Does my patient testing positive for hepatitis A IgM really have acute hepatitis A infection even though he is completely asymptomatic?

Not necessarily! A positive hepatitis A (HA) IgM in a patient without any symptoms could indicate a few different things: 1. Asymptomatic infection; 2. Prior HA infection with prolonged IgM presence; 3. False positive results due to cross-reacting antibodies; and 4. Commercial kits with a falsely low cutoff value.1

A 2013 retrospective study found that of patients testing positive for HA IgM antibody, only 11% could be confirmed to have acute HA infection; 57% had recent and/or resolved hepatitis and 29% had reasons to have elevated hepatic enzymes other than HA infection, at least some likely to be false-positive.1

Other viral illnesses and autoimmune conditions have been associated with false positive HA-IgM.1-3  One case report described a patient with malaise, fever, jaundice, and elevated liver enzymes who tested positive for HA-IgM but ultimately was found to be infected with Epstein-Barr virus (EBV)2. In another case report, a patient was described as having a drug-induced liver injury in the setting of infliximab usage. False positive Hep A IgM was suspected to be due to a polyclonal B-cell autoimmune-mediated response stimulated by the infliximab.3

So, even a positive HA-IgM should always be interpreted in the context of the patient’s history and likelihood of active HA infection based on epidemiological factors.1

Bonus Pearl: Did you know that modes of transmission of HA include person-to-person via saliva or sex, consuming raw/undercooked shellfish, or drinking contaminated drinking water?4

Contributed by Joseph Kinsella, Medical Student, A.T. Still Osteopathic Medical School,  Kirksville, Missouri

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References

  1. Alatoom A., Ansari M. Q, Cuthbert J. (2013). Multiple factors contribute to positive results for hepatitis a virus immunoglobulin M antibody. Arch Pathol Lab Med 2013;137:90–95. https://doi.org/10.5858/arpa.2011-0693-oa
  2. Valota M, Thienemann F, Misselwitz B. False-positive serologies for acute hepatitis A and autoimmune hepatitis in a patient with acute Epstein–Barr virus infection. BMJ Case Reports CP 2019;12: e228356.
  3. Tennant E, Post JJ. Production of false-positive immunoglobulin m antibodies to hepatitis a virus in autoimmune events. J Infect Dis 2016;213: 324–325. https://doi.org/10.1093/infdis/jiv417
  4. Mayo Foundation for Medical Education and Research. (2020, August 28). Hepatitis A. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/hepatitis-a/symptoms-causes/syc-20367007.

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis or its affiliate healthcare centers, Mass General Hospital, Harvard Medical School or its affiliated institutions. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Does my patient testing positive for hepatitis A IgM really have acute hepatitis A infection even though he is completely asymptomatic?

My patient with erythema multiforme has tested positive for Mycoplasma pneumoniae IgM antibody. Does this mean she has an acute M. pneumonia infection as the cause of her acute illness?

Not necessarily! Although detection of IgM in the serum of patients has proven valuable in diagnosing many infections during their early phase, particularly before IgG is detected, less well known is that false-positive IgM results are not uncommon. 1

More specific to M. pneumoniae IgM, false-positive results have been reported in 10-80% of patients without a clinical diagnosis of acute M. pneumoniae infection 2-4 and 3-15% of blood donors. 4

False-positive IgM results may also occur when testing for other infectious agents, such as the agent of Lyme disease (Borrelia burgdorferi), arboviruses (eg, Zika virus), and herpes simplex, Epstein-Barr, cytomegalovirus, hepatitis A and measles viruses. 1,5  

Reports of false positive IgM results include a patient with congestive heart failure and mildly elevated liver enzymes who had a false-positive hepatitis IgM which led to unnecessary public health investigation and exclusion from an adult day care center. 1 Another patient with sulfa rash had a false-positive measles IgM antibody resulting in callback of >100 patients and healthcare providers for testing!5

There are many potential mechanisms for false-positive IgM results, including polyclonal B cell activation, “vigorous immune response”, cross-reactive antibodies, autoimmune disease, subclinical reactivation of latent viruses, influenza vaccination, overreading weakly reactive results, and persistence of antibodies long after the resolution of the acute disease. 1,2

In our patient, a significant rise in M. pneumoniae IgG between acute and convalescent samples several weeks apart may be more helpful in diagnosing an acute infection accounting for her erythema multiforme.

 

References

  1. Landry ML. Immunoglobulin M for acute infection: true or false? Clin Vac Immunol 2016;23:540-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4933779/
  2. Csango PA, Pedersen JE, Hess RD. Comparison of four Mycoplasma pneumoniae IgM-, IgG- and IgA-specific enzyme immunoassays in blood donors and patients. Clin Micro Infect 2004;10:1089-1104. https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(14)63853-2/pdf
  3. Thacker WL, Talkington DF. Analysis of complement fixation and commercial enzyme immunoassays for detection of antibodies to Mycoplasma pneumoniae in human serum. Clin Diag Lab Immunol 2000;7:778-80. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC95955/
  4. Ryuta U, Juri O, Inoue Y, et al. Rapid detection of Mycoplasma pneumoniae IgM antibodies using immunoCard Mycoplasma kit compared with complement fixation (CF) tests and clinical application. European Respiratory Journal 2012; 40: P 2466 (Abstract). https://erj.ersjournals.com/content/40/Suppl_56/P2466 
  5. Woods CR. False-positive results for immunoglobulin M serologic results: explanations and examples. J Ped Infect Dis Soc 2013;2:87-90. https://www.ncbi.nlm.nih.gov/pubmed/26619450

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My patient with erythema multiforme has tested positive for Mycoplasma pneumoniae IgM antibody. Does this mean she has an acute M. pneumonia infection as the cause of her acute illness?