Endgames Picture Quiz

A skin rash to remember

BMJ 2012; 345 doi: http://dx.doi.org/10.1136/bmj.e6625 (Published 08 October 2012) Cite this as: BMJ 2012;345:e6625
  1. Peter J Moran, senior house officer in general medicine1,
  2. Pierce Geoghegan, senior house officer in general medicine1,
  3. Donal J Sexton, specialist registrar in nephrology1,
  4. Anthony O’Regan, consultant physician in respiratory and general medicine2
  1. 1University College Hospital Galway, Galway, Republic of Ireland
  2. 2Respiratory Medicine, Galway University Hospital, Galway
  1. petermoran{at}hotmail.com

A 30 year old man presented to the emergency department with a four to five day history of a painful disfiguring rash (fig 1). It started around his mouth but later spread to the rest of his face, as well as his neck and shoulders. He had a history of mild atopic dermatitis, but he had been otherwise well apart from a “cold sore” before the rash appeared. He was not taking any regular drugs, had no allergies, and had not treated the rash with any topical drugs. He was systemically well and the only abnormalities seen on routine blood tests were mild lymphopenia (0.8×109/L, reference range 1-4) with raised C reactive protein 64 mg/L (<0.6;1 mg/L=9.5 nmol/L). HIV testing was negative.

Questions

  • 1 What is the diagnosis?

  • 2 How would you make the diagnosis?

  • 3 What treatment should be instituted?

  • 4 What factors can predispose patients to this condition?

Answers

1 What is the diagnosis?

Short answer

Eczema herpeticum, with secondary staphylococcal superinfection. This is a dermatological emergency.

Long answer

Possible diagnoses include eczema herpeticum with secondary staphylococcal superinfection, viral xanthems (such as pox viruses), bacterial infection, drug eruption, contact dermatitis, erythema multiforme, or exacerbation of a primary skin disorder. The appearance of the rash is not typical of an isolated flare of atopic dermatitis. The absence of recent use of drugs excludes a drug eruption and the distribution is not consistent with contact dermatitis. Nor are the lesions typical of erythema multiforme. Given the recent history of a cold sore, the appearance of the rash with an initial monomorphic vesicular eruption, and subsequent punched out erosions and impetiginous change, the most likely diagnosis is eczema herpeticum, with secondary staphylococcal superinfection.

Eczema herpeticum is caused by herpes simplex virus (HSV) infection, usually in patients with atopic dermatitis, but more rarely it can occur in other conditions where mucosal integrity is disrupted. Susceptibility to HSV infection is thought to arise from a combination of impaired epidermal integrity, abnormalities in pattern recognition receptors, and a decrease in expression of antimicrobial peptide receptors. A susceptibility to superimposed Staphylococcus aureus infection in atopic dermatitis has been associated with polymorphisms in Toll-like receptors, although in eczema herpeticum, superinfection is probably related more to the inflamed and weeping skin.1 A high index of suspicion is needed because eczema herpeticum may mimic severe atopic dermatitis, and this can delay the diagnosis.2 3 Furthermore, lesions caused by infection with HSV type 1 (HSV-1) do not always present with the characteristic vesicles on an erythematous base and may resemble bacterial superinfection. Red flags in the history include a recent cold sore; contact with somebody who is infected with HSV (although often there is no history of either of these); or typical prodromal systemic features such as fever, malaise, lymphadenopathy, or tender skin.

2 How would you make the diagnosis?

Short answer

Viral polymerase chain reaction (PCR) and culture. A probable diagnosis can be made on the basis of a typical history and rash, however, and treatment should be started before laboratory confirmation.

Long answer

A probable diagnosis can be made on the basis of a typical history and rash, and treatment should be started before laboratory confirmation. Viral and bacterial swabs should be taken for one or more of the following tests: viral PCR, viral culture, or direct immunofluorescence studies. Viral PCR and culture are most useful in patients with active lesions. The sensitivity of viral culture is low (about 50%); it is highest when active vesicular lesions are present and declines as the lesions heal.4 Viral PCR is more sensitive and has excellent specificity, but it is used less often because of cost considerations.5 Direct fluorescent antibody testing can be performed, with antibodies against HSV-1 and HSV-2. The Tzank preparation is another useful test. It is performed by opening a vesicle and obtaining scrapings from both the base and underside and examining them on a slide with toluidine blue staining. A positive result confirms viral infection but is not virus specific.6

Because of the risk of bacterial superinfection, bacterial cultures should also be performed. To improve the diagnostic yield, scrapings should be taken from the base of a vesicle that has developed within the past 24-48 hours. However the sensitivity is relatively low at 7-25%.7

Cutaneous colonisation with S aureus complicates the diagnosis of bacterial superinfection in eczema herpeticum because skin cultures may be positive in the absence of true infection.8 Therefore the diagnosis of S aureus superinfection is based on clinical parameters such as fever, a sudden worsening of symptoms, impetiginous crusting, signs of sepsis, or a systemic inflammatory response.

3 What treatment should be instituted?

Short answer

Eczema herpeticum is a dermatological emergency. Start treatment immediately while awaiting virological confirmation. Treatment comprises aciclovir to treat the eczema herpeticum, flucloxacillin for the staphylococcal superinfection, and supportive treatment as needed (for example, fluids and analgesia).

Long answer

Aciclovir is a nucleoside analogue that inhibits the replication of HSV. There has been little formal investigation of its efficacy in adults with eczema herpeticum, and treatment protocols have been extrapolated from its use in childhood disease and genital infection. Typically, a dose of 400 mg five times daily for five to 10 days (intravenously or orally) is used in adult disease, with 15 mg per kg per day intravenously for a minimum of five days in patients who are immunocompromised or have severe disease (evidence of systemic infection or widespread cutaneous disease). Topical antivirals can be used in mild disease, where patients are systemically well. Adequate hydration is recommended if aciclovir is given intravenously to prevent acute kidney injury secondary to precipitation of aciclovir crystals in the renal tubular system.9

It is important to recognise and treat secondary bacterial infection because it is a common complication and can slow resolution if left untreated. A systemic antimicrobial that is effective against S aureus is usually needed. In cases without secondary bacterial infection, a topical antibiotic cream is recommended to prevent this developing.10

Other important measures include supportive treatments such as fluids and analgesia. Perform a full skin examination and treat any active atopic dermatitis because a severe flare-up will worsen the systemic upset. In cases like this, where the skin near the eyes is affected, an ophthalmology consultation is needed to exclude infection of the eye. If the patient is systemically unwell, consider the possibility of an underlying immunodeficiency—for example, HIV infection.

Do not use topical steroids or tacrolimus because they worsen the eczema herpeticum. The application of steroids or tacrolimus to an undiagnosed rash is dangerous and should be avoided.

In patients with a history of recurrent HSV-1 and HSV-2 infections, consider prophylactic oral antivirals (such as aciclovir orally, 400 mg twice a day). Poor absorption and poor adherence to drugs are the most common causes of recurrent infection despite prophylaxis. Oral famciclovir or valaciclovir may be more readily absorbed than aciclovir.11

4 What factors can predispose patients to this condition?

Short answer

Any skin condition that disrupts the integrity of the epidermal layer of the skin, most commonly atopic dermatitis.

Long answer

Atopic dermatitis is the most common predisposing factor for eczema herpeticum.12 The pathogenesis of atopic dermatitis is incompletely understood but probably involves a combination of intrinsic structural and functional abnormalities in the skin, which result in a defective epidermal barrier,13 as well as an abnormal immune inflammatory response to environmental factors.14 The condition is exacerbated by excessive bathing, stress, xerosis, and exposure to solvents and detergents.15 Simple measures such as skin hydration and removal of exacerbating factors may help restore the barrier function of the skin, and randomised evidence supports the use of treatments that target the immune system, such as topical steroids, ciclosporin, and ultraviolet light therapy.16 Although most cases of eczema herpeticum occur in patients with atopic dermatitis, bullous disorders, mycosis fungoides, seborrhoeic dermatitis, Darier’s disease, and Wiskott-Aldrich syndrome can also predispose patients to the condition.17 18

Patient outcome

The patient was reviewed in the dermatology clinic one month after discharge. His rash had completely resolved after treatment with intravenous aciclovir and flucloxacillin, followed by oral valaciclovir for one week (fig 2).

Figure2

Fig 2 The patient, one month after discharge

Notes

Cite this as: BMJ 2012;345:e6625

Footnotes

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Provenance and peer review: Not commissioned; externally peer reviewed.

  • Patient consent obtained.

References