Showing posts with label angioedema. Show all posts
Showing posts with label angioedema. Show all posts

Wednesday, September 25

Hereditary angioedema - Symptoms - Treatment


Hereditary angioedema (HAE) is a rare genetic disorder affecting up to 0.01% of the population with mortality rates estimated at 15–33%.
Hereditary angioedema causes episodic attacks of cutaneous and submucosal swellings affecting the face, extremities, respiratory tract, genitalia, and gastrointestinal tract.

Detecting the early symptoms help in the correct diagnosis, management and treatment of hereditary angioedema. 75% of the clinical HAE symptoms and manifestations are familial inheritance whereas 25% of the symptoms are caused by fresh mutations in the individuals. As the autosomal mutation is a dominant trait, a child has 50 percent chances for inheriting the disorder if one of the parent is affected by angioedema.

Hereditary angioedema types and causative factors

Bradykinin
The primary cause of this hereditary disorder is the increased release of bradykinin, a plasma kinin responsible for raised capillary permeability and leakage, hyperpermeability of small vessels, pain and edema. Low blood plasma levels of functional C1 esterase inhibitor proteins leads to overactivation of the kallikrein-kinin cascade. The overactivated kallikrein-kinin cascade leads to localized release of bradykinin.
Image of swollen hand of patient affected by hereditary angioedema
Hereditary angioedema - swollen hand
C1-esterase inhibitor (C1-INH)
C1 esterase inhibitor is an important protein regulating the release of bradykinin. Genetic mutations in the C1 inhibitor gene (C1-INH gene or SERPING1 gene), which is mapped to chromosome 11 (11q12-q13.1), can affect or alter the production of normal C1 esterase inhibitor protein.

In type I disorder, gene mutations cause inadequate levels of C1 esterase inhibitor production. 80-85% of hereditary angioedema afflictions come under type I.
In type II disorder, though gene mutations do not lower the production levels of C1 esterase inhibitor protein, the protein produced is ineffective or non-functional in regulating the bradykinin. About 15-20% of of HAE cases come under type II.
In type III disorder, there is no deficiency or inefficiency of C1 esterase inhibitor protein. There is increased levels of kininogenase activity causing increased levels of bradykinin. Increased levels of estrogen hormone can aggravate type III disorder symptoms. Affected Women on oral contraceptives may develop symptoms and have recurrent episodic attacks. They are also susceptible to recurrent episodes during pregnancy. Mutations in F12 gene coding for a serine protease called Factor XII cause type III disorder.

Symptoms of hereditary angioedema

Nonpitting cutaneous swelling is a common symptom affecting the face, hands and legs.
The gastrointestinal afflictions cause edema of the intestinal mucosa leading to symptoms like vomiting, stomach pain and intestinal spasms.
The respiratory tract afflictions can cause blocked airway, suffocation and asphyxiation. Edema of the respiratory tract is a life-threatening emergency requiring treatment at a hospital. Hereditary angioedema patients with the slightest throat or airway swelling symptoms should seek immediate emergency treatment.

Diagnosis of hereditary angioedema

Correct diagnosis of the symptoms of this disorder is vital for proper treatment to avoid potentially fatal consequences. The following symptoms can point to hereditary angioedema.
  • Frequent episodic symptoms of angioedema without hives,
  • frequent episodes of abdominal pain and vomiting,
  • frequent episodes of laryngeal swelling and edema of upper airway and
  • familial history of angioedema.
Blood tests taken during the episodes can help in right diagnosis. Quantitative and functional analysis of C1 esterase inhibitor is carried out.
Low C1 esterase inhibitor (C1-INH) level indicate type I.
The diagnosis may be complemented with radiography of the chest and abdomen and ultrasonography and CT scanning.

Hereditary angioedema treatment, management and prophylaxis

Hereditary angioedema does not respond to treatment with antihistamines, corticosteroids, or epinephrine.
Treatment of this hereditary disorder with C1 inhibitor replacement products, plasma kallikrein inhibitor, and bradykinin-receptor antagonist have given significant relief to the patients.

Treatment with plasma derived C1 inhibitor products like C1-INH concentrate replace the deficiency and take over the regulation of the mediating proteins. The nano-filtered C1-INH concentrate, Cinryze, is found to be effective in the treatment of acute episodic attacks.

Treatment with selective bradykinin B2 receptor antagonist, Icatibant, blocks the function of bradykinin.
The kallikrein inhibitor, ecallantide, when used prevents the release of bradykinin.
Attenuated androgens, such as danazol, have been found to reduce the severity as well as frequency of episodes when used on early symptoms. Treatment with these medications induces the body to produce more C1 inhibitor.

Treatment of hypertension with ACE inhibitor (or angiotensin-converting-enzyme inhibitor) drugs is contraindicated in this disorder, as these drugs can cause bradykinin accumulation and trigger the symptoms.
Fresh episodic symptoms may be triggered by dental and surgical procedures, stress, infections and even menstrual cycle. Specific triggers that have previously led to episodes of attacks may need to be avoided to prevent future hereditary angioedema attacks.

Image source: http://en.wikipedia.org/wiki/File:Swollen_hand_during_a_hereditary_angioedema_attack..jpg
Image author: LucyHAE | License: CC BY-SA 3.0

References:
1.Hemperly, SE; Agarwal, NS; Xu, YY; Zhi, YX; Craig, TJ (July 2013). "Recent Advances in the Management of Hereditary Angioedema". Journal of the American Osteopathic Association 113 (7): 546–555. doi:10.7556/jaoa.2013.006.
2.Zuraw BL, Bernstein JA, Lang DM, et al. A focused parameter update: hereditary angioedema, acquired C1 inhibitor deficiency, and angiotensin-converting enzyme inhibitor-associated angioedema. J Allergy Clin Immunol 2013; 131:1491.

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Monday, August 19

Symptoms of angioedema

Sudden swelling of the hands, feet, eyes, lips, tongue, throat or genitals are symptoms of angioedema.
However in some cases, a thorough differential diagnosis of the possible medical and toxic causes of swellings may be necessary to eliminate the potential presence of other pathological conditions with similar symptoms. Angioedema symptoms may manifest over the period of minutes to hours. It is impossible to predict when and where the next angioedema episode will occur.

The involvement of tongue or mucosa of the mouth or throat may cause stridor (a high-pitched wheezing sound) as the airway gets blocked progressively. In some cases anaphylaxis (anaphylactic shock) may occur characterized by a sharp drop in blood pressure. Both the situations require emergency medical care to prevent respiratory/cardiac arrest.

Appearance of symptoms of angioedema

The swellings may appear over the period of minutes to hours. The swellings usually appear on the face, normally around the eyes and the mouth. The tongue may be affected partially or totally. In some cases, the swellings may affect the mucosa of the oral cavity and throat. The swelling can also appear elsewhere on the body, typically on the hands, feet or genitals.
Image of tongue affected by angioedema
Image of angioedema of the tongue

The affected parts of the body may show symptoms like itching or pain. Usually the affected parts of the body feel warm or hot and is of the same color as the surrounding unaffected area. However, in some conditions, the affected region may appear pink or red with inflammation. In some patients urticaria may also occur simultaneously. The edema in the genital parts can interfere with urination and require medical help.

In hereditary angioedema there may be recurrent episodes of abdominal pain followed by vomiting and diarrhea. There may be significant rise in the white blood cell count, which decreases when the symptoms diminish. These abdominal episodes may be very severe, requiring hospitalization for pain management. The symptoms like  abdominal pain, vomiting and diarrhea are common to many abdominal ailments like appendicitis, gastric, duodenal and intestinal ulcers. Differential diagnosis and the study of the patient's history of earlier abdominal episodes may be able to pinpoint the cause of abdominal swellings and pain.

List of angioedema symptoms

  • swelling below the skin
  • presence of a firm swelling
  • swelling of the face, hands, throat, feet or genitals
  • painful sensation
  • itchy sensation
  • hot or warm sensation
  • edema of the conjunctiva
  • edema of the eyelids
  • edema of the tongue
  • edema of the oral cavity
  • edema of the inside of the throat.
Life-threatening symptoms include:
  • severe chest tightness and pain
  • stridor breathing
  • difficulty in breathing
  • trouble in swallowing
  • symptoms of anaphylactic shock
  • giddiness
  • lightheadedness
  • breathlessness
  • rapid progression of swelling
  • Abdominal pain or cramping
Avoiding triggers and taking antihistamines can reduce the severity of attacks. Many treatment options are now available to alleviate the symptoms of angioedema swellings.

Image source: http://en.wikipedia.org/wiki/File:Angioedema2013.JPG
Images author: James Heilman, MD
Images license: Creative Commons Attribution-Share Alike 3.0 Unported license.

 References:
1. Zuraw BL. Novel therapies for hereditary angioedema. Immunol Allergy Clin North Am. 2006 Nov;26(4):691-708.
2. Angioedema | University of Maryland Medical Center http://umm.edu/health/medical/altmed/condition/angioedema
3..13.Levi M, Choi G, Picavet C, Hack CE. Self-administration of C1-inhibitor concentrate in patients with hereditary or acquired angioedema caused by C1-inhibitor deficiency. J Allergy Clin Immunol 2006; 117:904.

 Current topic: Angioedema swellings and symptoms

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Monday, July 15

Skin diseases - Angioedema treatment

Mild case of angioedema clears up on its own in a few days without any specific treatment. To alleviate the mild symptoms, the patient may have cool bath and apply cold compress on the affected skin area.
Strenuous physical activities must be avoided as the warming up of the body may aggravate the angioedema condition.

Nonprescription antihistamines may be used in the angioedema treatment to get relief from itching and discomfort. If the mild symptoms are not clearing up in three or four days, if the symptoms persist even after taking medication or if there is progression of the condition, treatment of angioedema by a doctor becomes necessary.

Avoiding angioedema triggers

Identifying and avoiding allergins and other triggering factors that cause the angioedema goes a long way in preventing and lessening the intensity of symptoms. The causative factors may include certain types of food, alcohol, medicines, insect stings, insect bites, certain drugs and harsh chemicals. Individuals prone to severe attacks can avoid the severity by starting the treatment early.

Angioedema treatment with medication

A patient with moderate angioedema would be prescribed antihistamines and anti-inflammatory medicines like corticosteroids. For conditions caused by allergins as well as the * idiopathic angioedema, the treatment is the same. However for drug-induced angioedema, the immediate withdrawal of the culprit medicine and use of an alternative medication will provide relief.

Severe cases, where the patient has difficulty in breathing requires maintenance of airway and also use of inhaler medicines, subcutaneous epinephrine injections, antihistamines, corticosteroids and H1 and H2 blockers.

Hereditary angioedema treatment requires a preventative approach. Usually it does not respond to antihistamines, corticosteroids or epinephrine. Medications regulating levels of blood proteins, C1 inhibitor concentrate or inhibitor of plasma kallikrein may be administered to relieve the symptoms.

Antihistamines
Angioedema is an immune response to pathogens and triggering factors resulting in the production of inflammatory mediators such as histamine. The resultant inflammation causes dilation and leakage of blood vessels and fluid accumulation in the intercellular spaces. Antihistamines block the effects of histamine and reduce the inflammatory response. The Histamine-2 receptor antagonists like ranitidine or cimetidine are also effective. They may be used in conjunction with H1 blockers.

Based on the side effects and the chemical composition, antihistamines are categorized as older, first-generation and newer second-generation antihistamines. The new medicines generally do not cause drowsiness or reduce one's reaction time during angioedema treatment. Considering their chemical effects both the new and older medicines are categorized into nonprescription and prescription medicines.

Diphenhydramine and chlorpheniramine are nonprescription first-generation antihistamines. Hydroxyzine is a prescription first-generation antihistamine. Loratadine and cetirizine are nonprescription second-generation antihistamines. Desloratadine, fexofenadine and levocetirizine are prescription second-generation antihistamines.

Corticosteroids
Cotricosteroids (steroids) work by blocking the immune responses. In acute cases of angioedema unresponsive to regular antihistamine treatment, corticosteroids are used. Corticosteroids reduce inflammation and vascular permeability. Corticosteroids like prednisone, prednisolone and methylprednisolone are commonly prescribed.

Hereditary angioedema

In conditions which are hereditary in nature, there are medicines to prevent them and also medications to relieve symptoms. Anabolic steroids like danazol, C1 esterase inhibitor, or a kallikrein inhibitor are prescribed for preventing attacks and relieving symptoms.

Emergency treatment

Angioedema caused laryngeal edema can progress rapidly leading to severe throat swelling and airway obstruction.
It is a life-threatening emergency requiring establishment of airway and maintenance of respiration. Endotracheal tube may have to be inserted into the trachea and connected to oxygen supply to maintain respiration. In cases with excessive swelling of throat, endotracheal intubation becomes impossible. In such cases, the doctor may resort to tracheostomy, a procedure consisting of making an incision on the neck and opening a direct airway through an incision in the trachea.

Severe angioedema may also lead to anaphylaxis requiring immediate administration of epinephrine. Patients prone to anaphylaxis may have to carry a prescribed epinephrine autoinjector for use in case of emergency.
References:
1.68.Bork K, Hardt J, Schicketanz KH, Ressel N. Clinical studies of sudden upper airway obstruction in patients with hereditary angioedema due to C1 esterase inhibitor deficiency. Arch Intern Med 2003; 163:1229.
2.13.Levi M, Choi G, Picavet C, Hack CE. Self-administration of C1-inhibitor concentrate in patients with hereditary or acquired angioedema caused by C1-inhibitor deficiency. J Allergy Clin Immunol 2006; 117:904.

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Thursday, June 27

Skin diseases - Causes of angioedema

Home > List of skin diseases > Angioedema causes
Angioedema is the sudden swelling under the skin. The dermis, subcutaneous tissue, mucosa and submucosal tissues are involved in these inflammatory reactions.
Angioedema is often caused by the immune responses to the pathogens, allergins or other triggering factors. These deeper skin reactions are either hereditary or acquired. The acquired angioedema may be due to the reactions to allergens, drugs or unknown (idiopathic) causes. The skin edema may or may not be accompanied by hives. If there are severe swellings of the tongue or throat, they need to be taken seriously as they can cause difficulty in breathing.

Known triggering factors of acquired angioedema

Allergens such as certain types of food, medicines, insect stings, insect bites and harsh chemicals may trigger the angioedema associated swelling. Certain drugs may also induce the reactions. Many swelling reactions do not have known cause and are idiopathic in nature.

Allergic angioedema

  • Food items such as peanuts, fish, shellfish, canned vegetables, alcohol, caffeine, legumes, berries, chocolate, milk and eggs may cause the condition.
  • Medicines and antibiotics such as penicillin, sulfa drugs, anti-inflammatory drugs, vaccines and aspirin can be the triggering factors.
  • Stings of spiders, centipedes, wasps and bees may cause the condition.
  • Chemicals such as detergents, dyes and latex may trigger the condition.
  • Cosmetics, moisturizers and skin whiteners containing harsh chemicals can also cause angioedema.
  • Animal dander and pollen are known to trigger the condition.   

Non-allergic, drug-induced angioedema

In the treatment of high blood pressure, ACE (angiotensin converting enzyme) inhibitors and Beta-blockers are usually prescribed. In some patients these drugs may cause swelling of the face, throat and tongue. In patients who are already prone to hives, the drug reaction may be severe. The swellings are usually not itchy or painful, and the skin colour may be normal. Bupropion, selective serotonin reuptake inhibitors (antidepressant), COX-II inhibitors (painkillers), proton pump inhibitors (to treat stomach ulcers) and statins are also known to induce the swellings.

Idiopathic angioedema

If the exact cause is not known the swellings are considered idiopathic. Stress, infections, alcohol, spices, hot bath, tight clothes have been found to trigger this condition.

Hereditary angioedema

This is a rare condition in which C 1 esterase inhibitor enzyme (aka: C1-inhibitor or C1INH) levels are low. The low levels of C1INH result in bradykinin release leading to increased vascular permeability. The end result is the leakage of fluid and its rapid accumulation in the interstitium. The hereditary form is similar to ACE-induced form in that the swellings are not itchy or painful, and the skin colour is normal.

The hereditary type does not respond to antihistamines or steroids. The episodes may be recurrent and affect the stomach. The patients experience abdominal pain, intense vomiting, diarrhea and general weakness.

There are three types of hereditary angioedema. In type I, there is decrease in the levels of C1INH. In type II, though C1INH levels are normal, there is decreased function of C1INH. In type I and II are caused by mutation of C1NH (SERPING1) gene on chromosome 11, which encodes C1 inhibitor protein. In type III there is mutation in F12 gene on chromosome 12, which encodes coagulation factor XII. In type III the reactions are severe in women.

There are some conditions which can result in swellings of lips, eyes and face. These non-angioedema swellings may be caused by contact dermatitis, connective tissue disease, dermatomyositis, endocrine disease, myxedema, parasitic disease or SVC syndrome. These swellings are slow in progression. Angioedema is usually characterized by sudden swellings. A complete differential diagnosis may be required to exclude these above conditions.
References:
1.Dreskin SC. Urticaria and angioedema. In: Goldman L, Schafer AI, eds. Cecil Medicine. 24th ed. Philadelphia, Pa: Saunders Elsevier;2011:chap 260.
2.Wasserman SI. Approach to the person with allergic or immunologic disease. In: Goldman L, Schafer AI, eds. Cecil Medicine. 24th ed. Philadelphia, Pa: Saunders Elsevier;2011:chap 257.
3.Zuraw BL. Novel therapies for hereditary angioedema. Immunol Allergy Clin North Am. 2006 Nov;26(4):691-708.
4.Chinen J, Shearer WT. Advances in basic and clinical immunology. J Allergy Clin Immunol. 2007 Aug;120(2):263-70.

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Friday, May 31

Skin care - Angioedema definition

Home > Hives and angioedema > Definition of angioedema swellings.
Angioedema is an edema of the subcutaneous tissue usually caused by an allergic reaction to food or drugs. In hives the swelling is superficial skin reactions whereas in angioedema the reaction is under the skin.
The inflammation may range from small spots to large patches of several inches in diameter.

The swellings can occur on any part of the body, but generally occur on the face, around the eyes and lips, inside the mouth and throat and on the tongue. In most of the incidences these reactions resolve by themselves. In some cases when affecting the tongue or throat, the swelling may block the airway and become life threatening.

Angioedema is an immune response to pathogens and triggering factors. It results in production of inflammatory mediators such as histamine by the basophils and mast cells. The resultant inflammatory responses lead to dilation and leakage of blood vessels causing fluid accumulation in the intercellular spaces. In most of the incidences the exact cause may not be known. However many angioedema swelling triggering factors are known. The swelling is usually treated with antihistamine medications.

Medical definitions of angioedema
Wordnetweb.princeton.edu/perl/webwn: "recurrent large circumscribed areas of subcutaneous edema; onset is sudden and it disappears within 24 hours; seen mainly in young women, often as an allergic reaction to food or drugs."

According to thefreedictionary.com: "angioedema, a vascular reaction involving the deep dermis or subcutaneous or submucosal tissues, representing localized edema caused by dilatation and increased permeability of the capillaries, and characterized by the development of giant wheals."
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Wednesday, May 15

Skin care - Hives and angioedema

Home > Angioedema and hives
Hives and angioedema are skin or tissue reactions due to a complex release of inflammatory mediators, including histamine into the surrounding tissues or bloodstream.
In the majority of cases, it is not possible to determinate the exact cause. Many triggering factors of hives and angioedema are known.

Inflammatory mediators such as histamine are produced by basophils and mast cells in the integumentary system and mucosa. Their release is a part of an immune response to pathogens and triggering factors. These inflammatory responses lead to dilation and leakage of blood vessels. The resultant accumulation of body fluids in the intercellular spaces causing the swellings.

Appearance of hives and angioedema

Hives is the result of superficial skin reactions in the upper dermis, leading to pale red, raised bumps. They may cause itchy, stinging or burning sensation. These hives wheals can appear anywhere on the skin surface. The size of the bumps may vary from small spots to large patches of several inches in diameter. Hives may last from a few hours to several weeks.
1. Picture hives on hand
Angioedema is the result of inflammatory responses leading to rapid swelling of the dermis, subcutaneous tissue, mucosa and submucosal tissues. The angioedema often appears around the eyes, lips, cheeks, tongue and throat. It is also observed to develop on the hands, feet, genitals or intestinal tract. Rapidly progressing angioedema in the mouth and the throat must be treated as a medical emergency as the air passage may get blocked suffocating the patient.

Types and causes hives and angioedema

  • Hives is considered 'idiopathic' if the cause is not known.
  • The skin reaction completely resolving within six weeks is termed 'acute', whereas the condition lasting more than six weeks is known as 'chronic'.
  • Various drugs like dextroamphetamine, penicillin, sulfonamides and anticonvulsants have been found to cause allergic reactions.
  • Exposure to many physical factors such as stress, scratching, firm stroking (dermatographic), pressure, sweating events, exercise (cholinergic), bathing, sun (solar), heat, cold, water (aquagenic), pressure or some types of food can cause hives.
  • Allergens in pollen, animal dander, chemicals, latex, insect venom, cosmetics, detergents etc. can cause skin allergies.
    2. Angioedema of the tongue
  • Angioedema may occur with or without weals. It is classified as either acquired or hereditary.
  • The acquired skin reactions may be due to unknown causes (idiopathic).
  • The acquired angioedema can be classified as either immunologic or nonimmunologic.
  • It can occur as reactions to hypertension medications like ACE inhibitors.
  • Hereditary angioedema (HAE) is classified into three forms.
  • Hereditary angioedema type I is caused by mutations in the SERPING1 gene, which result in diminished levels of the C1-inhibitor protein.
  • HAE type II is caused by mutations in the SERPING1 gene, which result in the dysfunctional forms of the C1-inhibitor protein.
  • HAE type III is caused by mutations in the F12 gene.
  • All these mutations trigger the complement system causing swellings anywhere in the body.
  • In some persons vibration can cause angioedema, especially of hands.
  • In some patients, angioedema can progress rapidly into Anaphylaxis or anaphylactic shock causing death.

Signs and symptoms hives and angioedema

Symptoms of hives include superficial raised red, pale red or white wheals which can be of varying sizes with itchy sensation. Sometimes there may be burning or stinging sensations. The swellings may last for a few hours to a few days in the acute form and may last for months and years in chronic form.

Angioedema is characterized by large thick swelling. The affected area may be itchy, firm and warm and it may be painful when squeezed or pressed. The swellings may appear on any part of the body. Angioedema may appear as sudden and severe swelling. If it is associated with the gasstrointestinal system, 'abdominal attacks' may occur with symptoms like intense stomach pain and cramps. The swellings in the mouth, tongue, larynx or throat may show symptoms like gasping or wheezy inspiratory breath sounds.
The angioedema may sometime become life-threatening due to blocked airway.

Diagnosis and treatments for hives and angioedema

Mild hives or angioedema does not require treatment. Identifying triggers and avoiding them can help greatly. If the skin reaction is severe, persistent, very itchy or causing severe discomfort, many treatment options are available. Antihistamines are the drugs of choice for treating angioedema and hives.

First-generation antihistamines like hydroxyzine, diphenhydramine and chlorpheniramine are helpful when the symptoms of angioedema are severe and involve swelling on the face, tongue or throat. These medications can cause drowsiness, blurred vision, reduced reflex actions and reduced physical coordination.

Second-generation antihistamines include loratadine, desloratadine, fexofenadine, levocetirizine and cetirizine. These antihistamines have lesser side effects. Chronic cases of hives and angioedema may respond well to  steroid therapy with  prednisone, hydrocortisone, fluocinonide, or desonide. Type H2 antihistamines such as ranitidine, cimetidine and famotidine when given along with type H1 antihistamines treat angioedema and hives.

Epinephrine may be life-saving in severe rapidly progressing allergic angioedema. For treating hereditary angioedema certain androgens, such as dexamethasone, danazol and methyltestosterone have been found to be effective on a long-term basis. In treating hereditary angioedema, Cinryze and Berinert derived from human blood plasma have been found to be effective.
1.Image source: http://en.wikipedia.org/wiki/File:EMminor2010.JPG
2.Image source: http://en.wikipedia.org/wiki/File:Angioedema2013.JPG
Images author: James Heilman, MD
Images license: Creative Commons Attribution-Share Alike 3.0 Unported license.
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