Capillary Fragility in Zika Virus Infection
A 42-year-old Hispanic woman with no known medical history presented to the hospital with subjective fevers, rash, and arthralgias 5 days after returning to the US from Honduras. She reported multiple mosquito bites while abroad and noted that many relatives had similar symptoms over the preceding weeks. On arrival to the Emergency Department, her temperature was 36.78°C (98.2°F), blood pressure 110/72 mm Hg, and heart rate 66 beats/min. Examination was notable for a diffuse maculopapular rash on the trunk and extremities that spared the palms and soles, scattered petechiae in the upper palate, and mild synovitis in the metacarpophalangeal and proximal interphalangeal joints bilaterally. Laboratories including complete blood counts, electrolytes, creatinine, liver function tests, coagulation studies, complements, rheumatoid factor, and antinuclear antibodies were normal. Chest x-ray and urinalysis were similarly unremarkable. Given the patient’s recent travel history, reported mosquito bites, and clinical presentation, suspicion for an arbovirus infection was high. Serologic testing revealed positive Zika virus immunoglobulin M and Zika virus plaque-reduction neutralization assays (>1:40,960). Dengue and Chikungunya immunoglobulin M antibodies were negative. Urine pregnancy test was negative.
An interesting feature of the case we would like to highlight is a physical examination finding noted incidentally during the patient’s transfer from the Emergency Department to the medical observation floor. When the blood pressure cuff was removed from her arm after routine and normal measurements, linear petechial streaks were seen in the cuff distribution (Figure). This phenomenon, known as the Rumpel-Leede sign, can be seen in hypertensive patients who undergo prolonged continuous blood pressure monitoring.1 However, it has also been described in cases of dengue infection, regardless of platelet count,2 and in cases of Chikungunya,3 which rarely causes thrombocytopenia. When associated with the aforementioned arbovirus infections, the phenomenon has been attributed to an immunologic response leading to capillary fragility. The release of cytokines, particularly tumor necrosis factor alpha, is thought to disrupt adherens junctions on endothelial cells, undermining capillaries’ mechanical integrity.4 Subsequently, capillaries rupture and form petechiae in areas of high pressure, such as beneath linear folds of the blood pressure cuff or distally in the antecubital area. The Rumpel-Leede sign in our patient with Zika virus infection may indicate a similar pathophysiologic mechanism. Clarifying this mechanism may help elucidate the pathogenesis of manifestations of Zika virus infection. In the meantime, the finding could serve as a diagnostic clue, particularly if subsequent reports confirm and strengthen the association. Our patient received supportive care, noted rash resolution and synovitis improvement, and was discharged home after overnight observation.
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-Shradha A. Kulkarni, MD, Evan Strobelt, BA, Zaven Sargsyan, MD
This article originally appeared in the February 2017 issue of The American Journal of Medicine.