Viruses and Influenza

 

Herpes

Zoster (VZV)

aka Shingles

vesicular rash on erythematous base along one dermatome.  Usually does not cross the midline, though due to a small overlap of spinal nerves, may cross slightly.

 

It comes from the Latin ‘cingulus’ which means ‘girdle’. ‘Gird’ means to encircle as with a belt or band. A girdle is a device which encircles in such a fashion. With varicella’s tendency to follow a dermatome around the body, it is clear to what ‘cingulus’ refers.

 

EMEDhome:

The diagnosis of herpes zoster is based on clinical presentation. The primary differential diagnosis is zosteriform herpes simplex virus infection.  How does the clinician differentiate the two?Herpes simplex infection tends to produce a shorter and milder prodrome, followed by skin vesicles that are more uniform, smaller, and closely clustered. Herpes simplex is also more likely to be recurrent (Mayo Clin Proc, Vo. 79, pg. 1057).

 

The immunocompromised can have multi-dermatomal involvement.

Can give acyclovir if immunocompromised, eye involvement (suspect if nose affected), elderly, or disseminated

Use acyclovir, fam, or val.  Possible superiority of Valtrex, also less expensive (In long Run) and more compliance.  Steroids do not help prevent post neuralgia or outcome (NEJM 330:896).  The elderly should be treated with antivirals if less than 72 hours from rash onset as they will still derive benefit.

 

Acyclovir — Acyclovir (ACV) has an excellent safety profile but is only moderately active against VZV in vitro with a median effective concentration (EC50) of 2.3 to 4.0 µg/mL against clinical viral isolates [5]. Although oral ACV (800 mg five times daily for 7-10 days) has been the mainstay of herpes zoster treatment, its poor bioavailability and need for frequent daily dosing has prompted the design of newer antiviral agents (valacyclovir and famciclovir) with improved pharmacokinetics [6-9].

 

Valacyclovir — Valacyclovir is well absorbed from the gastrointestinal tract and is rapidly converted to ACV in vivo, thereby providing a three- to five-fold increase in ACV bioavailability [9,13]. (See “Valacyclovir: An overview”). Valacyclovir is approved by the United States Food and Drug Administration (FDA) for the treatment of herpes zoster in immunocompetent adults. (1000 mg PO three times daily for 7 to 14 days)

 

Famciclovir — Famciclovir, the prodrug of penciclovir, is well absorbed from the gastrointestinal tract and is rapidly converted in the intestinal wall and liver to the active compound penciclovir that has broad activity against VZV (500 mg given three times daily)

 

 

Localized herpes zoster in an immunocompetent host is only contagious from direct contact with open lesions.

The mechanism of zoster paresis has not been determined. Weakness develops abruptly within 2-3 weeks after the rash and can involve upper or lower extremities. The prognosis of zoster paresis is good (MMWR, June 6, 2008).

Herpes Zoster Keratitis

 

Hutchinson’s Sign

herpetic involvement of tip of nose, V1 distribution

treat c acycolvir, fam, or val.  Get Optho consult

can treat with oral if immunocompetent (N Engl J Med 2002 Aug 1;347(5):340-6.)

 

Ramsey Hunt Syndrome (Herpes Zoster Oticus)

Ramsey Hunt syndrome is characterized by unilateral facial paralysis, a herpetiform vesicular eruption, and vestibulocochlear dysfunction. Can see vesicles on ear drum and decreased taste.  The vesicular eruption may occur on the pinna, external auditory canal, tympanic membrane, soft palate, oral cavity, face, and neck as far down as the shoulder. There is considerably more pain than is associated with Bell’s palsy, and the pain is frequently out of proportion to physical findings. In addition, outcomes are worse than with Bell’s palsy, with a lower incidence of complete facial recovery and the possibility of sensorineural hearing loss. Therapy is similar to that for Bell’s palsy. Antiviral therapy for 7 to 10 days have been advocated, also steroids prednisone 60 mg c 3 week taper.

RAMSAY HUNT SYNDROME –

A Case Report

 

P.S. NAGAPUPRE

 

A Case Report

 

Prof & Head, Deptt of ENT, MGIMS Sevagram,

 

Wardha, Maharashtra -442102

 

Introduction :

 

In 1906 James Ramsay Hunt gave a classic

 

description of the syndrome consisting of blisters

 

facial paralysis, and inner ear disturbances due

 

to herpes zoster. Since his description, the name

 

Ramsay Hunt and the designation Herpes Zoster

 

Oticus have been synonymous.He felt the problem

 

to be geniculate ganglionitis due to the herpes

 

virus. Subsequent investigators with the benefit

 

of histopathologic studies of autopsy cases of

 

patients with herpes zoster oticus demonstrated

 

little, if any, ganglion involvement. They did find

 

heavy lymphocytic infiltration in the substance

 

of the facial nerve. These findings were present

 

in facial nerve in several patients with paralysis

 

who recovered (1).

 

Discussion :

 

Herpes zoster oticus or Ramsay Hunt

 

syndrome includes facial paralysis associated with

 

hearing loss, dizziness, and herpetic eruption

 

around the auricle (commonest site being the

 

concha of the auricle). Herpes zoster oticus is the

 

cause of 2 to 10% of all cases of facial paralysis,

 

including 3 to 12% of adults and approximately

 

5% of children.

 

The facial nerve is the commonest to be

 

involved followed by the ocular nerve. This is due

 

to the fact that these nerves pass through bony

 

canal in the skull. This course in the bony canal

 

increases the chances of entrapment.

 

Pathologically, the theory of inflammatory

 

changes as a cause of Bell’s palsy or facial paralysis

 

has been proposed by many authors. Sade described

 

casesoffacialparalysissecondarytoexternalotitis

 

with the inflammation traveling along the chorda

 

tympani or sensory anastomoses to the facial

 

nerve. Denny – Brown showed that pressure on a

 

nerve causes ischemic paralysis. Even a small

 

amount of inflammation will suffice to cause

 

pressure; thus, a relatively small amount of edema

 

or inflammatory exudates could cause strangulation

 

of the nerve. Fisch proved these changes

 

with photography of the inflammatory changes

 

in the labyrinthine portion of the facial nerve (1).

 

Hunt classified the disease into 4 grades

 

asfollow (7):

(1) Disease affecting the sensory portion of

the CN VII.

(2) Disease affecting the sensory and motor

divisions of the CN VII

(3) Disease affecting the sensory and motor

divisions of the CN VII with auditory

symptoms

(4) Disease affecting the sensory and motor

divisions of the CN VIIwith both auditory

and vestibular symptoms.

Many authors have shown that there is no

real difference between herpes zoster and Bell’s

palsy. Complement fixation test carried out by

Tomita et al (3) in 1973 found that 25% of patients

with Bell’s palsy had positive for complement

J MGIMS, January 2006, Vol 11, No (i), 55 – 57

fixation tests. Paralysis of herpes zoster may more

likely be a complete but predictability from

electrical tests, and the time of recovery seem

similar to those of Bell’s palsy however the

natural history between the two differs in several

ways (2).

1. Bell’s palsy recurs in 12% of cases, but

Herpes Zoster rarely recurs.

2. With Bell’s palsy the decrease in response

to electrical testing peaks in 5-10 days

but in Herpes zoster the peak is later

(10-14days).

3. 84% of those suffering from Bell’s palsy

have satisfactory recovery, but 60% of

those with Herpes zoster oticus recover

to a satisfactroy degree.

The medical management for facial

paralysis of herpes zoster is aimed at eliminating

inflammation and ischemia of the nerve, thereby

restoring facial function as quickly as possible.

Steroid dose as recommended for adults is a

daily total of 1mg/kg body weight in divided

dose. If the palsy is incomplete by the fifth day

the dosage can be tapered to zero during the next

5 days, if there is a question about the severity

or the progression of severity full dosage is

recommended for 10 days and then tapered

over the next 5 days(4,5).

Acyclovir, a virostatic drug developed

for the use in the treatment of herpes simplex

has been found to prevent replication of varicellazoster

virus. Acyclovir in the host cell is converted

to acyclovir triphosphate and gets incorporated

in the newly formed viral DNA, resulting in

termination of the DNA molecular chain. Because

VZV is generally less sensitive to acyclovir than

is HSV, higher dose must be used to treat VZV

infection. Oral Acyclovir is available; however,

absorption from the gastrointestinal tract is only

15% – 25% of the ingested dose. A dose of 800mg

five times a day has a modest beneficial effect to

localize the lesion. For these reason intravenous

dose of 10 mg/kg every 8 hours over a 7 days

hospitalization has been recommended. This

intravenous route has more inherent expenses

than an oral route of administration. Prognosis

depends primarily on immediate initiation of

therapy(6). Alternate antiviral agents such as

valacyclovir (1 g orally three times a day for 10

to 14 days) or famciclovir (500mg orally three

times a day for 10 days), which achieve adequate

levels by an oral route, are now available as an

alternative to intra-venous.

Bibliography :

1. Crabtree, J.A., Herpes Zoster Oticus and Facial

paralysis.

Otolarygologic clinnic of North America,

June 1974.

7(2): p. 369-373.

2. May, B.S.a.M., Disorder of the facial nerve. sixth

ed. Scott-Brown’s Otolaryngology, ed. A.G.

Kerr. Vol. vol. 3. 1997, Jordan Hill, Oxford:

Butterworth-Heinmann. 3/24/25.

3. Tomita, H., Hayakawa, W. and Hondo, R.,

varizella-Zoster virus in idiopathic facial palsy.

Archives otolayngology,

1972. 95: p. 364.

4. May, B.S.a.M., Causes and management of facial

paralysis. sixth edition ed. Disease of the ear, ed.

L.a. Wright, 198 madison avenue, New York:

Georgina Bentloff. 261.

5. Adour, k.K., Facial paralysis.

Trans. Am. Acad.

Ophthal. Otolaryng.,

1971. 76: p. 1284.

6. John R.E. Dickins, J.T., Sharon S. Graham,

Herpes zoster oticus : Treatment with intravenous

Acyclovir.

Laryngoscope, july 1988. 98: p.776-779.

7. Phillip A. Wackym, John S. Rhee., facial paralysis

sixteen ed. Ballenger’s Otorhinolaryngology

Head and Neck surgery, ed. Snow, J.B.Jr.,

Ballenger, J.J, 2003, BC Decker Inc., Hamilton.

Ontario: 492-494.

J MGIMS, January 2006, Vol 11, No (i), 55 – 57

 

 

Post-Herpetic Neuralgia

After zoster attack.

Persistent pain, Try TCAs.

Amitriptyline

10-25 mg PO OD

Gabapentin Postherpetic neuralgia: Day 1: 300 mg, Day 2: 300 mg twice daily, Day 3: 300 mg 3 times/day; dose may be titrated as needed for pain relief (range: 1800-3600 mg/day, daily doses >1800 mg do not generally show greater benefit)

 

Treatment of Herpes Zoster (EMEDhome)

• Antivirals: Antiviral agents reduce the duration of viral shedding, hasten rash healing, reduce the severity and duration of acute pain, and reduce the risk of progression to PHN. Antiviral treatment is specifically recommended for patients older than 50 years, those who have moderate or severe pain or rash, and those with involvement of nontruncal dermatomes (eg, the face) (1).It is often said that antivirals are not effective if prescribed more than 72 hours after onset of symptoms. In fact, in clinical trials, treatment has been initiated within 72 hours of rash onset, but this is an arbitrarily selected time point (1). Such a rapid initiation of treatment is often not feasible in clinical practice. Although the benefits of treatment that is begun later have not been studied, antiviral treatment should be considered even in patients who present more than 72 hours after rash onset, particularly in the presence of new vesicle formation or complications.
• Corticosteroids: Corticosteroids do not have any effect on PHN. In combination with antiviral therapy, they modestly reduce the severity and duration of acute symptoms (1-3). Corticosteroids are associated with a considerable number of adverse effects and hence should be used only in patients with severe symptoms at presentation or in whom no major contraindications to corticosteroids exist.

References:(1) Sampathkumar P, et al.  Herpes Zoster (Shingles) and Postherpetic Neuralgia Mayo Clin Proc 2009;84:274-280.(2) Harpaz R, et al. Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices  MMWR Recomm Rep 2008;57(RR-5):1-30. (2) Yawn BP, et al. A population-based study of the incidence and complication rates of herpes zoster before zoster vaccine introduction  Mayo Clin Proc 2007; 82: 1341-1349.

 

Oral Herpes Simplex (Cold Sores)

usually HSV I, but may be HSV II

penciclovir 1% cream 2g, apply every 2 hours for 4 days.  or Acyclovir 400 mg TID for 5 days

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CMV

can cause mono

 

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Epstein Barr Virus (EBV)

 

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PML

demyelination of CNS (white matter), paresis, personality changes, no enhancement c contrast

 

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Yellow Fever

black vomit from coagulopathy

 

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Dengue

 

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Hantavirus

aka the sin nombre virus (SRV)

the rodent reservoir is the deer mouse

sever noncardiogenic pulmonary edema (NCPE)

8 to 23 day incubation period after exposure

prodome of fever and severe myalgias

lymphocytosis

florid pulmonary edema with normal heart size

PCR for SNV

No treatment, mortality of 50%

 

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Paramyxoviridae

Viruses in the Paramyxoviridae family include many common, well-known agents associated with respiratory infections, such as respiratory syncytial virus, and childhood illnesses, including the viruses that cause mumps and measles. Some of these viruses are widespread, particularly during the winter season. Screening of specimens could therefore be expected to detect particles of these common viruses. At this point, it cannot be ruled out entirely that tests for the SARS agent are detecting such “background” viruses rather than the true causative agent. The Paramyxoviridae family also includes two recently recognized pathogens, Hendra virus and Nipah virus. These related viruses are unusual in the family in that they can infect and cause potentially fatal disease in a number of animal hosts, including humans. Most other viruses in the family tend to infect a single animal species only. Nipah virus first began to cause deaths in humans in Peninsular Malaysia in 1998 in persons in close contact with pigs. The outbreak caused 265 cases of human encephalitis, including 105 deaths. Two separate outbreaks of Hendra virus, associated with severe respiratory disease in horses, caused two human deaths in Australia in 1994 and 1995. No human-to-human transmission was documented in either outbreak. No treatment was available for cases caused by either of these two viruses. Human-to-human transmission did not occur.

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SARS

Corona Virus

Incubation period of 2-10 days

Spread by respiratory droplets perso to person, or by aerosolization during high risk procedures such as intubation or sputum induction

Most common lab abnormality was lymphopenia but can also see leukopenia thrombocytopenia, and elevated LFTs

Can dx with PCR, viral culture or EIA

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Influenza

randomized X2 blind, Type A and B, reduction in symptoms and time to complete cure

Four Tbl QD x 3 days of SAM (sambucol extract)

Sambucol for Influenza (J Altern and Complem Med 1:4, 1995, 361-369)

CDC Summary: Indications For Antiviral Agents Against InfluenzaMMWR Recommendations and Reports from the CDC discusses the use of antiviral agents for influenza.  Relevant portions of interest to EM practice are summarized below.  Recommended dosing of specific agents may be found in the EMedHome Database. TreatmentWhen administered within 2 days of illness onset to otherwise healthy adults, amantadine and rimantadine can reduce the duration of uncomplicated influenza A illness, and zanamivir and oseltamivir can reduce the duration of uncomplicated influenza A and B illness by approximately 1 day compared with placebo. More clinical data are available concerning the efficacy of zanamivir and oseltamivir for treatment of influenza A infection than for treatment of influenza B infection. None of the four antiviral agents has been demonstrated to be effective in preventing serious influenza-related complications (e.g., bacterial or viral pneumonia or exacerbation of chronic diseases).  Data are limited and inconclusive concerning the effectiveness of amantadine, rimantadine, zanamivir, and oseltamivir for treatment of influenza among persons at high risk for serious complications of influenza. Fewer studies of the efficacy of influenza antivirals have been conducted among pediatric populations compared with adults. One study of oseltamivir treatment documented a decreased incidence of otitis media among children. To reduce the emergence of antiviral drug-resistant viruses, amantadine or rimantadine therapy for persons with influenza A illness should be discontinued as soon as clinically warranted, typically after 3-5 days of treatment or within 24-48 hours after the disappearance of signs and symptoms. The recommended duration of treatment with either zanamivir or oseltamivir is 5 days. Chemoprophylaxis Chemoprophylactic drugs are not a substitute for vaccination, although they are critical adjuncts in the prevention and control of influenza. Both amantadine and rimantadine are indicated for the chemoprophylaxis of influenza A infection, but not influenza B. Both drugs are approximately 70%-90% effective in preventing illness from influenza A infection . When used as prophylaxis, these antiviral agents can prevent illness while permitting subclinical infection and the development of protective antibody against circulating influenza viruses. Therefore, certain persons who take these drugs will develop protective immune responses to circulating influenza viruses. Both drugs have been studied extensively among nursing home populations as a component of influenza outbreak control programs, which can limit the spread of influenza within chronic care institutions Among the neuraminidase inhibitor antivirals, zanamivir and oseltamivir, only oseltamivir has been approved for prophylaxis. When determining the timing and duration for administering influenza antiviral medications for prophylaxis, factors related to cost, compliance, and potential side effects should be considered. To be maximally effective as prophylaxis, the drug must be taken each day for the duration of influenza activity in the community. However, to be most cost-effective, one study of amantadine or rimantadine prophylaxis reported that the drugs should be taken only during the period of peak influenza activity in a community. Persons at High Risk Who Are Vaccinated After Influenza Activity Has Begun. Persons at high risk for complications of influenza still can be vaccinated after an outbreak of influenza has begun in a community. However, the development of antibodies in adults after vaccination can take approximately 2 weeks. When influenza vaccine is administered while influenza viruses are circulating, chemoprophylaxis should be considered for persons at high risk during the time from vaccination until immunity has developed. Persons Who Provide Care to Those at High Risk. Chemoprophylaxis during peak influenza activity can be considered for unvaccinated persons who have frequent contact with persons at high risk. Persons with frequent contact include employees of hospitals, clinics, and chronic-care facilities, household members, visiting nurses, and volunteer workers. Persons Who Have Immune Deficiency. Chemoprophylaxis can be considered for persons at high risk who are expected to have an inadequate antibody response to influenza vaccine. This category includes persons infected with HIV, chiefly those with advanced HIV disease. Source:  MMWR Recommendations and Reports:  April 25, 2003 / Vol. 52 / No. RR-08

 

(Arch Intern Med 163:1667, July 28, 2003 ) Tamiflu did not lower pneumonia rates.  The placebo group was sicker than the treatment group.

 

Clinical judgment was as good as CPR or rapid-flu test (Ann Emerg Med 2005;46(5):412)

 

Avian Influenza

Implications for ICUs (Inten Care Med 2006;32:823)

H5N1 increases chance of human spread

 

 

 

Cochrane review on tamiflu

Michelle Lin’s Paucis Verbis on who to treat

Differentiating between H1N1 Flu and CAP

(Thorax 2011;66:247)

derivation

• <=65 y/o
• Temp >=38
• WBC<=12
• Bilat Consolidation
• mental orientation

4 or 5 predicted H1N1 with LR+9.0

0 or 1 predicted CAP with LR+75

 

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Antivirals

Acyclovir, Famciclovir, and Valacyclovir

Herpes, EBV, and CMV

Ganciclovir

wider antiviral spectrum

Cidofovir

acyclovir resistant HSV and ganciclovir resistant CMV

Foscarnet

Herpes, HIV, HBV

Amantadine and Rimantadine

for Influenza

Ribavirin

RSV, Flu, HSV, HIV, HCV, and hemorrhagic fevers

Oseltamivir

Influenza

Zanamivir

Influenza

 

 

 

 

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