Introduction:

Rabies is a zoonotic disease caused by a neurotropic virus of the Lyssavirus genus. The virus is transmitted from animal to humans by bite, scratch or by direct exposure of mucosal surfaces to saliva from an infected animal (1). Human rabies can manifest in either encephalitic or paralytic forms (2). The clinical stages are: incubation, prodrome, acute neurological signs, coma, and inevitable death. The diagnosis is still challenging and often delayed, particularly the paralytic form (3).

Infection with the virus must be considered and treated soon after viral transmission; failure to diagnose and to intervene will usually result in disease progression and death (2).

We report a case of a patient who consulted our Emergency Department (ED) and whose clinical picture posed a diagnostic and therapeutic problem.

Observation:

A 61-year-old female with no past medical history presented to our ED for sleep disorders restlessness, anxiety, refusal of food, and watery disgust for two days. On examination, the patient appeared agitated and the laboratory investigations were normal. Due to the pandemic context of covid-19, a PCR test was performed and was negative. A brain and thoracic CT were done and also returned normal. The patient was discharged with symptomatic treatment.

After 24 hours, her condition worsened with abdominal pain and altered consciousness requiring medical service intervention. Upon arrival, the patient presented with cardiac arrest resuscitated within two minutes. Intubation and mechanical ventilation were performed with fluid resuscitation and therapy with vasopressors. After return of spontaneous circulation, the physical exam revealed no fever, blood pressure of 100/58 mmHg with 1mg/h of adrenaline, no peripheral signs of shock, and normal pulmonary exam. No sign deficit on neurological exam was noted. The ECG did not show arythmias and in particular there were no repolarization abnormalities suggestive of active myocardial ischemia. Initial diagnosis was septic shock. The patient received empirical antibiotic therapy, catecholamine. Cerebrospinal fluid exam was performed and was normal. Faced with the absence of an obvious cause for the cardiorespiratory arrest, shock and initial agitation a toxicological assessment was requested and was negative. On the five days of hospitalization, the patient presented multiple organ failure and death.

Upon re-interviewing the family, it turned out that the patient was raising around 20 cats and that there was the notion of an accidental bite by one of her cats 3 weeks before admission. No medical advice was sought and the family reported a completely healed wound. The patient did not receive any vaccination or serotherapy. Rabies serology came back positive and the diagnosis was confirmed after brain biopsy.

Discussion:

Rabies is a neurotropic RNA virus transmitted to humans through the saliva of infected animals, usually from bites (4). The virus is almost invariably fatal after the onset of neurologic symptoms (2). The rabies virus reaches the brain by centripetal propagation mediated by retrograde trans-neuronal transfer and the clinical stages of rabies are: incubation, prodromes, acute neurological signs, coma, and death (3). The incubation period or eclipse phase can vary from weeks to years, but lasts 1-3 months on average (5). The cause of this variation is probably multifactorial and can include the site of virus entry and the viral load, the species and strain of the infecting virus and the immunological competence of the host (6). Nonspecific prodromal symptoms include malaise, headache, fever, anxiety, and agitation. Paresthesias, pain, and pruritus are the earliest neurologic symptoms (5). Two classical forms of rabies are generally recognized: furious (also called encephalitic which develops in approximately 80% of cases) and paralytic (which occurs in approximately 20% of cases). The factors that determine the development of either form remain unclear (7,8), but each form may be characterized by specific symptoms, although case definition can typically be established with certainty only when the disease reaches the acute neurological phase (6). The paralytic form of disease differs from the encephalitic form in that muscle weakness develops early, whereas progression to coma and death often take longer than with the encephalitic form (3). In our case, the patient presented with signs and symptoms that commonly occur in the encephalitic phase of rabies, including agitation, hyper-excitability, and hydrophobia.

Infection with rabies virus can be difficult to diagnose ante-mortem (3). Hydrophobia is the most characteristic and no clinical signs of disease are pathognomonic for rabies (9). Given that the differential diagnosis for altered mental status is broad (reflecting impairment of affect, behavior, or cognition), the workup should start with reversible and life-threatening causes as recalled by use of the mnemonic “rule-out the WHIMPS.” Each letter of this acronym signifies 1 or more of the following conditions: Wernicke encephalopathy, hypoglycemia, hypoxia, hypoperfusion of the central nervous system, and hypertensive encephalopathy, infections and intracranial processes, metabolic derangements (such as hyponatremia/ hypernatremia, hypocalcemia/hypercalcemia, and hyperammonemia), poisons, and seizures. The workup should start with taking a history, looking for clues to etiology and to temporal relation-ships with symptoms, and then proceed to a thorough physical examination and laboratory testing ( an electrocardiogram, a complete blood count, a comprehensive metabolic panel, a toxicology screen, as well as measurement of levels of B12, ammonia, and thyroid-stimulating hormone, and a radiologic examination for intracranial lesions via computerized tomography or magnetic resonance imaging, a chest x-ray, and a urinalysis). Further diagnostic tests (such as electroencephalography and cerebrospinal fluid exam) may also be considered. In the appropriate setting (fever, flulike symptoms, or cerebrospinal fluid inflammation), microbiologic assays (spirochetes) would be recommended. In patients with a longer duration of altered mental status symptoms, neuro-psychologic testing and functional imaging may be ordered. In addition to pursuing potential medical and neurologic etiologies, psychologic ones also need to be investigated (5). For our patient, there is initially no history of bite or scratch and the symptoms were no specific.

The management of clinical rabies in nonvaccinated patients is largely palliative, and death is invariably expected (2). The onset of clinical symptoms of rabies and death can be prevented by adequate post-exposure prophylaxis (PEP) including vaccines and, if required, rabies immunoglobulin (RIG) (9).

Conclusion:

Human rabies is considered as a disease of complex neuropathogenetic mechanisms and diagnostic challenges: The infection can be treated after recognized exposures; however, medical management once the clinical disease develops has almost universally proved to be unsuccessful, resulting in fatal outcomes.

References:

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