Food-Induced Pulmonary Hemosiderosis

A two-month-old male with past medical history of recurrent diarrhea and failure to thrive presented with persistent cough, tachypnea and high inflammatory markers despite antibiotic treatment for pneumonia. One week earlier our patient was diagnosed with bilateral pneumonia based on same symptoms as well as chest x-ray findings, and was started on Amoxicillin 80mg/kg/day. There was no fever. Patient was born full-term via scheduled cesarean section, with no complications noted during pregnancy or delivery. Since birth, patient experienced a decrease in weight for age percentiles and watery diarrhea. He went through multiple types of formula and following positive stool lactoferrin, he was switched to a partially hydrolyzed formula. His diarrhea improved suggesting the patient had a food protein allergy. Otherwise, patient’s family and social history were non-contributory. On exam, patient was a febrile, showed no significant distress, mild nasal congestion with occasional cough and mild intercostals retractions. The chest auscultation was normal. There were no rashes. Remainder of the physical exam was unremarkable. Laboratory results included the following (reference ranges provided parenthetically): Hemoglobin of 9 gm/dl (9.0-15.0), WBC of 23.4 (5.0-19.5 X 10(9)/L), platelets of 919 (140-440 X10(9)/L), C-reactive protein of 33.4 mg/L (<6.0), erythrocyte sedimentation rate of >130 mm/hr (0-2). Procalcitonin, lactic acid, electrolyte panel, liver enzymes and the rest of the complete blood count (CBC) were unremarkable. A respiratory viral panel was negative. Sweat chloride test was also performed and found to be negative. Aspiration and tracheoesophageal fistula were deemed unlikely after evaluation with swallow study and upper gastrointestinal series with barium that showed lack of aspiration and normal anatomy with contrast staying within the gastrointestinal tract. Patient was started on azithromycin to cover atypical bacteria. Pulmonary infiltrates, tachypnea, high inflammatory markers and thrombocytosis persisted despite antibiotic treatment for pneumonia. Allergy/immunology, infectious disease, hematology and gastrointestinal consults were done. Primary thrombocytosis and hemophagocytic lymphohistiocytosis (HLH) were excluded by hematology team. From infectious disease, extreme thrombocytosis and leukocytosis was not related to the atypical pneumonia and the underlying cause was unclear. Given the history of possible food protein allergy, ongoing GI inflammation was suspected despite clinical improvement in diarrhea, and this was confirmed by repeating fecal lactoferrin and calprotectin that remained elevated on the partially hydrolyzed formula. With indication of inadequate control of food protein allergy, Heiner’s syndrome was suspected and patient was switched to an amino acid-based formula during this hospital admission. Cow’s milk IgG4 was found to be elevated to 10.20 mcg/mL (normal range; <0.15 mcg/mL). Cow’s milk IgE was normal (normal range; <0.35 kU/L). Improvement in inflammation and respiratory condition was noted only after switching to the amino acid based formula, suggesting pulmonary hemosiderosis and enteropathy due to milk allergy. Twenty days after discharge WBC, PLT, ESR and CRP values returned to normal limits. Repeat chest x-ray done at an outside hospital showed progressive improvement.