The Great Imitator (alsothe Great Masquerader) is a phrase used formedical conditions that featurenonspecific symptoms and may be confused with a number of other diseases.[1] The termconnotes especially difficultdifferential diagnosis, increased potential formisdiagnosis, and theprotean nature of some diseases. Most great imitators aresystemic in nature or have systemicsequelae, and an aspect ofnonspecific symptoms is logically almost always involved. In some cases, an assumption that a particular sign or symptom, or a particular pattern of several thereof, ispathognomonic turns out to be false, as the reality is that it is only nearly so.
As recently as the 1950s,syphilis was widely considered by physicians to be "the great imitator", and in the next few decades after that, several other candidates, mainlytuberculosis[2] but occasionally others,[3] were asserted as being "the second great imitator". In recent decades, more than a dozen diseases have been recognized in the medical literature as worthy of being considered great imitators, on the common theme of recurring misdiagnoses/missed diagnoses and protean manifestations.
The list of great imitators here relies on references in the medical literature applying that label, or on other references documenting a condition's especiallyrecurrent and poignant reputation for misdiagnoses.
Conditions or diseases sometimes referred to with this nickname include the following:
Paraneoplastic syndromes, inendocrine oncology: symptoms from any type of functioning (that is,hormone-producing) endocrine tumor; such tumors secrete excess hormones in a way that is homeostatically senseless, thus disruptinghomeostasis (in any of many diverse ways, depending on which hormone, what dosage, and which location)
Most generally, a caveat to obtainPET-CT in cases wheredifferential diagnosis seems to be repeatedly failing, as PET can "see" NETs better than other imaging can[10]
Thiamine deficiency (vitamin B₁ deficiency), with focus on subclinical forms and nonsevere clinical forms as well as the severe form called beriberi[12][13]
This topic overlaps substantially with the topic ofexcessive alcohol use, which impairs B₁ metabolism and leads tohepatic encephalopathy. Relatedly,alcohol use disorder has been implicated as a great imitator at least once in the medical literature.[3] But the topic of thiamine deficiency also has been identified as an important component not only ofmalnutrition in the classic senses of semistarvation orfood insecurity but also in the sense of high-calorie malnutrition,[12][13] even in people who do not use alcohol.Hepatic encephalopathy is a wide-ranging topic that includes covert, subclinical, minimal, mild, nonalcoholic, alcoholic, moderate, and severe forms, just as (relatedly)fatty liver disease also has covert, subclinical, minimal, mild, nonalcoholic, alcoholic, moderate, and severe forms. At bottom, it is established that theliver's function and thegut–brain axis affect the brain and thus the mind, although not everycorrelation is understood.
Vitamin B12 deficiency,[14] due to its wide presentation with neurologic, haematologic, psychiatric, and physiological symptoms.[15]
A general theme withautoimmune diseases is that strange signs and symptoms can result (and can makedifferential diagnosis difficult) "whenever the body is attacking its own cells in unusual ways"
Dysplastic diseases, some with precancerous or rheumatologic aspects
A general theme withendocrine diseases is that strange signs and symptoms can result (and can makedifferential diagnosis difficult) "whenever any endocrine gland or endocrine tumor is secreting hormones in unusual ways (either too much or too little)," because of the very nature of hormones as chemical messengers (thus deranged hormones cause deranged function)
Lyme disease, whose potential as a new great imitator provoked fear in the 1980s and 1990s because of reported cases of misdiagnosis with debilitating consequences;[39][40] today it is generally considered better understood and is treatable, making it no longer quite so fearfully mysterious,[41] but it remains worthy of consideration with compatible exam findings and when exposure to Lyme-carrying ticks is probable.[41]
Anymass effect inside the cranium (including from non-neoplastic causes):
Hydrocephalus, causing gait disturbances, poor memory, strange behavior, mental impairment, and urinary incontinence, sometimes leading to psychiatric misdiagnoses, especially in cases where the focal neurologic signs are absent; a warning to obtain CT or MRI of the brain to rule out other causes of apparently psychiatric symptoms
^abFroede, RC; Gordon, JD (November 1980). "Alcoholism--the second great imitator. An introduction to the problem of alcoholism".American Journal of Clinical Pathology.74 (5):719–20.doi:10.1093/ajcp/74.5.719.PMID7004168.
^Del Paggio, Joseph; et al. (2017). "Disturbances in blood flow and 'medicine's greatest imitator'".Internal Medicine Journal.47 (5):586–588.doi:10.1111/imj.13414.PMID28503874.S2CID3799976.
^Kellerman, Rick D.; Rakel, David (2018-12-06).Conn's Current Therapy 2019. Elsevier Health Sciences. p. 971.ISBN978-0-323-59650-3.Oral cancer has been called the great imitator, for it can appear as many different oral conditions.
^Guermazi, Ali (2005-10-05).Imaging of Kidney Cancer. Springer Science & Business Media. p. 104.ISBN978-3-540-21129-7.Because of its protean and often nonspecific clinical manifestation, RCC is sometimes referred to as the 'great imitator' by clinicians.
^abLonsdale, Derrick (2017).Thiamine deficiency disease, dysautonomia, and high calorie malnutrition. London, United Kingdom: Academic Press.ISBN978-0-12-810388-3.
^Wolfe, Scott W.; Pederson, William C.; Kozin, Scott H.; Cohen, Mark S. (2016-02-24).Green's Operative Hand Surgery. Elsevier Health Sciences. p. 1905.ISBN978-0-323-29534-5.Often called "the great imitator," gout may masquerade as septic arthritis, RA, or neoplasm, and the diagnosis is often delayed by weeks or months.
^Tchernev, G (2006). "Cutaneous sarcoidosis: The 'great imitator': Etiopathogenesis, morphology, differential diagnosis, and clinical management".American Journal of Clinical Dermatology.7 (6):375–82.doi:10.2165/00128071-200607060-00006.PMID17173472.S2CID12854713.
^Kopp, SA; et al. (2010). "Cutaneous manifestations of hypothyroidism". In Heymann, Warren R. (ed.).Thyroid disorders with cutaneous manifestations. London: Springer Science and Business Media.ISBN978-1-84800-187-9.
^Bieber, Eric J.; Sanfilippo, Joseph S.; Horowitz, Ira R.; Shafi, Mahmood I. (2015-04-23).Clinical Gynecology. Cambridge University Press. p. 341.ISBN978-1-107-04039-7.Scabies is called the great imitator because patients can present with a variety of lesions.
