Headache, Fever, Lesions Add Up to Disseminated Lyme Disease

A 15-year-old female presents to her pediatrician with a 14-day history of headaches, fever, and new multiple annular lesions on her legs, arms, and back. She lives in a “highly wooded area,” and is very active outdoors. She reports having a headache that was general, dull, and constant with pain only partially resolved by acetaminophen and ibuprofen. There is no diplopia or stiff neck. There are low-grade fevers that were 101 degrees F maximally. She denies phonophobia, but there is some photophobia.

Then, after 10 days of headache, she had multiple annular skin lesions on her extremities and back. The lesions are not itchy nor scaly. On the first day of the rash, she presented to an urgent care facility, where she was diagnosed with “ringworm.” She was prescribed topical antifungal cream. When the rash did not improve, she was taken to a community hospital emergency department. There was no evidence of heart block on EKG. She has no known tick bites. Her physical examination reveals a well-appearing adolescent with normal vital signs. Her HEENT examination is entirely normal. She has no nuchal rigidity. Her cardiac, pulmonary, and abdominal examinations are normal. Her neurologic examination reveals normal cranial nerves, normal DTRs, and strength. Her skin examination reveals multiple (greater than 10) lesions on her extremities and torso. There is annular erythema, and each is greater than 7 cm in the long axis.

Discussion: In the Mid-Atlantic area, the most likely diagnosis is disseminated Lyme disease. At her age, 15 years, the next most appropriate steps would be testing for Lyme antibodies from the serum, and treatment with oral doxycycline for 2 weeks. Despite the presence of headache, a lumbar puncture is not absolutely necessary.

Lyme disease, caused by the spirochete Borrelia burgdorferi, is the most common vector-borne infection in the United States, with approximately 22,000 to 29,000 cases reported to health departments each year, which may be a gross underestimate.

The clinical manifestations of Lyme disease occur in three distinct phases: early, disseminated, and late.

Clinical Manifestations of Lyme Disease

Early Lyme Disease

Is characterized by the appearance of erythema migrans (EM), the “bull’s eye” rash, on average 10 days following the tick bite. An EM rash of greater than 5 cm in diameter is highly predictive of Lyme disease in endemic areas—the Northeastern (Maine to Virginia) and upper Midwestern (Wisconsin, Michigan, Minnesota, Illinois) United States. In children, the appearance of a single EM rash may be diminished because more tick bites occur on the scalp as compared to adults. There may be associated fatigue and malaise at the early stage.

Disseminated Lyme Disease

May have cutaneous, cardiac, peripheral, or central nervous system findings. The classic presentation of disseminated Lyme disease comprises multiple EM rashes distributed over the body, although multiple EM rashes may be smaller than 5 cm. Other manifestations include peripheral facial nerve palsy, multiple cranial nerve palsies, meningitis, and carditis. Lyme meningitis may present acutely with headache, photophobia, nuchal rigidity, and lymphocyte predominant CSF pleocytosis. It may present subacutely with prolonged headache that gradually worsens. There may be papilledema on fundoscopic examination. Carditis may present with first to third degree heart block (although third degree occurs extremely rarely; fewer than 1% of patients with Lyme), or even pericarditis.

Late Lyme Disease

Is categorically arthritis in children. Lyme arthritis occurs in about 10% of adults with Lyme disease and less often in children (about 7%). The arthritis may affect one or more joints concurrently or sequentially. The affected joints typically have a large, boggy effusion, with ability to bear weight retained. The range of motion is usually limited by the size of the effusion, rather than the pain and intensity of the inflammatory process itself.

Lyme disease, caused by the spirochete Borrelia burgdorferi, is the most common vector-borne infection in the United States, transmitted by the bite of infected ticks. All manifestations of Lyme disease may be treated with 2 weeks of oral antibiotics, either doxycycline or a beta lactam antibiotic save 3. Only amoxicillin and cefuroxime axetil have been shown to be efficacious for the treatment of Lyme disease. Meningitis in children too young to take doxycycline requires 2 weeks of IV ceftriaxone. Third-degree heart block requires 2 to 4 weeks of IV ceftriaxone. Lyme arthritis requires 4 weeks of an oral agent, either doxycycline or a beta lactam.

In one large, randomized, double-blind, multicenter trial in Europe, and smaller randomized and observational trials, the use of oral doxycycline was not inferior to intravenous ceftriaxone for the treatment of CNS Lyme. There is excellent bioavailability with oral doxycycline and penetration of the CNS. In addition, the rates of adverse events and of severe adverse events were significantly lower in the oral doxycycline groups. Thus, many experts believe that if a child is old enough to take doxycycline, there is no need for IV ceftriaxone for the treatment of CNS Lyme. By extension, in the case of our patient, despite the presence of headache for 10 days, we did not recommend a lumbar puncture, as the presence of WBC in the CSF would not change therapy for the child:14 days of oral doxycycline.

References and Suggested Readings

Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43(9):1089-1134.

Ljostad U, et al. Oral doxycycline versus intravenous ceftriaxone for European Lyme neuroborreliosis: a multicenter, non-inferiority, double-blind, randomized trial. Lancet Neurol. 2008;7(8):690-695.

Red Book Online: Lyme Disease (Lyme Borreliosis, Borrelia Burgdorgeri). Accessed Oct. 29, 2015.

Referral Information

For information or to refer a patient to the Division of Infectious Diseases, call 267-425-3377. Information can be found at www.chop.edu/infectious-diseases.

The Vaccine Education Center at CHOP has a wealth of information for physicians and patient families. Please visit vaccine.chop.edu for information on all vaccines and for resources to use with families (print materials, videos, mobile app and more).