Herpes Zoster

Written by: Kevin Dyer, MD (NUEM PGY-3) Edited by: Simiao Li-Sauerwine, MD (NUEM Alum ‘18) Expert commentary by: David Zull, MD

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The Patient

A 76-year-old man with a history of metastatic colon cancer (on Bevacizumab), HTN, and DM2 presents with a skin rash on his back wrapping around to his groin. He went on to say that 4 days ago he began having a dull, aching pain in this region and about 18 hours ago this rash appeared. He denied having a rash in any other location, and also denied oral sores, vision changes, confusion, neck pain, fevers, cough, or shortness of breath. His last infusion of bevacizumab was 9 days prior to ED presentation and he did not receive the shingles vaccine.

Upon examination he had a unilateral erythematous vesicular rash in the distribution of his T12 and L1 dermatomes that was classic for Herpes Zoster (HZ) along with erythema at the base that was concerning for an underlying cellulitis. His labs were remarkable for a white count of 2,200 and an absolute neutrophil count of 1,200.

Given his immunocompromised status, he was given Acyclovir 750mg (10mg/kg) IV and Ancef 2g IV in the ED and admitted for continued IV anti-viral therapy.

Discussion

To me, this case was much more interesting than the average case of HZ given the patient’s immunocompromised status and it served as an important reminder that there are several pitfalls and complications surrounding HZ that the ED physician must be aware of and constantly on the lookout for.

Post-Herpetic Neuralgia (PHN)

PHN is defined as pain that persists more than 30 days after the onset of rash. Both the incidence (8-70%) and duration are directly correlated with the patient’s age.[1-3] Symptoms of PHN include pain, numbness, dysesthesias, and allodynia. While PHN is not applicable to the patient with an acute attack of HZ, it is included here because it is the most common complication of HZ and should be included in the counseling given to patients who are discharged from the ED.

Herpes Zoster Ophthalmicus

Herpes Zoster Ophthalmicus (HZO) is an ocular and peri-ocular disease that is the result of virus reactivation in the trigeminal ganglion.

Patients with HZO may present with a vesicular eruption along the trigeminal dermatome, conjunctivitis, episcleritis, and lid droop. Clinicians should also pay particular attention the nose and be on the lookout for vesicular lesions at the base, side, or tip of the nose. Commonly known as Hutchison’s sign, lesions on the nose indicate involvement of the nasociliary branch and are strong predictors of ocular involvement, which occurs in 50-72% of HZO cases.[4,5]

Corneal involvement can lead to significant vision loss and should be evaluated for via fluoroscein staining in all patients with suspected HZO. Keratitis may present as punctate or dendriform lesions that are easily mistaken for Herpes Simplex Keratitis.[5]

[6]

Herpes Zoster Oticus

Often referred to as Ramsay Hunt Syndrome (RHS), Herpes Zoster Oticus manifests as a triad of ipsilateral facial paralysis, ear pain, and vesicles in both the auditory canal and auricle. RHS is considered a polyneuropathy affecting cranial nerves V, VII, VIII, IX, and X.7 Involvement of these nerves leads to tinnitus, hearing loss, hyperacusis, dysgeusia, and vertigo. It is worth noting that when compared to those with Bell’s Palsy, patient’s with RHS were found to have more severe palsy and a less favorable recovery.[8]

Panel A displaying a crusted lesion in the ear of a patient with RHS. Panel B highlights the CN VII palsy that can be seen in RHS.[9]

Disseminated Zoster

Disseminated cutaneous HZ is a complication that is often accompanied by visceral organ involvement.[10] Though it is more common in immunocompromised hosts, it can also be seen in immunocompetent patients, as well. As the name implies, patients with disseminated zoster will have midline-crossing vesicular skin lesions in multiple dermatomes. Visceral involvement can be life threatening and may present as fulminant pneumonia, hepatitis, or encephalitis.11

[12]

Skin Infection

Patients with HZ lesions are at an increased risk for skin superinfection regardless of immune status. The most likely causative agents are Staphylococcus and Streptococcus species. When encountering a patient with HZ, the clinician should be sure to look for signs of bacterial infection and treat with antibiotics in addition to antivirals.

Treatment

In immunocompetent patients, antiviral therapy should be started within 72 hours of rash occurrence or if new lesions continue to occur as this is a sign of ongoing virus replication.[13] For immunocompromised patients, antiviral therapy should be started regardless of when the lesions appeared.

The three antivirals currently recommended for use are acyclovir, valacyclovir, and famciclovir, with dosing regimens as follows:

                  Acyclovir – 800mg, 5 times per day for 7 days

                  Valacyclovir – 1000mg, 3 times per day for 7 days

                  Famciclovir – 500mg 3 times per day for 7 days

A meta-analysis of placebo-controlled trials have shown that patients who received acyclovir within 72 hours of rash onset are more likely to have resolution of neuritis and PHN.[14] A commonly used alternative option is valacyclovir which, when compared to acyclovir, has equal efficacy in the resolution of cutaneous lesions, and the added benefit of accelerated resolution of neuritis.[15] The TID dosing is also thought by many clinicians to lead to better patient compliance. The caveat to this, however, is valacyclovir is much more expensive than acyclovir and can be cost prohibitive depending on the patient’s insurance status.

Patients should be treated with intravenous acyclovir 10 mg/kg if they are immunocompromised,  have disseminated zoster, are found to have sight threatening disease on exam, or if they have symptomatic meningitis, encephalitis, or myelitis.[12]

Disposition

The overwhelming majority of patients with HZ can be treated as outpatients with an oral agent as discussed above. Admission is indicated for patients who meet the criteria for IV acyclovir as outlined in the previous section.

Take Home Points

When caring for a patient with herpes zoster, be on the lookout for herpes zoster ophthalmicus, herpes zoster oticus, signs of disseminated zoster, and underlying cellulitis.

Initiate antivirals if the onset of rash is within 72 hours of presentation or if the patient is immunocompromised.

Oral antivirals are acceptable for the majority of patients with herpes zoster, but those who are immunocompromised, have disseminated zoster, sight threatening involvement, or signs of CNS involvement should be treated with IV acyclovir.

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Expert Commentary

It is estimated that up to one third of the population will develop Herpes Zoster virus infection (shingles) sometime during our lifetime, such that it is a very common ED presentation.    Emergency physicians should be keenly aware of the complications of HZV and be able to recognize it early.  Antiviral treatment within the first 72 hours of the skin eruption can limit progression of lesions, halt development of new lesions, minimize infectious risk to household contacts, decrease the risk of complications of HZV infection, and in particular ameliorate the severity of post herpetic neuralgia.

Ramsay Hunt syndrome is typically limited to a triad of Bell’s palsy (7th Nerve palsy), ear pain and vesicles in the auditory canal and external ear.  The skin lesions are often subtle and frequently limited to just a few papules such that the syndrome is often missed.  Other cranial nerves (5,8,9,10) can also be involved in Ramsay Hunt syndrome, most notably 8th nerve involvement with tinnitus, hearing loss or hyperacusis, and vertigo. 

Herpes Zoster ophthalmicus is usually limited to punctate keratitis and is not vision threatening.  Dendritic lesions can occur in HZV but they are referred to as pseudodendrites because they are composed of heaped up epithelial cells with no epithelial defects. These pseudodendrites do not take up fluorescein since the epithelium remains intact but fluorescein often collects at the edges thereby outlining the dendrites.  In contrast, the dendrites of HSV are comprised of denuded epithelium which do take up fluorescein.  The HSV dendrite can lead to corneal erosion, scarring, and even perforation.  HZV can also affect the corneal stroma and not the corneal epithelium leading to white rounded opacities with no overlying fluorescein uptake.  Pink eye can result from conjunctivitis or iritis but is often overlooked.   The most feared ocular complication of V-1 Zoster is acute retinal necrosis which leads to rapidly progressive vision loss often complicated further by retinal detachment.

Disseminated herpes zoster is defined as the presence of more than 20 lesions outside the involved dermatome. This unusual presentation is more common in immunosuppressed patients.  Lesions in an ipsilateral adjacent dermatome are usually not of concern.  Disseminated zoster can resemble acute varicella or smallpox, as well as acute vesiculating drug eruptions like erythema multiforme and toxic epidermal necrolysis.   Disseminated HZV is distinguished by the onset primarily in one dermatome before dissemination of lesions.  Systemic organ involvement can occur with dissemination of HZV including pneumonia, hepatitis, aseptic meningitis, encephalitis, motor neuropathy, myelitis, GBS, and CNS vasculitis with stroke.

Post herpetic neuralgia, a common complication of HZV infection, is best prevented by prompt antiviral therapy in the acute phase.  Although steroids may have some benefit in ameliorating the severity of pain in the acute setting, they have not been shown to decrease the development of PHN.  Pain management of PHD frequently requires use of TCA’s, gabapentin or pregabalin. 

A common complication of HZV dermatomal lesions is secondary bacterial infections with staph aureus, usually with an impetiginous superficial purulent discharge with or without local cellulitis.   Staph septicemia and toxic shock syndrome is a rare complication in dermatomal zoster but is well described in primary varicella infections in neonates and immunocompromised children.

The emergency physician should have a low threshold for initiating antiviral therapy acute shingle, typically Valcyclovir 1gm TID or Acyclovir 800mg five times per day, for 7 days in immunocompetent hosts with uncomplicated disease, or 14 days in compromised hosts and those experiencing complications of HZV.

David N. Zull, MD, FACEP, FACP

Professor of Emergency Medicine & Internal Medicine

Northwestern University

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How to Cite This Post

[Peer-Reviewed, Web Publication]  Dyer K, Li-Sauerwine S (2018, December 17). Herpes Zoster [NUEM Blog. Expert Commentary by Zull D]. Retrieved from http://www.nuemblog.com/blog/herpes-zoster

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Resources

1. Choo PW, Galil K, Donahue JG, Walker AM, Spiegelman D, Platt R. Risk factors for postherpetic neuralgia. Archives of internal medicine 1997;157:1217-24.

2. Gnann JW, Jr., Whitley RJ. Clinical practice. Herpes zoster. The New England journal of medicine 2002;347:340-6.

3. Ragozzino MW, Melton LJ, 3rd, Kurland LT, Chu CP, Perry HO. Population-based study of herpes zoster and its sequelae. Medicine 1982;61:310-6.

4. Zaal MJ, Volker-Dieben HJ, D'Amaro J. Prognostic value of Hutchinson's sign in acute herpes zoster ophthalmicus. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 2003;241:187-91.

5. Pavan-Langston D. Herpes zoster ophthalmicus. Neurology 1995;45:S50-1.

6. Shaikh S, Ta CN. Evaluation and management of herpes zoster ophthalmicus. American family physician 2002;66:1723-30.

7. Adour KK. Otological complications of herpes zoster. Annals of neurology 1994;35 Suppl:S62-4.

8. Robillard RB, Hilsinger RL, Jr., Adour KK. Ramsay Hunt facial paralysis: clinical analyses of 185 patients. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery 1986;95:292-7.

9. Espay AJ, Bull RJ. Petrositis in Ramsay Hunt Syndrome with multiple cranial neuropathies. Arch Neurol 2005;62(11):1774-5.

10. Locksley RM, Flournoy N, Sullivan KM, Meyers JD. Infection with varicella-zoster virus after marrow transplantation. The Journal of infectious diseases 1985;152:1172-81.

11. Jantsch J, Schmidt B, Bardutzky J, Bogdan C, Eckardt KU, Raff U. Lethal varicella-zoster virus reactivation without skin lesions following renal transplantation. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 2011;26:365-8.

12. Dworkin RH, Johnson RW, Breuer J, et al. Recommendations for the management of herpes zoster. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2007;44 Suppl 1:S1-26.

13. Cohen JI, Brunell PA, Straus SE, Krause PR. Recent advances in varicella-zoster virus infection. Annals of internal medicine 1999;130:922-32.

14. Jackson JL, Gibbons R, Meyer G, Inouye L. The effect of treating herpes zoster with oral acyclovir in preventing postherpetic neuralgia. A meta-analysis. Archives of internal medicine 1997;157:909-12.

15. Beutner KR, Friedman DJ, Forszpaniak C, Andersen PL, Wood MJ. Valaciclovir compared with acyclovir for improved therapy for herpes zoster in immunocompetent adults. Antimicrobial agents and chemotherapy 1995;39:1546-53.

Phytophotodermatitis

Written by: Luke Neill, MD (NUEM PGY-3) Edited by: Mitali Parmar, MD (NUEM Alum '18) Expert commentary by: Charles Pearce, MD

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Case

A 7 yo female with no significant past medical history presents with a two-day history of worsening asymmetric rash on the left neck, upper middle chest, right thigh, and the dorsal aspect of both hands. The rash is described as a painful, burning, 3/10 pain and non-pruritic. She denies any history of allergies, especially any allergies to outdoor plants or foods, and denies using any new types of lotions, sunscreen, or other new chemical products. She denies history of trauma. She denies fevers, chills, or recent infections. Denies arthralgias, myalgias, fatigue, or weakness. Denies SOB or chest pain. Denies peeling of her skin or blistering.  She takes no medications.

She is currently attending an outdoor day-time summer camp and her mother first noticed the rash after picking her up at the end of camp two days ago. The mother, due to concern for possible physical abuse would like to know your opinion on its cause. You ask to speak to patient in private and she adamantly denies any physical abuse. You check her vitals.

Vitals/Exam: 

HR: 65   BP:120/70 Temperature: 96.4 RR:16 O2:100

General: patient well appearing, watching TV

Skin: Multiple small areas of blotchy erythema over left neck, upper middle chest, right thigh, and dorsal aspect of hands in different patterns with no symmetry. Some appear to represent a hand print. The rash on the chest also appears to streak vertically.

Head: normocephalic, atraumatic

HEENT: oral mucosa moist, PERRL, EOM intact, TMs clear bilaterally

Neck: supple, trachea midline

Cardiovascular: regular rate/ rhythm, no murmurs, rubs, or gallops

Chest: non-tender

Pulmonary: clear to auscultation bilaterally

GI: non-distended, soft, non-tender 

MSK: no deformities

Neuro: CNII-XII intact, strength/sensation grossly intact

Skin Exam: 

Labs: CBC and BMP Unremarkable

Clinical Course:

In consultation with dermatology, patient revealed that she recently made limeade at her summer camp about 2 days prior to arrival, and had been out in the sun for outdoor activities. Given this history and appearance of the rash, the patient was diagnosed with phytophotodermatitis, and discharged home with instructions to stay indoors. She was seen in clinic after 5 days, and had developed multiple blisters over her hands, chest and thighs. The rash subsequently completely resolved in 2 weeks time.

Phytophotodermatitis

Pathophysiology:

Phytophotodermatitis, also known as “Lime Disease” or “Margarita Photodermatitis” is a phototoxic inflammatory eruption of the skin that occurs due to contact with light-sensitizing botanical substances and subsequent exposure to UV-A radiation. Interestingly, the reaction of phytophotodermatitis is actually independent of the immune system.

But How?

When furocoumarins, the photosensitizing chemical compound produced by certain plants, are struck by a photon in the UV-A range of (320-400), energy is absorbed causing the formation of an excited state from ground state. When the furocoumarin returns to ground state, energy is released in the form of heat and fluorescence, leading to both DNA and RNA damage and cell death.

Furocoumarin is present in:

• Limes

• Figs

• Parsley

• Celery

• Carrots

Timing:

• Skin eruption typically begins 24 hours after sun exposure

Manifestation:

• Burning erythema with blistering

• Post-inflammatory hyperpigmentation lasting weeks to months. 

Progression:

• Eruption peaks at approximately 48-72 hours

Below is an image illustrating the progression in days, of a person with phytophotodermatitis of the hand:

View fullsize

Epidemiology:

As phytophotodermatitis occurs independent of the immune system; any race, sex, or age group may be affected. However, it does appear that produce workers in grocery stores are at a much higher risk than the general population. A 1986 study showed that in one un-named nationwide grocery store chain, a randomly selected sample of all its stores revealed phytophotodermatitis occurrence in 13 of 17 states, with occurrence in 26% of the produce workers surveyed. In this instance, it was thought to be due to celery stock with higher levels of endogenous furocoumarin.

Treatment/Prognosis:

The prognosis of phytophotodermatitis is very good with proper identification and elimination of the offending plant. Patients who are affected should stay indoors avoiding UV-A rays to allow the dermatitis to self-resolve. 

Note: This is not the first time phytophotodermatitis has mimicked child abuse. A 1985 study looked at two separate cases of children who were initially thought to have hyper-pigmented skin lesions suggestive of child abuse and were later given a final diagnosis of phytophotodermatitis.

Takeaways/Learning Points:

• Consider phytophotodermatitis in your differential for rash in summer months.

• Although we ask about allergies, consider asking about recent food exposure.

• Don’t spill your drink!

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Expert Commentary

Great overview of phytophotodermatitis!  This is certainly a fascinating and easily missed phenomenon given its relative rarity, variable pattern of presentation and, on occasion, insidious exposures. In the Midwest, we are seeing additional exposure risks to phytophotodermatitis in the form of Wild Parsnip (known colloquially as poison parsnip), an invasive plant that was introduced from Europe over a century ago and whose range has continued to expand.  This expansion has lead to Department of Natural Resource and local media in a number of states working to educate the public as well as local and regional medical facilities about the potential threat.

As with lime juice, exposure to the sap of Wild Parsnip can be potentially non-apparent to the patient and the clinician.  In fact, the pattern of burns from Wild Parsnip are as variable as the methods of exposure- from linear lesions from unwittingly brushing against a plant to extensive hand/forearm involvement from attempted manual removal of a plant to a speckled burn pattern from mechanical disruption of the plant (think weed whacker or lawn mower).  This variability obviously heightens the diagnostic difficulty and uncertainty. 

Another consideration and as noted in your excellent review, phytophotodermatitis is a burn resultant of chemically induced cell death by cross linkage of the furan ring with pyrimidine bases in the presence of UV light.  And recognition of this phenomenon as a chemical burn does have bearing on management. A discussion with or referral to burn centers may be warranted, as with any burn, if there is significant TBSA involvement or depending on body area impacted.  And looking for and warning patients of the potential for super-infection is imperative.

As a ER physicians in rural Wisconsin, our practice sees a couple handfuls of phytophotodermatitis cases each summer.  Our local communities (namely farmers) are well aware of Wild Parsnip and the simple prevention of avoidance and washing exposed areas to remove sap.  As more and more people (hopefully) continue to venture out of cities and explore the hiking, biking and nature trails of the rural Midwest, broadening public awareness of a potentially painful exposure matters and so thank you for the chance to respond to your fantastic blog!

Charles Pearce, MD NUEM ’14

Madison Emergency Physicians

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How to Cite This Post

[Peer-Reviewed, Web Publication]   Neill L, Parmar M (2018, September 24). Phytophotodermatitis.  [NUEM Blog. Expert Commentary by Pearce C]. Retrieved from http://www.nuemblog.com/blog/phytophotodermatitis

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References

1. Berkley SF, Hightower AW, Beier RC, et al. Dermatitis in grocery workers associated with high natural concentrations of furanocoumarins in celery. Ann Intern Med. 1986 Sep. 105(3):351-5. 

2. Coffman K, Boyce WT, Hansen RC. Phytophotodermatitis simulating child abuse. Am J Dis Child. 1985 Mar. 139(3):239-40.

3. Marcos LA, Kahler R. Phytophotodermatitis. Int J Infect Dis. 2015 Sep. 38:7-8. 

4. Smith E, Kiss F, Porter RM, Anstey AV. A review of UVA-mediated photosensitivity disorders. Photochem Photobiol Sci. 2011 Dec 16. 11(1):199-206. 

5. Becker, M. (2017). Phytophotodermatitis Rash [Digital image]. Retrieved November 10, 2017, from https://findadermatologist.com/healthinfo/phytophotodermatitis-limes-sunshine-don’t-mix.

6. Kid, K (June 3, 2015) Phytophotodermatitis From Exposure to Lime Juice [Digital image]. Retrieved November 10, 2017, from https://upload.wikimedia.org/wikipedia/commons/thumb/b/be/Phytophotodermatitis_from_esposure_to_lime_juice.jpg