The great imitator

The great imitator
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 (DDx), especial 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". But because differential diagnosis is inherently subject to occasional difficulty and to false positives and false negatives, the idea that there are only one or two great imitators was more melodrama than objective description. 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. Nonetheless, not every DDx caveat (not every mimic) meets the threshold, because it is inherent to DDx generally that there are thousands of caveats (thousands of instances of the theme, "be careful to rule out X before diagnosing Y"); for example, ectopic pregnancy and ovarian neoplasia can mimic each other, as can myocardial infarction and panic attack, but they are not established as great imitators per se (rather, merely DDx considerations). 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 thus include the following:
Low blood sugar
Hypoglycemia as an imitator of a stroke
Tumors (neoplasms), especially cancerous tumors or any endocrine 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.
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
Breathing-related sleep disorders (sleep-disordered breathing)
Sleep apnea/hypopnea
Upper airway resistance syndrome
Proteinopathies
Amyloidosis
Mass effect inside the cranium
Any mass effect inside the cranium (including from non-neoplastic causes):
General theme: "anything inside the head that presses on the brain in unusual ways can cause strange signs or symptoms"
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
Symptoms