Abstract
Context: Scrub typhus is an acute febrile disease caused by Orientia tsutsugamushi. The disease can usually involve the lungs, heart, liver, spleen and brain through hematogenous dissemination. However, very rarely, acute transverse myelitis in the spinal cord develops from scrub typhus. We present a case of acute transverse myelitis following scrub typhus with a review of the literature.
Findings: A 66-year-old male visited a hospital for general myalgia, mild headache, and fever in October. He was noted to have thick, black papule skin on his abdomen, which was highly suggestive of scrub typhus. To confirm the diagnosis, O. tsutsugamushi antibody titers were examined and detected highly in serum by an indirect fluorescence antibody assay. Doxycycline, the standard treatment for scrub typhus, was administered. However, after seven days of treatment, he rapidly developed weakness in the right leg, paresthesia in both lower limbs, and voiding difficulty. Spinal magnetic resonance imaging (MRI) revealed lesions with high signal intensity involving the spinal cord at the thoracolumbar junction. Paraparesis gradually improved following steroid pulse therapy for five days. At one-year follow-up, he could walk without cane.
Conclusions: Orientia tsutsugamushi causes scrub typhus, which can affect not only the brain, but also the spinal cord. Although acute transverse myelitis develops rarely from scrub typhus, this should be considered as differential diagnosis in patients of fever with neurological deficit in endemic areas.
Keywords: Scrub typhus, Rickettsia, Transverse myelitis, Tsutsugamushi, Doxycycline
Introduction
Scrub typhus is an acute febrile illness and mite-borne bacterial infection caused by Orientia tsutsugamushi, an obligate gram-negative intracellular bacterium.1 The bacterium is transmitted by the bite of the trombiculid mite (chigger), which leaves the tell-tale pathognomonic eschar.1 Scrub typhus is known to occur throughout Asia, but recent evidence suggests that its range may be larger, with case reports in Asia-Pacific, including Korea.2 Patients with scrub typhus usually develop various complications, such as myocarditis, arrhythmia, and interstitial pneumonia.2 Neurological manifestations in scrub typhus are infrequent, but recently central nervous system (CNS) manifestations in the form of meningitis or meningoencephalitis have been reported.3,4 However, to our knowledge, scrub typhus invasion of the spinal cord is very rare.5 Hence, we present a case of acute transverse myelitis following scrub typhus with a review of the literature.
Case report
A 66-year-old male farmer visited a local hospital for general myalgia, mild headache, and fever. He was treated with cold medicine for one week, however, his symptoms did not improve and his myalgia and headache worsened. He visited our hospital for further evaluation. A thick, black papule, namely, eschar on his abdomen was found, that is highly suggestive of scrub typhus (Fig. 1). Serum O. tsutsugamushi antibody titers were detected by indirect fluorescence assay (IFA) (1:640; cut off, 1:10).6 He was diagnosed with scrub typhus and oral doxycycline (200 mg daily) treatment was initiated. Fever and myalgia improved after doxycycline treatment. However, after seven days of doxycycline treatment, the patient developed sudden onset of paresthesias in both ankles, urinary retention, loss of tendon reflexes and paraparesis, with change of motor grade in lower extremities from grade 5 to grade 1 (Injury Association Impairment Scale: ASIA B). Spinal magnetic resonance imaging (MRI) revealed high signal intensity lesion and swelling in the spinal cord at T11-12 level. Additionally, diffusion weighted imaging (DWI) showed a restriction at the lesion of high signal intensity on T2 weighted images (Fig. 2). Cerebrospinal fluid (CSF) examination showed glucose levels of 59 mg/dl, protein levels of 67 mg/dl, WBC count of 3/mm3, and O. tsutsugamushi IgG antibody titers of 1:110. Serum IFA titers increased to 1:2560. Based on the MRI findings and O. tsutsugamushi antibody titers, acute transverse myelitis following scrub typhus was diagnosed. Steroid pulse therapy with 1000 mg methylprednisolone (mix to normal saline 500mL, 170mL/hour) was administered for five days. Following steroidal therapy, leg weakness improved gradually to a motor grade 4. Follow-up MRI at six months indicated that the swelling lesion with high signal intensity remained but was reduced (Fig. 3). Serum IFA titers decreased from a maximal 1:2560 to 1:30. At one-year follow-up, the patient could walk without a cane (ASIA D). However, urinary retention remained despite treatment with an alpha blocker.
Figure 1.
Eschar (dark, black papule) on right middle quadrant abdomen.
Figure 2.
Acute transverse myelitis detected on MRI scans (A); (B) Intramedullary high signal intensity with spinal cord enlargement in sagittal T2 image and STIR image (white arrows); (C) T2 weighted axial image showing high signal intensity in right gray matter area at T11-12 level (white arrow)
STIR: Short tau inversion recovery.
Figure 3.
At 6 months follow-up MRI scans
(A), (B) Slightly decreased high signal intensity lesion and cord enlargement compared to initial MRI (white arrows).
Discussion
Scrub typhus has a latent period of 5 to 20 days, and symptoms include general malaise, headache, rash, lymphadenopathy, and fever.6 The eschar undergoes an ulcerative change, which is seen at the site of the mite bite. This skin lesion is found in 60–80% of patients with scrub typhus.7 The presence of an eschar is a useful dermatological factor in diagnosing scrub typhus even in cases in which a serologic diagnosis is not confirmed.8 For this case, a diagnosis of scrub typhus was suspected based on the presence of a typical eschar. However, in the absence of an eschar, it is difficult to make a diagnosis, and scrub typhus could be misdiagnosed. The present standard to diagnose scrub typhus is serologic testing, and the standard assay for detection of scrub typhus antibodies is IFA. Black et al.6 suggest that a diagnosis of scrub typhus using IFA should be based on a 4-fold titer increase.
Orientia tsutsugamushi invades the CSF; therefore, scrub typhus should be considered a cause of mononuclear meningitis. CSF cytology is useful in detecting meningitis associated with scrub typhus. Symptoms are similar with those things of viral meningitis, leptospirosis, and tuberculous meningitis.3,8 Furthermore, Pai et al. had suggested the possibility that CNS Orientia tsutsugamushi has a propensity for CNS invasion. They revealed that pleocytosis (increased white blood cell count in cerebrospinal fluid) occurs transiently in the early period of the infection of Orientia tsutsugamushi. According to Pai et al.'s study in 25 patients with scrub typhus involving the CNS, 48% (12/25) had CSF pleocytosis of mild severity.9 These patients presented with a WBC count of 0 to 110/mm3 and a lymphocyte rate of 51.9 ± 23.9%; 28% had elevated protein levels (≥50 mg/dl).9
Another pathogenic feature is involvement of blood vessels in the CNS that may produce vasculitis with a predominantly mononuclear cell response;10 this involvement was thought to be the cause of meningitis and encephalitis.5 Histopathologically, scrub typhus is accompanied by inflammation of local microvessels or vasculitis due to disseminated intravascular coagulation (DIC) in several organs, and the severity of vasculitis varies depending on the case.11 In this context, vasculitis could invade the CNS as well as the spinal cord and spinal meninges. Eventually, acute transverse myelitis could develop following scrub typhus.
Conclusion
Scrub typhus causes not only meningitis and meningoencephalitis, but also, very rarely, acute transverse myelitis. Therefore, in endemic areas, if patients have a fever and malaise with paraplegia, scrub typhus should be considered as a cause of spinal cord diseases.
Funding Statement
This work was supported by the Chonnam National University Hospital Biomedical Research Institute; under Grant CRI 160003-1.
Disclaimer statements
Contributors None.
Conflict of interest No potential conflict of interest was reported by the authors.
Ethics approval None.
Declaration of interest The authors report no declarations of interest.
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