Case-based learning: shingles

Shingles — also known as herpes zoster — is a painful, blister-filled rash caused by the reactivation of the varicella-zoster virus (VZV); the same virus that causes the primary infection varicella (i.e. chickenpox)​[1]​.

In the UK, the annual incidence is estimated to be around 1.85 to 3.9 cases per 1,000 people; this rises to 11 cases per 1,000 people in individuals aged over 80 years​[2,3]​. Individuals have a 20–30% risk of developing shingles during their lifetime​[4]​. Shingles can affect people of any age, but the risk, incidence and severity increase with age. This is because the immune system becomes less effective with age, so ageing therefore increases the risk of developing shingles​[4]​. 

This article outlines how to recognise the signs and symptoms of shingles, its causes and risk factors, and the role of pharmacists in managing treatment and preventing spread to vulnerable patients.

Causes

Shingles is caused by a secondary viral infection (i.e. a second infection from a previous viral infection) of an individual nerve and the skin surface that is served by that nerve; this is referred to as a dermatome​[1]​. The VZV lies dormant in the dorsal root ganglia, reactivating when the immune system is weakened, leading to herpes zoster infection​[5]​. Most people only have one lifetime incidence of shingles; however, risk factors can increase this incidence. Patients presenting with shingles will previously have had chickenpox, typically in childhood​[1]​.

The VZV is transmitted by direct skin-to-skin contact with a person who is actively shedding virus​[5]​. It is in this phase shingles is contagious; once the vesicles crust over, the patient is no longer infectious. Although the virus can be spread, as shingles is a secondary infection it is not possible to catch it directly from another person​[1]​. However, someone who has not had, or has been vaccinated against, chickenpox can contract that disease from contact with the fluid from open vesicles (i.e. burst blister) in active shingles​[1]​.

Risk factors

The following groups have an increased risk of VZV reactivation and subsequent complications:

• Older people, particularly those aged 50 years and over, peaking in individuals aged over 80 years owing to reduced effectiveness of the immune system;
• People who are immunosuppressed from disease states (e.g. haematological malignancies, HIV) or taking immunosuppressive medications (e.g. for autoimmune conditions, chemotherapy, organ transplant);
• People with asthma and chronic obstructive pulmonary disease, thought to be owing to systemic inflammation and disruption of the immune system;
• Women — this is thought to be owing to lower threshold for consultation so they are therefore are more likely to seek help, leading to increased numbers reported in female patients, and to gender differences in response to reactivation of latent viral disease;
• People of non-Hispanic white heritage are at a two-fold risk compared with black ethnicities. This is thought to be owing to an underlying genetic factor that modifies the risk of VZV reactivation; however, further studies are needed to support this;
• People with a history of dermatological presentations, including eczema/dermatitis or trauma;
• Limited evidence suggests that people taking statins may have an increased risk, speculated to be because statins lower immunity;
• Psychological stress has been shown to increase incidence, owing to initiation of the stress response affecting immune response capacity to deal with the virus​[6–12]​.

Symptoms

Symptoms typically include prodromal sensory phenomena (i.e. an early sensation) noted as tingling, prickling, burning and itching in a localised area along one or more dermatomes (an area of the skin supplied by nerves from a single spinal root) on the body. Other symptoms that may present, and can lead to incorrect diagnosis (see differential diagnosis below), include headaches, photophobia, malaise and fever​[13]​.

Around 48 hours after onset of prodromal symptoms, the rash appears as an erythematous, maculopapular rash, with both flat, discoloured skin lesions (‘macules’) and raised bumps (‘papules’) of small fluid-filled blisters (see Figure) in a unilateral pattern from the body midline, correlating to the involved dermatomes​[1]​. The most common areas involved are thoracic (58%) (see Figure 1A), cervical (20%) and ophthalmic (10–20%) locations (see Figure 1C)​[14]​. 

The red aspect of the rash presents slightly differently on people with a darker pigmentation, decreasing the prominence of the red/pink background upon which the vesicles protrude.

The vesicles are initially clear, but eventually cloud, rupture, crust and involute​[3]​. When the vesicles rupture they weep contagious fluid, increasing the transmission. In immunocompetent patients, the crusting occurs around day 7–10, with full resolution in 2–4 weeks. With patients that are immunocompromised, this can take longer and be more widespread, owing to the immune system’s reduced capacity to deal with the virus​[15]​. Scarring and pigmentation can persist if deeper epidermal and dermal layers have been compromised by excoriation, secondary infection or other complications​[16]​.

On rare occasions, the maculopapular rash might be absent — this is known as zoster sine herpete (ZSH)​[17]​.

Diagnosis

Diagnosis of shingles is based primarily on the patient’s history. Asking questions to help confirm a diagnosis is essential, including:

• If the patient has previously had chickenpox;
• The symptoms experienced, including location, duration and severity.

This should be paired with physical examination that should reveal the characteristic location, distinctive fluid-filled blister rash, localised pain and prodromal phenomena.

Converse to this, in the absence of a rash, either before its formation or in rare, atypical cases — such as ZSH — physical examination may be inconclusive.

Confirming diagnosis via laboratory testing typically has no value; however, where diagnosis is unclear, laboratory testing or specialist advice should be sought​[18]​. Samples obtained from a swab of an open vesicle, body fluid or skin scraping can be processed via polymer chain reaction to identify VZV DNA​[3]​. Referral should be made for patients in high-risk categories and those with atypical presentations, particularly in immunocompromised patients or in those with severe complications, such as meningitis, encephalitis, myelitis or ophthalmic distribution​[15]​.

Differential diagnosis

Herpes simplex virus infections may be recurrent and may appear in a dermatomal distribution mimicking shingles, leading to misdiagnosis​[9]​. Additionally, other common dermatological rashes may also be misdiagnosed, for example:

• Impetigo — more common in children and crusts yellow;
• Contact dermatitis — more common on the hands and face, where skin has come into contact with an irritant, causing it to become dry, cracked and irritated;
• Papular urticarial — allergic reaction on exposed areas, typically caused by bites;
• Candidal infection — lesion has a white discharge;
• Dermatitis herpetiformis — typically located on the backs of the elbows, the fronts of the knees, the scalp, bottom and back;
• Drug eruptions​[18]​.

Complications

Complications can occur in all patients, but the prevalence and severity is higher in those who are immunocompromised. Some patients experience a persistent or recurrent pain in the involved distribution, known as post-herpetic neuralgia (PHN). This is the most common complication of shingles, and defined as pain persisting for more than 90 days after onset of rash, owing to nerve damage​[19]​. It occurs in 10–13% of patients aged 60 years and over with the infection, and it is estimated that 14,000 cases of shingles result in PHN each year​[20]​. PHN pain varies in severity and can be constant, intermittent or triggered by trivial stimuli (e.g. stress)​[20]​. PHN risk and severity is linked with older age, rash severity and the extent of trigeminal or ophthalmic rash, with PHN lasting for around three to six months, although on some occasions it can last for years​[21]​.

Dermatological complications can also occur in all skin types, including scarring, pigmentation changes and secondary rash/keloid formation post-healing​[10,22]​. Secondary bacterial infections (typically staphylococcal or streptococcal) may also arise, resulting in cellulitis or life-threatening complications, such as necrotising fasciitis and sepsis​[3]​.

Ocular/nervous complications

Herpes zoster ophthalmic is characterised by V1 division of the ophthalmic nerve only, if left untreated. In severe cases, keratitis, corneal ulceration, optic neuritis, retinitis and blindness can occur​[3,23]​. Peripheral motor neuropathy may occur when a motor neurone is affected, resulting in movement disorders in the affected region, such as that seen in herpes zoster oticus (Ramsay Hunt syndrome), with associated acute peripheral facial nerve palsy, and vestibular and hearing problems​[2]​.

In severe cases, systemic complications occur when the virus disseminates into the bloodstream, resulting in viraemia and neurological complications, including meningitis and encephalitis​[22]​.

Management

Therapeutic choices depend on the severity of the patient’s symptoms, complications and risk factors. Generally, treatment provides the greatest benefit in people who are immunocompromised, those with prolonged or severe symptoms, and in those aged 50 years and over​[15]​.

Conservative therapy is useful for patients with milder symptoms. This tends to include symptoms management, such as application of wet compresses for 30–60 minutes 4–6 times daily, and colloidal oatmeal baths, which can help with itching and irritation. Calamine lotion may also be used as an antipruritic, in addition to its mild antiseptic properties, to prevent infections caused by scratching the affected areas​[24]​.

Antiviral therapy

Antivirals work by preventing viral replication, thus stopping further vesicle formation. Antivirals are more effective the earlier they are started, shortening infection duration and decreasing the severity of PHN. Ideally, therapy should be initiated within 72 hours of symptom onset. However, antivirals have been shown to reduce pain even when started beyond the 72-hour window and should be considered for treatment of acute zoster infection regardless of the time of presentation​[25]​.

Oral aciclovir, valaciclovir or famciclovir are antivirals that have all been shown to reduce viral shedding and the duration and pain severity associated with shingles​[25]​. This works by targeting the viral DNA polymerase, inhibiting viral DNA replication and hence stopping viral replication​[26]​. In severe or disseminated disease, intravenous therapy should be initiated. Topical antiviral therapy has not shown significant benefit and is therefore is not recommended​[13]​.

Research has shown that valaciclovir and famciclovir may be superior to acyclovir in resolving pain and increasing skin healing time. Valaciclovir therapy accelerated the resolution of acute neuritis compared with acyclovir, reducing the median duration of pain by 13 days. In addition, the proportion of patients with pain persisting for six months was modestly lower in the combined valaciclovir arms versus the acyclovir arm​[27]​. The reason for this is thought to be owing to higher plasma drug concentrations achievable with famciclovir and valacyclovir​[28]​.

Valaciclovir and famciclovir have improved pharmacokinetics and bioavailability compared with acyclovir, so less frequent dosing is required, making them favourable for improved adherence​[27]​. For immunocompetent patients, seven-day courses are sufficient, with longer courses needed in immunocompromised patients until two days after crusting of lesions​[28]​. See table below for further information on the medicine used to treat active shingles.

Pain can occur during and after a shingles infection and is the most debilitating symptom of the disease. Every effort should be made to reduce patients’ pain and suffering. Using a validated pain assessment scale, such as the visual analogue scale, allows subjective assessment to guide therapy​[29]​. 

Medications for pain relief include simple analgesia (e.g. paracetamol, non-steroidal anti-inflammatory drugs) and opioids (e.g. codeine, oxycodone). Tricyclic antidepressants (e.g. amitriptyline) and anticonvulsants (e.g. gabapentin, pregabalin) are effective for severe pain and PHN pains​[2]​. The choice of analgesic therapy should be based on contraindications, drug interactions and adverse effects. Topical capsaicin or lidocaine are options for patients with localised, mild-to-moderate PHN pain, where systemic therapies are not feasible​[30]​.

Corticosteroids have also been shown to be helpful in immunocompetent patients in the first 14 days following localised rash onset​[31]​. They are often used in combination with aciclovir in uncomplicated acute herpes zoster presentations in an attempt to improve quality of life, healing of lesions and reducing PHN. Despite this, a meta-analysis of five placebo-controlled trials versus aciclovir did not demonstrate any benefit of combination therapy on quality of life or the incidence of PHN​[31,32]​. Owing to the potential adverse effects of corticosteroids reducing the immune response, these drugs should only be used in cases of severe pain with neurological involvement (e.g. facial paralysis), or central nervous system involvement. Corticosteroids should not be given without antiviral therapy​[31]​.

Prevention

Prevention is particularly desirable in older patients, owing to prevalence and complications. A single zoster vaccine (Zostavax, Merck Sharp & Dohme Limited) dose aims to prevent shingles development in older patients (see below) and can significantly reduce secondary complications, such as PHNs​[6,7]​.

The NHS shingles vaccination is available if you are aged 70–78 years, with a 2-year grace period, extending the vaccination to people aged 80 years who meet the criteria. Owing to the reduction in vaccination efficacy because of functional declines in the innate and adaptive immune system associated with ageing, patients aged 80 years and above, or 70 years and below, are not routinely vaccinated​[33]​.

Zostavax is a live vaccine and should therefore be delayed in those that are acutely unwell and for 48 hours after the last dose of antiviral therapy. It is contraindicated in those on immunosuppressive or immunomodulatory therapies​[34]​.

When to refer

Patients should be referred for specialist advice in the following cases:

• New vesicles forming after seven days of antiviral treatment, owing to increased suspicion of an underlying immunodeficiency syndrome;
• Recurrent shingles, as this is an atypical reactivation of shingles and may be a sign of underlying immunodeficiency;
• Pain inadequately controlled or when use of a strong opioid is considered. Neuropathic pain can be hard to control and often requires specialist input;
• Pregnancy;
• Serious complications — such as meningitis, encephalitis or myelitis — are suspected;
• Ophthalmic shingle distribution of the trigeminal nerve, as detailed above;
• A severely immunocompromised person — related to medicine (e.g. corticosteroids or azathiopurine) or disease state (e.g. HIV) — or an immunocompromised person where the rash is severe, widespread or they are systemically unwell​[13]​.

It would be important to check the patient’s accommodation status (e.g. do they live with vulnerable adults/children?), and their role (e.g. would active shingles be hazardous to others, for example in a nursing home?).

Shingle-specific counselling points

In addition to recognising and understanding the treatment for shingles, pharmacists should provide the following advice to patients:

• Avoid contact with people who have not had chickenpox, especially those who are at heightened risk of complications or transmission (e.g. pregnant women, immunocompromised people and neonates);
• Wear loose-fitting clothes to reduce irritation;
• Cover lesions that are not under clothes while the rash is still weeping with virus-dense contagious fluid. Covering the rash will help avoid accidental touching or scratching;
• Avoid the use of topical creams and adhesive dressings, as they can cause irritation and delay rash healing;
• Keep the rash clean and dry to reduce the risk of bacterial infection. Medical advice should be sought if there is an increase in temperature, as this may indicate bacterial infection;
• Avoid sharing clothes and towels, and wash these at a high temperature after use;
• Avoid direct sunlight if taking acyclovir or valaciclovir, and consider long-sleeved clothing and sun cream;
• Avoid work, school or nursery if the rash is weeping and cannot be covered (i.e. if it is located on the face). If the lesions have dried or the rash is adequately covered (i.e. with gauze bandage or clothing), avoidance of these activities is not necessary if the patient feels systemically well. If the patient works in a healthcare setting, advise that they must consult their occupational health department for advice on returning to work​[30]​.

The following case studies help provide examples of how to approach patients with shingles in practice. The SOCRATES mnemonic provides specific questions that relate to pain and can be used to help ensure that the most is gained from consultations:

• Site — “Where exactly is the rash/pain?”
• Onset — “When did it start; was it constant/intermittent, gradual/sudden?”
• Character — “What is the pain like (e.g. sharp, burning, prickly)?”
• Radiation — “Does it radiate/move anywhere?”
• Associations — “Is there anything else associated with the pain/rash?”
• Time course — “Does it follow any time pattern, and how long ago did it present?”
• Exacerbating/relieving factors — “Does anything make it better or worse?”
• Severity — “How severe is the pain? Consider using the 1–10 scale.”​[35]​

 * All cases are fictional