Shingles

Description
  • Neuralgic pain and blistering skin eruptions that occur due to reactivation of the chicken pox virus - varicella zoster virus (VZV).
  • Incidence of herpes zoster (shingles) increases with decline in T-cell-mediated immunity, which may occur with age or immunosuppression.
  • Rash typically resolves in 2 to 4 weeks, but nerve pain may continue for months to years after lesions heal (post-herpetic neuralgia).
  • Occurs in approximately 0.4%-1% of adults per year.  Cumulative lifetime incidence of 10-20% of the population.
  • Shingles cannot be passed from one person to another.  However, the VZV can be spread; someone who has never had chickenpox could develop chickenpox if exposed to someone with shingles.  Transmission occurs via direct contact with the fluid from the blisters.  A person is not contagious before blisters appear or after crusts develop over the blisters.
  • Risk factors:
    • Age – major risk factor.  Immune control of varicella zoster virus declines with age.
    • Family history
    • Male gender
    • Caucasian
    • Severe immunosuppression (eg. HIV, certain cancers, chemotherapy, high dose chronic oral steroids)
    • Rheumatoid arthritis
    • Lupus
    • Inflammatory bowel disease
    • COPD
    • Asthma
    • Chronic kidney disease (CKD)
    • Depression
    • Type 1 diabetes mellitus
  • For more information, go to:
Signs and Symptoms
  • Characterized by a painful, blistering rash
    • Usually unilateral and follows dermatomal distribution, does not cross the body midline
    • May involve any area of skin, but thoracic, cranial (trigeminal nerve), lumbar and cervical dermatomes most common
    • Rash typically consists of macules or papules that evolve into vesicles or pustules:
      • Begins with macule formation, quickly turns into papules
      • Clear vesicles form within 1-2 days of rash onset; new ones appear over 3-5 days
      • Vesicles evolve into pustules within 1 week
      • Lesions ulcerate and crust 3-5 days later
      • Healing occurs within 2 to 4 weeks (but may take longer, especially if immunocompromised)
  • A prodromal stage of pain, burning, tingling or numbness around affected nerves may occur 1 to 5 days (sometimes weeks) before the rash appears.  Flu-like symptoms may also occur.
  • Secondary symptoms, such as fever, are uncommon unless complications (such as a bacterial superinfection).
  • Complications include:
    • Post-herpetic neuralgia (PHN); persistent nerve pain that continues months to years after rash resolves
      •  Incidence rates for PHN that persists:
        • 1 month after rash onset: 40%
        • 3 months after rash onset: 13%
        • 1 year after rash onset: 7%
      • Risk factors for developing PHN:
        • Older age
        • More severe pain during prodrome and onset of rash
        • Larger rash surface area
    • Skin changes, such as secondary bacterial infection, scarring or pigmentation changes
    • Ophthalmic complications (herpes zoster ophthalmicus) such as periorbital rash, conjunctivitis, keratitis or uveitis, which can lead to vision loss and debilitating pain.  May occur in 25% of herpes zoster cases
    • Facial paralysis
    • Ear involvement can lead to hearing and balance problems
    • Neurologic changes, including altered mental status, headache, muscle weakness, loss of coordination, or tremor may present rarely
Differential Assessments

Confirmation of shingles diagnosis is based on the presence of the characteristic symptoms described above and the patient's history. Rule out the following conditions that may present with similar symptoms:

  • Herpes simplex virus (HSV)
    • Most common alternate cause
    • Dermatomal presentation is rare with HSV; suspect HSV instead of shingles if rash follows atypical pattern
    • If patient has had a similar vesicular rash in the same location previously, suspect recurrent HSV rather than shingles
  • Contact dermatitis
    • Pruritic inflammation of the skin caused by contact with an allergen or irritant. History of allergies, exposure, shape and location of lesions may provide clues to the cause
  • Impetigo
    • Small pus-filled blisters and / or honey-colored, crusted erosions or other signs of secondary bacterial infection.  Refer to minor ailment guidelines for treating bacterial skin infections
  • Cellulitis
    • Typical presentation includes a rapidly enlarging, swollen, warm, tender and painful lesion.  Does not follow dermatomes. Refer for medical assessment, oral antibiotic treatment may be indicated
  • Insect bites and stings
  • Candidiasis
    • May occur on the trunk and consists of many papules with a random distribution.  Does not follow dermatomes.  Typically occurs in skin folds (under breast, buttocks, armpits, between toes / fingers)
  • Autoimmune blistering disease such as bullous pemphigoid
    • 1 to 4 cm urticarial plaques and bullae (blisters) typically in a bilateral, symmetric formation on the trunk and/or limbs. Does not follow dermatomes
  • Dermatitis herpetiformis
    • Related to celiac disease
    • Vesicles form most commonly on scalp, shoulders, buttocks, elbows and knees.  Typically not as wide-spread as a shingles rash and does not follow dermatomes.  Suspect if patient has celiac disease
  • Drug eruptions
    • Morbilliform - typically appears on trunk, then spreads to limbs symmetrically.  Rash consists of macules and papules and is commonly wide-spread. Suspect if patient recently started oral or topical treatment with a medication
    • Fixed drug eruption - erythematous edematous plaques that may blister - appear in same spot each time the patient is exposed to the same or a related drug. Rarely presents in a linear formation similar to herpes zoster
When to Refer
  • Immunocompromised patients (HIV, malignancies, uncontrolled diabetes, etc.) or on immunosuppressive drugs (see table below)
    • Higher potential for severe disease and complications

6-MP

Cytoxan

Chemotherapies (except tamoxifen and hydroxyurea)

Abatacept

Cyclosporin

Mycophenolate mofetil

Adalimumab

Etanercept

Rituximab

Alemtuzumab

Systemic corticosteroids (20mg/day or more of prednisone or equivalent) for 14 days or more

Sirolimus

Anti-thymocyte globulin

Infliximab

Tacrolimus

Azathioprine

Leflunomide

 

Basiliximab

Methotrexate

Cyclophosphamide

Mitoxantrone

 

  • Atypical rash presentation
    • May not be shingles and needs further assessment

  • Extensive or rapidly progressing signs & symptoms of secondary bacterial infection eg, cellulitis
    • Potential need for systemic antibiotic therapy
  • Neurologic changes (confusion, delirium)
    • May indicate severe disease; needs further assessment
  • Severe pain
    • Can indicate severe disease or need for systemic corticosteroids or stronger analgesics eg, opioids
  • Ophthalmic (vesicles on tip of nose, blurred vision, eye pain) or auricular involvement (vesicles in or around ear, reduced hearing, vertigo)
    • Higher likelihood of severe complications, such as visual or auditory impairment, and requires medical assessment and followup

  • Recurrent episode within a year of previous shingles episode
    • Frequent recurrences often manifest as more severe disease or high incidence of post-herpetic neuralgia, and may require additional treatment

  • Pregnancy
Treatment
    • Goals of Therapy
      • Stop viral replication
      • Accelerate healing of skin lesions
      • Relieve acute pain
      • Reduce or prevent post-herpetic neuralgia

    • Nonpharmacologic treatment
      • Keep rash clean and dry to reduce risk of bacterial superinfection.
      • Prevent transmission of the virus to another person:
        • Keep fluid-filled blisters and rash covered.
        • Wash hands often.
        • Do not touch or scratch the rash.
      • Avoid use of topical antibiotics and dressings with adhesives as these may cause irritation and delay rash healing.
      • Sterile dressings (wet or dry) may help relieve discomfort in some patients

    • Pharmacologic treatment
      • Systemic antivirals (acyclovir, famciclovir, valacyclovir).
      • Treatment of most benefit for patients at risk for prolonged or severe symptoms, i.e., immunocompromised people and persons older than 50 years.
      • When referring patients patients at high risk or with symptoms of complicated disease, consider initiating treatment with an antiviral especially if they do not have immediate access to medical care.
      • Benefit of treating younger and healthier populations has not been proven. Antiviral therapy is not routinely recommended but can consider if patient requests treatment.
      • Treatment must be initiated within 72 hours of rash onset for significant benefit.
        • If ocular involvement, immunocompromised patients initiation of an antiviral imay be considered up to 7 days after onset (these patients must also be referred to a physician).
      • Reduce duration of viral shedding, acute pain, appearance of new lesions, and hasten time to resolution.
      • Most data suggests lesion healing in 5 days with anti-viral treatment vs. 7 days without treatment.
      • Valacyclovir and famciclovir may provide greater pain reduction than acyclovir.
      • Valacyclovir may provide faster resolution of pain than acyclovir (38 days vs. 51 days).
      • Valacyclovir and famciclovir are reported to have equivalent efficacy.
      • Antiviral treatment in general does not appear to reduce the occurrence of post-herpetic neuralgia, though evidence is conflicting.  Famciclovir may decrease duration of post-herpetic neuralgia.
    • Dosing (7 day course):
      • Acyclovir 800mg five times daily
      • Famciclovir 500mg three times daily
      • Valacyclovir 1000mg three times daily
          • Adjustments required in renal dysfunction (value ranges indicate eGFR):

Acyclovir

Valacyclovir

Famciclovir

-

<10 ml/min: 500mg once daily

<20 ml/min: 250mg once daily

<10 ml/min: 800mg q12h

10-30 ml/min: 1000mg once daily

20-39 ml/min: 500mg once daily

10-25 ml/min: 800mg q8h

30-50 ml/min: 1000mg q12h

40-59 ml/min: 500mg q12h

>25 ml/min: No adjustment

>50 ml/min: No adjustment

>60ml/min: No adjustment

 

  • Topical antivirals are ineffective for treatment of shingles.
  • Oral corticosteroids may improve symptoms (especially pain), but do not accelerate healing or reduce incidence of post-herpetic neuralgia. This is an option the patient's physician might consider if pain is severe.
  • Acetaminophen and NSAIDs can be recommended for mild-to-moderate shingles pain.

  • Special population: Pediatrics
    • The benefit of treating shingles, with antivirals, in a pediatric population is uncertain.  
    • Developing shingles at a young age may indicate an underlying condition (eg. immunocompromise); assessment by a physician or nurse practitioner may be appropriate
    • May still prescribe for this population.  Only acyclovir has approved pediatric dosing - 80mg/kg/day, divided QID, max of 800mg/dose.
General Advice / Monitoring
  • Advice
    • Non-pharmacologic treatment as above.
    • Lesions should heal in 5 to 7 days
    • Caution that pain may persist for days to weeks after the lesions heal.

  • Follow-up in 7 days after treatment initiation
    • Assess benefit
      • Ensure adequate pain control
      • Advise patient to contact their physician or nurse practitioner if the pain persists long-term (postherpetic neuralgia)   
      • Majority of blisters should be scabbed over with no new vesicle formation
      • Refer if rash is not resolving
    • Assess for adverse effects
      • Oral antivirals are well tolerated.  Mild, transient headache and nausea are the most common side effects.
      • Advise patients to ask their doctor about the shingles vaccine in one year’s time. Shingles renews immunity in many people so immediate vaccination is not thought to be of benefit.
Products
Detailed information on contraindications, cautions, adverse effects and interactions is available in individual drug monographs in RxTx - CPS from CPhA, RxTx (Internet), Lexi-Comp, AHFS, www.drugs.com or other reliable drug monograph references. For comprehensive drug comparisons, see RxFiles charts (www.rxfiles.ca).
This information should be routinely consulted before prescribing.

Drug
Recommended Dose

Renal dosage (based on eGFR)

Approx. Cost 
(7 days)

Acyclovir

800mg five times per day for 7 days

<10 ml/min: 800mg q12h

10-25 ml/min: 800mg q8h

>25 ml/min: No adjustment

$75.00

Valacyclovir

1000mg three times per day for 7 days

<10 ml/min: 500mg once daily

10-30 ml/min: 1000mg once daily

30-50 ml/min: 1000mg q12h

>50 ml/min: No adjustment

$50.00

Famciclovir

500mg three times per day for 7 days

<20 ml/min: 250mg once daily

20-39 ml/min: 500mg once daily

40-59 ml/min: 500mg q12h

>60ml/min: No adjustment

$50.00

Prescribing and Billing Details
  • Prescribe 7 days of treatment only. No refills. 
  • Only products with an official indication from Health Canada for shingles are considered for these guidelines.  Only the active ingredients in the "products" section are approved for pharmacist prescribing. 
Treatment Flowchart
Pharmacist Assessment Documents
References / Suggested Reading
  1. Merck Manual: http://www.merckmanuals.com/professional/infectious_diseases/herpesviruses/herpes_zoster.html
  2. Evans, G. Herpesvirus infections. In CTC, RxTx  online databases. CPhA by subscription. Available in Saskatchewan through SHIRP (www.shirp.ca).
  3. Herpes Zoster.  Dynamed.  Available at https://dynamed.ebscohost.com/ by subscription. 
  4. Albrecht, M.  Treatment of herpes zoster in the immunocompetent host.  UpToDate.  Available at www.uptodate.com by subscription
  5. Janniger, C.  Herpes Zoster.  Medscape reference.  Available at http://emedicine.medscape.com/article/1132465-overview (free access, requires registration).
Prepared by medSask
Posted Feb 2018, Updated Mar 2018