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Bilateral optic atrophy in endemic typhus

2014; Elsevier BV; Volume: 49; Issue: 4 Linguagem: Inglês

10.1016/j.jcjo.2014.04.009

1715-3360

Angelina Espino Barros Palau, Michael L. Morgan, Andrew G. Lee,

Leptospirosis research and findings

Murine typhus is an infectious disease caused by Rickettsia typhus. The disease is transmitted to humans by rat fleas through direct inoculation.1Civen R. Ngo V. Murine typhus: an unrecognized suburban vectorborne disease.Clin Infect Dis. 2008; 46: 913-918Crossref PubMed Scopus (202) Google Scholar Southeast Texas has one of the highest incidence rates of endemic typhus in the United States.2Fergie J.E. Purcell K. Wanat D. Murine typhus in South Texas children.Pediatr Infect Dis J. 2000; 19: 535-538Crossref PubMed Scopus (54) Google Scholar, 3Purcell K. Fergie J. Richman K. Rocha L. Murine typhus in children, South Texas.Emerg Infect Dis. 2007; 13: 926-927Crossref PubMed Scopus (20) Google Scholar, 4Adjemian J. Parks S. McElroy K. et al.Murine typhus in Austin, Texas, USA, 2008.Emerg Infect Dis. 2010; 16: 412-417Crossref PubMed Scopus (69) Google Scholar, 5Dumler J.S. Taylor J.P. Walker DH. Clinical and laboratory features of murine typhus in south Texas, 1980 through 1987.JAMA. 1991; 266: 1365-1370Crossref PubMed Scopus (208) Google Scholar Ophthalmic manifestations of murine typhus include vitritis, retinal lesions, and retinal vascular leakage.6Hudson H.L. Thach A.B. Lopez P.F. Retinal manifestations of acute murine typhus.Int Ophthalmol. 1997; 21: 121-126Crossref PubMed Scopus (17) Google Scholar, 7Lu T.M. Kuo B.I. Chung Y.M. Liu C.Y. Murine typhus presenting with multiple white dots in the retina.Scand J Infect Dis. 1997; 29: 632-633Crossref PubMed Scopus (11) Google Scholar, 8Khairallah M. Ben Yahia S. Toumi A. et al.Ocular manifestations associated with murine typhus.Br J Ophthalmol. 2009; 93: 938-942Crossref PubMed Scopus (36) Google Scholar, 9Manor E. Politi F. Marmor A. Cohn D.F. Papilledema in endemic typhus.Am J Ophthalmol. 1977; 84: 559-562PubMed Scopus (10) Google Scholar, 10Brooks F. Fineberg R. Ocular manifestations of typhus fever. A review of the literature from 1867 to 1943.Am J Ophthalmol. 1951; 34: 605-608PubMed Scopus (7) Google Scholar Optic neuropathy in the setting of murine typhus has been rarely described and only in the setting of disc edema or optic neuritis.8Khairallah M. Ben Yahia S. Toumi A. et al.Ocular manifestations associated with murine typhus.Br J Ophthalmol. 2009; 93: 938-942Crossref PubMed Scopus (36) Google Scholar, 9Manor E. Politi F. Marmor A. Cohn D.F. Papilledema in endemic typhus.Am J Ophthalmol. 1977; 84: 559-562PubMed Scopus (10) Google Scholar, 10Brooks F. Fineberg R. Ocular manifestations of typhus fever. A review of the literature from 1867 to 1943.Am J Ophthalmol. 1951; 34: 605-608PubMed Scopus (7) Google Scholar, 11Zhang J. Pau D. Lee A.G. Postinfectious optic neuropathy in endemic typhus.J Neuroophthalmol. 2011; 31: 342-343Crossref PubMed Scopus (8) Google Scholar We present a rare case of bilateral optic atrophy as the presenting ophthalmic sign of R. typhus infection.A 55-year-old white male presented with a 1-month history of painless, bilateral progressive vision loss and floaters. Medical history was significant for well-controlled diabetes mellitus type 2 and systemic hypertension. Ocular history was significant for remote right-sided ocular trauma from injury with an arrow. The patient smoked cigarettes, 1 pack per day. He denied any recent travel or sick exposures. He denied exposure to chemicals, toxins, or poisons. He had a dog and a cat. He denied any recent tick bite.His symptoms started 1 month before presentation with fever and malaise. The constitutional symptoms were followed by blurred vision, floaters, and dyschromatopsia. His medical doctor diagnosed infectious mononucleosis. However, he subsequently experienced development of a cutaneous vesicular eruption on his right torso and was diagnosed with herpes zoster. He was treated with oral famciclovir. Around the same time, he was evaluated by an outside ophthalmologist. His acuity was 20/20 OU, but he had rare cells and vitreous haze OU. He was prescribed topical steroid drops in addition to the oral antiviral treatment. His vision worsened, and he was administered an intravitreal steroid injection in the right eye. His vision, however, further deteriorated. A fluorescein angiogram (FA) showed no optic disc leakage or vasculitis. Magnetic resonance imaging of the brain and orbits with and without contrast and fat suppression was unremarkable. Testing for HIV, syphilis, sarcoidosis including serum angiotensin-converting enzyme and lysozyme, antinuclear antibody, tuberculosis QuantiFERON-TB testing, and Lyme titer were all negative. Toxoplasma and Bartonella antibodies were also negative. A vitreous tap revealed only a few scattered lymphocytes and a few mononuclear cells. Special stains for fungus, acid-fast bacilli, and molecular testing were all negative. He was then referred to our neuro-ophthalmology clinic.On examination, his vision was 20/100 OD and 20/50 OS. He had no rash or history of insect/animal bite. Both pupils were poorly reactive, but he had no relative afferent pupillary defect. Slit-lamp examination showed iris atrophy in the inferior segment of his right eye, presumed secondary to the old foreign body (arrow) injury. However, there were also posterior synechiae at the inferior border and pigment deposition in the anterior lens capsule. There was no active anterior uveitis. Humphrey 24-4 visual field testing of the right eye showed a dense inferior altitudinal and superior arcuate defects with a mean deviation (MD) of –19.19. The left eye visual field had an inferior altitudinal and superior arcuate defect with a MD of –20.56. Ophthalmoscopy showed normal macula, vessels, and periphery in each eye. Both optic nerves, however, were pale with a cup-to-disc ratio of 0.3. OCT of the optic nerves confirmed the bilateral optic atrophy in the papillomacular bundle (Fig. 1).Lumbar puncture showed a normal opening pressure of 15 cm H2O. Cerebrospinal (CSF) protein was elevated at 105 mg/dL, but CSF cell count and glucose were within normal limits. CSF herpes simplex virus, varicella zoster virus, and Epstein–Barr virus (EBV) polymerase chain reaction were negative. Gram stain showed no infectious organism, and cultures were negative. Additional laboratory tests were sent including a complete blood cell count, EBV viral capsid antigen antibody (VCA IgG), EBV nuclear antigen antibody, rapid plasma reagin, West Nile virus antibodies, Histoplasma urine antigen, neuromyelitis optica antibody, and R. typhi antibodies. R. typhi antibodies came back positive with both IgM and IgG titers positive at greater than 1:256. In consultation with an infectious disease specialist, the patient received a 14-day course of doxycycline. His vision, unfortunately, did not improve, and he experienced development of optic atrophy.Murine typhus is a rickettsial disease characterized by high fever, constitutional symptoms, and typically a maculopapular rash. The rash, however, can be vesicular and may mimic herpes zoster. R. typhi is usually a mild and self-limited disease, although 10% of hospitalized patients require intensive care because of respiratory distress, renal failure, or severe neurologic involvement.5Dumler J.S. Taylor J.P. Walker DH. Clinical and laboratory features of murine typhus in south Texas, 1980 through 1987.JAMA. 1991; 266: 1365-1370Crossref PubMed Scopus (208) Google Scholar Ophthalmic involvement is rare and only a few reports on ophthalmic murine typhus can be found in the literature.6Hudson H.L. Thach A.B. Lopez P.F. Retinal manifestations of acute murine typhus.Int Ophthalmol. 1997; 21: 121-126Crossref PubMed Scopus (17) Google Scholar, 7Lu T.M. Kuo B.I. Chung Y.M. Liu C.Y. Murine typhus presenting with multiple white dots in the retina.Scand J Infect Dis. 1997; 29: 632-633Crossref PubMed Scopus (11) Google Scholar, 8Khairallah M. Ben Yahia S. Toumi A. et al.Ocular manifestations associated with murine typhus.Br J Ophthalmol. 2009; 93: 938-942Crossref PubMed Scopus (36) Google Scholar, 9Manor E. Politi F. Marmor A. Cohn D.F. Papilledema in endemic typhus.Am J Ophthalmol. 1977; 84: 559-562PubMed Scopus (10) Google Scholar, 11Zhang J. Pau D. Lee A.G. Postinfectious optic neuropathy in endemic typhus.J Neuroophthalmol. 2011; 31: 342-343Crossref PubMed Scopus (8) Google ScholarThe largest cases series of murine typhus–associated ophthalmic findings was reported by Khairallah et al.8Khairallah M. Ben Yahia S. Toumi A. et al.Ocular manifestations associated with murine typhus.Br J Ophthalmol. 2009; 93: 938-942Crossref PubMed Scopus (36) Google Scholar The most common ophthalmic findings, present in 50% of their patients, were white retinal lesions located in the inner retina associated with mild vitritis. These lesions were thought to represent areas of retinitis from either rickettsial multiplication or inflammatory cell accumulation. Similar retinal lesions have also been described by Hudson et al.6Hudson H.L. Thach A.B. Lopez P.F. Retinal manifestations of acute murine typhus.Int Ophthalmol. 1997; 21: 121-126Crossref PubMed Scopus (17) Google Scholar and by Lu et al.7Lu T.M. Kuo B.I. Chung Y.M. Liu C.Y. Murine typhus presenting with multiple white dots in the retina.Scand J Infect Dis. 1997; 29: 632-633Crossref PubMed Scopus (11) Google Scholar Angiographically confirmed retinal vasculitis (38.9%) and retinal hemorrhages (22.2%) were also common in Khairallah et al.'s series.8Khairallah M. Ben Yahia S. Toumi A. et al.Ocular manifestations associated with murine typhus.Br J Ophthalmol. 2009; 93: 938-942Crossref PubMed Scopus (36) Google ScholarOptic neuropathy has also been described in murine typhus. The exact mechanism of this typhus-associated optic neuropathy is unknown, but it probably represents an inflammatory reaction. In Khairallah et al.'s series,8Khairallah M. Ben Yahia S. Toumi A. et al.Ocular manifestations associated with murine typhus.Br J Ophthalmol. 2009; 93: 938-942Crossref PubMed Scopus (36) Google Scholar 66.6% of eyes had staining on FA, 11.1% had disc edema, and 1 had optic neuritis. Our patient's case is unique as, to our knowledge, there are no previous reports of bilateral simultaneous retrobulbar optic neuropathy associated with endemic typhus. Although optic atrophy may appear after disc edema has resolved, our patient did not demonstrate disc edema on funduscopy, nor was there leakage on FA. Unlike Khairallah et al.'s series8Khairallah M. Ben Yahia S. Toumi A. et al.Ocular manifestations associated with murine typhus.Br J Ophthalmol. 2009; 93: 938-942Crossref PubMed Scopus (36) Google Scholar in which most patients were asymptomatic, visual acuity was significantly decreased in our case.In conclusion, endemic typhus can present as a retrobulbar optic neuropathy with severe and irreversible vision loss. The differential diagnosis of a patient with vitritis-associated optic neuropathy should include infectious and inflammatory causes. Infectious disease merits stronger consideration when these ocular findings occur in the setting of a recent exanthematic illness. Although more common infectious agents should be investigated first, R. typhi infection should also be considered in endemic areas, such as the State of Texas. Murine typhus is an infectious disease caused by Rickettsia typhus. The disease is transmitted to humans by rat fleas through direct inoculation.1Civen R. Ngo V. Murine typhus: an unrecognized suburban vectorborne disease.Clin Infect Dis. 2008; 46: 913-918Crossref PubMed Scopus (202) Google Scholar Southeast Texas has one of the highest incidence rates of endemic typhus in the United States.2Fergie J.E. Purcell K. Wanat D. Murine typhus in South Texas children.Pediatr Infect Dis J. 2000; 19: 535-538Crossref PubMed Scopus (54) Google Scholar, 3Purcell K. Fergie J. Richman K. Rocha L. Murine typhus in children, South Texas.Emerg Infect Dis. 2007; 13: 926-927Crossref PubMed Scopus (20) Google Scholar, 4Adjemian J. Parks S. McElroy K. et al.Murine typhus in Austin, Texas, USA, 2008.Emerg Infect Dis. 2010; 16: 412-417Crossref PubMed Scopus (69) Google Scholar, 5Dumler J.S. Taylor J.P. Walker DH. Clinical and laboratory features of murine typhus in south Texas, 1980 through 1987.JAMA. 1991; 266: 1365-1370Crossref PubMed Scopus (208) Google Scholar Ophthalmic manifestations of murine typhus include vitritis, retinal lesions, and retinal vascular leakage.6Hudson H.L. Thach A.B. Lopez P.F. Retinal manifestations of acute murine typhus.Int Ophthalmol. 1997; 21: 121-126Crossref PubMed Scopus (17) Google Scholar, 7Lu T.M. Kuo B.I. Chung Y.M. Liu C.Y. Murine typhus presenting with multiple white dots in the retina.Scand J Infect Dis. 1997; 29: 632-633Crossref PubMed Scopus (11) Google Scholar, 8Khairallah M. Ben Yahia S. Toumi A. et al.Ocular manifestations associated with murine typhus.Br J Ophthalmol. 2009; 93: 938-942Crossref PubMed Scopus (36) Google Scholar, 9Manor E. Politi F. Marmor A. Cohn D.F. Papilledema in endemic typhus.Am J Ophthalmol. 1977; 84: 559-562PubMed Scopus (10) Google Scholar, 10Brooks F. Fineberg R. Ocular manifestations of typhus fever. A review of the literature from 1867 to 1943.Am J Ophthalmol. 1951; 34: 605-608PubMed Scopus (7) Google Scholar Optic neuropathy in the setting of murine typhus has been rarely described and only in the setting of disc edema or optic neuritis.8Khairallah M. Ben Yahia S. Toumi A. et al.Ocular manifestations associated with murine typhus.Br J Ophthalmol. 2009; 93: 938-942Crossref PubMed Scopus (36) Google Scholar, 9Manor E. Politi F. Marmor A. Cohn D.F. Papilledema in endemic typhus.Am J Ophthalmol. 1977; 84: 559-562PubMed Scopus (10) Google Scholar, 10Brooks F. Fineberg R. Ocular manifestations of typhus fever. A review of the literature from 1867 to 1943.Am J Ophthalmol. 1951; 34: 605-608PubMed Scopus (7) Google Scholar, 11Zhang J. Pau D. Lee A.G. Postinfectious optic neuropathy in endemic typhus.J Neuroophthalmol. 2011; 31: 342-343Crossref PubMed Scopus (8) Google Scholar We present a rare case of bilateral optic atrophy as the presenting ophthalmic sign of R. typhus infection. A 55-year-old white male presented with a 1-month history of painless, bilateral progressive vision loss and floaters. Medical history was significant for well-controlled diabetes mellitus type 2 and systemic hypertension. Ocular history was significant for remote right-sided ocular trauma from injury with an arrow. The patient smoked cigarettes, 1 pack per day. He denied any recent travel or sick exposures. He denied exposure to chemicals, toxins, or poisons. He had a dog and a cat. He denied any recent tick bite. His symptoms started 1 month before presentation with fever and malaise. The constitutional symptoms were followed by blurred vision, floaters, and dyschromatopsia. His medical doctor diagnosed infectious mononucleosis. However, he subsequently experienced development of a cutaneous vesicular eruption on his right torso and was diagnosed with herpes zoster. He was treated with oral famciclovir. Around the same time, he was evaluated by an outside ophthalmologist. His acuity was 20/20 OU, but he had rare cells and vitreous haze OU. He was prescribed topical steroid drops in addition to the oral antiviral treatment. His vision worsened, and he was administered an intravitreal steroid injection in the right eye. His vision, however, further deteriorated. A fluorescein angiogram (FA) showed no optic disc leakage or vasculitis. Magnetic resonance imaging of the brain and orbits with and without contrast and fat suppression was unremarkable. Testing for HIV, syphilis, sarcoidosis including serum angiotensin-converting enzyme and lysozyme, antinuclear antibody, tuberculosis QuantiFERON-TB testing, and Lyme titer were all negative. Toxoplasma and Bartonella antibodies were also negative. A vitreous tap revealed only a few scattered lymphocytes and a few mononuclear cells. Special stains for fungus, acid-fast bacilli, and molecular testing were all negative. He was then referred to our neuro-ophthalmology clinic. On examination, his vision was 20/100 OD and 20/50 OS. He had no rash or history of insect/animal bite. Both pupils were poorly reactive, but he had no relative afferent pupillary defect. Slit-lamp examination showed iris atrophy in the inferior segment of his right eye, presumed secondary to the old foreign body (arrow) injury. However, there were also posterior synechiae at the inferior border and pigment deposition in the anterior lens capsule. There was no active anterior uveitis. Humphrey 24-4 visual field testing of the right eye showed a dense inferior altitudinal and superior arcuate defects with a mean deviation (MD) of –19.19. The left eye visual field had an inferior altitudinal and superior arcuate defect with a MD of –20.56. Ophthalmoscopy showed normal macula, vessels, and periphery in each eye. Both optic nerves, however, were pale with a cup-to-disc ratio of 0.3. OCT of the optic nerves confirmed the bilateral optic atrophy in the papillomacular bundle (Fig. 1). Lumbar puncture showed a normal opening pressure of 15 cm H2O. Cerebrospinal (CSF) protein was elevated at 105 mg/dL, but CSF cell count and glucose were within normal limits. CSF herpes simplex virus, varicella zoster virus, and Epstein–Barr virus (EBV) polymerase chain reaction were negative. Gram stain showed no infectious organism, and cultures were negative. Additional laboratory tests were sent including a complete blood cell count, EBV viral capsid antigen antibody (VCA IgG), EBV nuclear antigen antibody, rapid plasma reagin, West Nile virus antibodies, Histoplasma urine antigen, neuromyelitis optica antibody, and R. typhi antibodies. R. typhi antibodies came back positive with both IgM and IgG titers positive at greater than 1:256. In consultation with an infectious disease specialist, the patient received a 14-day course of doxycycline. His vision, unfortunately, did not improve, and he experienced development of optic atrophy. Murine typhus is a rickettsial disease characterized by high fever, constitutional symptoms, and typically a maculopapular rash. The rash, however, can be vesicular and may mimic herpes zoster. R. typhi is usually a mild and self-limited disease, although 10% of hospitalized patients require intensive care because of respiratory distress, renal failure, or severe neurologic involvement.5Dumler J.S. Taylor J.P. Walker DH. Clinical and laboratory features of murine typhus in south Texas, 1980 through 1987.JAMA. 1991; 266: 1365-1370Crossref PubMed Scopus (208) Google Scholar Ophthalmic involvement is rare and only a few reports on ophthalmic murine typhus can be found in the literature.6Hudson H.L. Thach A.B. Lopez P.F. Retinal manifestations of acute murine typhus.Int Ophthalmol. 1997; 21: 121-126Crossref PubMed Scopus (17) Google Scholar, 7Lu T.M. Kuo B.I. Chung Y.M. Liu C.Y. Murine typhus presenting with multiple white dots in the retina.Scand J Infect Dis. 1997; 29: 632-633Crossref PubMed Scopus (11) Google Scholar, 8Khairallah M. Ben Yahia S. Toumi A. et al.Ocular manifestations associated with murine typhus.Br J Ophthalmol. 2009; 93: 938-942Crossref PubMed Scopus (36) Google Scholar, 9Manor E. Politi F. Marmor A. Cohn D.F. Papilledema in endemic typhus.Am J Ophthalmol. 1977; 84: 559-562PubMed Scopus (10) Google Scholar, 11Zhang J. Pau D. Lee A.G. Postinfectious optic neuropathy in endemic typhus.J Neuroophthalmol. 2011; 31: 342-343Crossref PubMed Scopus (8) Google Scholar The largest cases series of murine typhus–associated ophthalmic findings was reported by Khairallah et al.8Khairallah M. Ben Yahia S. Toumi A. et al.Ocular manifestations associated with murine typhus.Br J Ophthalmol. 2009; 93: 938-942Crossref PubMed Scopus (36) Google Scholar The most common ophthalmic findings, present in 50% of their patients, were white retinal lesions located in the inner retina associated with mild vitritis. These lesions were thought to represent areas of retinitis from either rickettsial multiplication or inflammatory cell accumulation. Similar retinal lesions have also been described by Hudson et al.6Hudson H.L. Thach A.B. Lopez P.F. Retinal manifestations of acute murine typhus.Int Ophthalmol. 1997; 21: 121-126Crossref PubMed Scopus (17) Google Scholar and by Lu et al.7Lu T.M. Kuo B.I. Chung Y.M. Liu C.Y. Murine typhus presenting with multiple white dots in the retina.Scand J Infect Dis. 1997; 29: 632-633Crossref PubMed Scopus (11) Google Scholar Angiographically confirmed retinal vasculitis (38.9%) and retinal hemorrhages (22.2%) were also common in Khairallah et al.'s series.8Khairallah M. Ben Yahia S. Toumi A. et al.Ocular manifestations associated with murine typhus.Br J Ophthalmol. 2009; 93: 938-942Crossref PubMed Scopus (36) Google Scholar Optic neuropathy has also been described in murine typhus. The exact mechanism of this typhus-associated optic neuropathy is unknown, but it probably represents an inflammatory reaction. In Khairallah et al.'s series,8Khairallah M. Ben Yahia S. Toumi A. et al.Ocular manifestations associated with murine typhus.Br J Ophthalmol. 2009; 93: 938-942Crossref PubMed Scopus (36) Google Scholar 66.6% of eyes had staining on FA, 11.1% had disc edema, and 1 had optic neuritis. Our patient's case is unique as, to our knowledge, there are no previous reports of bilateral simultaneous retrobulbar optic neuropathy associated with endemic typhus. Although optic atrophy may appear after disc edema has resolved, our patient did not demonstrate disc edema on funduscopy, nor was there leakage on FA. Unlike Khairallah et al.'s series8Khairallah M. Ben Yahia S. Toumi A. et al.Ocular manifestations associated with murine typhus.Br J Ophthalmol. 2009; 93: 938-942Crossref PubMed Scopus (36) Google Scholar in which most patients were asymptomatic, visual acuity was significantly decreased in our case. In conclusion, endemic typhus can present as a retrobulbar optic neuropathy with severe and irreversible vision loss. The differential diagnosis of a patient with vitritis-associated optic neuropathy should include infectious and inflammatory causes. Infectious disease merits stronger consideration when these ocular findings occur in the setting of a recent exanthematic illness. Although more common infectious agents should be investigated first, R. typhi infection should also be considered in endemic areas, such as the State of Texas.