Lyme disease becomes quite prevalent in the warmer months worldwide as one of the leading types of tick-borne disease. While the disease is associated with diverse symptoms, from rashes to neurological manifestations, the disease course is split into three main groups. Early localised, early disseminated, and late disseminated Lyme disease describe distinct stages of bacterial infection.

Learning about these stages of disease is important in understanding the relevant symptoms, treatments, and prognosis of each case of Lyme disease. In this article, we will first briefly introduce Lyme disease. We will then explain all three stages of the disease course, explaining the symptoms and the treatments associated with each.

Introduction to lyme disease

Lyme disease, also known as Lyme borreliosis, is the most common tick-borne disease in the United States and Europe.^1,2 It was first reported in the town of Old Lyme in Connecticut, hence its name.

The disease is caused by a species of bacteria called Borrelia burgdorferi. These bacteria are first found in deer and mice, and then further transmitted to deer ticks. When humans are bitten by the deer tick, most commonly in their immature lymph form, the Borrelia burgdorferi bacteria can enter the bloodstream and cause disease.

The bacteria only reach the bloodstream of an individual if the tick is attached to the body for over 36 hours. However, due to the small size of deer ticks, most individuals are unaware of their presence until Lyme disease symptoms arise. Outside of deer ticks, Lyme disease is not transmitted between humans.

Overview of lyme disease stages

Lyme disease is clinically divided into three main disease stages, governed by where the bacteria have spread within the body. Each stage comes with a different set of symptoms and may warrant distinct treatment options.

These three stages are:

Stage 1: Localised Lyme disease

• In this early stage, the bacteria are still mainly present within the site of the tick bite and have not spread around the body.

Stage 2: Early disseminated Lyme disease

• Here, the bacteria have spread around the body and disease symptoms are no longer localised.

Stage 3: Late disseminated Lyme disease

• In late disseminated stages, the bacteria have spread to joints and nerves around the individual's body

In Lyme disease, the progression and symptoms can vary greatly depending on the individual. Therefore, while these three stages have been documented in Lyme disease, an individual may not experience all stages and timelines may vary. Importantly, these stages are also not completely distinct, and symptoms may overlap. For example, some patients experience both stage 1 and 2 symptoms concurrently.

Early localised lyme disease (Stage 1)

Stage 1, early localised Lyme disease, normally lasts between 1 and 28 days after the tick bite.

Symptoms

The characteristic “bull’s-eye rash”

One of the first and most characteristic symptoms of Lyme disease is the “bull’s eye rash”, also known as erythema migrans, that develops in the area of the tick bite. While the rash starts as a small red spot at the tick bite site, it expands across the skin over multiple days. The name describes the rash’s appearance, which normally is surrounded by a red ring, with a clear centre region around the original red tick bite. This is one of the most common symptoms of Stage 1 Lyme disease, with up to 80% of patients presenting with a bull’s eye rash.¹

The colour of the rash can differ, from bright red to red-purple, depending on the individual’s skin tone. While it is visually distinguishable, the rash should not itch or be tender to touch. This can last up to several weeks, although it tends to clear as treatment starts.

Other symptoms of Lyme disease reported in Stage 1 include flu-like symptoms. Individuals may experience:

• Chills
• Fever
• Headache
• Muscle and joint aches
• Sore throat
• Swollen lymph nodes
• Fatigue

Diagnosis

Lyme disease is diagnosed by blood tests that test for disease antibodies produced by the body. However, during stage 1 of the disease, there are often insufficient antibody levels for a positive diagnosis to be confirmed by blood test. Therefore, during early infection, Lyme disease may be diagnosed by a healthcare professional in the presence of the bull’s-eye rash and other flu-like symptoms associated with Lyme disease³.

Treatment

If a deer tick has been discovered to have bitten an individual and remained attached for over 36 hours, antibiotic treatment can be started immediately. A 10-14 day course of oral antibiotics is often prescribed in stage 1 of Lyme disease. The commonly prescribed antibiotics are:⁴

• Doxycycline: This is the main antibiotic prescribed for Lyme disease. Most individuals above 8 years of age are given a 10-day course of doxycycline upon Lyme disease diagnosis
• Amoxicillin: This is normally prescribed in children under the age of 8 who are diagnosed with Lyme disease
• Cefuroxime: This is the preferred antibiotic for pregnant women with Lyme disease

Early disseminated lyme disease (Stage 2)

The early disseminated stage 2 of Lyme disease normally follows about 3-12 weeks after the initial tick bite. Only about 20% of Lyme disease patients progress to stage 2, with most cases resolving after early localised disease.¹

Symptoms

Symptoms of stage 2 Lyme disease are more varied than earlier localised disease. These can include:

• Multiple bull’s eye rashes (erythema migrans) present around the body
• Numbness or pain in hands and feet
• Facial nerve palsy or general weakness/paralysis in facial muscles
• Severe headaches
• Stiff neck
• Fever
• Abnormal heart beat⁵
• Arthritis, most commonly described in the knee joint
• Short-term memory loss or brain fog is reported in some patients

Treatment

At stage 2, Lyme disease is more commonly treated through intravenous antibiotics administration before a course of oral antibiotics. This not only treats the Lyme disease infection itself but has also been shown to alleviate symptoms of arthritis.

If heart function appears dysregulated, healthcare professionals may request patients to remain in the hospital overnight for monitoring.

Late disseminated lyme disease (Stage 3)

The third and final stage of Lyme disease is known as the late disseminated stage. This occurs only in a small subset of individuals with Lyme disease and can present many months or years after the initial tick bite.

Symptoms

The most common symptoms of late disseminated Lyme disease are arthritis and neurological manifestations.

Arthritis

Arthritis may resolve and reappear in one or more large joints over a period of months in individuals with stage 3 Lyme disease. These reoccurring episodes of arthritis most commonly affect the knees and cause affected joints to appear swollen.

Neuropathy

Patients also describe pain, numbness or tingling in the nerves. This can manifest in the limbs, but also in other muscles around the body.

Other symptoms

• Irregular heartbeat: Short-term heart block is reported in late disseminated Lyme disease. These normally last for a few days and may require heart pacing during these episodes. However, these normally do not last long and escalate
• Encephalopathy: Patients often describe this as “brain fog”, where they have difficulty with concentration and short-term memory
• Headaches, fatigue and muscle aches

Treatment

Treatment of late disseminated Lyme disease is normally treated similarly to stage 2. Intravenous and oral antibiotics are prescribed for up to a month in these patients. This is observed to alleviate the main symptoms of arthritis and neuropathy in individuals with late disseminated Lyme disease.

Conclusion

In conclusion, Lyme disease progression is split into three main parts: early localised disease (stage 1), early disseminated disease (stage 2), and late disseminated disease (stage 3). These refer to the extent of the spread of causative Borrelia burgdorferi bacteria around the body.

Different symptoms of the disease characterise each stage. Understanding the stages of Lyme disease can help patients and healthcare professionals decide the best treatment and management options for Lyme disease symptoms. However, it is important to remember that Lyme disease manifests very differently across individuals, with most experiencing only early localised (stage 1) Lyme disease. Even then, the presenting symptoms can be varied and personalised healthcare advice should always be sought from your healthcare professional.