Allergy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Marufa Marium, M.B.B.S[2]
Overview
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Allergy is a disorder of the immune system that is often called atopy. Allergic reactions occur to environmental substances known as allergens; these reactions are acquired, predictable and rapid. Strictly, allergy is one of four forms of hypersensitivity and is called type I (or immediate) hypersensitivity. It is characterized by excessive activation of certain white blood cells called mast cells and basophils by a type of antibody, known as IgE, resulting in an extreme inflammatory response. Common allergic reactions include eczema, hives, hay fever, asthma, food allergies, and reactions to the venom of stinging insects such as wasps and bees.[1]
Mild allergies like hay fever, are highly prevalent in the human population and cause symptoms such as allergic conjunctivitis, itchiness and runny nose. Similarly, conditions such as asthma are common, in which allergy plays a major role. In some people, severe allergies to environmental or dietary allergens, or to medication, occur that may result in life-threatening anaphylactic reactions and potentially death.
A variety of tests now exist to diagnose allergic conditions; these include testing the skin for responses to known allergens or analyzing the blood for the presence and levels of allergen-specific IgE. Treatments for allergies include allergen avoidance, use of antihistamines, steroids or other oral medications, immunotherapy to desensitize the response to allergen, and targeted therapy.
Historical Perspective
Allergy, as a concept, was first defined in the early 1900s. It has later developed into several different disease mechanisms related to disordered activation of immune system. The overall study of allergy, as a concept, drastically evolved in the 1960s with the discovery of immunoglobulin E (IgE) – Kimishige Ishizaka.
Pathophysiology
The development of allergic response occurs in two phases: acute and late-phase reaction. The body’s response varies largely on the type of phase and the advancement of chemical mediation.
Causes
Allergy causation can categorized as host or environmental factors. Biological factors are strongly familial related. Environmental factors very largely on the type of living environment. Allergies are more common in industrialized countries than in countries that are more traditional or agricultural, and there is a higher rate of allergic disease in urban populations versus rural populations.
Differentiating Allergy from other Diseases
Allergic response must be differentiated from other similar diseases such as vasomotor rhinitis. Proper diagnosis ensures that the patient receives the most appropriate course of treatment.
Diagnosis
History and Symptoms
Allergy has the potential to influence various organ systems differently. Depending of the rate of severity, it can cause cutaneous reactions, bronchoconstriction, edema, hypotension, coma and even death.
Treatment
Medical Therapy
Treatment for allergic response is primarily pharmacotherapeutic. Common methodologies include immunotherapy via desensitization or hyposensitization, enzyme potentiated desensitization.
Secondary Prevention
Once allergies have developed, treating the allergies and carefully avoiding those things that cause reactions can prevent allergies in the future.
References
Historical Perspective
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Marufa Marium, M.B.B.S[2]
Overview
The term “allergy” was first coined in the early 1900s. It has since evolved into a number of distinct disease mechanisms linked to immune system activation that is disordered. With the discovery of immunoglobulin E (IgE) – Kimishige Ishizaka – in the 1960s, the overall study of allergy as a concept changed dramatically.
Historical Perspective
Clemens von Pirquet, a Viennese pediatrician, coined the term “allergy” in 1906 after observing that some of his patients were hypersensitive to normally harmless substances such as dust, pollen, or certain foods. Pirquet coined the term “allergy” from the Greek words allos, which means “other,” and ergon, which means “work.”[1] All forms of hypersensitivity were previously categorized as allergies, and they were all believed to be caused by an inappropriate immune system activation. Later, it became apparent that several different disease mechanisms were involved, all of which were linked to a disordered immune system activation. Philip Gell and Robin Coombs devised a new classification scheme in 1963 that defined four types of hypersensitivity reactions, referred to as Type I to Type IV hypersensitivity.[2] The term “allergy” was now limited to type I hypersensitivities (also known as immediate hypersensitivity), which are characterized by rapidly developing reactions. The discovery of the antibody class labeled immunoglobulin E (IgE) in the 1960s was a significant breakthrough in understanding the mechanisms of allergy. Kimishige Ishizaka and co-workers were the first to isolate and characterize IgE.[3]
References
- ↑ Von Pirquet C (1906). “Allergie”. Munch Med Wochenschr. 53: 1457.
- ↑ Gell PGH, Coombs RRA. (1963). Clinical Aspects of Immunology. London: Blackwell.
- ↑ Ishizaka K, Ishizaka T, Hornbrook MM (1966). “Physico-chemical properties of human reaginic antibody. IV. Presence of a unique immunoglobulin as a carrier of reaginic activity”. J. Immunol. 97 (1): 75–85. PMID 4162440.
Classification
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Marufa Marium, M.B.B.S[2]
Overview
Allergy may be classified into four subtypes based on duration], type of allergen, Blood IgE test and Organ involvement.
Classification
Allergy may be classified according to duration], type of allergen, Blood IgE test and Organ involvement into four subtypes[1][2][3]:
| Duration | Early Phase Reaction, Late Phase Reaction, Chronic Allergic Reaction | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Type of Allergen | Pollen, Drug, Pet, Food, Insect, Latex, Mold | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Allergy | Blood IgE Test | Class 0 to class 4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Organ involvement | Systemic Anaphylaxis, Acute Urticaria, Asthma, Allergic Rhinitis, Food Allergy | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
References
- ↑ “Allergy and Hypersensitivity – Immunobiology – NCBI Bookshelf”.
- ↑ Siles RI, Hsieh FH (September 2011). “Allergy blood testing: A practical guide for clinicians”. Cleve Clin J Med. 78 (9): 585–92. doi:10.3949/ccjm.78a.11023. PMID 21885690.
- ↑ Galli SJ, Tsai M, Piliponsky AM (July 2008). “The development of allergic inflammation”. Nature. 454 (7203): 445–54. doi:10.1038/nature07204. PMC 3573758. PMID 18650915.
Pathophysiology
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Marufa Marium, M.B.B.S[2]
Overview
There are two stages to the development of an allergic reaction: acute and late-phase reaction. The body’s reaction depends a lot on the phase and how far chemical mediation has progressed.
Pathophysiology
There are two stages to the pathophysiology of allergic reactions. The first is an allergic reaction that occurs shortly after being exposed to an allergen. This phase can either fade away or progress into a “late phase reaction,” which can significantly prolong the symptoms of an allergic reaction and cause tissue damage.[1]
Acute Response
In the early stages of acute response:
| Early stage of Allergy or Type 1 hypersensitivity reaction | |||||||||||||||||||
| Encounter of allergen with T-helper cell | |||||||||||||||||||
| IL-4 production | |||||||||||||||||||
| [[TH2 cells]] stimulated by IL-4 started interacting with B-cell | |||||||||||||||||||
| Production of antibody IgE, and binding with IgE-specific receptor (a kind of Fc receptor called FcεRI on mast cells and basophils | |||||||||||||||||||
| Acute inflammatory response and Sensitization of IgE coated cell to allaergen | |||||||||||||||||||
In the late stage of acute response:
| Binding of similar allergen to IgE coated mast cells and basophils | |||||||||||||||||||
| Cross-linking of the IgE and Fc receptors | |||||||||||||||||||
| Activation and Degranulation of mast cells and basophils | |||||||||||||||||||
| Release of histamine and other inflammatory chemical mediators (cytokines, interleukins, leukotrienes, and prostaglandins) | |||||||||||||||||||
| Production of antibody IgE, and binding with IgE-specific receptor (a kind of Fc receptor called FcεRI on mast cells and basophils | |||||||||||||||||||
| Systemic effects: vasodilation, mucous secretion, nerve stimulation and smooth muscle contraction | |||||||||||||||||||
Acute inflammatory response causes systemic inflammatory reaction like vasodilation, mucous secretion, nerve stimulation and smooth muscle contraction. Rhinorrhea, itchiness, dyspnea, and anaphylaxis are all symptoms of this. The symptoms may be system-wide (classical anaphylaxis) or localized to specific body systems (asthma is localized to the respiratory system and eczema is localized to the dermis) depending on the individual, allergen, and mode of introduction.
Late-phase Response
Late phase responses are common after the chemical mediators of the acute response have subsided. This is due to the migration of other leukocytes to the initial site, such as neutrophils, lymphocytes, eosinophils, and macrophages. The reaction appears 2–24 hours after the initial reaction.[2] Mast cell cytokines may also contribute to the persistence of long-term effects. Although late phase responses in asthma are slightly different from those seen in other allergic reactions, they are still triggered by eosinophil mediator release and are still dependent on TH2 cell activity.[3]
References
- ↑ Galli SJ, Tsai M, Piliponsky AM (July 2008). “The development of allergic inflammation”. Nature. 454 (7203): 445–54. doi:10.1038/nature07204. PMC 3573758. PMID 18650915.
- ↑ Grimbaldeston MA, Metz M, Yu M, Tsai M, Galli SJ (2006). “Effector and potential immunoregulatory roles of mast cells in IgE-associated acquired immune responses”. Curr. Opin. Immunol. 18 (6): 751–60. doi:10.1016/j.coi.2006.09.011. PMID 17011762.
- ↑ Holt PG, Sly PD (2007). “Th2 cytokines in the asthma late-phase response”. Lancet. 370 (9596): 1396–8. doi:10.1016/S0140-6736(07)61587-6. PMID 17950849.
Causes
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Marufa Marium, M.B.B.S[2]
Overview
Allergy may be caused by genetic, environmental and infectious factors.
CauseAllergy
Allergy may be caused by genetic, environmental and infectious factors. Anaphylaxis is a life-threatening cause of Allergy.
Common Causes
Common genetic causes of allergy may include[1][2] :
- HLA class 2 genes
- Th2 cytokine genes
- Degranulation and pro-inflammatory responses
Common environmental causes of allergy may include[3]:
- Exposure to allergen:
- Foods( Peanut, soy, eggs, shellfish), Drugs (Antibiotics, NSAIDS, Aspirin, Sulfur containing medications etc), Insects(honeybee, bumblebee, Hornet, fire ant etc), Contrast allergy, Latex, Exercise, vaccinations
- Environmental pollution
- Alteration of microbiota
- Agricultural etiology
Common infectious causes of allergy may include[4][5]:
- Intestinal parasites
Less Common Causes
Less common causes of allergy include:
- PRR Genes
- Th differentiation
- Hormonal imbalance
- Emotional stress
- Chronic disease flare up
- Excessive hygiene
- Nutritional deficiencies
References
- ↑ Janeway, Charles (2001). Immunobiology; Fifth Edition. New York and London: Garland Science. pp. e–book. ISBN 0-8153-4101-6. Unknown parameter
|coauthors=ignored (help). - ↑ Galli SJ (2000). “Allergy”. Curr. Biol. 10 (3): R93–5. PMID 10679332.
- ↑ Cooper PJ (2004). “Intestinal worms and human allergy”. Parasite Immunol. 26 (11–12): 455–67. doi:10.1111/j.0141-9838.2004.00728.x. PMID 15771681.
- ↑ Macpherson CN, Gottstein B, Geerts S (2000). “Parasitic food-borne and water-borne zoonoses”. Rev. – Off. Int. Epizoot. 19 (1): 240–58. PMID 11189719.
- ↑ Carvalho EM, Bastos LS, Araújo MI (2006). “Worms and allergy”. Parasite Immunol. 28 (10): 525–34. doi:10.1111/j.1365-3024.2006.00894.x. PMID 16965288.
Differentiating Allergy from other Diseases
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Marufa Marium, M.B.B.S[2]
Overview
Allergy must be differentiated from other diseases that cause Dermatological (Urticaria, pruritus, flushing, Angioedema), Respiratory (Rhinorrhea,chest tightness,Wheezing, Dyspnoea, Sneezing, Shortness of breath) Mucosal (Mucosal swelling affecting nose, lips, tongue, larynx, pharynx, conjunctiva, GIT) Ocular (Periorbital edema, Conjunctival Congesion, Itching), Systemic (Hypotension). Allergy can be differentiated according to the type of allergy.
Allergy must be differentiated from other diseases that cause Dermatological (Urticaria, pruritus, flushing, Angioedema), Respiratory (Rhinorrhea,chest tightness,Wheezing, Dyspnoea, Sneezing, Shortness of breath) Mucosal (Mucosal swelling affecting nose, lips, tongue, larynx, pharynx, conjunctiva, GIT) Ocular (Periorbital edema, Conjunctival Congesion, Itching), Systemic (Hypotension). Allergy can be differentiated according to the types of allergy.
Differentiating Allergy from other diseases on the basis of Dermatological, Respiratory, Mucosal, Ocular, Systemic Manifestations
On the basis Dermatological, Respiratory, Mucosal, Ocular, Systemic Manifestations, Allergy must be differentiated according to the types of allergy.
- Food Allergy is differentiated from enzyme deficiencies like lactose intolerance, fructose intolerance and malabsorption, Celiac Disease, Toxic reactions, Irritable bowel syndrome, Tyramine or caffeine toxicity.
- Allergic Rhinitis is differentiated from Acute Infectious rhinitis, Irritant rhinitis, Acute Rhinosinusitis, Hormonal Rhinitis, Vasomotor rhinitis, Gustatory Rhinitis.
- Drug Allergy can be differentiated under 2 headings, they are IgE mediated (Carcinoid Syndrome, Mastocytosis) and Non-IgE mediated (Kawasaki disease, Acute Viral or streptococcal infection, Acute graft-versus host disease, Hereditary angioedema).
- Asthma is differentiated from several respiratory diseases for example COPD, Allergic bronchopulmonary aspergillosis, Bronchiectasis, OSA, Chrug-strauss syndrome, Anxiety, Foreign Body in respiratory tract.
- Atopic Dermatitis can be differentiated from Seborrheic dermatitis, Psoriasis, Contact dermatitis, Psoriasis, Scabies, Nutrient deficiency ( Zinc, Vitamin B3, Vitamin B6), Hyper IgE syndrome, Wiskott-Aldrich syndrome, IPEX syndrome, Brutons Agammaglobulinemia.
| Diseases | Clinical manifestations | Para-clinical findings | Gold standard | Additional findings | |||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Symptoms | Physical examination | ||||||||||||||||||||||||||||||||||||
| Lab Findings | Imaging | Histopathology | |||||||||||||||||||||||||||||||||||
| Abdominal Pain | Diarrhea/ Nausea/Vomiting | Dysphagia/Chest Pain | Bloating/Flatulence | Regurgitation/Reflux | Urticaria/Angioedema / Mucosal Swelling/ Oral Ulcer | Dyspnea/ Rhinorrhea /Sneezing /Nasal congesion | Pruritus/Flushing/Conjunctival or OcularIrritation | Gastrointestinal | Dermatological | Respiratory | Mucosal | Ocular | Systemic and Other | Complete blood count and Complete metabolic panel | Specific Laboratory test | Hydrogen/Fructose breath Test, lactose intolerance test | Toxin or Others | Stool analysis Or Urine Analysis | Ultrasonography and Endoscopy | Colonoscopy, Sigmoidoscopy or Bronchoscopy | Barium Enema and X-ray | CT | MRI | ||||||||||||||
| Enzyme deficiencies and Malabsorption | +(Diffuse Mild abdominal pain) | +(Steatorrhea/Osmotic Diarrhea) | – | + | – | – | – | – | Abdominal distention, Mild tenderness -/+, Osmotic diarrhea Hepatomegaly -/+, Ascites -/+ | Koilonychia, Edema, Dermatitis, Easy Bruisability, ecchymoses, Follicular Hyperkeratosis, Pale mucosa | Tachypnea -/+ | Glossitis/Cheilosis/Stomatitis | Keratitis, Xeropthalmia, Night blindness, | weight loss, Failure to thrive, Fatigue , Generalized and muscle weakness, Arthralgia, Bone fracture, rickets/osteomalacia, Paresthesia, Ataxia | Iron deficiency anemia, Anemia of chronic disease, Increased ESR, Electrolyte imbalance, Serum Pr/globulin, | – | + in lactose and fructose intolerance | -/ Autoantibodies(ANA in Connective tissue disease, Antimitochondrial Ab in PBC), CFTR mutation in CF, Immunoglobulins in Immunodeficiency, HIV-ELISA/Western blot in HIV, 5-HIA in Carcinoid, Gastrin in Zollinger Ellison syndrome, TSH in Dysfunctional thyroid gland | Stool analysis: Decreased pH, Increased Fecal Fat, Increased electrolyte, Increased osmotic gap, stool WBC, Calprotectin | USG rule out ascites, lymphadenopathy, hepatobiliiary disease, lymphangiectasia, gastrinoma, somatostatinoma | – | – | to rule out pancreatic cause of malabsorption, malignancy | – | Hydrogen breath test for Carbohydrate intolerance, Antimitochondrial Ab in PBC, CFTR mutation in CF, Immunoglobulins in Immunodeficiency, HIV-ELISA/Western blot in HIV, 5-HIA in Carcinoid, Gastrin in Zollinger Ellison syndrome | – | |||||||||||
| Inflammatory Bowel Disease | +(Right LQ pain in Crohn’s Disease, Colicky abdominal or rectal pain in UC) | + (Bloody diarrhea or Mucus or pus in stool) | – | + | – | + | – | – | Abdominal distention, RUQ or LLQ or rectal tenderness -/+, Bloody diarrhea Hepatomegaly -/+, Ascites -/+ | Pyoderma gangrenosum, Erythema nodosum | – | Aphthous Stomatitis | Uveitis, Episcleritis, scleritis | Weight loss, Ankylosing spondylitis, Sacroiliitis, Arthralgia, Osteoporosis, Primary biliary cholangitis, Nephrolithiasis | Anemia of chronic disease, Increased ESR, Electrolyte imbalance, Serum Pr/globulin, Ferritin, CRP, Hypoalbuminemia,low B12 | – | – | – | Saccharomyces cerevisiae Ab, P-ANCA | Stool culture is performed to rule out infectious cause | Small bowel thickening | Aphthous ulcer, erythematous GI mucosa, erosions, spontaneous bleeding, fistula or stricture | Aphthous ulcers, cobblestoning, Skip lesion present in CD, edematous friable mucosa , erosions, paleness, granular mucosa are shown in UC | Thickened small bowel, or fistula | To rule out complication of Inflammatory bowel disease | Endoscopy with Ilieocolonoscopy | – | ||||||||||
| Celiac Disease | +/-, cramping | + | – | + | + | Gingivitis/Stomatitis/Cheilosis | – | – | Tenderness, Loose watery Diarrhea, Nausea, Vomiting, enamel erosion, aphthous ulcer, hyposplenism, constipation, acid reflux | Dermatitis herpetiformis, acne, eczema, seborrheic dermatitis, brittle nails | Asthma, tachypnea, wheezing-/+ | Gingivitis/Stomatitis/Cheilosis | – | Fatigue, weight loss, arthralgia, arthritis, muscle cramping, peripheral neuropathy, headche, dizziness, ataxia, menstrual abnormalities | IDA, Anemia of chronic disease, Increased ESR, Electrolyte imbalance, Serum Pr/globulin, Ferritin, CRP, Hypoalbuminemia, low vitamin B12, low vitamin D | + | – | DNA PCR, HLA Haplotypes, IgA or IgG deaminated gliadin peptide Ab | – | Refractory Celiac disease | IgA or IgG anti TTG, HLA-DQ2/DQ8 | ||||||||||||||||
| Toxic reactions | |||||||||||||||||||||||||||||||||||||
| Irritable bowel syndrome | |||||||||||||||||||||||||||||||||||||
| Tyramine or caffeine toxicity | |||||||||||||||||||||||||||||||||||||
| Gustatory Rhinitis | |||||||||||||||||||||||||||||||||||||
| Acute Infectious rhinitis | |||||||||||||||||||||||||||||||||||||
| Irritant rhinitis | |||||||||||||||||||||||||||||||||||||
| Acute Rhinosinusitis | |||||||||||||||||||||||||||||||||||||
| Hormonal Rhinitis | |||||||||||||||||||||||||||||||||||||
| Vasomotor rhinitis | |||||||||||||||||||||||||||||||||||||
| IgE mediated (Carcinoid Syndrome, Mastocytosis) | |||||||||||||||||||||||||||||||||||||
| Non-IgE mediated (Kawasaki disease, Acute Viral or streptococcal infection, Acute graft-versus host disease, Hereditary angioedema) | |||||||||||||||||||||||||||||||||||||
| COPD | Spirometry | ||||||||||||||||||||||||||||||||||||
| Allergic bronchopulmonary aspergillosis | |||||||||||||||||||||||||||||||||||||
| Bronchiectasis | |||||||||||||||||||||||||||||||||||||
| OSA | |||||||||||||||||||||||||||||||||||||
| Chrug-strauss syndrome | |||||||||||||||||||||||||||||||||||||
| Anxiety | |||||||||||||||||||||||||||||||||||||
| Foreign Body in respiratory tract | |||||||||||||||||||||||||||||||||||||
| Seborrheic dermatitis | |||||||||||||||||||||||||||||||||||||
| Psoriasis | |||||||||||||||||||||||||||||||||||||
| Contact dermatitis | |||||||||||||||||||||||||||||||||||||
| Scabies | |||||||||||||||||||||||||||||||||||||
| Nutrient deficiency ( Zinc, Vitamin B3, Vitamin B6) | |||||||||||||||||||||||||||||||||||||
| Hyper IgE syndrome | |||||||||||||||||||||||||||||||||||||
| Wiskott-Aldrich syndrome | |||||||||||||||||||||||||||||||||||||
| IPEX syndrome | |||||||||||||||||||||||||||||||||||||
| Brutons Agammaglobulinemia | |||||||||||||||||||||||||||||||||||||
References
Epidemiology and Demographics
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Marufa Marium, M.B.B.S[2]
Overview
Epidemiology and Demographics
Incidence
- The incidence of [[allergy] is approximately more than fifty million in a year in US.
Prevalence
Case-fatality rate/Mortality rate
- In [year], the incidence of [disease name] is approximately [number range] per 100,000 individuals with a case-fatality rate/mortality rate of [number range]%.
- The case-fatality rate/mortality rate of [disease name] is approximately [number range].
Age
Allergy prevalence varies with age of population and type of allergic reaction. For example, Allergic skin condition or food allergy may show propensity towards children and younger population while respiratory allergic reaction affects older population more.[2]
Race
- Allergy usually affects individuals of the African American race. Hispanic individuals are less likely to develop allergy.[2]
Gender
Region
- The majority of [[allergy] cases are reported in industrialized region.
Developed Countries
Developing Countries
References
References
Risk Factors
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References
Screening
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References
Natural History, Complications and Prognosis
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
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Complications
- Anaphylaxis (life-threatening allergic reaction).
- Breathing problems and discomfort during the allergic reaction.
- Drowsiness and other side effects of medicines.
Prognosis
Most allergies can be easily treated with medication. Some children may outgrow an allergy. This is particularly true of food allergies. However, as a general rule, once a substance has triggered an allergic reaction, it continues to affect the person.
Allergy shots are most effective when used to treat those with hay fever symptoms and severe insect sting allergies. They are not used to treat food allergies because of the danger of a severe reaction. Allergy shots may require years of treatment, but they work in most cases. However, they may cause uncomfortable side effects (such as hives and rash) and dangerous outcomes (such as anaphylaxis).
References
Diagnosis
Diagnosis
Diagnostic study of choice | History and Symptoms | Physical Examination | Laboratory Findings | Electrocardiogram | X-Ray Findings | Echocardiography and Ultrasound | CT-Scan Findings | MRI Findings | Other Imaging Findings | Other Diagnostic Studies
Treatment
Treatment
Medical Therapy | Interventions | Surgery | Primary Prevention | Secondary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies
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