key: cord-0930979-f5ywjhw6 authors: Gkogkou, E.; Broux, I.; Kempeneers, C.; Boboli, H.; Viellevoye, R.; Janssen, A.; Seghaye, M.-C.; Mastouri, M. title: Diffuse alveolar hemorrhage in infants: Report of five cases date: 2020-06-11 journal: Respir Med Case Rep DOI: 10.1016/j.rmcr.2020.101121 sha: 1c691168b0097773e142e388b6cec14b67dbff16 doc_id: 930979 cord_uid: f5ywjhw6 Diffuse alveolar hemorrhage (DAH) is a rare life-threatening condition in children. In this entity, the bleeding originates from the pulmonary microvasculature as a result of microvascular damage leading to blood leakage into the alveolar spaces. DAH can occur as an isolated medical entity or may be associated with other organ system injury or dysfunction. The classic triad of symptoms includes hemoptysis, anemia and diffuse pulmonary infiltrates. Hemoptysis is the usual presenting symptom but is not constant. A variety of diseases is associated with the development of DAH. Current classification organize the etiologies of diffuse alveolar hemorrhage based on the presence of severe immune disorders (such as systemic vasculitis and collagenosis) or non-immunodeficiency disorders (with an identified cardiac or non-cardiac origin, or idiopathic). The five cases of DAH presented in this study were all diagnosed in full-term infants, four males and one female, with normal neonatal adaptation and without family history of notable diseases. In all cases the diagnosis was made between the age of three and eighteen weeks-old. Moreover, all five patients, at the time of diagnosis, presented with hemoptysis, mild or severe dyspnea, anemia and abnormal chest X-rays. Consequently, the diagnosis of DAH was strongly suspected and, eventually, confirmed by bronchoscopy. Additional laboratory tests, as well as selected serologic and radiographic studies were performed in order to identify a specific etiology. The final diagnoses reflect a variety of causes: infections, idiopathic pulmonary hemosiderosis, accidental suffocation and Heiner syndrome. Treatment included oral corticosteroids except from one patient that received antimicrobial therapy. hypoxemia (SpO2 95% on room air). There was no fever, no central cyanosis, The chest radiograph showed diffuse alveolar infiltrates mostly in the right lung 154 (Fig. 1a) . Chest computed tomography (CT) showed consolidated opacities 155 mainly in the right lung (Fig. 1b) . Within the first hour of hospitalization, the oxygen saturation decreased (SpO2 157 75%), and the anemia worsened(hemoglobin of 8,5 g/dL); therefore, a 158 supportive therapy including volume expansion, ventilatory support, and 159 transfusion of packed red blood cells at a dose of 20ml/kg was necessary. The was not contributive (see Table 1 ). The diagnosis of idiopathic hemosiderosis 168 was proposed. The immunosuppressive therapy was prescribed using 2 mg/kg of prednisolone 170 daily. The infant was extubated on day 2, and discharged 7 days after admission. The infant returned home on steroid therapy (2mg/kg/day during one month and 172 followed by a gradual dose reduction), with hypoallergenic amino acid-based 173 milk and under home cardio-respiratory monitoring. The patient is regularly 174 followed in the respiratory outpatient clinic, and he is doing very well. At 3 175 months of age, the chest radiograph and the CT were normalized. 199 Chest x-ray revealed bilateral alveolo-interstitial opacities and left lower lobe 200 parenchymal consolidation (Fig. 2a) . Chest CT showed diffuse bilateral alveolar 201 and ground-glass opacities (Fig. 2b) . The infant received packed red cells but no ventilatory support was necessary. A Trachomatis on BAL culture (see Table 1 ). The diagnosis of an interstitial 208 pneumonitis with subsequent diffuse alveolar hemorrhage was made. Antimicrobial therapy using oral clarithromycin 15mg/kg/day for 21 days was Table 1 ) was performed but was not contributive. Two days later, packed red blood cells were transfused for anemia and 243 intravenous antibiotics were administered for suspected infection (fever and 244 raised inflammatory markers). Blood culture and nasopharyngeal aspiration 245 were obtained for viral and bacterial screening. Thoracic angiography scan 246 showed consolidated opacities mainly within the right lung, and arteriovenous 247 malformation were excluded (Fig. 3a, 3b, 3c ). The echocardiography confirmed days after admission, excluding active bleeding. BAL was not performed 250 because of the patient's respiratory instability. The first extubation attempt was done on day 3, but reintubation was necessary 252 due to the recurrent bleeding episode and respiratory distress. The patient initially continued to present fresh blood and clots aspirated from Table 1 ). During hospitalization, 290 he received prednisone 2mg/kg/day and he was discharged after one week with 291 the diagnosis of AH probably due to accidental suffocation, as he was found On admission, the infant was eupneic and normoxic (SpO2 98% on room air). Physical examination and in particular the pulmonary auscultation was normal. One hour later, he developed dyspnea with moderate chest retractions. Central 306 venous blood gases showed a respiratory acidosis (pH of 7.08 and partial 307 pressure of carbon dioxide of 71 mm Hg). Initial laboratory study showed 308 anemia (hemoglobin level: 9.4 g/dL, hematocrit value: 29.3%), thrombocytosis 309 (platelet count: 595.000/mm³), hyperleukocytosis (WBC count: 18.530/mm3, 310 54% lymphocytes, 39% neutrophils) but normal C-reactive protein levels. Further routine laboratory results including septic, hemostatic, renal, and hepatic 312 profile returned normal. Urinalysis was also normal. Chest x-ray revealed diffuse interstitial opacities in the right lung (Fig. 5a) , 314 Thoracic angiography scan confirmed diffuse interstitial opacities in the right 315 lung and excluded vascular malformation (Fig. 5b) . A bronchial fibroscopy was performed on day 4 after the episode of bleeding 317 and did not demonstrate any active bleeding. Hemosiderin-laden macrophages 318 (siderophages) at 89%, and a positive Golde score at 212% were demonstrated 319 in the BAL, confirming DAH. The infant received prednisone 2mg/kg/day. A 320 complete etiologic assessment for DAH (see Table 1 ) was done and was not 321 contributive except for the positivity of precipitins against cow's milk proteins 322 (see Table 2 ). The diagnosis of Heiner syndrome was made. Hypoallergenic 323 amino acid-based milk diet was proposed. The patient's evolution during the hospitalization was favorable and no In all cases, the diagnosis of DAH was confirmed by the bronchoscopy. Subsequently and in order to identify a specific etiology, we proceeded to 359 additional laboratory tests, as well as selected serologic and radiographic 360 studies. In our first case, as no underlying pathology was found, the diagnosis of components to exclude in the differential diagnosis of pulmonary hemorrhage. In our last case, serum immunoglobulin levels (IgG, IgA, IgM, IgE) and milk-394 specific serum IgE were normal but interestingly high precipitating cow's milk 395 proteins antibodies titers was found and Heiner syndrome (HS) was diagnosed. 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