Made by DATEXIS (Data Science and Text-based Information Systems) at Beuth University of Applied Sciences Berlin
Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
Funded by The Federal Ministry for Economic Affairs and Energy; Grant: 01MD19013D, Smart-MD Project, Digital Technologies
List of symptoms that has been observed in those with autistic catatonia:
- Stupor
- Mutism
- Hyperactivity
- Agitation
- Excitement
- Posing
- Negativism
- Rigidity
- Waxy flexibility
- Automatic obedience
- Combativeness (during excitement)
- Aggressivity
- Stereotypies
- Tics
- Grimacing
- Echolalia
- Echopraxia
- Perseveration
- Verbigeration
- Staring
- Withdrawal
- Immobility
- Challenging behaviour
- Tremor
- Slowness
- Amotivation
- Grasp reflex
- Mannerism
- Gaze fixation
- Choreoathetoid movements of the trunk and extremities
- Autonomic instability (during excitement)
- Cannot start actions
- Cannot stop actions (if during excitement episodes needs acute psychiatric care)
- Freezing
- Impulsivity
- Bizarre/psychotic
- Sleep problems
- Urinary or Fecal incontinence
- Odd gait
- Passivity
- Reversal of day and night
- Eyerolling
- Stiff muscles
- Catalepsy
- Physiological pillow
- Difficulty crossing lines
- Gegenhalten
- Mitgehen
- Mitmachen
- Ambitendency
- Rituals
Neuroleptic induced deficit syndrome is principally characterized by the same symptoms that constitute the negative symptoms of schizophrenia: emotional blunting, apathy, hypobulia, anhedonia, indifference, difficulty in thinking, difficulty or total inability in concentrating, lack of initiative, attention deficits, and desocialization. This can easily lead to misdiagnosis and mistreatment. Instead of decreasing the antipsychotic, the doctor may increase their dose to try to "improve" what they perceive to be negative symptoms of schizophrenia, rather than antipsychotic side effects. The concept of neuroleptic induced deficit syndrome was initially presented for schizophrenia, and it has rarely been associated in other mental disorders. In recent years, atypical neuroleptics are being more often managed to patients with bipolar disorder, so some studies about neuroleptic-induced deficit syndrome in bipolar disorder patients now available.
There are significant difficulties in the differential diagnosis of primary negative symptoms and neuroleptic deficiency syndrome (secondary negative symptoms), as well as depression.
Depressive Disorder Not Otherwise Specified (DD-NOS) is designated by the code "311" in the DSM-IV for depressive disorders that are impairing but do not fit any of the officially specified diagnoses. According to the DSM-IV, DD-NOS encompasses "any depressive disorder that does not meet the criteria for a specific disorder." In the DSM-5, it is called unspecified depressive disorder.
Examples of disorders in this category include those sometimes described as minor depressive disorder and recurrent brief depression.
"Depression" refers to a spectrum of disturbances in mood that vary from mild to severe and from short periods to constant illness. DD-NOS is diagnosed if a patients symptoms fail to meet the criteria more common depressive disorders such as major depressive disorder or dysthymia. Although DD-NOS shares similar symptoms to dysthymia, dysthymia is classified by a period of at least 2 years of constantly recurring depressed mood, where as DD-NOS is classified by much shorter periods of depressed moods.
For most people who suffer the condition, their life will be significantly affected. DD-NOS can make many aspects of a person's daily life difficult to manage, inhibiting their ability to enjoy the things that used to make them happy. Sufferers of the disorder tend to isolate themselves from their friends and families, lose interest in some activities, and experience behavioural changes and sleeping disorders. Some sufferers also experience suicidal tendencies or suicide attempts. In addition to having these symptoms, a diagnosis of DD-NOS will only be made if the symptoms cause significant distress or impairment in social, occupational, or other important areas of functioning. For the diagnosis to be accurate, a psychiatrist is required to spend extensive time with the patient.
Symptoms of the disorder may arise due to several reasons. These include:
- Distress due to medical conditions
- Environmental effects and situations
However, the effects of drugs or medication or bereavement are not classified under the diagnosis.
A person will not be diagnosed with the condition if they have or have had any of the following: a major depressive episode, manic episode, mixed episode or hypomanic episode.
A diagnosis of the disorder will look like: "Depressive Disorder NOS 311".
Depressive mixed states occur when patients experience depression and non-euphoric, usually subsyndromal, hypomania at the same time. As mentioned previously, it is particularly difficult to diagnose BP-II when a patient is in this state.
In a mixed state, mood is depressed, but the following symptoms of hypomania present as well:
- Irritability
- Mental overactivity
- Behavioral overactivity
Mixed states are associated with greater levels of suicidality than non-mixed depression. Antidepressants may increase this risk.
It is during depressive episodes that BP-II patients often seek help. Symptoms may be syndromal or subsyndromal. Depressive BP-II symptoms may include five or more of the below symptoms (at least one of them must be either depressed mood or loss of interest/pleasure). In order to be diagnosed, they need to be present only during the same two-week period, as a change from previous hypomanic functioning:
- Depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad, empty, or hopeless) or observation made by others (e.g., appears tearful). (Note: In children and adolescents, can be irritable mood.)
- Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation).
- Significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a month), or decrease or increase in appetite nearly every day. (Note: In children, consider failure to make expected weight gain.)
- Insomnia or hypersomnia nearly every day.
- Psychomotor agitation or retardation nearly every day (observable by others; not merely subjective feelings of restlessness or being slowed down).
- Fatigue or loss of energy nearly every day.
- Feelings of worthlessness or excessive or inappropriate guilt nearly every day (not merely self-reproach or guilt about being sick).
- Diminished ability to think or concentrate, possible irritability or indecisiveness, nearly every day (either by subjective account or as observed by others).
- Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, a suicide attempt, or a specific plan for committing suicide.
Evidence also suggests that BP-II is strongly associated with atypical depression. Essentially, this means that many BP-II patients exhibit reverse vegetative symptoms. BP-II patients may have a tendency to oversleep and overeat, while typically depressed patients sleep and eat less than usual.
Bipolar I disorder (BD-I; pronounced "type one bipolar disorder") is a bipolar spectrum disorder characterized by the occurrence of at least one manic or mixed episode. Most patients also, at other times, have one or more depressive episodes, and all experience a hypomanic stage before progressing to full mania.
It is a type of bipolar disorder, and conforms to the classic concept of manic-depressive illness, which can include psychosis during mood episodes. The difference with bipolar II disorder is that the latter requires that the individual must never have experienced a full manic or mixed-manic episode - only less severe hypomanic episode(s).
Because these are frequently found in cases of autistic disorders, criteria could be met for multiple neurological disorders, or cause severe symptoms.
Some examples include:
1. Learning difficulties symptoms such as dyslexia, dysgraphia, dyscalcula, NVLD, slow learning, poor memory, etc.
2. AD/HD symptoms such as poor concentration, poor decision making, poor judgement, impulsiveness, difficulty sitting still, etc.
3. Synesthesia.
4. Neurological sleep disorders such as narcolepsy, insomnia, circadian rhythm disorder, etc.
5. Conditions affecting perceptions and/or cognition, such as agnosia, aphasia, etc.
6. Tourette syndrome or Tic disorder.
7. Epilepsy or Seizure disorder.
8. Parkinsonian syndrome features such as tremors, stiff movements, etc.
The essential feature of bipolar I disorder is a clinical course characterized by the occurrence of one or more manic episodes or mixed episodes (DSM-IV-TR, 2000). Often, individuals have had one or more major depressive episodes. One episode of mania is sufficient to make the diagnosis of bipolar disorder; the patient may or may not have history of major depressive disorder. Episodes of substance-induced mood disorder due to the direct effects of a medication, or other somatic treatments for depression, drug abuse, or toxin exposure, or of mood disorder due to a general medical condition need to be excluded before a diagnosis of bipolar I disorder can be made. In addition, the episodes must not be better accounted for by schizoaffective disorder or superimposed on schizophrenia, schizophreniform disorder, delusional disorder, or a psychotic disorder not otherwise specified.
Cyclothymia is characterized by short cycles of baseline, stable periods of not over two months and numerous swings between depression and hypomania that fail to meet the severity of sustained duration criterion for major affective syndromes for at least two years.
Depressive/dysthymic episodes. Symptoms of the "depressive/dysthymic phase" may include any of the following conditions:difficulty making decisions, problems concentrating, poor memory recall, guilt, self-criticism, low self-esteem, pessimism, self-destructive thinking, constant sadness, apathy, hopelessness, helplessness and irritability. Also common are quick temper, poor judgment, lack of motivation, social withdrawal, appetite change, lack of sexual desire, self-neglect, fatigue, insomnia and sleepiness.
Hypomanic episodes. Symptoms of the "hypomanic episode" may include any of the following conditions: unusually good mood or cheerfulness (euphoria), extreme optimism, inflated self-esteem, rapid speech, racing thoughts, aggressive or hostile behavior, lack of consideration for others, agitation, massively increased physical activity, risky behavior, spending sprees, increased drive to perform or achieve goals, increased sexual drive, decreased need for sleep, tendency to be easily distracted, and inability to concentrate.
Schizoaffective disorder is defined by "mood disorder-free psychosis" in the context of a long-term psychotic and mood disorder. Psychosis must meet criterion A for schizophrenia which may include delusions, hallucinations, disorganized speech, thinking or behavior and negative symptoms. Both delusions and hallucinations are classic symptoms of psychosis. Delusions are false beliefs which are strongly held despite evidence to the contrary. Beliefs should not be considered delusional if they are in keeping with cultural beliefs. Delusional beliefs may or may not reflect mood symptoms (for example, someone experiencing depression may or may not experience delusions of guilt). Hallucinations are disturbances in perception involving any of the five senses, although auditory hallucinations (or "hearing voices") are the most common. A lack of responsiveness or negative symptoms include alogia (lack of spontaneous speech), blunted affect (reduced intensity of outward emotional expression), avolition (loss of motivation), and anhedonia (inability to experience pleasure). Negative symptoms can be more lasting and more debilitating than positive symptoms of psychosis.
Mood symptoms are of mania, hypomania, mixed episode, or depression, and tend to be episodic rather than continuous. A mixed episode represents a combination of symptoms of mania and depression at the same time. Symptoms of mania include elevated or irritable mood, grandiosity (inflated self-esteem), agitation, risk-taking behavior, decreased need for sleep, poor concentration, rapid speech, and racing thoughts. Symptoms of depression include low mood, apathy, changes in appetite or weight, disturbances in sleep, changes in motor activity, fatigue, guilt or feelings of worthlessness, and suicidal thinking.
The affective spectrum is a spectrum of affective disorders (mood disorders). It is a grouping of related psychiatric and medical disorders which may accompany bipolar, unipolar, and schizoaffective disorders at statistically higher rates than would normally be expected. These disorders are identified by a common positive response to the same types of pharmacologic treatments. They also aggregate strongly in families and may therefore share common heritable underlying physiologic anomalies.
Affective spectrum disorders include:
- Attention deficit hyperactivity disorder
- Bipolar disorder
- Body dysmorphic disorder
- Bulimia nervosa and other eating disorders
- Cataplexy
- Dysthymia
- Generalized anxiety disorder
- Hypersexuality
- Irritable bowel syndrome
- Impulse-control disorders
- Kleptomania
- Migraine
- Major depressive disorder
- Obsessive-compulsive disorder
- Oppositional defiant disorder
- Panic disorder
- Posttraumatic stress disorder
- Premenstrual dysphoric disorder
- Social anxiety disorder
- Fibromyalgia
The following may also be part of the spectrum accompanying affective disorders.
- Chronic pain
- Intermittent explosive disorder
- Pathological gambling
- Personality disorder
- Pyromania
- Substance abuse and addiction (includes alcoholism)
- Trichotillomania
Also, there are now studies linking heart disease.
Many of the terms above overlap. The American Psychiatric Association's definitions of these terms can be found in the "Diagnostic and Statistical Manual of Mental Disorders" (DSM).
Somatic manifestations of MD are distinguished by an extreme diversity and include headaches, back pain, abdominal pain etc. Pathological behaviour masking depression may take the form of compulsive gambling, compulsive work, changes in arousal or orgasmic function, decreased libido or, on the contrary, impulsive sexual behaviour, alcoholism, drug addiction and more.
Masked depression (MD) was a proposed form of atypical depression in which somatic symptoms or behavioural disturbances dominate the clinical picture and disguise the underlying affective disorder. The concept is not currently supported by the mental health profession.
Mania is a distinct period of at least one week of elevated or irritable mood, which can range from euphoria to delirium, and those experiencing hypo- or mania may exhibit three or more of the following behaviors: speak in a rapid, uninterruptible manner, short attention span, racing thoughts, increased goal-oriented activities, agitation, or they may exhibit behaviors characterized as impulsive or high-risk, such as hypersexuality or excessive spending. To meet the definition for a manic episode, these behaviors must impair the individual's ability to socialize or work. If untreated, a manic episode usually lasts three to six months.
People with hypomania or mania may experience a decreased need of sleep, impaired judgment, and speak excessively and very rapidly. Manic individuals often have a history of substance abuse developed over years as a form of "self-medication". At the more extreme, a person in a full blown manic state can experience psychosis; a break with reality, a state in which thinking is affected along with mood. They may feel unstoppable, or as if they have been "chosen" and are on a "special mission", or have other grandiose or delusional ideas. This may lead to violent behavior and, sometimes, hospitalization in an inpatient psychiatric hospital. The severity of manic symptoms can be measured by rating scales such as the Young Mania Rating Scale, though questions remain about the reliability of these scales.
The onset of a manic or depressive episode is often foreshadowed by sleep disturbances. Mood changes, psychomotor and appetite changes, and an increase in anxiety can also occur up to three weeks before a manic episode develops.
Recurrent brief depression (RBD) defines a mental disorder characterized by intermittent depressive episodes, not related to menstrual cycles in women, occurring between approximately 6-12 times per year, over at least one year or more fulfilling the diagnostic criteria for major depressive episodes (DSM-IV and ICD-10) except for duration which in RBD is less than 14 days, typically 2–4 days. Despite the short duration of the depressive episodes, such episodes are severe and suicidal ideation and impaired function is rather common. The majority of patients with RBD also report symptoms of anxiety and increased irritability. Hypersomnia is also rather frequent. About 1/2 of patients fulfilling diagnostic criteria for RBD may have additional short episodes of brief hypomania which is a severity marker of RBD. RBD may be the only mental disorder present, but RBD may also occur as part of a history of recurrent major depressive episodes or bipolar disorders. RBD is also seen among some patients with personality disorders.
Symptoms of the depressive phase of bipolar disorder include persistent feelings of sadness, irritability or anger, loss of interest in previously enjoyed activities, excessive or inappropriate guilt, hopelessness, sleeping too much or not enough, changes in appetite and/or weight, fatigue, problems concentrating, self-loathing or feelings of worthlessness, and thoughts of death or suicide. In severe cases, the individual may develop symptoms of psychosis, a condition also known as severe bipolar disorder with psychotic features. These symptoms include delusions and hallucinations. A major depressive episode persists for at least two weeks, and may result in suicide if left untreated.
The earlier the age of onset, the more likely the first few episodes are to be depressive. Since a diagnosis of bipolar disorder requires a manic or hypomanic episode, many affected individuals are initially misdiagnosed as having major depression and then incorrectly treated with prescribed antidepressants.
SAD is a type of major depressive disorder, and sufferers may exhibit any of the associated symptoms, such as feelings of hopelessness and worthlessness, thoughts of suicide, loss of interest in activities, withdrawal from social interaction, sleep and appetite problems, difficulty with concentrating and making decisions, decreased sex drive, a lack of energy, or agitation. Symptoms of winter SAD often include oversleeping or difficulty waking up in the morning, nausea, and a tendency to over eat, often with a craving for carbohydrates, which leads to weight gain. SAD is typically associated with winter depression, but springtime lethargy or other seasonal mood patterns are not uncommon. Although each individual case is different, in contrast to winter SAD, people who experience spring and summer depression may be more likely to show symptoms such as insomnia, decreased appetite and weight loss, and agitation or anxiety.
Neuroleptic-induced deficit syndrome (NIDS) is a psychopathological syndrome that develops in some patients who take high doses of an antipsychotic for an extended time. It is most often caused by high-potency typical antipsychotics, but can also be caused by high doses of many atypicals, especially those closer in profile to typical ones (that have higher D dopamine receptor affinity and relatively low 5-HT serotonin receptor binding affinity), like risperidone and amisulpride.
Cyclothymia (), also called cyclothymic disorder, is a type of chronic mood disorder widely considered to be a more chronic but milder or subthreshold form of bipolar disorder. Cyclothymia is characterized by numerous mood swings, with periods of hypomanic symptoms that do not meet criteria for a manic episode, alternating with periods of mild or moderate symptoms of depression that do not meet criteria for a major depressive episode.
An individual with cyclothymia may feel stable at a baseline level but experience a noticeable shift to an emotional high during subthreshold hypomanic episodes of elation or euphoria, with symptoms similar to those of mania but less severe, and often cycle to emotional lows with moderate depressive symptoms. To meet the diagnostic criteria for cyclothymia, a person must experience this alternating pattern of emotional highs and lows for a period of at least two years with no more than two consecutive symptom-free months. For children and adolescents, the duration must be at least one year.
The diagnosis of cyclothymia is rare compared to other mood disorders. Diagnosis of cyclothymia entails the absence of any major depressive episode, manic episode or mixed episode, which would qualify the individual for diagnosis of other mood disorders. When a major episode manifests after an initial diagnosis of cyclothymia, the individual may qualify for a diagnosis of bipolar I or bipolar II disorder. Although estimates vary greatly, 15–50% of cases of cyclothymia later advance to the diagnostic criteria for bipolar I and/or bipolar II disorder (with cyclothymic features). Although the emotional highs and lows of cyclothymia are less extreme than those of bipolar disorder and generally do not cause the same conditions, the symptomatology, longitudinal course, family history and treatment response of cyclothymia are consistent with bipolar spectrum.
Lifetime prevalence of cyclothymic disorder is 0.4–1%. Frequency appears similar in men and women, though women more often seek treatment. People with cyclothymia during periodic hypomania (euphoria) tend to feel an inflated self-worth, self-confidence and elation, often with rapid speech, racing thoughts, not much need to sleep, increased aggression and impulsive behavior, showing little regard for consequences of decisions—but may sometimes be somewhat, fully or hyper-productive for a period of several days at a time.
Bipolar disorder is difficult to diagnose. If a person displays some symptoms of bipolar disorder but not others, the clinician may diagnose bipolar NOS. The diagnosis of bipolar NOS is indicated when there is a rapid change (days) between manic and depressive symptoms and can also include recurring episodes of hypomania. Bipolar NOS may be diagnosed when it is difficult to tell whether bipolar is the primary disorder due to another general medical condition, such as a substance use disorder.
These symptoms are not due to situations such as, person is depressed because of difficulty making friends. It is normal to experience dysfunctional emotions and behaviors at times.
Criteria are met for a neurotic or personality disorder, preferably at least two.
Some symptoms may include:
1. Depression.
2. Mania.
3. Anxiety.
4. Anger.
5. Dissociative symptoms such as depersonalization, derealization, deja vu, etc.
6. Emotional instability.
7. Psychopathic behavior.
8. Narcissism.
9. Paranoia.
10. Obsessive-compulsive behavior.
Bipolar disorder not otherwise specified (BD-NOS) is a diagnosis for bipolar disorder (BD) when it does not fall within the other established sub-types. Bipolar disorder NOS is sometimes referred to as subthreshold bipolar disorder.
311- Depressive Disorder Not Otherwise Specified (NOS)
The Depressive disorder NOS category includes disorders with depressive features that do not meet the criteria for Major Depressive Disorder, Dysthymic disorder, Adjustment Disorder with Depressed Mood or Adjustment Disorder with Mixed Anxiety and Depressed Mood. Sometimes depressive symptoms can present as part of an Anxiety Disorder Not otherwise Specified. Examples of Depressive Disorder Not Otherwise Specified include.
- Premenstrual Dysphoric Disorder: in most menstrual cycles during the past years, (e.g., markedly depressed mood, marked anxiety, marked affective lability, or decreased interest in activities) regularly occurred during the onset of menses. These symptoms must be severe enough to markedly interfere with work, school, or usual activities and be entirely absent for at least 1 week post menses.
- Minor depressive disorder: episodes of at least 2 weeks of depressive symptoms but with fewer than the five items required for Major Depressive Disorder.
- Recurrent brief depressive disorder: depressive episodes lasting from 2 days up to 2 weeks, occurring at least once a month for 12 months (not associated with the menstrual cycle)
- Post psychotic depressive Disorder of schizophrenia: a Major Depressive Episode that occurs during the residual phase of schizophrenia.
- A Major Depressive Episode superimposed on delusional disorder, Psychotic Disorder Not Otherwise Specified, or the active phase of schizophrenia.
- Situations in which the clinician has concluded that a depressive disorder is present but is unable to determine whether it is primary, due to a general medical condition, or substance induced.
Symptoms of the disorder may arise due to several reasons. These include:
- Distress due to medical conditions
- Environmental effects and situations
Schizoaffective disorder (SZA, SZD or SAD) is a mental disorder characterized by abnormal thought processes and deregulated emotions. The diagnosis is made when the person has features of both schizophrenia and a mood disorder—either bipolar disorder or depression—but does not strictly meet diagnostic criteria for either alone. The bipolar type is distinguished by symptoms of mania, hypomania, or mixed episode; the depressive type by symptoms of depression only. Common symptoms of the disorder include hallucinations, paranoid delusions, and disorganized speech and thinking. The onset of symptoms usually begins in young adulthood, currently with an uncertain lifetime prevalence because the disorder was redefined, but DSM-IV prevalence estimates were less than 1 percent of the population, in the range of 0.5 to 0.8 percent. Diagnosis is based on observed behavior and the person's reported experiences.
Genetics, neurobiology, early and current environment, behavioral, social, and experiential components appear to be important contributory factors; some recreational and prescription drugs may cause or worsen symptoms. No single isolated organic cause has been found, but extensive evidence exists for abnormalities in the metabolism of tetrahydrobiopterin (BH4), dopamine, and glutamic acid in people with schizophrenia, psychotic mood disorders, and schizoaffective disorder. People with schizoaffective disorder are likely to have co-occurring conditions, including anxiety disorders and substance use disorder. Social problems such as long-term unemployment, poverty and homelessness are common. The average life expectancy of people with the disorder is shorter than those without it, due to increased physical health problems from an absence of health promoting behaviors such as a sedentary lifestyle, and a higher suicide rate.
The mainstay of current treatment is antipsychotic medication combined with mood stabilizer medication or antidepressant medication, or both. There is growing concern by some researchers that antidepressants may increase psychosis, mania, and long-term mood episode cycling in the disorder. When there is risk to self or others, usually early in treatment, hospitalization may be necessary. Psychiatric rehabilitation, psychotherapy, and vocational rehabilitation are very important for recovery of higher psychosocial function. As a group, people with schizoaffective disorder diagnosed using DSM-IV and criteria have a better outcome than people with schizophrenia, but have variable individual psychosocial functional outcomes compared to people with mood disorders, from worse to the same. Outcomes for people with DSM-5 diagnosed schizoaffective disorder depend on data from prospective cohort studies, which haven't been completed yet.
In DSM-5 and ICD-10, schizoaffective disorder is in the same diagnostic class as schizophrenia, but not in the same class as mood disorders. The diagnosis was introduced in 1933, and its definition was slightly changed in the DSM-5, published in May 2013, because the DSM-IV schizoaffective disorder definition leads to excessive misdiagnosis. The changes made to the schizoaffective disorder definition were intended to make the DSM-5 diagnosis more consistent (or reliable), and to substantially reduce the use of the diagnosis. Additionally, the DSM-5 schizoaffective disorder diagnosis can no longer be used for first episode psychosis.
"Mood disorder due to a general medical condition" is used to describe manic or depressive episodes which occur secondary to a medical condition. There are many medical conditions that can trigger mood episodes, including neurological disorders (e.g. dementias), metabolic disorders (e.g. electrolyte disturbances), gastrointestinal diseases (e.g. cirrhosis), endocrine disease (e.g. thyroid abnormalities), cardiovascular disease (e.g. heart attack), pulmonary disease (e.g. chronic obstructive pulmonary disease), cancer, and autoimmune diseases (e.g. rheumatoid arthritis).