Cases & Commentaries
Hiding in Plain Sight
A 65-year-old woman presented to an emergency department (ED) with 48 hours of nontraumatic left lower back pain and general malaise. She was diagnosed with a musculoskeletal injury and discharged from the ED with muscle relaxants and antiinflammatory medications. She returned to the ED the following day with increased back pain described as shooting and burning in nature. Physical examination was reported as unremarkable, and basic laboratory tests and an abdominal computed tomography (CT) study came up normal as well. The patient was unable to ambulate due to pain and developed nausea related to her narcotic therapy. She was later admitted for observation and additional analgesics. The admitting hospitalist evaluated the patient and started her on intravenous analgesics. He did not document any evidence of neurologic deficits or an acute abdomen.
The next morning, the hospitalist assuming care for the patient readily noted a vesicular rash in the exact distribution of her pain symptoms and correctly diagnosed a herpes zoster infection (shingles). The patient was treated with prednisone and acyclovir and was discharged with improved symptoms. The patient initially reported the rash more than 24 hours prior to her hospitalization but didn't think it was related to her pain. She stated, "Nobody actually looked at my skin until the following morning." The patient had a full recovery but likely underwent unnecessary testing and delays to appropriate, disease-specific treatment.
This case strikingly emphasizes the need for a thorough physical examination, particularly of the skin. If a complete examination had been performed, it would have saved this patient unnecessary testing and expedited appropriate therapy.
Herpes zoster (or shingles) occurs in approximately 1 million people annually in the United States. The principal risk factor for herpes zoster (HZ) is prior history of varicella zoster virus (VZV) exposure (Table).(1) Any person who has had chickenpox or received the VZV vaccine as a child (more than 90% of the US adult population has had one or the other) is at risk for HZ.(2) Age is also an important predictor of HZ, with most disease incidence occurring after age 45, and half of all cases reported in individuals older than age 60.(3,4) This association with advancing years is due to the age-related decline in VZV-specific cell-mediated immunity. Childhood HZ is rare, although cases have been reported in children as young as 4 months. The incidence of HZ in children younger than 10, however, is only 0.74 per 1000 person-years.(4)
Immunocompromised patients or those receiving immunosuppressive drugs are also at increased risk for HZ.(1) Thus, HIV patients have a higher incidence (29.4 cases per 100 patient-years in one study) of HZ than individuals with a healthy immune system.(5) Immunocompromised persons often get VZV viremia, which may lead to disseminated disease, involving the lungs, liver, central nervous system, or other organs. Patients undergoing bone marrow or organ transplant and treated with immunosuppressive drugs are known to develop HZ with increased frequency.(1)
The characteristic feature of HZ is a vesicular rash of unilateral distribution limited to one to three adjacent dermatomes (Figure). The onset of the rash, however, often is preceded by a prodromal phase.(6) Beginning 4 days to 2 weeks before lesions appear, patients often note pain and paresthesia in what will become the HZ-affected dermatome. The pain can be intermittent or continuous and has been described by patients variably as throbbing, sharp, stabbing, burning, or shooting pain.(6) They may also complain of abnormal skin sensations such as tingling or itching. Malaise, dysesthesia, and itching are frequent elements of the prodrome as well. The rash generally appears proximally and then spreads distally along the affected dermatome. The initial lesions appear as erythematous maculopapules, which turn into vesicles within 12 to 24 hours. The vesicles become pustules in about 3 days and form scabs 7 to 10 days later.(6,7)
Complications of HZ include severe pain during the infection as well as postherpetic neuralgia, herpes zoster ophthalmicus (which can lead to blindness), pneumonia, myelopathy, paresis, vasculopathy, and myocarditis. These complications have an impact on health care costs, productivity, and quality of life for those afflicted. Approximately 60% to 90% of HZ patients experience local neuritic pain (6) and hypersensitivity in association with the acute herpetic rash. This pain is likely due to an immediate nociceptive response: local inflammation and tissue damage stimulate the primary afferent neurons of the skin and subcutaneous tissue, which neurologically manifests as pain.
Therapy for acute HZ is often of minimal benefit. Antiviral drugs or combination regimens using antivirals plus corticosteroids may reduce the severity or duration of the HZ rash (8-10), while certain antiepileptics, tricyclic antidepressants, opioids, and topical treatments can decrease the pain of postherpetic neuralgia. None of these agents, however, can prevent HZ or its most common complication, postherpetic neuralgia. Therefore, many patients are left with substantial morbidity and chronic neuropathic pain that require ongoing medical attention. Patients with long-standing pain or other complications are also more likely to complain of poor quality of life and dissatisfaction with treatment, despite aggressive use of therapies.(11)
A live attenuated VZV vaccine was approved several years ago by the FDA for the prevention of HZ in individuals 60 years of age and older. In a randomized, double-blind, placebo-controlled trial of 38,546 adults 60 years of age or older, the use of the VZV vaccine reduced the burden of illness from HZ by 61.1% (PPP3) Presently, the VZV vaccine is recommended for the prevention of HZ in individuals 60 years of age and older.
Diagnostic Errors with Zoster
There are several clinical scenarios when the diagnosis of HZ is missed or not "seen" by health care providers. For example, I saw a patient recently who presented with a resolving dermatomal eruption in the thoracic area. She experienced no pain and only considered the possibility that it might be "shingles" when this was suggested to her by a friend. A second scenario might be a patient who suffers from an extensive or painful outbreak but is unable to access medical attention before the eruption resolves. A third and more troubling scenario is when the diagnosis is missed by health care providers—as in the case presented.
Cases of HZ can be missed when a full history and physical examination are not performed, or when the presentation is atypical of HZ. For example, a thoracic dermatomal rash may not be continuous, so it may be necessary to examine the front and back of the patient and "connect the dots." Or, when HZ occurs fully or partially under the scalp, it can also lead to a missed diagnosis. Therefore, it is important to carefully examine patients with facial crusts and/or pain, particularly since such patients may go on to develop HZ ophthalmicus. Except for such cases with ocular involvement, delays in diagnosis generally carry little overall risk. As previously noted, acute treatment with antivirals is of minimal benefit and will not prevent postherpetic neuralgia. Corticosteroids may help reduce acute pain, but they will also not reduce the incidence of postherpetic neuralgia. All of these treatment limitations argue for increased utilization of the VZV vaccine.
Finally, it is important to acknowledge the few conditions that can often be mistaken for HZ. Sacral herpes simplex virus infections, caused by HSV-2, are often confused with HZ. These can be differentiated by a history of recurrence in the case of sacral HSV, and by viral culture or direct fluorescent antibody testing. Unilateral allergic contact dermatitis, as often occurs with cases of poison ivy, is also in the differential diagnosis, but would be associated with pruritus rather than pain.
Perhaps the greatest risk to patients from a missed diagnosis of HZ is from an aggressive approach to the wrong diagnosis. More than one patient has been taken to the cardiac catheterization laboratory because of an "acute MI" after he presented with left sided chest pain, tachycardia, and nonspecific electrocardiogram (ECG) changes. Other unfortunate patients have had their appendices or gall bladders removed. Some diagnostic confusion is inevitable because the pain of HZ can emerge well before the rash (and there is no accurate diagnostic test during this prodrome), but in some of the cases, subtle clues of early skin involvement were missed. The key is to maintain a high index of suspicion for HZ—particularly when a patient's new pain is in a dermatomal distribution, when the pain is "zoster-like," and when the evidence for other diseases is less compelling—and to do a thorough skin examination.
This patient's experience illustrates several key points about properly evaluating and managing HZ:
- Perform a full history and physical examination in any patient where HZ is a consideration, such as patients presenting with a unilateral skin eruption or localized pain and paresthesias.
- Always consider HZ in the differential diagnosis of any patient presenting with facial pain and/or evidence of vesicles and scabbing.
- Refer patients with suspected HZ ophthalmicus to an ophthalmologist emergently.
- Consider administering the VZV vaccine to eligible patients, as it is the only intervention shown to reduce the incidence of HZ and postherpetic neuralgia.
Jeffrey M. Weinberg, MD Assistant Professor of Clinical Dermatology
Columbia University College of Physicians and Surgeons
Disclosure: Dr. Weinberg is on the speakers' bureau for Merck.
1. Arvin AM. Varicella-zoster virus. Clin Microbiol Rev. 1996;9:361-381. [go to PubMed]
2. Gnann JW Jr, Whitley RJ. Clinical practice. Herpes zoster. N Engl J Med. 2002;347:340-346. [go to PubMed]
3. Oxman MN, Levin MJ, Johnson GR, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005;352:2271-2284. [go to PubMed]
4. Insinga RP, Itzler RF, Pellissier JM, Saddier P, Nikas AA. The incidence of herpes zoster in a United States administrative database. J Gen Intern Med. 2005;20:748-753. [go to PubMed]
5. Buchbinder SP, Katz MH, Hessol NA, et al. Herpes zoster and human immunodeficiency virus infection. J Infect Dis. 1992;166:1153-1156. [go to PubMed]
6. Wood MJ, Easterbrook P. Shingles, scourge of the elderly. The acute illness. In: Sacks SL, Straus SE, Whitley RJ, Griffiths PD, eds. Clinical Management of Herpes Viruses. Washington, DC: IOS Press; 1995:193-209. ISBN: 9789051992274.
7. Johnson RW, Whitton TL. Management of herpes zoster (shingles) and postherpetic neuralgia. Expert Opin Pharmacother. 2004;5:551-559. [go to PubMed]
8. Mounsey AL, Matthew LG, Slawson DC. Herpes zoster and postherpetic neuralgia: prevention and management. Am Fam Physician. 2005;72:1075-1080. [go to PubMed]
9. Wood MJ, Johnson RW, McKendrick MW, Taylor J, Mandal BK, Crooks J. A randomized trial of acyclovir for 7 days or 21 days with and without prednisolone for treatment of acute herpes zoster. N Engl J Med. 1994;330:896-900. [go to PubMed]
10. Whitley RJ, Weiss H, Gnann JW Jr, et al. Acyclovir with and without prednisone for the treatment of herpes zoster. A randomized, placebo-controlled trial. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. Ann Intern Med. 1996;125:376-383. [go to PubMed]
11. McDermott AM, Toelle TR, Rowbotham DJ, Schaefer CP, Dukes EM. The burden of neuropathic pain: results from a cross-sectional survey. Eur J Pain. 2006;10:127-135. [go to PubMed]
Table. Risk Factors and Potential Risk Factors for VZV Reactivation.(1)
Figure. Herpes zoster.
Image from Wikimedia Commons. Available at:
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