The great imitator
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The Great Imitator (also the Great Masquerader) is a phrase used for
medical condition A disease is a particular abnormal condition that negatively affects the structure or function (biology), function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medica ...
s that feature
nonspecific symptoms Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality showin ...
and may be confused with a number of other diseases.J.C. Segen.
The Dictionary of Modern Medicine
'. CRC Press; 1992. . p. 265.
The term connotes especially difficult
differential diagnosis In healthcare, a differential diagnosis (abbreviated DDx) is a method of analysis of a patient's history and physical examination to arrive at the correct diagnosis. It involves distinguishing a particular disease or condition from others that p ...
(DDx), especial potential for
misdiagnosis A medical error is a preventable adverse effect of care ("iatrogenesis"), whether or not it is evident or harmful to the patient. This might include an inaccurate or incomplete diagnosis or treatment of a disease, injury, syndrome, behavior, i ...
, and the
protean In Greek mythology, Proteus (; Ancient Greek: Πρωτεύς, ''Prōteus'') is an early prophetic sea-god or god of rivers and oceanic bodies of water, one of several deities whom Homer calls the "Old Man of the Sea" ''(hálios gérôn)''. ...
nature of some diseases. Most great imitators are
systemic Systemic fundamental to a predominant social, economic, or political practice. This refers to: In medicine In medicine, ''systemic'' means affecting the whole body, or at least multiple organ systems. It is in contrast with ''topical'' or ''loc ...
in nature or have systemic
sequela A sequela (, ; usually used in the plural, sequelae ) is a pathological condition resulting from a disease, injury, therapy, or other trauma. Derived from the Latin word, meaning “sequel”, it is used in the medical field to mean a complication ...
e, and an aspect of
nonspecific symptom Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality showin ...
s 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 Pathognomonic (rare synonym ''pathognomic'') is a term, often used in medicine, that means "characteristic for a particular disease". A pathognomonic sign is a particular sign whose presence means that a particular disease is present beyond any doub ...
turns out to be false, as the reality is that it is only nearly so. As recently as the 1950s,
syphilis Syphilis () is a sexually transmitted infection caused by the bacterium ''Treponema pallidum'' subspecies ''pallidum''. The signs and symptoms of syphilis vary depending in which of the four stages it presents (primary, secondary, latent, an ...
was widely considered by physicians to be "the great imitator", and in the next few decades after that, several other candidates, mainly
tuberculosis Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in ...
but occasionally others, were asserted as being "the second great imitator". But because
differential diagnosis In healthcare, a differential diagnosis (abbreviated DDx) is a method of analysis of a patient's history and physical examination to arrive at the correct diagnosis. It involves distinguishing a particular disease or condition from others that p ...
is inherently subject to occasional difficulty and to
false positives and false negatives A false positive is an error in binary classification in which a test result incorrectly indicates the presence of a condition (such as a disease when the disease is not present), while a false negative is the opposite error, where the test result ...
, 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 Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose belo ...
as an imitator of a stroke


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

*
Cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
s generally **
Intravascular large B-cell lymphoma Intravascular lymphomas (IVL) are rare cancers in which malignant lymphocytes proliferate and accumulate within blood vessels. Almost all other tyes of lymphoma involve the proliferation and accumulation of malignant lymphocytes in lymph nodes, ...
**
Mycosis fungoides Mycosis fungoides, also known as Alibert-Bazin syndrome or granuloma fungoides, is the most common form of cutaneous T-cell lymphoma. It generally affects the skin, but may progress internally over time. Symptoms include rash, tumors, skin lesion ...
** Malignant metastases *** Cutaneous metastases *
Oral cancer Oral cancer, also known as mouth cancer, is cancer of the lining of the lips, mouth, or upper throat. In the mouth, it most commonly starts as a painless white patch, that thickens, develops red patches, an ulcer, and continues to grow. When on ...
*
Pheochromocytoma Pheochromocytoma (PHEO or PCC) is a rare tumor of the adrenal medulla composed of chromaffin cells, also known as pheochromocytes. When a tumor composed of the same cells as a pheochromocytoma develops outside the adrenal gland, it is referred t ...
*
Paraneoplastic syndrome A paraneoplastic syndrome is a syndrome (a set of signs and symptoms) that is the consequence of a tumor in the body (usually a cancerous one), specifically due to the production of chemical signaling molecules (such as hormones or cytokines) by ...
s, in
endocrine oncology Endocrine oncology refers to a medical speciality dealing with hormone producing tumors, i.e. a combination of endocrinology and oncology. Few centres are specializing in hormone producing tumors only, due to the relatively low Incidence (epidemiol ...
: symptoms from any type of functioning (that is,
hormone A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...
-producing) endocrine tumor; such tumors secrete excess hormones in a way that is homeostatically senseless, thus disrupting
homeostasis In biology, homeostasis (British English, British also homoeostasis) Help:IPA/English, (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physics, physical, and chemistry, chemical conditions maintained by organism, living systems. Thi ...
(in any of many diverse ways, depending on which hormone, what dosage, and which location) ** Functioning
neuroendocrine tumor Neuroendocrine tumors (NETs) are neoplasms that arise from cells of the endocrine (hormonal) and nervous systems. They most commonly occur in the intestine, where they are often called carcinoid tumors, but they are also found in the pancreas, lun ...
s (NETs) *** Most generally, a caveat to obtain
PET-CT Positron emission tomography–computed tomography (better known as PET-CT or PET/CT) is a nuclear medicine technique which combines, in a single gantry, a positron emission tomography (PET) scanner and an x-ray computed tomography (CT) scann ...
in cases where
differential diagnosis In healthcare, a differential diagnosis (abbreviated DDx) is a method of analysis of a patient's history and physical examination to arrive at the correct diagnosis. It involves distinguishing a particular disease or condition from others that p ...
seems to be repeatedly failing, as PET can "see" NETs better than other imaging can *** Functioning
pancreatic neuroendocrine tumor Pancreatic neuroendocrine tumours (PanNETs, PETs, or PNETs), often referred to as "islet cell tumours", or "pancreatic endocrine tumours" are neuroendocrine neoplasms that arise from cells of the endocrine (hormonal) and nervous system within t ...
s (panNETs or pNETs) (example: intractable
diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...
resistant to differential diagnosis) *
Renal cell carcinoma Renal cell carcinoma (RCC) is a kidney cancer that originates in the lining of the proximal convoluted tubule, a part of the very small tubes in the kidney that transport primary urine. RCC is the most common type of kidney cancer in adults, resp ...
* See also: any mass effect inside the cranium (including from non-neoplastic causes)


Vitamin deficiency

*
Thiamine deficiency Thiamine deficiency is a medical condition of low levels of thiamine (Vitamin B1). A severe and chronic form is known as beriberi. The two main types in adults are wet beriberi and dry beriberi. Wet beriberi affects the cardiovascular system, r ...
(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 Hepatic encephalopathy (HE) is an altered level of consciousness as a result of liver failure. Its onset may be gradual or sudden. Other symptoms may include movement problems, changes in mood, or changes in personality. In the advanced stages ...
. Relatedly,
alcohol use disorder Alcoholism is, broadly, any drinking of alcohol that results in significant mental or physical health problems. Because there is disagreement on the definition of the word ''alcoholism'', it is not a recognized diagnostic entity. Predomin ...
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 Malnutrition occurs when an organism gets too few or too many nutrients, resulting in health problems. Specifically, it is "a deficiency, excess, or imbalance of energy, protein and other nutrients" which adversely affects the body's tissues a ...
in the classic senses of semi
starvation Starvation is a severe deficiency in caloric energy intake, below the level needed to maintain an organism's life. It is the most extreme form of malnutrition. In humans, prolonged starvation can cause permanent organ damage and eventually, dea ...
or
food insecurity Food security speaks to the availability of food in a country (or geography) and the ability of individuals within that country (geography) to access, afford, and source adequate foodstuffs. According to the United Nations' Committee on World F ...
but also in the sense of high-calorie malnutrition, even in people who do not use alcohol.
Hepatic encephalopathy Hepatic encephalopathy (HE) is an altered level of consciousness as a result of liver failure. Its onset may be gradual or sudden. Other symptoms may include movement problems, changes in mood, or changes in personality. In the advanced stages ...
is a wide-ranging topic that includes covert, subclinical, minimal, mild, nonalcoholic, alcoholic, moderate, and severe forms, just as (relatedly)
fatty liver disease Fatty liver disease (FLD), also known as hepatic steatosis, is a condition where excess fat builds up in the liver. Often there are no or few symptoms. Occasionally there may be tiredness or pain in the upper right side of the abdomen. Complicat ...
also has covert, subclinical, minimal, mild, nonalcoholic, alcoholic, moderate, and severe forms. At bottom, it is established that the
liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
's function and the
gut–brain axis The gut–brain axis is the two-way biochemical signaling that takes place between the gastrointestinal tract (GI tract) and the central nervous system (CNS). The term "gut–brain axis" is occasionally used to refer to the role of the gut micr ...
affect the brain and thus the mind, although not every
correlation In statistics, correlation or dependence is any statistical relationship, whether causal or not, between two random variables or bivariate data. Although in the broadest sense, "correlation" may indicate any type of association, in statistics ...
is understood.


Substance abuse

*
Substance abuse Substance abuse, also known as drug abuse, is the use of a drug in amounts or by methods which are harmful to the individual or others. It is a form of substance-related disorder. Differing definitions of drug abuse are used in public health, ...
can be confused with medical, psychiatric, and surgical conditions.


Rheumatic diseases (most with autoimmune components)

* Various rheumatic diseases, including: **
Fibromyalgia Fibromyalgia (FM) is a medical condition defined by the presence of chronic widespread pain, fatigue, waking unrefreshed, cognitive symptoms, lower abdominal pain or cramps, and depression. Other symptoms include insomnia and a general hyp ...
**
Psoriatic arthritis Psoriatic arthritis is a long-term inflammatory arthritis that occurs in people affected by the autoimmune disease psoriasis. The classic feature of psoriatic arthritis is swelling of entire fingers and toes with a sausage-like appearance. Thi ...
**
Lupus erythematosus Lupus erythematosus is a collection of autoimmune diseases in which the human immune system becomes hyperactive and attacks healthy tissues. Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blo ...
***
Systemic lupus erythematosus Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Comm ...
**
Gout Gout ( ) is a form of inflammatory arthritis characterized by recurrent attacks of a red, tender, hot and swollen joint, caused by deposition of monosodium urate monohydrate crystals. Pain typically comes on rapidly, reaching maximal intensit ...
* A general theme with
autoimmune disease An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...
s is that strange signs and symptoms can result (and can make
differential diagnosis In healthcare, a differential diagnosis (abbreviated DDx) is a method of analysis of a patient's history and physical examination to arrive at the correct diagnosis. It involves distinguishing a particular disease or condition from others that p ...
difficult) "whenever the body is attacking its own cells in unusual ways"


Dysplastic diseases, some with precancerous or rheumatologic aspects

*
Sarcoidosis Sarcoidosis (also known as ''Besnier-Boeck-Schaumann disease'') is a disease involving abnormal collections of inflammatory cells that form lumps known as granulomata. The disease usually begins in the lungs, skin, or lymph nodes. Less commonly af ...
*
Endometriosis Endometriosis is a disease of the female reproductive system in which cells similar to those in the endometrium, the layer of tissue that normally covers the inside of the uterus, grow outside the uterus. Most often this is on the ovaries, f ...
, often misdiagnosed


Neurologic disorders

*
Multiple sclerosis Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This d ...


Gut diseases

*
Celiac disease Coeliac disease (British English) or celiac disease (American English) is a long-term autoimmune disorder, primarily affecting the small intestine, where individuals develop intolerance to gluten, present in foods such as wheat, rye and barl ...
* Closely related to gut function is liver function; see information on vitamin bioactivity


Abdominal inflammations or their mimics

*
Appendicitis Appendicitis is inflammation of the appendix. Symptoms commonly include right lower abdominal pain, nausea, vomiting, and decreased appetite. However, approximately 40% of people do not have these typical symptoms. Severe complications of a rup ...
or its mimics *
Pancreatitis Pancreatitis is a condition characterized by inflammation of the pancreas. The pancreas is a large organ behind the stomach that produces digestive enzymes and a number of hormones. There are two main types: acute pancreatitis, and chronic pancr ...


Endocrine disorders

* Adrenal insufficiency, especially
Addison's disease Addison's disease, also known as primary adrenal insufficiency, is a rare long-term endocrine disorder characterized by inadequate production of the steroid hormones cortisol and aldosterone by the two outer layers of the cells of the adrenal ...
*
Hypothyroidism Hypothyroidism (also called ''underactive thyroid'', ''low thyroid'' or ''hypothyreosis'') is a disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormone. It can cause a number of symptoms, such as po ...
* Endocrine tumors: see tumor information * A general theme with
endocrine disease Endocrine diseases are disorders of the endocrine system. The branch of medicine associated with endocrine disorders is known as endocrinology. Types of disease Broadly speaking, endocrine disorders may be subdivided into three groups: # Endocrin ...
s is that strange signs and symptoms can result (and can make
differential diagnosis In healthcare, a differential diagnosis (abbreviated DDx) is a method of analysis of a patient's history and physical examination to arrive at the correct diagnosis. It involves distinguishing a particular disease or condition from others that p ...
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 Pulmonary embolism (PE) is a blockage of an pulmonary artery, artery in the lungs by a substance that has moved from elsewhere in the body through the bloodstream (embolism). Symptoms of a PE may include dyspnea, shortness of breath, chest pain p ...
*
Stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
, stroke mimics, and stroke chameleons **
Hypoglycemia Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose belo ...
as an imitator of a
stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...


Infectious diseases

* Various
infectious diseases An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...
, including: **
Syphilis Syphilis () is a sexually transmitted infection caused by the bacterium ''Treponema pallidum'' subspecies ''pallidum''. The signs and symptoms of syphilis vary depending in which of the four stages it presents (primary, secondary, latent, an ...
**
Lyme disease Lyme disease, also known as Lyme borreliosis, is a vector-borne disease caused by the ''Borrelia'' bacterium, which is spread by ticks in the genus ''Ixodes''. The most common sign of infection is an expanding red rash, known as erythema migran ...
, 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 Nocardiosis is an infectious disease affecting either the lungs (''pulmonary nocardiosis'') or the whole body (''systemic nocardiosis''). It is due to infection by a bacterium of the genus '' Nocardia'', most commonly ''Nocardia asteroides'' or '' ...
**
Tuberculosis Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in ...
***
Pulmonary tuberculosis Tuberculosis (TB) is an infectious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in w ...
*** Cutaneous tuberculosis **
Brucellosis Brucellosis is a highly contagious zoonosis caused by ingestion of unpasteurized milk or undercooked meat from infected animals, or close contact with their secretions. It is also known as undulant fever, Malta fever, and Mediterranean fever. The ...
**
Infective endocarditis Infective endocarditis is an infection of the inner surface of the heart, usually the valves. Signs and symptoms may include fever, small areas of bleeding into the skin, heart murmur, feeling tired, and low red blood cell count. Complications ...
**
Malaria Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. S ...
**
Leprosy Leprosy, also known as Hansen's disease (HD), is a long-term infection by the bacteria ''Mycobacterium leprae'' or ''Mycobacterium lepromatosis''. Infection can lead to damage of the nerves, respiratory tract, skin, and eyes. This nerve damag ...
**
Leishmaniasis Leishmaniasis is a wide array of clinical manifestations caused by parasites of the trypanosome genus ''Leishmania''. It is generally spread through the bite of phlebotomine sandflies, ''Phlebotomus'' and ''Lutzomyia'', and occurs most freq ...
** Viral
exanthem An exanthem is a widespread rash occurring on the outside of the body and usually occurring in children. An exanthem can be caused by toxins, drugs, or microorganisms, or can result from autoimmune disease. The term exanthem is from the Greek ...
s in children ** Gastrointestinal infections: when appendicitis or pancreatitis have infectious causes


Breathing-related sleep disorders (sleep-disordered breathing)

*
Sleep apnea Sleep apnea, also spelled sleep apnoea, is a sleep disorder in which pauses in breathing or periods of shallow breathing during sleep occur more often than normal. Each pause can last for a few seconds to a few minutes and they happen many times ...
/
hypopnea Hypopnea is overly shallow breathing or an abnormally low respiratory rate. Hypopnea is defined by some to be less severe than apnea (the complete cessation of breathing), while other researchers have discovered hypopnea to have a "similar if n ...
* Upper airway resistance syndrome


Proteinopathies

*
Amyloidosis Amyloidosis is a group of diseases in which abnormal proteins, known as amyloid fibrils, build up in tissue. There are several non-specific and vague signs and symptoms associated with amyloidosis. These include fatigue, peripheral edema, weight ...


Mass effect inside the cranium

* Any
mass effect ''Mass Effect'' is a military science fiction media franchise created by Casey Hudson, Drew Karpyshyn and Preston Watamaniuk. The franchise depicts a distant future where humanity and several alien civilizations have colonized the known univers ...
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 Hydrocephalus is a condition in which an accumulation of cerebrospinal fluid (CSF) occurs within the brain. This typically causes increased intracranial pressure, pressure inside the skull. Older people may have headaches, double vision, poor ...
, 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 Intracranial hemorrhage (ICH), also known as intracranial bleed, is bleeding within the skull. Subtypes are intracerebral bleeds ( intraventricular bleeds and intraparenchymal bleeds), subarachnoid bleeds, epidural bleeds, and subdural bleeds. ...
: see thromboembolic events or their mimics **
Brain tumor A brain tumor occurs when abnormal cells form within the brain. There are two main types of tumors: malignant tumors and benign (non-cancerous) tumors. These can be further classified as primary tumors, which start within the brain, and seconda ...
: see
Tumors A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...


Skin conditions

*
Scabies Scabies (; also sometimes known as the seven-year itch) is a contagious skin infestation by the mite ''Sarcoptes scabiei''. The most common symptoms are severe itchiness and a pimple-like rash. Occasionally, tiny burrows may appear on the skin ...


References

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