Rabies differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

The differential diagnosis for rabies deals with eliminating diseases with similar symptoms from the diagnosis. There are many viruses that can appear similar to rabies such as encephalitis and the herpes simplex virus. It is very important to rule out certain diseases such as echovirus and poliovirus. Rabies is a serious disease that needs to be treated quickly if someone is suspected to be infected with the virus.

Differentiating Rabies from other Diseases

The differential diagnosis in a case of suspected human rabies may initially include any cause of

Differentiating symptomatic rabies from other diseases that decrease consciousness

• Encephalitis
• Particularly infection with viruses such as:
  • Herpesviruses, enteroviruses
  • Arboviruses(e.g., West Nile virus).
• The most important viruses to rule out are:
  • Herpes simplex virus type 1
  • Varicella-zoster virus
  • (Less commonly) Enteroviruses including:
    • Coxsackieviruses
    • Echoviruses
    • Polioviruses
    • Human enteroviruses 68 to 71.
• A specific diagnosis may be made by a variety of diagnostic techniques, including:
  • Polymerase chain reaction (PCR) testing of:
  • Cerebrospinal fluid
  • viral culture
  • Serology.
• In addition, consideration should be given to the local epidemiology of encephalitis caused by arboviruses belonging to several taxonomic groups, including:
  • Eastern equine encephalitis viruses
  • Western equine encephalitis viruses
  • St. Louis encephalitis virus
  • Powassan virus
  • The California encephalitis virus serogroup
  • La Crosse virus.

New causes of viral encephalitis are also possible, as was evidenced by the recent outbreak in Malaysia of some 300 cases of encephalitis (mortality rate, 40%) caused by Nipah virus, a newly recognized paramyxovirus. Similarly, well-known viruses may be introduced into new locations, as is illustrated by the recent outbreak of encephalitis due to West Nile virus in the eastern United States. Epidemiologic factors (e.g., season, geographic location, and the patient’s age, travel history, and possible exposure to animal bites, rodents, and ticks) may help direct the diagnostic workup.

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Diseases	History and Physical					Diagnostic tests		Other Findings
	Prodromal symptoms	Fever	Headache	LOC	Neuro Onset	Laboratory Findings	Imaging
Rabies infection	+	+	+	+	Insidious			Hydrophobia, aerophobia, dysphagia, and localized pain, weakness or paresthesias
Meningitis	+	+	+	-	Sudden	CSF analysis: ↑ Leukocytes ↑ Protein ↓ Glucose		Fever, neck, rigidity
encephalitis	+			+				Accompany a meningoencephalitis, seizures, hemiparesis, cranial nerve palsies, photophobia, nausea
Autoimmune encephalitis	-	+/-	+	+/-	Insidious			Memory deficit, dyskinesias, seizures, autonomic instability
CNS abscess	+	+	+	+	Insidious	CSF analysis: ↑ leukocytes ↓ glucose ↑ protien	MRI is more sensitive and specific	High grade fever, fatigue,nausea, vomiting
Poliomyelitis					Sudden	PCR of CSF		Asymmetric paralysis following a flu-like syndrome.
Neurosyphilis					Insidious	CSF VDRL-specifc CSF FTA-Ab -sensitive	MRI & Lumbar puncture	History of unprotected sex or multiple sexual partners, and genital ulcer (chancre) Blindness, confusion, depression, abnormal gait
Tick paralysis (Dermacentor tick)				+	Insidious	-	-	History of outdoor activity in Northeastern United States. The tick is often still latched to the patient at presentation (often in head and neck area)
Adult Botulism					Sudden	Toxin test, Blood, Wound, or Stool culture		Diplopia, Hyporeflexia, Hypotonia, possible respiratory paralysis, Floppy baby syndrome
Electrolyte disturbance					Insidious	Electrolyte panel: ↓Ca++, ↓Mg++, ↓K+		Possible arrhythmia
Tetrodotoxin poisoning					Sudden	-	-	History of consumption of puffer fish species.
Metabolic disturbances (electrolyte imbalance, hypoglycemia)	-	+/-	-	+	Sudden	Hypoglycemia, hypo and hypernatremia, hypo and hyperkalemia		Confusion, seizure, palpitations, sweating, dizziness, hypoglycemia
Drug toxicity/Neuroleptic malignant syndrome	-	-	-	+				Causative medications (eg, neuroleptics, antiemetics, concomitant lithium), dopaminergic withdrawal, elevated creatine kinase
Organophosphate toxicity					Sudden	Clinical suspicion confirmed with RBC AchE activity		History of exposure to insecticide or living in farming environment. with : Diarrhea, Urination, Miosis, Bradycardia, Lacrimation, Emesis, Salivation, Sweating
Ischemic stroke					Sudden		MRI +ve for ischemia or hemorrhage	Sudden unilateral motor and sensory deficit in a patient with a history of atherosclerotic risk factors (diabetes, hypertension, smoking) or atrial fibrillation.
Hemorrhagic stroke			+	+	Sudden	-	CT scan without contrast	Neck stiffness
Subdural hemorrhage			+	+	Sudden	CSF analysis: Xanthochromia	CT scan without contrast	Confusion, dizziness, nausea, vomiting
Hypertensive encephalopathy	-	-	+	+	Sudden		-	Delirium, cortical blindness, cerebral edema, seizure
Wernicke’s encephalopathy	-	-	-	+	Sudden		-	Ophthalmoplegia, confusion
Guillian-Barre syndrome					Insidious	CSF: ↑Protein ↓Cells	-	Progressive ascending paralysis following infection, possible respiratory paralysis
Amyotrophic lateral sclerosis					Insidious	Normal LP (to rule out DDx)	MRI	Patient initially presents with upper motor neuron deficit (spasticity) followed by lower motor neuron deficit (flaccidity).
Diffuse glioma					Insidious	GFAP Normal CSF	MRI (expansile, T2 hyperintense lesion)
Primary or secondary central nervous system lymphoma					Insidious	CSF cytology, flow cytometry, and stereotactic brain biopsy	MRI (parenchymal or leptomeningeal enhancement)