Abdominal Pain in a Normal Host
Abdominal Pain in a Normal Host
Ajit P. Limaye
for the Photo Quiz.)
Diagnosis: Herpes simplex hepatitis with Cowdry cells Initial intraoperative pathology of the liver biopsy showed cellular infiltrate and Kupffer cell proliferation consistent with acute hepatitis (Figure 2). Acute and chronic, focally necrotizing hepatitis due to Herpes simplex virus was diagnosed, because of enlarged cells with inclusions, or Cowdry cells, pathognomonic of herpes virus (Figure 3). Consultation with Dermatology noted 2 other lesions on his chest, which raised concern for disseminated Herpes simplex. He was started on IV acyclovir with gradual resolution of fever and right upper quadrant (RUQ) abdominal pain. The patient noted no prior history of herpes infection. He reports being sexually active with only his wife of 30 years. His wife had a recurrent lesion on her buttock for years, but a diagnosis was never obtained. Serum herpes simplex virus type 1 (HSV1) and HSV2 immunoglobulin M (IgM) were positive. HSV2 DNA was detected in the serum. HSV polymerase chain reaction (PCR) of liver biopsy was positive, and immunohistochemical stains showed strong, predominantly subcapsular reactivity with HSV2 antibody and some reactivity with HSV1. Other viral immunostains (cytomegalovirus [CMV], Epstein-Barr virus [EBV], adenovirus, hepatitis B virus [HBV], and Varicella) were all negative. PCR of all 3 skin lesions were positive for HSV2. Human immunodeficiency virus (HIV), rapid plasma reagin (RPR), antinuclear antibodies (ANA), anti-smooth muscle antibody, CMV, EBV (IgM), HAV, HBV, and HCV were all negative. Serum protein electrophoresis and immunoglobulins were normal. CD4 count was normal, with abnormally high CD4/CD8 ratio of 8.19. CD8 cells were low 73 (5%), normal 410-1590 (13%-41%). CD8 suppressor cells are instrumental in response to HSV infection, and few CD8 cells were seen in this inflamed liver. Idiopathic CD8 deficiency persists, 78 cells/cucm (6%), 1 year after presentation.
Background Herpes Simplex Virus Hepatitis
HSV hepatitis is a rare entity with one literature review citing
only 137 cases from 1969 to 2006 [
]. HSV hepatitis more often
affects immunocompromised patients and pregnant women,
but in a study of patients with acute liver failure related to
HSV, one fourth of the patients were immunocompetent [
Presentation varies and usually includes a documented fever
as well as myalgias and abdominal pain, but only 30%–50%
present with skin lesions. Some refer to the lab findings of
HSV hepatitis as “anicteric hepatitis,” which show elevated
alanine aminotransferease (AST) and aspartate aminotransferease
(ALT) in the setting of normal or low bilirubin [
HSV can lead to acute liver failure requiring liver
transplant. In the Norvell study noted above, 74% of the cases
Figure 2. H&E stain (×100) with periportal and subcapsular cellular infiltrate.
Figure 3. Trichrome stain (×200) with higher magnification of cellular proliferation.
of acute liver failure related to HSV hepatitis progressed to
to have the highest sensitivity and specificity of the disease
death or liver transplant. The study notes that in over half of
the cases the diagnosis was made post-mortem with autopsy.
The literature points out that early recognition or
consideration of HSV as a cause of hepatitis leads to treatment with
acyclovir that does make a difference in outcomes. In patients
with hepatitis and acute liver failure without a known cause,
acyclovir should be started empirically while testing is
Two types of intranuclear inclusions are identified in liver cells
located at the interface of the necrotic and viable regions and are
pathognomonic of HSV:
Cowdry type A: Large and eosinophilic, with a peripherally
located “clear” space or halo.
Cowdry type B: Basophilic, filling up the entire nucleus
(ground-glass appearance), with a peripheral rim of finely
Cowdry inclusion bodies are found inside the nucleus of
macrophages in patients with HSV. The virus causes
“ballooning of cells” where “cells lose intact plasma membranes
multinucleated giant cells.” The subsequent cell
lysis makes for the vesicular fluid inside the vesicles of HSV
on the skin or mucosa [
]. The cytologic diagnostic criteria
of HSV has been defined as “multinucleation, margination
of nuclear chromatin, ground glass chromatin and
intranuclear inclusions” although ground glass chromatin is noted
Potential conflicts of interest. All authors: No reported conflicts of
interest. All authors have submitted the ICMJE Form for Disclosure of
Potential Conflicts of Interest. Conflicts that the editors consider relevant to
the content of the manuscript have been disclosed.
Erica D. Wadas,1 Scott A. Hirschman,2 Byron F. Santos,1,2 and Thomas H. Taylor1,2
Clinical Infectious Diseases®
Published by Oxford University Press for the Infectious Diseases Society of America 2018.
This work is written by (a) US Government employee(s) and is in the public domain in the US.
ANSWER TO THE PHOTO QUIZ • CID 2018:66 (1 May) • 1477
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