URTICARIA Etymology: Latin urtica, nettle

Prof. IHAB YOUNIS, M.D.

Classification

1- Ordinary Urticaria

• Acute

• Chronic 2- Immune complex urticaria

• Serum sickness

• Urticarial vasculitis 3- Physical urticaria

4- Contact urticaria

5- Angioedema

1 -Ordinary UrticariaAcute Urticaria

• First described in the English literature in 1772

• The natural course of the acute disease lasts up to 6 weeks

Etiology• Urticaria affects 15 -20% of the population

at some point in their lives

• Females have a slightly higher prevalence (61%) than males

• A definitive provoking agent can be identified in 40 -50% of cases of acute urticaria

• Histamine is the most important biochemical mediator

• It is released

from mast cells and basophils

• Histamine is the ligand (a molecule that binds to a receptor) for at least 2 types of receptors, H1 and H2

• The activation of H1 histamine receptors on smooth muscle cells and endothelial cells leads to cellular contraction and increased vascular permeability

• The activation of H2 histamine receptors causes vasodilation resulting in extravasation of plasma into the dermis

• Acute urticaria may be caused by an immune or a non-immune mechanism:

Immune-mediated urticaria

Caused by 3 of the 4 types of immune mechanisms:

Type I: allergic IgE response is initiated by antigen-mediated IgE immune complexes that bind and cross-link Fc receptors on the surface of mast cells and basophils. The types of antigens that bind to IgE are varied and include:

• Recent infection from a viral syndrome or an upper respiratory illness

• Medications : eg, ACE inhibitors, aspirin, nonsteroidal anti-inflammatory drugs, sulfa-based drugs, penicillins, cephalosporins, tetracyclines, diuretics, opioids.(usually occurring within 36h of drug administration. It is unusual to develop urticaria from a drug taken continuously for months)

• Food and food additives :e.g. nuts, fish, shellfish, eggs, chocolate, strawberries, salicylate, benzoates.Many cases go unreported and usually, reactions occur within minutes

• Parasitic infections (e.g. Ascaris, Ancylostoma, Strongyloides, Echinococcus, Trichinella, Filaria)

• Physical stimulants : e.g. cold, pressure, aquagenic

• Chemicals :e.g. latex, ammonium persulfate in hair chemicals

• Intravenous radiocontrast media

• Arthropod bites(bees and wasps)

• In one recent study, causes were identified as:

-Upper respiratory tract infection in

39.5%

-Analgesics in 9%

-Food intolerance in 0.9%

Type II: responses are mediated by cytotoxic T cells. The disease process activates byproducts that cause urticarial vasculitis or bullous pemphigoid

Type III: immune-complex disease is associated with systemic lupus erythematosus and other connective tissue disorders that activate urticaria

Non–immune-mediated

• Some chemicals can directly induce mast cell degranulation, presumably by altering the membrane properties

• Common agents are opiates, antibiotics, curare, radiocontrast media, azo dyes, aspirin, aspirin derivatives and radiocontrast media

Clinically

• Wheals:edematous, evanescent, erythematous plaques

• Lesions vary from several millimeters to large, continuous plaques

•

Plaques have smooth surfaces with polycyclic curved borders

• Lesions show an intense erythema in the newest areas, with a trailing clearing region in older areas

• Individual lesions remain for less than 24 hours, exhibiting a transitory and migratory behavior

• Greater than 80% of new-onset urticaria cases resolve in 2 weeks and greater than 95% of new-onset cases resolves by 3 months

Treatment

• Avoidence of the cause

• Antihistamines

• Systemic corticosteroids

Chronic Urticaria

Urticaria that persists for longer than 6 weeks

Etiology

1-Medications: common drugs include aspirin, nonsteroidal anti-inflammatory drugs, opioids, penicillins, cephalosporins, angiotensin-converting enzyme inhibitors, and alcohol

2-Infections:

• Viral infections are a frequent cause due to a non-specific effect of circulating pro-inflammatory cytokines or chemokines, either acting on mast cells or leading to expression of adhesion molecules on endothelial cells

• Bacterial infections (e.g.sinusitis or urinary)and parasitic infestations are a rare cause of chronic urticaria

3-Contactants: Contact urticaria syndrome refers to the onset of urticaria within 30-60 minutes of contact with an inciting agent. The lesions may be localized or generalized. Precipitating factors include latex (especially in health care workers), plants, animals (e.g. caterpillars, dander), medications, and food (e.g. fish, garlic, onions, tomato)

4-Foods and food additives:

• Numerous foods (Shellfish, eggs, nuts, strawberries) have been blamed as a cause of urticaria. However, an allergic cause for all ordinary urticarias was found in fewer than 3.5%

• Reactions to additives is considered to be important in fewer than 10% of patients

• More frequently implicated food additives are azo dyes e.g. tartrazine (gives food lemon-yellow color) and amaranth (gives food a deep red color)

5-Arthropod assault: It is the most common cause of papular urticaria. Although patients who are bitten by mosquitoes are likely to be aware of the source of the problem, patients with scabies, bedbug bites, flea bites, or other similar problems may not be aware

6-Inhalents:Grass pollens, mould spores, animal danders, house dust and even tobacco smoke, may rarely provoke urticaria

7-Autoimmune disease: SLE, cryoglobulin-emia, juvenile rheumatoid arthritis, and autoimmune thyroid disease

8-Malignancies: Little evidence exists to support the concern that chronic urticaria is a cutaneous sign of occult internal malignancy

9-Emotional factors: their role remains controversial

Investigations• CBC with differential: Elevated eosinophil

count may be found in parasitic infections or drug reactions

• Stool ova and parasites: Consider this test in patients with GIT tract symptoms, an elevated eosinophil count, or a positive travel history

• Skin testing may be useful if contact urticaria is suggested

• Provocation tests

Treatment 1-Avoid the cause

2-Prevent scratching by cooling the skin:cold compresses or cooling lotions that contain menthol (Dermocalm)

3-Systemic therapy:

• 2nd and 3rd generation antihistamines are the drugs of choice

• If sedation is required a 1st generation antihistamine (especially hydroxizine) is used

• If there is no response to non sedating antihistamines, double the dose or use another non sedating drug or add a sedating antihistamine or use a combination of H1 & H2 antihistamines

• In refractory cases, when all diagnostic and therapeutic methods have been exhausted, a 2-week course of corticosteroids (starting at 40 to 60 mg prednisone or equivalent) will temporarily suppress the disease

• Plasmapheresis has been effective in some severe, unremitting cases

• The use of many other immuno-suppressive agents in the treatment of urticaria including tacrolimus, azathioprine, cyclophosphamide, intravenous immunoglobulin,IFN-α has been reported

• Antileukotriene medications such as zileuton (Zyflo), zafirlukast (Accolate) and montelukast (Singulair), have been used off-label especially in combination with antihistamines

2-Immune-complex urticaria

A-Serum sickness

Etiology• Immune complexes consisting of antigen

and IgG activate complement and are deposited in tissues including skin (type III reaction)

• Complement-containing immune complexes generate an influx of polymorphs into the vessel wall, where proteolytic enzymes are released causing the widespread vasculitic lesions seen

• Drugs : e.g.allopurinol , barbiturates, captopril , cephalosporins, griseofulvin, sulfonamides, penicillin and radiocontrast media

• Heterologous serum used in the prophylaxis and/or treatment of botulism, diphtheria, gas gangrene, organ transplant rejection, and snake and spider bites

• Blood products

• Hormones

• Vaccines

Clinically

• Onset is after 1-3 weeks• Fever in almost all patients• Skin symptoms: Urticaria (95%),

morbilliform or scarlatiniform rash, palpable purpura

• Arthritis (10-50%), usually in the metacarpophalangeal and knee joints

• Facial edema• Generalized lymphadenopathy and

splenomegaly

Treatment

• NSAI e.g. Ibuprofen 200-800 mg PO qid and antihistamines provide symptomatic relief

• Severe cases may warrant a brief course of corticosteroids e.g. Prednisone 20-40 mg/d PO

B-Urticarial Vasculitis

Etiology• Type III like serum sickness

• Most cases are idiopathic

• Rarely causes like those of serum sickness can be found

• 2.1% of 1310 patients with urticaria were found to have urticarial vasculitis

Clinically

• Wheals last for more than

24 hours in a fixed

location

• Often accompanied by a

painful or burning sensation

• Lesions resolve with postinflammatory pigmentation

• Overall, the disease has a relatively benign course lasting an average of 3 years

• Systemic involvement is common:

-The most frequent symptom is

arthralgia (50%)

-Abdominal pain, nausea and vomiting

(20 (%

Investigations• Investigations should include a search for

the occasional associated disease, and for systemic involvement e.g.

-CBC -ESR -Urinalysis -Renal and liver function -Immunoglobulins -Chest X-ray -Serum complement and

Histopathology• There is leukocytoclastic vasculitis of small vessels• Perivascular infiltrate of neutro- phils with leuko- cytoclasis together with eosinofills• Vessels are dilated and their walls show

fibrin deposition• Later, the infiltrate may become a mixture

of lymphocytes and neutrophils

Treatment

• For patients with cutaneous involvement only, antihistamines or NSAIDs may provide symptomatic relief

• If these agents do not work, prescribe colchicine (0.6 mg PO bid/tid), hydroxychloroquine(50 mg/d PO initial; can be increased by 50 mg/wk to 300 mg/d), or dapsone (6.5 mg/kg PO)

• If all other treatment modalities have failed or if the patient has systemic involvement, consider initiating treatment with systemic steroids (0.5-1.5 mg/kg/d PO (. If the patient requires long-term treatment with corticosteroids, consider every-other-day dosing of the steroid or the addition of azathioprine as a steroid-reducing agent

3-Physical urticarias• They are a distinct subgroup of urticarias in

which a specific physical stimulus induces reproducible whealing

• It accounts for 19% of urticaria cases in a dermatology clinics

• whealing caused by physical stimuli usually occurs in minutes at the site of contact with the skin and persists for less than 2h

A-Dermographism• It is a triple response (erythema, edema, flare)

which may arise from firm stroking of the skin• It is postulated that mast cells sensitized with

immunoglobulins (especially IgE) react to an antigen induced by mechanical stimulation of the skin and release their mediators

• This reaction is normal but in 5% of normal people this physiological response is sufficiently exaggerated to warrant the term dermographism

• Patients complain of whealing and itching at sites of trauma, friction with clothing or scratching the skin

• The rash tends to

last less than an hour

• The condition tends

to improve or

disappear gradually

over a few years

• It is easily diagnosed by using

the dermographometer which

has a spring-loaded stylus, the

pressure of which can be adjusted

to a predetermined setting

• Stroking the skin

at a pressure of

less than 36g/mm

induces a linear

itching weal

within 10min.

Treatment

• Low-sedating H 1 antihistamines are often effective, sometimes in low doses

• For the more severely affected patients some improvement may be obtained with UVB or PUVA therapy

B- Delayed pressure urticaria• The underlying mechanism is unclear

• It occurs to some degree in up to 37% of patients with chronic ordinary urticaria, although they may not be aware of it unless directly questioned

• whealing occurs at sites of sustained pressure applied to the skin after a delay of 30min to 9h, but usually 4-8h, and lasts 12-72h

• Wheals occur frequently under tight clothing on the hands after manual work, the buttocks after sitting and on the feet after walking

• Lesions may be itchy, but are often tender or painful, particularly on the soles and scalp

• It may be accompanied by systemic symptoms of malaise, flu-like symptoms, arthralgia, myalgia and leukocytosis

• Delayed pressure urticaria responds poorly to antihistamine therapy

• Cetirizine in high doses (10mg three times a day) has been advocated as being more specific, as it also inhibits eosinophils

• Although non-steroidal anti-inflammatory drugs may be helpful, they may exacerbate the ordinary urticarial wheals

• Systemic steroids can provide symptomatic relief but in doses that are usually unjustifiable for long-term therapy, although they can be used short term for exacerbations

• The prognosis is variable: the symptoms fluctuate in severity; they may show spontaneous improvement or last for many years

C-Heat urticaria

1-Cholinergic urticaria

• Cholinergic urticaria is common

• It occurs in about 0.2% of patients in an outpatient dermatologic clinic

• It occurs in 5-11% of persons with urticaria

• The prevalence is higher in persons with atopy

• Seems to be more common in men than in women

• The condition usually begins in people aged 10 -30 years, with an average age at onset of 16 years

• The average duration was 7.5 years, with a range of 3-16 years in one study

Etiology

A rise in core body temperature resulting in sweating causes the rash. Common triggers include:• Exercise• Hot baths/showers• Fever• Occlusive dressings• Eating spicy foods• Emotional stress

• The pathogenesis is still not clear

• Intracutaneous injection of cholinergic agents such as acetylcholine produces wheals in approximately ⅓ of patients

• Thus, acetylcholine released from sympathetic nerve endings of sweat glands has been hypothesised to induce histamine release in some way

• Cholinergic agents released at the nerve ending may become excessive and stimulate the sensory nerves directly, resulting in cholinergic itching and pain

• Aspirin aggravated the condition in 52% of patients

Clinically• Lesions appear usually within a

few minutes after the onset of

sweating, and they last from a

half-hour to an hour or more

• Often, itching, burning, tingling, warmth, or irritation precedes the onset of numerous small (1- 4 mm in diameter)

pruritic wheals with large

surrounding flares

                          

   

                          

    

             

                 

• Lesions may appear anywhere on the body, except on the palms or the soles and rarely in the axillae

• Sometimes, flares are the

only presentation. Patients

who are more severely affected may experience systemic symptomatology, such as fainting, abdominal cramping, diarrhea, salivation, and headaches

Treatment• A few patients find that they can bring on a

severe attack by suitable exertion, and in this way can achieve freedom for up to 24h

• Sometimes, an attack can be aborted by rapid cooling

• Some patients get partial relief from antihistamines used either regularly or before they forecast attacks, but most have to modify their lifestyle by reducing exercise

• For selected severely affected patients not responding to antihistamines, the attenuated androgen danazol(1X3) improved whealing. Usefulness is limited by its side-effects and, due to potential abuse in sport

• Beta-blockers, such as propranolol, have been reported to be useful

2-Localized heat urticaria

• This is one of the rarest forms of physical urticaria

• Localized warming of skin at temperatures varying from 38 to 50°C for 2-5min induces whealing at the test site lasting 1h

• Treatment with antihistamines or induction of tolerance by repeated heat exposure may be helpful

D- Cold urticaria

• The population most affected is young adults age 18 to 25 years

• Patients with cold urticaria may also have dermographism and cholinergic urticaria

• Severe reactions can be seen with exposure to cold water. Swimming in cold water is the most common cause of a severe reaction. This can cause a massive release of histamine resulting in low blood pressure, fainting, shock, and even death

Clinically• Occurs in two forms: - The common form presents with the rapid onset of urticaria on the face, neck, or hands after exposure to cold- The rare form is hereditary and manifests as urticaria all over the body 9 to 18 hours after cold exposure• It lasts for an average of 5 to 6 years

• Cold urticaria is diagnosed by holding an ice cube against the skin of the forearm for 1 to 5 minutes. Urticarial wheals should develop in positive cases

Treatment

• Patients with cold urticaria should learn to protect themselves from a rapid drop in body temperature

• Regular antihistamines are not generally effective

• Cyproheptadine (Triactin), doxepin and ketotifen (Zaditin) have been found to be a useful treatment

E-Aquagenic urticaria• It is a rare condition in which urticaria

develops within 1 to 15 minutes after contact with water

• Urticaria lasts for 10 to 120 minutes• It does not seem to be caused by

histamine release like the other physical urticarias. Most investigators believe that this condition is actually exquisite skin sensitivity to additives in the water such as chlorine

• Aquagenic urticaria is diagnosed by applying tap water and distilled water to the skin and observing the reaction

• Treatment is with capsaicin cream(Zostrix) applied to the irritated skin. Antihistamines are of questionable benefit since histamine is not the causative factor in water urticaria

F-Solar urticaria• It is rare • Urticarial lesions appear minutes after

sunlight exposure and disappear rapidly after sun avoidance

• It is most common in females & young adults• Phototesting is required to make the

diagnosis with testing against UVA, UVB, and visible light

• Antihistamines, broad-spectrum sunscreens, and graded exposure to increasing amounts of light or PUVA desensitization are effective treatments

4-Contact Urticaria syndrome

• Much of the epidemiologic data regarding contact urticaria syndrome is from occupational studies, which may therefore skew the reported etiologies. Little data exist regarding CUS in the general population

Classification & Etiology

• Can be classified into 2 broad categories: 1-Nonimmunologic contact urticaria : does not require presensitization of the patient's immune system to an allergen . It is mediated by prostaglandins and not histamine

• 2- Immunologic contact urticaria: presensitization is required.It is a type 1 hypersensitivity reaction mediated by immunoglobulin IgE antibodies specific to the eliciting substance

• Some of the more commonly reported causes of NICU include balsam of Peru ( perfumes & deodorants, insect repellents, toothpastes) , benzoic acid (food preservative), cinnamic alcohol(perfumes)

• Reported causes of ICU include natural rubber latex, raw meat and fish, semen, many antibiotics, some metals (e.g. platinum, nickel)

Clinically

• Wheals occur at sites of contact with the allergen, usually therefore on the hands and round the mouth.They disappear in 24 hours

• Extracutaneous manifestations include rhinitis, chest wheezing and conjunctivitis

Treatment

• Avoidance of the cause

• Antihistamines

5-Angioedema

• Angioedema and urticaria are varying manifestations of the same process

• Postcapillary venule inflammation results in fluid leakage and edema in both conditions. However, angioedema involves vessels in the layers of the skin below the dermis, while urticaria is localized superficial to the dermis

• Occurs in 40% of patients with urticaria but can occur alone

• Women tend to have more occurrences than men do

• It commonly involves the lips, eyelids, face, extremities, and genitalia in an asymmetrical manner

• Angioedema can also involve the gastrointestinal tract and cause abdominal pain, nausea, vomiting, and diarrhea

Types

1-Ordinary angioedema:Has the same multiple etiology and frequent lack of precise diagnosis as in chronic urticaria

2-ACEIs induced angioedema: related to the ability of ACEI to prolong bradykinin survival and potentiate its effects. Symptoms may be severe and laryngeal involvement may be life-threatening. Can occur at any time during treatment

3-Hereditary angio-oedema:

-1% of all cases of angio-oedema

-Due to C1 esterase inhibitor deficiency

transmitted as an autosomal dominant trait

-Onset is usually in early childhood

-May be precipitated by local trauma (e.g.

dental procedures, tonsillectomy)

-Often associated with laryngeal edema,

nausea, vomiting, colic and urinary

symptoms

-Ordinary urticaria does not occur

-Treatment : Danazol orally (1 X 3) or

Epsilon- aminocaproic acid IV

ANTIHISTAMINES

General consideration

• The first H1-antihistamine was discovered by Jeff Forneau and Daniel Bovet in 1933 in their efforts to develop a guinea pig animal-model for anaphylaxis at Ryerson University(Toronto). Bovet went on to win the 1957 Nobel Prize in Physiology

• Benadryl® was the first antihistamine introduced in 1945

• IMS Health reports that prescription antihistamine sales in the USA totaled more than $4.3 billion in 2001

Histamine receptors

There are four known histamine receptors:

• The H1 receptors: found in smooth muscles, on vascular endothelial cells, in the heart, and in the central nervous system. Stimulation causes systemic vasodilation & increased cell permeability

• The H2 receptors: found in gastric parietal cells,vascular smooth muscles, neutrophils,CNS, heart & uterus. Stimulation causes gastric acid secretion & smooth muscle relaxation

• The H3 receptors:found in CNS & peripheral nerves

• The H4 receptors:found in bone marrow & leukocytes

H1 Antihistamines

First- Generation H1

(sedating)antihistamines

Chemical nameTrade name

ContentAdult dose

Pediatr.dose

ChlorpheniramineAnallerge, Allergyl

4mg/tab 2mg/ts

1x1 up to 1x4

1x1 up to

1x2

PheniramineAvil75mg/tab

10mg/ts

1x1 up to

1x3

½x1up to 1x1

ChlorphenoxamineAllergex20mg/tab

3.5mg/ts

1x21x2

HydroxyzineAtarax10&20mg/tab

1x2 for the 2conc

No syrup

AcrivastineSemprex8 mg/tab1x1No syrup

Chemical nameTrade name

ContentAdult dose Pediatr. dose

CyproheptadineTriactin4 mg/tab

2 mg/ts

1x31x2

ClemastineTavegyl1 mg/tab

0.5 mg/ts

1x21x2

DimethindeneFenistil1 mg/tab

4 mg/cap

0.5 mg/ts

1x3 (tab)

1x1 (cap)

1x1 up to

1x2

1x1= qd = once a day(from the Latin quaque die) 1x2= bid= two times a day(from the Latin bis in die(1x3= tid = three times a day (from the Latin ter in die)1x4=qid = 4 times a day (from the Latin quater in die)

Side Effects

• Occur in about 25 percent of patients

• Sedation is the most common problem, however, there are considerable individual variations

• The sedative effect ameliorates in most individuals within a few days

• Other CNS effects include dizziness, tinnitus, disturbed coordination, inability to concentrate & blurred vision

• A Canadian study on the relation between H1-type antihistamines and automobile fatalities suggested that antihistamines may affect driving skills sufficiently to result in fatal automobile accidents

• The CNS effects at times may be stimulatory (nervousness, irritability, insomnia, tremors) especially with Anallerge, Avil, Allergex

• Anticholinergic effects, include: dry mucous membranes, difficulty in micturition, urinary retention, dysuria, urinary frequency, and impotence

• Allergic contact dermatitis may develop after the topical application

• Accentuation of the central depressive effects when taken in combination with alcohol or other therapeutic agents with CNS depressant effects, such as diazepam

• Metabolism occurs via the hepatic microsomal cytochrome P-450 system. Thus, the half life may be prolonged by patients receiving microsomal oxygenase inhibitors such as ketoconazole, erythromycin, doxepin or cimetidine

• Other side-effects of these antihistamines include tachycardia, with prolongation of the QT interval on ECG and other arrythmias

Use in pregnancy

DrugSafety

AnallergeB

AvilB

AllergexNo available information

AtaraxC

TriactinB

TavegylB

FenistilC

B= Usually safe but benefits must outweigh the risks

C =Safety for use during pregnancy has not been established

Second-Generation H1

(Low-sedating)

antihistamines

Chemical name

Trade name

ContentAdult

dose

Pediatr.

dose

LoratidineClaritine, Lorano, Mosedine,Loratan

10 mg/tab1x1 ½-1x1

CetrizineZyrtec, Histazine1,Cetrac

10 mg/tab1x1 -½1x1

EbastineEvastine, Kestin

10 mg/tab1x1No syp

Cetirizine• It is a metabolite of hydroxyzine and is

less sedating than it

• It is not metabolized in the liver

• Peak plasma concentrations are achieved in 1 h

• It suppresses cutaneous wheal-and-erythema reactions for as long as 24 h

• When assessed by actual driving, the critical tracking test, and the dividedattention test, cetirizine was more sedating than placebo and loratadine

• When assessed by pharmacodymanic comparisons, cetirizine was not more sedating than other second-generation H1-type antihistamines

• There are no restrictions on the ability to take cetirizine with other medications

• Cardiac side effects have not been reported

• Food may decrease the rate of absorption but does not interfere with the extent of absorption

Loratadine• Peak serum concentrations are achieved in 1

to 1.5 h

• Causes no greater sedative or anticholinergic side effects than does a placebo

• It is metabolised in the liver via the CYP3A4 pathway. Concurrent administration of loratidine with ketoconazole or erythromycin (both CYP3A4 inhibitors) was associated with significantly increased plasma concentration and elimination

• Cardiac side effects have not been reported

• There are no restrictions on the ability to take this agent with food or other medications

• Two cases of hepatotoxicity with liver failure have been reported

• Small amounts of loratadine are excreted in breast milk

Ebastine

• Has peak plasma concentrations at 2.6 h

• It is metabolised in the liver via the CYP3A4 pathway. Concurrent administration of ebastine with ketoconazole or erythromycin causes significantly increased plasma concentration and elimination

• The effects of impaired renal function and hepatic cirrhosis on its pharmacokinetics are minimal

• It has no sedative or cardiac side effects ,

nor does it interact with alcohol or diazepam

Third-Generation H1

antihistamines

Chemical name

Trade name

ContentDose

adult

Dose

ped

FexofenadineTelfast,

Fexon, Allerfen

120/180 mg/tab

1x1 No liquid

DesloratidineAireus,

Desa

5 mg/tab1x1 Not available

LevocitrizineXyzal5 mg/tab 1x1 Not available

Fexofenadine• It is the metabolite of terfenadine

• Ppeak plasma concentrations occur at 2.6 h.

• Plasma half-life is greater in individuals over 65 years of age and in those with renal impairment

• Pharmacokinetics in patients with hepaticdisease do not differ from those in healthy subjects

• Has no anticholinergic effects

• It lacks adverse effects at doses up to 480mg/day

• QT interval was not affected when administered with erythromycin or ketoconazole

Desloratadine A survey published in 2003 concluded:

"When severity of disease was controlled for analysis amongst loratadine-dissatisfied patients who converted to desloratadine, there was a consistent pattern favoring desloratadine, with statistically significant results reported for sum of adverse effects, nighttime awakening due to symptoms, symptom severity just prior to the next dose, and overall satisfaction (p < 0.05)."

Levocetrizine

• Studies done in 2001 & 2002 showed that levocetrizine was more potent at suppressing weal and flare than ebastine, fexofenadine, and loratadine

• Skin rash (rarely), headache, and fatigue have been reported as side effects

• It does not produce any deleterious effect on cognitive and psychometric functions

H2-Type Antihistamines

• They are less hydrophilic, which presumably accounts for their lack of CNS effects

• Although these agents were originally developed to treat peptic ulcer disease, they have been used in the treatment of dermatologic disorders because of the presence of H2 receptors on the cutaneous microvasculature

Chemical name

Trade name

ContentDose

CimetidinTagamet, Cimetidine

200 & 400 mg tab

400-800 mg bid

RanitidineZantac, Ranitac

150 & 300 mg tab

150 mg bid

FamotidineAntodine, Famotin

20 & 40 mg tab

20 - 40 mg bid

• Combined H1 and H2 antihistamine therapy is statistically more effective than H1 antihistamines alone in controlling the symptoms of chronic urticaria

• Famotidine is the safest of this group as cimitidine commonly causes mental confusion in elderly patients

• Ranitidine does not have these side effects but interacts with fentanyl, midazolam,nifedipine, theophylline, and warfarin

Other Therapeutic Agents with Antihistaminic Activity

Ketotifen(Zaditen)• It prevents histamine release from mast cells • Ketotifen also is an H1-type antihistamine

and a calcium-channel blocker

• Sedation and weight gain are side effects

• Dose: Adults 1x2 (1 mg / tab) Pediatr. ½ -1x1 (1mg / ts)

Doxepin (Sinequan)

• Is a tricyclic antidepressant

• Acts on both H1 and H2 receptors

• More potent than chlorpheniramine in inhibiting experimental wheals induced by histamine

• Dose10-150 mg/d

• Not available in Egypt