Association between idiopathic pulmonary hemosiderosis and celiac disease in pediatric patients: A scoping review of the literature over the past 50 years

Abstract

Introduction: Idiopathic pulmonary hemosiderosis (IPH) is a rare cause of diffuse alveolar hemorrhage, the mechanism of which is currently unknown. Nearly onethird of pediatric patients with IPH test positive for Celiac disease (CD) serology.Several hypothetical mechanisms have been proposed to unify the coexistence of these two entities, also referred to as Lane-Hamilton syndrome (LHS).Method: This manuscript is a scoping review of the medical literature. Medline, Embase, and PubMed Central databases were searched between 1971 and 2021 with appropriate search words to identify all cases of pediatric LHS.Results: A total of 20 manuscripts with 23 pediatric patients with LHS were identified. The mean age was 11 years, and 13/23 (56.5%) of the children were boys.Hemoptysis was present in 57% of patients during diagnosis. Bronchoscopy with bronchoalveolar lavage demonstrating hemosiderin laden macrophages was the primary mode of diagnostic confirmation. Only three patients underwent lung biopsy. Any significant GI symptom was reported in a minority of patients (22%). Iron deficiency anemia on presentation was described in 83% of children. The majority of patients were malnourished. Serology for CD was positive in all patients, as was the histopathologic analysis of the small bowel biopsy. No patients had any other autoantibody positivity. The introduction of gluten free diet (GFD) was associated with a positive response in 20/23 patients. Conclusion:All pediatric patients with IPH should undergo screening for CD. Low serum ferritin in patients with IPH could be suggestive of coexisting CD. Strict GFD should be tried as the initial therapy.

Comparative Analysis of Adult Patients With Idiopathic Pulmonary Hemosiderosis and Lane-Hamilton Syndrome: A Systematic Review of the Literature in the Period 1971-2022

“…Less than 20% of patients complained of any significant GI symptoms at the time of IPH diagnosis. Similar findings were also seen in pediatric patients with LHS [ 77 ]. Although malabsorption leading to developmental delay is common in children with LHS, this is rarely the case in adults [ 53 ].…”

“…The fact that the prevalence is so high in children and adults, and the number is significantly higher than the general population, raises concerns for unifying the underlying pathobiology of this co-occurrence. Several hypothetical mechanisms of DAH in CD have been considered, such as food allergen-induced immune-complex deposition, anti-reticulin antibody-mediated alveolar basement membrane damage, and molecular mimicry of an infectious pathogen [ 75 - 77 ]. However, there has never been any histopathologic proof to support any of them.…”

Hemosiderin‐laden macrophages in the bronchoalveolar lavage fluid of a 6‐year‐old girl

“…All paediatric patients with IPH should undergo screening for celiac disease. 3,4 Therefore, the identification of hemosiderin-laden macrophages from BALF specimens is suggestive, but not diagnostic, of IPH. Moreover, another study 5 reported a large number of hemosiderin-laden macrophages were also observed in the gastric lavage of an infant boy, which could lead to an early diagnosis of IPH.…”

“…This is due to the good prognosis associated with a gluten‐free diet. All paediatric patients with IPH should undergo screening for celiac disease 3,4 . Therefore, the identification of hemosiderin‐laden macrophages from BALF specimens is suggestive, but not diagnostic, of IPH.…”

The Spectrum of Autoantibodies in Adult Patients With Idiopathic Pulmonary Hemosiderosis: A Brief Review of the Literature

“…We have recently discussed the prevalence of autoantibodies in a cohort of adult IPH patients as reported in the literature [ 13 ]. Similar to pediatric patients, a majority of these patients had antibodies suggestive of celiac disease (CD), a combination known as Lane Hamilton syndrome (LHS) [ 12 , 14 , 15 ].…”