2020/34/2/123/300925 Introduction Cow's milk protein allergy (CMPA) commonly presents with atopic dermatitis in infancy. [ijaai.in]

Herein, we describe our experience with three recent cases of Heiner syndrome presenting with different symptoms and clinical courses. 2. Case Reports We describe three patients who presented with different initial symptoms. [mdpi.com]

Pulmonary disease caused by milk allergy may be a rare presentation but should be thought of in a child with recurrent infections and pulmonary infiltrates. [consultant360.com]

Case Presentation A sixteen week old male infant who was a product of term gestation presented with poor weight gain and respiratory distress noticed at 10th week of life. [ncbi.nlm.nih.gov]

Clinically, gastrointestinal signs and symptoms, ane-mia, recurrent fever and failure to thrive can be also present. Chest X-rays can show patchy infiltrates miming pneumonia. Clinical manifestations usually disappear after a milk-free diet. [moh-it.pure.elsevier.com]

• Anemia

  Other clinical manifestations include poor growth, gastrointestinal signs and symptoms, iron deficiency anemia and pulmonary hemosiderosis (PH). [encyclopedia.pub]

  D., a nine-month-old Caucasian female, was first admitted to West Virginia University Hospital on March 14,1964, because of failure to grow,anemia, and chronic recurrent lung disease. [pubs.rsna.org]

  Children with precipitins usually have an increased incidence of recurrent respiratory tract diseases, anemia and hepatosplenomegalia. [mdpi.com]

  Laboratory studies showed a hemoglobin level of 3.8 g/dL and hypochromic microcytic anemia. The patient was subsequently transferred to the pediatric ICU for evaluation. [contemporarypediatrics.com]

  A syndrome including poor growth, gastrointestinal symptoms, evidence of allergy, iron deficiency anemia, and pulmonary hemosiderosis. Am. J. Dis. [pubmed.ncbi.nlm.nih.gov]

• Fever

  Clinically, gastrointestinal signs and symptoms, ane-mia, recurrent fever and failure to thrive can be also present. Chest X-rays can show patchy infiltrates miming pneumonia. Clinical manifestations usually disappear after a milk-free diet. [moh-it.pure.elsevier.com]

  The patient was discharged on Feb. 21 but readmitted three days later with a left upper lobe atelectasis, high fever, and positive nasopharyngeal cultures for Hemophilus injluenzae. A favorable response was obtained with antibiotic therapy. [pubs.rsna.org]

  The most commonly described systemic clinical manifestations were intermittent fever, progressive anorexia and FTT. Inflammatory markers were usually found to be high. [encyclopedia.pub]

  His mother had no fever or rash all through the antenatal period. Apgar scores were 8 and 10 in the first and fifth minutes respectively. [ncbi.nlm.nih.gov]

  The symptoms were in the form of cough in seven, wheezing in three, hemoptysis in two, nasal congestion in three, dyspnea in one, recurrent otitis media (OM) in three, recurrent fever in four, anorexia, vomiting, colic or diarrhea in five, hematochezia [pubmed.ncbi.nlm.nih.gov]

• Poor Growth

  Multiple precipitins to cow's milk in chronic respiratory disease: a syndrome including poor growth, gastrointestinal symptoms, evidence of allergy, iron deficiency anemia, and pulmonary hemosiderosis. [ncbi.nlm.nih.gov]

  A syndrome including poor growth, gastrointestinal symptoms, evidence of allergy, iron deficiency anemia, and pulmonary hemosiderosis. Am J Dis Child 1962;103:634-54. 3. Sicherer SH, Sampson HA. [ijaai.in]

  Other clinical manifestations include poor growth, gastrointestinal signs and symptoms, iron deficiency anemia and pulmonary hemosiderosis (PH). [mdpi.com]

• Recurrent Otitis Media

  Patients may have prolonged exposure to cow’s milk and a history of chronic rhinitis, recurrent otitis media, persistent cough, or failure to thrive. The immune-mediated response in Heiner syndrome is not completely understood. [consultant360.com]

  The symptoms were in the form of cough in seven, wheezing in three, hemoptysis in two, nasal congestion in three, dyspnea in one, recurrent otitis media (OM) in three, recurrent fever in four, anorexia, vomiting, colic or diarrhea in five, hematochezia [pubmed.ncbi.nlm.nih.gov]

  otitis media (OM) (3/9); recurrent fever (4/9); gastrointestinal symptoms (5/9); in 7/8; hematochezia (1/9); FTT (2/9); eosinophilia in 5/8 yes (9/9) yes (1/9) NS yes (6/6) NS sIgE (1/3), SPT (1/2) yes (8/9) positive challenge (3/3) 10 Sigua, 2013 USA [encyclopedia.pub]

• Anorexia

  The symptoms were in the form of cough in seven, wheezing in three, hemoptysis in two, nasal congestion in three, dyspnea in one, recurrent otitis media (OM) in three, recurrent fever in four, anorexia, vomiting, colic or diarrhea in five, hematochezia [pubmed.ncbi.nlm.nih.gov]

  The most commonly described systemic clinical manifestations were intermittent fever, progressive anorexia and FTT. Inflammatory markers were usually found to be high. [encyclopedia.pub]

  Some patients with the condition have also been reported to have gastrointestinal symptoms such as anorexia, vomiting, diarrhoea, abdominal pain and bloody stools1,2. [ncbi.nlm.nih.gov]

• Hemoptysis

  The present case highlights the need for exploring food allergies, other than milk, as a probable culprit in cases of unexplained hemoptysis. [ijaai.in]

  61 Gkogkou E...Mastouri M 32802736 2020 3 Heiner Syndrome: An uncommon cause of failure to thrive. 61 Ojuawo AB...Mokuolu OA 31839894 2019 4 A different clinical presentation of Heiner syndrome: The case of diffuse alveolar hemorrhage causing massive hemoptysis [malacards.org]

  Hemoptysis recurred at the age of 3; therefore, he underwent a comprehensive work-up including lung biopsy, which confirmed pulmonary hemosiderosis. [mdpi.com]

  The lung biopsy obtained in patients who had hemoptysis showed an abnormal accumulation of hemosiderin in the lungs, which resulted in alveolar hemorrhage or PH [2]. [encyclopedia.pub]

  Severe cases may be complicated with PH, which should be suspected in the presence of anemia or hemoptysis and be confirmed with the demonstration of ILM. [pubmed.ncbi.nlm.nih.gov]

• Cough

  A 16-month-old girl was initially brought to her primary care physician because of persistent nonproductive cough of 1 to 2 weeks’ duration, with lethargy, poor feeding, and worsening cough for the past 36 hours. She had been afebrile. [contemporarypediatrics.com]

  Photoclinic A 16-month-old girl was initially brought to her primary care physician because of persistent nonproductive cough of 1 to 2 weeks’ duration, with lethargy, poor feeding, and worsening cough for the past 36 hours. She had been afebrile. [consultant360.com]

  There was associated cough and nasal discharge. No wheeze and no ear discharge. [ncbi.nlm.nih.gov]

  Clinical Characteristics Respiratory features of the disease included persistent cough, dyspnea, tachypnea, wheezing, occasional sputum production and rales. [encyclopedia.pub]

• Pneumonia

  Chest X-rays can show patchy infiltrates miming pneumonia. Clinical manifestations usually disappear after a milk-free diet. [moh-it.pure.elsevier.com]

  The peculiarity of pneumonia in these case series was the refractoriness of antibiotic treatments. [mdpi.com]

  It is characterised by recurrent respiratory tract symptoms, infiltrates mimicking pneumonia on chest radiograph, fever, anaemia and failure to thrive. [ncbi.nlm.nih.gov]

• Rhinitis

  However, his parents on a follow up outpatient visit affirmed to occasional cough and rhinitis whenever milk based diet was reintroduced and they were appropriately counselled on avoidance. [ncbi.nlm.nih.gov]

  Patients may have prolonged exposure to cow’s milk and a history of chronic rhinitis, recurrent otitis media, persistent cough, or failure to thrive. The immune-mediated response in Heiner syndrome is not completely understood. [consultant360.com]

  BAL IgG NS sIgE +ve yes doubtful, based on CH 13 Alsukhon, 2017 USA 1 2 FTT; recurrent diarrhea; persistent cough; tachypnea; high inflammatory markers yes (CXR) NS NS IgG4 NS sIgE –ve yes NS 14 Ojuawo, 2019 Nigeria 1 4 FTT; cough; dyspnea; wheeze; rhinitis [encyclopedia.pub]

  It is a disease characterised by failure to thrive, respiratory symptoms like cough, dyspnoea, wheeze and rhinitis with accompanying chest infiltrates on chest radiograph; gastrointestinal symptoms like vomiting, diarrhoea; and anaemia. [pubmed.ncbi.nlm.nih.gov]

• Dyspnea

  Clinical Characteristics Respiratory features of the disease included persistent cough, dyspnea, tachypnea, wheezing, occasional sputum production and rales. [encyclopedia.pub]

  The symptoms were in the form of cough in seven, wheezing in three, hemoptysis in two, nasal congestion in three, dyspnea in one, recurrent otitis media (OM) in three, recurrent fever in four, anorexia, vomiting, colic or diarrhea in five, hematochezia [pubmed.ncbi.nlm.nih.gov]

  Shortly after this, dyspnea significantly improved, and eosinophils decreased to 1%. Chest roentgenograms showed that pulmonary infiltrates cleared within 5 days (Figure 1c), and the CT scan was normal (Figure 1d). [frontiersin.org]

• Failure to Thrive

  Keywords: Cow milk proteins; Failure to thrive; Heiner syndrome; Hypersensitivity; Infant formula. © 2019 The College of Medicine and the Medical Association of Malawi. [pubmed.ncbi.nlm.nih.gov]

  It is characterised by recurrent respiratory tract symptoms, infiltrates mimicking pneumonia on chest radiograph, fever, anaemia and failure to thrive. [ncbi.nlm.nih.gov]

  Patients may have prolonged exposure to cow’s milk and a history of chronic rhinitis, recurrent otitis media, persistent cough, or failure to thrive. The immune-mediated response in Heiner syndrome is not completely understood. [consultant360.com]

  Clinically, gastrointestinal signs and symptoms, ane-mia, recurrent fever and failure to thrive can be also present. Chest X-rays can show patchy infiltrates miming pneumonia. Clinical manifestations usually disappear after a milk-free diet. [moh-it.pure.elsevier.com]

• Diarrhea

  A syndrome, comprised of chronic pulmonary disease, iron-deficiency anemia, recurrent diarrhea, and failure to thrive in the presence of precipitating serum antibodies against cow's milk, was described by Heiner, Sears, and Kniker (11) in 1962. [pubs.rsna.org]

  Gastrointestinal manifestations were reported in about half of the patients and included frequent vomiting or diarrhea. Rarely, lymph node hypertrophy with hepatomegaly, splenomegaly and hypertrophied tonsils or adenoids were labeled [8]. [encyclopedia.pub]

  PH in early infancy is associated with eosinophilia, elevated IgE levels, chronic nasal discharge, diarrhea, and upper airway obstruction.4 Tests for anti-GBM and c-ANCA antibodies are helpful in ruling out other causes of PH.5 Chest radiography may be [consultant360.com]

  The clinical history showed that the boy underwent a milk-free diet from the first to the tenth month of age because of suspected non-IgE-mediated CM non-bloody diarrhea. HS appeared at CM reintroduction. [mdpi.com]

• Hematemesis

  Mastouri M 32802736 2020 3 Heiner Syndrome: An uncommon cause of failure to thrive. 61 Ojuawo AB...Mokuolu OA 31839894 2019 4 A different clinical presentation of Heiner syndrome: The case of diffuse alveolar hemorrhage causing massive hemoptysis and hematemesis [malacards.org]

  The clinical presentations are variable in Heiner syndrome; the patient in Case 1 showed anemia and mild fever, while the patient in Case 2 exhibited hematemesis. [mdpi.com]

  A different clinical presentation of Heiner syndrome: The case of diffuse alveolar hemorrhage causing massive hemoptysis and hematemesis. Koc AS, Sucu A, Celik U. Koc AS, et al. [pubmed.ncbi.nlm.nih.gov]

• Vomiting

  Some patients with the condition have also been reported to have gastrointestinal symptoms such as anorexia, vomiting, diarrhoea, abdominal pain and bloody stools1,2. [ncbi.nlm.nih.gov]

  Gastrointestinal manifestations were reported in about half of the patients and included frequent vomiting or diarrhea. Rarely, lymph node hypertrophy with hepatomegaly, splenomegaly and hypertrophied tonsils or adenoids were labeled [8]. [encyclopedia.pub]

  The symptoms were in the form of cough in seven, wheezing in three, hemoptysis in two, nasal congestion in three, dyspnea in one, recurrent otitis media (OM) in three, recurrent fever in four, anorexia, vomiting, colic or diarrhea in five, hematochezia [pubmed.ncbi.nlm.nih.gov]

  Gastrointestinal manifestations were reported in about half of the patients and included frequent vomiting or diarrhea. Rarely, lymph node hypertrophy with hepatomegaly, splenomegaly and hypertrophied tonsils or adenoids were labeled [7]. [mdpi.com]

• Rectal Bleeding

  Similar articles Rectal bleeding in infancy: clinical, allergological, and microbiological examination. Arvola T, Ruuska T, Keränen J, Hyöty H, Salminen S, Isolauri E. Arvola T, et al. Pediatrics. 2006 Apr;117(4):e760-8. doi: 10.1542/peds.2005-1069. [pubmed.ncbi.nlm.nih.gov]

  Lymphonodular hyperplasia can also be a potential source of rectal bleeding of infants (6, 10), and infants with severe rectal bleeding should be undergo an enteroscope examination and biopsy. [frontiersin.org]

The atopy patch test in the diagnostic workup of suspected food-related symptoms in children. J Allergy Clin Immunol. 2006 Oct. 118(4):923-9. [Medline]. Boyce JA, Assa'ad A, Burks AW, Jones SM, Sampson HA, Wood RA, et al. [medscape.com]

• Pulmonary Infiltrate

  (B) Resolution of diffuse pulmonary infiltrates after 2 months of systemic corticosteroid treatment and cow’s milk restriction. (C) Recurrence of pulmonary infiltrate after cow’s milk provocation test. Table 1. [mdpi.com]

  Without treatment, PH can progress to pulmonary fibrosis and ultimately respiratory failure. Pulmonary disease caused by milk allergy may be a rare presentation but should be thought of in a child with recurrent infections and pulmonary infiltrates. [consultant360.com]

  After 2 yr of milk avoidance in one patient, milk challenge was tolerated for 2 months, and then the patient developed symptoms, serum milk precipitins, pulmonary infiltrate, and ILM. [pubmed.ncbi.nlm.nih.gov]

  The syndrome includes: rectal blood loss with hypochromic microcytic anemia pulmonary infiltrates (often recurrent) hypoproteinemia See also pulmonary hemosiderosis References Promoted articles (advertising) [radiopaedia.org]

• Microcytic Anemia

  The syndrome includes: rectal blood loss with hypochromic microcytic anemia pulmonary infiltrates (often recurrent) hypoproteinemia See also pulmonary hemosiderosis References Promoted articles (advertising) [radiopaedia.org]

  Laboratory studies showed a hemoglobin level of 3.8 g/dL and hypochromic microcytic anemia. The patient was subsequently transferred to the pediatric ICU for evaluation. [contemporarypediatrics.com]

  Laboratory studies showed a hemoglobin level of 3.8 g/dL and hypochromic microcytic anemia. The patient was subsequently transferred to the pediatric ICU for evaluation. On admission, the infant was pale and tachypneic. [consultant360.com]

Corticosteroids remain the first line of treatment. In more severe cases, immunosuppressive therapy with agents such as cyclophosphamide( may be indicated. Without treatment, PH can progress to pulmonary fibrosis and ultimately respiratory failure. [consultant360.com]

Corticosteroids remain the first line of treatment. In more severe cases, immunosuppressive therapy with agents such as cyclophosphamide may be indicated. Without treatment, PH can progress to pulmonary fibrosis and ultimately respiratory failure. [contemporarypediatrics.com]

His clinical course was uneventful and the corticosteroid dose was gradually tapered after the first month of treatment. However, he was re-admitted due to hemoptysis. [mdpi.com]

The diagnosis was further confirmed based on the positive response to the treatment and the elimination of milk. [frontiersin.org]

The peculiarity of pneumonia in these case series was the refractoriness of antibiotic treatments. [encyclopedia.pub]

PMID: 12839117 Prognosis Sabra A, Bellanti JA, Rais JM, Castro HJ, de Inocencio JM, Sabra S Ann Allergy Asthma Immunol 2003 Jun;90(6 Suppl 3):71-6. doi: 10.1016/s1081-1206(10)61664-x. PMID: 12839117 [ncbi.nlm.nih.gov]

The authors here emphasize the importance of the differential diagnosis of Heiner syndrome as the prognosis and management are different from those of IPH. [mdpi.com]

Patients with PH as a result of exposure to cow’s milk have a better prognosis than do those with other forms of hemosiderosis. [consultant360.com]

Patients with PH as a result of exposure to cow’s milk have a better prognosis than do those with other forms of hemosiderosis. References: REFERENCES: 1. Dearborn DG. Pulmonary hemorrhage in infants and children. [contemporarypediatrics.com]

PMID: 16176405 [The role of specific IgE to evolution and prognosis of cow's milk protein allergies in children]. Constantinide P, Trandafir LM, Burlea M. Constantinide P, et al. Rev Med Chir Soc Med Nat Iasi. 2011 Oct-Dec;115(4):1012-7. [pubmed.ncbi.nlm.nih.gov]

Crescentic glomerulonephritis in a child with Heiner syndrome. 61 Yavuz S...Anarat A 26388600 2014 7 Heiner syndrome mimicking an immune deficiency. 61 Sigua JA...Zacharisen M 24734417 2013 8 [Heiner syndrome in a case]. 61 Shi LF...Li J 21055273 2010 9 Etiology [malacards.org]

Discussion Diffuse alveolar hemorrhage or pulmonary hemosiderosis is a chronic disease in children with varied etiologies. [ijaai.in]

Etiology of hemoptysis in children: a single institutional series of 40 cases. Allergy Asthma Immunol Res. (2009)1:41–4. doi: 10.4168/aair.2009.1.1.41 PubMed Abstract | CrossRef Full Text | Google Scholar 3. [frontiersin.org]

Etiology Although HS is more likely to be induced by homogenized CM, the disease also may occur in some infants fed with CM-derived formula. [encyclopedia.pub]

Some clinical, epidemiological and immunological aspects. Høst A. Høst A. Pediatr Allergy Immunol. 1994;5(5 Suppl):1-36. Pediatr Allergy Immunol. 1994. PMID: 7704117 Review. [pubmed.ncbi.nlm.nih.gov]

Division of Biological Sciences, University of California, San Diego, La Jolla, California. d Department of Mathematics and Computer Science, University of Bremen, Bremen, Alemania. e Department of Biostatistics, Epidemiology, Biostatistics and Prevention [jacc.elsevier.es]

Food allergy: A review and update on epidemiology, pathogenesis, diagnosis, prevention, and management. J Allergy Clin Immunol 2018;141:41-58. 4. Moissidis I, Chaidaroon D, Vichyanond P, Bahna SL. [ijaai.in]

Epidemiology of food allergy. J Allergy Clin Immunol. 2011 Mar. 127(3):594-602. [Medline]. Gupta R, Warren C, Smith B, et al. Prevalence and Severity of Food Allergies Among US Adults. [medscape.com]

Articles related to Heiner Syndrome: (show all 11) # Title Authors PMID Year 1 Cow's Milk Protein Allergy in Term and Preterm Infants: Clinical Manifestations, Immunologic Pathophysiology, and Management Strategies. 61 33262206 2020 2 Diffuse alveolar [malacards.org]

Diverse non-IgE-based mechanisms have been postulated for its pathophysiology, but nothing is conclusive. We were able to demonstrate an IgE-mediated food hypersensitivity in an infant with Heiner's syndrome. [ijaai.in]

Food hypersensitivity and atopic dermatitis: pathophysiology, epidemiology, diagnosis, and management. J Allergy Clin Immunol. 1999 Sep. 104(3 Pt 2):S114-22. [Medline]. Burks AW, James JM, Hiegel A, et al. [medscape.com]

The pathophysiology of IPH has not been delineated, but the combination of genetic predisposition with environmental triggers such as toxin-producing fungus (Stachybotryschatarum) has been proposed [5,6]. [mdpi.com]

Centers for Disease Control and Prevention. Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2011. MMWR Morb Mortal Wkly Rep. 2011 Aug 26. 60(33):1128-32. [Medline]. [medscape.com]

Division of Biological Sciences, University of California, San Diego, La Jolla, California. d Department of Mathematics and Computer Science, University of Bremen, Bremen, Alemania. e Department of Biostatistics, Epidemiology, Biostatistics and Prevention [jacc.elsevier.es]

Food allergy: A review and update on epidemiology, pathogenesis, diagnosis, prevention, and management. J Allergy Clin Immunol 2018;141:41-58. 4. Moissidis I, Chaidaroon D, Vichyanond P, Bahna SL. [ijaai.in]

Early diagnosis is critical to initiate proper treatment and to prevent recurrent hemorrhagic episodes that lead to pulmonary fibrotic changes, and thus to increase the survival rate of affected patients. [mdpi.com]