Autoimmune Myelofibrosis: A Case Review

In May 2013, the patient was admitted to the hospital due to fever. An infection workup was negative. The laboratory tests were consistent with Coombs-positive autoimmune hemolytic anemia. The serum lactate dehydrogenase (LDH) was 921 U/L: hapto­globin

Unfortunately, the patient was shortly readmitted with sepsis secondary to perineal cellulitis, pancytopenia and fevers. The decision was made to treat the patient with a course of IVIG 1 g/kg/infusion. Following the third dose, her cell counts started to improve (leukocyte count of 8,000/mm3; differential: neutrophils 87%; lymphocytes 7%; monocytes 2%; hemoglobin 10.4 g/dL; hematocrit 32%; platelet count 151/mm3). The patient was discharged home on a dose of prednisone 50 mg daily.

Discussion

AMF has been defined by the following criteria: Grade 3 or 4 reticulin fibrosis of the bone marrow, lymphocyte infiltration of the bone marrow, lack of osteosclerosis, absent or mild splenomegaly, presence of autoantibodies and the absence of a disorder known to be associated with myelofibrosis (e.g., lack of clustered or atypical megakaryocytes, myeloid or erythroid dysplasia, eosinophilia and basophilia).³ SLE seems to be the leading cause of AMF in the literature.1 It’s difficult to calculate the true incidence and prevalence of AMF. Mehta et al performed a database analysis and found that among the 1,753 patients diagnosed with a secondary myelofibrosis, 54 (3.1%) had SLE as their primary diagnosis.⁴ Wanitpongpun et al evaluated a cohort of 44 patients with SLE and cytopenias and found that 20 had bone marrow abnormalities, but only 5% had signs of myelofibrosis.⁵ The level of fibrosis can vary between patients. For example, Voulgarelis et al found mild to marginal signs of fibrosis (Bauermeister score 1+ and 2+) in 60% of patients (n=40) with cytopenias, while the remaining 40% presented with moderate to severe signs of fibrosis.⁶ The etiology for AMF is unknown. It’s believed that lymphocytes directly,⁷ or indirectly through immune complexes,⁸ stimulate megakaryocytes to secrete transforming growth factor β, vascular endothelial growth factor and fibroblast growth factor. These cytokines activate and stimulate fibroblasts to produce fibronectin, type IV collagen, chondroitin, dermatan and proteglycans. Glucocorticoids are the first-line treatment for AMF. A review of 17 patients with AMF and SLE by Kagenyama et al noted improvement in the 14 of 16 patients who received steroids.⁹ There is improvement in the appearance of the peripheral smear, and in the bone marrow, there may be a concomitant decrease or resolution of fibrosis.¹⁰ Due to lack of randomized controlled studies, the optimal dose of steroids is unknown.^11,12 The use of IVIG 2 g/kg divided over five days has shown good results.¹³ Splenectomy has also been reported to improve cytopenias.¹⁴ Our patient repeatedly responded to IVIG and varying doses of steroids including methylprednisolone pulse (1 g IV for three days) and maintenance dose of prednisone 20 mg. To date, we have been unable to completely discontinue the drug.