By Dean L. Winslow, MD, FACP, FIDSA

Professor of Medicine, Division of General Medical Disciplines, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine

Dr. Winslow reports no financial relationships relevant to this field of study.

SYNOPSIS: Researchers reviewed 19 cases of meningoencephalitis associated with spotted fever rickettsioses. Fever was present in all cases. Rash was present in 100% of pediatric patients but in only 50% of adult patients. Cerebrospinal fluide pleocytosis was present in 88% of patients. Ninety percent of patients required ICU admission, and only 46% of patients recovered completely.

SOURCE: Bradshaw MJ, Carpenter Byrge K, Ivey KS, et al. Meningoencephalitis due to spotted fever rickettsioses, including Rocky Mountain spotted fever. Clin Infect Dis 2019; doi:10.1093/cid/ciz776. [Epub ahead of print].

Nineteen patients (11 children and eight adults) met the criteria for spotted fever rickettsioses encephalitis. Patients were identified through hospital laboratory-based surveillance or through the Tennessee Unexplained Encephalitis Study. Chart reviews were conducted for cases that met inclusion criteria; when available, independent reviews of the neuroimaging were performed.

Rash was significantly more common in children than in adults (100% vs. 50%), but other clinical features were similar between the two groups. One-third of patients had no history of tick exposure. Cerebrospinal fluid (CSF) pleocytosis and protein elevation each were present in 87.5% of cases; hypoglycorrhachia was found in 18.8% of cases. Leukocytosis and mild thrombocytopenia were common.

Mild elevations of serum transaminases were present in all but one case. CSF pleocytosis was mild (median 41 cells/µL), and neutrophil predominance was present in one-third of cases. Median CSF protein was 83 mg/dL, and mild hypoglycorrhachia was seen in a few cases. The starry sky sign (multifocal, punctate diffusion restricting or T2 hyperintense lesions) was noted on MRI in all children, but it was not seen in any adult patients.

Ninety percent of patients required ICU admission, and 39% were intubated. The outcomes were similar between adults and children, with only 46% of patients making a complete recovery by discharge. Late deaths due to disease occurred, and many patients who survived were left with significant residual neurological deficits.

COMMENTARY

This is a very important paper that reminds clinicians to always consider rickettsial infection in the differential diagnosis of meningoencephalitis in areas where rickettsioses are common, and especially in febrile patients during the warmer months. Considering rickettsial disease is particularly important in febrile patients with or without meningoencephalitis, even in patients without a history of a tick bite and in those without a rash. Doxycycline should be started empirically in both adults and children with febrile illnesses who are at risk for rickettsial disease. (Doxycycline is a relatively weak chelating agent compared to older tetracyclines and, with short courses, it is unlikely to cause dental discoloration in children.) Importantly, serology can be negative at initial presentation. Confirmation of diagnosis often can be made by repeating convalescent serology at two weeks.

Although the patients reported in this case series may have been sicker than those with Rocky Mountain spotted fever without clinical evidence of encephalitis, it is also telling that doxycycline was not initiated until seven to eight days after the onset of fever in these patients, and likely contributed to the poor outcome. Interestingly, pediatricians started empiric doxycycline on the day of admission in all of their patients. However, adult patients in this study did not receive doxycycline until a median of three days after admission.