Recurrent Bilateral Wunderlich Syndrome Following Hydroxyurea Therapy in Triple-Negative Myelofibrosis: The First Reported Case Suggesting an Immune-Mediated Vasculitic Mechanism
Materials and Methods/Case Presentation/Objective:
Case Presentation
A 58-year-old woman with intermediate-2 risk primary triple-negative MF was initiated on HU (500 mg/day) and low-dose aspirin. Sixty days after treatment initiation, she developed severe bilateral flank pain and gross hematuria. Contrast-enhanced abdominal computed tomography demonstrated bilateral intrarenal and perirenal hemorrhage without evidence of renal masses, angiomyolipoma, aneurysm, or vascular malformation. Aspirin was discontinued, supportive treatment was administered, and bleeding resolved without intervention. One month later, she experienced recurrent bilateral hemorrhage despite the absence of aspirin exposure. Laboratory evaluation showed marked neutrophilic leukocytosis and worsening anemia, whereas coagulation studies were not compatible with disseminated intravascular coagulation. During the second episode, purpuric skin lesions, positive antinuclear antibodies (1:160), and decreased complement C3 levels suggested an immune-mediated vasculitic process. Hydroxyurea was discontinued because of suspected drug-associated vascular injury. The patient initially recovered with conservative management but subsequently deteriorated and died from an undetermined cause.
Results/Description/Main Outcome Measure(s):
Results
Alternative causes of spontaneous renal hemorrhage, including structural renal pathology, vascular abnormalities, and consumptive coagulopathy, were excluded. The recurrence of bilateral hemorrhage after aspirin withdrawal, together with concomitant immunologic abnormalities and cutaneous vasculitic findings, supported HU-associated vascular injury as the most plausible explanation. Application of the Naranjo Adverse Drug Reaction Probability Scale yielded a score consistent with a probable adverse drug reaction. A structured literature review identified no previously published cases of HU-associated WS in patients with myelofibrosis or other myeloproliferative neoplasms.
Conclusion(s).:
Conclusion
This case expands the recognized spectrum of HU-related toxicities by describing the first reported association between HU therapy and recurrent bilateral WS in primary triple-negative MF. Clinicians should consider WS in HU-treated patients presenting with acute flank pain or gross hematuria, particularly when accompanied by cutaneous or serologic findings suggestive of immune-mediated vascular injury. Early recognition, prompt imaging, and timely discontinuation of HU may be critical to preventing recurrent hemorrhage and improving patient outcomes.
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