia and hemoglobinopathies probably developed over 7000 years ago as a defense against malaria. In simple terms, thalassemia is caused by a mutation in either the â-globin chain or the á-globin chain which combine equally in red cells to form hemoglobin. These mutations lead to varying degree of anemia resulting into thalassemia minor, intermedia or major. Present write up relates to advances in the management of â-thalassemia major.

Idiopathic pulmonary haemosiderosis: complete remission with steroids.

A 13-year-old boy was diagnosed as a case of idiopathic pulmonary haemosiderosis on the basis of clinical presentation, radiological assessment and open lung biopsy. The patient had a complete clinical and radiological remissions with oral corticosteroids.

Hemossiderose pulmonar idiopática tratada com azatioprina: relato de caso em criança / Idiopathic pulmonary hemosiderosis treated with azathioprine in a child

A hemossiderose pulmonar idiopática (HPI), principal causa de hemossiderose pulmonar em crianças, cursa com sangramento alveolar intermitente e presença de hemossiderófagos no escarro ou no lavado gástrico. O tratamento é baseado nos corticoesteróides e citostáticos, em condições especiais. Descreve-se o caso de uma menina de sete anos com HPI, que conseguiu controle parcial da doença mediante altas doses de corticoesteróide. O tratamento, no entanto, necessitou ser suspenso gradualmente visto a paciente ter desenvolvido fácies cushingóide. Foi iniciada a associação da azatioprina ao corticóide até a substituição total por azatioprina isolada, cujo uso foi mantido por quatro anos, com ótimo resultado.

Idiopathic pulmonary hemosiderosis (IPH), the main cause of pulmonary hemosiderosis in children, is characterized by intermittent alveolar bleeding and hemosiderin-laden macrophages in sputum and in gastric lavage. The treatment is based on corticosteroids and cytotoxic drugs, under special conditions. We describe the case of a 7-year-old girl with IPH who achieved partial clinical remission with high doses of corticosteroids. However, the treatment had to be discontinued because the patient developed Cushing's syndrome. Treatment was started with an azathioprine-corticosteroid combination and then changed to azathioprine alone, which was maintained for four years, with excellent results.

Life threatening exacerbation in idiopathic pulmonary hemosiderosis salvaged by cyclophosphamide infusion.

A seven-year-old girl presented with frequent fever, cough and shortness of breath of three months duration. On the basis of her clinical features, peripheral blood and sputum findings, she was diagnosed as a case of idiopathic pulmonary hemosiderosis. After initial stabilisation with steroids and chloroquine, she presented four years later with massive pulmonary hemorrhage and respiratory failure, which responded dramatically to cyclophosphamide infusion. The rare occurrence of pulmonary hemosiderosis and different treatment regimens is discussed.

Hemosiderosis pulmonar idiopática / Idiopathic pulmonary hemosiderosis

La hemosiderosis pulmonar idiopática (HPI) es un desorden raro caracterizado por hemorragia alveolar difusa. La etiología es aún desconocida y el pronóstico impredecible. Esta revisión describe las características clínicas y la respuesta al tratamiento en niños con HPI luego de 5 años de seguimiento.El uso de un protocolo terapéutico ordenado permitió una sobrevida adecuada. El uso de corticoidesinhalatorios puede permitir reducir los efectos secundarios de los esteroides sistémicos.

Autoantibodies in thalassaemia major: relationship with oral iron chelator L1.

Ninety patients with thalassaemia major were investigated for the occurrence of antinuclear antibodies (ANA), and those with ANA were tested for antibodies to histones (AHA). ANA were detected in 7 of 27 thalassemics on oral iron chelator L1, and in 2 of 63 thalassaemics not on L1 (p < 0.01). AHA were seen in 4 of 7 thalassemics receiving L1 with positive ANA, and in none of the 2 not receiving L1 (p < 0.03). Joint pains were seen in patients receiving L1, but in none of the patients not receiving L1. There was no correlation between hepatitis B or HIV positivity and presence of ANA or joint pains. While some amount of background ANA-positivity was found in patients with thalassaemia major, it was significantly more in patients receiving L1. Laboratory evidence of drug-induced lupus-like reaction was seen only in patients who received L1. In view of serious concerns about the safety of L1 and wide variations in the incidence and severity of adverse reactions reported by different sources, an urgent regulatory audit of all trial centres is essential.

Hemosiderosis pulmonar idiopática (HPI) / Idiopathic pulmonary hemosiderosis

Se estudió una niña de 3 años con signos clínicos, radiológicos y datos de laboratorio compatibles con hemosiderosis pulmonar idiopática. El diagnóstico se vio apoyado con el estudio del aspirado bronquial. Se trató con prednisona y azatiorpina. Ha tenido un curso clínico satisfactorio con desaparición de la sintomatología clínica