Abstract
We report a case of a 34‐year‐old woman with systemic lupus erythematosus (SLE) who developed thrombocytopenia and was diagnosed with lupus‐associated autoimmune myelofibrosis. She was treated with hydroxychloroquine, tofacitinib (5 mg twice daily), intravenous Ig, and prednisone (5 mg twice daily, tapered to 5 mg daily after one month). After 10 months of this regimen, her bone marrow showed complete resolution of myelofibrosis. This case highlights the effectiveness of tofacitinib in the treatment of autoimmune myelofibrosis associated with SLE.
Introduction
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder that affects multiple organs and tissues. Hematologic manifestations are common in SLE, often presenting as autoimmune peripheral cytopenia, including anemia, leukopenia, and thrombocytopenia. However, autoimmune myelofibrosis, a rare cause of cytopenia, can also occur in patients with SLE. In autoimmune myelofibrosis, peripheral blood cytopenia often shows a partial or complete response to glucocorticoid therapy. However, the underlying bone marrow fibrosis, a hallmark of myelofibrosis, may not fully regress with steroid treatment alone, leaving patients with persistent hematologic abnormalities. 1
On the other hand, JAK inhibitors, including tofacitinib, have demonstrated promise as treatments for SLE. Tofacitinib, a selective JAK1/3 inhibitor, has been shown to reduce cholesterol levels, improve vascular function, and decrease the type I interferon signature, a key pathogenic factor in SLE. 2 These effects suggest that tofacitinib may have broader immunomodulatory properties that could also address the underlying immune dysregulation in lupus‐associated autoimmune myelofibrosis. Given the potential therapeutic benefits of tofacitinib in managing SLE and its plausible effects on hematologic manifestations, there is a strong rationale to explore its use in lupus‐associated autoimmune myelofibrosis; therefore, this study aimed to investigate the efficacy and safety of tofacitinib in the successful management of lupus‐associated autoimmune myelofibrosis.
Case report
A 34‐year‐old woman with a history of lupus presented with severe joint pain and stiffness in both hands, along with a platelet count of 40,000 cells/μL and petechiae on her lower limbs. Further investigations revealed mild megakaryocytic hyperplasia, lymphoid aggregates, and grade 3 reticulin fibrosis in the bone marrow aspiration. She was diagnosed with thrombocytopenia and lupus‐associated autoimmune myelofibrosis. Treatment included hydroxychloroquine, tofacitinib, intravenous Ig (IVIG) (40 g), and prednisone. Hydroxychloroquine was prescribed at a dose of 200 mg daily, tofacitinib at 5 mg twice daily, and prednisone at 5 mg twice daily, which was tapered to 5 mg daily after one month. After 10 months of combination therapy, bone marrow evaluation showed complete resolution of myelofibrosis.
Figure 1 shows sections show bone trabeculae and marrow spaces. Marrow is hypercellular with megakaryocytic preponderance.
Figure 1.
Shows sections show bone trabeculae and marrow spaces. Marrow is hypercellular with megakaryocytic preponderance. (A) In reticulin stain, reticulin fibrosis is evident. Trichrome stain is negative (40X). (B) Reticulin and trichrome stains are negative (10X, and 40X).
Laboratory results for diagnostic criteria of disease were as follows:
Anti‐Smith, positive; anti‐RNP, negative; anti‐SSA (Ro), negative; and anti‐SSB (La), negative
Complement C4 value, 8 mg/dL (reference range 10–40 mg/dL)
Complement C3 value, 70 mg/dL (reference range 90–80 mg/dL)
Anti‐dsDNA antibody result, positive; value, 45 IU/mL (reference range <30 IU/mL)
Antinuclear antibody result, positive; titer, 1:320; pattern, homogeneous
Discussion
There are several treatment options available for management of lupus‐associated autoimmune myelofibrosis. Previous treatments for lupus‐associated autoimmune myelofibrosis have focused on steroids and immunosuppressive therapies. These include high‐dose glucocorticoids, mycophenolate mofetil, IVIG, methylprednisone, prednisone, hydrocortisone, and combinations of these several drugs. 3 Other therapies have focused on the combination of glucocorticoids with cyclosporine. 4
In this study, the patient was treated with a combination of hydroxychloroquine, tofacitinib, and prednisone. After 10 months of this therapy, her myelofibrosis completely resolved. The key difference between our study and other research lies in the dosage of prednisone.
We administered a very low dose of prednisone and found that the therapeutic efficacy was primarily attributed to tofacitinib, which had not been extensively studied in this specific context. However, other studies have relied on significantly higher doses of prednisone, including 60 mg/day in the treatment of lupus‐associated autoimmune myelofibrosis. 5
Therefore, our findings show tofacitinib as a novel therapeutic approach for lupus‐associated autoimmune myelofibrosis and suggest a potential role for JAK inhibitors in managing this rare and challenging condition. Further studies are necessary to evaluate the efficacy and safety of tofacitinib as well as other JAK inhibitors for this disease.
AUTHOR CONTRIBUTIONS
All authors contributed to at least one of the following manuscript preparation roles: conceptualization AND/OR methodology, software, investigation, formal analysis, data curation, visualization, and validation AND drafting or reviewing/editing the final draft. As corresponding author, Dr Soltani confirms that all authors have provided the final approval of the version to be published, and takes responsibility for the affirmations regarding article submission (eg, not under consideration by another journal), the integrity of the data presented, and the statements regarding compliance with institutional review board/Declaration of Helsinki requirements.
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Supporting information
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Hamidreza Soltani, MD, Ali Dehghan, MD: Department of Rheumatology, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Author disclosures are available at https://onlinelibrary.wiley.com/doi/10.1002/acr2.70017.
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