Disseminated Lyme


A 33-year-old male presents to the ED with ongoing left lower extremity pain and a few days of malaise. He has a history of bipolar I disorder, as well as chronic alcohol, tobacco and marijuana use. He first presented to his primary care doctor six days ago with erythema and pain over the left medial malleolus. At that time he had no other symptoms and physical exam was otherwise unremarkable. He was treated for presumed cellulitis with doxycycline, which he took at half of the prescribed dose due to a miscommunication with his doctor.

Over the subsequent days, the rash on his leg did not improve and he developed myalgias, fever/chills, neck pain and headaches. He presented to the emergency department for reevaluation of the rash, which was still felt to be consistent with cellulitis and he was discharged home to continue doxycycline at the correct dosage. He returns one day later  to the emergency department because his rash is not improving and he has noticed new lesions on his right forearm.

On exam, he is afebrile with vital signs within normal limits. He has a violaceous and erythematous lesion involving the left lower extremity above the medial malleolus with surrounding petechiae. There is no fluctuance. He has scattered pink macules on his bilateral upper and lower extremities. He endorses head and neck pain with motion but there is no meningismus and physical examination is otherwise normal.


Figure 1. Lower extremity lesions

Since outpatient management has failed thus far, he is admitted for workup of his rash and systemic symptoms. In the hospital, he tests positive for Lyme disease, with negative ehrlichia/anaplasma, blood culture and parasite smear. He has had no known tick bites, but remembers that he was walking through tall grass a week before his rash first began. 


Given the patient’s findings of expanding, oval-shaped ankle rash and secondary arm lesions and neck pain, there was concern for early disseminated Lyme disease. While the lesion on the medial ankle was not the typical targetoid rash of erythema migrans, the initial presentation can be quite variable. In addition to cellulitis and other dermatologic pathologies, Lyme should be considered in patients with an expanding rash who have spent time in endemic regions.

The progression of his rash and the development of systemic symptoms after treatment with doxycycline is likely representative of the Jarisch-Herxheimer reaction. This reaction represents an acute inflammatory response that occurs after antibiotics cause the breakdown of the spirochetes. The exact mechanism is unknown, but it is thought to occur due to the release of spirochete lipoproteins and reactive cytokines into the bloodstream. It usually occurs within the first 24 hours of treatment, which is consistent with when our patient began taking the correct therapeutic dose of doxycycline.

This reaction is characterized by worsening of skin findings, as well as systemic symptoms such as fever and chills (often with widely variable temperatures). Patients can also experience rigors, nausea and vomiting, myalgia, and in severe cases, changes in hemodynamic parameters. Jarisch-Herxheimer reaction is less common in Lyme than in other spirochetal infections (i.e. syphilis), and the clinical course is often milder. However, studies have shown it to be present in 7-30% of patients upon initiation of Lyme treatment.

Treatment for Lyme with a Jarisch-Herxheimer reaction includes continuation of antibiotics to eradicate the bacterial infection, with the addition of supportive care such as NSAIDs for fever, chills, and myalgias. The antibiotic should not be changed, as this reaction represents a response to treatment. 

While many cases of Jarisch-Herxheimer reaction are mild and can be managed at home, more severe cases can produce hypotension and hemodynamic instability requiring hospital admission. Blood pressure should be monitored and IV fluids should be initiated if hypotension occurs. Treatment with corticosteroids, vasopressors, inotropic support and transient dialysis have been reported in severe cases and may be useful depending on the severity of symptoms. 


Our patient is started on twice daily doxycycline, and improvement in his rash and systemic symptoms is seen during his two-day hospital stay. He is discharged home with doxycycline to complete his 21 day course.

Author: Katherine Barry is a fourth year medical student at the Warren Alpert Medical School of Brown University.

Faculty Reviewer: Kristina McAteer, MD is an attending physician at Rhode Island Hospital and Newport Hospital.


  • Butler T. (2017). The Jarisch-Herxheimer Reaction After Antibiotic Treatment of Spirochetal Infections: A Review of Recent Cases and Our Understanding of Pathogenesis. The American journal of tropical medicine and hygiene96(1), 46–52. https://doi.org/10.4269/ajtmh.16-0434

  • Dhakal A, Sbar E. Jarisch Herxheimer Reaction. [Updated 2021 May 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557820/

Source: brownemblog.com

Disseminated Lyme