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Introduction   

Lyme disease is the most common vector-borne disease in the United States and one of the most frequently diagnosed tick-borne infections globally (1, 11). Each year, approximately 30,000 cases of Lyme disease are reported to the Centers for Disease Control and Prevention (CDC) by state health departments, but this does not reflect all cases. Insurance companies report approximately 480,000 cases of Lyme disease in Americans (1).

Lyme disease is most prevalent in the Northeastern United States, stretching from northeastern Virginia to Maine. Specific states that are affected include Connecticut, Delaware, Maine, Maryland, Massachusetts, Minnesota, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, Vermont, Virginia, and Wisconsin. Some cases have been reported in Northern California, Oregon, and Washington (1, 11).

In the states with the highest reported cases, the incidence is roughly 40 per 100,000 people (11). Most reports of the illness occur during the months when people spend time outdoors: spring, summer, and early fall.

The incidence of Lyme disease is higher in Caucasians than in darker-skinned individuals, but some researchers think this is due to the associated skin lesion being easier to determine in lighter-skinned people (11). The disease affects more women than men and is found in people of all ages. Most cases of Lyme disease have positive outcomes when treated with antibiotics.

Chronic fatigue syndrome, which often accompanies Lyme disease, is a multisystem condition that affects more than two million Americans and is often difficult to diagnose (10). Many healthcare providers do not receive adequate teaching about the syndrome while in school, and thus are not able to effectively diagnose and treat the condition (10). Additionally, many healthcare providers erroneously perceive chronic fatigue syndrome to be a psychological disorder when in reality it is a biological condition with a pathogenesis that is not widely understood (10). To make the situation worse, the medical profession and CDC have been steadfast in denying that Lyme disease can turn chronic until recently (4).

Interestingly, the situation that swayed the CDC’s standing was COVID. Patients with the virus began experiencing long-term symptoms which the medical community called “long COVID.” Two of these long-term symptoms were fatigue and cognitive dysfunction, which are also found in patients with Lyme disease and chronic fatigue syndrome.

The CDC surveyed in 2022 and found that 18 million Americans suffered from long COVID symptoms. These findings prompted the National Academy of Science, Engineering, and Medicine (NASEM) to explore the hypothesis of “infection-associated chronic illness” in June 2023 (4).

Today, the CDC recognizes the following disease agents as being linked to chronic symptoms, including fatigue (4):

• Borrelia burgdorferi (Lyme disease)
• Coxiella burnetti (Q fever)
• Campylobacter
• Chikungunya virus
• Dengue virus
• Ebola virus
• Epstein Barr virus
• Enterovirus
• Poliovirus
• Covid-19 (SARS-CoV-2)
• West Nile Virus

The term “Post Treatment Lyme Disease Syndrome (PTLDS)” is now used to describe the lingering symptoms of fatigue, myalgia, and cognitive disturbances that do not resolve after treatment of Lyme disease with antibiotics (7).

Pathophysiology

Lyme disease is caused by the Borrelia burgdorferi bacterium and is transmitted to humans through the bite of infected Ixodes scapularis black-legged ticks. The most common pathology of the disease is the erythema migrans rash that occurs in 70% to 80% of infected persons and appears anywhere on the body. Migrans rash occurs one to two weeks after tick exposure in an endemic area, but it can also be accompanied by tinea and nummular eczema.

The image below is Black-legged tick (Ixodes scapularis):

(1)

The image below is an erythema migrans rash in Lyme disease.

(1)

If left untreated, Lyme disease can cause arthritis in 30% of cases, neurological symptoms in 15% of patients, and cardiac complications in 2% of individuals (1, 11).

Lyme disease is divided into three stages: early localized, early disseminated, and late. The first two stages are signifiers of early infection, and the third stage indicates chronic disease.

Stage 1: Occurs 1 to 28 days following tick bite and includes low-grade fever, myalgia, neck stiffness, headache, and erythema migrans. Erythema migrans may burn, itch, or be warm to the touch, and it spreads gradually with the ability to exceed 12 inches in length. The rash may have the appearance of concentric circles that resemble a target with a bull’s eye, and if left untreated, it will persist for two to three weeks. Roughly 20% of patients experience a recurrent rash while 30% with the initial rash will have no further progression of symptoms (11).

Stage 2: Exists 3 to 12 weeks after tick bite and can last 12 to 20 weeks. This stage includes malaise, fever, dizziness, headache, muscle pain, angina, heart palpitations, dyspnea, diplopia, keratitis, and eye pain. Additional complications can include joint pain (knee, ankle, wrist), encephalopathy, meningitis, cranial nerve neuropathy, and Bell palsy. Encephalopathy symptoms are changes in personality, memory loss, and deficits in cognition, especially concentration. The patient can also experience extreme irritability and depression (11).

Stage 3: This stage can include aseptic meningitis, Bell palsy, arthritis, dysesthesia, radicular pain, and cognitive deficits and can occur as late as many months or years after initial infection. The symptoms are noted to mimic fibromyalgia at this stage. In older women, acrodermatitis chronica atrophicans can appear on the dorsum of the hands and feet. Arrhythmias and heart block can also be present (11).

Chronic fatigue syndrome, also called myalgic encephalomyelitis, causes chronic symptoms of fatigue and malaise that interfere with the patient’s activities of daily living for six months or more. Symptoms can include severe fatigue, cognitive dysfunction, sleep disturbances, autonomic dysfunction, and post-exertional malaise. Chronic fatigue syndrome is now recognized as being a primary set of symptoms that accompany Lyme disease that leads to longer-term post-treatment Lyme disease syndrome (PTLDS) (4). However, the term PTLDS is also used to describe symptoms in patients who do not have diagnostic or clinical evidence of infection with Borrelia burgdorferi (7).

The leading contributors of chronic fatigue syndrome are (10):

• Immune system alterations: Natural killer (NK) cells, interleukins, and T-cell alterations are responsible for the ongoing inflammation and malaise symptoms of chronic fatigue syndrome. The pro-inflammatory state is marked by the activation of glial cells and glial toxins produced by bacteria. Lower levels of immunoglobulins IgG1 and IgG3, and increased levels of IgA and IgM, indicate chronic fatigue syndrome. Autoantibodies against certain neurotransmitters and neurons lead to disrupted sleep patterns and altered cognition associated with chronic fatigue syndrome.
• Increased oxidative stress: An increase in oxidative stress biomarkers like oxidized low-density lipoproteins (LDL) and certain prostaglandins, and an accompanying decrease in antioxidants like glutathione, can lead to chronic fatigue syndrome. The oxidative stress transforms proteins and fatty acids into immunogenic targets. Free radicals damage the electron transport chain, impairing mitochondria and cellular energy production.
• Neuroendocrine system alterations: Excess levels of serotonin and its metabolites in the central nervous system led to decreased motor activity and excessive fatigue. Low cortisol levels due to a malfunctioning hypothalamic-pituitary axis decrease the cortisol awakening response that causes post-exertional malaise in patients with chronic fatigue syndrome.

Additionally, epigenetic modification of deoxyribonucleic acid (DNA) methylation has been shown to lead to the development of chronic fatigue syndrome (10).

It is not clear why some patients experience post-treatment Lyme disease syndrome and others do not. However, the Borrelia burgdorferi bacterium can trigger an autoimmune response that causes symptoms to last well after treatment of the infection.

Risk Factors

The individuals who are at the highest risk for Lyme disease are those who spend time outdoors in regions where the Ixodes scapularis black-legged tick is common. These can include hikers and other outdoor recreational enthusiasts, hunters, and individuals who have outdoor occupations. Living in wooded or grassy areas and rural communities can increase risk. Being an owner of pets who spends time outdoors can also be a risk factor.

There are no reported cases of Lyme disease transmission from person to person or animal to person. The condition cannot be transmitted sexually, by kissing, or by drinking out of the same glass as someone who has Lyme disease (1).

Chronic fatigue syndrome is higher in individuals aged 40 to 70, and it affects Caucasian women more than men and women of other races. It also affects individuals from lower-income environments than those who come from higher-income and higher-educated cohorts. This indicates that stress can be a major catalyst for the condition (10).

Signs and Symptoms

Most symptoms of Lyme disease occur within three to 30 days (the average is seven days) after a tick bite (1).

Lyme disease signs and symptoms include (1, 11):

• Fever
• Fatigue
• Arthritis
• Dyspnea
• Dizziness
• Heart block
• Neuropathy
• Encephalitis
• Lymphedema
• Radiculopathy
• Myopericarditis
• Erythema migrans
• Visual disturbances
• Musculoskeletal pain
• Lymphocytic meningitis
• Facial nerve palsy (cranial nerve-VII)
• Headache and neck stiffness

Arthritis occurs in the larger joints, particularly the knees, and can surface months after the tick bite. Muscle, bone, and nerve pain, especially shooting nerve pain and numbness and tingling in the hands and feet can be present (1, 11).

Nurses need to understand that a bite from a tick that does not carry Lyme disease leaves a blemish that resembles a mosquito bite (small, red bump). This goes away in one to two days and is not a sign of Lyme disease. In Southern tick-associated rash illness (STARI), the rash is like erythema migrans, but it is not indicative of Lyme disease. Ticks carry other organisms in addition to Lyme disease, which can cause various types of rashes (1).

The signs and symptoms associated with chronic fatigue syndrome are (2, 10):

• Fatigue that is worsened by exertion and low upright posture that cannot be relieved by rest.
• Malaise and post-exertional malaise follow regular activities of daily living that take a day or more from which to recover.
• Chronic headaches, dizziness, photophobia
• Myalgias, particularly of the joints
• Disturbed sleep patterns that lead to daytime hypersomnolence and nighttime insomnia
• Cognitive decline is marked by slow mental processing speed, impaired learning abilities, memory decline, decreased attention, impaired multitasking abilities, and poor learning ability.
• Sore throat
• Nausea, vomiting
• Night sweats, chills
• Lymphadenopathy
• Intolerance, sensitivities, or allergies to alcohol, medications, foods, odors, and chemicals
• Anxiety, depression, panic attacks, and impaired social functioning

Roughly 20% of individuals who have chronic fatigue syndrome also have an underlying undiagnosed depressive illness (10). Most patients with chronic fatigue syndrome experience relationship challenges and the inability to maintain education or employment responsibilities.

Several tools can be used to determine the presence and severity of the signs and symptoms of post-treatment Lyme disease syndrome, including fatigue, pain, sleep quality, and depression. These tools are the Fatigue Severity Scale (FSS), Short-Form McGill Pain Questionnaire (SF-MPQ), Pittsburgh Sleep Quality Index (PSQI), and Beck Depression Inventory-II (BDI) (9).

Prevention

An interdisciplinary approach is most effective for Lyme disease prevention and can include infectious disease, dermatology, and neurology healthcare team members (11).

Individuals should be taught to take the following measures when hiking or working outdoors (1, 11):

• Remove underbrush to reduce tick habitat.
• Apply pesticides to the environment to reduce tick burden.
• Wear long sleeves, long pants, socks, and closed-in shoes.
• Wear insect repellant.
• Remove ticks from the human host promptly and properly.
• Monitor pets for tick exposure and remove ticks promptly and properly.

There is a vaccine available for Lyme disease, but the effects have not proven to be reliable or long-lasting and therefore, it is not a sound measure of prevention (11).

The same preventative measures for Lyme disease apply to post-treatment Lyme disease syndrome and chronic fatigue syndrome. The most crucial factor is for patients to develop rapport with a trusted healthcare provider who can provide care and guidance. Since there is no quick cure for post-treatment Lyme disease syndrome and chronic fatigue syndrome, patients may benefit from the support of mental health providers, community resources, and friends and family (10).

Diagnostics and Treatment

Lyme disease is diagnosed based on patient symptoms, assessment findings, and the patient’s potential exposure to infected ticks. Early recognition of symptoms, diagnosis, and treatment are critical in preventing late Lyme disease (1). Since serological testing can be insensitive during the first few weeks of infection, patients may be treated based on clinical symptoms (11).

Most Lyme disease tests measure antibodies made by the body in response to infection, but antibodies can take several weeks to develop, so patients may test negative if recently infected. Antibodies persist in the blood for months and years after the infection is gone, so they are not a reliable resource for detecting the patient’s cure rate. Additionally, false positive test results occur in the presence of other diseases besides Lyme disease, which can make the tests unreliable (1).

The past recommendation for diagnosis was to implement a sensitive enzyme immunoassay (EIA) or immunofluorescence assay, followed by a western immunoblot assay for specimens yielding positive or equivocal results. The current recommendation uses a second EIA in place of the western immunoblot assay, the screening tests for serum antibodies to Borrelia burgdorferi (6). Serological diagnosis is greater than 80% for patients who experience neurologic or cardiac manifestations (11).

If a biopsy of erythema migrans is conducted, findings can include cellular infiltration of histiocytes, lymphocytes, and plasma cells, as well as eosinophilic infiltrates and spirochetes. Cerebral spinal fluid analysis is not necessary to diagnose Lyme meningitis, but it can be used to detect potential alternative causes of illness, such as bacterial meningitis. Joint aspiration is only performed if septic arthritis is suspected (11).

Bloodwork can reveal an elevated erythrocyte sedimentation rate (ESR), leukopenia, and thrombocytopenia (11). An electrocardiogram (ECG) can detect atrioventricular block and brain imaging can show abnormalities in 20% of patients with central nervous symptoms, such as punctate lesions of the periventricular white matter (11).

The main treatment for erythema migrans in Lyme disease is the use of antibiotics, and those individuals who utilize the treatment in the early stages of the disease can prevent long-term symptoms. The patient’s age, medical history, current health conditions, pregnancy status, and allergies should be considered before administering antibiotics to patients (1, 11).

The most common antibiotics used to treat erythema migrans and Lyme carditis are (1):

• Doxycycline: 100 milligrams one time per day orally for 10-14 days
• Amoxicillin: 500 milligrams three times per day orally for 14 days
• Cefuroxime: 500 milligrams twice per day orally for 14 days. In cases of severe heart block, two grams of cefuroxime are given intravenously once a day for 14 to 21 days.

Doxycycline 100 milligrams taken twice per day orally is used to treat the neurological symptoms associated with Lyme disease. Lyme meningitis is treated with 200 milligrams of doxycycline per day orally, divided into one or two doses. Ceftriaxone two grams administered once per day intravenously can also be used in severe cases (1).

Lyme arthritis is treated with antibiotics for four weeks and a second course may be needed after the initial treatment. If the patient continues to experience symptoms after two courses of antibiotics, they should be referred to a rheumatologist. If antibiotics are not initiated early on, permanent joint damage can occur. The most common treatment includes (1):

• Doxycycline: 100 milligrams twice per day orally for 28 days
• Amoxicillin: 500 milligrams three times per day orally for 28 days
• Cefuroxime: 500 milligrams twice per day orally for 28 days. In severe cases, two grams of cefuroxime are given intravenously once a day for 14 to 28 days.

The Jarisch-Herxheimer reaction, a cytokine-mediated reaction to the antibiotic destruction of spirochetes, occurs in 5% to 15% of patients and resolves within one day (11).

Individuals with Lyme carditis should be observed until the risk of heart block subsides. For individuals who cannot close one or both eyes due to facial paralysis, an eye patch can be worn, and eye drops are used to prevent irritation. Topical steroids can also be used for ocular pain (1, 11). Treatment is typically curative with 5% of patients experiencing lingering symptoms of myalgia and fatigue for six months or more (11).

The diagnosis of chronic fatigue syndrome is based on clinical findings with the main focus centering on the patient’s fatigue. The fatigue should have a definite beginning, be severe and disabling, and affect the patient’s psychological and physical functioning. The symptoms should be present for at least six months and affect the patient more than 50% of the time. Myalgias, sleep disturbances, and mood changes may also be present. Exclusionary diagnostic criteria are schizophrenia, mania, depression, disordered eating, substance abuse, and organic brain pathology (10).

In 2015, the Institute of Medicine (IOM) released diagnostic criteria for chronic fatigue syndrome.

Three symptoms and at least two additional manifestations are required for diagnosis. The three required symptoms are (2):

1. A substantial reduction or impairment in the ability to engage in pre-illness levels of activity (occupational, educational, social, or personal life) that:
   • It lasts for more than 6 months.
   • Is accompanied by fatigue that is:
     • Often profound
     • Of new onset (not life-long)
     • Not the result of ongoing or unusual excessive exertion
     • Not substantially alleviated by rest
2. Post-exertional malaise (PEM)—worsening of symptoms after physical, mental, or emotional exertion that would not have caused a problem before the illness. PEM often puts the patient in relapse which may last days, weeks, or even longer. For some patients, sensory overload (light and sound) can induce PEM. The symptoms typically get worse 12 to 48 hours after the activity or exposure and can last for days or even weeks.
3. Unrefreshing sleep—patients with chronic fatigue syndrome may not feel better or less tired even after a full night of sleep despite the absence of specific objective sleep alterations.

At least one of the following two additional manifestations must be present (2):

Cognitive impairment—patients have problems with thinking, memory, executive function, and information processing, as well as attention deficit and impaired psychomotor functions. All can be exacerbated by exertion, effort, prolonged upright posture, stress, or time pressure, and may have serious consequences on a patient’s ability to maintain a job or attend school full time.

Orthostatic intolerance—patients develop a worsening of symptoms upon assuming and maintaining an upright posture as measured by objective heart rate and blood pressure abnormalities during standing, bedside orthostatic vital signs, or head-up tilt testing. Orthostatic symptoms including lightheadedness, fainting, increased fatigue, cognitive worsening, headaches, or nausea are worsened with quiet upright posture (either standing or sitting) during day-to-day life and are improved (though not necessarily fully resolved) with lying down. Orthostatic intolerance is often the most bothersome manifestation of chronic fatigue syndrome among adolescents.

The treatment for chronic fatigue syndrome includes both pharmacological and non-pharmacological approaches.

The pharmacological treatments for chronic fatigue syndrome include (10):

• Pain medications: Non-steroidal anti-inflammatory drugs (NSAIDS), including COX-2 inhibitors, can decrease symptoms of pain and inflammation. Opioid medications are avoided due to their addictive properties.
• Tricyclic antidepressants: These medications can improve sleep, pain, and fatigue severity. The dosages used are typically lower than the ones used to treat depression.
• Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs): These medications do not treat the underlying pathophysiology of chronic fatigue syndrome, but they can help reduce the symptoms of anxiety and depression that many patients with chronic diseases experience. SSRIs like fluoxetine, sertraline, and paroxetine can treat psychological symptoms whereas SRNIs can provide neuropathic pain relief in addition to treating anxiety and depression.
• Other medications: Antivirals like acyclovir, valacyclovir, and ganciclovir have been used in conjunction with interferons, but the evidence is inconclusive regarding their benefit. Immunoglobulins and corticosteroids have not been shown to be effective in treating the symptoms of chronic fatigue syndrome.
• Complementary medications: Fatty acids, magnesium, acetyl-1-carnitine, vitamin B12, and antioxidants have been shown to have partial benefit.

Newer treatments like rintatolimod and rituximab have not been shown to have much effectiveness in the treatment of chronic fatigue syndrome (10). However, alterations in gastrointestinal microbiota accompany chronic fatigue syndrome and are believed to be one of the etiologies for the condition. Fecal microbiota transplantation occurs when feces from a healthy donor are transferred to a patient’s gut, and this approach is showing promising results (10).

Non-pharmacological treatments for chronic fatigue syndrome are deep breathing techniques, muscle relaxation, massage, yoga, and tai chi. Cognitive behavioral therapy (CBT) has been shown to improve mood, fatigue, and post-exertional malaise. Graded exercise therapy (GET) is a supervised, gradual increase in the duration and intensity of physical activity, which encourages participants to gradually increase their physical activity until they reach the goal of 30 minutes of light exercise five days a week. Adaptive pacing therapy (APT) teaches the patient how to balance activity and rest sessions to avoid flare-ups (10).

Complications and Long-Term Effects

Lyme carditis occurs when the Borrelia burgdorferi bacteria enters the cardiac tissue and causes arrhythmias and heart block. This complication is present in one out of every 100 individuals with Lyme disease reported to the CDC (1). Symptoms include syncope, vertigo, dyspnea, heart palpitations, and angina. Treatment includes antibiotics and possible pacemakers, and antibiotics should be started immediately without waiting for Lyme disease test results. Patients typically recover in one to six weeks even though 11 patients globally died from Lyme carditis between the years 1985 and 2019 (1).

Lyme carditis requires immediate hospitalization and continued monitoring. Nurses should ask their patients with suspected or diagnosed Lyme disease about cardiac symptoms, such as angina, dyspnea, and vertigo. If patients present with cardiac symptoms for unknown reasons, the nurse should ask about possible exposure to ticks.

Lyme arthritis occurs when the Borrelia burgdorferi bacteria enters the joint tissue and causes inflammation. If the condition is left untreated, permanent damage to the joints can occur. One out of four patients with Lyme disease reports Lyme arthritis to the CDC (1). The knees are affected most often followed by the shoulder, ankle, elbow, jaw, wrist, and hip. Symptoms include warmth to the touch and pain during movement and can move between joints in an exacerbation and remission cycle (1).

Other complications include rheumatoid arthritis, acute memory disorders, ankylosing spondylitis, atrioventricular nodal block, cellulitis, contact dermatitis, gout and pseudogout, granuloma annulare, and prion-related diseases. Long-term Lyme disease triggers an autoimmune response that causes symptoms long after the infection is gone from the body, resulting in post-treatment Lyme disease syndrome. Long-term antibiotics in the treatment of this condition have not been found to improve outcomes (1, 5, 11).

Complications of chronic fatigue syndrome and post-treatment Lyme disease syndrome are anxiety and depression. The unpredictability of experiencing good days and bad days can lead to feelings of stress and hopelessness in these individuals (10).

Patients with post-treatment Lyme disease syndrome suffer a worse quality of life than patients with other chronic conditions, including heart failure, diabetes, multiple sclerosis, and arthritis with over 70% of patients with post-treatment Lyme disease syndrome reporting fair or poor health (5). Over 40% of patients with post-treatment Lyme disease syndrome reported that they are unable to work and 24% of patients admit to receiving disability assistance at some point during their illness (5).

Quality of Life in Patients with Chronic Illness (5): 

Patient Education

All healthcare team members, but especially nurses, should educate patients about measures to prevent tick bites when outdoors and how to effectively remove ticks from the skin and pets. Signs and symptoms of cardiac, neurologic, and immune complications should also be taught, as well as when to seek medical assistance (11).

Patients who are prescribed antibiotics and other medications should be taught the administration, contraindications, and adverse effects. Non-pharmacological measures, such as preventing headache triggers, using over-the-counter medications for pain relief, and getting plenty of rest are also emphasized.

Individuals should also be taught the potential adverse effects of using insect repellants, such as DEET (11).

Most people with chronic fatigue syndrome are healthy before the diagnosis, which makes the decline in the patient’s health difficult to accept (10). These patients should be taught the importance of both pharmacological and nonpharmacological measures for controlling symptoms. Eating a balanced and nutrient-rich diet, drinking plenty of water, and getting fresh air and sunshine can provide health benefits.

Research Findings

Nootkatone is a naturally occurring compound found in grapefruit, Alaska yellow cedar trees, and some herbs, and it can repel and kill ticks. In 2020, the compound was registered with the Environmental Protection Agency (EPA) and is being used in commercial repellant products as of 2022.

Clothing treated with permethrin has been studied by the CDC and universities and is highly irritating to ticks, causing them to drop off and decrease their activity for 24 hours after contact with the chemical (1).

The CDC supports The Tick Project which determines whether neighborhood-based interventions of two tick control methods can reduce the prevalence of Lyme disease. Twenty-four neighborhoods with over 1,000 households are included in the research project (1).

Advanced molecular detection (AMD) methods that sequence the full genome of bacteria have identified Borrelia mayonii as a cause of Lyme disease in upper Midwestern states. The process also identified twelve tickborne species of bacteria, including two not previously associated with human illness (1).

The National Institute of Allergy and Infectious Disease (NIAID) funded three placebo-controlled clinical trials on the effectiveness of prolonged antibiotic therapy in post-treatment Lyme disease syndrome. The first study treated patients with 30 days of intravenous antibiotics followed by 60 days or oral antibiotics and did not find long-term antibiotic therapy effective. In the second study, some patients received 28 days of intravenous antibiotics and another group received a placebo. The study participants who received the antibiotics reported an improvement in fatigue over the placebo group; however, there were no improvements in cognitive function and several of the patients’ experienced complications related to the antibiotics for which they were hospitalized. NIAID deduced that the evidence for long-term antibiotic use in post-treatment Lyme disease syndrome was not nonexistent (7).

In a third study conducted with the National Institute of Neurological Disorders and Stroke (NINDS), it was determined that long-term antibiotic use to manage the cognitive symptoms associated with post-treatment Lyme disease syndrome was not effective. Patients were administered intravenous ceftriaxone versus an intravenous placebo for 10 weeks. Adverse effects of ceftriaxone appeared in 26% of patients (7).

In another study conducted in the Netherlands in 2016, researchers concluded that the long-term treatment with antibiotics for post-treatment Lyme disease syndrome did not provide additional benefits compared with shorter-term therapies (7).

Several studies have found that Borrelia burgdorferi persists in mice and nonhuman primates after antibiotic therapy. Research is also emerging that indicates Borrelia burgdorferi can become resistant to medications (7).

Newer research indicates there is a link between gastrointestinal microbiome and chronic fatigue syndrome. Studies, where fecal samples were taken from geographically diverse subjects with chronic fatigue syndrome and those from healthy controls, found key differences in microbiome diversity, quantity, metabolic pathways, and interactions between the species of gut bacteria. This indicates that there is a significant rewiring of bacterial networks in chronic fatigue syndrome (7).

Patients with chronic fatigue syndrome had abnormally low levels of several bacteria compared to the control group, including Faecalibacterium prausnitzii and Eubacterium rectale. These bacteria promote gut health by producing the short-chain fatty acid butyrate. Butyrate is the primary energy source for cells that line the gut, and it supports the gut immune system by providing up to 70% of the cells’ energy requirements and protecting against gastrointestinal diseases. Faecalibacterium prausnitzii overabundance is also linked to fatigue severity in chronic fatigue syndrome. Other bacteria, Enterocloster bolteae and Ruminococcus gnavus, are increased in the presence of chronic fatigue syndrome and lead to inflammatory bowel disease (7).

Additional research shows that patients with long-term chronic fatigue syndrome have a more balanced microbiome but experience more severe clinical symptoms than other groups. Future study findings may inform diagnostic tests, disease classification, and treatments (7).

Case Study

T.S. is a 45-year-old Caucasian woman who presents to the emergency outpatient clinic with extreme headache, photophobia, a pain rating of 10 out of 10 for neck stiffness, malaise, excessive fatigue, and a progressive rash on her back. T.S. states, “My head feels like it is going to explode, and my neck is killing me, but I’m so tired that I can’t seem to be able to figure out what to do to make it all better.”

The woman tells the nurse that she went hiking in the woods with her Labrador retriever roughly one week ago in early September while visiting Maine during which she sat on a towel in a clearing and enjoyed a picnic lunch. Upon returning home, she checked herself and her dog for ticks but did not see any. T.S. denies using any insect repellant prior to or after the hike; however, she states that her dog receives a monthly topical dose of flea medication that is also supposed to decrease the incidence of tick involvement.

The patient states that her back had started to itch shortly after the hike, but since she lives alone, she was unable to determine the root cause. She started taking over-the-counter ibuprofen for the headache and neck pain and diphenhydramine for the itching. She has stayed in bed in a dark bedroom due to photophobia and malaise and has not been able to drive, use electronics, or go to work. T.S. called a friend to bring her to the clinic, and this friend observed the rash on the patient’s back and took a photo to share with the patient. T.S. stated to her friend during the car ride to the clinic, “It looks like a red target with a darker bull’s eye. It looks like something bit me because I see a dark scab.”

T.S.’s pertinent past medical history includes seasonal allergies; perimenopausal symptoms of hot flashes, insomnia, and a 10-pound weight gain over the past 12 months; mild asthma; and tonsillectomy at age 10. Medications include over-the-counter antihistamines for allergies, progesterone for menopause symptoms, and a steroid inhaler for asthma symptoms.

T.S.’s family history is that both parents are deceased due to a motor vehicle accident at ages 65 and 68 when T.S. was 35 years old and a younger brother (age 40) with major depressive disorder. The brother is compliant with medication and psychotherapy regimens.

The patient’s assessment findings are temperature 102.5 degrees Fahrenheit, pulse 72 beats per minute, respirations 22 breaths per minute, and oxygen saturation 99% on room air. The bilateral lung sounds are clear to auscultation and the cardiovascular exam reveals a regular rate and rhythm without murmurs and capillary refill of the fingernails is brisk. Radial, pedal, and dorsal pedal pulses are normal bilaterally. Bowel sounds are heard in all four quadrants upon auscultation.

T.S. is oriented to date, place, and time, but she confirms that at times she seems to get a little confused, which is unlike her. The rash on T.S.’s back is red with a bull’s-eye appearance and measures 18 x 22 centimeters in diameter. The palpation of the major joints does not reveal redness or warmth, but T.S. states that her knees and elbows feel tender to the nurse’s touch. Palpation of the patient’s throat and clavicle reveals lymphadenopathy.

The nurse performs a skin assessment to rule out the rash appearing in another location other than T.S.’s back and to assess the skin for any additional evidence of insect bite marks. The findings are negative. Laboratory findings reveal white blood cell count, red blood cell count, hemoglobin, hematocrit, and platelet count all to be within normal ranges. The metabolic panel findings are also within the normal range.

The EIA test for Lyme disease is negative. The patient is prescribed amoxicillin 500 milligrams twice a day to be taken orally for 14 days. She can continue with over-the-counter ibuprofen and diphenhydramine for pain and itching, respectively. T.S. is also advised to eat a well-balanced diet, drink plenty of water, and allow time for rest between activities.

After five days of rest at home, T.S. begins to feel slightly better and returns to work. However, after several weeks, she notices that upon returning home from work each evening, she still goes straight to bed and sleeps all night, waking feeling fatigued and not refreshed. She also continues to experience intermittent headaches, malaise, and some residual neck stiffness and photophobia.

T.S. also notes new symptoms of chronic knee pain, diplopia, dyspnea upon exertion, and tingling in her feet. She calls the nurse at the clinic and receives another amoxicillin prescription 500 milligrams twice a day to be taken orally for 14 days, as well as gabapentin 900 milligrams each evening before bed. The patient is advised to return to the clinic for a follow-up appointment.

During the follow-up appointment, which occurs six weeks after the date of T.S.’s hike, a second EIA test is performed, which shows antibodies positive for the Borrelia burgdorferi bacterium. The rash on T.S.’s back is biopsied and is negative for spirochetes.

T.S. is compliant with her therapy, but a couple of months after her last visit to the clinic, she still experiences symptoms with new ones appearing. Now growing increasingly concerned, she visits her primary care physician who refers her to an infectious disease specialist.

It takes six weeks for T.S. to get an appointment with the specialist. Once at that appointment, she tells the physician, “I have not felt good for six months now. Although some of my symptoms improve at times, they don’t completely go away. My rash is much better, but now I’m experiencing things that are scaring me, like sensitivity to sound, paralysis on the right side of my face, and shortness of breath when doing normal things like laundry. I just don’t understand this. I used to be an avid hiker and now I’m so tired and sick that I can barely fix a bowl of cereal. I’ve had to hire a dog walker because I can no longer walk my dog. What is happening to me? Am I dying?”

T.S. continues to be treated by the infectious disease specialist, but she is also referred to as a rheumatologist for the increasing knee pain and a neurologist for the headaches, photophobia, sound sensitivity, and facial palsy. Several months after visiting with the specialists, T.S.’s symptoms now include those consistent with chronic fatigue syndrome, and she is required to use a cane when walking.

Conclusion

Most individuals with Lyme disease can expect a full recovery with no residual effects. Only a few patients may develop recurrent infection and even fewer patients can experience serious cardiac, neurological, and immune complications. However, when patients do develop the more serious symptoms associated with post-treatment Lyme disease syndrome, this can be debilitating and lead to relationship stress, school and job disruption, and mental health challenges, such as anxiety and depression.

Research has found that long-term treatment with antibiotics is not effective in the treatment of Lyme disease, but there is a correlation between gut microbiome and some of the symptoms associated with Lyme disease, such as chronic fatigue.

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