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Prevalence of autoantibodies in pediatric patients with idiopathic pulmonary hemosiderosis: a scoping review of the literature in the period 1980–2021

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Abstract

Idiopathic pulmonary hemosiderosis (IPH) is a rare disease of unknown etiology. Due to the frequent findings of autoimmune antibodies — autoantibodies, immunologic causation of the diffuse alveolar hemorrhage in IPH has been proposed, to assess the prevalence/frequency and type of autoantibodies in pediatric patients with IPH. In addition, the patient demographics, diagnostic modalities used to diagnose IPH, treatment, and outcomes were also evaluated. Scoping review: The PubMed, Medline, and Embase databases were searched with appropriate MeSH terms to identify relevant papers consistent with the defined inclusion criteria. Thirteen observational studies comprising a total of 352 pediatric patients were included in this review. The majority of subjects were girls 217 out of 352 (61.6%). The mean and median ages of patients ranged from 3.1–6.5 years to 2.3–7 years, respectively. In the 10 studies that specified the number of patients in their cohorts with either at least one positive autoantibody or no antibody, the overall prevalence of autoantibodies was 76 out of 288 patients (26.4%). The prevalence of specific antibodies was as follows: ANA, 20.3%; ANCA, 17%; anti-dsDNA, 9.1%; RF, 12%; anti-SMA, 23.2%; and celiac antibodies, 25.9%. Cow’s milk protein allergy was present in 16.2% of the children. The significance of an association between IPH and the presence of autoantibodies has not been clarified. The autoantibodies could be suggestive of an overall immune dysregulation rather than causation. However, limited evidence based on a single study suggests that the presence of ANA may be associated with a higher risk of recurrence and worse outcomes. Further research, including prospective studies, will be crucial to explore a possible genetic linkage between vasculitides, systemic rheumatologic diseases, and IPH.

Key Points

• Approximately one in four pediatric patients with IPH demonstrate autoantibodies.

• Antibodies suggestive of celiac disease are the most prevalent autoantibody.

• The presence of antinuclear autoantibody may be associated with unfavorable outcomes.

• All patients with a positive ANCA demonstrated anti-myeloperoxidase (MPO-ANCA) antibody.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

AAV:

ANCA-associated vasculitis

ANA:

Antinuclear antibody

ANCA:

Antineutrophil cytoplasmic antibody

BAL:

Bronchoalveolar lavage

CCP:

Cyclic citrullinated peptide

DAH:

Diffuse alveolar hemorrhage

dsDNA:

Double-stranded DNA

ELISA:

Enzyme-linked immunosorbent assay

IIF:

Indirect immunofluorescence assay

IPH:

Idiopathic pulmonary hemosiderosis

MPO:

Myeloperoxidase

PR3:

Proteinase 3

RF:

Rheumatoid factor

SMS:

Smooth muscle antibody

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Authors and Affiliations

  1. Division of Pulmonary and Critical Care Medicine, Ozarks Medical Center, 1100 Kentucky Avenue, West Plains, MO, 65775, USA

    Biplab K. Saha

  2. Goldfarb School of Nursing at Barnes-Jewish College, Saint Louis, MO, USA

    Alyssa Bonnier

  3. Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, Saint Louis, MO, USA

    Praveen Chenna

  4. Department of Clinical Biochemistry, Næstved Hospital, University College Zealand, 4700, Næstved, Denmark

    Nils T. Milman

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BKS and AB were involved in the planning and collection of data. BKS, AB, and PC analyzed the data and prepared the initial manuscript. NTM supervised the preparation of the initial manuscript. All authors contributed in the finalization of the manuscript.

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Saha, B.K., Bonnier, A., Chenna, P. et al. Prevalence of autoantibodies in pediatric patients with idiopathic pulmonary hemosiderosis: a scoping review of the literature in the period 1980–2021. Clin Rheumatol 41, 977–990 (2022). https://doi.org/10.1007/s10067-021-06029-3

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