|LETTER TO EDITOR
|Ahead of print publication
Systemic lupus erythematosus presenting as autoimmune myelofibrosis and acquired hemophilia A
Mansoor C Abdulla
Department of General Medicine, M.E.S. Medical College, Perinthalmanna, Kerala, India
|Date of Submission||04-Oct-2020|
|Date of Acceptance||17-Dec-2020|
Mansoor C Abdulla,
Department of General Medicine, M.E.S. Medical College, Perinthalmanna - 679 338, Kerala
Source of Support: None, Conflict of Interest: None
Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease with variable multisystem involvement and heterogeneous clinical features, ranging from mild to life-threatening. Hematological abnormalities are common manifestations of this autoimmune disease. SLE can present with hematological manifestations alone or associated with features of involvement of other systems. Common hematological abnormalities in SLE include leukopenia, lymphopenia, thrombocytopenia, autoimmune hemolytic anemia, the antiphospholipid antibody syndrome, and thrombotic thrombocytopenic purpura. A 44-year-old woman who presented with two rare hematological manifestations of SLE-Autoimmune myelofibrosis (AIMF) and Acquired hemophilia A (AHA) simultaneously is presented here, which was not reported previously.
A 44-year-old woman was admitted with echymotic patches over right forearm for 2 months and bleeding gums for 3 weeks. She had menorrhagia for 8 months. She denied history of weight loss, had no sick contacts, and had no history of addictions. She had three children with no previous fetomaternal complications. She had hypothyroidism for 3 years and diabetes mellitus for 1 year (on glimipride and metformin). She had pallor and multiple echymotic patches over the right forearm. There were no other bleeding manifestations. Systemic examination was unremarkable.
Hemoglobin was 9.9 g/dl, total leukocyte count 5400/μl, platelet count 0.10 × 109/L, erythrocyte sedimentation rate 95, and CRP was normal. The hematocrit-corrected ESR level was 74 mm/h. In the peripheral smear, RBCs were normocytic, normochromic with no signs of hemolysis, white blood cell's were normal and platelet count was reduced [Figure 1]a. Direct coombs test was positive. Urinalysis was normal. Blood chemistries were normal except for high blood sugars and glycosylated hemoglobin. Prothrombin time was normal, and partial thromboplastin time was prolonged (86 s). Serum LDH was 338 IU/L. HIV, hepatitis B and hepatitis C serologies were negative. Bonemarrrow aspirate yielded a dry tap and trephine biopsy showed hypocellular marrow with no dysplastic features in any of the lineages, especially the megakaryocytes. Reticulin stain showed grade 1 marrow fibrosis [Figure 1]b, [Figure 1]c, [Figure 1]d.
|Figure 1: Peripheral smear showing severe thrombocytopenia (a). Bone marrow aspirate smear (dry tap) without marrow particles (b) and trephine biopsy showing hypocellular marrow with no dysplastic features in any of the lineages (c). Reticulin stain showing grade 1 marrow fibrosis (d)|
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The molecular biology analysis was negative for the JAK2-V617F, JAK2EXON 12, MPL-W515 L/K and CALR mutations. Anti-nuclear antibody (immunofluorescence method) was positive and anti-double-stranded DNA was strongly positive. C3 and C4 levels were low (43 mg/dl and 9 g/dl respectively). IgG and IgM APLA, IgG and IgM beta2 glycoprotein and lupus anticoagulant tests were negative. Coagulation tests revealed reduced factor VIII activity (2.6%) and factor VIII inhibitor was high (54 Bethesda units/ml).
This 44-year-old female who presented with bleeding manifestations had SLE with AIMF and acquired hemophilia. She was started on intravenous methylprednisolone 500 mg daily for 3 days followed by oral prednisolone 1 mg/kg and hydroxychloroquine. The platelet count improved after 5 days to 0.50 × 109/L. She had no further bleeding manifestations and a repeat bone marrow study after 3 months of steroids was normal. The repeat partial thromboplastin time was also normal. The follow-up complement levels were normal but anti-nuclear antibody and anti-double stranded DNA were still positive.
Hematologic manifestations are seen in 85% of patients with SLE. The common manifestations include: autoimmune hemolysis/leukopenia/thrombocytopenia, chronic inflammatory anemia, and anti-phospholipid syndrome.
Myelofibrosis (MF) in SLE patients can be either primary MF or autoimmune. The mechanisms underlying pathogenesis of AIMF remains poorly understood. Cytokine-dependent mechanisms is responsible for fibrosis in both AIMF and primary myelofibrosis (PMF); however, the predominant source of cytokines – including transforming growth factor beta, interferon gamma, interleukin 8 (IL-8), IL-2, IL-17, and lipocalin-2 – likely differs, with cytokines derived from lymphoid aggregates driving AIMF and those derived from megakaryocytes and platelets mediating fibrosis in PMF., Both AIMF and PMF presents with cytopenias, but PMF patients are more symptomatic. Splenomegaly is more common in patients with PMF. Peripheral blood leukoerythroblastosis, teardrop red blood cells, poikilocytosis, eosinophilia, and basophilia, are classic findings in PMF. The absence of atypical megakaryocytes in bonemarrow study is probably the most important criterion that helps to distinguish between AIMF and PMF. Clonality is a major distinguishing factor between PMF and AIMF. Mutations in the three driver genes (JAK2, CALR, and MPL) are found in 90% of cases of PMF. Our patient had features (clinical, laboratory and histopathological) of AIMF and showed good response to steroids. Literature review shows 46 cases of AIMF secondary to SLE.
AHA is an unusual disease resulting from autoantibodies against coagulation factor VIII and clinically manifests as bleeding. AHA should be suspected in patients who have spontaneous hemorrhagic events with an isolated prolonged activated partial thromboplastin time. A diagnosis of AHA can be made if the patient have reduced factor VIII activity, presence of factor VIII inhibitor, and a negative lupus anticoagulant. AHA as the presenting manifestation in SLE is extremely rare.,,
A patient with bleeding manifestations secondary to two rare hematologic complications (AIMF and AHA) in SLE together at the onset of disease is described here, which to our knowledge is the first such report.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
The author would like to thank Dr. Asik Siddique Professor, Department of Pathology, M.E.S. Medical College, Perinthalmanna for his valuable advice and help.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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