# Human Granulocytic Ehrlichiosis Complicating  Early Pregnancy

Authors: Tyler Muffly; T. Chad  McCormick; Christopher Cook; Jeffrey Wall
Journal: Infectious Diseases in Obstetrics and Gynecology
 (2008)

---

## Abstract

Background. The goal of this case is to review the zoonotic infection, human granulocytic ehrlichiosis, presenting with pyrexia. Case. A 22-year-old multigravid female presented to the emergency department with a painful skin rash, high fever, and severe myalgias. The patient underwent a diagnostic evaluation for zoonotic infections due to her geographical and seasonal risk factors. Treatment of human granulocytic ehrlichiosis was successful though the patient spontaneously aborted presumably due to the severity of the acute illness.
Conclusion. Treatment of human granulocytic ehrlichiosis in pregnancy presents unique challenges. Management of pyrexia during pregnancy is limited to external cooling in the setting of thrombocytopenia and elevated aminotransferases. Extensive counseling regarding teratogenic potential of medications allows the patient to weigh the pros and cons of treatment.


---

## Body

## 1. Introduction

The tick-borne illness, human granulocytic
ehrlichiosis (HGE), is rare during pregnancy.
A MEDLINE search from January 1966 through November 2007 using the key
words “ehrlichiosis” and “pregnancy” found 21 English language articles. We
comment on the therapeutic dilemmas of this unusual combination of hyperthermia
and pregnancy that has not been previously described.


## 2. Case

A 22-year-old multigravid female at seven weeks gestational age presented to the emergency
department at a rural referring hospital with symptoms of a rash for three
days, vomiting, nonproductive cough, and complaining of “sore throat and
burning skin.” The severe burning pain
was constant and localized to the areas of the rash. Her prenatal care started
at five weeks and was complicated by tobacco use and one episode of suspected
streptococcal pharyngitis treated
with penicillin six days prior. After evaluation at the referring emergency
department, she was transferred to our facility via air medical service.On examination, the patient was found to be diaphoretic,
febrile to 102.1 degrees Fahrenheit, and normotensive. Physical examination
showed a diffuse maculopapular rash sparing the palms and soles. A bedside
abdominal ultrasound study confirmed fetal movement and a fetal heart rate of
160 beats per minute. Of note, she was leukopenic, thrombocytopenic,
and had elevated plasma aminotransferases to ten times normal values. Our
suspicion was high for human granulocytic ehrlichiosis due to her presentation
from rural Missouri, symptomatology, and classic laboratory findings of leukopenia,
thrombocytopenia, and elevated aminotransferases. Thus, with her informed
consent, empiric doxycycline treatment was administered. Over the next 24
hours, the patient became progressively more febrile spiking temperatures to
103.9 degrees Fahrenheit.Over hospital days two and three,
her aminotransferases decreased, however she continued to have fevers and the
patient remained ill-appearing. The patient’s symptoms of burning skin pain, myalgias,
and malaise decreased slowly. On the third day of the hospitalization, she
began having vaginal bleeding and passed tissue consistent with a seven-week
gestation. Clinical examination and falling beta-HCG levels confirmed a
complete abortion. The painful skin rash improved but limited her range of
movement. After nine days of doxycycline
the patient improved and was discharged to home in good condition. The rash
cleared and the patient had no residual symptoms of disease.


## 3. Comment

Human granulocytic ehrlichiosis is an underreported tick-borne
illness. Ehrlichiosis should be included in the differential diagnosis of any
patient presenting with thrombocytopenia, elevation of aminotransferases,
painful skin rash, and high fevers. Our patient had no recollection of a tick or insect bite, but she lives in rural Missouri
which is mostly wooded containing multiple forms of wildlife. Human granulocytic ehrlichiosis
is endemic to Missouri with 0.01–11.9 cases per million persons yearly. Other disease processes with similar pyrogenic
presentations include viral exanthems, Epstein-Barr virus, leptospirosis, Rocky
Mountain spotted fever, cytomegalovirus, Lyme disease, and Q fever [1]. These
illnesses that cause hyperthermia during pregnancy are of particular concern
because immunosuppression may cause a more severe disease presentation.Zoonotic infections of pregnant women have been documented in the literature. Pregnant women outdoors during
the spring and fall tend to wear less clothing which may increase their risk
for zoonosis. Fever and rash in a pregnant patient are symptoms that should
initiate a differential diagnosis including zoonotic infections. Rocky Mountain
spotted fever presents in a specific geographic area with a fall and spring
temporal distribution. The maculopapular rash in Rocky Mountain spotted fever is similar to that of other tick-borne
illnesses. The main clinical factor that discriminates Rocky Mountain spotted
fever from HGE is the lack of temperature above 102 degrees Fahrenheit.
Leptospirosis has also been reported in pregnant women and is the most common
zoonosis worldwide [2]. Conjunctival
suffusion is pathognomonic for leptospirosis in a patient with nonspecific
febrile illness and myalgias. Exposure to lake, river, and stream water
contaminated with animal waste increases the risk of acquiring Leptospira interrogans [3]. Q fever is
caused by inhalation of infected particles of animal feces. The disease can
present with fever, rash, and flu-like illness. Also, Q fever presentation
tends to be age-specific, with younger patients developing hepatitis and the
older population acquiring pneumonia. Coxiella burnetti infection should be
considered in patients who have first trimester obstetric complications and
fever [4]. Lyme disease manifests with intermittent fevers and chills. The
classic Lyme disease rash is an asymptomatic erythema migrans which presents as
central clearing within an erythematous base. The list of potential parasitic
zoonoses is quite large, however careful history and physical examination can
lead to early detection [2].In the pregnant patient, maternal hyperthermia greater than 103 degrees Fahrenheit denatures proteins causing cell death,
membrane disruption, vascular disruption, and placental infarction during organogenesis. Treatment of infectious febrile illnesses during
pregnancy can be accomplished with pharmacologic and external cooling methods
[5]. However, nonsteroidal anti-inflammatory agents, and acetaminophen are
relatively contraindicated antipyretics in a patient with thrombocytopenia and
elevated aminotransferases. Antipyretic agents work
by lowering the hypothalamic setpoint, which is increased during pyrexia [6].
Endogenous pyrogens, such as interleukin-1 and interleukin-6, cause febrile
response by stimulating cerebral prostaglandin-E synthesis [7]. Antipyretic
agents block this process by inhibiting the arachidonic acid cycle in the brain
[8]. The result is a lowering of the hypothalamic setpoint, which activates the
body’s two principle mechanisms for heat dissipation: vasodilation and
sweating. External cooling methods attempt to maximize the amount of heat
diffused by convection, conduction, and radiation. External cooling methods
used to maintain normothermia include water-flow blankets, ice packs to the
axillae and groin, intravenous and oral hydration with cool fluids, or
immersion in a tepid bath. Shivering causes increased heat production and is a
sign to halt cooling efforts.Some diseases have a limited array of pharmacologic treatments and may potentially
cause harm to the fetus. The view that doxycycline, to treat HGE, is
relatively contraindicated in pregnancy due to its effects on fetal teeth and
bones is no longer accepted as a valid point of medical dogma.
Doxycycline is no longer absolutely contraindicated in pregnancy [9]. Alternative
treatment for ehrlichiosis during pregnancy includes rifampin in a limited
number of patients. Microscopy of buffy coat smear, PCR, and cell culture are
ideal methods to confirm the diagnosis of HGE [10]. Wright’s stained buffy coat
of peripheral blood will show morulae characteristics on histopathology.
Elevated serum antibody titers to HGE can also eliminate rickettsial disease.
We suspect that there is much more to be known about the effects of ehrlichiosis on pregnancy.The case here, with abortion, hyperpyrexia, consumptive
coagulopathy, and hepatic involvement, contradicts the recent observation that
ehrlichosis was not particularly fulminant in pregnancy. The literature
describes human granulocytic ehrlichiosis as a mild illness because of the
immunosuppression during pregnancy [11]. The severity of the laboratory
findings, clinical presentation, and gestational age make this case unique.



---

*Source: 359172-2008-05-22.xml*