Can scrub typhus cause neuropathy?

Scrub Typhus and Neuropathy

Yes, scrub typhus definitively causes neuropathy through multiple mechanisms affecting both the peripheral and central nervous systems, occurring in approximately 20% of patients with this infection. 1

Mechanisms of Neurologic Injury

Scrub typhus causes neuropathy through three primary pathophysiologic mechanisms:

• Direct vasculitic injury: Orientia tsutsugamushi multiplies in endothelial cells, causing vasculitis that damages nerve tissue through ischemic injury 2
• Direct organism invasion: The pathogen can directly invade neural tissue, particularly affecting peripheral nerves 1
• Immune-mediated damage: Post-infectious immune mechanisms trigger inflammatory injury to nerves, similar to other post-infectious neuropathies 1, 3

Specific Neuropathic Manifestations

Peripheral Nervous System Involvement

Guillain-Barré syndrome (GBS) represents the most well-documented peripheral neuropathy associated with scrub typhus:

• Multiple case reports confirm scrub typhus as an antecedent infection triggering GBS, with nerve conduction studies demonstrating sensory-motor polyneuropathy 4
• Patients present with progressive weakness, hyporeflexic deep tendon reflexes, and evidence of axonopathy on electrodiagnostic testing 5
• Treatment requires both doxycycline for the infection and intravenous immunoglobulin for the immune-mediated neuropathy 5

Polyradiculoneuropathy with cranial neuropathy has been documented as a distinct presentation:

• This involves multiple nerve roots and cranial nerves simultaneously 3
• Cranial nerve palsies include abducens nerve palsy (causing diplopia), facial nerve palsy, and other cranial nerve involvement 3, 6

Isolated peripheral neuropathies occur less commonly:

• Myositis (muscle inflammation with neuropathic features) has been reported 3
• Acute transverse myelitis affecting the spinal cord can produce lower motor neuron findings 3

Central Nervous System Involvement with Neuropathic Features

While primarily CNS manifestations, these conditions produce neuropathic symptoms:

• Meningoencephalitis is the most common neurological complication, affecting approximately 20% of patients 1
• Acute disseminated encephalomyelitis (ADEM) causes multifocal demyelination with both central and peripheral nerve involvement 1
• Longitudinally extensive transverse myelitis produces extensive spinal cord damage with neuropathic pain and motor deficits 1

Clinical Recognition

Key Diagnostic Features

The eschar is pathognomonic but not always present:

• A painless, necrotic lesion with black crust surrounded by erythema at the site of mite bite 2
• Absence of eschar cannot exclude scrub typhus diagnosis 1, 3
• Careful examination of all skin surfaces, including hidden areas, is essential 1

Neurological symptoms typically emerge in the context of acute febrile illness:

• Fever begins 6-10 days after chigger bite, accompanied by headache, myalgia, and malaise 2
• Neurological manifestations usually appear during or shortly after the febrile phase 1
• History of travel to or residence in endemic regions (South Asia, Southeast Asia, Western Pacific) is crucial 2, 1

Diagnostic Testing

Serologic confirmation is the primary diagnostic method:

• IgM antibody detection by ELISA or indirect fluorescent antibody test is standard 1
• Elevated indirect immunofluorescent antibody titer for Orientia tsutsugamushi confirms diagnosis 4

Electrodiagnostic studies document neuropathy:

• Nerve conduction studies demonstrate sensory-motor polyneuropathy patterns in GBS cases 4, 5
• Evidence of axonopathy may be present on nerve conduction studies 5

Treatment Approach

Immediate Antibiotic Therapy

Doxycycline is the definitive treatment and should never be delayed:

• Adults: 100 mg twice daily (oral or IV) for at least 3 days after fever subsides, minimum 5-7 days total 2
• Children under 45 kg: 2.2 mg/kg twice daily 2
• Intravenous therapy is mandatory for hospitalized patients with neurological complications 2

Clinical response timing guides management:

• Patients with early disease typically respond within 24-48 hours 2
• Severely ill patients with multi-organ dysfunction (including neurological involvement) may require >48 hours before improvement 2
• Lack of response within 48 hours in early disease should prompt consideration of alternative diagnoses 2

Adjunctive Therapy for Immune-Mediated Neuropathy

When GBS or other immune-mediated neuropathy is present:

• Intravenous immunoglobulin therapy is indicated in addition to doxycycline 5
• Supportive care including respiratory support may be necessary for severe GBS 5
• Immune-mediated mechanisms likely mediate pathogenesis in most neurological cases 3

Critical Clinical Pitfalls

Do not wait for laboratory confirmation before initiating treatment:

• Delay can lead to severe disease, long-term sequelae, or death 2
• Mortality rates up to 4% have been reported, largely attributable to delayed diagnosis 2

Consider scrub typhus in any acute neurological syndrome with fever in endemic regions:

• Even with unremarkable neuroimaging findings, scrub typhus should remain in the differential 3
• Co-infection with dengue or chikungunya may occur, complicating the clinical picture 1

Recognize that neurological manifestations can be the predominant presenting feature:

• Approximately 14% (50/354) of scrub typhus cases present with predominantly neurological manifestations 3
• The entire neural axis except the myoneural junction can be involved 1

Most neurological manifestations respond to doxycycline therapy:

• Early antibiotic treatment prevents progression and improves outcomes 1
• Some cases require additional immunomodulatory therapy for immune-mediated complications 5