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) [1] 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 [2] 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 [3] Rickettsia helvetica Ixodes ricinus Rash: spotted, red dots. Respiratory symptoms (dyspnea, cough), muscle pain, and headaches.
Ehrlichiosis (Anaplasmosis) [4] 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 [5] Francisella tularensis Dermacentor andersoni, Dermacentor variabilis Ulceroglandular, glandular, oculoglandular, oroglandular, pneumonic, typhoidal.
Viral Infection
Tick-borne meningoencephalitis [6] 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 [7] 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 [8] 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
Staphylococcus aureus
Streptococcus pyogenes

Streptococcal pneumonia

  • Healthy adults with spleenic dysfunction
Groups B Streptococcal infection
  • Healthy adults with spleenic dysfunction
Neisseria gonorrhoeae
Gram-negative bacilli
Haemophilus influenzae
  • Unimmunized children[15]
Anaerobes
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
Mycoplasma hominis
  • Recent history of urinary tract procedure
Viral arthritis
HIV infection
  • History of multiple sexual partners
  • History of IVDA
Reactive arthritis
  • Recent gastrointestinal/ genitourinary infection
Endocarditis

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

Lyme disease must be differentiated from other causes of rash and arthritis[18][19][20]

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

  1. Lyme Disease Information for HealthCare Professionals. Centers for Disease Control and Prevention (2015). http://www.cdc.gov/lyme/healthcare/index.html Accessed on December 30, 2015
  2. Relapsing Fever Information. Centers for Disease Control and Prevention (2015). http://www.cdc.gov/relapsing-fever/ Accessed on December 30, 2015
  3. Rocky Mountain Spotted Fever Information. Centers for Disease Control and Prevention (2015). http://www.cdc.gov/rmsf/ Accessed on December 30, 2015
  4. Disease index General Information (2015). http://www.cdc.gov/parasites/babesiosis/health_professionals/index.html Accessed on December 30, 2015
  5. Rocky Mountain Spotted Fever Information. Centers for Disease Control and Prevention (2015). \http://www.cdc.gov/tularemia/index.html Accessed on December 30, 2015
  6. General Disease Information (TBE). Centers for Disease Control and Prevention (2015). http://www.cdc.gov/vhf/tbe/ Accessed on December 30, 2015
  7. General Tick Deisease Information. Centers for Disease Control and Prevention (2015). http://www.cdc.gov/coloradotickfever/index.html Accessed on December 30, 2015
  8. Babesiosis. Centers for Disease Control and Prevention (2015). http://www.cdc.gov/parasites/babesiosis/disease.htmlAccessed December 8, 2015.
  9. Goldenberg DL, Cohen AS (1976) Acute infectious arthritis. A review of patients with nongonococcal joint infections (with emphasis on therapy and prognosis). Am J Med 60 (3):369-77. PMID: 769545
  10. 10.0 10.1 Le Dantec L, Maury F, Flipo RM, Laskri S, Cortet B, Duquesnoy B et al. (1996) Peripheral pyogenic arthritis. A study of one hundred seventy-nine cases. Rev Rhum Engl Ed 63 (2):103-10. PMID: 8689280
  11. Vassilopoulos D, Chalasani P, Jurado RL, Workowski K, Agudelo CA (1997) Musculoskeletal infections in patients with human immunodeficiency virus infection. Medicine (Baltimore) 76 (4):284-94. PMID: 9279334
  12. Morgan DS, Fisher D, Merianos A, Currie BJ (1996) An 18 year clinical review of septic arthritis from tropical Australia. Epidemiol Infect 117 (3):423-8. PMID: 8972665
  13. Schattner A, Vosti KL (1998) Bacterial arthritis due to beta-hemolytic streptococci of serogroups A, B, C, F, and G. Analysis of 23 cases and a review of the literature. Medicine (Baltimore) 77 (2):122-39. PMID: 9556703
  14. Deesomchok U, Tumrasvin T (1990) Clinical study of culture-proven cases of non-gonococcal arthritis. J Med Assoc Thai 73 (11):615-23. PMID: 2283490
  15. De Jonghe M, Glaesener G (1995) [Type B Haemophilus influenzae infections. Experience at the Pediatric Hospital of Luxembourg.] Bull Soc Sci Med Grand Duche Luxemb 132 (2):17-20. PMID: 7497542
  16. Luttrell LM, Kanj SS, Corey GR, Lins RE, Spinner RJ, Mallon WJ et al. (1994) Mycoplasma hominis septic arthritis: two case reports and review. Clin Infect Dis 19 (6):1067-70. PMID: 7888535
  17. "Lyme Disease Diseases With Similar Symptoms - Lyme Disease Health Information - NY Times Health". Retrieved 2013-03-14.
  18. Rompalo AM, Hook EW, Roberts PL, Ramsey PG, Handsfield HH, Holmes KK (1987). "The acute arthritis-dermatitis syndrome. The changing importance of Neisseria gonorrhoeae and Neisseria meningitidis". Arch Intern Med. 147 (2): 281–3. PMID 3101626.
  19. Rice PA (2005). "Gonococcal arthritis (disseminated gonococcal infection)". Infect Dis Clin North Am. 19 (4): 853–61. doi:10.1016/j.idc.2005.07.003. PMID 16297736.
  20. Bleich AT, Sheffield JS, Wendel GD, Sigman A, Cunningham FG (2012). "Disseminated gonococcal infection in women". Obstet Gynecol. 119 (3): 597–602. doi:10.1097/AOG.0b013e318244eda9. PMID 22353959.


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