1. Dermatology A.Prof.Dr.mohammed yassin Lec: 3 Urticaria(HIVES)
Urticaria is a vascular reaction of the skin characterized by the appearance of wheals, generally surrounded by a red halo or flare & associated with sever itching, stinging or pricking sensations. Individual
hives can last as briefly as 30 minutes to 36 hrs. They can be as small as a millimeter or 6–8 inches in diameter (giant urticaria)
These wheals are caused by localized edema, clearing of the central region may occur & lesions may coalesce, producing an annular or polycyclic pattern, Hives occur at any age up to 20% of the population will have at least one episode.
*subcutaneous swellings (Angioedema) may accompany the Hives which may target the gastrointestinal & respiratory tracts resulting in abdominal pain & respiratory problems, anaphylaxis & hypotension may also occur.

3. Clinical classification of urticaria.
1 Ordinary urticaria
Acute
Episodic (acute and chronic intermittent)
Chronic (previously qualifi ed as ‘idiopathic’ prior to recognition of the
autoimmune subtype)
2 Physical and cholinergic urticarias
3 Urticarial vasculitis
4 Contact urticaria
5 Angio-oedema without weals
6 Other syndromes resembling urticaria or angio-oedema, or with urticaria as a

4. Classification:
1. Acute urticaria: evolves over days-weeks producing evanescent wheals that individually rarely last more than 12 hours with complete resolution of the urticaria with in 6 weeks of onset.
Acute urticaria common in children & young adults.
2. Chronic urticaria: daily episodes of urticaria &/or angioedema lasting more than 6 weeks.
Chronic urticaria predominantly affects adults & is twice as common in women as in men.
*non immunologic mechanisms can produce mast cell deregulation.
*>50% of chronic urticaria is idiopathic.
*physical stimuli represent 7-17% of chronic urticaria .
-physical stimuli or physical urticaria( dermatographism, cold, heat, cholinergic, solar, vibratory & exercise induced urticaria).

5. Pathogenesis:
*skin lesions & pruritus occur by allergic or no allergic mechanisms.
*Histamine is thought to be the most important mediator in urticaria
*acute urticaria is IgE-mediated, or complement mediated or non-immune mediated
*type Ι (IgE-mediated) hypersensitivity reaction responsible for most cases of acute urticaria(circulating antigens such as foods, drugs or inhalants).
*complement mediated or immune-complex mediated acute urticaria can be caused administration of whole blood, plasma, immunoglobines, drugs, insect bites.
*non-immunologic release of histamine (pharmacologic mediators such as acetylcholine, opiates, polymyxine B & strawberries).
*chronic urticaria is induced by histamine released from mast cell & basophiles.
*chronic urticaria has been associated with antithyroid auto-antibodies

7. Etiologic factors:
1. drugs: are the most frequent cause of acute urticaria, penicillin & related antibiotics are the most frequent offenders.
*urticaria reaction can occur 14 days after course of treatment has stopped.
*non allergic release of Histamine by (asprin, NSAIDs, opiates, polymyxin, ciprofloxacin, rifampicin, vancomycin).
2. food: are a frequent cause of acute urticaria where as in chronic urticaria is less frequent factor.
*the most allergic foods are chocolate, shellfish, nuts, peanuts, tomatoes, strawberries, melons, cheese, garlic, onions, eggs, milk, and spices.
3. Food additives:
*natural food addictives (yeast, salicylates, citric acid, eggs & fish albumin).
*synthetic additives (azo dyes, benzoic acid derivatives, sulfite and penicillin).
*yeast found in (bread, bread stuffs, sausages, grapes, cheese).
*azo dyes & benzoic acid found in (soft drink, jelly, custard, various cakes, mayonnaise).

8. 4. Infections:
*acute urticaria may be associated with upper respiratory tract infections, especially streptococcal infections.
*localized infections in tonsils, tooth, sinuses, gall bladder, prostate, urinary bladder & kidney.
*chronic viral infections such as hepatitis B & C.
*helimenthes may cause urticaria these are ( ascaris, ankylostomas, strangyloids, filarial, echinococcus, schistosoma, trichinella, toxocara & liver flukes.
5. Emotional stress:
Persons under sever emotional stress may have more marked urticaria.
6. Menthol:
It is found in mentholated cigarettes, candy, cough drops, aerosol sprays & topical medications.
7.Neoplasms:
Urticaria has been associated with carcinoma & Hodgkin's dis.
8. Inhalants:
Grass pollens, house dust mites, feathers, formaldehyde, acrolein, castor bean, soy bean dust.

9. 9. Alcohol:
The mechanisms of indirect mast cell stimulation are unknown.
10. Hormonal causes:
-Endocrine tumors
-Ovarian pathology
-Oral contraceptive use
11. Physical causes (physical urticaria):
Cold, pressure, vibration, cholinergic (triggered by heat, exercise or emotional stress), sunlight, water, exercise.
Typical features:
*Typical lesions are described as edematous pink or red wheals of variable size surrounding erythema.
*The lesions are generally pruritic, a painful or burning sensations often associated with angioedema.
*Dermographism is often observed in conjunction with urticaria itching, erythema occur in areas that are scratched or stroked.
*Individual lesions usually fade within 24 hrs, but new lesions may be developed.

10. PHYSICAL URTICARIA/ ANGIOEDEMA
Dermographism :is the most
common form of physical urticaria and is the one
most likely to be confused with chronic urticaria.
A lesion appears as a linear wheal with a flare at a
site in which the skin is briskly stroked with a firm object

12. PRESSURE URTICARIA. Delayed pressure urticaria appears as erythematous, deep, local swellings,often painful, that arise from 3 to 6 hours after sustained pressure has been applied to the skin Spontaneous episodes are elicited on areas of contact
after sitting on a hard chair, under shoulder straps
and belts, on the feet after running, and on the hands
after manual labor

13. COLD URTICARIA. There are both acquired and
inherited forms of cold urticaria/angioedema; however,
the familial form is rare
Idiopathic or primary acquired cold urticaria may be associated with headache,hypotension, syncope.The elicitation of a wheal after the application of ice has been called a diagnostic:
cold contact test

15. CHOLINERGIC URTICARIA
develops after an increase in core body temperature,
such as during a warm bath, prolonged
exercise, or episodes of fever.The highest prevalence
is observed in individuals aged 23–28 years. The eruption
appears as distinctive, pruritic, small, 1- to 2-mm
wheals that are surrounded by large areas of erythema

18. *does the patient have any recent or chronic infections.
Questions to be asked to a patient with urticaria *are the Hives associated with any foods or new foods added?
*is the patient take any regular medication or have any new medicines, ask about (aspirin, NSAIDs, antibiotics).
*does the patient have any recent or chronic infections.
*are the Hives caused by physical stimuli (heat, cold, pressure).
*does the patient have any chronic medical conditions.
*is the urticaria associated with substances inhaled.
*is the urticaria associated with insect bites.
Differential diagnosis:
Bullous pemphigoid (urticarial stage).
Dermatitis herpetiformis.
Drug eruptions.
Erythema marginatum.
Erythema multiform.
Papular urticaria.
Pruritic urticarial papules & plagues of pregnancy.

19. 8. Still disease.
9. Urticaria pigmentosa.
10 .Urticarial vasculitis.
Laboratory studies:
*skin test or radioallergosorbent assay test (specific Ig-E)
-selected allergy test can be performed if food allergy or stinging insect skin testing can be preformed.
*screening laboratory studies:
1. CBc with differential.
2. Total eosinophil count.
3. Sedementation rate
4. Urinolysis
5. Liver function test
*Evaluation of complement system
*Thyroid studies include thyroid autoantibody

20. Treatment:
*acute urticaria:
-The mainstay of treatment of acute urticaria is antihistamines
-If the cause can be identified avoiding that trigger should be stressed
-Treat with oral H1 antagonists
-Add H2 antagonists for resistant cases.
-Non sedating H1 antihistamines are the first choice of treatment.
(Loratidine(Claridin 10mg), Cetirizine(Zyrtee), Fexofenadine,)
-older sedating H1 antihistamines are more effective & should be used to treat severs urticaria
( Diphenhydramine(Allermine 25mg), Hydroxyzine(atarax), Cyproheptadine(periactin)
*chronic urticaria:
-The mainstay for treating chronic urticaria is again administration of antihistamines; these should be taken on daily basis.
-the 2nd generation H1 antihistaines (Cetrizine, Loratidine) are large, Lipophilic molecules with charged side chains that bind extensively to proteins, preventing the drugs from crossing the blood brain barrier, thus they produce less sedation in most patients.

22. -Doxepin atricyclic antidepressant with potent H1 antihistaminic activity may be added to existing antihistamine, & used at bed time.
-The combination of H1 & H2 antihistamines such cimetidine or rantidine may be effective.
-Rantidine or Cimetidine should not be used alone in treatment of urticaria.
-Other 2nd line treatments:
.Phototherapy
.Calcium channel antagonist(Nifedipine)
.Antimalarial medications ,dapson,gold,azathioprine
.Low does cyclosporine
.Terbutaline ..
-For local treatment, tepid or cold tub bath or showers may be freely advocated.
Topical camphor & menthol can provide symptomatic relief
-Other lines of treatment include chronic immunosuppressive therapy, plasmapheresis or intravenous immunoglobulin (IVIG).
-leukotriene receptor antagonists: Zafirlnkast (accolade), Montelukast (sirgulaim) especially in combination with antihistamines.

23. Other urticarial variants:
-Angioedema: is an acute, evanescent, circumscribed edema that usually affects the most distensible tissues, such as eyelide, lips, lobes of ears & external genitalia, or the mucous membranes of the mouth, tongue, or larynx.
*the swelling occurs in the deeper parts of the dermis, the overlying skin is unaltered, edematous or rarely ecchymotic.
*there may be diffuse swelling on the hands, forearms, feet ankles.
*frequently the condition begins during night & is found on awakening.
-There are two distinct subsets of angioedema, the 1st is considered a deep form of urticaria & may be observed as solitary or multiple sites of angioedema alone or in combination of urticaria.
The 2nd type associated with C1 esterase inhibitor deficiency is not associated with hives & there is no pruritus.
Hereditary Angioedema:
-characteristically appears in 2nd-4th decade.
-Sudden attacks as frequently as every 2 weeks, lasting 2-5 days.
-swelling is typically asymmetrical, & urticaria or itching does not occur
-patients may experience local swelling in subcutaneous tissues (face, hands, arms, legs, genitals & buttocks), abdominal organs (stomach, intestines, bladder) mimicking surgical emergencies &the upper air way (larynx) that can be life threatening.

24. -inherited in autosomal-dominant.
-triggering factors (minor trauma, surgery, & change in temperature or sudden emotional stress.
-the screening test of choice C4 will be low & also low C1, C1q, C2 levels.
-treatment of choice replacement with concetrates or fresh frozen plasma.
-short term prophylaxis in (eg: dental care, endoscopy or intubation for surgery) can be obtained from stanozolol.
-Antifibrinolytic tranexamic acid.
Acquired Angioedema:
-patients indistinguishable from hereditary Angioedema but:
-the onset after the 4th decade of life & lacking family history.
-there is no associated pruritus or urticaria.
-associated with lymphomas (B cell), chronic lymphcytic leukemias, myloma, myelofibrosis.
-there is acquired C1 Esterase inhibitor deficiency.
-Management:
By replacement of C1 esterase inhibitor with concentrates or fresh frozen plasma.
-some patients develop resistance agents such as aminolaproic acid or tranexmic acid can be used.
-synthetic androgens such as danazol may be helpful.

25. Icatibant, abradykinin B-2 receptor antagonist, has been approved
for acute treatment in Europe but not in the United
States. It is given by subcutaneous injection. Kalbitor,
a plasma kallikrein inhibitor (ecallantide), has been
approved for the treatment of acute attacks of HAE in
the United States.

26. Hereditary angioedema

27. ANGIOTENSIN-CONVERTING ENZYME INHIBITORS
Angioedema has been associated with the
administration of ACE inhibitor.
The frequency of angioedema occurring after ACE inhibitor therapy is 0.07%-0.1%
Angioedema develops during the first week of therapy in up to 72% of affected individuals and usually
involves the head and neck, including the mouth,tongue, pharynx, and larynx