Primary autoimmune myelofibrosis: A case report in a child

Abstract Autoimmune myelofibrosis (AIMF) is an uncommon cause of myelofibrosis associated with favorable outcome. Primary AIMF, AIMF without a known systemic autoimmune disorder, has been described in adults, but never in children. Here, we present, for the first time, an apparent case of primary AIMF in a 15‐year‐old boy admitted with profound hypoproliferative anemia.


INTRODUCTION
Autoimmune myelofibrosis (AIMF) is a rare entity that manifests by autoimmune phenomena, bone marrow fibrosis (BMF), cytopenias, and minimal or no splenomegaly. It is classified into primary AIMF when autoantibodies are found in the absence of a known systemic autoimmune disorder and secondary when is associated with an established autoimmune disease. The pathophysiology of AIMF is poorly understood, however, immune dysregulation is known to play a pivotal role.
Hence, the treatment of choice is immunosuppressive therapy.

CASE REPORT
A 15-year-old boy presented to his general practitioner in August 2018 complaining of headaches that worsened with physical activity and severe pallor was observed. A complete blood count (CBC) revels; normocytic anemia (hemoglobin = 5.9 g/dL, mean corpuscular volume [MCV] = 78 fL, and 1% of reticulocyte) and the patient was referred to his local hospital.
The patient's previous medical history included bilateral sensorineural and conductive hearing loss diagnosed during childhood,

DISCUSSION
Hypoproliferative or central origin anemia, characterized by an inap- AIMF is a benign and rare entity characterized by cytopenias, autoimmune phenomena, BMF, and minimal or no splenomegaly [4,5]. Primary AIMF refers to patients that present autoantibodies in the absence of an identifiable systemic autoimmune disorder [4].
When AIMF is found in association with systemic lupus erythematosus or other established autoimmune conditions, it is termed secondary AIMF. No pediatric cases of primary AIMF have been reported; however, several adult cases have been published [6,7]. and (8) absence of a disorder known to cause myelofibrosis [8,9].
Although the pathophysiology of AIMF is poorly understood, aberrant cytokine production has been described as having a pivotal role.
Harrison and colleagues [10] reported increased serum levels of transforming growth factor beta and substance P in an AIMF patient, which Immunosuppressive agents, especially prednisone, are the main treatment for primary AIMF with rapid improvement in most cases [6][7][8], as in ours case. Patients who fail to respond to corticosteroids may benefit from other immunosuppressive modalities. Despite recovery from cytopenia, in some cases BMF does not resolve, suggesting that the pathogenesis independently leads to altered hematopoiesis, in addition to induction of fibrosis [8].
To the best of our knowledge, no case reports of presumed primary AIMF in children have been published, and therefore, the long-term prognosis of these patients remains unknown.
In conclusion, primary AIMF is a rare disease in adults; the present case study appears to be the first description of a pediatric case.
This condition requires meticulous clinical assessment, including a high degree of suspicion of autoimmune etiology. Additional studies are needed to shed more light on the effect of aberrant cytokine production on primary AIMF, and define its clinical picture and natural history, particularly in children.

ACKNOWLEDGMENTS
Dr Levin treated the patient, elaborated the differential diagnosis, reviewed, and revised the manuscript. Drs Hexner-Erlichman and Yacobovich drafted the initial manuscript, and reviewed and revised the manuscript. Dr Spiegel reviewed and revised the manuscript.
Drs Trougouboff, Avraham-Kelbert, Eitam, and Yeganeh performed and wrote specific analysis and revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

CONFLICT OF INTEREST
The authors declare that there is no conflict of interest.

CONSENT TO PUBLISH
The participant's parents have consented to the submission of the case report to the journal.

DATA SHARING STATEMENT
We shall share information concerning patient's history, physical examination, imaging studies, and laboratory studies. The appropriate consent to participate and publish has been described as well.