Migratory large vessel vasculitis preceding acute myeloid leukemia: a case report
© The Author(s). 2017
Received: 20 October 2016
Accepted: 12 February 2017
Published: 16 March 2017
Large vessel vasculitis is a rare disorder usually occurring in the context of the autoimmune conditions of giant cell arteritis and Takayasu’s arteritis. Case reports have described large vessel vasculitis occurring in individuals with myelodysplastic syndrome, preceding transformation to acute myeloid leukemia.
A 56-year-old Afghanistan-born woman presented with fever, a tender left carotid artery, and raised inflammatory markers. Computed tomography revealed thickening of the wall of her left carotid artery. Her symptoms resolved spontaneously; however, they recurred weeks later on the contralateral side, along with abdominal pain after eating. Further imaging with computed tomography and positron emission tomography demonstrated resolution of her left carotid artery abnormality, but new wall thickening and inflammation in her right carotid artery, abdominal aorta, and superior mesenteric artery. She was diagnosed as having large vessel vasculitis, which resolved with corticosteroids and methotrexate. Five months later, she developed acute myeloid leukemia. She had no known history of myelodysplastic syndrome at the time of diagnosis with vasculitis.
Large vessel vasculitis in older individuals presenting with atypical clinical features, such as a migratory pattern of affected vessels, vessel wall tenderness, and marked systemic inflammation, should prompt a search for underlying myelodysplasia. Clinicians should be vigilant for progression to acute myeloid leukemia.
KeywordsLarge vessel Vasculitis Acute myeloid leukemia AML Autoimmune Myelodysplasia MDS Migratory
Large vessel vasculitis is a rare condition characterized by inflammation within the walls of the aorta and its major branches. It can occur in a range of autoimmune disorders, including Takayasu’s arteritis (TA) and giant cell arteritis (GCA), and typically requires treatment with high doses of corticosteroids and other immunosuppressive agents. In the literature, there have been case reports of large vessel vasculitis occurring in individuals with myelodysplastic syndrome (MDS), some of whom have later developed acute myeloid leukemia (AML). We describe a patient with an atypical presentation of large vessel vasculitis, which was migratory in nature and accompanied by marked systemic inflammatory features. Unlike previous case reports, our patient did not have a prior diagnosis of MDS, but subsequently developed AML.
She was treated with methylprednisolone (500 mg daily for 3 days) administered intravenously with immediate resolution of her abdominal and neck pain and fevers. She was subsequently commenced on methotrexate 15 mg/week administered orally and prednisone 50 mg/day. She remained well over the following 5 months, with continuation of methotrexate, and her prednisone dose was gradually reduced to 15 mg/day.
We present a case of large vessel vasculitis with atypical features, including a migratory involvement of affected vessels and marked systemic inflammatory features, with subsequent progression to AML.
Large vessel vasculitis associated with MDS has rarely been described . In some cases, the diagnoses of MDS and large vessel vasculitis are made simultaneously, and in others, the MDS has been pre-existing. Our patient did not have a previous diagnosis of MDS before the development of vasculitis, and on presentation, had only minimally reduced hemoglobin (112 g/L). Over the following weeks, her peripheral blood neutrophil count fluctuated between normal and mildly reduced (1.4 to 3.4 × 109 cells/L), as did her monocyte count (0.5 to 1.8 × 109 cells/L); however, her platelet count remained normal. With high dose glucocorticoids, her neutrophil count rose to 6.0 × 109 cells/L; however, the absence of a steroid-induced neutrophilia may also suggest a degree of myelodysplasia. The mild monocytosis, although not specific in the context of inflammation, may have been significant, given that her subsequent AML blasts aberrantly expressed CD4, which is normally expressed on monocytes.
Large vessel vasculitis can occur in autoimmune disorders, including extracranial GCA and TA. Marked systemic inflammation may be a feature of TA, however this disorder classically affects individuals younger than 50 years of age [3, 4]. GCA, more frequently seen in older individuals, typically involves smaller vessels such as the temporal arteries, but can also affect the aorta and its major branches. The few reported cases of MDS-associated large vessel vasculitis presented in a similar manner to our patient: at an age >50 years, with acute inflammation, including tender vessels and a highly raised CRP [2, 5, 6], exceeding the median CRP of 52 mg/L in patients with temporal artery biopsy-proven GCA .
In one review, five of eight patients with MDS-associated large vessel vasculitis developed AML, often refractory, usually within a year of presentation with vasculitis . The timing of large vessel vasculitis preceding AML, and the unusual clinical features of acute inflammation with vessel wall tenderness and highly elevated inflammatory markers, suggest that the vasculitis in these patients may be a paraneoplastic phenomenon. The cytopenias in some forms of MDS may be immune mediated , with activated T cells inducing cytokine-mediated apoptosis of myeloid stem cells via tumor necrosis factor (TNF) and interferon gamma [5, 9]. Dysregulated immune mechanisms may thus be involved in the pathogenesis of MDS . The association between MDS and autoimmune phenomena, such as arthritis, vasculitis, and connective tissue diseases, is well recognized in the literature [11, 12]; however MDS-associated vasculitis more commonly affects small caliber vessels [11, 13, 14].
Although the vasculitis in our patient responded promptly to glucocorticoids, the subsequent emergence of AML raises the possibility that immunosuppression impaired the cytotoxic anti-tumor response, and thus unmasked the AML. The majority of cases of patients reported with both large vessel vasculitis and MDS, however, received no steroid-sparing agent, yet several still progressed to AML . In light of the poor prognosis when given corticosteroids, it is important to recognize the high risk of progression to AML in these individuals. Consideration may be given to simultaneous treatment for MDS, including azacitidine or even high intensity chemotherapy followed by allogeneic stem cell transplantation in selected patients with good performance status. A recent multicenter study confirmed that treatment with azacitidine in patients with both MDS and a systemic inflammatory or autoimmune disease appeared to have a positive effect on their inflammatory condition ; however, whether this treatment would reduce progression to AML in individuals with concurrent large vessel vasculitis is undetermined.
In summary, we present a 56-year-old woman with a large vessel vasculitis with migratory features, vessel wall tenderness, and marked systemic inflammation, who subsequently developed AML. Large vessel vasculitis with atypical clinical features in older individuals should prompt a search for underlying myelodysplasia, and vigilance for progression to AML.
Acute myeloid leukemia
Giant cell arteritis
Human leukocyte antigen-antigen D related
Internal tandem duplication
Mean corpuscular volume
Positron emission tomography
Tumor necrosis factor
We acknowledge Dr Maansi Joshi (Department of Haematology, Westmead Hospital, NSW Australia) for providing the bone marrow aspirate images.
Availability of data and materials
DC, AA, WB, MV, and LJB were involved in patient care. DC, AA, and LJB wrote the manuscript. All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
Consent for publication
Written informed consent was obtained from the patient’s next-of-kin for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
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