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Progression of Lyme disease to Bell’s Palsy despite treatment with doxycycline

  • Luis A. Marcos
    Correspondence
    Corresponding author at: Division of Infectious Diseases, 101 Nicolls Rd, HSC T 16, Room 027J, Stony Brook, NY, 11794, USA. Tel.: +1 631 444 3490; fax: +1 631 444 7518.
    Affiliations
    Department of Medicine (Infectious Diseases), Department of Microbiology and Molecular Genetics; and Global Health Institute, Stony Brook University, Stony Brook, NY, USA
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  • Zengmin Yan
    Affiliations
    Department of Radiology, Stony Brook University, Stony Brook, USA
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Open AccessPublished:July 10, 2017DOI:https://doi.org/10.1016/j.ijid.2017.07.004

      Highlights

      • Treatment of choice for Lyme disease remains controversial.
      • Bell’s palsy developed despite being on doxycycline.
      • Progression of disease may be related to a strong host immune response.
      • Prompt clinical response to minocycline needs further investigation.

      Case description

      A 54 year-old healthy woman presented to the emergency department with a right sided facial paralysis. About 3 weeks ago, she woke up and noticed an attached engorged tick in her right lower extremity. A week later, she noticed a mild to moderate right jaw pain which progressed to a severe right facial pain so she visited her doctor. On physical, II to XII cranial nerve examination was unremarkable. Doppler ultrasound did not show any vascular abnormalities in temporal artery. Her inflammatory markers were within normal limits (C-reactive protein:0.3 mg/dL; sedimentation rate:6 mm/h). Further brain imaging by MRI revealed no abnormalities. Lyme serology (antibodies against purified VlsE-1 and PepC10 antigens) was negative (index value 0.6; ≤ 0.90 negative). Complete blood count and metabolic panel were within normal limits. The only objective physical finding was a right erythematous ear canal so the patient was prescribed a 7-day course of amoxicillin/clavulonic acid. Two days later, the rash in the right leg increased in size. It was described as a 4 cm rash circular with erythematous edges, clearing and central erythema consistent with erythema migrans (EM) (bull’s eye). She was prescribed doxycycline 100 mg orally twice a day. Five days later the patient went to see a neurologist due to worsening right facial shooting pain. Patient had minimal gastrointestinal side effects from the antibiotic and continued taking it every 12 hours without interruption. Physical exam revealed facial symmetry, and numbness in right chin in nerve distribution. She was diagnosed with possible Lyme cranial neuritis. Doxycycline was continued and pregabalin was started. On day #10 of doxycycline, she woke up and noticed that her right face was paralyzed and was unable to close the right eye, so she went to the local emergency department. The EM was improved from 4 to 2 cm residual rash. Because of her headaches, a lumbar puncture and brain MRI were recommended. Cerebrospinal spinal fluid analysis revealed only 3 WBCs, protein 30.2 g/dL, glucose 62 mg/L, Lyme serology pair CSF fluid O.D. = 0.114 (borderline), serum Lyme serology pair O.D. = 0.409 (reactive), serum IgM Western blot positive (bands present: 23 and 41 kDa), serum IgG Western blot indeterminate (bands: 41,58 and 93 kDa), CRP remained less than 0.1 mg/dL. MRI of the brain showed new increased enhancement involving the right facial nerve (Figure 1). She was discharged on minocycline 100 mg orally twice a day for 21 days. Two days later, her right side headaches improved significantly. The facial paralysis completely resolved after 1 week. At 3 months follow-up, she recovered completely without any complications.
      Figure 1
      Figure 1MRI Post contrast T1 –weighted axial image shows abnormal enhancement of right facial nerve involving labyrinthine segment (short yellow arrow) and geniculate ganglion (long green arrow).

      Discussion

      Lyme disease (LD) is the most common vector-borne disease in the US. Lyme meningitis and other manifestations of early neurologic Lyme disease (radiculopathy) can be treated with parenteral therapy including ceftriaxone, cefotaxime or penicillin G or oral therapy that include doxycycline (200–400 mg per day in 2 divided doses orally for 10–28 days) (
      • Wormser G.P.
      • Dattwyler R.J.
      • Shapiro E.D.
      • Halperin J.J.
      • Steere A.C.
      • Klempner M.S.
      • 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.
      ). Most recent evidence showed that Lyme cranial nerve palsy can be safely treated with oral doxycycline (
      • Kowalski T.J.
      • Berth W.L.
      • Mathiason M.A.
      • Agger W.A.
      Oral antibiotic treatment and long-term outcomes of Lyme facial nerve palsy.
      ). Thus the trend nowadays is that neuroborreliosis treatment may be sufficient with oral antibiotics in some patients but severe cases may require 2-4 week parenteral antibiotic therapy (
      • Halperin J.J.
      Nervous system Lyme disease.
      ).
      Some recent data show that minocycline could be a substitute for doxycycline in some clinical scenarios including LD prophylaxis (
      • Carris N.W.
      • Pardo J.
      • Montero J.
      • Shaeer K.M.
      Minocycline as A Substitute for Doxycycline in Targeted Scenarios: A Systematic Review.
      ). Minocycline has a bacteriostatic effect and the antimicrobial activity is by the inhibition of protein synthesis. Minocycline can cross the blood-brain barrier and achieve mean brain concentrations between 30 and 40% of the equivalent systemic exposure in rats (
      • Colovic M.
      • Caccia S.
      Liquid chromatographic determination of minocycline in brain-to-plasma distribution studies in the rat.
      ). Minocycline has a high in vitro activity against Borrelia burgdorferi sensu lato and provides good protection in an animal model against Lyme (
      • Li M.
      • Masuzawa T.
      • Wang J.
      • Kawabata M.
      • Yanagihara Y.
      In-vitro and in-vivo antibiotic susceptibilities of Lyme disease Borrelia isolated in China.
      ). Doxycycline has been the most common tetracycline used for treatment of LD. A study showed that the effect of doxycycline and minocycline against LD may be both antimicrobial and anti-inflammatory by reducing the production of tumor necrosis factor-alpha, interleukin (IL)-6, and IL-8 in a dose-dependent manner (
      • Bernardino A.L.
      • Kaushal D.
      • Philipp M.T.
      The antibiotics doxycycline and minocycline inhibit the inflammatory responses to the Lyme disease spirochete Borrelia burgdorferi.
      ); and thus, in theory this antibiotic may help on the inflammatory response associated with LD. Despite the fact that doxycycline is the drug of choice nowadays to treat LD even for cranial nerve paralysis (
      • Dotevall L.
      • Hagberg L.
      Successful oral doxycycline treatment of Lyme disease—associated facial palsy and meningitis.
      ), minocycline is in theory more lipid soluble than doxycycline which means that it may have more penetration into the central nervous system.. No clinical trials are available to compare doxycycline versus minocycline for early disseminated LD.
      As our patient failed to have an improvement after 10 days of doxycycline (developed Bell’s palsy on this antibiotic despite good compliance), our approach was to switch to minocycline 100 mg orally twice a day as suggested by others (
      • Cunha B.A.
      Minocycline versus doxycycline in the treatment of Lyme neuroborreliosis.
      ) with an excellent response within 3-7 days, and complete resolution of symptoms at 21 days of therapy. As LD therapy remains a controversial topic in the infectious disease arena, this case illustrates how an infection can progress even after effective antibiotics. It is difficult to determine if the worsening symptoms were related to an inflammatory reaction after destruction of Borrelia from amoxicillin or doxycycline, or because of the natural course of LD. It is unlikely that the patient had the Jarisch-Herxheimer reaction after amoxicillin or doxycycline since the rash improved on the latter antibiotic and there were no fevers or chills associated during either therapy (
      • Butler T.
      The Jarisch-Herxheimer Reaction After Antibiotic Treatment of Spirochetal Infections: A Review of Recent Cases and Our Understanding of Pathogenesis.
      ). Future studies are needed to determine if minocycline could do better than doxycycline in patients with LD in clinical practice and especially on the long term effects of the so-called Post-Lyme Disease Syndrome.

      Transparency declarations

      None to declare.

      Funding

      None.

      Conflict of interest

      None.

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