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Background
This disease is completely known as Human granulocytotropic ehrlichiosis. It is a tick-borne, acute, nonspecific febrile illness that was first described in 1994. The tick vector is Ixodes scapularis, the same vector of some cases of Lyme disease. The disease has flu-like symptoms with non-specific laboratory findings. Doxycycline provides rapid and effective treatment.
OUTLINE
EPIDEMIOLOGY CHARACTERIZATION SYNONYMS Human granulocytic ehrlichiosis INCIDENCE/PREVALENCE
The prevalence of Borrelia burgdorfieri (Spirochaetales: spirochaetaceae) and the agent of human granulocytic ehrlichiosis (Rickettsiaceae: Ehrlichieae) in Ixodes scapularis (Acari:Ixodidae) collected during 1998 and 1999 from Minnesota.Layfield D, Guilfoile P.
Department of Biology, Bemidji State University, MN 56601, USA
J Med Entomol. 2002 Jan;39(1):218-20. Abstract quote We tested 103 adult Ixodes scapularis Say from 12 counties in Minnesota for the presence of Borrelia burgdorferi and the causative agent of human granulocytic ehrlichiosis (HGE), using polymerase chain reaction (PCR).
A total of 17 ticks (16.5%) was positive for B. burgdoiferi using nested PCR for the flagellin gene. or both PCR for the ospA gene and nested PCR for the flagellin gene. A total of four ticks (3.8%) was positive for the agent of HGE using nested PCR for 16S rDNA.
Counties in Minnesota with established and recently reported populations of I. scapularis both had ticks infected with B. burgdorferi. The agent of HGE was only detected in counties with established I. scapularis populations.
AGE SEX GEOGRAPHY EUROPE
Human granulocytic ehrlichiosis in Europe.Blanco JR, Oteo JA.
Internal Medicine and Infectious Diseases Service, Hospital de La Rioja, Logrono, Spain.
Clin Microbiol Infect. 2002 Dec;8(12):763-72. Abstract quote Ehrlichiosis comprises a group of emerging tick-borne infectious diseases caused by obligate intracellular Gram-negative bacteria that infect leukocytes. Infections caused by members of the genus Ehrlichia have been described in animals and humans, but to date there are no convincing reports of the presence of other types of human ehrlichiosis different from human granulocytic ehrlichiosis (HGE) in Europe.
The European vector is the same as that of Lyme borreliosis, the hard tick Ixodes ricinus, and HGE has a similar epidemiology to that of Borrelia burgdorferi infection. Across Europe, I. ricinus is infected to a variable extent (0.4-66.7%) with the causative agent Ehrlichia (Anaplasma) phagocytophila genogroup, and since its first description in Slovenia in 1997, details of 15 patients have been published. Diagnosis requires careful consideration of all circumstances and symptoms (history of tick bite and the presence of a flu-like syndrome with variable degrees of anemia, thrombocytopenia, and leukopenia, and elevated liver enzymes). Some differences can be seen between US and European HGE patients.
European HGE cases have a less severe course, and the presence of morulae is uncommon. In Europe, verification of HGE has been based on PCR and immunofluorescence antibody tests, because no isolation from humans has been reported.
Human disease in Europe caused by a granulocytic Ehrlichia species.Petrovec M, Lotric Furlan S, Zupanc TA, Strle F, Brouqui P, Roux V, Dumler JS.
Institute of Microbiology and Immunology, Medical Faculty, University of Ljubljana, Slovenia.
J Clin Microbiol. 1997 Jun;35(6):1556-9. Abstract quote Human granulocytic ehrlichiosis (HGE) was recently described in North America. It is caused by an Ehrlichia species closely related to Ehrlichia phagocytophila and Ehrlichia equi, recognized to infect mostly ruminants and horses, respectively.
The vector in North America is the tick Ixodes scapularis, which is also the vector of the Lyme disease agent, Borrelia burgdorferi. Previous serologic studies in patients with a diagnosis of Lyme borreliosis indicate that HGE may exist in Europe. We report the first documented case of HGE in Europe. The diagnosis was established by seroconversion to E. equi and the HGE agent and by PCR with sequence analysis of the gene encoding the HGE agent 16S rRNA. Interestingly, the patient presented with a self-limited but moderately severe illness.
Thus, European physicians need to be aware that HGE exists in Europe and that the diagnosis should be considered in febrile patients with tick bites in areas where Lyme disease is endemic.
DISEASE ASSOCIATIONS CHARACTERIZATION LYME DISEASE
Coinfection of Ixodes ricinus (Acari: Ixodidae) in northern Poland with the agents of Lyme borreliosis (LB) and human granulocytic ehrlichiosis (HGE).Stanczak J, Racewicz M, Kruminis-Lozowska W, Kubica-Biernat B.
Department of Tropical Parasitology, Institute of Maritime and Tropical Medicine, Gdynia, Poland.
Int J Med Microbiol. 2002 Jun;291 Suppl 33:198-201. Abstract quote Adult Ixodes ricinus ticks were collected from Pomerania province, northern Poland, to determine the presence of infection with agents of human granulocytic ehrlichiosis (HGE) and Lyme borreliosis by using the polymerase chain reaction (PCR).
Of the 424 ticks 19.2% and 11.6% contained ehrlichiae and spirochetes, respectively. Frequency of single infection with the HGE agent was 63/424 while frequency of single infection with Borrelia burgdorferi sensu lato was 28/424. As many as 21/424 ticks (5%) contained both pathogens.
This finding supports suggestions that both HGE agent and B. burgdorferi s. l. perpetuate in the same foci and frequently co-infect the same tick vector thereby increasing the risk of humans acquiring mixed infection.TRANSPLANTATION
Human granulocytic ehrlichiosis in a renal allograft recipient: review of the clinical spectrum of disease in solid organ transplant patients.Vannorsdall MD, Thomas S, Smith RP, Zimmerman R, Christman R, Vella JP.
Division of Nephrology and Renal Transplantation, Maine Medical Center, 22 Bramhall Street, Portland, ME 04102, USA.
Transpl Infect Dis. 2002 Jun;4(2):97-101. Abstract quote BACKGROUND: Ehrlichiosis is a recently described zoonotic infection with two major expressions: human granulocytic ehrlichiosis (HGE) and human monocytic ehrlichiosis (HME). The organisms associated with HGE and HME have been detected in a tick vector in several regions of United States and cases of ehrlichiosis have been reported in the general population.
METHODS: We report a case of HGE in a renal allograft recipient and review the clinical spectrum of disease in solid organ transplant recipients and the epidemiological basis for risk.
RESULTS: Our patient demonstrated the typical epidemiological, clinical and laboratory features of human granulocytic ehrlichiosis and responded to treatment with doxycycline.
CONCLUSIONS: Human ehrlichiosis should be considered in the differential diagnosis of patients with solid organ transplants, who present with fever and thrombocytopenia. The incidence of ehrlichiosis in the solid organ transplant population is similar to that in the United States general population. As reported in immunocompetent patients, prompt diagnosis and treatment results in the rapid resolution of symptoms in transplanted individuals.
PATHOGENESIS CHARACTERIZATION TICK VECTOR
Ixodes dammini as a potential vector of human granulocytic ehrlichiosis.Pancholi P, Kolbert CP, Mitchell PD, Reed KD Jr, Dumler JS, Bakken JS, Telford SR 3rd, Persing DH.
Division of Clinical Microbiology, Mayo Clinic, Rochester, MN 55905, USA.
J Infect Dis. 1995 Oct;172(4):1007-12. Abstract quote Little is known about the epidemiology and mode of transmission of the agent of human granulocytic ehrlichiosis (HGE). Analyses of an engorged female Ixodes dammini tick removed from an HGE patient and 101 field-collected I. dammini and Dermacentor variabilis from three Wisconsin counties for Borrelia burgdorferi and Ehrlichia phagocytophila/Ehrlichia equi DNA revealed that the patient tick and 7 of 68 I. dammini ticks from Washburn County collected in 1982 and 1991 were positive for ehrlichial DNA; 10 ticks from the same collections were positive for B. burgdorferi.
Two specimens (2.2%) were positive for both organisms. Serologic evidence for exposure to the agent of HGE or its relatives was detected in 3 of 25 Lyme disease patients from the upper Midwest.
These data argue that I. dammini is a common vector for transmission of both Lyme disease and HGE.
LABORATORY/
RADIOLOGIC/
OTHER TESTSCHARACTERIZATION RADIOLOGIC LABORATORY MARKERS SEROLOGY
Positive Lyme disease serology in patients with clinical and laboratory evidence of human granulocytic ehrlichiosis.
Wormser GP, Horowitz HW, Nowakowski J, McKenna D, Dumler JS, Varde S, Schwartz I, Carbonaro C, Aguero-Rosenfeld M.
Department of Medicine, New York Medical College, Valhalla, USA.
Am J Clin Pathol. 1997 Feb;107(2):142-7 Abstract quote In 10 consecutive patients with an acute febrile illness, human granulocytic ehrlichiosis was confirmed with specific polymerase chain reaction studies, serologic conversion, or both.
Although no patients had the clinical features most suggestive of early Lyme disease (eg, erythema migrans or cranial nerve palsy), tests for antibody to Borrelia burgdorferi produced a reaction in most patients. In 6 of 7 patients (86%) with evaluable results, enzyme-linked immunosorbent assay yielded positive or equivocal findings, and an immunoblot technique yielded positive findings in 60% to 90% of patients, depending on the criteria used for interpretation. Inasmuch as approximately 25% of nymphal Ixodes scapularis ticks in Westchester County, New York, are infected with B burgdorferi, the probability that at least 9 of these patients were coinfected with B burgdorferi and human granulocytic ehrlichiosis by the same tick bite is estimated to be .00003.
These observations suggest that serodiagnosis is insufficient to establish the presence of coinfection with B burgdorferi.
GROSS APPEARANCE/
CLINICAL VARIANTSCHARACTERIZATION GENERAL
Human ehrlichioses.Olano JP, Walker DH.
Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
Med Clin North Am. 2002 Mar;86(2):375-92. Abstract quote Human ehrlichioses represent one of the best examples of newly emergent infectious diseases in which the classic triad of host, infectious agent, and environment are intertwined closely. These pathogens have existed for eons on the planet, and some were described as veterinary pathogens decades ago.
Because of dramatic increases of deer and small mammal populations in certain areas and the subsequent increased populations of particular blood-feeding ticks, the risk of developing these diseases is higher than before.
Increasing human populations in suburban areas and increased immunosuppressed populations (transplant patients, human immunodeficiency virus patients, and cancer survivors) also have increased risk of developing severe forms of these diseases.
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL Characteristic morulae (clusters of bacteria in leukocyte cytoplasm) can frequently be found in the cytoplasm of circulating neutrophils after careful inspection of the peripheral blood smear
Characteristic peripheral blood findings in human ehrlichiosis.
Hamilton KS, Standaert SM, Kinney MC.
Department of Pathology, Division of Infectious Disease, Vanderbilt University Medical Center, Nashville, TN 37232-5310, USA.
Mod Pathol. 2004 May;17(5):512-7. Abstract quote
Human ehrlichiosis is a potentially fatal tick-borne illness if not treated promptly. Ehrlichia infection is difficult to diagnose as the organism does not grow in standard blood culture medium and serological confirmation of infection takes several days to weeks.
The most timely way of confirming Ehrlichia infection is identification of characteristic cytoplasmic morulae in peripheral blood leukocytes. A total of 23 patients with clinical and laboratory findings suggesting a rickettsial infection were tested for Ehrlichia using polymerase chain reaction and culture: 16 cases contained Ehrlichia DNA by polymerase chain reaction (15 E. chaffeensis, one E. ewingii), including 14 cases in which the blood culture grew Ehrlichia. The cases that contained Ehrlichia DNA by polymerase chain reaction had lower mean white blood cell and platelet counts and more numerous atypical lymphocytes and pronounced toxic change than cases in which Ehrlichia DNA was not detected. Cytoplasmic morulae were identified on peripheral blood smears in six (five E. chaffeensis, one E. ewingii) of 16 (38%) of the cases that contained Ehrlichia DNA, including 4/4 (100%) immunocompromised and 2/12 (17%) immunocompetent patients. Morulae were present in monocytes in E. chaffeensis-infected cases and granulocytes in the E. ewingii-infected case. In two immunocompromised patients, the number of infected cells was 1-10%, but in four patients it was <0.2%.
In conclusion, peripheral blood film examination is diagnostic in a substantial number of Ehrlichia infections, particularly in immunocompromised patients. The number of infected white blood cells may be less than 0.2%, requiring examination of more than 500 white blood cells. Associated changes prompting careful film review include prominent toxic granulation and atypical large granular lymphocytes.Human ehrlichiosis: hematopathology and immunohistologic detection of Ehrlichia chaffeensis.
Dumler JS, Dawson JE, Walker DH.
Department of Pathology, University of Texas Medical Branch, Galveston.
Hum Pathol. 1993 Apr;24(4):391-6. Abstract quote
Human ehrlichiosis is a recently described zoonosis caused by a rickettsia that infects leukocytes. Most patients have fever, headache, chills, and myalgias and develop leukopenia, thrombocytopenia, anemia, and elevations in serum hepatic aminotransferases. The cause of the peripheral leukopenia and thrombocytopenia is not known.
We studied peripheral blood smears, bone marrow aspirates, and bone marrow biopsy specimens from patients with serologically proven ehrlichiosis to characterize the pathologic changes associated with leukopenia or thrombocytopenia, to detect the presence of immunohistologically demonstrable ehrlichiae, and to establish the infected host target cell(s).
Specimens were obtained from 12 patients, and immunohistology for Ehrlichia chaffeensis was performed on tissue sections, aspirated bone marrow, and peripheral blood smears. Mean leukocyte and platelet counts available for nine patients were white blood cell count 3,300/microL (range, 1,100 to 10,300/microL) and platelets 61,000/microL (range, 40,000 to 82,000/microL). Findings included myeloid hyperplasia (eight cases), megakaryocytosis (seven cases), granulomas (eight cases), marrow histiocytosis (one case), myeloid hypoplasia (one case), pancellular hypoplasia (one case), and normocellular marrow (two cases). Morulae of E chaffeensis were detected in four of 10 cases examined by immunohistology. Most ehrlichiae were detected within histiocytes, although morulae were rarely present within lymphocytes. Leukopenia, thrombocytopenia, or pancytopenia apparently most often results from peripheral sequestration or destruction; however, hypoplasia of marrow elements is present occasionally.
Immunohistologic demonstration of E chaffeensis offers a direct means for establishing the etiologic diagnosis. These observations show the relatively frequent occurrence of bone marrow granulomas and suggest that infection of cells of the reticuloendothelial system may participate in the pathogenesis of human ehrlichiosis.
TREATMENT CHARACTERIZATION GENERAL ANTIBIOTICS
Treatment of tick-borne diseases.Donovan BJ, Weber DJ, Rublein JC, Raasch RH.
Infectious Diseases Pharmacotherapy, Department of Pharmacy, University of North Carolina Hospitals, Chapel Hill, NC, USA.
Ann Pharmacother. 2002 Oct;36(10):1590-7. Abstract quote OBJECTIVE: To review the data regarding the pharmacotherapy of Lyme disease, Rocky Mountain spotted fever (RMSF), and the human ehrlichioses.
DATA SOURCES: English-language literature was identified via MEDLINE (1966-January 2002) using the keywords Lyme disease, Rocky Mountain spotted fever, and ehrlichiosis. Textbooks and other pertinent resources were also reviewed.
STUDY SELECTION AND DATA EXTRACTION: All articles identified through the data sources above were evaluated and reviewed if pertinent to the objective.
DATA SYNTHESIS: Tick-borne diseases are the most common vector-transmitted diseases in North America. Each disease causes significant morbidity and, in the case of RMSF, mortality if patients go untreated. If the disease syndromes are recognized early and treatment is initiated, complications are greatly reduced. Doxycycline is active against each of the causative organisms, simplifying empiric treatment.
CONCLUSIONS: Effective pharmacotherapy exists to treat each of these diseases, assuming diagnosis is made quickly. The beta-lactam and tetracycline antibiotics appear to be the most effective therapy for Lyme disease. The tetracyclines, but not the beta-lactams, are effective for RMSF and the human ehrlichioses. Since Borrelia burgdorferi and the human granulocytic ehrlichiosis agent are becoming more common coinfecting pathogens, tetracycline or doxycycline should be considered the drugs of choice for patients from endemic areas where exposure to both pathogens may have occurred. Doxycycline is the preferred agent because of decreased frequency of administration and adverse effects.Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Eight Edition. Mosby 1996.
Sternberg S. Diagnostic Surgical Pathology. Third Edition. Lipincott Williams and Wilkins 1999.
Robbins Pathologic Basis of Disease. Sixth Edition. WB Saunders 1999.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.
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