Tag: virology

Microbiology Case Study: An Unusual Case of Herpes Reactivation

Case history

A 37-year-old female with a past medical history of psoriasis and common variable immunodeficiency disorder (CVID) presented to her dermatologist for an ulceration on her right buttock following a camping trip about 1 month ago. She thought that she had been bitten by a bug, for the lesion became extremely pruritic and painful. The patient was self-treating the area with over-the-counter antibiotic ointment and an anti-itch cream, but the symptoms persisted. At the time, the dermatologist was also treating a lower extremity dermatophyte infection, and the antibiotic cream and anti-itch cream were discontinued and replaced with clobetasol 0.05% ointment for potential allergic dermatitis. The patient returned to the dermatologist about a month later as the site was becoming increasingly inflamed and painful. The patient had also started experiencing night sweats and fever, so she was transferred and further evaluated in the emergency department. In the ED, the differential included soft tissue infection, cellulitis, or abscess of a fungal, viral, or bacterial etiology. Labs showed evidence of inflammation with an elevated ESR and CRP. A punch biopsy was performed and pathologic examination showed an ulcer bed with prominent acute inflammatory cell infiltrate and necrosis. The infected squamous epithelium showed the3 Ms findings (Molding, Margination, Multinucleation) consistent with herpetic infection (figure 1). The diagnosis was confirmed with HSV complex IHC (figure 2) and PCR testing of the lesion came back positive for HSV-2. Of note, the patient did have a history of genital herpes; however, she was not having a typical flare, and she had been treated with a 10-day course of valacyclovir 2 weeks prior to her ED visit. The gram stain showed no evidence of neutrophils, squamous epithelial cells, or organisms, but bacterial cultures came back positive for MRSA.

Figure1. H&E section showing mixed acute and chronic inflammation with squamous cells
showing herpes viral cytopathic effect (400x magnification)
Figure 2. HSV complex (HSV1 and 2) IHC staining virally infected epithelial cells (200x).

Discussion

Herpes simplex virus (HSV) is a large, double-stranded DNA virus from the Herpesviridae family.1,2 HSV-2 is generally considered a sexually transmitted infection because it can be transmitted by contact with infected genital secretions.2,3 The viral particles within these secretions can enter epithelial cells and begin replicating, causing the characteristic intranuclear inclusions and multinucleated giant cells that can be seen under the microscope.2 When the virus infects the cells in this manner, it can also cause these infected cells to separate from each other and form grouped vesicles filled with these cell remnants.2 The virus infects nerve endings and then travels backwards to the sacral ganglia, and it can remain latent there permanently, giving it the ability to recur during the infected person’s lifetime.1 A patient can initially present with symptoms of dysuria, lymphadenopathy, fever, headaches, and myalgias, but more than half of patients may not know they have genital herpes.1,3 Recurrences can present with symptoms of tingling, burning, itching, and pain in the nerve’s distribution pattern, similar to the pain and pruritis in our presented case.2 When there is a suspected HSV infection, PCR for HSV DNA is generally the best diagnostic tool, and it is faster and more sensitive than viral culture.1,2 A patient with known herpes infection should be treated with antivirals; however, the lesions should also self-resolve within 3 weeks if the patient is not treated.1

One abnormality in our presented case was that the patient’s reactivation of genital herpes was on the buttocks. A repeat infection with HSV at a site other than genitalia is more common when the primary infection also occurred at a site other than the genitalia.4 Infections occurring at non-genital sites such as the buttocks can also occur due to self-inoculation, which may have been the case in our patient.4 Additionally, repeat infections with HSV in non-genital sites are more common when the initial infection was with HSV1, but our patient’s PCR showed the presence of HSV-2 DNA.4 One explanation for this phenomenon is that HSV-2 recurrences can occur on the buttocks due to the retrograde transport to the root ganglia in the areas that correspond to these dermatomes.4

Another abnormality in our presented case involves the patient’s persistent infection despite treatment with a course of valacyclovir for 10 days. Generally, an initial herpes infection self-resolves in a matter of weeks, and a recurrent episode will self-resolve in a matter of days, usually less than ten.1,2 It is unusual that her infection persisted despite therapy, but the patient does have a medical history significant for CVID. Patients with weakened immune systems can take longer to fight off herpes infections even if they are taking antivirals.2 Additionally, there is a theory that herpes buttocks infections last longer than in other regions due to the greater travel distance along the nerves as well as a higher concentration of nerve endings in this region.4 The patient in our case also had tissue cultures that were positive for MRSA, meaning she had a concomitant bacterial and viral infection of the buttock region, and treatment with an antiviral would not be sufficient to eradicate her coinfection.

References

1.  Johnston C, Corey L. Current Concepts for Genital Herpes Simplex Virus Infection: Diagnostics and Pathogenesis of Genital Tract Shedding. Clin Microbiol Rev. Jan 2016;29(1):149-61. doi:10.1128/cmr.00043-15

2.  Gupta R, Warren T, Wald A. Genital herpes. Lancet. Dec 22 2007;370(9605):2127-37. doi:10.1016/s0140-6736(07)61908-4

3.  Groves MJ. Genital Herpes: A Review. Am Fam Physician. Jun 1 2016;93(11):928-34.

4.  Benedetti JK, Zeh J, Selke S, Corey L. Frequency and reactivation of nongenital lesions among patients with genital herpes simplex virus. Am J Med. Mar 1995;98(3):237-42. doi:10.1016/s0002-9343(99)80369-6

-Lillian Acree is a fourth-year medical student at the Medical College of Georgia. She is interested in head and neck pathology.

-Hasan Samra, MD, is the Director of Clinical Microbiology at Augusta University and an Assistant Professor at the Medical College of Georgia.

Microbiology Case Study: A 7 Month Old Female with Fever and Seizure-Like Episodes

Case History

A 7 month old female presented to the emergency department (ED) due to fever and seizure-like episodes. Her mother reported the child had been persistently febrile for 5 days (Tmax 103.9°F) with rhinorrhea, fussiness and decreased oral intake. The patient experienced 3 seizure-like episodes on the day of admission, which the mother described as periods of “shaking” with eyes rolling back. The child was unresponsive during these episodes, which lasted 1 to 2 minutes each. The child had been taken to her pediatrician the day prior to presentation to the ED where she was given a shot of ceftriaxone for presumed otitis media. The child received a chest x-ray, influenza testing, and blood and urine cultures were collected. She also had a lumbar puncture performed and the cerebral spinal fluid (CSF) was sent for chemistries, bacterial culture and polymerase chain reaction (PCR) testing for meningitis/encephalitis pathogens. She was started on IV ceftriaxone.

Laboratory Testing

The child’s white blood cell count from peripheral blood was 7.1 TH/cm2 and chest x-ray, urinalysis and flu testing were unremarkable. The CSF was clear and colorless with 7 WBC/cm2, glucose of 57 mg/dL and protein of 21 mg/dL. The cytospin Gram stain identified no organisms. The meningitis/encephalitis panel detected the presence of human herpesvirus 6 (HHV-6).

Discussion

Human herpesvirus 6 is a member of the Herpesviridae family and was the sixth herpes virus identified. Structurally, HHV-6 possesses a double stranded DNA genome and is enveloped. Clinically, it is the etiologic agent of roseola infantum (exanthum subitum) in infants and toddlers. Primary infection occurs in early childhood and those infected can be asymptomatic or have a non-specific febrile illness while only the minority present with the characteristic red macular rash prominent on the trunk and extremities, lymphadenopathy and high fevers. HHV-6 is highly neurotropic and as such causes viral encephalitis with 5-15% of children experiencing febrile seizures as a result of this illness. HHV-6 is highly prevalent with a greater than ninety percent seropervalence rate. HHV-6 establishes latency in T lymphocytes and can reactivate & cause disease, especially in immunocompromised patients such as those recipients of stem cell or solid organ transplants.

Traditional laboratory methods of identification for HHV-6 were challenging as viral culture, while once the gold standard for active disease, is not practical for most labs and is no longer used in routine diagnostics. PCR from serum, plasma or CSF has become the preferred test as there are now FDA-cleared, commercial platforms that are easy to use, allow for rapid turnaround time and in the case of multiplex PCR panels, the ability to target multiple pathogens from one test. Serology, while helpful in the diagnosis of primary infections, may not be provide conclusive results in a timely manner and is of limited utility in reactivation. Other less commonly used methods include immunohistochemistry, in situ hybridization and electron microscopy.

The prognosis for patients infected with HHV-6 is generally good with self-limited illness not requiring treatment. Rarely, multi-organ involvement can occur and HHV-6 infection in immunosuppressed patients can be a major cause of morbidity and mortality. There is no antiviral therapy licensed for the treatment of reactivated disease in this setting, but approaches using ganciclovir and valganciclovir have been proposed.

In the case of our patient, her blood, urine and CSF cultures were negative and her antibiotics were stopped after cultures were no growth at 24 hours. She required no treatment other than supportive care with acetaminophen for fever control. Prior to discharge, she developed a fine rash on her face, the back of her neck and trunk that was characteristic of an HHV-6 rash. This case demonstrates the utility of multiplex PCR testing in providing rapid identification of pathogenic organisms allowing for real time diagnosis and the limiting of unnecessary treatment.

 

ET

-Eric Tillotson, MD, is a second year Anatomic and Clinical Pathology resident at the University of Mississippi Medical Center.

Stempak

-Lisa Stempak, MD, is an Assistant Professor of Pathology at the University of Mississippi Medical Center in Jackson, MS. She is certified by the American Board of Pathology in Anatomic and Clinical Pathology as well as Medical Microbiology. She is the director of the Microbiology and Serology Laboratories. Her interests include infectious disease histology, process and quality improvement and resident education.