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The Great Imitator

Disease that shows symptoms of another

Summary

Disease that shows symptoms of another

The Great Imitator (also the Great Masquerader) is a phrase used for medical conditions that feature nonspecific symptoms and may be confused with a number of other diseases. The term connotes especially difficult differential diagnosis, increased potential for misdiagnosis, and the protean nature of some diseases. Most great imitators are systemic in nature or have systemic sequelae, and an aspect of nonspecific symptoms is logically almost always involved. In some cases, an assumption that a particular sign or symptom, or a particular pattern of several thereof, is pathognomonic 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, mainly tuberculosis but occasionally others, 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 especially recurrent and poignant reputation for misdiagnoses.

Conditions or diseases sometimes referred to with this nickname include the following:

Low blood sugar

  • Hypoglycemia as an imitator of a stroke

Tumors (neoplasms), especially cancerous tumors or any endocrine tumors

Tumors

  • Cancers generally

    • Intravascular large B-cell lymphoma
    • Mycosis fungoides
    • Malignant metastases
      • Cutaneous metastases

  • Oral cancer

  • Pheochromocytoma

  • Paraneoplastic syndromes, in endocrine 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 disrupting homeostasis (in any of many diverse ways, depending on which hormone, what dosage, and which location)

    • Functioning neuroendocrine tumors (NETs)
      • Most generally, a caveat to obtain PET-CT in cases where differential diagnosis seems to be repeatedly failing, as PET can "see" NETs better than other imaging can
      • Functioning pancreatic neuroendocrine tumors (panNETs or pNETs) (example: intractable diarrhea resistant to differential diagnosis)

  • Renal cell carcinoma

  • See also: any mass effect inside the cranium (including from non-neoplastic causes)

Vitamin deficiency

  • Thiamine deficiency (vitamin B₁ deficiency), with focus on subclinical forms and nonsevere clinical forms as well as the severe form called beriberi
    • This topic overlaps substantially with the topic of excessive alcohol use, which impairs B₁ metabolism and leads to hepatic encephalopathy. Relatedly, alcohol use disorder has been implicated as a great imitator at least once in the medical literature. But the topic of thiamine deficiency also has been identified as an important component not only of malnutrition in the classic senses of semistarvation or food insecurity but also in the sense of high-calorie malnutrition, 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 the liver's function and the gut–brain axis affect the brain and thus the mind, although not every correlation is understood.
  • Vitamin B12 deficiency, due to its wide presentation with neurologic, haematologic, psychiatric, and physiological symptoms.

Substance abuse

  • Substance abuse can be confused with medical, psychiatric, and surgical conditions.

Rheumatic diseases (most with autoimmune components)

  • Various rheumatic diseases, including:
    • Fibromyalgia
    • Psoriatic arthritis
    • Lupus erythematosus
      • Systemic lupus erythematosus
    • Gout
  • A general theme with autoimmune diseases is that strange signs and symptoms can result (and can make differential diagnosis difficult) "whenever the body is attacking its own cells in unusual ways"

Dysplastic diseases, some with precancerous or rheumatologic aspects

  • Sarcoidosis
  • Endometriosis, often misdiagnosed

Neurologic disorders

  • Multiple sclerosis

Gut diseases

  • Celiac disease
  • Closely related to gut function is liver function; see information on vitamin bioactivity

Abdominal inflammations or their mimics

  • Appendicitis or its mimics
  • Pancreatitis

Endocrine disorders

  • Adrenal insufficiency, especially Addison's disease
  • Hypothyroidism
  • Endocrine tumors: see tumor information
  • A general theme with endocrine diseases is that strange signs and symptoms can result (and can make differential 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)

Thromboembolic events or their mimics

  • Pulmonary embolism
  • Stroke, stroke mimics, and stroke chameleons
    • Hypoglycemia as an imitator of a stroke

Infectious diseases

  • Various infectious diseases, including:
    • Syphilis
    • 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; today it is generally considered better understood and is treatable, making it no longer quite so fearfully mysterious, but it remains worthy of consideration with compatible exam findings and when exposure to Lyme-carrying ticks is probable.
    • Nocardiosis
    • Tuberculosis
      • Pulmonary tuberculosis
      • Cutaneous tuberculosis
    • Brucellosis
    • Infective endocarditis
    • Malaria
    • Leprosy
    • Leishmaniasis
    • Viral exanthems in children
    • Gastrointestinal infections: when appendicitis or pancreatitis have infectious causes
    • Rabies (prodromal phase)
    • Cryptococcal pneumonia

Proteinopathies

  • Amyloidosis

Mass effect inside the cranium

  • Any mass 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
    • Intracranial hemorrhage: see thromboembolic events or their mimics
    • Brain tumor: see Tumors

Skin conditions

  • Scabies

References

References

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  2. (November 1980). "Alcoholism--the second great imitator. An introduction to the problem of alcoholism.". American Journal of Clinical Pathology.
  3. (2017). "Stroke mimics in patients with clinical signs of stroke.". Caspian Journal of Internal Medicine.
  4. Kufe, Donald W.. (2009). "Holland-Frei cancer medicine". McGraw-Hill Medical.
  5. Del Paggio, Joseph. (2017). "Disturbances in blood flow and 'medicine's greatest imitator'". Internal Medicine Journal.
  6. (2019-05-01). "Mycosis fungoides: a great imitator.". Clinics in Dermatology.
  7. (2020-03-01). "Cutaneous metastases: a great imitator.". Clinics in Dermatology.
  8. (2018-12-06). "Conn's Current Therapy 2019". Elsevier Health Sciences.
  9. (17 December 2022). "Her crippling digestive problems were caused by a 'zebra' malady [pNETs].". Washington Post.
  10. Guermazi, Ali. (2005-10-05). "Imaging of Kidney Cancer". Springer Science & Business Media.
  11. (2017). "Thiamine deficiency disease, dysautonomia, and high calorie malnutrition". Academic Press.
  12. (2015-11-04). "Beriberi, the Great Imitator". CRM Health and Fitness.
  13. Qazimllari, Blerta. "VITAMIN B12 DEFICIENCY: A GREAT MIMICKER".
  14. (2023-11-20). "Vitamin B12". BMJ.
  15. (2016-03-17). "The Medical Basis of Psychiatry". Springer.
  16. [http://www.fibromyalgia-symptoms.org/fibromyalgia_great_imitator.html Fibromyalgia as the great imitator], retrieved December 16th, 2006
  17. (29 Jan 2017). "Psoriatic arthritis".
  18. (12 June 2014). "Right Care".
  19. (2005). "SLE: The great imitator strikes again". American Journal of Kidney Diseases.
  20. (2005). "Systemic lupus erythematosus: Unmasking a great imitator". Nursing.
  21. (2016-02-24). "Green's Operative Hand Surgery". Elsevier Health Sciences.
  22. (2019-05-01). "Sarcoidosis: a great imitator.". Clinics in Dermatology.
  23. (2006). "Cutaneous sarcoidosis: The 'great imitator': Etiopathogenesis, morphology, differential diagnosis, and clinical management". American Journal of Clinical Dermatology.
  24. (November 2013). "The social and psychological impact of endometriosis on women's lives: a critical narrative review.". Human Reproduction Update.
  25. (2021-04-28). "They Call It a 'Women's Disease.' She Wants to Redefine It. Profiles in Science feature.".
  26. [http://www.lcmedia.com/mind366.htm Multiple Sclerosis as the great imitator] {{Webarchive. link. (2009-01-04 , retrieved December 16th, 2006)
  27. Woods, William. (1 January 2004). "Coeliac disease: the great imitator". Med. J. Aust..
  28. (April 2006). "Appendiceal appearances: the great imitator.". Archives of Disease in Childhood.
  29. (2014). "Mimickers of acute appendicitis". J Am Osteopath Coll Radiol.
  30. (2010). "The Great Imitator". The American Journal of Medicine.
  31. (2010). "Thyroid disorders with cutaneous manifestations". Springer Science and Business Media.
  32. (1976). "Pulmonary embolism: The great imitator". Disease-a-Month.
  33. (February 2019). "Stroke mimics and chameleons.". Current Opinion in Neurology.
  34. (November 2017). "Acute stroke differential diagnosis: Stroke mimics.". European Journal of Radiology.
  35. (2019-05-01). "Syphilis: a great imitator.". Clinics in Dermatology.
  36. (July 2020). "Congenital syphilis, the great imitator—case report and review.". The Lancet. Infectious Diseases.
  37. "Syphilis Basics". CDC National Prevention Information Network.
  38. (September 1989). "Neurologic manifestations of Lyme disease, the new "great imitator".". Reviews of Infectious Diseases.
  39. (June 1988). "Lyme disease: the latest great imitator.". The Pediatric Infectious Disease Journal.
  40. (October 2014). "Lyme disease: authentic imitator or wishful imitation?". JAMA Neurology.
  41. (2004). "A Case Series and Focused Review of Nocardiosis". Medicine.
  42. (3 June 1961). "The Second "Great Imitator"—Tuberculosis". JAMA.
  43. (2019-05-01). "Cutaneous tuberculosis: a great imitator.". Clinics in Dermatology.
  44. http://www.malariasite.com/clinical-features.htm{{Dead link. (June 2018)
  45. (2019-05-01). "Leprosy: a great imitator.". Clinics in Dermatology.
  46. (2020-03-01). "Cutaneous leishmaniasis: a great imitator.". Clinics in Dermatology.
  47. (2019-05-01). "Viral exanthems in children: a great imitator.". Clinics in Dermatology.
  48. (2017). "Cryptococcal pneumonia: the great mimicker". BJR Case Reports.
  49. (2015-04-23). "Clinical Gynecology". Cambridge University Press.
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