Diffuse alveolar hemorrhage in children with trisomy 21

Abstract

Background Respiratory conditions are the leading cause of hospitalization and death in children with Trisomy 21 (T21). Diffuse alveolar hemorrhage (DAH) occurs at higher frequency in children with T21; yet, it is not widely studied nor is there a standardized approach to diagnosis or management. The objective of this study was to identify children with T21 and DAH in order to understand contributing factors and identify opportunities to improve outcomes. We identified 5 children with T21 at a single institution with histology-proven DAH over 10 years and discuss their presentation, evaluation, management, and outcomes. We also reviewed the cases in the literature. Case presentation Patient 1 died at age seven due to secondary hemophagocytic lymphohistiocytosis. DAH was seen on autopsy. Patient 2 was a three-year-old with systemic-onset juvenile idiopathic arthritis diagnosed with DAH after presenting for hypoxia. Patient 3 was diagnosed with DAH at age nine after presenting with recurrent suspected pneumonia and aspiration. Patient 4 was diagnosed with DAH at age eight after presenting with pallor and fatigue. She had additional ICU admissions for DAH with infections. Patient 5 developed hemoptysis at age three and had recurrent DAH for 10 years. Four patients responded positively to immune-modulation such as intravenous immunoglobulin, glucocorticoids, and rituximab. Of the 19 patients identified in the literature, only one was from the United States. The majority had anemia, respiratory distress, autoantibodies, and recurrences. Very few patients had hemoptysis. Idiopathic pulmonary hemosiderosis was the most common diagnosis. Almost all received glucocorticoids with or without additional immunosuppression. The majority of our patients and those in the literature had positive auto-antibodies such as anti-neutrophil cytoplasmic antibodies and anti-nuclear antigen antibodies. Diagnostic clues included respiratory distress, hypoxia, anemia, recurrent pneumonia, and/or ground glass opacities on imaging. We identified four contributors to DAH: structural lung abnormalities, pulmonary arterial hypertension, infection/aspiration, and autoimmune disease/immune dysregulation. Conclusion These cases demonstrate the need for an increased index of suspicion for DAH in children with T21, particularly given the low frequency of hemoptysis at presentation, enrich the understanding of risk factors, and highlight the favorable response to immunosuppressive therapies in this vulnerable population.

Diffuse alveolar haemorrhage in children: an international multicentre study

“…The overall incidence of DAH is unknown. In children with IPH, the incidence has been estimated to 0.24 -1.23 / million children per year but the incidence is highly elevated in children with trisomy 21 (3)(4)(5). The clinical presentation of DAH is very heterogenous from chronic cough and dyspnoea to haemoptysis, acute respiratory failure and severe anaemia (6)(7)(8).…”

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“…Рентгенологические проявления зубочелюстных аномалий. REJR 2023; 13 (1): [5][6][7][8][9][10][11][12][13][14][15][16][17]. DOI: 10.21569/2222-7415-2023-13-1-5-17.…”

“…Национальное когортное исследование в США, в котором приняли участие более 3,4 миллиона пациентов, в том числе более 387 000 пациентов с COVID-19, включая более 7500 пациентов с ХОБЛ, продемонстрировало связь между ХОБЛ и смертностью от COVID-19 (OR: 2,1, 95% ДИ: 1,96-2,26), после корректировки на возраст, пол и сопутствующие заболевания [16]. Аналогичным 1,49, 95% ДИ: 1,16-1,92), после корректировки данных, включая возраст, пол, этническую принадлежность, основные демографические данные и сопутствующие заболевания [17].…”

“…Неоадъювантная химиотерапия (НХТ) в настоящее время все чаще используется не только при местно-распространенных (неоперабельных), но и операбельных формах злокачественных новообразований (ЗНО) полости рта и ротоглотки [15,16]. Несмотря на то, что при сравнительном анализе эффективности неоадъювантной и адъювантной химиотерапии существенных отличий в отношении показателей безрецидивной и общей выживаемости не выявлено [15].…”

“…Так же, как и в работах Min Jae Cha и соавт., Puntmann VO и соавт., Rudolph A и соавт., результаты нашего исследования не позволяют говорить о возможности дифференцировать причину гипертрофии ЛЖ по характеру структурного поражения миокарда [11,15,16]. В нашей работе у пациентов с АГ отмечались меньшие значения массы и доли фиброза и серой зоны миокарда ЛЖ, однако при сопоставлении пациентов со схожей выраженностью гипертрофии ЛЖ выраженной разницы не отмечалось, определялось большее количество сегментов с наличием участков фиброза миокарда в группе пациентов с ГКМП по сравнению с АГ, а также выделялась характерная локализация участков фиброза у пациентов с ГКМП.…”