Zhang, Jason BA; Pau, Derrick MD; Lee, Andrew G. MD
Department of Ophthalmology (JZ, DP, AGL), The Methodist Hospital, Houston, Texas
Departments of Ophthalmology, Neurology, and Neurosurgery (AGL), Weill Cornell Medical College, New York, New York; University of Iowa Hospitals and Clinics, Iowa City, Iowa; and The University of Texas Medical Branch, Galveston, Texas.
The authors report no conflicts of interest.
Address correspondence to Andrew G. Lee, MD, Department of Ophthalmology, Methodist Hospital, 6560 Fannin Street, Scurlock 450, Houston, TX 77030; E-mail: firstname.lastname@example.org
Abstract: Endemic typhus (Rickettsia typhi), also known as murine typhus, is a flea-borne bacterial disease rarely found in most of the developed world. Known ocular manifestations linked to endemic typhus include mild vitritis, retinal lesions, and retinal vascular leakage. Optic neuropathy, however, is rarely associated with R. typhi, and postinfectious optic neuropathy is even less common. To highlight this unusual complication, we report a patient who developed postinfectious optic neuropathy a few weeks after he was successfully treated for endemic typhus.
Endemic typhus (Rickettsia typhi), also known as murine typhus, is a flea-borne bacterial disease rarely found in most of the developed world (1). Known ocular manifestations linked to endemic typhus include vitritis, retinal lesions, and retinal vascular leakage (2–4). Optic neuropathy is rarely associated with R. typhi, and postinfectious optic neuropathy is even less common. To highlight this unusual complication, we report a patient who developed postinfectious optic neuropathy a few weeks after he was successfully treated for endemic typhus.
A 63-year-old white man was hospitalized 2 months prior to his visual symptoms for serologically confirmed endemic typhus (Rickettsia typhi). During that hospitalization, he had high fever, a diffuse maculopapular rash, and delirium. He subsequently developed hepatic and renal failure, meningoencephalitis, and pancytopenia secondary to hemophagocytosis. Extensive testing for infectious, inflammatory, and infiltrative etiologies was negative except for R. typhi titers for IgM (1:8192) and IgG (1:256). The patient received a 2-week regimen of doxycycline and was discharged after he completely recovered from his multiorgan failure, with a return to baseline of his laboratory abnormalities. Three weeks later, the patient presented to the emergency room with acute painless visual loss in the right eye. He had no other significant medical history.
On neuro-ophthalmic examination, the patient was afebrile, with visual acuity of 20/800, right eye, and 20/25, left eye. There was a right relative afferent pupillary defect (RAPD). Slit-lamp biomicroscopy showed no anterior uveitis. Extraocular movements, external examination, and intraocular pressures were normal. Ophthalmoscopy revealed mild vitritis and optic disc edema in the right eye (Fig. 1) while the left fundus was normal. The left optic disc had a cup-to-disc ratio of 0.3. Automated visual fields (10-2) showed a central scotoma and the mean deviation (MD) of −11.38 dB on the right eye while the left visual field was normal. Fluorescein angiography showed mild right optic disc leakage.
Repeat serological testing for R. typhi showed an IgM titer of 1:256 and IgG titer of 1:512. MRI of the brain and orbits showed no optic nerve or meningeal enhancement. Cerebrospinal fluid analysis was unremarkable. The patient was treated with systemic doxycycline and a tapering course of intravenous corticosteroids. Three months later, his visual acuity was 20/200 in the right eye. The right optic disc was pale (Fig. 2), and optical coherence tomography of the right eye showed decreased peripapillary retinal nerve fiber layer thickness of 70 μm (normal: 100 ± 10 μm). Repeat right visual field testing (automated 24-2) demonstrated an MD of −0.74 dB, with reduction in the size and density of the central scotoma.
The ocular manifestations of endemic typhus previously have been described, and retinal abnormalities predominate (2–4). In a prospective study of 9 patients (2), the most common ocular findings were vitritis (55.6%), white retinal lesions (50%), and retinal vascular leakage (38.9%). Symptoms were largely bilateral and often accompanied by choroidal involvement. One patient presented with left optic neuritis associated with a sudden decrease in vision to 20/40, a left RAPD, and a swollen optic disc. Over an 8-week period, vision improved to 20/25 and the left disc became pale. While the patient was asymptomatic in the right eye, white retinal lesions and retinal vascular leakage were noted in that eye.
While previous reports mainly documented rickettsia-associated ocular manifestations in the context of active infection, our patient is unusual in that his visual symptoms developed weeks after recovery from the acute illness. He presented with mild vitritis without evidence of chorioretinal abnormalities. The absence of these findings suggests a different pathogenesis in the postinfectious state or possibly these fundus abnormalities had resolved by the time of examination. Our case is also atypical in the severity of the vision loss. In previous endemic typhus cases, ocular changes were mostly asymptomatic (2–4). In the report by Khairallah et al (2), only 3 of 9 patients had ocular complaints with visual acuity ranging from 20/20 to 20/40.
The exact mechanism of endemic typhus–associated optic neuropathy is unknown but is likely on an immune basis. It has been speculated that retinal manifestations arise from rickettsia-induced deposition of intraretinal immune complexes and inflammatory cells (2). Repeat serological tests in our patient were positive for R. typhi, and falling convalescent IgM titers make recrudescent typhus (Brill-Zinsser disease) unlikely. In addition, the timing of visual loss in our patient supports an immunological mechanism. Treatment of postinfectious optic neuropathy with high-dose corticosteroids appears reasonable but should be avoided during active infection.
The possibility of nonarteritic anterior ischemic optic neuropathy was considered in our patient. However, the close temporal relationship between the systemic illness and the optic neuropathy, the absence of vasculopathic risk factors (e.g., diabetes, hypertension, elevated cholesterol), and the absence of a “disc at risk” in the fellow eye made this diagnosis unlikely.
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2. Khairallah M, Yahia SB, Toumi A, Jelliti B, Loussaief C, Romdhane FB, Messaoud R, Chakroun M. Ocular manifestations associated with murine typhus. Br J Ophthalmol. 2009;93:938–942
3. Lu TM, Kuo BI, Chung YM, Liu CY. Murine typhus presenting with multiple white dots in the retina. Scand J Infect Dis. 1997;29:632–633
4. Thach AB, Lopez PF. Retinal manifestations of acute murine typhus. Int Ophthalmol. 1997;21:121–126
© 2011 Lippincott Williams & Wilkins, Inc.