An Older Woman with Pain on the Right Side of the Chest
A 75-year-old woman complains of right-sided chest pain. Close questioning reveals her “chest pain” is actually breast pain along the lateral breast and below to the base of the sternum. The pain is sharp, but nonpleuritic. There is no associated fever, dyspnea, cough, or sputum production.
History
The patient has mild hypertension that is controlled by metroprolol. She also has mild type 2 diabetes mellitus, which is reasonably well-controlled with oral agents.
Physical Examination
Physical exam reveals temperature normal at 37°C and blood pressure at 130/80 mm Hg. Chest exam is negative for rales or signs of consolidation. On the lateral and inferior aspects of her breast, a pink-red maculopapular rash that extends below and onto the chest wall and abdomen for a distance of 2 to 3 inches was noticed. The lesions do not cross the midline. No rash or eruption were visible anywhere else on her body.
Laboratory Results
Hemogram, including white blood cell count, was normal. Her comprehensive metabolic panel was normal, with the exception of a random glucose level of 147 mg. A chest x-ray was negative for infiltrates, cardiomegaly, or masses.
Which of the following is the correct statement regarding the presented patient’s illness?
A. After her recovery, vaccination can lower risk but will not guarantee that she will not have a recurrent episode later in life.
B. Patients who are of advanced age should avoid vaccination due to decreased efficacy and complications associated with vaccination in this group.
C. Diagnosis usually requires biopsy with PCR confirmation of presence of virus.
D. Optimal acute therapy is acyclovir rather than other antiviral agents.
(Answer and discussion on next page)
Correct Answer: A. After her recovery, vaccination can lower risk but will not guarantee that she will not have a recurrent episode later in life.
This patient has herpes zoster, otherwise known as shingles, which is a reactivation of infection with the varicella-zoster virus (VZV). This virus belongs to the herpes virus family. Viruses in this family are responsible for a variety of human infections, including herpes labialis (caused by herpes simplex virus type 1), genital herpes (caused by herpes simplex virus type 2), infectious mononucleosis (caused by Epstein-Barr virus), Kaposi sarcoma (caused by herpes virus 8), and roseola infantum (caused by herpes viruses 6 and 7).
Varicella is an extremely common infection. In children, it causes a febrile, usually benign illness commonly known as chickenpox. After the illness, the virus remains latent in dorsal root ganglia. If it is reactivated later in the patient’s life, it causes a cutaneous eruption in the distribution along the sensory nerve of the dermatome.
Incidence
Zoster is a quite common condition with an annual rate of 3 to 4 cases per 1000 persons. And, the incidence is rising with an estimated risk of 50% of unvaccinated people living to 85 years.1
Reactivation of the VZV is associated with age and the reduction in the level of T cell immunity to VZV, which correlates far better with protection against zoster than levels of virus specific antibodies.1,2 The major risk factors for VZV include age, gender (women are more receptive than men), and race (whites are more at risk than blacks).
Other causes of diminished T cell immunity that are associated with herpes zoster include lymphoma, chronic lymphocytic leukemia, immunosuppressive therapy (eg, corticosteroids and anti-rejection regimens), and HIV infection. These patients, in particular, are at increased risk for infection and severe disease.
Diagnosis and Treatment
In the unusual, confusing cases where diagnosis remains uncertain, the optimal test is likely a polymerase chain reaction (PCR) for herpes zoster virus at the base of an unroofed lesion—with sensitivity of 95% and specificity of near 100%.1 However, this is an unusual circumstance and Answer C is not correct here.
A variety of agents have been tested and used to treat acute herpes zoster. Therapy is indicated to reduce the formation of new lesions, hasten the healing of all lesions, and to reduce viral shedding and pain. Regardless of the agent, treatment should be prompt with initiation within 72 hours (the sooner the better) and given for 7 days.
In immunocompromised patients more aggressive methods, intravenous treatment, or hospitalization is recommended. Pharmacologic data reveals better drug levels and more ease of administration with valacylovir and/or famciclovir (dosed 3 times a day) compared to acyclovir (dosed 5 times a day) so they are preferred1,3 and Answer D is not correct.
Clinical Picture
This patient’s presentation is highly typical: A prodrome of neuropathic pain in the affected skin dermatomes followed within 1 to 5 days by the development of a maculopapular, then vesicular eruption. Typically, a diagnosis is made clinically. Only rarely are more refined studies, such as direct immunofluorescence or polymerase chain reaction (PCR) for viral identification, required or used. This patient has involvement predominantly of the T4 dermatome, with overflow to contiguous dermatomes. The rash should not cross the midline. True disseminated herpes zoster is usually defined as more than 5 vesicles in noncontiguous dermatomes; thus, it is not present here.
Clinical efficacy trials of a live attenuated herpes zoster vaccine have shown prevention efficacy of 70% in people age 50 to 59 years; 64% in people age 60 to 69 years, and 38% in people above 70 years old. But efficacy against postherpetic neuralgia, a serious and debilitating sequela, is greater than 65% in essentially all age groups.4 Therefore, the vaccine has been recommended by the Advisory Committee on Immunization for all persons 60 years or older, and Answer B is not correct.
The vaccine can indeed be administered after a zoster event. Repeat attacks are possible and seem to be increasing in frequency, although the risk is relatively low and because there is a “booster” response to cellular immunity after a zoster event.5 Since vaccine effectiveness decays over time and the presence of the immunity “booster effect” previously mentioned, a 3-year delay after the zoster event has been suggested to optimize length of time of protection. Thus, Answer A is a correct statement.
Outcome of The Case
The diagnosis of herpes zoster was made clinically and the patient was immediately started on valacyclovir qid. Vesicles erupted over the course of the next 48 hours but then ceased. All lesions healed within 2 weeks and the patient reported mild postherpetic neuralgia controlled by acetaminophen at bedtime. There is planned vaccination at a later date.
Take-Home Message
Herpes zoster, or shingles, is an extremely common illness—particularly in people over 60 years old. Age related decline in T cell immunity is the major risk factor. Typical presentation involves acute onset of varying pain syndromes in a dermatomal distribution, followed by the typical, maculopapular, then vesicular rash at the site within 1 to 5 days. Prompt initiation of antiviral therapy, particularly valacyclovir, hastens resolution of acute findings but postherpatic neuralgia remains a significant problem in this illness. Live attenuated virus vaccine is effective in reducing the incidence of zoster in both nonvaccinated and vaccinated persons.
Ronald Rubin, MD, is a professor of medicine at Temple University School of Medicine and chief of clinical hematology in the department of medicine at Temple University Hospital, both in Philadelphia.
References:
1. Cohen JI. Herpes zoster. N Eng J Med. 2013;
369:255-263.
2. Arvin A. Aging, immunity, and the varicella zoster virus. N Eng J Med. 2005;352:2266-2267.
3. Stankus JS, Dlugopolski M, Packer D. Management of herpes zoster (shingles) and postherpetic neuralgia. Am Fam Physician. 2000;61:
2437-2444.
4. Kimberlin DW, Whitney RJ. Varicella-zoster vaccine for the prevention of herpes zoster. N Eng J Med. 2007;356:1338-1343.
5. Tseng HF, Chi M, Smith N, et al. Herpes zoster vaccine and the incidence of recurrent herpes zoster in an immunocompetent elderly population. J Infect Dis. 2012;206:190-196.