Development of bilateral facial nerve palsies while receiving doxycycline for early disseminated Lyme disease

Abstract

Background

Disease progression is uncommon in patients diagnosed with Lyme disease who receive appropriate therapy. Here we report a case of a patient developing bilateral facial nerve palsies while receiving oral doxycycline therapy for early disseminated Lyme disease and review the literature of similar cases.

Case report

A 58-year-old previously healthy male from the mid-Atlantic area in the U.S. presented with a multifocal erythematous rash consistent with erythema migrans after international travel. His clinical presentation and two-step Lyme-serology testing confirmed a diagnosis of Lyme disease. Four days into initiation of doxycycline therapy, he developed bilateral facial weakness including difficulty raising the corners of his mouth and lifting his eyebrows bilaterally. He experienced neurologic improvement with ongoing antimicrobial therapy with ceftriaxone and subsequent doxycycline and had complete recovery 7 weeks later.

Conclusion

This case describes an uncommon presentation of neuroborreliosis with bilateral facial palsies which developed after initiation of treatment of early disseminated Lyme disease. The manifestations in this case may be due to host immune reaction as seen in other spirochetal diseases. The findings resolved with continued therapy. In our review of the literature, we identified three additional cases of neuroborreliosis which progressed on treatment but also had eventual resolution of signs and symptoms. Clinicians should be aware that facial palsies rarely can occur on therapy for Lyme disease but do not necessarily imply a worse prognosis.

Introduction

Borrelia burgdorferi is transferred to humans and other vertebrate hosts by the Ixodes tick and causes Lyme disease. [1] Borrelia burgdorferi can evade the host innate and adaptive immune system via various mechanisms. [2] While some cases of early localized Lyme disease self-resolve, they may progress to early and late disseminated disease without treatment. [3] Lyme neuroborreliosis encompasses the neurologic manifestations of Borrelia burgdorferi infection, with common presentations including meningitis, cranial neuropathy, and radiculopathy. [4] Here we report a case of a patient developing bilateral facial nerve palsies while receiving appropriate antibiotic therapy for early disseminated Lyme disease and review the literature of similar cases.

Case report

A 58-year-old previously healthy male resident of the mid-Atlantic area in the United States presented to the outpatient clinic with an erythematous rash on his left calf that was noted 9 days prior to presentation. Of note, he recently tested positive for SARS-CoV-2 four weeks prior to presentation. His symptoms resolved with no specific therapy and follow-up testing was negative at the time of his presentation. He often enjoyed outdoor activities and was working outdoors clearing brush 3 weeks prior to presentation but did not notice any tick bites.

Two weeks prior to presentation, he departed for a trip to Singapore where he was mostly indoors in hotels except for one trip to a botanical garden. He had multiple negative SARS-CoV-2 tests while on travel. A colleague noted the rash on the patient’s left calf as he was waiting in the airport for his return trip to the U.S. (Fig. 1) 9 days prior to presentation. Two days after his return home (6 days prior to presentation), he felt weak, had poor appetite, and developed fever with accompanying photophobia. He was referred to the emergency department the following day where his laboratory values were within normal limits except for a mild lymphocytosis with a white blood cell (WBC) count of 5800 cells per microliter (reference range 3980–10,040 cells per microliter). A chest x-ray was reportedly normal, and he was discharged to home. The photophobia resolved, but daily fevers continued. Three days prior to presentation, he was seen in a dermatology clinic to receive scheduled botulinum toxin injections to his forehead. He was prescribed a topical steroid for the rash.

Fig. 1.

Erythema migrans and bilateral facial palsies. A. Initial left leg erythematous patch consistent with erythema migrans. B. Bilateral drooping of corners of the mouth, consistent with bilateral facial palsies.

One day prior to presentation, he developed a similar rash on his arms, chest, abdomen, and legs. The lesions were not painful or pruritic. Review of systems was otherwise negative. On physical examination, the skin showed multiple large lesions with central clearing. The original lesion on the left leg was less erythematous than previous. The rest of the physical examination was normal. Laboratory parameters were normal except for elevated alanine and aspartate aminotransferase, both three times the upper limit of normal. Borrelia bergdorferi polymerase chain reaction performed on blood was negative, but Lyme serology by initial enzyme immunoassay was positive, and subsequent Western blot was positive for IgM (p41, p23) and negative for IgG (p23). He was prescribed doxycycline 100 mg twice daily for a planned 14-day course for early disseminated Lyme disease.

Within two days of therapy, his fever and rashes resolved. Four days into therapy, he noted new bilateral jaw pain. The next day, he noted inability to smile, difficulty lifting his eyebrows, difficulty eating due to food accumulating under his lower lip and in both cheeks, and diplopia. He contacted the clinic, and, given his diplopia, his doxycycline was held due to initial concern of secondary intracranial hypertension that has been reported with this drug. [5]

He returned to clinic on day eight of therapy. His complaints of facial weakness continued unchanged. He noted watery eyes and inability to completely close his eyes. He had no facial paresthesias or numbness, stiff neck or neck weakness, or headache. He noted normal hearing and no tinnitus. He had no dysphagia. He did not have limb sensory changes or weakness, bowel, or bladder difficulties.

His vital signs at that time were within normal limits. On examination, he had severe facial weakness bilaterally with absent eyebrow lift and inability to close his eyes tightly or smile (Fig. 1B). The House-Brackmann score was five, indicating severe disease. [6] The rest of the neurological examination was normal. Laboratory evaluations were all within normal limits, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). He was admitted and received ceftriaxone 2 g intravenously once daily as his neurologic symptoms had appeared on doxycycline. A magnetic resonance imaging (MRI) of the brain showed slightly increased bilateral symmetric enhancement of the labyrinthine segment of the facial nerves, consistent with inflammation. Lumbar puncture obtained after antibiotics showed clear fluid with opening pressure of 19.0 centimeters of water, with 1 WBC per microliter and 1 red blood cell (RBC) per microliter. Cerebral spinal fluid (CSF) glucose was 59 milligrams per deciliter (mg/dL) (reference range 40–70 mg/dL) with a peripheral blood glucose of 93 mg/dL (reference range 70–99 mg/dL), and CSF protein was 42 mg/dL (reference range 15–40 mg/dL). CSF Lyme IgG screen was positive, and supplemental testing with CSF Lyme IgG Index was negative.

Over three days of admission, his ability to eat and use a straw improved, but his House-Brackmann score remained five. He was discharged to receive two weeks of ceftriaxone, followed by an additional 7-day course of doxycycline. Neurologic improvement started 1 week after initiation of ceftriaxone, and he had complete recovery from the bilateral facial palsies an additional 5 weeks later. The case is summarized in Fig. 2.

Fig. 2.

Timeline of clinical events.

Discussion

We describe a case of progressive Lyme disease while on appropriate treatment. Lyme disease is a common tick-borne illness in the northern hemisphere. In the United States, it is caused by the spirochete Borrelia burgdorferi and is transferred to humans and other vertebrate hosts by the Ixodes tick. It is endemic in the mid-Atlantic area. [7] Our patient presented with a multifocal rash after international travel. His recent COVID-19 infection and infections related to his travel to Singapore were considered and excluded from the differential diagnosis. The diagnosis was made by taking a relevant exposure history and recognition of the rash consistent with erythema migrans, classically a large, circular patch with central clearing that is often painless, as in this case, on physical exam. Erythema migrans is a common manifestation of Lyme disease which appears in 70–80% of infected individuals and is an early symptom of disease. Other common early symptoms may include fever, chills, fatigue, headache, and myalgias. [3] Our patient was diagnosed with early disseminated Lyme disease based on epidemiology, clinical presentation, and supporting Lyme serology. His photophobia and facial nerve palsies clinically support CNS involvement as part of the dissemination. Notably, antibody index in Lyme has an imperfect sensitivity of 55–80%, therefore his negative index does not exclude early CNS involvement. [8,9] Patient’s CSF was also obtained after antibiotics.

Borrelia burgdorferi can evade the host innate and adaptive immune system via various mechanisms. [2] While some cases of early localized Lyme disease self-resolve, they may progress to early and late disseminated disease without treatment. [3] What is unique about this case is the development of bilateral facial nerve palsies while receiving appropriate antibiotic treatment. Bilateral facial nerve palsy is exceedingly rare, comprising of 0.3–2% of all facial palsies. [10] It has been reported in early disseminated Lyme disease, although unilateral disease remains more common. [11,12] Our patient’s development of bilateral facial nerve palsies may be indicative of central nervous system involvement and a host immune response following therapy. Our patient received an additional two weeks of parenteral therapy, the effect of which is unknown, and an additional one week of oral therapy after symptom improvement. Of note, parenteral ceftriaxone is commonly used as an initial therapy in Lyme neuroborreliosis in the inpatient setting, though oral doxycycline is equally effective as demonstrated by a randomized trial comparing the two regimens. [13] Both ceftriaxone and doxycycline are preferred regimens for neurologic manifestations of Lyme disease in the 2020 AAN/ACR/IDSA guidelines. [14,15] Here, ceftriaxone was selected as patient’s neurologic symptoms had developed on doxycycline and initial concern for secondary intracranial hypertension (which was later thought to be unlikely), though this change in therapy may not have been necessary. Our patient was not treated with steroids as there is a paucity of data showing improved outcome with steroids in Lyme-associated facial nerve palsy to date. [12]

The development of our patient’s facial palsies early after starting therapy also raises consideration of an inflammatory etiology. While Jarisch-Herxheimer reaction (JHR) was considered in the differential diagnosis, this is unlikely as onset of JHR has typically been described within the first 24 h of therapy and is often accompanied by systemic symptoms, including mild hypotension, tachypnea, and tachycardia. [3] JHR has most classically been described in syphilis, but may also be seen in other spirochete infections including Lyme disease and leptospirosis. The frequency of JHR during Lyme disease has been estimated to be 7–30%, including after administration of doxycycline, and clinical symptoms are often milder in Lyme disease than in other spirochete infections. [16] A limitation of this report is, in the absence of detailed immunologic studies, it remains difficult to discern if his neurologic symptoms may be due to natural progression of disease or a delayed immune-mediated worsening, and future research is needed.

In addition, this report represents a single case which limits its generalizability. In our review of the literature, we identified three additional detailed cases of neuroborreliosis which progressed on treatment (Table 1). In the two cases described by Kohler et al., patients experienced neuroborreliosis findings simultaneously with erythema migrans. Erythema migrans promptly resolved with initiation of intravenous penicillin G, while additional cranial nerve palsies and peripheral limb paresthesis developed within 17 days subsequently. [17] In the case described by Marcos et al., the patient developed right facial paralysis 10 days after starting doxycycline. [18] In all cases, Jarisch-Herxheimer reaction was not observed though authors noted increased inflammatory reaction due to destruction of Borrelia by antibiotics may have contributed to the neurologic symptoms. Neurologic symptoms in all cases resolved. Additionally, in a case series of 29 patients with Lyme neuroborreliosis in Sweden, 7 patients developed new onset facial palsy after antibiotic therapy. Five patients with unilateral facial palsy developed contralateral facial palsy within 1–12 days (mean, 6 days) after antibiotic therapy, 2 of which were retreated with complete recovery without sequelae within 8 weeks. Two patients with Lyme disease-associated meningoradiculitis developed unilateral facial paresis during antibiotic therapy. Overall, 26 out of 29 patients (90%) recovered without sequelae within 6 months, although the outcomes of the remaining 5 patients who developed facial palsy on treatment were not explicitly reported. [15]

Table 1.

Published studies describing progression of neuroborreliosis after initiation of Lyme disease treatment.

Case	Year Reported	Age/ Gender	Antibiotic Therapy	Onset after Initiation of Therapy	Time to Resolution from Onset	Additional Symptoms	Borrelia burgdorferi Diagnostic Test	Resolution
Left abducens, left facial nerve paresis Kohler et al. [17]	1989	71	Penicillin G 10 million units BID x 10 days	VI: 8 Days VII: 17 days	“several months”	Erythema migrans, left thoracic pain radiating to arm	CSF IgG positive; serum IgG positive; Western blot IgM, IgG positive	Presumed complete
Foot, toe extensor palsy Kohler et al. [17]	1989	53	Penicillin G 10 million units TID x 14 days	7 Days	“several months”	Erythema migrans, left lumbar sciatic pain	CSF IgG positive; serum IgG positive	Presumed complete
Right facial nerve paralysis Marcos et al. [18]	2017	54 F	Doxycycline 100 mg PO BID x 10 days followed by Minocycline 100 mg PO BID x 21 days	10 Days	7 days	Erythema migrans, right jaw pain, right facial pain and numbness, right erythematous ear canal, right headache	Serology pair CSF borderline, serum reactive; serum IgM Western blot positive, serum IgG Western blot indeterminate	Complete
Bilateral facial nerve palsies Chang et al.	2026	58 M	Doxycycline 100 mg PO BID x 6 days followed by Ceftriaxone 2 g IV daily x 14 days followed by Doxycycline 100 mg PO BID x 7 days	4 days	7 weeks	Erythema migrans, fever, malaise, photophobia, diplopia	Blood polymerase chain reaction negative; Serology positive, Western blot IgM positive, IgG negative; CSF IgG screen positive, IgG index negative	Complete

Abbreviations; mg, milligram; PO, per os; IV, intravenous; BID, twice a day; TID, three times a day; CSF, cerebral spinal fluid

Conclusions

This case describes an uncommon presentation of neuroborreliosis with bilateral facial palsies which developed after initiation of treatment of early disseminated Lyme disease with erythema migrans. Our review of the literature found three additional detailed cases of neuroborreliosis which occurred after initiation of treatment for erythema migrans. Multiple erythema migrans lesions are a cardinal manifestation of early disseminated Lyme disease, and clinicians should be aware that additional symptoms of early disseminated disease (e.g. neurologic symptoms) may become evident after starting treatment. The development of additional signs and symptoms may reflect an inflammatory response similar to the Jarisch-Herxheimer reaction seen in Lyme disease and other spirochetal diseases, though Jarisch-Herxheimer more typically presents within the first 24 h of therapy with systemic symptoms of inflammation. The cases of facial paralysis on therapy occurred within 1–3 weeks after initiation of therapy. All 4 cases, including ours, had eventual resolution of signs and symptoms, suggesting that the development of new findings on therapy does not necessarily denote a worse prognosis.

CRediT authorship contribution statement

Bickey H. Chang: Writing – review & editing, Writing – original draft, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. Veronique R. Nussenblatt: Writing – review & editing, Supervision, Methodology, Investigation, Conceptualization. Joel A. Goldberg: Writing – review & editing, Data curation. Mohamed Hamie: Writing – review & editing, Data curation. John H. Powers: Writing – review & editing, Writing – original draft, Supervision, Resources, Methodology, Investigation, Funding acquisition, Data curation, Conceptualization.

Patient consent statement

The patient's written consent was obtained and identifying information was removed from the manuscript. Procedures were performed in accordance with the Helsinki declaration.

Funding

This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under NCI Contract No. 75N91019D00024, Task Order No.75N91019F00130. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.