Weeks, M G

eVols at University of Hawaii at Manoa

Case of the MonthEhrlichiosis...in Hawaii?An Unusual PresentationMatthew G. Weeks, MD, CPT, MC, USADepartment of Family PracticeTripler Army Medical CenterHonolulu, HawaiiTick-borne disease like Rocky Mountain Spotted Fever. tularemia, and relapsing fever, have long been recognized but have beenjoined in the past two decades by newly described diseases such asLyrne disease, babesiosis, and ehrlichiosis. The first case of humanehrlichiosis in the western hemisphere was recorded in 1986.’Human ehrlichiosis is a geographically diverse tick-borne diseasethat has two pathologically distinct but clinically similar forms.Human monocytic ehrlichiosis (HME) and human granulocyticehrlichiosis (HGE) have been reported in 32 states on the U.S.mainland, Western Europe, Scandinavia, and Africa.2 Indigenousand introduced species of ticks may be found in Hawaii, but nonehave been implicated as vectors for ehrlichiosis or other humanpathogens. The incubation period for ehrlichiosis ranges from 0-34days, but symptoms generally occur one week after tick exposure.If untreated. ehrlichiosis can lead to multi-organ failure and death.The following case illustrates that clinicians living in non endemicareas must obtain a remote history of a tick bite or travel into areasendemic for tick-borne illness.Case ReportA previously healthy 29-year-old Hispanic male soldier presentedto a military hospital in Hawaii with a two-week history of severeretro-orbital headaches, photophobia. intermittent fevers up to 103degrees F, rigors, anorexia, nausea, and vomiting. The patient wastreated for suspected sinusitis with Bactrim and reported no resolution of his symptoms. He was referred to an Otolaryngologist.Evaluation with nasopharyngolaryngoscopy and CT scans failed toreveal evidence of sinusitis.This soldier was stationed at Schofield Barracks, Hawaii. Histravel history included attendance at field exercises in Texas andAlaska. ten and six weeks prior to presentation, respectively. InTexas, he recalled a tick bite to his left groin.His physical examination revealed a temperature of 101 .8 degreesF. moderate distress secondary to headache, pain on extraocularmovement, photophobia. and bilateral inguinal and axillary adenopathy. Pertinent negative findings included normal fundi. norhinorrhea. no meningismus. and no focal neurological deficits.Initial laboratory values were significant for elevated hepatictransaminases: AST-4 15 UIL. ALT-S 17 U/L. GGT- 128 UIL. alkaline phosphatase 260 U/L, and total bil i rubin level of 1.7 mg/dl. Thepatient was noted to have thrombocytopenia with a platelet level of94 XlO(9)/L. A normal WBC count of 8.1 Xl0(9)/L. hemoglobinof 15.3 g/dl. and hematocrit of 44.4%. A lumbar puncture wasperformed and spinal fluid analysis was normal with respect toglucose, protein, cell count, gram stain, and culture. Other pertinentnegative lab tests included serum chemistry, Lyme, Babesia, RockyMountain Spotted Fever, Leptospirosis, EBV, CMV, HIV, Hepatitis A/B/C, and Toxoplasmosis serologies.The patient was empirically started on Doxycycline 100 ing p0bid for 14 days. His symptoms and laboratory abnormalitiesresolved rapidly over the next two days and he had a full recovery.An admission serum titer was positive for Ehrlichia c/iat’ensis IgGat 1:256 and convalescent testing was not performed given the highacute titer and clinical criteria consistent with the diagnosis ofHuman Monocytic Ehrlichiosis.DiscussionEhrlichiae are obligate intracellular gram negative bacteria.Ehrlichia chaffeensis is the agent responsible for HME and a yetunnamed organism genetically similar toEhrlichia equi and Ehrlichiaphagocytophilia results in HGE.34’5 The ticks responsible fortransmission of HME are Dermacentor variabilis (Dog tick) andAmblyomma americanum (Lone Star tick). The organism responsible for HGE is also carried by Dermacentor variabilis as well asIxodes scapularis (Deer tick).(2) Neither Hawaii nor Alaska havereported a case of HME or HGE, but both are endemic in Texas.Human Ehrlichiosis is usually suspected on the basis of a historyof a recent tick bite. The usual incubation period is one to thirty fourdays.(6) Common presenting symptoms include fever, rigors.malaise, myalgia. and headaches. Less frequently, one may seediaphoresis. cough, pharyngitis, lymphadenopathy. anorexia, nausea, vomiting, diarrhea. abdominal pain, arthralgias. mental confusion, or a non-specific rash. Other clinical features describedinclude ARDS. toxic shock syndrome. myocardial involvement(e.g. left ventricular dilatation), brachial plexopathy. prolongedfever, hypotension. pharyngitis. and conjunctivitis.2Laboratory findings most commonly seen include thrombocytopenia, lymphocytopenia, leukopenia, and elevated hepatic transaminase levels. Less frequent laboratory findings include anemia,elevated cerebrospinal fluid protein and pleocytosis. fibrin splitproducts, hyponatremia. elevated ESR, elevated blood urea nitrogen and creatinine, elevated CPK and elevated bilirubin.2 On aWright stain of the peripheral smear there may be morulae (intracellular inclusions) seen in either monocytes or granulocytes.’Complications of untreated Human Ehrlichiosis include severecough with pulmonary infiltrates, gastrointestinal bleeding, gastroenteritis, meningitis, pericarditis, hepatitis with focal hepatic necrosis, renal failure, disseminated intravascular coagulopathy, opportunistic infections, and multi-organ failure.6The emergence of ehrlichiosis has broadened the differentialdiagnosis of patients with “flu-like” symptoms. The clinical presentation mimics many infectious diseases, to include leptospirosis.mononucleosis, viral hepatitis. gastroenteritis. endocarditis. pneumonia, and meningoencephalitis. It also may resemble non infectious diseases, such as hernatologic malignancies and collagenvascular diseases.Ehrlichiosis should be considered in any febrile patient withexposure to ticks within the preceding three weeks, particularly ifleukopenia. thrombocytopenia. or elevated hepatic transaminasesare seen. However, as this case illustrates, prolonged incubationperiods occur and clinicians must take this into acount.Currently the diagnosis of HME and HGE is made by a fourfoldHAWAII MEDICAL JOURNAL, VOL 59. MAY 2009182rise or fall in immunofluorescent antibody (IFA) titer with a peaktiter of 64 or greater in a clinically compatible case.7 Observation ofmorulae in a blood smear or a buffy coat preparation is insensitivebut should be pursued, as it can help establish the diagnosis immediately. Other diagnostic techniques include immunohistochemistry, and culture.2 PCR primer sets have also been developed for thediagnosis of both HGE and HME.8Doxycycline 100 mg P0 bid for 10-14 days is the treatment ofchoice.67 For children, chioramphenicol is recommended but hasbeen shown to be less effective.2 Treatment should not be withheldpending laboratory confirmation, as delays in diagnosis may beassociated with worse outcomes.This case was unusual in that it either represents a prolongedincubation period if aquired in the endemic area of Texas, or a caseof transmission of the disease occurring in Alaska or Hawaii— stateswhere there have been no prior reported cases of ehrlichiosis. It ispresumed that this most likely represents a prolonged incubationperiod based on the history of a tick bite in Texas. Although noendemic tick-borne disease is found in Hawaii, the increased recognition and prevalance of emerging tick-borne diseases worldwidewill impact healthcare providers here. The differential diagnosis inthe febrile traveler continues to expand and ehrlichiosis is yetanother disease to be considered.Geographic Distribution ofHuman Ehrlichiosis 1986-1996No reported cases Human Granulocytic Ebrlichiosis (HGE)CD HGE and HME Human Monocytic Ehrlichiosis (HME)References1 Maeda K, Markowitz N, Hawley RC, et al. Human infection with Ehrlichia canis, a leukocytic rickeffsia,N Eng J Med 316: 853-856, 1987.2. Fritz CL, Glaser CA. Ehrlichiosis. Infectious Disease Clinics of North America. 1998, 12: 123-136.3. Damson JE, Anderson BE, Fishbein DB, et al. Isolation and characterization of an Ehrlichia sp. Froma patient diagnosed with human ehrlichiosis. J Clin Microbiol. 29: 2741-2745, 19914. Chen SM, Dumler JS, Bakken JS, et al. Identification of a granulocytotropic Ehrlichia species as theetiologic agent of human disease. J Clin Microbiol, 32: 589-595, 1994.5. Madigan HE, Richter PJ, Kimsey RB, et al, Transmission and passage of horses of the agent of humangranulocytic ehrlichiosis. J Infect Dis, 172: 1141-1144, 1995.6. Eng TR, Harkess JR, Fishbein DB, et al. Epidemiologic, clinical and laboratory findings of humanehrlichiosis in the United States. 1988. JAMA 264:2251-2258, 1990.7. Centers for Disease Control and Prevention: Human ehrlichiosis- Maryland, 1994. MMWR 45: 798-802, 1996.8. Everett ED, Evans KA, Henry RB. et al: Human ehdichiosis in adults after tick exposure: Diagnosisusing polymerase chain reaction. Ann Intern Med 120: 730-735. 1994.Letter to the EditorSir:Mrs. Norma Whelan, Dr. Thomas Whelan’s wife, mailed my daughter, Sandra, and I copies of the Hawaii Medical Journal specialmemorial issue on Dr. Thomas J. Whelan, Jr. I have read each articlewritten by his children and professional colleagues, but I sawnothing of his compassion for his patients and the patients family.His compassion is what I believe made him a great surgeon.I met Dr. Whelan in August 1962 when he was chief of vascularsurgery at Walter Reed Medical Center when my 7-year-old daughter, Sandra, had been referred to him with a large liver tumor. Dr.Whelan removed the tumor in a 12 hour complicated procedure thatI later learned few surgeons in the United States were qualified toperform.What really impressed my wife, Louise, and I was Dr. Whelan’scompassion and concern for his patients and their family. Hearranged accommodations for my wife and I at Walter Reed andspent hours with Sandra while she was in surgical intensive care.After Sandra’s release from the hospital, she was followed for yearsby Dr. Whelan. While sitting in the doctor’s office during follow upvisits I’ve heard Dr. Whelan make telephone calls to arrangetransportation to Washington, DC and accommodations near WalterReed Medical Center while a family member was undergoing andrecovering from a major surgical procedure. Mrs. Whelan told methat Doctor Whelan often made house calls. And over the ensuingyears I remained in touch with Dr. Whelan and on my frequent visitsto Hawaii a must for me was a call to a doctor.My family and I are fortunate and honored to have met a manpossessing so great a professional skill and so much concern for hispatients and their families. I am fortunate to have met and know sowonderful a man. To my family he was special.Sincerely.John IrelandThomas J. Whelan, Jr., MD192 1-1999HAWAM MED[CAL JOURNAL, VOL 59, MAY 2000183

Ehrlichiosis ... in Hawaii? An unusual presentation.

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Ehrlichiosis ... in Hawaii? An unusual presentation.

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