Lyme disease (and erythema migrans)

Lyme disease is an infection caused by the spirochaete Borrelia burgdorferi (B. burgdorferi). It is named after the town Lyme in Connecticut, USA, where the condition was first recognised. The characteristic cutaneous presentation is that of erythema migrans. Disseminated disease can affect the central nervous system, joints, and heart. 

This chapter is set out as follows:

• The principal vector of B.burgdorferi infection is the Ixodes tick. Lyme disease risk areas correlate with the habitats of infected Ixodes ticks (black-legged ticks), which thrive in wooded, brushy, and long-grass environments. Key high-risk regions vary globally. In the UK high-risk hotspots include the Scottish Highlands, the New Forest, Exmoor, the Lake District, South Downs, and Thetford Forest, although infected ticks are found throughout the UK and Ireland 
   
• The Ixodes tick progresses through four stages of development: egg, larva, nymph, and adult. Only larvae, nymphs, and adult female ticks require blood meals, and only ticks in the nymphal and adult stages can transmit B burgdorferi. The adult lays eggs in the spring, and the larvae emerge in the summer. The following spring, the larvae emerge as nymphs, which feed once, in the spring and summer, with small mammals as their preferred feeding source. Nymphs molt into adults the following autumn, which feed once on a larger animal, often a deer
   
• Affected patients usually live close to, or have visited, woodland areas where the ticks can be found along with their predominant hosts 
   
• The risk of Lyme disease is highest in the spring and summer when Ixodes ticks in the nymphal stage are seeking a blood meal. Nymphs are responsible for 90% of human disease transmissions because of the great abundance of nymphs; the increase in human outdoor activity in the summer (the peak feeding season of nymphs); and the small size of nymphs, which makes them less likely to be detected and removed before disease transmission occurs
   
• It takes hours for the tick to attach fully to the host, and experimental studies have indicated that in most cases nymphs must feed for 36-48 hours, and adults for 48-72 hours, to transmit B burgdorferi. Despite the length of time required to transmit the infection many patients do not remember a tick bite

• The cutaneous features (erythema migrans) usually becomes visible from 1 to 4 weeks after the bite (but can appear from 3 days to 3 months); up to 30% of patients do not get a rash. Untreated, the rash usually fades within 3-4 weeks, but can last many months
   
• Consider the possibility of Lyme disease in people presenting with several of the following symptoms, because Lyme disease is a possible but uncommon cause of:
  • fever and sweats 
  • swollen glands
  • malaise / fatigue
  • neck pain or stiffness
  • migratory joint or muscle aches and pain
  • cognitive impairment, such as memory problems and difficulty concentrating (sometimes described as 'brain fog')
  • headache
  • paraesthesia
     
• In untreated cases, or where there has been a significant delaying in the initiation of treatment, up to two-thirds of patients develop further symptoms

Erythema migrans

Unlike a typical insect bite, the rash is not usually itchy, hot or painful. In most, but not all cases, erythema migrans develops at the site of the bite in which case a central punctum may be evident. The clinical features can include:

• A spreading erythema with a well-demarcated edge that typically expands over days
• Usually round or oval but can be triangular or linear
• As the rash expands there can be clearing behind the leading edge giving rise to an annular appearance; however, this is not always the case; some individuals present with a confluent patch
• Often flat but can be palpable; occasionally there is a fine scale
• Single lesions typically achieve a diameter of approximately 15 cm; lesions as large as 70 cm have been reported

Disseminated disease

• Can occur within days or weeks of the initial infection and can cause:
  • Arthritis - the most common complication, with inflammation of the large joints (the knee is the most affected joint)
  • Early neuroborreliosis - Bell's palsy and other cranial nerve palsies, aseptic meningitis, polyradiculitis
  • Cardiac involvement - pericarditis and myocarditis with associated conduction defects
  • Other skin lesions - numerous smaller and less migratory lesions

Late-stage Lyme disease

• Occurs months to years after infection. Most patients presenting with late disease do not have a history of erythema migrans, because the rash typically leads to earlier treatment, which prevents the development of late disease
   
• Longer-term sequelae are mainly rheumatological and neurological
  • Chronic Lyme arthritis (chronic severe joint pain and swelling) in one or more large joints, mostly the knee (more common in North America than in Europe)
  • Chronic neurological disorders such shooting pains, confusion, dizziness, short-term memory loss
     
• Acrodermatitis chronica atrophicans (ACA), found almost exclusively in European patients, has the following clinical features:
  • Typically presents with unilateral involvement of the extensor parts of the upper or lower limbs, especially the dorsum of the hand, elbow, instep, ankle, or knee. However, it can appear anywhere on the body and can be bilateral
  • Acute phase - ill-defined reddish discolouration and swelling of the affected area. The skin may be tender or painful
  • Atrophic stage - the skin is thin and often violaceous with dilated blood vessels, and loss of adnexal structures such as sweat glands and hair

• The current recommendation is that if a rash is suggestive of Lyme disease then treatment should be commenced immediately without going on to do investigations. If a person thinks they have been bitten by a tick and do not develop a rash then consider checking serology at six weeks (see below), or earlier if the patient becomes symptomatic - infection is more likely if the tick is attached to a person's skin for more than 24 hours
   
• Investigations sometimes performed:
  • Confirmation is usually by serology looking for antibodies to B. burgdorferi, although results can be negative in the first six weeks of infection 
  • For detailed information on who and how to test refer to the NICE guidelines

Lyme disease prevention (in endemic areas) - advice

• When walking in high grass or woodland, wear white clothes (so the tick can be seen more easily) with long sleeves, long trousers tucked into socks, or long boots
• Use repellents/pesticides
• After returning from a walk in an endemic area change your clothes and check your whole body carefully. The next day check your body for ticks again
• If a tick is observed remove it immediately - use tweezers to carefully and steadily pull the tick out from the skin and disinfect the site 
• Watch the site of the tick bite for several weeks. If a rash appears or you have 'flu-like' symptoms, consult your doctor

Treatment of Lyme disease

• Treatment must not be delayed - a diagnosis can be made on the presence of erythema migrans (or sometimes other symptoms), with or without evidence of a tick bite. Laboratory tests are usually not necessary in the early stage of erythema migrans as they can be false-negative. Cure rates decrease the longer treatment is delayed
   
• Localised cases - erythema migrans 
  • Doxycycline 100 mg twice a day, or 200 mg once a day, for 21 days
  • Tetracycline's should not be used if contraindicated eg allergy and children under 12 years of age (NICE guidelines recommend that the management of Lyme disease in children and young people should be discussed with a specialist). For Lyme disease suspected during pregnancy, use appropriate antibiotics for the stage of pregnancy. Other treatment options include:
    • First option - amoxicillin 1 g three times a day for 21 days
    • Second option - oral azithromycin 500 mg once a day for 17 days. Do not use azithromycin to treat people with cardiac abnormalities associated with Lyme disease because of its effect on QT interval
       
• Systemic cases are harder to treat and may require parenteral antibiotics - refer to the NICE Guidelines
   
• Tick bites may transmit other infections like tick-born encephalitis, anaplasmosis and babesiosis. Co-infections should be considered if symptoms of Lyme disease are severe or prolonged, in case of high fever, and abnormal blood test results (leukopenia, thrombocytopenia, elevation of liver transaminases)
   
• Post-treatment Lyme borreliosis syndrome (PTLDS) - also known as post-treatment Lyme disease syndrome (PTLDS) - refers to debilitating, ongoing symptoms like severe fatigue, widespread body pain, and cognitive issues (brain fog) that last for more than six months after receiving standard, appropriate antibiotic treatment for Lyme disease. It is believed to be an autoimmune response. Prolonged antibiotic treatment does not appear to be of benefit

• For further information refer to the Lyme Disease Action Group