SYSTEMIC CONDITIONS
Understanding Lyme Disease
While this disease is prevalent in the Northeast, it has been diagnosed in nearly every state.
by Deepak Gupta, O.D., .F.A.A.O.

Lyme disease has classically been thought of as a disease of the Northeastern United States. When you look at the statistics of incidence, more than 90% of cases occur in Connecticut, Rhode Island, New York, New Jersey, Pennsylvania, Wisconsin, Maryland and Massachusetts. In fact, these areas have been identified as endemic for Lyme disease. The incidence can be as high as 200 cases per 100,000 in these areas, vs. 3.5 per 100,000 nationwide. However, Lyme disease has been diagnosed in 46 states and every continent except Antarctica. It can occur any time three components come together: the bacteria that causes the disease, the tick that transmits it, and the mammal or bird that nourishes the tick. As primary care providers, we must be aware of the signs and symptoms, both ocular and systemic.

The Ixodes tick transmits Lyme disease while feeding.

Stages of disease

The organism responsible for Lyme disease is called Borrelia burgdorferi. The major vectors for transmission include Ixodes ticks. These creatures have a two-year life cycle that includes three blood feedings. Adults deposit tick eggs in the spring. The larvae hatch and feed once on small animals towards the end of summer before they molt into nymphs. Nymphs typically feed once in the following spring or early summer and molt into adults later in the summer. Adult ticks feed once on larger animals, such as white-tailed deer.

Lyme disease is classified as early or late, localized or disseminated. Let's review the various stages of the condition.

Early localized Lyme disease

Lyme disease in this stage usually manifests days to weeks after the infection. Some 75% of patients in this stage will develop erythema migrans, which may appear within 1-30 days. This typically presents at the site of inoculation and is pathogno-momic for Lyme disease. Erythema migrans begins as a red maculae or papule that continues to grow into a circular erythematous rash. In many cases, the center may remain clear, resulting in a bull's eye appearance. At the early, localized stage of infection, the spirochete presumably is constrained to the area of the lesion. The erythema migrans will fade within three to four weeks even without treatment, making early diagnosis difficult. In addition, the size and rate of expansion is variable. Size ranges from 2cm by 3cm to 40cm and may last anywhere from one to four weeks after its appearance. The lesion may feel warmer than the surrounding skin, but is asymptomatic in most patients. Some may also report burning, itching, pain and tenderness around the area.

If dissemination of Lyme disease occurs, the spread of B. burgdorferi through the blood may result in several erythema migrans lesions. Other common symptoms in this stage are muscle and joint pain, flu-like symptoms, headaches and swollen lymph nodes.

Early disseminated disease

During this stage, the disease progresses and begins to impact normal body functions. This stage may occur weeks or sometimes months after the initial infection. The most common clinical manifestations involve a flu-like illness three to 30 days after the tick bite. Symptoms include fever, chills, headache, stiff neck, mild joint pain and lymphadenopathy. Other manifestations can involve neurologic, cardiac, dermatologic and musculoskeletal systems.

The most common neurologic complications in this stage involve meningitis and peripheral cranial nerve VII neuropathy. From a clinical standpoint, unilateral facial muscle palsy secondary to Lyme is indistinguishable from Bell's palsy. Some patients in this stage of the disease will suffer from meningitis, which is lymphocytic and accompanied by elevated protein in the cerebrospinal fluid.

Additional neurological complications of early, disseminated Lyme disease include other cranial nerve palsies, optic neuritis, neuroretinitis and radiculoneuropathy. Patients may complain often of numbness and pain in the arms and legs. Patients with early, disseminated Lyme infection should undergo a baseline electrocardiogram because there is a possibility of cardiac complications such as heart palpita-tions, arrhythmias and, in rare cases, myocarditis. Lastly, patients with this stage of Lyme disease often suffer from transitory and recurrent joint pain.

Late chronic disease

Histopathology shows Borrelia burgdorferi spirochetes in Lyme disease.

This stage comes weeks, months or years after initial infection in patients who did not receive proper treatment or whose treatment did not eradicate the bacteria. The long latency period further complicates proper diagnosis and treatment. The primary complication of late-stage Lyme disease is chronic arthritis.

Another major complication of late-stage Lyme disease is progressive neurological deficits. For example, encephalitis, which typically leads to cognitive deficits including loss of memory and concentration. If CSF findings are positive for Lyme infection, the recommended treatment for this stage is parenteral antibiotic therapy for at least two to four weeks.

Ocular manifestations

Ocular complications are relatively rare in the early stages. The most common is a nonspecific follicular conjunctivitis, occurring in up to 10% of cases. In most cases, it will resolve spontaneously or with topical antibiotic therapy. Other ocular complications may develop during the early, disseminated and late stages of the disease. The most common are pars planitis and granulomatous anterior chamber inflammation. In rare cases, some patients may exhibit papilledema, which may mimic the clinical presentation of pseudotumor cerebri.

Diagnostic pearls

Researchers continue to investigate the complete history and clinical manifestations of Lyme disease. However, diagnosis is often difficult due to varying presentations and the lack of a definitive laboratory test. Diagnose Lyme disease based on the patient's history, symptoms and laboratory results. While serologic assays may confirm the presence of B. burgdorferi, laboratory testing alone is insufficient for a definitive diagnosis.

The vast majority of patients with Lyme disease don't recall a tick bite, but the presence of erythema migrans is sufficient evidence for a clinical diagnosis. Laboratory testing for Lyme disease has demonstrated significant improvements in the last couple of years, but there is no "gold standard" to confirm diagnosis. Current testing methods will help tell whether the patient has been exposed to the disease, but do not indicate whether a patient has an active infection.

One of the major problems with laboratory tests is that the gap in time between infection and the appearance of antibodies may result in early, false-negative test results. Therefore, even if a patient who appears to have been infected demonstrates early negative test results, repeat the serology one month later. IgG antibodies remain in the system of infected individuals for years, sometimes permanently, and therefore cannot be used to measure the success of treatment. One of the other problems with serology testing for Lyme disease is that cross-reactivity occurs with other microorganisms (especially Treponema pallidum) and autoimmune disorders.

Although there is no consensus on what lab tests to order for suspected cases, many choose a shotgun approach involving ELISA (enzyme-linked immuno-fluorescence antibody) and IFA (indirect immunofluorescence antibody) tests, which identify antibodies against the spirochete B. burgdorferi. Of the two, ELISA is automated and provides more objective results. The chief problems with both tests involves serovariability and relatively high rates of false positive and false negative results.

In addition to ELISA and IFA, many order Western blot testing and a test such as RPR (Rapid Plasma Reagin) and VDRL (Venereal Disease Research Laboratory) to rule out syphilis.

Medical treatment

Depending on the severity and stage at the time of diagnosis, Lyme disease requires oral antibiotics, or intravenous administration if significant neurologic disease is present. Many early cases respond well to oral antibiotics. Erythema migrans responds rapidly to treatment. One of the more common regimens involves amoxicillin 500mg t.i.d. for 10-21 days or doxycycline 100mg b.i.d. for 10-21 days. For children under the age of ten and pregnant women, the recommended regimen is amoxicillin 40mg/kg in three divided doses. For patients with contraindications for amoxicillin and doxycycline, Ceftin (cefur-oxime axetil, GlaxoSmithKline) is a viable option. If none of those are viable options, erythro-mycin 250mg q.i.d. for 10-21 days can be used as well, but the results are less effective.

In advanced cases of Lyme disease with cranial neuropathy or meningitis, the recommended treatment is Rocephin (ceftriaxone sodium, Roche) 2g, q.d. p.o. for 21-28 days or cefotaxime 2g q.8.h. p.o. for 21-28 days. For patients suffering from arthritis due to Lyme disease, use amoxicillin, doxycycline, Rocephin or Claforan (cefotaxime, Aventis) as dosed above for 28 days. Intravenous Rocephin may be indicated in severe cases.

Preventive measures

As with any disease, the best treatment is prevention. In the case of Lyme disease, prevention consists of three main areas: avoiding tick bites, managing tick bites and immunization. Although avoidance is ideal, tick bites are difficult to avoid in endemic areas. Encourage patients to use preventive measures such as long-sleeve shirts, tick repellents and daily checks. Body checks for ticks should be done when outdoors, especially for patients living in endemic areas. If you find a tick on your body, remove it as soon as possible. The longer an infected Ixodes tick attaches to a host, the greater the likelihood of B. burgdorferi transmission.

Patient education regarding tick removal is vital. Ticks should be removed with tweezers, pulling slowly from the base of the tick. Once successfully removed, apply antiseptic to the area of the bite and monitor for the appearance of a lesion.

In recent years we have seen the emergence of two variations of a vaccine designed to help prevent transmission of Lyme disease. The premise is to inactivate spirochetes of B. burgdorferi within the gut of the Ixodes prior to inoculation. Both have a fairly good safety profile and offer good inoculation with two doses and optimal protection with three doses.

Dr. Gupta practices full scope optometry in Stamford, Conn. He also serves as clinical director of The Center for Keratoconus at Stamford Ophthalmology. Send e-mail to Deegup4919@hotmail.com.