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Shingles (Herpes Zoster)

Essentials

  • Diagnosis is usually based on the clinical picture.
  • Antiviral medication should be considered case by case, particularly if less than 3 days have elapsed since the eruption of the rash.
  • Antiviral medication should always be started for patients with immunodeficiency, if the disease is located in the trigeminus area, if the patient is older (over 60) or if the clinical picture is severe.
  • Remember to ensure effective analgesic treatment of acute shingles pain and any postherpetic neuralgia.

Aetiology

  • Shingles, also known as herpes zoster, is caused by the varicella zoster virus (VZV) remaining in the paraspinal ganglia after a varicella infection.
    • Shingles represents reactivation of the virus.
    • Even people vaccinated against varicella may develop shingles.

Symptoms and findings

  • Clearly defined erythema usually confined to one side of the midline in the area of a single dermatome, with vesicles in linear formation.
  • A more extensive clinical picture, appearing in several dermatomes, is also possible.
  • Typically occurs on the trunk (particularly in dermatomes T1-L2 ) and the face (dermatomes V1-V3); more rarely on the extremities and in the genital area (Images 1 2 3 4).
  • In 1-2 weeks, the vesicles turn into pustules with ulceration and crusting.
  • Mild general symptoms may occur, including fever, headaches, malaise and fatigue.
  • Acute shingles pain
    • Local skin pain may be constant or periodical.
    • Shooting pain (dysaesthesia) or tenderness to touch (allodynia, hyperalgesia) may begin several (2-3) days before the eruption of the rash.
  • Remember shingles in the differential diagnosis of chest, abdominal and back pain; always check the skin of patients with pain (Image 6).
  • Remember the possibility of immunosuppression particularly in patients with severe shingles or disease spreading beyond the boundaries of one dermatome.
  • Very rarely, patients may have only pain without a rash (zoster sine herpete).
  • The rash usually heals in about 2-4 weeks but scars may remain.
  • In contrast with Herpes simplex Herpes Simplex Infection of the Skin, herpes zoster rarely recurs.

Contagiousness

  • A patient with shingles is less likely to transmit the virus than a chickenpox patient.
  • It is recommended to avoid contact especially with people who belong to high-risk groups and who have not had chickenpox or chickenpox vaccination.
    • Young children
    • Pregnant women
    • Immunodeficiency states (e.g. immunosuppressive drugs, cancer and transplant patients)
  • Shingles contagiousness usually stops when skin lesions form scabs (about 1-2 weeks after the onset of symptoms).

Complications

  • Postherpetic neuralgia
    • Pain persisting after the rash has healed (usually subsides within 6 to 12 months but may in some cases continue for years)
    • People over 70 represent a particular risk group.
  • Eye complications if the ophthalmic nerve is affected
    • Keratitis, corneal ulceration and iritis, for example
    • The eye(s) is/are probably also affected if there is rash along the side of the nose (dermatome of the nasociliary nerve; Image 7).
    • May lead to permanent eye problems.
    • Absolute indications for urgent consultation of an ophthalmologist: the eye is clearly red, the sensation of the cornea is impaired when tested with a cotton wool probe or visual acuity is decreased.
    • Consultation of an ophthalmologist should not delay the start of antiviral medication.
  • Other complications
    • Secondary bacterial infection (cellulitis)
    • Peripheral nerve paralysis (e.g. facial palsy in patients with Ramsay Hunt syndrome (herpes zoster oticus) Peripheral Facial Paralysis)
    • Permanent nerve damage
    • Disseminated shingles
    • Encephalitis (usually in patients with immunodeficiency)

Workup

  • Diagnosis is usually based on the clinical picture.
  • In unclear cases, the virus should be detected on the skin or on the mucosa (nucleic acid detection).
  • For differential diagnosis (impetigo Impetigo, cellulitis Erysipelas), bacterial culture from skin wounds may be necessary.
  • Uncomplicated shingles will not usually elevate inflammatory markers (CRP, leukocytes) unlike erysipelas or cellulitis; in patients with shingles, CRP levels usually remain below 20-30 mg/l.

Differential diagnosis

  • Herpes simplex infection
    • If the patient has fever, and the rash is not situated in one or two dermatomes on one side of the body, the cause may be a primary Herpes simplex infection.
    • A recurrent vesicular rash resembling shingles is very likely caused by Herpes simplex.
  • Acute eczemas Allergic Contact Dermatitis (acute allergic contact eczema, in particular): the main symptoms are itching, erythema and blisters, no fever
  • Impetigo Impetigo: usually few symptoms, may be asymmetric, patchy skin erosions covered with yellow crust
  • Erysipelas Erysipelas: hot, clearly defined erythema, possibly with blisters, usually fever, not that painful, not following the boundaries of dermatomes
  • Cellulitis Erysipelas and severe soft tissue infections Severe Infections of the Skin and Soft Tissues: erythema and blisters, necrotic dark and blueish patches, ulcers, malaise, fever

Treatment

  • Treatment started early (within 3 days from the eruption of the rash) will shorten the duration of the disease and may prevent complications (particularly eye complications and neuralgia) Antiviral Drugs for Preventing Postherpetic Neuralgia.
  • Antiviral medication should be considered case by case, particularly if fewer than 3 days have elapsed since the eruption of the rash.
  • Antiviral medication should always be started (also later in the course of the disease)
    • in immunosuppressed patients (severe systemic disease, poorly controlled diabetes, cancer, primary immunosuppression, HIV infection, or taking immunosuppressants, such as oral glucocorticoids)
    • in patients with trigeminal shingles (remember eye complications!)
    • in the elderly (over 60)
    • in patients with severe, painful disease.

Antiviral drugs

DrugStandard dose, usually for 7 daysComment
Valaciclovir1 g 3 times dailyTaken less frequently, more expensive
Aciclovir800 mg 5 times dailyAffordable
Famciclovir250 mg 3 times daily or 500 mg twice dailyLess commonly used, most expensive
  • N.B.: dose adjustment in patients with various degrees of renal failure
  • For patients with immunodeficiency, eye complications or slow response to treatment, the course of antiviral treatment may need to be extended to 2 to 3 weeks, for example.
  • For patients with immunodeficiency and a severe course of disease, hospital treatment and i.v. aciclovir (10 mg/kg 3 times daily) may be necessary.

Topical treatment

  • Antiviral ointments play no role in the treatment of shingles.
  • Topical treatments such as moist compresses and zinc paste, for instance, may alleviate the symptoms in the initial phase.
  • Antiseptic and antimicrobial creams have also been used (to prevent secondary bacterial infections).

Acute shingles pain and postherpetic neuralgia Corticosteroids for Preventing Postherpetic Neuralgia

  • Nearly all patients have pain or skin hyperaesthesia for a few weeks even after the rash has disappeared.
  • Antiviral treatment given in the acute phase slightly alleviates acute pain and reduces its duration and may reduce the incidence of postherpetic neuralgia Antiviral Drugs for Preventing Postherpetic Neuralgia.
  • In postherpetic neuralgia the pain is prolonged (continuing long after the skin changes have disappeared or continuing for more than 3 months, for example). It usually disappears in 6-12 months, but in the elderly, in particular, the neuralgia may last for years.

Acute shingles pain

  • Usually paracetamol and/or NSAIDs using sufficient dosage.
    • Paracetamol is the safer alternative in children and elderly persons.
  • A mild opioid (codeine, tramadol) may be added to the regimen, as necessary.
  • Topical treatment may help: a zinc ointment or paste, a cooling gel.
  • If the treatment response is poor in acute shingles pain, all medications intended for postherpetic neuralgia (such as amitriptyline or pregabalin, see below) have also been used to treat prolonged acute pain and for possible prevention of neuralgia.

Postherpetic neuralgia

  • See also the article on chronic pain Chronic Pain
  • Tricyclic antidepressants
    • Remember anticholinergic and sedative effects
    • Suitable especially for relatively young, otherwise healthy patients.
    • Contraindications: arrhythmias, urinary difficulties or orthostatic hypotension
    • Start with a small dose in the evening, 10-25 mg, for example, and increase the dose by 5-10 mg every few days until a good analgesic effect is reached or potential adverse effects prevent increasing the dose further (tiredness, dryness of mouth, constipation, urinary difficulties, orthostatic hypotension).
    • 25-75 mg amitriptyline once daily, can be increased up to 100 mg once daily, in single doses in the evening
    • First 10-25 mg nortriptyline once daily, increased by 10-25 mg weekly to the target dose of 75-150 mg daily, in single doses or divided into 2 doses
  • Antiepileptic drugs
    • Pregabalin and gabapentin are first-line drugs for patients with contraindications to tricyclic antidepressants. These may, however, be strongly sedative.
    • Pregabalin starting at 75 mg twice daily and, if needed, increasing after 1-2 weeks to the dose 150 mg twice daily and thereafter, if needed, further up to the dose 300 mg twice daily
    • GabapentinGabapentin for Chronic Neuropathic Pain in Adults, starting at 300 mg in the evening and increasing the dosage in 300-mg steps at intervals of 1-3 days up to 3 600 mg daily, if needed. The daily dose should be taken in 3 divided doses.
  • The SNRIs duloxetine, initial dose (30-)60 mg once daily, or venlafaxine, initial dose (37.5-)75 mg once daily (no official indication, fewer anticholinergic adverse effects compared to tricyclic antidepressants)
    • May be a better and safer alternative compared with tricyclic antidepressants in elderly patients.
  • Secondary treatments
  • Treatment in elderly persons
    • All the aforementioned drugs may usually be used, but the initial and maintenance doses are smaller.
      • In the elderly, the initial and maintenance doses are usually half that of people in working age (start, for example, with the lowest possible dose and increase dose slowly).
      • Potentially impaired kidney function must be taken into account.
      • SNRI drugs are the safest.
      • Tricyclic antidepressants have the strongest anticolinergic effects (confusion, memory impairment, urinary retention, constipation and worsening of glaucoma).
      • The sedative effect is strongest in antiepileptic drugs (pregabalin, gabapentin); remember the falling risk.

Shingles vaccination Corticosteroids for Preventing Postherpetic Neuralgia, Vaccination for Preventing Postherpetic Neuralgia

  • Herpes zoster vaccines reduce the incidence of shingles Vaccines for Herpes Zoster in Older Adults and its complications, e.g. postherpetic neuralgia Vaccination for Preventing Postherpetic Neuralgia, eye complications, encephalitis).
  • Recombinant vaccine (Shingrix® ) (2 doses at an interval of 2 months; does not contain live virus and hence can also be used in immunocompromized persons). Intended for people over 50 years of age with normal shingles risk and for people over 18 years of age with increased shingles risk.
  • Zostavax® contains attenuated live virus (single dose; not suitable for severely ill, immunocompromized persons). Intended for people over 50 years of age.

Specialist consultation

  • For patients with immunodeficiency or particularly severe disease, hospital treatment and initial treatment with i.v. aciclovir may be necessary.
  • In the case of postherpetic neuralgia that is difficult to manage consult specialized care, as necessary.

    References

    • Le P, Rothberg M. Herpes zoster infection. BMJ 2019;364:k5095 [PubMed].
    • Werner RN, Nikkels AF, Marinovic B et al. European consensus-based (S2k) Guideline on the Management of Herpes Zoster - guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV), Part 1: Diagnosis. J Eur Acad Dermatol Venereol 2017;31(1):9-19. [PubMed]
    • Schuster AK, Harder BC, Schlichtenbrede FC et al. Valacyclovir versus acyclovir for the treatment of herpes zoster ophthalmicus in immunocompetent patients. Cochrane Database Syst Rev 2016;11():CD011503. [PubMed]
    • Snedecor SJ, Sudharshan L, Cappelleri JC et al. Systematic review and meta-analysis of pharmacological therapies for pain associated with postherpetic neuralgia and less common neuropathic conditions. Int J Clin Pract 2014;68(7):900-18. [PubMed]
    • Feller L, Khammissa RAG, Fourie J et al. Postherpetic Neuralgia and Trigeminal Neuralgia. Pain Res Treat 2017;2017():1681765. [PubMed]
    • Finnerup NB, Attal N, Haroutounian S et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol 2015;14(2):162-73. [PubMed]
    • Tricco AC, Zarin W, Cardoso R et al. Efficacy, effectiveness, and safety of herpes zoster vaccines in adults aged 50 and older: systematic review and network meta-analysis. BMJ 2018;363():k4029. [PubMed]
    • Cunningham AL, Lal H, Kovac M et al. Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older. N Engl J Med 2016;375(11):1019-32. [PubMed][PubMed]
    • Marra F, Parhar K, Huang B et al. Risk Factors for Herpes Zoster Infection: A Meta-Analysis. Open Forum Infect Dis 2020;7(1):ofaa005. [PubMed]
    • Kim J, Kim MK, Choi GJ ym. Pharmacological and non-pharmacological strategies for preventing postherpetic neuralgia: a systematic review and network meta-analysis. Korean J Pain 2021;34(4):509-533. [PubMed]

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