Localized Lyme disease is characterized by erythema migrans occurring 1 to 2 weeks after tick exposure in an endemic area. The differential diagnosis for early Lyme disease with erythema migrans includes other skin conditions such as tinea and nummular eczema. If not treated in the localized stage, patients may go on to develop early disseminated or late disease manifestations. Early neurologic Lyme disease manifestations include facial nerve (CN-VII) palsy, lymphocytic meningitis, or radiculopathy. Cardiac involvement includes myopericarditis and typically presents with heart block. Lyme arthritis is mono- or pauciarticular, generally involving large joints, most commonly the knee, and occurring months removed from the initial tick bite.

Because the symptoms are not very specific, one should consider other infections transmitted by ticks like coinfection with babesia microti and Ehrlichia. Co-infection has been reported in about 10% of patients.

Like syphilis, Lyme is classified into 3 stages: localized, disseminated and persistent. The first two stages are part of early infection and the third stage is part of persistent or chronic disease. Stage 3 usually occurs within 12 months of the infection.

Stage 1: Early localized disease that may present with erythema migrans and alow grade fever. This stage usually occurs within 1-28 days following the tick bite.

The classic rash is seen in 70% of patients and may develop between 5-7 days following the tick bite. The uniform rash usually occurs at the site of the tick bite, may burn, itch or be asymptomatic. The rash tends to expand for a few days and concentric rings may be visible. If left untreated, the rash persists for 2-3 weeks. About 20% may have recurrent episodes of the rash and multiple lesions are not uncommon. At the same time flu-like symptoms may be present. The fever is low grade and may be associated with myalgia, neck stiffness and headache. Visual problems include eye redness and tearing. About 30% of patients with the rash will have no further progression of symptoms.

Stage 2: Usually develops 3-12 weeks after the initial infection. Features may include general malaise, fever, neurological features (dizziness, headache), muscle pain and cardiac symptoms (chest pain, palpitations, and dyspnea). Cranial neuropathy may present as diplopia. Eye pain and keratitis have also been reported. The knee, ankle and wrist joint are often involved. These symptoms may last 12-20 weeks, but recurrence is rare. Often when a single joint is involved, it may be mistaken for septic arthritis. About 20% of patients have CNS involvement including encephalopathy, meningitis and cranial nerve neuropathy. Bell palsy is seen in about 5% of patients. When meningeal symptoms are present,  lumbar puncture is warranted to rule out other causes. Encephalopathy presents with deficits in concentration, cognition, memory loss and changes in personality. Extreme irritability and depression are also common.

Borrelia lymphocytoma is a rare presentation of early Lyme disease that has been reported in Europe. It presents as a nodular red-bluish swelling that usually occurs on the ear lobe or areola of the nipple. The lesions can be painful to touch.

Stage 3: Late Lyme disease may occur many months or years after the initial infection. The typical features include neurological and rheumatological involvement. Many patients may not have a history of erythema migrans. However, these individuals may present with aseptic meningitis, Bell palsy, arthritis or dysesthesias. Cognitive deficits are common. The key feature of late-stage Lyme is arthritis which tends to affect the knee. the neurological and psychiatric symptoms mimic fibromyalgia. Radicular pain is common. Borrelia encephalomyelitis is rare and can present with ataxia, seizures, hemiparesis, autonomic dysfunction and hearing loss. Acrodermatitis chronica atrophicans is typically seen in older women and tends to occur on the dorsum of the hands and feet.

Cardiac involvement may present with arrhythmias or transient heart block. Conduction abnormalities are not uncommon but most cases are isolated and rarely last more than a few days. Rarely does a patient require permament pacing

In endemic areas with features of the classic rash and recent tick exposure, treatment can be started without waiting for blood work. However, in the vast majority of patients the symptoms are vague and testing is needed. Others may not recall a tick bite or develop the rash.

Serologic testing is insensitive during the first few weeks of infection, and patients presenting with erythema migrans rash and history of residing in or traveling to an endemic region may be treated based on clinical findings. In later stages of the disease, a 2-step approach is recommended for the serologic diagnosis of Lyme disease. The first step is to perform a quantitative screening test for serum antibodies to B. burgdorferi using a sensitive enzyme immunoassay (EIA) or immunofluorescent antibody assay (IFA). A Western blot should follow specimens with positive or equivocal results. Serologic diagnosis is sensitive (greater than 80%) for patients presenting with neurologic or cardiac manifestations.[8][9][10]

Sequential use of serological testing is not recommended in the acute state because antibody titers often remain elevated for a long time. Testing the tick is not recommended either. And biopsy of the skin is rarely done.

Other blood work may reveal elevated ESR, leukopenia and thrombocytopenia. Joint aspiration is only recommended if one suspects septic arthtitis.

In children lyme meningitis is rare if:

• the headache is less than 7 days
• CSF has less than 70% mononuclear cells
• Absence of 7th or other cranial nerve palsy

The ECG may reveal an AV block. Brain imaging may show abnormality in 20% of patients with CNS symptoms. Most common are punctate lesions of the periventricular white matter.

Borrelia species are had to culture and not routinely done.

Specific treatment is dependent upon the age of the patient and stage of the disease. For patients older than 8 years of age with early, localized disease, doxycycline is recommended for 10 days. Patients under the age of 8 should receive amoxicillin or cefuroxime for 14 days to avoid the potential for tooth staining caused by tetracycline use in young children. Longer courses and parenteral antibiotics may be required for more severe manifestations such as arthritis, atrioventricular heart block, carditis, meningitis or encephalitis, although European data and newer studies demonstrate that oral treatment regimens or transitioning to oral therapy at hospital discharge may be appropriate for some patients.[11][12][13]

Doxycycline is used in most patients except in children and pregnant women. In children, amoxicillin remains the drug of choice. Pregnant women show a good response to ceftriaxone.

Patients with Lyme carditis should be admitted and monitored until the ECG features of a block subside. Lyme arthritis usually resolves in 6-8 weeks. CNS Lyme disease responds well to the antibiotics. Clinicians should monitor patients for the Jarisch-Herxheimer reaction when starting therapy.

The ocular feature of Lyme disease do respond to topical steroids and IV ceftriaxone or penicillin.

Some patients may experience post-treatment Lyme disease syndrome with nonspecific symptoms. These symptoms do not respond to antibiotics.

In patients with erythema migrans, a careful history and physical examination are all that is required to establish the diagnosis of Lyme disease. However, many patients with Lyme disease present with erythema migrans or extracutaneous symptoms where diagnosis becomes a challenge. In those cases, erythema migrans may never have occurred, may not have been recognized, or may not have been correctly diagnosed by the clinician.

Other problems include the following:

• Acute memory disorders
• Ankylosing spondylitis and rheumatoid arthritis
• Atrioventricular nodal block
• Cellulitis
• Contact dermatitis
• Gout and pseudogout
• Granuloma annulare
• Prion-related diseases

Stages of Lyme Disease

1. Stage 1: Localized disease associated with erythema migrans and flu-like symptoms; Duration 1 to 30 days
2. Stage 2: Early disseminated disease with malaise, pain, and flu-like symptoms; May affect the neurological, ocular, and musculoskeletal organs; Duration 3 to 10 weeks
3. Stage 3: Late or chronic disease chiefly affects the joints, muscles, and nerves, May last months or years, Lyme arthritis is a hallmark of this stage.
4. The occurrence of post-treatment Lyme syndrome is debatable.

For early cases, treatment is usually curative. However, treatment may be complicated due to late diagnosis, antibiotic treatment failure, and concomitant infection with other tick-borne diseases such as ehrlichiosis, babesiosis, and immune suppression.

Approximately 5% of patients will have lingering symptoms of fatigue, pain, or joint and muscle aches after treatment. These symptoms can last for 6 or more months. This is called post-treatment Lyme disease syndrome. Chronic Lyme disease is generally managed similarly to fibromyalgia or chronic fatigue syndrome. Whether chronic disorder exists remains debatable. The reason is that there are many non-validated testing systems on the market which are often falsely positive. In addition, there has been a public hysteria about chronic Lyme disease, with patients demanding treatment. In most cases of so-called chronic Lyme disease, the workup is usually negative. Further, there is no evidence that long term antibiotic therapy helps. Most patients eventually recover without any residual sequelae.

• Arthritis
• Carditis
• Neurological deficits
• Ocular manifestations
• Acrodermatitis chronica atrophicans

• Infectious disease expert
• Dermatologist
• Neurologist

Based on the geographic distribution of the shared vector Ixodes scapularis, co-infections with Lyme disease and human granulocytic anaplasmosis and/or babesiosis can occur. Co-infected patients may be more severely ill at presentation, have a persistent fever longer than 48 hours after initiating antibiotic therapy for Lyme disease, or present with anemia, leukopenia, and/or thrombocytopenia. When co-infection is suspected or confirmed, treatment with an appropriate antimicrobial regimen for each infection is necessary for resolution of illness.

The key to Lyme disease is prevention and this requires an interprofessional team approach. All healthcare workers including the nurse practitioner, pharmacist, and primary care provider should provide patient education on measures to prevent tick bites while hiking or working outdoors. In areas where ticks are common, cleaning up of the environment by removing the underbrush and spraying an insecticide may reduce the tick burden in the area. The outdoors person should be told to wear appropriate garments and be familiar with the skin features of the tick bite. The nurse should educate the patient on how to remove the tick from the skin and when to seek medical assistance. The pharmacist should educate the patient on medication compliance for those who have been confirmed to have acquired Lyme disease. 

Nurses should educate parents how to inspect their children for ticks at the end of an outdoor event, in an endemic area. While there are many repellants on the market, it is best to avoid them as the risk of harm is greater than any benefit. If one is going to use a repellant, DEET is the one product that is safe, however, it is not 100% effective. finally, the pharmacist should educate the patient about the harms of taking prophylactic doxycycline; a better strategy is to remove the tick as soon as it is visualized.

Finally, pets can also develop Lyme disease and carry the tick. Hence, pet owners should examine their pets on a regular basis and remove the tick. There is no risk of acquiring Lyme disease by removing the tick.

Patients need to be told that there are many unvalidated tests for Lyme disease which offer false-positive results. Even though there is a Lyme vaccine the public should be educated that the effects of the vaccine are not consistent or long-lasting; hence one should not rely on the vaccine to prevent Lyme disease.[14][15] (Level V)

Outcomes

The prognosis for patients who are treated for Lyme disease is excellent with no residual deficits. However, a few individuals may develop a recurrent infection if an infected tick bites them. Individuals who receive late treatment may develop neurological and musculoskeletal symptoms. Lyme arthritis is not uncommon. Some patients may develop Lyme carditis that results in a heart block and requires temporary pacing of the heart. Despite the large numbers of people affected, Lyme disease is not fatal. There continues to be a debate about the existence of post-treatment Lyme disease, but so far, this diagnosis has been promoted by the lay public and media as there is no good evidence that such a condition exists.[16][17] (Level V)