Lyme disease in Indian patients: Diagnosis & management
M3 India Newsdesk Oct 03, 2018
The CDC has updated its criteria to standardise surveillance for Lyme disease making it relevant to us since India is now seeing more and more cases of this. Lyme borreliosis serology presently uses a two-test approach for demonstration of specific antibodies as laboratory evidence of infection. Detection of B. burgdorferi by PCR skin biopsy also helps to diagnose Lyme disease.
Introduction
Lyme disease is a multi-organ disease that is transmitted by the tick, Ixodes. It is caused by the strains of the spirochete Borrelia burgdorferi sensu lato. The incidence of Lyme disease has risen globally due to more travel and novel habitats of the vector whereas earlier it was primarily seen in the temperate regions of the world.
The Indian subcontinent is also seeing a few cases. The earliest signs of Lyme disease are seen in the form of skin lesions which after proper diagnosis and treatment, help in the prevention of complications that are mainly neurological in origin.
Erythema chronicum migrans (ECM), Borrelial lymphocytoma (BL) and Acrodermatitis chronica atrophicans (ACA) are the three main dermatological manifestations. Dermatological conditions such as morphea, lichen sclerosus and off late B cell lymphoma can also be seen due to Lyme disease.
Neuroretinitis is rarely found in India, in which a focal inflammation of the optic nerve and peripapillary retina or macula is seen, and if the patient comes from a forested area, Lyme disease needs to be considered in the differential diagnosis of neuroretinitis.
Diagnosis
A history of exposure to tick bite, travel to an endemic area, or a characteristic clinical finding and serology usually enable the physician to diagnose Lyme disease. Neuroretinitis, however, is diagnosed by exclusion in Lyme disease. Erythema chronicum migrans (ECM) is the characteristic lesion of early Lyme disease and this is diagnosed mainly by the clinical presentation.
Laboratory tests and evidences acts largely as a supporting tool and helps in early treatment and complication prevention. Detection of B. burgdorferi by culture is expensive and lacks sensitivity. Therefore, in clinically suspected atypical ECM manifestations, detection of B. burgdorferi by polymerase chain reaction of skin biopsy helps to diagnose Lyme disease. Lyme borreliosis is diagnosed mainly by serology as it is the most practical and commonly used method.
A two-test approach that first involves initial screening with enzyme-linked immunosorbent assay (ELISA) or indirect immunofluorescence assay (IFA), and then getting positive and equivocal results with Western blot provides demonstration of specific antibodies and laboratory evidence of infection.
In the future, a single‑step ELISA using recombinant proteins (such as C6 peptide) may substitute for the standard two‑tiered testing format. After the rash appears, within 2-4 weeks, IgM antibody can be detected, whereas IgG takes 4-6 weeks to start rising and peaks 6 months after the infection and may remain elevated for months to years.
A false negative result may be detected since B. burgdorferi antibodies may not be present early in the disease. Since mononucleosis, autoimmune diseases and Treponema pallidum infections may give false positive results, serologic testing is not recommended when the pretest likelihood of Lyme disease is low (<20%).
CDC updates
The clinical and serologic criteria have been recently updated by the CDC to standardise surveillance for Lyme disease. The CDC state that only these following criteria can confirm a case of Lyme disease:
- Erythema chronicum migrans (ECM) with known exposure to the tick or laboratory evidence of infection
- Late manifestations of the disease with laboratory evidence of infection alone even without history of exposure
A normal or raised white blood cell count may be seen. Haemoglobin, haematocrit, creatinine, and urinalysis results are usually not deranged. PCR testing of skin biopsies should be reserved for atypical presentations since it is more sensitive and specific than either serology or culture.
A greater sensitivity with the skin biopsies is possible by combining two different primer sets of PCR. Culture and PCR are more sensitive than serology in early ECM. Diagnosis of skin borreliosis cannot be made by urine PCR. For Lyme borreliosis, immunoblotting with many B. burgdorferi antigens can serve as a confirmatory test.
Nutech Functional Score
There is a lack of a discrete and exhaustive clinical scoring system for patients with Lyme disease, and low specificity and sensitivity is seen with the serological testing and other laboratory tests. Hence, a novel tool, the Nutech functional Score (NFS) which is a numeric scoring system is now available and this can help doctors to validate and confirm the diagnosis of LD for patients globally. The limitation with this scoring system is that it can be used only in parts according to the clinical condition of the patient, i.e., the changes of the individual symptoms that are present in the patient can only be described.
Treatment
Lyme disease therapy is most effective if drugs are given early on in the course of the disease.
- Doxycycline 100 mg orally is the antibiotic of choice, and this is given twice daily for 14 to 21 days in cases of ECM, and for 3 to 4 weeks in cases of BL and ACA
- A few studies on erythema migrans found that treatment with azithromycin 500 mg twice daily on the first day, and then 500 mg once daily for the next four days is as effective as treating with doxycycline
- Amoxicillin, cefuroxime and erythromycin are other drug options that can be used
- In cases of multiple EM lesions, pregnant ladies and immunodeficient patients, parenteral IV ceftriaxone 2 g once daily, or penicillin G 18-24 million units daily, divided four hourly for 10-14 days is also useful; persistent cases of ACA may also require the same regime
- In children below 8 years of age, lower doses of various antibiotics are to be used per day as follows:
- Amoxicillin 25-50 mg/kg
- Azithromycin (20 mg/kg for day 1 with 10 mg/kg for the remaining days)
- Cefuroxime 30-40 mg/kg, all for the same duration as mentioned for adults
Doxycycline is not prescribed to children younger than eight years of age, pregnant, and breastfeeding women. Amoxycillin, azithromycin and third generation cephalosporins, in the same dose and duration are the drugs of choice irrespective of pregnancy status in ladies.
Neurological or rheumatological involvement which may present as late manifestations are harder to treat and may not respond to antibiotics alone. However, treatment with prednisone and doxycycline has been shown to resolve neuroretinitis.
Prevention
Vaccines are not currently very effective against Lyme disease. Hence, there is greater need for the early recognition of cutaneous manifestations and early treatment to prevent multi-organ complications.
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