Lyme disease differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anmol Pitliya, M.B.B.S. M.D.[2]

Overview

Lyme disease must be differentiated from babesiosis, leptospirosis, mononucleosis, viral meningitis, and chronic diseases such as SLE, fibromyalgia, and chronic fatigue syndrome.Lyme disease must be differentiated from other diseases that may cause arthralgia, fever, and skin manifestations and that are associated with a history of tick exposure. Lyme disease should also be differentiated from other causes of infectious arthritis as well as acute arthritis.

Differentiating Lyme disease from other tick-borne diseases

Lyme disease must be differentiated from other diseases that may cause arthralgia, fever, and skin manifestations and that are associated with a history of tick exposure.

Disease		Organism	Vector	Symptoms
Bacterial Infection
Borreliosis (Lyme Disease)		Borrelia burgdorferi sensu lato complex and B. mayonii	I. scapularis, I. pacificus, I. ricinus, and I. persulcatus	Erythema migrans, flu-like illness(fatigue, fever), Lyme arthritis, neuroborreliosis, and carditis.
Relapsing Fever	Tick-borne relapsing fever (TBRF):	Borrelia duttoni, Borrelia hermsii, and Borrelia parkerii	Ornithodoros species	Consistently documented high fevers, flu-like illness, headaches, muscular soreness or joint pain, altered mental status, painful urination, rash, and rigors.
	Louse-borne relapsing fever (LBRF) :	Borrelia recurrentis	Pediculus humanus
Typhus (Rickettsia)
Rocky Mountain Spotted Fever		Rickettsia rickettsii	Dermacentor variabilis, Dermacentor andersoni	Fever, altered mental status, myalgia, rash, and headaches.
Helvetica Spotted Fever		Rickettsia helvetica	Ixodes ricinus	Rash: spotted, red dots. Respiratory symptoms (dyspnea, cough), muscle pain, and headaches.
Ehrlichiosis (Anaplasmosis)		Ehrlichia chaffeensis, Ehrlichia ewingii	Amblyomma americanum, Ixodes scapularis	Fever, headache, chills, malaise, muscle pain, nausea, confusion, conjunctivitis, or rash (60% in children and 30% in adults).
Tularemia		Francisella tularensis	Dermacentor andersoni, Dermacentor variabilis	Ulceroglandular, glandular, oculoglandular, oroglandular, pneumonic, typhoidal.
Viral Infection
Tick-borne meningoencephalitis		TBEV virus	Ixodes scapularis, I. ricinus, I. persulcatus	Early Phase: Non-specific symptoms including fever, malaise, anorexia, muscle pains, headaches, nausea, and vomiting. Second Phase: Meningitis symptoms, headache, stiff neck, encephalitis, drowsiness, sensory disturbances, and potential paralysis.
Colorado Tick Fever		CTF virus	Dermacentor andersoni	Common symptoms include fever, chills, headache, body aches, and lethargy. Other symptoms associated with the disease include sore throat, abdominal pain, vomiting, and a skin rash. A biphasic fever is a hallmark of Colorado Tick Fever and presents in nearly 50% of infected patients.
Crimean-Congo Hemorrhagic Fever		CCHF virus	Hyalomma marginatum, Rhipicephalus bursa	Initially infected patients will likely feel a few of the following symptoms: headache, high fever, back and joint pain, stomach pain, vomiting, flushed face, red throat petechiae of the palate, and potentially changes in mood as well as sensory perception.
Protozoan Infection
Babesiosis		Babesia microti, Babesia divergens, Babesia equi	Ixodes scapularis, I. pacificus	Non-specific flu-like symptoms.

Differentiating Lyme Arthritis from other causes of Infectious Arthritis

Microorganism or other infectious disease	Associated risk factors	Key clinical clues
Lyme disease	Living in endemic area or history of recent visit to endemic area Exposure to ticks	History of erythema migrans
Staphylococcus aureus	Rheumatoid arthritis Diabetes mellitus HIV patients	Healthy adult with skin lesions and previously history of damaged joint (e.g, rheumatoid arthritis) or prosthetic joint
Streptococcus pyogenes Streptococcal pneumonia	Autoimmune diseases Chronic skin infections Trauma	Healthy adults with spleenic dysfunction
Groups B Streptococcal infection	Immunocompromised patients Diabetes mellitus Malignancy Severe genitourinary or gastrointestinal infections	Healthy adults with spleenic dysfunction
Neisseria gonorrhoeae	Complement deficiency Systemic lupus erythematosus Male homosexuality low socioeconomic status	Healthy young and sexually active adult with Tenosynovitis Skin lesions such as vesicular pustules Complement deficiency (C5-9 deficiency) Culture negativity on synovial fluid analysis
Gram-negative bacilli Pseudomonas Escherichia coli	History of intravenous drug abuse Extremes of age Immunocompromised patients	Immunocompromised patients Recent history gastrointestinal infections such as infectious diarrhea caused by Shigella, Salmonella, Campylobacter, or Yersinia
Haemophilus influenzae	Unimmunized children
Anaerobes	Diabetes mellitus Patients with prosthetic joints	Immunocompromised hosts Recent history of gastrointestinal infection
Mycobacterium spp.	Recent history of travel to endemic areas	Immunocompromised patients Recent history of travel to endemic areas (e.g. India, South Africa, Mexico etc.) Incidious onset of monoarthritis
Fungal infection such as Blastomycosis Cryptococcus Coccidioidomycosis Sporotrichosis	Immunocompromised patients	Immunocompromised patients Incidious onset of monoarthritis
Mycoplasma hominis	Recent history of urinary tract procedure	Immunocompromised patients Recent history of urinary tract procedure
Viral arthritis	Immunocompromised patient	Polyarthritis Fever Rash
HIV infection	History of multiple sexual partners History of IVDA	Sterile, acute synovitis or reactive arthritis
Reactive arthritis	Recent gastrointestinal/ genitourinary infection	Recent gastrointestinal/ genitourinary infection Enthesopathy Skin lesions Uveitis Conjunctivitis
Endocarditis	History of endocarditis Damaged heart valves Congenital heart diseases	Fever New onset of heart murmur Septic and sterile synovitis Septic joint more common in IVDA

Differentiating Lyme arthritis from other causes of Acute Arthritis

Lyme disease can be differentiated from other causes of acute arthritis on the basis of synovial fluid analysis.

Type of Arthritis	Color	Transparency	Viscosity	Volume (in ml)	WBC count (per mm3)	PMN cellcount (%)	Gram stain	Gram Culture	polymerase chain reaction (PCR) test	Crystals
Normal	Clear	Transparent	High/thick	< 3.5	< 200	< 25	Negative	Negative	Negative	Negative
Lyme arthritis	Yellow	Cloudy	Low	Often >3.5	3,000 to 100,000 (mean: 25,000)	> 50	Negative	Negative	Positive (85 percent)	Negative
Gonococcal arthritis	Yellow	Cloudy-opaque	Low	Often >3.5	34,000 to 68,000	> 75	Variable (< 50 percent)	Positive (25 to 70 percent)	Positive (> 75 percent)	Negative
Non-gonococcal arthritis	Yellowish-green	Opaque	Very low	Often >3.5	> 50,000 (> 100,000 is more specific)	> 75	Positive (60 to 80 percent)	Positive (> 90 percent)	--	Negative
Inflammatory: crystalline arthritis (e.g.Gout, Pseudogout)	Yellow	Cloudy	Low/thin	Often >3.5	2,000 to 100,000	> 50	Negative	Negative	Negative	Positive
Inflammatory: non-crystalline arthritis (e.g. Rheumatoid arthritis, reactive arthritis)	Yellow	Cloudy	Low/thin	Often >3.5	2,000 to 100,000	> 50	Negative	Negative	Negative	Negative
Noninflammatory arthritis (e.g. Osteoarthritis)	Straw	Translucent	High/thick	Often >3.5	200 to 2,000	< 25	Negative	Negative	Negative	Negative
Hemorrhagic	Red	Bloody	Variable	Usually >3.5	Variable	50-75	Negative	Negative	Negative	Negative

Differentiating Lyme disease from other diseases

• Allergic reaction to the tick
• Babesiosis
• Chronic fatigue syndrome (CFS)
• Depression
• Fibromyalgia
• Human granulocytic anaplasmosis (HGA)
• Leptospirosis
• Mononucleosis
• Other insect bites
• Reiter's syndrome
• Rheumatoid arthritis
• Scleroderma
• Systemic lupus erythematosus (SLE)
• Tick-borne diseases
• Viral meningitis

Lyme disease must be differentiated from other causes of rash and arthritis

Disease	Findings
Nongonococcal septic arthritis	Presents with an acute onset of joint swelling and pain (usually monoarticular) Culture of joint fluid reveals organisms
Acute rheumatic fever	Presents with polyarthritis and rash (rare presentation) in young adults. Microbiologic or serologic evidence of a recent streptococcal infection confirm the diagnosis. Poststreptococcal arthritis have a rapid response to salicylates or other antiinflammatory drugs.
Syphilis	Presents with acute secondary syphilis usually presents with generalized, pustular lesions at the palms and soles with generalized lymphadenopathy Rapid plasma reagin (RPR), Venereal Disease Research Laboratory (VDRL) and Fluorescent treponemal antibody absorption (FTA-ABS) tests confirm the presence of the causative agent.
Reactive arthritis (Reiter syndrome)	Musculoskeletal manifestation include arthritis, tenosynovitis, dactylitis, and low back pain. Extraarticular manifestation include conjunctivitis, urethritis, and genital and oral lesions. Reactive arthritis is a clinical diagnosis based upon the pattern of findings and there is no definitive diagnostic test
Hepatitis B virus (HBV) infection	Presents with fever, chills, polyarthritis, tenosynovitis, and urticarial rash Synovial fluid analysis usually shows noninflammatory fluid Elevated serum aminotransaminases and evidence of acute HBV infection on serologic testing confirm the presence of the HBV.
Herpes simplex virus (HSV)	Genital and extragenital lesions can mimic the skin lesions that occur in disseminated gonococcal infection Viral culture, polymerase chain reaction (PCR), and direct fluorescence antibody confirm the presence of the causative agent.
HIV infection	Present with generalized rash with mucus membrane involvement, fever, chills, and arthralgia. Joint effusions are uncommon
Gout and other crystal-induced arthritis	Presents with acute monoarthritis with fever and chills Synovial fluid analysis confirm the diagnosis.
Lyme disease	Present with erythema chronicum migrans rash and monoarthritis as a later presentation. Clinical characteristics of the rash and and serologic testing confirm the diagnosis.

References

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