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Errancy on Lyme Diagnosis

      To the Editor:
      We read with great interest the article by Goddard,
      • Goddard J.
      Not all Erythema migrans lesions are Lyme disease.
      “Not All Erythema Migrans Lesions Are Lyme Disease,” in the September issue of The American Journal of Medicine and congratulate the authors. Erythema migrans usually is easily diagnosed, making serology useless. However, according to the author's study, all erythema migrans lesions might not be due to the agent of Lyme disease (Borrelia burgdorferi).
      Indeed, coinfections frequently occur, and a large number of different germs can be transmitted by tick bites. May we put forward that formal serology could be insufficient to rule out Lyme disease diagnosis.
      In the present study, the serology that was performed 3 weeks after symptom onset could be negative because antibodies are produced slowly, particularly at the early stage of disease. This serology positivity may be delayed in time or remain negative even in chronic Lyme disease.
      • Alby K.
      • Capraro G.A.
      Alternatives to serologic testing for diagnosis of Lyme disease.
      • Stricker R.B.
      • Johnson L.
      Lyme disease: the next decade.
      This may be explained by the limits of the tests and the multiple serotype variants of Borrelia species causing Lyme disease. Indeed, all species may not be detected by the serology tests. Furthermore, false-negative results of serology could be due to antibiotherapy, sequestration of antibodies to Borrelia into immune complexes, or the intracellular location with quiescent metabolism of the cystic form.
      • Schutzer S.E.
      • Coyle P.K.
      • Belman A.L.
      • Golightly M.G.
      • Drulle J.
      Sequestration of antibody to Borrelia burgdorferi in immune complexes in seronegative Lyme disease.
      Alternative techniques to the classic serology tests, such as polymerase chain reaction or Enzyme-Linked ImmunoSpot, could be more sensitive.
      • Bil-Lula I.
      • Matuszek P.
      • Pfeiffer T.
      • Woźniak M.
      Lyme Borreliosis–the utility of improved real-time PCR assay in the detection of Borrelia burgdorferi infections.
      We report the case of a 41-year-old woman presenting with a demyelinating peripheral neuropathy causing asthenia, weakness, and diffuse paresthesia. Electromyography assessment showed mild demyelination; cerebrospinal fluid analysis and magnetic resonance imaging of the brainstem, medulla, and nerve roots showed normal results. Of note, Lyme serology was negative (serum and cerebrospinal fluid enzyme-linked immunosorbent assay, serum Western blot). Intravenous immunoglobulin treatment was performed 8 times with subsequent partial response and relapse. The diagnosis of chronic inflammatory demyelinating polyneuropathy was made. Of note, 10 months after the onset of the clinical symptoms, a serum polymerase chain reaction analysis (including Burgdorferi, Afzelii, Garinii, Valaisiana, Andersonii, Spielmanii, Lusitaniae, Japonica, Sinica, Tanukii, and Turdi detection) disclosed the presence of Borrelia (100 copies/mL). After 6 weeks of antibiotherapy (doxycycline and hydroxychloroquine), a dramatic clinical improvement showed complete disappearance of the neurologic signs.
      In our opinion, Lyme formal serology negativity is insufficient to rule out early (erythema migrans) and late chronic Lyme disease diagnosis.

      References

        • Goddard J.
        Not all Erythema migrans lesions are Lyme disease.
        Am J Med. 2017; 130: 231-233
        • Alby K.
        • Capraro G.A.
        Alternatives to serologic testing for diagnosis of Lyme disease.
        Clin Lab Med. 2015; 35: 815-825
        • Stricker R.B.
        • Johnson L.
        Lyme disease: the next decade.
        Infect Drug Resist. 2011; 4: 1-9
        • Schutzer S.E.
        • Coyle P.K.
        • Belman A.L.
        • Golightly M.G.
        • Drulle J.
        Sequestration of antibody to Borrelia burgdorferi in immune complexes in seronegative Lyme disease.
        Lancet. 1990; 335: 312-315
        • Bil-Lula I.
        • Matuszek P.
        • Pfeiffer T.
        • Woźniak M.
        Lyme Borreliosis–the utility of improved real-time PCR assay in the detection of Borrelia burgdorferi infections.
        Adv Clin Exp Med. 2015; 24: 663-670

      Linked Article

      • The Reply
        The American Journal of MedicineVol. 130Issue 5
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          I thank Perronne et al for their thoughtful response to my brief observation, “Not All Erythema Migrans Lesions Are Lyme Disease,” published in the September issue of The American Journal of Medicine.1 The authors point out that there may be issues with serologic tests for Lyme disease, leading to false-negatives. Incidentally, other readers also have responded to my original article by e-mail, saying that Lyme disease is present—even widespread—in the southern United States and that this article does a disservice both to patients and to physicians alike.
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      • Dealing with Lyme Disease Treatment
        The American Journal of MedicineVol. 130Issue 5
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          Regarding the article entitled “Errancy on Lyme Diagnosis,”1 we want to add some comments regarding the therapy issues in Lyme disease we mentioned in response to Goddard's article.2
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