Human Granulocytic Ehrlichiosis Complicating Early Pregnancy (2023)

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.

1. INTRODUCTION

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

2. CASE

A 22-year-old multigravid female at seven weeks gestational age presented to the emergencydepartment at a rural referring hospital with symptoms of a rash for threedays, vomiting, nonproductive cough, and complaining of “sore throat andburning skin.” The severe burning painwas constant and localized to the areas of the rash. Her prenatal care startedat five weeks and was complicated by tobacco use and one episode of suspectedstreptococcal pharyngitis treatedwith penicillin six days prior. After evaluation at the referring emergencydepartment, 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 examinationshowed a diffuse maculopapular rash sparing the palms and soles. A bedsideabdominal ultrasound study confirmed fetal movement and a fetal heart rate of160 beats per minute. Of note, she was leukopenic, thrombocytopenic,and had elevated plasma aminotransferases to ten times normal values. Oursuspicion was high for human granulocytic ehrlichiosis due to her presentationfrom rural Missouri, symptomatology, and classic laboratory findings of leukopenia,thrombocytopenia, and elevated aminotransferases. Thus, with her informedconsent, empiric doxycycline treatment was administered. Over the next 24hours, the patient became progressively more febrile spiking temperatures to103.9 degrees Fahrenheit.

Over hospital days two and three,her aminotransferases decreased, however she continued to have fevers and thepatient remained ill-appearing. The patient’s symptoms of burning skin pain, myalgias,and malaise decreased slowly. On the third day of the hospitalization, shebegan having vaginal bleeding and passed tissue consistent with a seven-weekgestation. Clinical examination and falling beta-HCG levels confirmed acomplete abortion. The painful skin rash improved but limited her range ofmovement. After nine days of doxycyclinethe patient improved and was discharged to home in good condition. The rashcleared and the patient had no residual symptoms of disease.

3. COMMENT

Human granulocytic ehrlichiosis is an underreported tick-borneillness. Ehrlichiosis should be included in the differential diagnosis of anypatient 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 Missouriwhich is mostly wooded containing multiple forms of wildlife. Human granulocytic ehrlichiosisis endemic to Missouri with 0.01–11.9 cases per million persons yearly. Other disease processes with similar pyrogenicpresentations include viral exanthems, Epstein-Barr virus, leptospirosis, RockyMountain spotted fever, cytomegalovirus, Lyme disease, and Q fever [1]. Theseillnesses that cause hyperthermia during pregnancy are of particular concernbecause immunosuppression may cause a more severe disease presentation.

Zoonotic infections of pregnant women have been documented in the literature. Pregnant women outdoors duringthe spring and fall tend to wear less clothing which may increase their riskfor zoonosis. Fever and rash in a pregnant patient are symptoms that shouldinitiate a differential diagnosis including zoonotic infections. Rocky Mountainspotted fever presents in a specific geographic area with a fall and springtemporal distribution. The maculopapular rash in Rocky Mountain spotted fever is similar to that of other tick-borneillnesses. The main clinical factor that discriminates Rocky Mountain spottedfever from HGE is the lack of temperature above 102 degrees Fahrenheit.Leptospirosis has also been reported in pregnant women and is the most commonzoonosis worldwide [2]. Conjunctivalsuffusion is pathognomonic for leptospirosis in a patient with nonspecificfebrile illness and myalgias. Exposure to lake, river, and stream watercontaminated with animal waste increases the risk of acquiring Leptospira interrogans [3]. Q fever iscaused by inhalation of infected particles of animal feces. The disease canpresent with fever, rash, and flu-like illness. Also, Q fever presentationtends to be age-specific, with younger patients developing hepatitis and theolder population acquiring pneumonia. Coxiella burnetti infection should beconsidered in patients who have first trimester obstetric complications andfever [4]. Lyme disease manifests with intermittent fevers and chills. Theclassic Lyme disease rash is an asymptomatic erythema migrans which presents ascentral clearing within an erythematous base. The list of potential parasiticzoonoses is quite large, however careful history and physical examination canlead 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 duringpregnancy can be accomplished with pharmacologic and external cooling methods[5]. However, nonsteroidal anti-inflammatory agents, and acetaminophen arerelatively contraindicated antipyretics in a patient with thrombocytopenia andelevated aminotransferases. Antipyretic agents workby lowering the hypothalamic setpoint, which is increased during pyrexia [6].Endogenous pyrogens, such as interleukin-1 and interleukin-6, cause febrileresponse by stimulating cerebral prostaglandin-E synthesis [7]. Antipyreticagents block this process by inhibiting the arachidonic acid cycle in the brain[8]. The result is a lowering of the hypothalamic setpoint, which activates thebody’s two principle mechanisms for heat dissipation: vasodilation andsweating. External cooling methods attempt to maximize the amount of heatdiffused by convection, conduction, and radiation. External cooling methodsused to maintain normothermia include water-flow blankets, ice packs to theaxillae and groin, intravenous and oral hydration with cool fluids, orimmersion in a tepid bath. Shivering causes increased heat production and is asign to halt cooling efforts.

Some diseases have a limited array of pharmacologic treatments and may potentiallycause harm to the fetus. The view that doxycycline, to treat HGE, isrelatively contraindicated in pregnancy due to its effects on fetal teeth andbones is no longer accepted as a valid point of medical dogma.Doxycycline is no longer absolutely contraindicated in pregnancy [9]. Alternativetreatment for ehrlichiosis during pregnancy includes rifampin in a limitednumber of patients. Microscopy of buffy coat smear, PCR, and cell culture areideal methods to confirm the diagnosis of HGE [10]. Wright’s stained buffy coatof 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, consumptivecoagulopathy, and hepatic involvement, contradicts the recent observation thatehrlichosis was not particularly fulminant in pregnancy. The literaturedescribes human granulocytic ehrlichiosis as a mild illness because of theimmunosuppression during pregnancy [11]. The severity of the laboratoryfindings, clinical presentation, and gestational age make this case unique.

ACKNOWLEDGMENTS

We would like to thank Roger P. Smith, M.D. at the University of Missouri at Kansas Cityfor his continued support. Therewas no financial support given for this study. The authors received no writingassistance. This paper has not been presented in any meetings.

References