Rabies differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mahshid Mir, M.D. [2]

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

Rabies should be differentiated from other causes of headache and decrease consciousness:

Diseases	History and Physical					Diagnostic tests		Other Findings
	Prodromal symptoms	Fever	Headache	LOC	Neuro Onset	Laboratory Findings	Imaging preferance
Rabies infection	+	+	+	+	Insidious	Antibody detection in serology Skin biopsy of injured skin	MRI	Hydrophobia, aerophobia, dysphagia, and localized pain, weakness or paresthesias
Meningitis	+	+	+	-	Sudden	CSF analysis: ↑ Leukocytes ↑ Protein ↓ Glucose	CT scan: First choice MRI: Best choice	Fever, neck, rigidity
Encephalitis	+	+	+	+	Sudden	PCR CSF analysis and culture reveal the responsible micro-organism	MRI	Accompany a meningoencephalitis, seizures, hemiparesis, cranial nerve palsies, photophobia, nausea
Autoimmune encephalitis	-	+/-	+	+/-	Insidious	Autoantibodies present in both serum and CSF	MRI EEG	Memory deficit, dyskinesias, seizures, autonomic instability
CNS abscess	+	+	+	+	Insidious	CSF analysis: ↑ Leukocytes ↓ Glucose ↑ Protein	MRI is more sensitive and specific	High grade fever, fatigue,nausea, vomiting
Poliomyelitis	+	+	+	+	Sudden	PCR of CSF	MRI	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 Tick often still latched to the patient at presentation (often in head and neck area)
Botulism	-	-	-	-	Sudden	Toxin test, blood, wound, or stool culture	-	Diplopia, Hyporeflexia, Hypotonia, possible respiratory paralysis, Floppy baby syndrome
Tetrodotoxin poisoning	-	-	+/-	+/-	Sudden	-	-	History of consumption of puffer fish species
Metabolic disturbances (electrolyte imbalance, hypoglycemia)	-	+/-	-	+	Sudden	Hypoglycemia, hypo and hypernatremia	MRI	Confusion, seizure, palpitations, sweating, dizziness, hypoglycemia
Electrolyte disturbance	-	-	-	+/-	Insidious	Hypocalcemia, hypomagnesemia, hypo- or hyperkalemia		Possible arrhythmia
Drug toxicity/Neuroleptic malignant syndrome	-	+	-	+	Sudden	Elevated serum creatine kianse Hypocalcemia, hypomagnesemia, hypo- and hypernatremia, hyperkalemia, and metabolic acidosis	Generalized slow wave EEG	Causative medications (eg, neuroleptics, antiemetics, concomitant lithium), dopaminergic withdrawal Mental status change, rigidity, or dysautonomia
Organophosphate toxicity	-	-	-	+	Sudden	Clinical suspicion confirmed with RBC AchE activity	-	History of exposure to insecticide or living in farming environment with : Diarrhea, Miosis, Bradycardia, Lacrimation, Emesis, Salivation, Sweating
Ischemic stroke	-	-	+/-	+	Sudden	-	MRI for ischemia	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
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 gliomatosis	-	-	+	-	Insidious	Cancer specific molecular characteristics Normal CSF	MRI (expansile, T2 hyperintense lesion)	Seizures, memory loss, motor weakness, visual symptoms, language deficit, and cognitive and personality changes
Central nervous system lymphoma	+	-	+	+/-	Insidious	CSF cytology, flow cytometry, and stereotactic brain biopsy	MRI (parenchymal or leptomeningeal enhancement)	Associated with immunodeficiency Focal neurological deficits, neuropsychiatric symptoms, signs of raised intracranial pressure, seizures, and ocular symptoms

The most important differential diagnosis when it comes to the rabies presentations include meningitis and encephalitis. It is important to differentiate different rabies from each one of the causes of meningitis/encephalitis, which may differ based on the season of occurrence and the geographical region.

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

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. Epidemiological 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.