Varicella-Zoster Case File

Varicella-Zoster Case File

Eugene C.Toy, MD, Cynthia Debord, PHD, Audrey Wanger, PHD, Gilbert Castro, PHD, James D. Kettering, PHD, Donald Briscoe, MD

CASE 38

A 65-year-old man comes to your office for the evaluation of lower back pain. For the past 3 days, he has had a sharp, burning pain in his left lower back, which would radiate to his flank and, sometimes, all the way around to his abdomen. The pain comes and goes, feels like an “electric shock,” is unrelated to activity, and can be severe. He has had no injury to his back and has no history of back problems in the past. He denies fever, urinary symptoms, or gastrointestinal symptoms. His examination today, including careful back and abdominal examination, is normal. You prescribe a nonsteroidal antiinflammatory drug for the pain. The next day, he returns to your office stating that he has had an allergic reaction to the medication because he’s developed a rash. The rash is in the area where he had the pain for which he was seen the day before. On examination now, he has an eruption consisting of patches of erythema with clusters of vesicles extending in a dermatomal distribution from his left lower back to the midline of his abdomen.

◆ What is the cause of this rash?

◆ What is the mechanism for the dermatomal distribution of the rash?

ANSWERS TO CASE 38: VARICELLA-ZOSTER

Summary: A 65-year-old man has a painful, dermatomal rash.

◆ Cause of this rash: The most likely cause of this man’s rash is reactivation of varicella-zoster virus, causing the appearance of shingles.

◆ Mechanism for the dermatomal distribution of the rash: The dermatomal distribution of this rash is caused by reactivation of a latent varicella infection of a dorsal root ganglion with viral spread along the pathway of the nerve distribution.

CLINICAL CORRELATION

Varicella-zoster virus (VZV) is the causative agent of both chickenpox and shingles. Primary infection with chickenpox occurs mostly in children, with 90 percent of the population acquiring antibodies to VZV by age 10. After primary infection, the virus becomes latent in the dorsal root ganglia, where it may be reactivated later in life. Reactivation of VZV infection results in the unilateral eruption of a painful rash known as herpes zoster or shingles.

APPROACH TO SUSPECTED VZV INFECTION

Objectives

1. Be able to describe the characteristics of the virus.
2. Be able to describe the strategies for prevention and treatment of the infection.

Definitions

Dermatome: An area of skin served by one sensory spinal nerve.

Neuropathic pain: Pain disseminating from the peripheral nervous system.

DISCUSSION

Characteristics of VZV That Impact Transmission

VZV is a member of the Alphaherpesvirinae subfamily of the herpesviruses, which also include HSV-1 and HSV-2. Similar to other herpesviruses, VZV is a large, enveloped virus with a double-stranded DNA genome. As an enveloped virus, VZV is sensitive to drying and many detergents, necessitating its spread from person to person via respiratory droplets or direct contact with skin lesions. Initial VZV infection and replication occur in the epithelium of the respiratory tract, followed by viremic spread to the skin The virus binds to specific receptors, and the viral envelope fuses with the cell membrane. The capsid delivers the genome to the host cell nucleus where transcription and replication occur.

VZV can cause both lytic and latent infections. In lytic infections, new virions are assembled in the host nucleus, acquire an envelope from the nuclear or Golgi membrane, and are released by exocytosis or lysis of the host cell. In latent infections, the viral genome is not replicated, and only certain viral genes are transcribed. Latent infection of dorsal root or cranial nerve ganglia can occur during the initial infection. The virus spreads by viremia or lymphatic dissemination to the reticuloendothelial system. A secondary viremia then occurs, which disseminates VZV to the skin and other organs. VZV can also form syncytia and spread directly from cell to cell.

Diagnosis

Viremic spread to the skin results in classic varicella infection or chickenpox. Typically, crops of vesicles and pustules form on erythematous bases, starting on the head and trunk and progressing centripetally to the extremities. The appearance of these lesions is often described as “dewdrops on a rose petal.” Both humoral and cell-mediated immunity contribute to control of the infection. VZV is a common childhood disease, and infection usually confers lifelong immunity against future disseminated disease. However, reactivation of latent VZV infections of nerve root ganglia may result and is classically described as herpes zoster or shingles. The causes of the reactivation are not entirely known, but it tends to be more common in older persons as cellular immunity decreases, in immunosuppressed individuals or in otherwise immunecompetent individuals during times of emotional stress. The reactivated virus replicates and is released along the dermatomal distribution of the nerve, causing the characteristic unilateral vesicular eruption of shingles. The rash is frequently preceded by pain along the course of a sensory nerve days to weeks prior to the onset of rash. Neuropathic pain may continue to persist for weeks or months after the rash clears, indicating damage to the nerve root. Secondary bacterial infections may also complicate reactivation. Reactivations of VZV tend to be infrequent and sporadic.

Similar to HSV-1 and HSV-2, VZV can be diagnosed by examining a Tzanck smear of cells scraped from vesicular lesions for the presence of multinucleated giant cells. However, direct fluorescent-antibody staining of vesicular lesion scrapings remains the most rapid, sensitive, and specific assay for diagnosing VZV infections.

Treatment and Prevention

Several viral DNA polymerase inhibitors are available for treating VZV infections including: acyclovir, famciclovir, and valacyclovir. Treatment with these drugs has shown to be effective in reducing fever and skin lesions if treatment is begun within 3 days of onset of infection, prior to the eruption of lesions. These drugs have also shown some efficacy in reducing viral dissemination in immunocompromised patients. Additionally, analgesics and other pain killers can help with the patient’s neuralgia.

Prevention of infection spread involves respiratory and contact isolation of infected patients. Passive immunization of high-titer varicilla-zoster immunoglobulin (VZIg) can be administered to immunocompromised patients if given within 3 days of exposure. This treatment is effective only for inhibiting primary infection in high-risk patients. More recently, a live vaccine has been used in the United States since 1995 to prevent primary childhood infections. A single dose has been shown to be 80 percent effective in children 1–13 years of age, and two doses have been shown to be 70 percent effective in adults. A new, live-attenuated virus vaccine, Zostavax, is recommended to reduce the incidence of shingles for adults over the age of 60.

COMPREHENSION QUESTIONS

[38.1] A Tzanck smear is obtained from a scraping of a patient’s skin lesion, and analysis of the smear shows the presence of multinucleated giant cells. Which of the following viruses are known to cause this type cytopathic effect in infected cells?

A. Cytomegalovirus

B. Epstein-Barr virus

C. Herspes simplex virus- type 2

D. Human papillomavirus

E. Human herpesvirus 8

[38.2] A 3-year-old girl presented to her pediatrician’s office with fever, swollen lymph nodes, and a vesicular rash on her chest and upper arms. The vesicles were at various stages of development: some were newly forming, while some were crusted over. Which of the following infectious agents is the most likely cause of this girl’s rash?

A. Smallpox

B. Parvovirus B19

C. Epstein-Barr virus

D. Measles virus

E. Varicella-zoster virus

[38.3] Based on information provided in the previous question, which of the following clinical specimens should be collected to confirm diagnosis of VZV infection?

A. Saliva

B. Blood

C. Vesicle fluid

D. Cerebrospinal fluid

E. Urine

Answers

[38.1] C. HSV-1, HSV-2, and VZV are all known to produce multinucleated giant cells resulting in a positive Tzanck smear, whereas CMV, EBV, HPV, and human herpesvirus 8 do not.

[38.2] E. VZV produces a vesicular rash commonly seen in children, and different “crops” of vesicles generally appear on the head and trunk then moving outward; answers A, B, C, and D are incorrect, smallpox infection produces a vesicular rash with all lesions being at the same stage of development, whereas parvovirus B19, EBV, and the measles virus does produce a rash, but not consisting of vesicular lesions.

[38.3] C. VZV-specific antigens or viral DNA can be detected in vesicle fluid leading to a definitive diagnosis of VZV infection; answers A, B, D, and E are incorrect: CMV can be detected in saliva, blood, and urine; VZV is not commonly detected in CSF specimens.

MICROBIOLOGY PEARLS ❖ Primary lytic infection: chickenpox or varicella; recurrent latent infection: shingles or zoster. ❖ Clinical manifestations: unilateral eruption of a painful rash in a single dermatome. ❖ Prevention of varicella is by immunization of children and adults over the age of 60, respiratory and contact isolation of infected persons. ❖ Treatment: viral DNA polymerase inhibitors such as acyclovir, famciclovir, and valacyclovir.

REFERENCES

Fields BN, Knipe DM, Howley PM, et al. Herpesviridae. Fields Virology, 3rd ed. Philadelphia, PA: Lippincott-Raven, 1996:2525–41. 

Murray PR, Rosenthal KS, Pfaller MA. Medical Microbiology, 5th ed. St. Louis, MO: Mosby, 2005:550–3. 

Ryan JR, Ray CG. Sherris Medical Microbiology, 4th ed. New York: McGraw-Hill, 2004:562–6.

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