Differential diagnosis

Encyclopedia

A

, or at least, rendering of the probabilities of candidate conditions to negligible levels. In this sense, probabilities are, in fact, imaginative parameters in the mind or hardware of the diagnostician or system, while in reality the target (such as a patient) either has a condition or not with an actual probability of either 0 or 100%.

Differential diagnostic procedures are used by physician

s, psychiatrists

, and other trained medical professionals to diagnose

the specific disease

in a patient

, or, at least, to eliminate any imminently life-threatening conditions.

Differential diagnosis can be regarded as implementing aspects of the hypothetico-deductive method in the sense that the potential presence of candidate diseases or conditions can be viewed as hypotheses which are further processed as being true or false.

A differential diagnostic procedure can be performed by that the doctor first gathers all information about the patient and create a symptoms list. The list can be in writing or in the doctor's head, as long as he or she makes a list. Second, the doctor should make a list of all possible causes (also termed "candidate conditions") of the symptoms. Again, this can be in writing or in the doctor's head but it must be done. Third, the doctor should prioritize the list by placing the most urgently dangerous possible cause of the symptoms at the top of the list. Fourth, the doctor should rule out or treat the possible causes beginning with the most urgently dangerous condition and working his or her way down the list. "Rule out" practically means to use tests and other scientific methods to render a condition of clinically negligible probability of being the cause.

In some cases, there will remain

Mnemonic

s are routinely taught to medical students to ensure that all possible pathological processes are considered, for example

,

,

/

,

/

,

/

,

,

s).

For example, in case of medical emergency

, there may not be enough time to do any detailed calculations or estimations of different probabilities, in which case the ABC protocol may be more appropriate. At a later, less acute, situation, there may be a switch to a more comprehensive differential diagnostic procedure.

The differential diagnostic procedure may be easier in the finding of a

for further actions.

, where:

The total probability of the presentation to have occurred in the individual can be approximated as the sum of the individual candidate conditions:

Also, the probability of the presentation to have been caused by any candidate condition is proportional to the probability of the condition, depending on what rate it causes the presentation:

, where:

The probability that a condition would have occurred in the first place in an individual is approximately equal to that of a population that is as similar to the individual as possible except for the current presentation, compensated where possible by relative risk

s given by known risk factor

that distinguish the individual from the population:

, where:

**differential diagnosis**(sometimes abbreviated**DDx**,**ddx**,**DD**,**D/Dx**, or**ΔΔ**) is a systematic diagnostic method used to identify the presence of an entity where multiple alternatives are possible (and the process may be termed**differential diagnostic procedure**), and may also refer to any of the included candidate alternatives (which may also be termed**candidate condition**). This method is essentially a process of eliminationProcess of elimination

Process of elimination is a method to identify an entity of interest among several ones by excluding all other entities.-In education testing:...

, or at least, rendering of the probabilities of candidate conditions to negligible levels. In this sense, probabilities are, in fact, imaginative parameters in the mind or hardware of the diagnostician or system, while in reality the target (such as a patient) either has a condition or not with an actual probability of either 0 or 100%.

Differential diagnostic procedures are used by physician

Physician

A physician is a health care provider who practices the profession of medicine, which is concerned with promoting, maintaining or restoring human health through the study, diagnosis, and treatment of disease, injury and other physical and mental impairments...

s, psychiatrists

Psychiatry

Psychiatry is the medical specialty devoted to the study and treatment of mental disorders. These mental disorders include various affective, behavioural, cognitive and perceptual abnormalities...

, and other trained medical professionals to diagnose

Medical diagnosis

Medical diagnosis refers both to the process of attempting to determine or identify a possible disease or disorder , and to the opinion reached by this process...

the specific disease

Disease

A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...

in a patient

Patient

A patient is any recipient of healthcare services. The patient is most often ill or injured and in need of treatment by a physician, advanced practice registered nurse, veterinarian, or other health care provider....

, or, at least, to eliminate any imminently life-threatening conditions.

Differential diagnosis can be regarded as implementing aspects of the hypothetico-deductive method in the sense that the potential presence of candidate diseases or conditions can be viewed as hypotheses which are further processed as being true or false.

## General components

There are various methods of performing a differential diagnostic procedure, but in general, it is based on the idea that one begins by first considering the most common diagnosis first: a head cold versus meningitis, for example. As a reminder, medical students are taught the adage, "When you hear hoofbeats, look for horses, not zebras," which means look for the simplest, most common explanation first. Only after the simplest diagnosis has been ruled out should the clinician consider more complex or exotic diagnoses.A differential diagnostic procedure can be performed by that the doctor first gathers all information about the patient and create a symptoms list. The list can be in writing or in the doctor's head, as long as he or she makes a list. Second, the doctor should make a list of all possible causes (also termed "candidate conditions") of the symptoms. Again, this can be in writing or in the doctor's head but it must be done. Third, the doctor should prioritize the list by placing the most urgently dangerous possible cause of the symptoms at the top of the list. Fourth, the doctor should rule out or treat the possible causes beginning with the most urgently dangerous condition and working his or her way down the list. "Rule out" practically means to use tests and other scientific methods to render a condition of clinically negligible probability of being the cause.

In some cases, there will remain

*no*diagnosis; this suggests the physician has made an error, or that the true diagnosis is unknown to medicine. Removing diagnoses from the list is done by making observations and using tests that should have different results, depending on which diagnosis is correct.Mnemonic

Mnemonic

A mnemonic , or mnemonic device, is any learning technique that aids memory. To improve long term memory, mnemonic systems are used to make memorization easier. Commonly encountered mnemonics are often verbal, such as a very short poem or a special word used to help a person remember something,...

s are routinely taught to medical students to ensure that all possible pathological processes are considered, for example

*VINDICATE*:**V**ascularVascular disease

Vascular disease is a form of cardiovascular disease primarily affecting the blood vessels.Some conditions, such as angina and myocardial ischemia, can be considered both vascular diseases and heart diseases .Cigarette smoking is the major risk factor....

,

**I**nflammatoryInflammation

Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...

,

**N**eoplastic,**D**egenerativeDegenerative disease

A degenerative disease, also called neurodegenerative disease, is a disease in which the function or structure of the affected tissues or organs will progressively deteriorate over time, whether due to normal bodily wear or lifestyle choices such as exercise or eating habits...

/

**D**efficiencyDeficiency (medicine)

In medicine, a deficiency is a lack or shortage of a functional entity, by less than normal or necessary supply or function.-Nutrients:Malnutrition can cause various effects by deficiency of one or more nutrients...

,

**I**diopathicIdiopathic

Idiopathic is an adjective used primarily in medicine meaning arising spontaneously or from an obscure or unknown cause. From Greek ἴδιος, idios + πάθος, pathos , it means approximately "a disease of its own kind". It is technically a term from nosology, the classification of disease...

/

**I**ntoxication,**C**ongenitalCongenital disorder

A congenital disorder, or congenital disease, is a condition existing at birth and often before birth, or that develops during the first month of life , regardless of causation...

,

**A**utoimmuneAutoimmune disease

Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body actually attacks its own cells. The immune system mistakes some part of the body as a pathogen and attacks it. This may be restricted to...

/

**A**llergicAllergy

An Allergy is a hypersensitivity disorder of the immune system. Allergic reactions occur when a person's immune system reacts to normally harmless substances in the environment. A substance that causes a reaction is called an allergen. These reactions are acquired, predictable, and rapid...

,

**T**raumaticTrauma (medicine)

Trauma refers to "a body wound or shock produced by sudden physical injury, as from violence or accident." It can also be described as "a physical wound or injury, such as a fracture or blow." Major trauma can result in secondary complications such as circulatory shock, respiratory failure and death...

,

**E**ndocrineEndocrine disease

Endocrine diseases are disorders of the endocrine system. The branch of medicine associated with endocrine disorders is known as endocrinology.-Types of endocrine disease:Broadly speaking, endocrine disorders may be subdivided into three groups:...

## Specific methods

There are several methods for performing a differential diagnostic procedure, and several variants among those in turn. Furthermore, a differential diagnostic procedure can be used concomitantly or switchingly with protocols, guidelines or other diagnostic procedures (such as pattern-recognition or using medical algorithmMedical algorithm

A medical algorithm is any computation, formula, statistical survey, nomogram, or look-up table, useful in healthcare. Medical algorithms include decision tree approaches to healthcare treatment and also less clear-cut tools aimed at reducing or defining uncertainty.-Scope:Medical algorithms are...

s).

For example, in case of medical emergency

Medical emergency

A medical emergency is an injury or illness that is acute and poses an immediate risk to a person's life or long term health. These emergencies may require assistance from another person, who should ideally be suitably qualified to do so, although some of these emergencies can be dealt with by the...

, there may not be enough time to do any detailed calculations or estimations of different probabilities, in which case the ABC protocol may be more appropriate. At a later, less acute, situation, there may be a switch to a more comprehensive differential diagnostic procedure.

The differential diagnostic procedure may be easier in the finding of a

*pathognomonic*

sign or symptom, in which it is almost certain that the target condition is present, and in the absence of finding aPathognomonic

Pathognomonic 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 doubt...

*sine qua non*

sign or symptom, in which case it is almost certain that the target condition is absent. In reality, however, the subjective probability of the presence of a condition is never exactly 100% or 0%, so in reality the procedure is usually aimed at specifying the various probabilities in order to form indicationsSine qua non

Sine qua non or condicio sine qua non refers to an indispensable and essential action, condition, or ingredient...

Indication (medicine)

In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. The opposite of indication is contraindication.-Drugs:...

for further actions.

### By epidemiology

One method of performing a differential diagnosis by epidemiology aims to estimate the probability of each candidate condition by comparing their probabilities to have occurred in the first place in the individual. It is based on probabilities related both to the presentation (such as pain) and probabilities of the various candidate conditions (such as diseases).#### Theory

The probability that a presentation or condition would have occurred in the first place in an individual is not same as the probability that the presentation or condition*has*occurred in the individual, because the presentation*has*occurred by 100% certainty in the individual. Yet, the contributive probability fractions of each condition are assumed to be the same, relatively:, where:

*P(Presentation is caused by condition in individual)*is the probability that the presentation is caused by condition in the individual*condition*without further specification refers to any candidate condition*P(Presentation has occurred in individual)*is the probability that the presentation has occurred in the individual, which is 100%*P(Presentation WHOIFPI by condition)*is the probability that the presentation Would Have Occurred In the First Place in the Individual by condition*P(Presentation WHOIFPI)*is the probability that the presentation Would Have Occurred In the First Place in the Individual

*P(Presentation has occurred in individual)*is 100% and can therefore be replaced by 1, and can be ignored since division by 1 does not make any difference:The total probability of the presentation to have occurred in the individual can be approximated as the sum of the individual candidate conditions:

Also, the probability of the presentation to have been caused by any candidate condition is proportional to the probability of the condition, depending on what rate it causes the presentation:

, where:

*P(Presentation WHOIFPI by condition)*is the probability that the presentation Would Have Occurred In the First Place in the Individual by condition*P(Condition WHOIFPI)*is the probability that the condition Would Have Occurred In the First Place in the Individual- r
_{Condition→presentation}is the rate for which condition causes the presentation, that is, the fraction of people with condition that manifest with the presentation

The probability that a condition would have occurred in the first place in an individual is approximately equal to that of a population that is as similar to the individual as possible except for the current presentation, compensated where possible by relative risk

Relative risk

In statistics and mathematical epidemiology, relative risk is the risk of an event relative to exposure. Relative risk is a ratio of the probability of the event occurring in the exposed group versus a non-exposed group....

s given by known risk factor

Risk factor

In epidemiology, a risk factor is a variable associated with an increased risk of disease or infection. Sometimes, determinant is also used, being a variable associated with either increased or decreased risk.-Correlation vs causation:...

that distinguish the individual from the population:

, where:

*P(Condition WHOIFPI)*is the probability that the condition Would Have Occurred In the First Place in the Individual*RR*is the relative risk_{condition}Relative riskIn statistics and mathematical epidemiology, relative risk is the risk of an event relative to exposure. Relative risk is a ratio of the probability of the event occurring in the exposed group versus a non-exposed group....

for condition conferred by known risk factorRisk factorIn epidemiology, a risk factor is a variable associated with an increased risk of disease or infection. Sometimes, determinant is also used, being a variable associated with either increased or decreased risk.-Correlation vs causation:...

s in the individual that are not present in the population*P(Condition in population) is the probability that the condition occurs in a population that is as similar to the individual as possible except for the presentation*

The following table demonstrates how these relations can be made for a series of candidate conditions:

One additional "candidate condition" is the instance of there being no abnormality, and the presentation is only a (usually relatively unlikely) appearance of a basically normal state. Its probability in the population (P(No abnormality in population)) is complementary to the sum of probabilities of "abnormal" candidate conditions.

s, while in reality there are often simply rough estimations, such as of likelihoods being "very high", "high", "low" or "very low", but still using the general principles of the method.

For an individual (who becomes the "patient" in this example), a blood test

of, for example, serum calcium shows a result just above the standard reference range, which, by most definitions, classifies as hypercalcemia, which becomes the "presentation" in this case. A physician (who becomes the "diagnostician" in this example), who does not currently see the patient, gets to know about his finding.

By practical reasons, the physician considers that there is enough test indication to have a look at the patient’s medical record

s. For simplicity, let’s say that the only information given in the medical records is a family history

of primary hyperparathyroidism

(here abbreviated as PH), which may explain the finding of hypercalcemia. For this patient, let’s say that the resultant hereditary risk factor

is estimated to confer a relative risk

of 10 (RR

The physician considers that there is enough motivation to perform a differential diagnostic procedure for the finding of hypercalcemia. The main causes of hypercalcemia are primary hyperparathyroidism

(PH) and cancer

, so for simplicity, the list of candidate conditions that the physician could think of can be given as:

The the probability that

Let’s say that the last blood test taken by the patient was half a year ago and was normal, and that the incidence of primary hyperparathyroidism in a general population that appropriately matches the individual (except for the presentation and mentioned heredity) is 1 in 4000 per year. Ignoring more detailed retrospective analyses (such as including speed of disease progress and lag time of medical diagnosis), the time-at-risk for having developed primary hyperparathyroidism can roughly be regarded as being the last half year, because a previously developed hypercalcemia would probably have been caught up by the previous blood test. This corresponds to a probability of primary hyperparathyroidism (PH) in the population of:

With the relative risk conferred from the family history, the probability that primary hyperparathyroidism (PH) would have occurred in the first place in the individual given from the currently available information becomes:

Primary hyperparathyroidism can be assumed to cause hypercalcemia in essentially 100% of the time (r

For

For simplicity, let’s say that any association between a family history of primary hyperparathyroidism and risk of cancer is ignored, so the relative risk for the individual to have contracted cancer in the first place is similar to that of the population (RR

However, hypercalcemia only occurs in, very approximately, 10% of cancers, (r

The probabilities that hypercalcemia would have occurred in the first place by other candidate conditions can be calculated in a similar manner. However, for simplicity, let’s say that that the probability that any of these would have occurred in the first place is calculated to be 0.0005 in this example.

For the instance of there being

The probability that the individual would be healthy in the first place can be assumed to be the same:

The rate at which the case of no abnormal condition still ends up in a measurement of serum calcium of being above the standard reference range (thereby classifying as hypercalcemia) is, by the definition of standard reference range, less than 2.5%. However, this probability can be further specified by considering how much the measurement deviates from the mean in the standard reference range. Let’s say that the serum calcium measurement was 1.30 mmol/L, which, with a standard reference range established at 1.05 to 1.25 mmol/L, corresponds to a standard score of 3 and a corresponding probability of 0.14% that such degree of hypercalcemia would have occurred in the first place in the case of no abnormality:

Subsequently, the probability that hypercalemia would have resulted from no disease can be calculated as:

The probability that hypercalcemia would have occurred in the first place in the individual can thus be calculated as:

Subsequently, the probability that hypercalcemia is caused by primary hyperparathyroidism (PH) in the individual can be calculated as:

Similarly, the probability that hypercalcemia is caused by cancer in the individual can be calculated as:

, and for other candidate conditions:

, and the probability that there actually is no disease:

For clarification, these calculations are given as the table in the method description:

Thus, this method estimates that the probabilities that the hypercalcemia is caused by primary hyperparathyroidism, cancer, other conditions or no disease at all are 37.3%, 6.0%, 14.9% and 41.8%, respectively, which may be used in estimating further test indications.

This case is continued in the example of the method described in the next section.

in favor of the condition, and one probability that is relative to the entire profile of conditions and their odds respectively.

, where:

The profile-relative probabilities correspond to the probabilities of each condition of causing the presentation (P(Presentation is caused by condition in individual)), and are more clinically useful than the individually calculated odds, similarly to that the probabilities of conditions having occurred are more clinically useful than that the conditions would have occurred in the first place as mentioned in the epidemiology-based method. Therefore, it is the profile-relative probabilities that are used for estimating the indications

for further medical test

s, treatments or other actions in this method.

If there is an indication for a test, and it returns with a result, then the procedure is repeated by making new estimations of independently calculated odds for candidate conditions where they have likely changed, in turn likely resulting in a different sum of all independently calculated odds, and thereby different profile-relative probabilities. With different profile-relative probabilities, the indications for further tests, treatments or other actions have changed as well, and are therefore estimated anew, and so the procedure can be repeated until an end point where there no longer is any indication for currently performing further actions. Such an end point mainly occurs when one candidate condition becomes so certain that no test can be found that is powerful enough to change the relative probability-profile enough to motivate any current change in further actions. Tactics for reaching such an end point with as few tests as possible includes making tests with high specificity

for conditions of already outstandingly high profile-relative probability, because the high likelihood ratio positive for such tests is very high, bringing all less likely conditions to relatively lower probabilities. Alternatively, tests with high sensitivity

for competing candidate conditions, such tests have a high likelihood ratio negative, potentially bringing the probabilities for competing candidate conditions to negligible levels. If such negligible probabilities are achieved, these conditions can be decided to be ruled out, and the differential diagnostic procedure continues with only the remaining candidate conditions.

If two conditions appear as certain by their independently calculated probabilities, then there is a strong indication that the condition is a combination of the two, which can be added to the list of candidate conditions and be calculated independently for further evaluation.

Comparing to the previously mentioned epidemiology-based method, this method can be used with much more ease for including additional tests. However, this method is not so good at establishing initial probabilities, but can, on the other hand, be a good complementing method upon which to continue previously calculated probabilities from, for example, an epidemiology-based method.

The probabilities that the presentation would have occurred in the first place for each condition ("P(Presentation WHOIFPI by condition) can initially be set as the individually calculated probabilities, and the resultant probabilities of each condition of causing the presentation can initially be set as the profile relative probabilities:

The condition of highest profile-relative probability (except “no disease”) is primary hyperparathyroidismPrimary hyperparathyroidism causes hypercalcemia through the excessive secretion of parathyroid hormone , usually by an adenoma of the parathyroid glands.-Epidemiology:...

(PH), but cancer is still of major concern, because if it is the actual causative condition for the hypercalcemia, then the choice of whether to treat or not likely means life or death for the patient, in effect potentially putting the indication at a similar level for further tests for both of these conditions. Because the

Here, let’s say that the physician considers the profile-relative probabilities of being of enough concern to indicate to send the patient a call for a doctor's visit

, with an additional visit to the medical laboratory

for an additional blood test complemented with further analyses, including parathyroid hormone

for the suspicion of primary hyperparathyroidism.

For simplicity, let’s say that the doctor first receives the result for the parathyroid hormone analysis, and that it showed a parathyroid hormone level that is elevated relatively to what would be expected by the calcium level.

Such a constellation can be estimated to have a sensitivity

of approximately 70% and a specificitySensitivity and specificity are statistical measures of the performance of a binary classification test, also known in statistics as classification function. Sensitivity measures the proportion of actual positives which are correctly identified as such Sensitivity and specificity are statistical...

of approximately 90% for primary hyperparathyroidism. This confers a likelihood ratio positive of 7 for primary hyperparathyroidism.

The target value in this method is the independently calculated odds in favor of primary hyperparathyroidism, denoted

, where:

Here, the difference between odds and probability is negligible because the value is very low.

The same can be done for the other candidate conditions, also resulting in negligible differences between odds and probabilities (although such differences can be substantial at higher values):

With the likelihood ratio positive of 7 for the calcium- and parathyroid hormone related test, the post-test odds is calculated as:

, where:

Subsequently, the sum of all independently calculated odds after the calcium- and parathyroid hormone related test becomes:

The profile-relative probability for primary hyperparathyroidism (PH) after this test is calculated as:

, where:

These are calculated similarly for the other conditions, but in this case with independently calculated post-test odds being same as pre-test odds, resulting as:

These “new” percentages, including a profile-relative probability of 80% for primary hyperparathyroidism, underlie any indications for further tests, treatments or other actions. In this case, let's say that the physician continues the plan for the patient to attend a doctor's visit

for further checkup, especially focused at primary hyperparathyroidism.

A doctor's visit can, theoretically, be regarded as a series of tests, including both questions in a medical history

and components of a physical examination

, where the post-test probability of a previous test can be used as the pre-test probability of the next. The indications for choosing the next test is dynamically influenced by the results of previous tests.

Let's say that the patient in this example is revealed to have depression, bone pain, joint pain and constipation of more severerity than what would be expected by the hypercalcemia itself, supporting the suspicion of primary hyperparathyroidism, and let's say that the likelihood ratios for the tests, when multiplied together, roughly results in a product of 10 for primary hyperparathyroidism.

All the tests of the history and examination can concomitantly be used to estimate likelihood ratios for the presence of cancer, and let's say that the product of the likelihood ratios is estimated to be 3.

Tests for other conditions were basically all negative, and let's say that the resultant probability after the history and examination becomes 0.0005.

Continuing from the calcium- and parathyroid hormone related test, its post-test independently calculated odds are used as pre-test independently calculated odds for the medical history and physical examination (here abbreviated as H&E), with the ensuing calculations following the same overall pattern as the previous calcium- and parathyroid hormone related test:

These profile relative probabilities after the history and examination may make the physician confident enough to plan the patient for surgery for a parathyroidectomy

to resect the affected tissue.

At this point, the profile-relative probability of "other conditions" is so low that the physician cannot think of any test for them that could make a difference that would be substantial enough to form an indication for such a test, and the physician thereby regards "other conditions" as ruled out, in this case not primarily by specific test for such other conditions that were negative, but rather by the absence of positive tests so far.

For "cancer", the cutoff at which to confidently regard it as ruled out may be more stringent because of severe consequences of missing it, so the physician may consider that at least a histopathologic examination

of the resected tissue is indicated.

Let's say that the ensuing surgery and histopathologic examination

of the resected tissue confirms primary hyperparathyroidism, having a very high specificity, and let's say that it gives a likelihood ratio of 1000 in this case. However, let's also say that the histopathologic examination also showed a malignant pattern, and let's say that this pattern gives a likelihood ratio for cancer of 1000 as well. The resultant independently calculated odds in favor of primary hyperparathyroidism and cancer become 87.5 and 0.6, respectively, with profile-relative probabilities of 99.3% and 0.7%, respectively. However, at this point, the individually calculated odds in favor of cancer of 0.6, corresponding to an individually calculated probability of 37.5%, are high enough to consider that the patient actually has a combination of primary hyperparathyroidism and cancer, that is, in this case, parathyroid carcinoma

. To evaluate its possibility by this method, the combination can be added to the list of candidate conditions, followed by processing by every relevant test performed so far. By an initial method by epidemiology, the incidence of parathyroid carcinoma is estimated at about 1 in 6 million people per year, giving a very low probability before taking any tests into consideration. Still, the probability that a non-malignant primary hyperparathyroidism would have occurred at the same time as an unrelated non-carcinoma cancer that presents with malignant cells in the parathyroid gland is calculated by multiplying the probabilities of the two, resulting in a negligible probability in comparison. So, focusing on parathyroid carcinoma, let's say that a review in regard to the subsequent blood tests, medical history, physical examination, surgery observations and histopathological examination result in rather high likelihood ratios, in turn resulting in a profile-relative probability high enough for an indication for making a confirmatory test for parathyroid cancer. In reality, the histopathologist may have recognized parathyroid carcinoma by pattern-recognition directly and, with or without specific tissue processing, may have given a certain diagnostic opinion of parathyroid carcinoma.

Let's finally say that the diagnosis of parathyroid carcinoma resulted in an extended surgery that removed remaining malignant tissue before it had metastasized

, and the patient lived happily ever after.

to partly or fully make a differential diagnosis. It may be regarded as an application of artificial intelligence.

Many studies demonstrate improvement of quality of care and reduction of medical errors by using such decision support systems. Some of these systems are designed for a specific medical problem such as schizophrenia, Lyme disease or ventilator-associated pneumonia. Others such as Iliad, QMR, DiagnosisPro, and VisualDx are designed to cover all major clinical and diagnostic findings to assist physicians with faster and more accurate diagnosis.

However, these tools all still require advanced medical skills in order to rate the symptoms and choose additional tests to deduce the probabilities of different diagnoses. Thus, non-professionals still need to see a health care provider

in order to get a proper diagnosis.

. It is more systematic than the old-fashioned method of diagnosis by

to identify and classify organisms, living and extinct. For example, after finding an unknown species, there can first be a listing of all potential species, followed by ruling out of one by one until, optimally, only one potential choice remains.

The following table demonstrates how these relations can be made for a series of candidate conditions:

Candidate condition 1 | Candidate condition 2 | Candidate condition 3 | |

P(Condition in population) |
P(Condition 1 in population) |
P(Condition 2 in population) |
P(Condition 3 in population) |

RR_{condition} |
RR_{ 1} |
RR_{ 2} |
RR_{ 3} |

P(Condition WHOIFPI) |
P(Condition 1 WHOIFPI) |
P(Condition 2 WHOIFPI) |
P(Condition 3 WHOIFPI) |

r_{Condition→presentation} |
r_{Condition 1→presentation} |
r_{Condition 2→presentation} |
r_{Condition 3→presentation} |

P(Presentation WHOIFPI by condition) |
P(Presentation WHOIFPI by condition 1) |
P(Presentation WHOIFPI by condition 2) |
P(Presentation WHOIFPI by condition 3) |

P(Presentation WHOIFPI) = the sum of the probabilities in row just above | |||

P(Presentation is caused by condition in individual) | P(Presentation is caused by condition 1 in individual) | P(Presentation is caused by condition 2 in individual) | P(Presentation is caused by condition 3 in individual) |

One additional "candidate condition" is the instance of there being no abnormality, and the presentation is only a (usually relatively unlikely) appearance of a basically normal state. Its probability in the population (P(No abnormality in population)) is complementary to the sum of probabilities of "abnormal" candidate conditions.

#### Example

This example case is made to demonstrate how this method may be applied, but does not intend to be a guideline for handling similar cases in reality. Also, the example uses relatively specified numbers with sometimes several decimalDecimal

The decimal numeral system has ten as its base. It is the numerical base most widely used by modern civilizations....

s, while in reality there are often simply rough estimations, such as of likelihoods being "very high", "high", "low" or "very low", but still using the general principles of the method.

For an individual (who becomes the "patient" in this example), a blood test

Blood test

A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....

of, for example, serum calcium shows a result just above the standard reference range, which, by most definitions, classifies as hypercalcemia, which becomes the "presentation" in this case. A physician (who becomes the "diagnostician" in this example), who does not currently see the patient, gets to know about his finding.

By practical reasons, the physician considers that there is enough test indication to have a look at the patient’s medical record

Medical record

The terms medical record, health record, and medical chart are used somewhat interchangeably to describe the systematic documentation of a single patient's medical history and care across time within one particular health care provider's jurisdiction....

s. For simplicity, let’s say that the only information given in the medical records is a family history

Family history (medicine)

In medicine, a family history consists of information about disorders from which the direct blood relatives of the patient have suffered. Genealogy typically includes very little of the medical history of the family, but the medical history could be considered a specific subset of the total history...

of primary hyperparathyroidism

Primary hyperparathyroidism

Primary hyperparathyroidism causes hypercalcemia through the excessive secretion of parathyroid hormone , usually by an adenoma of the parathyroid glands.-Epidemiology:...

(here abbreviated as PH), which may explain the finding of hypercalcemia. For this patient, let’s say that the resultant hereditary risk factor

Risk factor

In epidemiology, a risk factor is a variable associated with an increased risk of disease or infection. Sometimes, determinant is also used, being a variable associated with either increased or decreased risk.-Correlation vs causation:...

is estimated to confer a relative risk

Relative risk

In statistics and mathematical epidemiology, relative risk is the risk of an event relative to exposure. Relative risk is a ratio of the probability of the event occurring in the exposed group versus a non-exposed group....

of 10 (RR

_{PH}= 10).The physician considers that there is enough motivation to perform a differential diagnostic procedure for the finding of hypercalcemia. The main causes of hypercalcemia are primary hyperparathyroidism

Primary hyperparathyroidism

Primary hyperparathyroidism causes hypercalcemia through the excessive secretion of parathyroid hormone , usually by an adenoma of the parathyroid glands.-Epidemiology:...

(PH) and cancer

Cancer

Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

, so for simplicity, the list of candidate conditions that the physician could think of can be given as:

- Primary hyperparathyroidism (PH)
- Cancer
- Other diseases that the physician could think of (which is simply termed "other conditions" for the rest of this example)
- No disease (or no abnormality), and the finding is caused entirely by statistical variability

The the probability that

**primary hyperparathyroidism**(PH) would have occurred in the first place in the individual (P(PH WHOIFPI)) can be calculated as follows:Let’s say that the last blood test taken by the patient was half a year ago and was normal, and that the incidence of primary hyperparathyroidism in a general population that appropriately matches the individual (except for the presentation and mentioned heredity) is 1 in 4000 per year. Ignoring more detailed retrospective analyses (such as including speed of disease progress and lag time of medical diagnosis), the time-at-risk for having developed primary hyperparathyroidism can roughly be regarded as being the last half year, because a previously developed hypercalcemia would probably have been caught up by the previous blood test. This corresponds to a probability of primary hyperparathyroidism (PH) in the population of:

With the relative risk conferred from the family history, the probability that primary hyperparathyroidism (PH) would have occurred in the first place in the individual given from the currently available information becomes:

Primary hyperparathyroidism can be assumed to cause hypercalcemia in essentially 100% of the time (r

_{PH &rarr hypercalcemia}= 1), so this independently calculated probability of primary hyperparathyroidism (PH) can be assumed to be the same as the probability of being a cause of the presentation:For

**cancer**, the same time-at-risk is assumed for simplicity, and let’s say that the incidence of cancer in the area is estimated at 1 in 250 per year, giving an population probability of cancer of:For simplicity, let’s say that any association between a family history of primary hyperparathyroidism and risk of cancer is ignored, so the relative risk for the individual to have contracted cancer in the first place is similar to that of the population (RR

_{cancer}= 1):However, hypercalcemia only occurs in, very approximately, 10% of cancers, (r

_{cancer &rarr hypercalcemia}= 0.1), so:The probabilities that hypercalcemia would have occurred in the first place by other candidate conditions can be calculated in a similar manner. However, for simplicity, let’s say that that the probability that any of these would have occurred in the first place is calculated to be 0.0005 in this example.

For the instance of there being

**no disease**, the corresponding probability in the population is complementary to the sum of probabilities for other conditions:The probability that the individual would be healthy in the first place can be assumed to be the same:

The rate at which the case of no abnormal condition still ends up in a measurement of serum calcium of being above the standard reference range (thereby classifying as hypercalcemia) is, by the definition of standard reference range, less than 2.5%. However, this probability can be further specified by considering how much the measurement deviates from the mean in the standard reference range. Let’s say that the serum calcium measurement was 1.30 mmol/L, which, with a standard reference range established at 1.05 to 1.25 mmol/L, corresponds to a standard score of 3 and a corresponding probability of 0.14% that such degree of hypercalcemia would have occurred in the first place in the case of no abnormality:

Subsequently, the probability that hypercalemia would have resulted from no disease can be calculated as:

The probability that hypercalcemia would have occurred in the first place in the individual can thus be calculated as:

Subsequently, the probability that hypercalcemia is caused by primary hyperparathyroidism (PH) in the individual can be calculated as:

Similarly, the probability that hypercalcemia is caused by cancer in the individual can be calculated as:

, and for other candidate conditions:

, and the probability that there actually is no disease:

For clarification, these calculations are given as the table in the method description:

PH | Cancer | Other conditions | No disease | |

P(Condition in population) |
0.000125 | 0.002 | - | 0.997 |

RR_{x} |
10 | 1 | - | - |

P(Condition WHOIFPI) |
0.00125 | 0.002 | - | - |

r_{Condition →hypercalcemia} |
1 | 0.1 | - | 0.0014 |

P(hypercalcemia WHOIFPI by condition) |
0.00125 | 0.0002 | 0.0005 | 0.0014 |

P(hypercalcemia WHOIFPI) = 0.00335 | ||||

P(hypercalcemia is caused by condition in individual) | 37.3% | 6.0% | 14.9% | 41.8% |

Thus, this method estimates that the probabilities that the hypercalcemia is caused by primary hyperparathyroidism, cancer, other conditions or no disease at all are 37.3%, 6.0%, 14.9% and 41.8%, respectively, which may be used in estimating further test indications.

This case is continued in the example of the method described in the next section.

### By independently and profile-relative probabilities

The procedure of differential diagnosis can become extremely complex if it would fully take additional tests and treatments into consideration. One method that is somewhat a tradeoff between being clinically perfect and being relatively simple to calculate is one that assigns two kinds of likelihood parameters for each disease or other condition that is included in the list of differential diagnoses; one independently calculated oddsOdds

The odds in favor of an event or a proposition are expressed as the ratio of a pair of integers, which is the ratio of the probability that an event will happen to the probability that it will not happen...

in favor of the condition, and one probability that is relative to the entire profile of conditions and their odds respectively.

#### Theory

For each candidate condition, this method first estimates an independently calculated odds in favor*, which initially corresponds to the probability that the individual would have developed the condition in the first place, as used in the previously mentioned method using epidemiology. If previously calculated as a probability, it can be converted to*odds in favor*by:*

These independently calculated odds in favor, in the format of their valueto one, are summed together in this method, and the resultant value is be used to estimate a profile-relative probability for each candidate condition, as follows:These independently calculated odds in favor, in the format of their value

, where:

- PRP
_{condition}is the profile-relative probability of a condition - ICO
_{condition}is the independently calculated odds in favor of a condition as a cause of the presentation - ICO
_{all}is the sum of all independently calculated odds in favor, of all candidate conditions

The profile-relative probabilities correspond to the probabilities of each condition of causing the presentation (P(Presentation is caused by condition in individual)), and are more clinically useful than the individually calculated odds, similarly to that the probabilities of conditions having occurred are more clinically useful than that the conditions would have occurred in the first place as mentioned in the epidemiology-based method. Therefore, it is the profile-relative probabilities that are used for estimating the indications

Indication (medicine)

In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. The opposite of indication is contraindication.-Drugs:...

for further medical test

Medical test

A diagnostic test is any kind of medical test performed to aid in the diagnosis or detection of disease. For example:* to diagnose diseases, and preferably sub-classify it regarding, for example, severity and treatability...

s, treatments or other actions in this method.

If there is an indication for a test, and it returns with a result, then the procedure is repeated by making new estimations of independently calculated odds for candidate conditions where they have likely changed, in turn likely resulting in a different sum of all independently calculated odds, and thereby different profile-relative probabilities. With different profile-relative probabilities, the indications for further tests, treatments or other actions have changed as well, and are therefore estimated anew, and so the procedure can be repeated until an end point where there no longer is any indication for currently performing further actions. Such an end point mainly occurs when one candidate condition becomes so certain that no test can be found that is powerful enough to change the relative probability-profile enough to motivate any current change in further actions. Tactics for reaching such an end point with as few tests as possible includes making tests with high specificity

Sensitivity and specificity

Sensitivity and specificity are statistical measures of the performance of a binary classification test, also known in statistics as classification function. Sensitivity measures the proportion of actual positives which are correctly identified as such Sensitivity and specificity are statistical...

for conditions of already outstandingly high profile-relative probability, because the high likelihood ratio positive for such tests is very high, bringing all less likely conditions to relatively lower probabilities. Alternatively, tests with high sensitivity

Sensitivity and specificity

Sensitivity and specificity are statistical measures of the performance of a binary classification test, also known in statistics as classification function. Sensitivity measures the proportion of actual positives which are correctly identified as such Sensitivity and specificity are statistical...

for competing candidate conditions, such tests have a high likelihood ratio negative, potentially bringing the probabilities for competing candidate conditions to negligible levels. If such negligible probabilities are achieved, these conditions can be decided to be ruled out, and the differential diagnostic procedure continues with only the remaining candidate conditions.

If two conditions appear as certain by their independently calculated probabilities, then there is a strong indication that the condition is a combination of the two, which can be added to the list of candidate conditions and be calculated independently for further evaluation.

Comparing to the previously mentioned epidemiology-based method, this method can be used with much more ease for including additional tests. However, this method is not so good at establishing initial probabilities, but can, on the other hand, be a good complementing method upon which to continue previously calculated probabilities from, for example, an epidemiology-based method.

#### Example

This example continues for the same patient as in the example for the epidemiology-based method. As with the previous example of epidemiology-based method, this example case is made to demonstrate how this method may be applied, but does not intend to be a guideline for handling similar cases in reality. Also, the example uses relatively specified numbers, while in reality there are often just rough estimations.The probabilities that the presentation would have occurred in the first place for each condition ("P(Presentation WHOIFPI by condition) can initially be set as the individually calculated probabilities, and the resultant probabilities of each condition of causing the presentation can initially be set as the profile relative probabilities:

PH Primary hyperparathyroidism Primary hyperparathyroidism causes hypercalcemia through the excessive secretion of parathyroid hormone , usually by an adenoma of the parathyroid glands.-Epidemiology:... |
Cancer | Other conditions | No disease | |

Independently calculated probability (ICP) | 0.00125 | 0.0002 | 0.0005 | 0.0014 |

Profile-relative probability (PRP) | 37.3% | 6.0% | 14.9% | 41.8% |

The condition of highest profile-relative probability (except “no disease”) is primary hyperparathyroidism

Primary hyperparathyroidism

(PH), but cancer is still of major concern, because if it is the actual causative condition for the hypercalcemia, then the choice of whether to treat or not likely means life or death for the patient, in effect potentially putting the indication at a similar level for further tests for both of these conditions. Because the

Here, let’s say that the physician considers the profile-relative probabilities of being of enough concern to indicate to send the patient a call for a doctor's visit

Doctor's visit

A doctor's visit, also known as "doctor's office visit" or "physician office visit", is a meeting between a patient with a physician to get health advice or treatment for a symptom or condition...

, with an additional visit to the medical laboratory

Medical laboratory

A medical laboratory or clinical laboratory is a laboratory where tests are done on clinical specimens in order to get information about the health of a patient as pertaining to the diagnosis, treatment, and prevention of disease.-Departments:...

for an additional blood test complemented with further analyses, including parathyroid hormone

Parathyroid hormone

Parathyroid hormone , parathormone or parathyrin, is secreted by the chief cells of the parathyroid glands as a polypeptide containing 84 amino acids...

for the suspicion of primary hyperparathyroidism.

For simplicity, let’s say that the doctor first receives the result for the parathyroid hormone analysis, and that it showed a parathyroid hormone level that is elevated relatively to what would be expected by the calcium level.

Such a constellation can be estimated to have a sensitivity

Sensitivity and specificity

Sensitivity and specificity are statistical measures of the performance of a binary classification test, also known in statistics as classification function. Sensitivity measures the proportion of actual positives which are correctly identified as such Sensitivity and specificity are statistical...

of approximately 70% and a specificity

Sensitivity and specificity

of approximately 90% for primary hyperparathyroidism. This confers a likelihood ratio positive of 7 for primary hyperparathyroidism.

The target value in this method is the independently calculated odds in favor of primary hyperparathyroidism, denoted

*Pre-CaP*because it corresponds to before (Latin preposition*prae*means before) the calcium- and parathyroid hormone related test., where:

*PreCaP ICO*is the independently calculated odds_{PH}OddsThe odds in favor of an event or a proposition are expressed as the ratio of a pair of integers, which is the ratio of the probability that an event will happen to the probability that it will not happen...

in favor of primary hyperparathyroidism before the calcium and parathyroid hormone related test*ICP*is the independently calculated probability_{PH}ProbabilityProbability is ordinarily used to describe an attitude of mind towards some proposition of whose truth we arenot certain. The proposition of interest is usually of the form "Will a specific event occur?" The attitude of mind is of the form "How certain are we that the event will occur?" The...

for primary hyperparathyroidism before the calcium and parathyroid hormone related test, previously given as 0.00125, resulting in:

Here, the difference between odds and probability is negligible because the value is very low.

The same can be done for the other candidate conditions, also resulting in negligible differences between odds and probabilities (although such differences can be substantial at higher values):

PH Primary hyperparathyroidism |
Cancer | Other conditions | No disease | |

Independently calculated probability (ICP) | 0.00125 | 0.0002 | 0.0005 | 0.0014 |

Pre-CaP ICO | 0.00125 | 0.0002 | 0.0005 | 0.0014 |

With the likelihood ratio positive of 7 for the calcium- and parathyroid hormone related test, the post-

, where:

*PostCaP ICO*is the independently calculated odds for primary hyperparathyroidism after the calcium and parathyroid hormone related test, given at 0.00125_{PH}*PreCaP ICO*is the independently calculated odds_{PH}OddsThe odds in favor of an event or a proposition are expressed as the ratio of a pair of integers, which is the ratio of the probability that an event will happen to the probability that it will not happen...

in favor of primary hyperparathyroidism before the calcium and parathyroid hormone related test*LH+*is the likelihood ratio positive for the test

Subsequently, the sum of all independently calculated odds after the calcium- and parathyroid hormone related test becomes:

The profile-relative probability for primary hyperparathyroidism (PH) after this test is calculated as:

, where:

*PostCaP PRP*is the profile-relative probability for primary hyperparathyroidism after the calcium and parathyroid hormone related test_{PH}*PostCaP ICO*is the sum of all independently calculated odds after the calcium- and parathyroid hormone related test_{all}*PostCaP ICO*is the independently calculated odds for primary hyperparathyroidism after the calcium and parathyroid hormone related test_{PH}

These are calculated similarly for the other conditions, but in this case with independently calculated post-test odds being same as pre-test odds, resulting as:

PH Primary hyperparathyroidism |
Cancer | Other conditions | No disease | |

PostCaP ICO | 0.00875 | 0.0002 | 0.0005 | 0.0014 |

PostCaP PRP | 80.6% | 1.8% | 4.6% | 12.9% |

These “new” percentages, including a profile-relative probability of 80% for primary hyperparathyroidism, underlie any indications for further tests, treatments or other actions. In this case, let's say that the physician continues the plan for the patient to attend a doctor's visit

Doctor's visit

A doctor's visit, also known as "doctor's office visit" or "physician office visit", is a meeting between a patient with a physician to get health advice or treatment for a symptom or condition...

for further checkup, especially focused at primary hyperparathyroidism.

A doctor's visit can, theoretically, be regarded as a series of tests, including both questions in a medical history

Medical history

The medical history or anamnesis of a patient is information gained by a physician by asking specific questions, either of the patient or of other people who know the person and can give suitable information , with the aim of obtaining information useful in formulating a diagnosis and providing...

and components of a physical examination

Physical examination

Physical examination or clinical examination is the process by which a doctor investigates the body of a patient for signs of disease. It generally follows the taking of the medical history — an account of the symptoms as experienced by the patient...

, where the post-test probability of a previous test can be used as the pre-test probability of the next. The indications for choosing the next test is dynamically influenced by the results of previous tests.

Let's say that the patient in this example is revealed to have depression, bone pain, joint pain and constipation of more severerity than what would be expected by the hypercalcemia itself, supporting the suspicion of primary hyperparathyroidism, and let's say that the likelihood ratios for the tests, when multiplied together, roughly results in a product of 10 for primary hyperparathyroidism.

All the tests of the history and examination can concomitantly be used to estimate likelihood ratios for the presence of cancer, and let's say that the product of the likelihood ratios is estimated to be 3.

Tests for other conditions were basically all negative, and let's say that the resultant probability after the history and examination becomes 0.0005.

Continuing from the calcium- and parathyroid hormone related test, its post-test independently calculated odds are used as pre-test independently calculated odds for the medical history and physical examination (here abbreviated as H&E), with the ensuing calculations following the same overall pattern as the previous calcium- and parathyroid hormone related test:

PH Primary hyperparathyroidism |
Cancer | Other conditions | No disease | |

PreH&E ICO | 0.00875 | 0.0002 | 0.0005 | 0.0014 |

Likelihood ratio by H&E | 10 | 3 | - | - |

PostH&E ICO | 0.0875 | 0.0006 | 0.0005 | 0.0014 |

PostH&E ICO_{all} |
0.09 | |||

PostH&E PRP | 97.2% | 0.7% | 0.6% | 1.6% |

These profile relative probabilities after the history and examination may make the physician confident enough to plan the patient for surgery for a parathyroidectomy

Parathyroidectomy

Also known as "Parathyroid gland removal", Parathyroidectomy is the surgical removal of one or more parathyroid glands. This procedure is used to remove primary tumors or hyperplasia of the glands, especially when they produce excessive parathyroid hormone. As drugs such as Fosamax do not treat the...

to resect the affected tissue.

At this point, the profile-relative probability of "other conditions" is so low that the physician cannot think of any test for them that could make a difference that would be substantial enough to form an indication for such a test, and the physician thereby regards "other conditions" as ruled out, in this case not primarily by specific test for such other conditions that were negative, but rather by the absence of positive tests so far.

For "cancer", the cutoff at which to confidently regard it as ruled out may be more stringent because of severe consequences of missing it, so the physician may consider that at least a histopathologic examination

Histopathology

Histopathology refers to the microscopic examination of tissue in order to study the manifestations of disease...

of the resected tissue is indicated.

Let's say that the ensuing surgery and histopathologic examination

Histopathology

Histopathology refers to the microscopic examination of tissue in order to study the manifestations of disease...

of the resected tissue confirms primary hyperparathyroidism, having a very high specificity, and let's say that it gives a likelihood ratio of 1000 in this case. However, let's also say that the histopathologic examination also showed a malignant pattern, and let's say that this pattern gives a likelihood ratio for cancer of 1000 as well. The resultant independently calculated odds in favor of primary hyperparathyroidism and cancer become 87.5 and 0.6, respectively, with profile-relative probabilities of 99.3% and 0.7%, respectively. However, at this point, the individually calculated odds in favor of cancer of 0.6, corresponding to an individually calculated probability of 37.5%, are high enough to consider that the patient actually has a combination of primary hyperparathyroidism and cancer, that is, in this case, parathyroid carcinoma

Parathyroid carcinoma

Parathyroid carcinoma is a rare cause of hypercalcemia. It forms in tissues of one or more of the parathyroid glands ....

. To evaluate its possibility by this method, the combination can be added to the list of candidate conditions, followed by processing by every relevant test performed so far. By an initial method by epidemiology, the incidence of parathyroid carcinoma is estimated at about 1 in 6 million people per year, giving a very low probability before taking any tests into consideration. Still, the probability that a non-malignant primary hyperparathyroidism would have occurred at the same time as an unrelated non-carcinoma cancer that presents with malignant cells in the parathyroid gland is calculated by multiplying the probabilities of the two, resulting in a negligible probability in comparison. So, focusing on parathyroid carcinoma, let's say that a review in regard to the subsequent blood tests, medical history, physical examination, surgery observations and histopathological examination result in rather high likelihood ratios, in turn resulting in a profile-relative probability high enough for an indication for making a confirmatory test for parathyroid cancer. In reality, the histopathologist may have recognized parathyroid carcinoma by pattern-recognition directly and, with or without specific tissue processing, may have given a certain diagnostic opinion of parathyroid carcinoma.

Let's finally say that the diagnosis of parathyroid carcinoma resulted in an extended surgery that removed remaining malignant tissue before it had metastasized

Metastasis

Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...

, and the patient lived happily ever after.

#### Finding candidate conditions

The validity of both methods described above are dependent of inclusion of candidate conditions that are responsible for as large part as possible of the probability of having developed the condition, and it's clinically important to include those where relatively fast initiation of therapy is most likely to result in greatest benefit. The need to find more candidate conditions for inclusion increases with increasing severity of the presentation itself. For example, if the only presentation is a deviating laboratory parameter and all common harmful underlying conditions have been ruled out, then it may be acceptable to stop finding more candidate conditions, but this would much more likely be unacceptable if the presentation would have been severe pain.## Machine differential diagnosis

Machine differential diagnosis is the use of computer softwareComputer software

Computer software, or just software, is a collection of computer programs and related data that provide the instructions for telling a computer what to do and how to do it....

to partly or fully make a differential diagnosis. It may be regarded as an application of artificial intelligence.

Many studies demonstrate improvement of quality of care and reduction of medical errors by using such decision support systems. Some of these systems are designed for a specific medical problem such as schizophrenia, Lyme disease or ventilator-associated pneumonia. Others such as Iliad, QMR, DiagnosisPro, and VisualDx are designed to cover all major clinical and diagnostic findings to assist physicians with faster and more accurate diagnosis.

However, these tools all still require advanced medical skills in order to rate the symptoms and choose additional tests to deduce the probabilities of different diagnoses. Thus, non-professionals still need to see a health care provider

Health care provider

A health care provider is an individual or an institution that provides preventive, curative, promotional or rehabilitative health care services in a systematic way to individuals, families or communities....

in order to get a proper diagnosis.

## History

The method of differential diagnosis was first suggested for use in the diagnosis of mental disorders by Emil KraepelinEmil Kraepelin

Emil Kraepelin was a German psychiatrist. H.J. Eysenck's Encyclopedia of Psychology identifies him as the founder of modern scientific psychiatry, as well as of psychopharmacology and psychiatric genetics. Kraepelin believed the chief origin of psychiatric disease to be biological and genetic...

. It is more systematic than the old-fashioned method of diagnosis by

*gestalt*

(impression).Gestalt therapy

Gestalt therapy is an existential/experiential form of psychotherapy that emphasizes personal responsibility, and that focuses upon the individual's experience in the present moment, the therapist-client relationship, the environmental and social contexts of a person's life, and the self-regulating...

## Alternative medical meanings

*Differential diagnosis*is also used more loosely, to refer simply to a list of the most common causes of a given symptom, to a list of disorders similar to a given disorder, or to such lists when they are annotated with advice on how to narrow the list down (the book*French's Index of Differential Diagnosis*, ISBN 0340810475, is an example). Thus, a differential diagnosis in this sense is medical information specially organized to aid in diagnosis.## Usage apart from in medicine

Methods similar to those of differential diagnostic processes in medicine are also is used by biological taxonomistsTaxonomy

Taxonomy is the science of identifying and naming species, and arranging them into a classification. The field of taxonomy, sometimes referred to as "biological taxonomy", revolves around the description and use of taxonomic units, known as taxa...

to identify and classify organisms, living and extinct. For example, after finding an unknown species, there can first be a listing of all potential species, followed by ruling out of one by one until, optimally, only one potential choice remains.

## See also

- List of medical symptoms
- Diagnosis of exclusionDiagnosis of exclusionA diagnosis of exclusion is a medical condition reached by a process of elimination, which may be necessary if presence cannot be established with complete confidence from examination or testing...
- ComorbidityComorbidityIn medicine, comorbidity is either the presence of one or more disorders in addition to a primary disease or disorder, or the effect of such additional disorders or diseases.- In medicine :...
- Dual diagnosisDual diagnosisThe term dual diagnosis is used to describe the comorbid condition of a person considered to be suffering from a mental illness and a substance abuse problem. There is considerable debate surrounding the appropriateness of the term being used to describe a heterogeneous group of individuals with...

## Further reading

- The
*Merck Manual of Diagnosis and Therapy*has 11 index entries describing the topic as differential diagnosis.Merck Manual of Diagnosis and TherapyThe Merck Manual of Diagnosis and Therapy, often called simply The Merck Manual, is the world's best-selling medical textbook. First published in 1899, it is now in its 19th edition.-Professional Edition:...