2
Recurrent Fever and Thrombocytopenia in a 4-Year-Old Girl Gwenn Skar, MD, Jessica Snowden, MD Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE.
CASE 2 PRESENTATION
AUTHOR DISCLOSURE Drs Skar and Snowden have disclosed no financial relationships relevant to this article. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.
A 4-year-old girl presents with recurrent fevers for 5 weeks. During the first episode, she had a headache, body aches, and one episode of diarrhea and temperatures reaching 106.0°F (41.1°C). She was evaluated in the emergency department and diagnosed as having a viral syndrome. Her symptoms resolved after 3 days. After 10 days without fever, she again had high temperatures with chills, headache, body aches, and one episode of emesis. The patient was admitted and found to have significant thrombocytopenia (platelets, 44 103/mL [44 109/L]), mild anemia (hemoglobin, 9.5 g/dL [95 g/L]), and an elevated C-reactive protein level (25.5 mg/L). Blood and urine culture results were negative. Abdominal ultrasonography revealed mild splenomegaly, but findings were otherwise unremarkable. Her symptoms resolved after 3 days without antibiotics, and she was discharged. She had 2 subsequent episodes of fever, the most recent resolving 5 days before her clinic appointment. She has no other symptoms associated with these episodes except anorexia and a 1-lb weight loss. She has no sick contacts with similar symptoms. The patient and her family spent 2 weeks in Colorado hiking and staying in a cabin in June, returning 1 week before her first febrile episode. During that trip, she had multiple bites over her lower shins, assumed to be mosquito bites. She has no other significant exposures. Her medical, surgical, and family history is unremarkable. During this visit, she is afebrile (97.9°F [36.6°C]) with normal vital signs. Her examination findings are within normal limits. Serologic testing confirms the diagnosis suggested by her history.
CASE 2 DISCUSSION Because of her recurrent fever, thrombocytopenia, and travel history, she was suspected to have tick-borne relapsing fever (TBRF). A thin smear was considered, but it was thought to be low yield because the patient was afebrile. Borrelia serologic testing was ordered, and she was empirically treated with erythromycin for presumptive TBRF. She received her first dose of erythromycin under hospital observation because of the possibility of Jarisch-Herxheimer reaction. She tolerated her first dose without incident and was discharged to complete a 10-day course of oral therapy. She has done well after treatment with no other fever. Her Borrelia hermsii IgM test result was negative, but her IgG test result was positive at 1:512, consistent with a diagnosis of TBRF.
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The Condition TBRF is characterized by recurrent episodes of fever accompanied by nonspecific symptoms, including headache, arthralgia, myalgia, chills, vomiting, and abdominal pain. Other less common findings include conjunctivitis, cough, nuchal rigidity, hepatomegaly, or splenomegaly. Moderate to severe thrombocytopenia often occurs in TBRF. Typically, febrile episodes last for 3 days and are separated by 7-day periods without symptoms, similar to the history provided by this patient. Patients may experience up to 5 episodes of recurrent fever before symptoms resolve. TBRF is caused by Borrelia species that vary their surface antigens, causing repeated spirochetemia and resulting in recurrent febrile episodes. There are 3 species in the United States that have been identified as causing TBRF: B hermsii, Borrelia turicatae, and Borrelia parkeri. The most common species in the western United States is B hermsii. B hermsii is transmitted by the bite of infected Ornithodoros ticks. These ticks are argasid (soft) ticks that are quick nocturnal feeders with painless bites. Therefore, patients with TBRF rarely report tick bites or exposure. Infection in humans typically occurs when infected ticks, living in rodent nests within human dwellings, feed on humans. TBRF should be distinguished from louse-borne relapsing fever, caused by Borrelia recurrentis. This disease, although clinically similar, is transmitted by the body louse and occurs in developing countries, particularly among the refugee and homeless populations. It is rare in the United States. TBRF is reported rarely in children in the United States. It may be underreported in children because they are more likely to receive oral antibiotics for treatment of fever than are adults, treating the spirochetemia without definitive diagnosis. TBRF most commonly occurs in endemic areas of the western United States, particularly the limestone caves of central Texas and forested areas of varying elevation in mountainous regions of the western United States. The incubation period is 2 to 18 days (mean, 7 days); therefore, symptoms may not be apparent until after the patient has left endemic locales.
Diagnosis Laboratory evaluation may reveal normal to mildly increased white blood cell counts and thrombocytopenia, as seen in this patient. Additional abnormalities may include mildly elevated bilirubin levels, elevated inflammatory markers, and a mild prolongation in prothrombin time and partial thromboplastin time. Most cases of TBRF are diagnosed clinically on the basis of history and treated empirically. Diagnosis may be confirmed by the presence of spirochetes in peripheral smears or positive Borrelia serologic test results, available via reference or public health laboratories. High
levels of spirochetemia are characteristic of the febrile periods, with a mean of 5 organisms visible per oil immersion field on peripheral smear. During afebrile, asymptomatic periods, spirochetes are often microscopically undetectable in peripheral smears. B hermsii can be identified with a monoclonal antibody. Serologic confirmation occurs with a 4-fold increase between acute and convalescent titers or a sample that is diagnostically reactive. These antibodies may crossreact with other spirochetes, such as Treponema pallidum and leptospira. In addition, patients with TBRF may have a falsepositive result for Lyme disease.
Management TBRF responds well to antibiotic therapy, and mortality is rare. Choices for antibiotics include doxycycline, tetracycline, erythromycin, and penicillin. Penicillin and erythromycin are the antibiotics of choice for children younger than 8 years. Treatment can be complicated by Jarisch-Herxheimer reactions, although reactions are reported to be milder in children. Patients should be observed for several hours after receiving their first antibiotic dose to monitor for these reactions. This patient was clinically diagnosed as having TBRF on the basis of multiple episodes of recurring fever, thrombocytopenia, and a history of travel to an area where TBRF is endemic. Positive Borrelia IgG serologic test results supported the diagnosis of TBRF. As in this case, it is important to obtain a thorough exposure and travel history and include TBRF in the differential diagnosis of recurrent fever or fever without an apparent source.
Lessons for the Clinician • TBRF is characterized by up to 5 episodes of recurrent fever that typically last for 3 days and are separated by 7 days. Patients may also have nonspecific symptoms (eg, headache and myalgias) and thrombocytopenia. • It is important to ask about travel history when evaluating children with recurrent fever. Patients usually report a history of travel to or residence in the western United States. Although ticks transmit TBRF, patients typically do not report a tick bite because these ticks feed for brief periods at night. • The diagnosis of TBRF can be confirmed by peripheral smear or Borrelia serologic testing. • Children with suspected TBRF are treated with doxycycline (if older than 8 years) or erythromycin or penicillin (if younger than 8 years) and are monitored for possible Jarisch-Herxheimer reaction after the first dose of antibiotics. View the Suggested Reading list for this case at http://pedsinreview. aappublications.org/content/36/3/130.full.
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MARCH 2015
131
Case 2: Recurrent Fever and Thrombocytopenia in a 4-Year-Old Girl Gwenn Skar and Jessica Snowden Pediatrics in Review 2015;36;130 DOI: 10.1542/pir.36-3-130
Updated Information & Services
including high resolution figures, can be found at: http://pedsinreview.aappublications.org/content/36/3/130
References
This article cites 7 articles, 3 of which you can access for free at: http://pedsinreview.aappublications.org/content/36/3/130#BIBL
Subspecialty Collections
This article, along with others on similar topics, appears in the following collection(s): Infectious Diseases http://pedsinreview.aappublications.org/cgi/collection/infectious_dis eases_sub
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Case 2: Recurrent Fever and Thrombocytopenia in a 4-Year-Old Girl Gwenn Skar and Jessica Snowden Pediatrics in Review 2015;36;130 DOI: 10.1542/pir.36-3-130
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://pedsinreview.aappublications.org/content/36/3/130
Pediatrics in Review is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1979. Pediatrics in Review is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2015 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0191-9601.
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Recurrent Fever and Thrombocytopenia in a 4-Year-Old Girl Gwenn Skar, MD, Jessica Snowden, MD Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE.
CASE 2 PRESENTATION
AUTHOR DISCLOSURE Drs Skar and Snowden have disclosed no financial relationships relevant to this article. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.
A 4-year-old girl presents with recurrent fevers for 5 weeks. During the first episode, she had a headache, body aches, and one episode of diarrhea and temperatures reaching 106.0°F (41.1°C). She was evaluated in the emergency department and diagnosed as having a viral syndrome. Her symptoms resolved after 3 days. After 10 days without fever, she again had high temperatures with chills, headache, body aches, and one episode of emesis. The patient was admitted and found to have significant thrombocytopenia (platelets, 44 103/mL [44 109/L]), mild anemia (hemoglobin, 9.5 g/dL [95 g/L]), and an elevated C-reactive protein level (25.5 mg/L). Blood and urine culture results were negative. Abdominal ultrasonography revealed mild splenomegaly, but findings were otherwise unremarkable. Her symptoms resolved after 3 days without antibiotics, and she was discharged. She had 2 subsequent episodes of fever, the most recent resolving 5 days before her clinic appointment. She has no other symptoms associated with these episodes except anorexia and a 1-lb weight loss. She has no sick contacts with similar symptoms. The patient and her family spent 2 weeks in Colorado hiking and staying in a cabin in June, returning 1 week before her first febrile episode. During that trip, she had multiple bites over her lower shins, assumed to be mosquito bites. She has no other significant exposures. Her medical, surgical, and family history is unremarkable. During this visit, she is afebrile (97.9°F [36.6°C]) with normal vital signs. Her examination findings are within normal limits. Serologic testing confirms the diagnosis suggested by her history.
CASE 2 DISCUSSION Because of her recurrent fever, thrombocytopenia, and travel history, she was suspected to have tick-borne relapsing fever (TBRF). A thin smear was considered, but it was thought to be low yield because the patient was afebrile. Borrelia serologic testing was ordered, and she was empirically treated with erythromycin for presumptive TBRF. She received her first dose of erythromycin under hospital observation because of the possibility of Jarisch-Herxheimer reaction. She tolerated her first dose without incident and was discharged to complete a 10-day course of oral therapy. She has done well after treatment with no other fever. Her Borrelia hermsii IgM test result was negative, but her IgG test result was positive at 1:512, consistent with a diagnosis of TBRF.
130
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The Condition TBRF is characterized by recurrent episodes of fever accompanied by nonspecific symptoms, including headache, arthralgia, myalgia, chills, vomiting, and abdominal pain. Other less common findings include conjunctivitis, cough, nuchal rigidity, hepatomegaly, or splenomegaly. Moderate to severe thrombocytopenia often occurs in TBRF. Typically, febrile episodes last for 3 days and are separated by 7-day periods without symptoms, similar to the history provided by this patient. Patients may experience up to 5 episodes of recurrent fever before symptoms resolve. TBRF is caused by Borrelia species that vary their surface antigens, causing repeated spirochetemia and resulting in recurrent febrile episodes. There are 3 species in the United States that have been identified as causing TBRF: B hermsii, Borrelia turicatae, and Borrelia parkeri. The most common species in the western United States is B hermsii. B hermsii is transmitted by the bite of infected Ornithodoros ticks. These ticks are argasid (soft) ticks that are quick nocturnal feeders with painless bites. Therefore, patients with TBRF rarely report tick bites or exposure. Infection in humans typically occurs when infected ticks, living in rodent nests within human dwellings, feed on humans. TBRF should be distinguished from louse-borne relapsing fever, caused by Borrelia recurrentis. This disease, although clinically similar, is transmitted by the body louse and occurs in developing countries, particularly among the refugee and homeless populations. It is rare in the United States. TBRF is reported rarely in children in the United States. It may be underreported in children because they are more likely to receive oral antibiotics for treatment of fever than are adults, treating the spirochetemia without definitive diagnosis. TBRF most commonly occurs in endemic areas of the western United States, particularly the limestone caves of central Texas and forested areas of varying elevation in mountainous regions of the western United States. The incubation period is 2 to 18 days (mean, 7 days); therefore, symptoms may not be apparent until after the patient has left endemic locales.
Diagnosis Laboratory evaluation may reveal normal to mildly increased white blood cell counts and thrombocytopenia, as seen in this patient. Additional abnormalities may include mildly elevated bilirubin levels, elevated inflammatory markers, and a mild prolongation in prothrombin time and partial thromboplastin time. Most cases of TBRF are diagnosed clinically on the basis of history and treated empirically. Diagnosis may be confirmed by the presence of spirochetes in peripheral smears or positive Borrelia serologic test results, available via reference or public health laboratories. High
levels of spirochetemia are characteristic of the febrile periods, with a mean of 5 organisms visible per oil immersion field on peripheral smear. During afebrile, asymptomatic periods, spirochetes are often microscopically undetectable in peripheral smears. B hermsii can be identified with a monoclonal antibody. Serologic confirmation occurs with a 4-fold increase between acute and convalescent titers or a sample that is diagnostically reactive. These antibodies may crossreact with other spirochetes, such as Treponema pallidum and leptospira. In addition, patients with TBRF may have a falsepositive result for Lyme disease.
Management TBRF responds well to antibiotic therapy, and mortality is rare. Choices for antibiotics include doxycycline, tetracycline, erythromycin, and penicillin. Penicillin and erythromycin are the antibiotics of choice for children younger than 8 years. Treatment can be complicated by Jarisch-Herxheimer reactions, although reactions are reported to be milder in children. Patients should be observed for several hours after receiving their first antibiotic dose to monitor for these reactions. This patient was clinically diagnosed as having TBRF on the basis of multiple episodes of recurring fever, thrombocytopenia, and a history of travel to an area where TBRF is endemic. Positive Borrelia IgG serologic test results supported the diagnosis of TBRF. As in this case, it is important to obtain a thorough exposure and travel history and include TBRF in the differential diagnosis of recurrent fever or fever without an apparent source.
Lessons for the Clinician • TBRF is characterized by up to 5 episodes of recurrent fever that typically last for 3 days and are separated by 7 days. Patients may also have nonspecific symptoms (eg, headache and myalgias) and thrombocytopenia. • It is important to ask about travel history when evaluating children with recurrent fever. Patients usually report a history of travel to or residence in the western United States. Although ticks transmit TBRF, patients typically do not report a tick bite because these ticks feed for brief periods at night. • The diagnosis of TBRF can be confirmed by peripheral smear or Borrelia serologic testing. • Children with suspected TBRF are treated with doxycycline (if older than 8 years) or erythromycin or penicillin (if younger than 8 years) and are monitored for possible Jarisch-Herxheimer reaction after the first dose of antibiotics. View the Suggested Reading list for this case at http://pedsinreview. aappublications.org/content/36/3/130.full.
Vol. 36 No. 3 Downloaded from http://pedsinreview.aappublications.org/ at Uab Lister Hill Library on March 2, 2015
MARCH 2015
131
Case 2: Recurrent Fever and Thrombocytopenia in a 4-Year-Old Girl Gwenn Skar and Jessica Snowden Pediatrics in Review 2015;36;130 DOI: 10.1542/pir.36-3-130
Updated Information & Services
including high resolution figures, can be found at: http://pedsinreview.aappublications.org/content/36/3/130
References
This article cites 7 articles, 3 of which you can access for free at: http://pedsinreview.aappublications.org/content/36/3/130#BIBL
Subspecialty Collections
This article, along with others on similar topics, appears in the following collection(s): Infectious Diseases http://pedsinreview.aappublications.org/cgi/collection/infectious_dis eases_sub
Permissions & Licensing
Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://pedsinreview.aappublications.org/site/misc/Permissions.xhtml
Reprints
Information about ordering reprints can be found online: http://pedsinreview.aappublications.org/site/misc/reprints.xhtml
Downloaded from http://pedsinreview.aappublications.org/ at Uab Lister Hill Library on March 2, 2015
Case 2: Recurrent Fever and Thrombocytopenia in a 4-Year-Old Girl Gwenn Skar and Jessica Snowden Pediatrics in Review 2015;36;130 DOI: 10.1542/pir.36-3-130
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://pedsinreview.aappublications.org/content/36/3/130
Pediatrics in Review is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1979. Pediatrics in Review is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2015 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0191-9601.
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