Dengue triggered fatal case of HLH in Texas woman

A patient who developed hemophagocytic lymphohistiocytosis and later died was found to have dengue virus infection on a postmortem bone marrow biopsy, CDC investigators reported in MMWR.

On Sept. 2, 2012, a 63-year-old women presented to a clinic in Texas with a history of fatigue, anorexia, headache, hematuria and leg pain. She was febrile, hypotensive and had low oxygen saturation; laboratory testing revealed leukopenia. Two days later, the patient visited her primary care physician for continued symptoms, and a West Nile virus serology was weakly positive.

On Sept. 22, the woman visited the ED for persistent symptoms, where she was found to be hypotensive, tachycardic, afebrile and had low oxygen saturation. Laboratory testing revealed thrombocytopenia and anemia, as well as acute liver injury. On physical examination, she had icteric sclerae. She was transferred to inpatient care.

During the hospital stay, she developed bibasilar posterior respiratory crackles on day 3. After insertion of a central venous catheter, she developed pitting pedal edema, wheezing with productive cough and bleeding from the site of catheter insertion. The serum ferritin and partial thromboplastin time were increased, and the serum fibrinogen was decreased.

On day 5, she had fever, tachypenia, neutropenia and elevated liver enzymes. Chest radiography showed infiltrates with opacity in the lower lobe of the left lung, and titers for antinuclear antibodies and rheumatoid factor were positive. At this point, the presumptive diagnosis was virus-induced hemophagocytic lymphohistiocytosis (HLH).

During the next 7 days, she developed bilateral pleural effusions, splenomegaly, anasarca, hemoptysis and watery diarrhea with blood. A liver biopsy revealed fulminant hepatitis, and the West Nile virus serology was weakly negative. She began interferon treatment and hemodialysis because of kidney failure, and then she was intubated because of respiratory distress.

The patient was diagnosed with severe metabolic acidosis and volume overload and died Oct. 3. Liver and bone marrow biopsies were sent to the CDC and underwent further testing. On Nov. 7, the CDC confirmed dengue virus type 3 (DENV-3).

An epidemiologic investigation found that the patient had traveled with her husband from Texas to Santa Fe, N.M., on Aug. 1, where they spent a lot of time outdoors. She and her husband returned to Texas on Aug. 28. Four other people traveled with the couple, and all four, as well as the husband, had no evidence of recent or past dengue infection. Among the 18 people in Texas who donated blood that was given to the patient, 17 were contacted and none reported a fever. Fourteen of the donors provided serum for testing, and none had evidence of recent or past dengue infection.

“Clinicians and public health professionals in the United States should be vigilant for and report cases of travel-associated and locally acquired dengue and request that both molecular and serologic diagnostics be performed in suspected cases,” the investigators wrote. “Clinicians in areas with endemic dengue should be aware of HLH as a potential complication of dengue and of the recommended HLH treatment regimen.”

Disclosure: The researchers report no relevant financial disclosures.

A patient who developed hemophagocytic lymphohistiocytosis and later died was found to have dengue virus infection on a postmortem bone marrow biopsy, CDC investigators reported in MMWR.

On Sept. 2, 2012, a 63-year-old women presented to a clinic in Texas with a history of fatigue, anorexia, headache, hematuria and leg pain. She was febrile, hypotensive and had low oxygen saturation; laboratory testing revealed leukopenia. Two days later, the patient visited her primary care physician for continued symptoms, and a West Nile virus serology was weakly positive.

On Sept. 22, the woman visited the ED for persistent symptoms, where she was found to be hypotensive, tachycardic, afebrile and had low oxygen saturation. Laboratory testing revealed thrombocytopenia and anemia, as well as acute liver injury. On physical examination, she had icteric sclerae. She was transferred to inpatient care.

During the hospital stay, she developed bibasilar posterior respiratory crackles on day 3. After insertion of a central venous catheter, she developed pitting pedal edema, wheezing with productive cough and bleeding from the site of catheter insertion. The serum ferritin and partial thromboplastin time were increased, and the serum fibrinogen was decreased.

On day 5, she had fever, tachypenia, neutropenia and elevated liver enzymes. Chest radiography showed infiltrates with opacity in the lower lobe of the left lung, and titers for antinuclear antibodies and rheumatoid factor were positive. At this point, the presumptive diagnosis was virus-induced hemophagocytic lymphohistiocytosis (HLH).

During the next 7 days, she developed bilateral pleural effusions, splenomegaly, anasarca, hemoptysis and watery diarrhea with blood. A liver biopsy revealed fulminant hepatitis, and the West Nile virus serology was weakly negative. She began interferon treatment and hemodialysis because of kidney failure, and then she was intubated because of respiratory distress.

The patient was diagnosed with severe metabolic acidosis and volume overload and died Oct. 3. Liver and bone marrow biopsies were sent to the CDC and underwent further testing. On Nov. 7, the CDC confirmed dengue virus type 3 (DENV-3).

An epidemiologic investigation found that the patient had traveled with her husband from Texas to Santa Fe, N.M., on Aug. 1, where they spent a lot of time outdoors. She and her husband returned to Texas on Aug. 28. Four other people traveled with the couple, and all four, as well as the husband, had no evidence of recent or past dengue infection. Among the 18 people in Texas who donated blood that was given to the patient, 17 were contacted and none reported a fever. Fourteen of the donors provided serum for testing, and none had evidence of recent or past dengue infection.

“Clinicians and public health professionals in the United States should be vigilant for and report cases of travel-associated and locally acquired dengue and request that both molecular and serologic diagnostics be performed in suspected cases,” the investigators wrote. “Clinicians in areas with endemic dengue should be aware of HLH as a potential complication of dengue and of the recommended HLH treatment regimen.”

Disclosure: The researchers report no relevant financial disclosures.