Lyme Disease

Lyme disease is a tick-borne infection caused by the gram-negative spirochete Spirochete Treponema is a gram-negative, microaerophilic spirochete. Owing to its very thin structure, it is not easily seen on Gram stain, but can be visualized using dark-field microscopy. This spirochete contains endoflagella, which allow for a characteristic corkscrew movement. Treponema Borrelia Borrelia Borrelia are gram-negative microaerophilic spirochetes. Owing to their small size, they are not easily seen on Gram stain but can be visualized using dark-field microscopy, Giemsa, or Wright stain. Spirochetes are motile and move in a characteristic spinning fashion due to axial filaments in the periplasmic space. Borrelia burgdorferi. Lyme disease is transmitted by the black-legged Ixodes tick (commonly known as a deer tick), which is only found in specific geographic regions. Patient presentation can vary depending on the stage of the disease and may include a characteristic erythema migrans rash. Neurologic, cardiac, ocular, and joint manifestations are also common in later stages. Diagnosis relies on clinical findings and tick exposure, and is supported by serological testing. Antibiotics are used for treatment. Avoidance of tick exposure is key to prevention in endemic areas.

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Overview

Epidemiology

  • First recognized in 1977 as “Lyme arthritis” in Connecticut
  • Most common tick-borne infection in North America and Europe
    • United States endemic areas: Northeast and Midwest regions
    • European endemic areas: central and eastern European countries
    • Geographic distribution appears to be increasing and may be related to:
      • Climate change
      • Land-use practices
      • Increasing virulent strains
  • > 30,000 cases reported in the United States each year
  • 5%–35% of Ixodes ticks are infected with Borrelia Borrelia Borrelia are gram-negative microaerophilic spirochetes. Owing to their small size, they are not easily seen on Gram stain but can be visualized using dark-field microscopy, Giemsa, or Wright stain. Spirochetes are motile and move in a characteristic spinning fashion due to axial filaments in the periplasmic space. Borrelia.
  • Infection can occur from March to October and peaks around June–July.

Etiology

  • Causative organism: 
    • Spirochete (gram-negative bacterium)
    • Most common species in North America: Borrelia Borrelia Borrelia are gram-negative microaerophilic spirochetes. Owing to their small size, they are not easily seen on Gram stain but can be visualized using dark-field microscopy, Giemsa, or Wright stain. Spirochetes are motile and move in a characteristic spinning fashion due to axial filaments in the periplasmic space. Borrelia burgdorferi 
    • Most common species in Europe:
      • B. afzelii
      • B. garinii
  • Reservoir hosts:
    • Small mammals (white-footed mouse)
    • White-tailed deer 
  • Vector for transmission: Ixodes tick
    • Transmission occurs through saliva injection during feeding
    • Longer attachment is associated with a higher risk of transmission (typically 36–72 hours)
  • At-risk groups:
    • Hikers
    • Woodworkers
Life cycle and reservoirs of b. Burgdorferi

Lifecycle, reservoirs, and vector transmission of B. burgdorferi

Image by Lecturio.

Pathophysiology

  • Tick attachment and feeding → Borrelia Borrelia Borrelia are gram-negative microaerophilic spirochetes. Owing to their small size, they are not easily seen on Gram stain but can be visualized using dark-field microscopy, Giemsa, or Wright stain. Spirochetes are motile and move in a characteristic spinning fashion due to axial filaments in the periplasmic space. Borrelia (found in saliva) is injected into the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin:
    • May be eliminated by the immune system
    • Otherwise, will produce an erythema migrans skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin lesion
  • Spirochetes then spread to the blood and regional lymph nodes within days to weeks.
  • Eventual spread to multiple organs (e.g., heart, joints, central nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. General Structure of the Nervous System, eyes)
  • Manifestations are secondary to the host’s immune response:
    • Induction of autoantibodies against neuronal and glial antigens
    • Cross-reactivity of Borrelia Borrelia Borrelia are gram-negative microaerophilic spirochetes. Owing to their small size, they are not easily seen on Gram stain but can be visualized using dark-field microscopy, Giemsa, or Wright stain. Spirochetes are motile and move in a characteristic spinning fashion due to axial filaments in the periplasmic space. Borrelia antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins with neural and connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue
    • T-cell–mediated immune response
  • There may be some weak endotoxin-like activity.
Pathophysiology of lyme disease

Progression of Lyme disease after a tick bite

Image by Lecturio.

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Clinical Presentation

The incubation period for Lyme disease is 3–30 days (mean of 7 days). The clinical manifestations of Lyme disease are broken down into 3 stages: early localized disease, early disseminated disease, and late disease.

Early localized disease

Symptoms appear in 1–5 weeks and resolve in approximately 30 days.

  • Erythema chronicum migrans (EM)
    • Occurs in approximately 80% of patients
    • Classic “bull’s-eye” rash with slowly expanding red ring and central clearing
    • Appears at the site of the tick bite
  • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
  • Myalgia
  • Arthralgia
  • Fatigue
  • Lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy

Early disseminated disease

Symptoms develop in weeks to months in untreated patients.

  • Musculoskeletal:
    • Migratory arthralgias
    • Myalgias
  • Cardiac (approximately 8% of patients): 
    • Myocarditis Myocarditis Myocarditis is an inflammatory disease of the myocardium, which may occur alone or in association with a systemic process. There are numerous etiologies of myocarditis, but all lead to inflammation and myocyte injury, most often leading to signs and symptoms of heart failure. Myocarditis
      • Inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation to the myocardium, which affects the muscle and electrical system of the heart
      • Manifests as chest pain Chest Pain Chest pain is one of the most common and challenging complaints that may present in an inpatient and outpatient setting. The differential diagnosis of chest pain is large and includes cardiac, gastrointestinal, pulmonary, musculoskeletal, and psychiatric etiologies. Chest Pain and shortness of breath
      • Can lead to congestive heart failure Congestive heart failure Congestive heart failure refers to the inability of the heart to supply the body with normal cardiac output to meet metabolic needs. Echocardiography can confirm the diagnosis and give information about the ejection fraction. Congestive Heart Failure
    • Pericarditis Pericarditis Pericarditis is an inflammation of the pericardium, often with fluid accumulation. It can be caused by infection (often viral), myocardial infarction, drugs, malignancies, metabolic disorders, autoimmune disorders, or trauma. Acute, subacute, and chronic forms exist. Pericarditis
      • Inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the pericardium
      • Manifests as sudden onset of sharp chest pain Chest Pain Chest pain is one of the most common and challenging complaints that may present in an inpatient and outpatient setting. The differential diagnosis of chest pain is large and includes cardiac, gastrointestinal, pulmonary, musculoskeletal, and psychiatric etiologies. Chest Pain
    • Atrioventricular (AV) block 
      • Secondary to myocarditis
      • Most common cardiac manifestation
  • Neurologic (approximately 15% of patients):
    • Facial nerve palsy (Bell’s palsy)
      • Typically bilateral
      • Most common neurologic manifestation
    • Meningoradiculitis (Bannwarth syndrome):
      • Radiculopathy and paresthesia
      • Follows a dermatome distribution
    • Polyneuropathy Polyneuropathy Polyneuropathy is any disease process affecting the function of or causing damage to multiple nerves of the peripheral nervous system. There are numerous etiologies of polyneuropathy, most of which are systemic and the most common of which is diabetic neuropathy. Polyneuropathy
    • Lymphocytic meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis
    • Encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis
  • Cutaneous:
    • Multiple secondary EM lesions
      • Due to spirochetemia (presence of Borrelia Borrelia Borrelia are gram-negative microaerophilic spirochetes. Owing to their small size, they are not easily seen on Gram stain but can be visualized using dark-field microscopy, Giemsa, or Wright stain. Spirochetes are motile and move in a characteristic spinning fashion due to axial filaments in the periplasmic space. Borrelia in the blood)
      • Not from multiple tick bites
    • Lymphadenosis cutis benigna (also known as pseudolymphoma or borrelial lymphocytoma)
      • Rare, more often seen in Europe
      • Blue-red swelling, usually of the earlobe or near the nipple
  • Ocular:
    • Conjunctivitis Conjunctivitis Conjunctivitis is a common inflammation of the bulbar and/or palpebral conjunctiva. It can be classified into infectious (mostly viral) and noninfectious conjunctivitis, which includes allergic causes. Patients commonly present with red eyes, increased tearing, burning, foreign body sensation, and photophobia. Conjunctivitis (10% of patients)
    • Rare manifestations:
      • Keratitis (inflammation of the cornea)
      • Retinal vasculitis
      • Optic neuropathy
      • Uveitis Uveitis Uveitis is the inflammation of the uvea, the pigmented middle layer of the eye, which comprises the iris, ciliary body, and choroid. The condition is categorized based on the site of disease; anterior uveitis is the most common. Diseases of the Uvea (inflammation of the uvea)

Late disease

Symptoms develop in months to years in untreated patients.

  • Migratory polyarthritis (60% of patients)
    • Large joints, particularly the knee
    • Intermittent joint swelling and pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
    • Baker cysts can form.
  • Neurologic symptoms:
    • Lyme encephalopathy: subtle cognitive, mood, and sleep Sleep Sleep is a reversible phase of diminished responsiveness, motor activity, and metabolism. This process is a complex and dynamic phenomenon, occurring in 4-5 cycles a night, and generally divided into non-rapid eye movement (NREM) sleep and REM sleep stages. Physiology of Sleep disturbances
    • Chronic axonal polyneuropathy
      • Spinal radicular pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
      • Distal paresthesias
    • Chronic encephalomyelitis
      • Spastic paraparesis
      • Cranial neuropathy
      • Cognitive impairment
  • Acrodermatitis chronica atrophicans 
    • More common in Europe due to B. afzelii
    • Starts with unilateral bluish-red discoloration and swelling
    • Atrophy eventually develops and vasculature appears more prominent.

Mnemonic

Common symptoms of Lyme disease can be remembered by the mnemonic phrase “a key Lyme pie to the FACE.”

  • Facial nerve palsy
  • Arthritis
  • Cardiac block
  • Erythema migrans

Diagnosis

Diagnostic algorithm

Lyme disease diagnosis

Diagnostic algorithm for Lyme disease

ELISA: enzyme-linked immunosorbent assay

Image by Lecturio.
  • A Lyme disease diagnosis is based on the clinical picture and supported by serologic testing.
  • Blinical symptoms largely depend on the stage of disease.
  • Lyme testing is not warranted for:
    • Screening asymptomatic patients
    • Patients with only nonspecific symptoms (fatigue, myalgia)

Laboratory testing

Laboratory tests are only significant in conjunction with the clinical history due to a high false-positive and false-negative rate.

  • Antibody testing
    • Enzyme-linked immunosorbent assay (ELISA)
      • Initial test
      • Detects antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins through a coupled enzyme-antibody complex, which produces a color change
      • False-positives can occur due to other infections (e.g., syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis) or autoimmune disease.
      • False-negatives can occur in the early stage; thus, ELISA is not done if the characteristic EM rash is seen.
    • Western blot
      • Confirmation test if the ELISA is positive
      • Detects antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins to individual protein components of B. burgdorferi using electrophoresis
  • Polymerase chain reaction (PCR)
    • May be performed on cerebrospinal fluid and synovial fluid for those who present with meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis or arthritis.
    • High false-negative rate
    • Can remain positive for years after treatment
Western blotting of b. Burgdorferi

Western blotting of B. burgdorferi.
A, B, and C: positive controls for specific monoclonal antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins
D and E: seropositive patients for IgM
F: positive control
G: negative control
H: white control
MW: molecular weight

Image: “Western blotting of B. burgdorferi” by Department of Biomedicine and Biotecnology, Alcalá University, 28871 Alcalá de Henares, Spain. License: CC BY 3.0

Management

Treatment

Oral antibiotics:

  • Doxycycline
  • Amoxicillin
  • Cefuroxime
  • Used in all stages of Lyme disease

Intravenous (IV) antibiotics:

  • Ceftriaxone
  • Used for:
    • Those who cannot tolerate oral antibiotics
    • Early disseminated disease with meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis, encephalomyelitis, or severe cardiac manifestations (3rd-degree AV block AV block Atrioventricular (AV) block is a bradyarrhythmia caused by delay, or interruption, in the electrical conduction between the atria and the ventricles. Atrioventricular block occurs due to either anatomic or functional impairment, and is classified into 3 types. Atrioventricular Block)
    • Late disease with neurologic manifestations
    • Recurrent arthritis despite oral therapy

Additional considerations:

  • 3rd-degree AV block AV block Atrioventricular (AV) block is a bradyarrhythmia caused by delay, or interruption, in the electrical conduction between the atria and the ventricles. Atrioventricular block occurs due to either anatomic or functional impairment, and is classified into 3 types. Atrioventricular Block
    • May require temporary pacing
    • AV block AV block Atrioventricular (AV) block is a bradyarrhythmia caused by delay, or interruption, in the electrical conduction between the atria and the ventricles. Atrioventricular block occurs due to either anatomic or functional impairment, and is classified into 3 types. Atrioventricular Block is usually short-lived with treatment.
  • Jarisch-Herxheimer reaction
    • Seen in 15% of patients with early Lyme disease
    • Transient worsening of symptoms during the initial 24 hours of treatment
    • Due to an immune response to the antigens released by dying spirochetes
Table: Summary of the management of the different clinical manifestations of Lyme disease
Clinical manifestations Management
Asymptomatic patient with a tick bite requires no prophylactic treatment unless:
  • Known Ixodes scapularis bite
  • Tick attached for ≥ 36 hours
  • In an endemic area
If meets criteria, then must receive prophylactic doxycycline within 72 hours of bite
Early disseminated disease:
  • Erythema migrans lesions
  • Risk of exposure
  • Doxycycline
  • Amoxicillin or cefuroxime
Facial nerve palsy or joint involvement
  • Doxycycline
  • Amoxicillin or cefuroxime
Cardiac and neurologic manifestations Intravenous ceftriaxone
Reinfection Same antibiotic as recommended for a primary infection

Post-Lyme disease syndrome (PLDS) and chronic Lyme disease

  • Controversial syndromes
  • Persistent or recurrent symptoms despite treatment
  • Chronic subjective symptoms are not thought to be due to persistent infection.
  • Patients should be reevaluated since this may be due to:
    • Incorrect Lyme diagnosis
    • Coinfection with another tick-borne disease ( Babesia Babesia Babesiosis is an infection caused by a protozoa belonging to the genus, Babesia. The most common Babesia seen in the United States is B. microti, which is transmitted by the Ixodes tick. The protozoa thrive and replicate within host erythrocytes. Lysis of erythrocytes and the body's immune response result in clinical symptoms. Babesia/Babesiosis, Anaplasma)
    • Another concurrent condition ( fibromyalgia Fibromyalgia Fibromyalgia is a chronic pain syndrome characterized by widespread body pain, chronic fatigue, mood disturbance, and cognitive disturbance. It also presents with other comorbid symptoms such as migraine headaches, depression, sleep disturbance, and irritable bowel syndrome. Fibromyalgia, depression)
    • Permanent tissue damage (particularly from neurologic involvement)
  • No proven benefit to additional antibiotics

Prevention and Prophylaxis

  • If the tick is removed within the first 12 hours, the infection risk is very low.
  • Do not assume immunity is developed after a previous infection.
  • For persons from non-endemic areas, there is no need for prophylactic antibiotics, but the tick site should be observed.

Precautions against ticks

  • Protective clothing
  • Repellents
  • Scanning the body for ticks after being outside
  • Removing ticks from bite sites as soon as possible with a tweezer

Doxycycline prophylaxis

Doxycycline prophylaxis is indicated if all the following criteria are met:

  • Tick is identified as Ixodes scapularis.
  • Tick has been attached for ≥ 36 hours.
  • Prophylaxis will start within 72 hours of tick removal.
  • Rate of B. burgdorferi infection of ticks in the area is ≥ 20%.
  • Doxycycline is not contraindicated.

Differential Diagnosis

  • Babesiosis Babesiosis Babesiosis is an infection caused by a protozoa belonging to the genus, Babesia. The most common Babesia seen in the United States is B. microti, which is transmitted by the Ixodes tick. The protozoa thrive and replicate within host erythrocytes. Lysis of erythrocytes and the body's immune response result in clinical symptoms. Babesia/Babesiosis: a tick-borne infection caused by Babesia Babesia Babesiosis is an infection caused by a protozoa belonging to the genus, Babesia. The most common Babesia seen in the United States is B. microti, which is transmitted by the Ixodes tick. The protozoa thrive and replicate within host erythrocytes. Lysis of erythrocytes and the body's immune response result in clinical symptoms. Babesia/Babesiosis. Patients can be asymptomatic or develop fever, fatigue, malaise, and arthralgias. Asplenic, immunocompromised, and elderly patients are at risk for severe disease, causing hemolytic anemia Hemolytic Anemia Hemolytic anemia (HA) is the term given to a large group of anemias that are caused by the premature destruction/hemolysis of circulating red blood cells (RBCs). Hemolysis can occur within (intravascular hemolysis) or outside the blood vessels (extravascular hemolysis). Hemolytic Anemia, thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia, hepatosplenomegaly, renal failure, and death. Diagnosis is confirmed with a peripheral blood smear, serologic testing, and PCR. Treatment includes antibiotics, such as atovaquone plus azithromycin.
  • Ehrlichiosis Ehrlichiosis Ehrlichiosis is a tick-borne bacterial infection. The most common causative species include Ehrlichia chaffeensis, which infect and multiply within monocytes. The clinical presentation can vary widely, but often includes fever, malaise, headache, myalgia, and arthralgias. Ehrlichiosis and Anaplasmosis and anaplasmosis Anaplasmosis Anaplasmosis is a tick-borne bacterial infection. The most common causative species include Anaplasma phagocytophilum, which infect and multiply within granulocytes. The clinical presentation can vary widely, but often includes fever, malaise, headache, myalgia, and arthralgias. Ehrlichiosis and Anaplasmosis: tick-borne infections caused by Ehrlichia chaffeensis and Anaplasmosis phagocytophilum, respectively. Symptoms include fever, headache, and malaise. A rash is uncommon, but can appear petechial or maculopapular. The diagnosis is made with a PCR test. Treatment of both diseases is with doxycycline.
  • Rocky Mountain spotted fever Rocky Mountain Spotted Fever Rocky Mountain spotted fever (RMSF) is a bacterial infection caused by the obligate intracellular parasite Rickettsia rickettsii. Transmission occurs through an arthropod vector, most commonly the American dog tick (Dermacentor variabilis). Early signs and symptoms of RMSF are nonspecific and include a high fever, severe headache, and rash. Rocky Mountain Spotted Fever: a disease caused by Rickettsia Rickettsia Rickettsiae are a diverse collection of obligate intracellular, gram-negative bacteria that have a tropism for vascular endothelial cells. The vectors for transmission vary by species but include ticks, fleas, mites, and lice. Rickettsia rickettsii that presents with fever, fatigue, headache, and a rash following a tick bite. However, this disease is associated with the Dermacentor tick, and the rash begins on the distal extremities and spreads centrally. Diagnosis is made based on the clinical features, biopsy of the rash, and serologic testing. Treatment involves antibiotics, including doxycycline.
  • Epidemic typhus Epidemic Typhus Epidemic typhus is a febrile illness caused by the obligate intracellular gram-negative bacterium, Rickettsia prowazekii. Epidemic typhus is also known as louse-borne typhus or jail fever, and its symptoms include high fever, headache, myalgias, dry cough, delirium, stupor, and rash. Epidemic Typhus: a disease caused by Rickettsia Rickettsia Rickettsiae are a diverse collection of obligate intracellular, gram-negative bacteria that have a tropism for vascular endothelial cells. The vectors for transmission vary by species but include ticks, fleas, mites, and lice. Rickettsia prowazeki that presents with myalgia, arthralgia, rash, and encephalitis. A rash starts on the trunk and spreads outward to the extremities. Epidemic typhus Epidemic Typhus Epidemic typhus is a febrile illness caused by the obligate intracellular gram-negative bacterium, Rickettsia prowazekii. Epidemic typhus is also known as louse-borne typhus or jail fever, and its symptoms include high fever, headache, myalgias, dry cough, delirium, stupor, and rash. Epidemic Typhus is transmitted to humans by lice. Diagnosis is based on the clinical picture, biopsy of the rash, and serologic testing. Treatment involves antibiotics, including doxycycline. 
  • Infectious mononucleosis Mononucleosis Infectious mononucleosis (IM), also known as "the kissing disease," is a highly contagious viral infection caused by the Epstein-Barr virus. Its common name is derived from its main method of transmission: the spread of infected saliva via kissing. Clinical manifestations of IM include fever, tonsillar pharyngitis, and lymphadenopathy. Mononucleosis: a disease caused by the Epstein-Barr virus Epstein-Barr Virus Epstein-Barr virus (EBV) is a linear, double-stranded DNA virus belonging to the Herpesviridae family. This highly prevalent virus is mostly transmitted through contact with oropharyngeal secretions from an infected individual. The virus can infect epithelial cells and B lymphocytes, where it can undergo lytic replication or latency. Epstein-Barr Virus that is characterized by fever, fatigue, lymphadenopathy, and pharyngitis Pharyngitis Pharyngitis is an inflammation of the back of the throat (pharynx). Pharyngitis is usually caused by an upper respiratory tract infection, which is viral in most cases. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, and hoarseness. Pharyngitis. Diagnosis is based on clinical features and testing, such as a heterophile antibody test or serology. Treatment is supportive. The use of amoxicillin can cause a characteristic maculopapular rash. 
  • Juvenile idiopathic arthritis Juvenile Idiopathic Arthritis Juvenile idiopathic arthritis (JIA), formerly known as juvenile rheumatoid arthritis, is a heterogeneous group of inflammatory diseases characterized by inflammation of 1 or more joints and is the most common pediatric rheumatic disease. Juvenile Idiopathic Arthritis: a group of rheumatic diseases that cause arthritis, fever, rash, adenopathy, splenomegaly Splenomegaly Splenomegaly is pathologic enlargement of the spleen that is attributable to numerous causes, including infections, hemoglobinopathies, infiltrative processes, and outflow obstruction of the portal vein. Splenomegaly, and iridocyclitis in children under 16 years of age. The rash may vary, but can appear macular with a central clearing. Diagnosis is based on the clinical picture and an autoimmune workup, including rheumatoid factor (RF), antinuclear antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins (ANA), anticyclic citrullinated peptide antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins (anti-CCP), and human leukocyte antigen (HLA)-B27. Treatment includes corticosteroids and disease-modifying antirheumatic drugs Disease-modifying antirheumatic drugs Disease-modifying antirheumatic drugs are antiinflammatory medications used to manage rheumatoid arthritis. The medications slow, but do not cure, the progression of the disease. The medications are classified as either synthetic or biologic agents and each has unique mechanisms of action and side effects. Disease-modifying Antirheumatic Drugs (DMARDs).
  • Rheumatoid arthritis: an autoimmune disease of the joints, causing an inflammatory and destructive arthritis. Patients typically have swelling and pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain of the peripheral joints (e.g., hands, wrists, knees, ankles). Associated extra-articular manifestations include pericarditis, lymphadenopathy, episcleritis, or mononeuritis multiplex. Diagnosis is based on the clinical picture, inflammatory markers, RF, and anti-CCP. Treatment usually starts with glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids, DMARDs, and nonsteroidal anti-inflammatory drugs (NSAIDs).
  • Reactive arthritis Reactive arthritis Reactive arthritis is a seronegative autoimmune spondyloarthropathy that occurs in response to a previous gastrointestinal (GI) or genitourinary (GU) infection. The disease manifests as asymmetric oligoarthritis (particularly of large joints in the lower extremities), enthesopathy, dactylitis, and/or sacroiliitis. Reactive Arthritis: a spondyloarthropathy that is often precipitated by a gastrointestinal or genitourinary infection. Patients may present with an asymmetric arthritis, typically of the lower extremities. This arthritis can be associated with fever, tendinitis, enthesitis, mucocutaneous ulcers, and conjunctivitis. Diagnosis is clinical. Treatment includes NSAIDs, DMARDs, and treatment of the infection.

References

  1. Bush, L.M., and Vazquez-Pertejo, M.T. (2020). Lyme disease. [online] MSD Manual Professional Version. Retrieved December 5, 2020, from https://www.msdmanuals.com/professional/infectious-diseases/spirochetes/lyme-disease
  2. Mead, P., and Schwartz, A. (2020). Epidemiology of Lyme disease. In Mitty, J. (Ed.), UpToDate. Retrieved December 5, 2020, from https://www.uptodate.com/contents/epidemiology-of-lyme-disease
  3. Hu, L. (2020). Clinical manifestations of Lyme disease in adults. In Mitty, J. (Ed.), UpToDate. Retrieved December 5, 2020, from https://www.uptodate.com/contents/clinical-manifestations-of-lyme-disease-in-adults
  4. Hu, L. (2019). Diagnosis of Lyme disease. In Mitty, J. (Ed.), update. Retrieved December 5, 2020, from https://www.uptodate.com/contents/diagnosis-of-lyme-disease
  5. Hu, L. (2020). Treatment of Lyme disease. In Mitty, J. (Ed.), Uptodate. Retrieved December 5, 2020, from https://www.uptodate.com/contents/treatment-of-lyme-disease
  6. Meyerhoff, J.O., Steele, R.W., and Zaidman, G.W. (2019). Lyme disease. In Diamond, H.S. (Ed.), Medscape. Retrieved December 5, 2020, from https://emedicine.medscape.com/article/330178-overview

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