14.6.2. Hypersensitivity Reactions Urticaria (hives) is common in children.

The primary wheal is an erythematous, edematous papule or plaque produced by a sudden increase in interstitial fluid within the upper dermis. Most cases of acute urticaria result from type I, IgE-mediated hypersensitivity, but chronic urticaria may be precipitated by other pathogenetic mechanisms. The mast cell plays a central role as the effector cell in all forms of urticaria (see Sec. 11.13). Acute urticaria is the most common form of urticaria in children. Red or pink wheals appear suddenly, persist for 2 to 12 hours, then resolve or shift to new sites. The wheals can be pale or dusky blue in the center, producing a target-like appearance that may be confused with erythema multiforme or vasculitis (Color Plate 10). Intense pruritus is usually present but may be absent. Lesions vary in size from a few millimeters to many centimeters and are often annular or geographic in configuration. The lesions may be associated with deep cutaneous edema (angioedema) or less frequently with respiratory tract involvement, producing laryngospasm or bronchospasm. The differential diagnosis includes erythema multiforme, vasculitis, exanthems, nonurticarial drug eruptions, and papular urticaria caused by insect bites. Acute urticaria can be distinguished from all these conditions by the evanescent nature of the lesions. As the wheals resolve or change shape within 12 hours, outlining lesions with ink to follow their progression or disappearance is helpful in distinguishing urticaria from erythema multiforme or urticarial vasculitis. Assessment and management of the airway takes precedence over treatment of skin lesions. If there is evidence of respiratory distress or anaphylaxis, epinephrine in oil (Susphrine, 0.005 ml/kg, maximum 0.15 ml, given subcutaneously) is indicated. Antihistamines are the mainstay of therapy for cutaneous disease. In contrast to most other pruritic disorders, their role in urticaria is to prevent wheal formation and not simply to control pruritus. Diphenhydramine (5 mg/kg/d), hydroxyzine (24 mg/kg/d) or cyproheptidine (0.250.5 mg/kg/d) should be given in three to four divided doses. Combination therapy with two antihistamines may be required. Therapy should be continued until the child has been hive-free for at least 72 hours; thereafter the drug dosage is slowly tapered. Systemic corticosteroids are occasionally used when high doses of antihistamines are ineffective. A precipitating antigen should be searched for by a careful history, including dietary and drug history, and thorough physical examination. Most cases of urticaria in children are caused by benign viral illnesses. Specific infections such as hepatitis A and B and Hymenoptera stings should be considered. Foods that cause acute urticaria include shellfish, nuts, and strawberries. The most common drugs that induce urticarial reactions are penicillins, cephalosporins (especially cefaclor), and sulfonamides. These patients are at risk for anaphylaxis upon reexposure (see Sec. 11.15). Contact urticaria occurs within minutes to a few hours after direct skin contact with a food or chemical. It is a relatively common condition and may occur at any age. Many agents including fish, tomato, and cosmetic ingredients have been causally implicated. Chronic urticaria persisting for weeks, months, or even years may be idiopathic or caused by physical factors. Physical urticarias are precipitated by environmental factors, such as pressure, cold, ultraviolet light, and exercise. Dermographism is a common form of physical urticaria in which the pressure from moderate stroking results in urticarial wheals. Although sufficient stroke pressure will induce wheals on normal skin, in dermographism the threshold is much reduced. If necessary, symptoms may be minimized by preventive, antihistamine therapy (see above). Cold urticaria is precipitated by exposure to cold water or air, resulting in urticaria or painless swelling of exposed areas such as the face and hands. Respiratory symptoms, such as

wheezing or dyspnea, may also develop. The diagnosis is confirmed with the ice cube test, in which localized urticaria is induced by applying an ice cube to the skin for 10 minutes. Cyproheptadine, 0.25 to 0.5 mg/kg/d divided every eight hours, is usually beneficial. Because of the risk of anaphylaxis, sudden exposure to cold, such as diving into cold water, must be avoided. Cholinergic urticaria is a distinctive form of urticaria, P.1196 relatively common in adolescents, in which multiple 1- to 2-mm wheals surrounded by macular halos of erythema are precipitated by exercise and sweating. Respiratory symptoms may also develop. Oral antihistamines are occasionally required for treatment. Hereditary angioedema is a rare, dominantly inherited condition resulting from a deficiency or defect of C1 esterase inhibitor. Patients usually present in childhood with recurrent episodes of angioedema. These episodes differ clinically from acute urticaria in several ways: superficial wheals are absent; lesions are painful, rather than pruritic, and persistent; the swellings are unresponsive to antihistamine or corticosteroid therapy; and the family history is often positive. The diagnosis is established by finding low serum levels of C4 and C1 esterase inhibitor. Erythema multiforme (EM), sometimes called EM minor, is a hypersensitivity reaction confined to the skin and/or mouth, without systemic toxicity. Infections, particularly with the herpes simplex virus, are the most common cause of EM minor, although no evidence of active herpetic lesions may be present at the time the erythema multiforme develops. The skin lesions of EM usually have an abrupt onset but may develop during several days as crops of new lesions appear. Typical lesions begin as erythematous macules, which rapidly evolve into edematous, erythematous plaques. The central portion of the lesions may become dusky, necrotic, or blistered, with variable rings of concentric color change, including an intensification of redness at the periphery of the lesions ( target lesions) (Color Plate 10). Multiple, symmetric lesions occur on the extremities, including the palms and soles. The face, groin, and neck are often affected as well. Lesions on the trunk are less prominent than those on the extremities (centrifugal distribution). Mucosal involvement usually begins at the same time as the skin eruption but may precede or follow it by several days. Multiple erosions, with or without overlying pseudomembranes, may develop on the lips, tongue, and palate, but these erosions do not tend to be severe. In Stevens-Johnson syndrome, sometimes called EM major, mucosal lesions predominate, occur at more than one site, and are usually noted before cutaneous lesions (Fig. 14-19). Severe erosions of the lips and oral mucous membranes lead to marked pain. Involvement of the ocular, genital, and anal mucosae may also be severe. An extensive eruption of erythematous macules and raised lesions, often with blisters and erosions, on the face, trunk, extremities, and genitalia is associated with the mucosal lesions. Atypical target lesions and blue macules are occasionally seen as well. Toxic epidermal necrolysis (TEN) is defined as full-thickness epidermal necrosis of more than 30% of the body surface. Many consider TEN and Stevens-Johnson syndrome to be related disorders with a similar pathomechanism; overlapping cases with manifestations that resemble both Stevens-Johnson syndrome and TEN may occur with blistering and epidermal detachment of more than 10% of the body surface area. In Stevens-Johnson syndrome with bullae or in TEN, stroking of the skin at the edge of a blister may extend it (positive Nikolsky sign). Systemic toxicity in patients with Stevens-Johnson syndrome or TEN is often severe, particularly with fever, dysphagia from esophageal erosions, tracheal and bronchial erosions, respiratory

abnormalities, noninfectious hepatitis, lymphadenopathy, glomerulonephritis and acute tubular necrosis, and myocarditis. Long-term sequelae can include dyspigmentation and mucosal scarring, particularly of the eyes with resultant symblepharon, synechiae, entropion and ectropion, trichiasis, corneal opacities, and pannus formation. Strictures of the esophagus, bronchus, urethra, vagina, or anus may occasionally occur. A Sjgren-like syndrome caused by damage to the lacrimal and salivary glands may also ensue. The mortality rate from massive loss of fluid and electrolytes and infection is particularly high in patients with TEN (25%). Most cases of either Stevens-Johnson syndrome or TEN are precipitated by drugs, particularly sulfonamides and the aromatic anticonvulsants (eg, phenytoin, phenobarbital, and carbamazepine). Other drugs including penicillins, cephalosporins, and lamotrigine have also been implicated. Stevens-Johnson syndrome may also be triggered by infections, and an association with Mycoplasma pneumoniae is well-recognized. TEN may also develop in severe, acute graft-versus-host disease. The differential diagnosis of EM includes urticaria, vasculitis, and other types of generalized drug eruptions or viral exanthems. SJS may be distinguished from Kawasaki disease by the presence of blistering on the lips and oral mucosa. TEN must be differentiated from staphylococcal scalded-skin syndrome (SSSS), which also presents with tender red skin. Patients with SSSS do not have mucosal blistering and do not have full-thickness epidermal detachment. If necessary, these disorders can easily be distinguished by skin biopsy (demonstrating extensive epidermal necrosis in TEN versus a subcorneal blister overlying a normal-appearing epidermis in SSSS) or by a Tzanck preparation performed on detached epidermis (demonstrating acantholytic cells in SSSS). Editors: Rudolph, Colin D.; Rudolph, Abraham M.; Hostetter, Margaret K.; Lister, George; Siegel, Norman J. Title: Rudolph's Pediatrics, 21st Edition Copyright 2003 McGraw-Hill
81 Urticaria, Angioedema, and Anaphylaxis ETIOLOGY Urticaria and angioedema are caused by an allergic, IgE-mediated reaction to an allergen that activates mast cells in the skin. Anaphylactic reactions, which are mediated by IgE, and anaphylactoid reactions, which result from mechanisms that are not IgE mediated, are acute, severe, life-threatening reactions caused by a massive release of inflammatory mediators. Urticaria, angioedema, and anaphylaxis are best considered as symptoms because they have a variety of causes. Urticaria and angioedema occur in response to the release of inflammatory mediators, including histamine, leukotrienes, platelet-activating factor, prostaglandins, and cytokines from mast cells present in the skin. A variety of stimuli can trigger mast cells and basophils to release their chemical mediators. Typically, mast cell degranulation results when cross-linking of the membrane-bound IgE occurs. Release of these mediators results in vasodilation, increased vascular leakage, and pruritus. Basophils from the

circulatory system also can localize in tissue and release mediators similar to mast cells. Patients with urticaria have elevated histamine content in the skin that is more readily released.

Table 81-1. Etiology of Acute Urticaria Foods Egg, milk, wheat, peanuts, tree nuts, soy, shellfish, fish, strawberries (direct mast cell degranulation) Medications Suspect all medications, even over-the- counter or homeopathic Insect stings Hymenoptera (honeybee, yellow jacket, hornets, wasp, fire ants), biting insects (papular urticaria) Infections Bacterial (streptococcal pharyngitis, Mycoplasma, sinusitis); viral (hepatitis, mononucleosis [EBV], coxsackievirus A and B); parasitic (Ascaris, Ancylostoma, Echinococcus, Fasciola, Filaria, Schistosoma, Strongyloides, Toxocara, Trichinella); fungal (dermatophytes, Candida) Contact Latex, pollen, animal saliva, nettle plants, caterpillars allergy Transfusion Blood, blood products, or IV immunoglobulin administration reactions Idiopathic
EBV, Epstein-Barr virus. From Lasley MV, Kennedy MS, Altman LC: Urticaria and angioedema. In Altman LC, Becker JW, Williams PV (eds): Allergy in Primary Care. Philadelphia, WB Saunders, 2000, p 232. Not all mast cell activation is IgE mediated. Immunologic, nonimmunologic, physical, and chemical stimuli can produce degranulation of mast cells and basophils. Anaphylatoxins, C3a and C5a, can cause histamine release in a non-IgE-mediated reaction. Anaphylatoxins are generated in serum sickness, which occurs in reactions to blood transfusions and with infectious, neoplastic, and rheumatic diseases. In addition, mast cell degranulation can occur from a direct pharmacologic effect or physical or mechanical activation, such as urticaria after exposure to opiate medications and dermatographism. By definition, acute urticaria and angioedema are hives and diffuse swelling that last less than 6 weeks. Often the patient's history is quite helpful in eliciting the cause of this acute reaction (Table 81-1). An IgE mechanism is more common in acute urticaria than in chronic urticaria. Chronic urticaria and angioedema are characterized by persistence of symptoms beyond 6 weeks (Table 81-2). Some have daily symptoms of hives and swelling, whereas others have intermittent or recurrent episodes. Most cases of chronic urticaria do not have a determinable cause and are labeled chronic idiopathic urticaria, which is a diagnosis of exclusion. Physical urticaria and angioedema are characterized by environmental factors triggering these reactions. The most common physical urticaria is dermatographism, affecting 2% to 5% of the general population. Dermatographism means "writing on the skin" and is easy to diagnose by firmly scratching the skin with a blunt point, such as the wooden tip of a cotton swab or tongue depressor. It is characterized by an urticarial reaction localized to the site of skin trauma. It has been suggested that trauma induces an IgE-mediated reaction causing histamine to be released from the mast cells.

Cholinergic urticaria, characterized by the appearance of 1- to 3-mm wheals surrounded by large erythematous flares after an increase in core body temperature, occurs commonly in young adults. Lesions may develop during strenuous exercise after a hot bath or emotional stress. It may be confused with exercise-induced anaphylaxis, although there are no airway symptoms with cholinergic urticaria.

Table 81-2. Etiology of Chronic Urticaria Idiopathic 75%-90% of cases 25%-50% of adult patients have IgG, anti-IgE, and anti-Fc RI (high- affinity IgE receptor alpha chain) autoantibodies Physical Dermatographism Cholinergic urticaria Cold urticaria Delayed pressure urticaria Solar urticaria Vibratory urticaria Aquagenic urticaria Rheumatologic Systemic lupus erythematosus Juvenile rheumatoid arthritis Endocrine Hyperthyroidism Hypothyroidism Neoplastic Lymphoma Mastocytosis Leukemia Angioedema Hereditary angioedema (autosomal dominant inherited deficiency of C1-esterase inhibitor) Acquired angioedema Angiotensin-converting enzyme inhibitors From Lasley MV, Kennedy MS, Altman LC: Urticaria and angioedema. In Altman LC, Becker JW, Williams PV (eds): Allergy in Primary Care. Philadelphia, WB Saunders, 2000, p 234.
Cold urticaria occurs with exposure to cold and may develop within minutes on areas directly exposed to cold or on rewarming of the affected parts. Ingestion of cold drinks may result in lip swelling. Cold urticaria syndromes can be categorized into acquired and familial disorders. Severe reactions resulting in death can occur with swimming or diving into cold water. It is imperative that patients never swim alone, avoid total body exposure to cold, and have injectable epinephrine available. Autoimmune diseases have been associated with urticaria and angioedema and are more commonly found in adults than children. Connective tissue diseases that have been associated with chronic urticaria and angioedema include systemic lupus erythematosus, Sjgren syndrome, polymyositis, and various forms of leukocytoclastic vasculitis. A specific auto-immune disorder causing urticaria has been identified in patients who seem to have IgG anti-IgE receptor antibody directed against IgE and the IgE

receptor. These antibodies trigger the mast cell and basophils to degranulate. Skin testing with autologous serum elicits an immediate wheal and flare response and cellular degranulation. Hereditary angioedema is an uncommon but treatable type of angioedema that involves an autosomal dominant inherited deficiency of C1-esterase inhibitor (see Chapter 75). Deficiency of this regulatory protein results in complement activation. Most patients have type I hereditary angioedema with low levels of C1-esterase inhibitor; approximately 15% have type II hereditary angioedema with normal levels but dysfunctional C1-esterase inhibitor protein. Patients with hereditary angioedema have recurrent, circumscribed edema typically affecting the extremities and face brought about by minor tissue trauma. One fourth of affected patients die as a result of laryngeal edema. These patients rarely have urticaria associated with angioedema. A low C4 level serves as a good initial screening test. During acute attacks, patients also may have reduced levels of C2. Patients with reduced C4 should have quantitative and functional levels of C1-esterase inhibitor measured. Angiotensin-converting enzyme inhibitors also account for an increasing proportion of angioedema, especially in elderly patients. Anaphylactic reactions are type I, IgE-mediated reactions and result from many causes (Table 81-3). Cross-linking of the IgE molecule with the allergen leads to IgE receptor activation on the mast cell and basophil. The activated cells release their mediators, including histamine, tryptase, tumor necrosis factor, platelet-activating factor, leukotrienes, prostaglandins, and cytokines. Other cell types involved in the reactions include monocytes, macrophages, eosinophils, neutrophils, and platelets. The mediator release results in the clinical picture of anaphylaxis.

Table 81-3. Common Causes of Anaphylaxis in Children* Foods Peanuts, tree nuts, milk, eggs, fish, shellfish, seeds, fruits, grains Drugs Penicillins, cephalosporins, sulfonamides, nonsteroidal anti- inflammatory drugs, opiates, muscle relaxants, vancomycin, dextran, thiamine, vitamin B12, insulin, thiopental, local anesthetics Hymenoptera Honeybee, yellow jacket, wasp, hornet, fire ant venom Latex Allergen immunotherapy Exercise Food-specific exercise, postprandial (non-food-specific) exercise Vaccinations Tetanus, measles, mumps, influenza Miscellaneous Radiocontrast media, immunoglobulin, cold temperature, chemotherapeutic agents, blood products, inhalants Idiopathic *In order of frequency. From Young MC: General treatment of anaphylaxis. In Leung DYM, Sampson HA, Geha RS, Szefler SJ (eds): Pediatric Allergy: Principles and Practice. St Louis, Mosby, 2003, p 644.
Anaphylactoid reactions are due to nonimmunologic mechanisms. Mast cells and basophils can be activated by direct, nonspecific stimulation, although the exact underlying mechanism is unknown.

Reactions to agents such as opiates and radiocontrast material are classic examples. Complement system activation also can result in mast cell and basophil activation. Anaphylatoxins, C3a and C5a, are named because of their ability to trigger mediator release and are generated in serum sickness. The most common cause of this type of reaction is transfusion with blood products. There are other causes of anaphylactoid reactions for which the mechanism has not been clarified. EPIDEMIOLOGY Urticaria and angioedema are common conditions affecting children and adults. Acute urticaria and angioedema are more common in children and young adults, whereas chronic urticaria and angioedema are more common in adults. The incidence of anaphylaxis in children is unknown. CLINICAL MANIFESTATIONS Raised, erythematous lesions with pale centers that are intensely pruritic characterize urticaria, commonly called hives. The lesions vary in size and can occur anywhere on the body. Typically, urticaria arises suddenly and may resolve within 1 to 2 hours or may persist for 24 hours. Angioedema is a similar process that involves the deeper dermis or subcutaneous tissue, with swelling as the principal symptom. Generally, angioedema is not pruritic, may be mildly painful, and persists longer than 24 hours. In rare cases, it may become life-threatening when swelling affects the upper airway. The clinical manifestations of anaphylaxis and anaphylactoid reactions are the same for children and adults. The signs and symptoms vary and can range from mild dermatologic symptoms to a fatal reaction, with 90% of patients presenting with cutaneous symptoms, including urticaria, angioedema, flushing, and warmth. The absence of cutaneous symptoms does not exclude the diagnosis of anaphylaxis. Other affected organ systems include the respiratory tract (with rhinorrhea, oropharyngeal edema, laryngeal edema, hoarseness, stridor, wheezing, dyspnea, and asphyxiation), cardiovascular system (with tachycardia, hypotension, shock, syncope, and arrhythmias), gastrointestinal tract (with nausea, abdominal pain, crampy diarrhea, and vomiting) and neurologic system (with syncope, seizure, dizziness, and a sense of impending doom). The severity of an anaphylactic reaction is often proportional to the speed of symptom onset. LABORATORY AND IMAGING STUDIES The laboratory evaluation of patients with urticaria and angioedema must be tailored to the clinical situation. Acute urticaria and angioedema do not require specific laboratory evaluation except to document the suspected cause. For patients with chronic urticaria and angioedema, laboratory evaluation should be performed to exclude important underlying diseases (Table 81-4). Patients with recurrent angioedema without urticaria should be evaluated for hereditary angioedema (Table 81-5).

Table 81-4. Suggested Testing for Chronic Urticaria/Angioedema of Unknown Etiology Basic Tests Discretionary Tests Based on Complete blood count with If vasculitis is suspected differential

Erythrocyte sedimentation rate Urinalysis Liver function tests Thyroid function and autoantibodies Anti-Fc R autoantibody (if available)

Antinuclear antibody Skin biopsy CH50 If liver function tests abnormal Serology for viral hepatitis

From Zuraw B: Urticaria and angioedema. In Leung DYM, Sampson HA, Geha RS, Szefler SJ (eds): Pediatric Allergy: Principles and Practice. St Louis, Mosby, 2003, p 580. Table 81-5. Complement Evaluation of Patients with Recurrent Angioedema Acquired C1Esterase Type I Type II Idiopathic Inhibitor Hereditary Hereditary Deficiency Angioedema Angioedema Assay Angioedema C4 Normal Low Low Low C4d/C4 ratio Normal C1-esterase Normal inhibitor level C1-esterase Normal inhibitor function C1q Normal C3 Normal High Low Low Normal Normal High Normal Low Normal Normal High Low Low Low Normal

Vasculitis Low or normal High or normal Normal Normal Low or normal Low or normal

From Zuraw B: Urticaria and angioedema. In Leung DYM, Sampson HA, Geha RS, Szefler SJ (eds): Pediatric Allergy: Principles and Practice. St Louis, Mosby, 2003, p 580.
Measurement of the mast cell mediators histamine and tryptase may be helpful when the diagnosis of anaphylaxis is in question. A tryptase level is a more useful test because histamine is released quickly, has a short half-life, and is often difficult to detect in the serum. Serum tryptase levels peak 1 to 1.5 hours after anaphylaxis, and elevated levels may be helpful in establishing the diagnosis of anaphylaxis. Normal tryptase levels do not rule out this diagnosis, however. It is best to measure a serum tryptase

level 1 to 2 hours after the onset of symptoms. It also can be ordered retrospectively on stored serum that is 1 to 2 days old. DIFFERENTIAL DIAGNOSIS The diagnosis of urticaria and angioedema is straightforward; finding the etiology may be more difficult. Other dermatologic conditions can mimic urticaria. Erythema multiforme has target-shaped, erythematous, macular or papular lesions that may look similar to the lesions seen in urticaria. A differentiating feature of erythema multiforme is that the lesions are fixed, last for several days, and do not respond to subcutaneous epinephrine. Other dermatologic diseases include dermatitis herpetiformis and bullous pemphigoid, which are quite pruritic, and early on, the lesions may resemble urticaria. Mastocytosis is characterized by mast cell infiltration of various organs, including the skin. Some patients have skin lesions similar in appearance to urticaria rather than the classic urticaria pigmentosa. Urticaria pigmentosa appears as hyperpigmented, red-brown macules, which may coalesce. When these lesions are stroked, they urticate, which is called Darier sign. A rare disorder that should be included in the differential diagnosis of urticaria is Muckle-Wells syndrome. It is an autosomal dominant disorder characterized by episodic urticaria presenting in infancy, with sensorineural deafness, amyloidosis, arthralgias, and skeletal abnormalities. Another rare syndrome is Schnitzler syndrome, which is characterized by chronic urticaria and macroglobulinemia. These patients also have bone pain, anemia, fever, fatigue, and weight loss. Urticarial vasculitis represents a small vessel vasculitis with histologic features of a leukocytoclastic response. The main distinguishing feature of urticarial vasculitis is that the lesions last longer than 24 hours, may be tender, and leave behind skin pigmentation. Skin biopsy is required for definitive diagnosis. The diagnosis of anaphylaxis is usually apparent from the acute and often dramatic onset of multisystem involvement of the skin, respiratory tract, and cardiovascular system. Sudden cardiovascular collapse in the absence of cutaneous symptoms suggests vasovagal collapse, seizure disorder, aspiration, pulmonary embolism, or myocardial infarction. Laryngeal edema, especially with abdominal pain, suggests hereditary angioedema. Many patients with anaphylaxis are initially thought to have septic shock (see Chapter 40). TREATMENT Avoidance of triggering agents is important in management of urticaria and angioedema. The mainstay of pharmacologic treatment is H1 antihistamines. Second-generation H1 antihistamines, such as cetirizine, fexo-fenadine, loratadine, and desloratadine, are preferred because they have fewer adverse effects. If a second-generation H1 antihistamine by itself does not provide adequate relief, the next step is to add a sedating H1 antihistamine given at bedtime or H2 antihistamines, such as cimetidine or ranitidine. Tricyclic antidepressants, such as doxepin and amitriptyline, block H1 and H2 histamine receptors. Corticosteroids are effective in treating urticaria and angioedema, although adverse effects from long-term use mandate that they be used at the lowest dose for the shortest time. When urticaria is resistant to treatment, other immunomodulating agents have been used, including cyclosporine,

hydroxychloroquine, and IV immunoglobulin. These modalities require more intensive monitoring and cost.

Table 81-6. Management of Acute Anaphylaxis Immediate Rapid assessment of airway, breathing, circulation; dermatologic examination; mental status assessment Epinephrine, 0.01 mg/kg (1 : 1000) IM; repeat every 20 min as needed* Oxygen 100%, secure and maintain airway Start large-bore IV line for venous access and fluids IV isotonic fluids, 20 mL/kg, repeat as necessary Frequent vital signs, cardiac monitor, pulse oximetry Rapid history for acute triggering event, known allergy and anaphylaxis history, current medications, history of asthma symptoms, concomitant medical conditions Subacute H1 antagonist, diphenhydramine, 1-2 mg/kg PO, IM, IV Corticosteroids, administered PO, prednisone, 1 mg/kg, or IV, methylprednisolone, 1-2 mg/kg Nebulized albuterol, 1.25-2.5 mg every 20 minutes or continuously Secondary H2 antagonist, ranitidine, 1.5 mg/kg administered PO or IV Glucagon, 0.1 mg/kg IV, if refractory to initial treatment above and if patient is receiving blockers Observe at least 4 hr for biphasic anaphylaxis Disposition If still symptomatic, admit for further treatment If unstable vital signs, angioedema of upper airway, or refractory bronchospasm, admit patient to ICU If symptoms have resolved without biphasic response, discharge patient on 72 hr of antihistamine, prednisone, and, if bronchospasm occurred with episode, albuterol metered-dose inhaler Discuss allergen trigger and avoidance and EpiPen instructions and prescriptions Follow-up with allergist *May require continuous IV epinephrine infusion. From Young MC: General treatment of anaphylaxis. In Leung DYM, Sampson HA, Geha RS, Szefler SJ (eds): Pediatric Allergy: Principles and Practice. St Louis, Mosby, 2003, p 646.
Anaphylaxis is a medical emergency; prompt recognition and immediate treatment are crucial (Table 816). Early administration of IM epinephrine is the mainstay of therapy and should be given at the same time basic measures of cardiopulmonary resuscitation are being performed. If the child is not in a medical setting, emergency medical services should be called. Supplemental 100% oxygen and IV fluid should be administered. Intubation or tracheotomy may be required. Additional pharmacologic

therapies, such as corticosteroids, antihistamines, H2-receptor antagonists, and bronchodilators, may be given to improve symptoms and lessen the biphasic response. A biphasic reaction can occur in 5% to 20% of patients with anaphylaxis with recurrence of symptoms 4 to 6 hours after the initial event. PREVENTION Prevention of urticaria, angioedema, and anaphylaxis focuses on avoidance of known triggers. A referral to an allergy specialist for a thorough history, diagnostic testing, and recommendations for avoidance is suggested for patients with severe reactions or anaphylaxis. Skin testing and serum IgE-specific testing are available for foods, inhalants, insect venoms, drugs (penicillin), vaccines, and latex. Educating the patient and family members about the signs and symptoms of anaphylaxis and using self-administered epinephrine early result in better outcomes. Fatal anaphylaxis has occurred, however, despite timely and appropriate treatment. A MedicAlert bracelet with appropriate information should be worn. Medications such as -blockers, angiotensin-converting enzyme inhibitors, and monoamine oxidase inhibitors should be discontinued because they may exacerbate anaphylaxis or interfere with treatment. Nelson Essentials of Pediatrics [2007]

PHYSICAL URTICARIA.

Physically induced urticaria and angioedema share the common property of being induced by environmental factors, such as a change in temperature or by direct stimulation of the skin with pressure, stroking, vibration, or light ( Table 147-3 ). TABLE 147-3 -- Diagnostic Testing for Urticaria and Angioedema DIAGNOSIS DIAGNOSTIC TESTING Food and drug reactions Autoimmune urticaria Thyroiditis Infections Elimination of offending agent, skin testing, and challenge with suspected foods Autologous serum skin test; anti-thyroid antibodies TSH;anti-thyroid antibodies Appropriate cultures or serology

Collagen vascular diseases and Skin biopsy, CH50, C1q, C4, C3, factor B, immunofluorescence cutaneous vasculitis of tissues, antinuclear antibodies, cryoglobulins Malignancy with angioedema Cold urticaria Solar urticaria Dermatographism Pressure urticaria CH50, C1q, C4, C1 INH determinations Ice cube test Exposure to defined wavelengths of light, red cell protoporphyrin, fecal protoporphyrin, and coproporphyrin Stroking with narrow object,(e.g., tongue blade, fingernail) Application of pressure for defined time and intensity

DIAGNOSIS Vibratory urticaria Aquagenic urticaria Urticaria pigmentosa Hereditary angioedema Familial cold urticaria

DIAGNOSTIC TESTING Vibration for 4 min Challenge with tap water at various temperatures Skin biopsy, test for dermographism C4, C2, CH50, C1 INH by protein and function Challenge by cold exposure, measurement of temperature, white blood cell count, erythrocyte sedimentation rate, and skin biopsy C3, factor B, C3b inactivator determinations Skin biopsy, immunofluorescence (negative result), autologous skin test

C3b inactivator deficiency Chronic idiopathic urticaria

TSH, thyroid-stimulating hormone.

Cold-Dependent Disorders.

Cold urticaria is characterized by the rapid onset of localized pruritus, erythema, and urticaria/angioedema after exposure to a cold stimulus. Total-body exposure such as occurs with swimming can cause massive release of vasoactive mediators, resulting in hypotension and even death if not promptly treated. The diagnosis is confirmed by challenge testing for an isomorphic cold reaction with an ice cube placed on the patient's skin for 1015 min. Patients with cold urticaria have a positive reaction on rewarming of the chilled skin. Cold urticaria can be associated with the presence of cryoproteins such as cold agglutinins, cryoglobulins, cryofibrinogen, and the Donath-Landsteiner antibody seen in secondary syphilis (paroxysmal cold hemoglobinuria). In patients with cryoglobulins, the isolated proteins appear to transfer cold sensitivity and activate the complement cascade on in vitro incubation with normal plasma. The term idiopathic cold urticaria generally applies to patients without abnormal circulating plasma proteins such as cryoglobulins. Cold urticaria has also been reported after viral infections. Cold urticaria must be distinguished from the familial cold autoinflammatory syndrome.
Cholinergic Urticaria.

This form of urticaria is characterized by the onset of small punctate wheals surrounded by a prominent erythematous flare associated with exercise, hot showers, and sweating. When the patient cools down, the rash usually subsides in 3060 min. Also occasionally seen are symptoms of more generalized cholinergic stimulation such as lacrimation, wheezing, salivation, and syncope. These symptoms are mediated by cholinergic nerve fibers that innervate the musculature via parasympathetic neurons and innervate the sweat glands by cholinergic fibers that travel with the sympathetic nerves. Elevated plasma histamine levels parallel the onset of urticaria triggered by changes in body temperature.

Dermatographism.

The ability to write on skin, termed dermatographism (also called dermographism or urticaria factitia), can occur as an isolated disorder or accompany chronic urticaria or other physical urticaria such as cholinergic and cold urticaria. It can be diagnosed by observing the skin after stroking it with a tongue depressor or fingernail. In such patients, a linear response occurs secondary to reflex vasoconstriction, followed by pruritus, erythema, and a linear wheal.

Pressure-Induced Urticaria and Angioedema.

Pressure-induced urticaria differs from most types of urticaria or angioedema in that symptoms typically occur 46 hr after pressure has been applied. The disorder is clinically heterogeneous in that some patients may complain of swelling secondary to pressure with normal-appearing skin (no urticaria), so that the term angioedema is more appropriate. Others are predominantly urticarial and may or may not be associated with significant swelling. When urticaria is present, an infiltrative skin lesion is seen, characterized by a perivascular mononuclear cell infiltrate and dermal edema similar to that seen in chronic idiopathic urticaria. Symptoms occur at sites of tight clothing; foot swelling is common after walking; and buttock swelling may be prominent after sitting for a few hr. This condition can coexist with chronic idiopathic urticaria or can occur separately. The diagnosis is confirmed by challenge testing by pressure applied perpendicular to the skin.
Solar Urticaria.

Solar urticaria is a rare disorder in which urticaria develops within 13 min of sun exposure. Typically, pruritus occurs 1st, in about 30 sec, followed by edema confined to the light-exposed area and surrounded by a prominent erythematous zone caused by an axon reflex. The lesions usually disappear within 13 hr after sun exposure is avoided. When large areas of the body are exposed, systemic symptoms may occur, including hypotension and wheezing. Solar urticaria has been classified into 6 types, depending on (1) the wavelength of light that induces skin lesions and (2) the ability or inability to transfer the disorder passively with serum IgE. The rare inborn error of metabolism erythropoietic protoporphyria can be confused with solar urticaria because of the development of itching and burning of exposed skin immediately after sun exposure. In erythropoietic protoporphyria, fluorescence of UV-irradiated red blood cells can be demonstrated.
Aquagenic Urticaria.

Patients with aquagenic urticaria develop small wheals after contact with water, regardless of its temperature, and are therefore distinguishable from patients with cold urticaria or cholinergic urticaria. Direct application of a compress of water to the skin is used to test for its presence.

CHRONIC IDIOPATHIC URTICARIA AND ANGIOEDEMA.

This is a common disorder of unknown origin that is often associated with normal routine laboratory studies and no evidence of systemic disease. Chronic urticaria does not appear to be an allergic reaction. It differs from allergen-induced skin reactions or from physically induced urticaria in that histologic studies reveal a cellular infiltrate predominantly about small venules. Skin examination reveals infiltrative hives with palpably elevated borders, sometimes varying greatly in size and/or shape but generally being rounded. Biopsy of the typical lesion reveals non-necrotizing, perivascular, mononuclear cellular infiltration. Many types of histopathologic processes can occur in the skin and manifest as urticaria. Patients with hypocomplementemia and cutaneous vasculitis can have urticaria and/or angioedema. Biopsy of these lesions in patients with urticaria, arthralgias, myalgias, and an elevated ESR as manifestations of necrotizing venulitis can reveal fibrinoid necrosis with a predominant neutrophilic infiltrate. Yet the urticarial lesions may be clinically indistinguishable from those seen in the more typical, nonvasculitis cases. There is an increased association of chronic urticaria with the presence of antithyroid antibodies. Such patients generally have antibodies to thyroglobulin or a microsomal-derived antigen (peroxidase) even if they are euthyroid. The incidence of elevated thyroid antibodies in patients with chronic urticaria is 12% compared with 36% in the general population. Although some patients show clinical reduction of their urticaria on thyroid replacement therapy, others do not. Therefore, many investigators believe that these are associated, parallel, autoimmune events, although some believe that thyroid autoimmunity is driving the urticaria. There is currently no strong evidence to support the latter hypothesis. Thirty-five to 40% of patients with chronic urticaria have a positive autologous skin test: If serum from the patient is intradermally injected into their skin, a significant wheal and flare reaction develops. Such patients frequently have a complement-activating IgG antibody directed to the subunit of the IgE receptor that can cross link the IgE receptor ( subunit) and degranulate mast cells and basophils. An additional 510% of chronic urticaria patients have anti-IgE antibodies rather than anti-IgE receptor antibody. These patients, who are classified as having autoimmune urticaria, tend to have a somewhat more severe clinical course than patients without evidence of autoantibodies, but the difference is not dramatic.
DIAGNOSIS.

The diagnosis of both acute and chronic urticaria is primarily clinical and requires that the physician be aware of the various forms of urticaria. Urticaria is transient, pruritic, erythematous, raised wheals, with flat tops and edema that may become tense and painful. The lesions may coalesce and form polycyclic, serpiginous, or annular lesions (Figs. 147-1 and 147-2 [1] [2]). Individual lesions usually last20 min to 3 hr, and rarely more than 24 hr. The lesions often disappear and reappear. Angioedema involves the deeper subcutaneous tissues such as the eyelids, lips, tongue, genitals, and dorsum of the hands or feet.

Drugs and foods are the most common causes of acute urticaria. Allergy skin testing for foods can be helpful in sorting out causes of acute urticaria, especially when supported by historical evidence. The role of an offending food can then be proven by elimination and careful challenge in a controlled setting. In the absence of any clue suggesting an ingestant cause, skin testing for foods and implementation of elimination diets are generally not useful for either acute or chronic urticaria. Skin testing for aeroallergens is not indicated unless there is a concern about contact urticaria (animal dander). Dermatographism is frequent in patients with urticaria and can complicate allergy skin testing by causing false-positive reactions, but this is usually discernable. An exogenous cause of chronic urticaria is rarely identified, reflecting its autoimmune or idiopathic etiology. An autologous serum skin test is useful to establish the diagnosis of autoimmune urticaria. In vitro testing for antibodies to Fc receptor I (Fc RI) may soon be available. The differential diagnosis of chronic urticaria includes cutaneous or systemic mastocytosis, complement-mediated disorders, malignancies, mixed connective tissue diseases, and cutaneous blistering disorders (e.g., bullous pemphigoid) (see Table 147-2 ). In general, laboratory testing should be limited to a complete blood cell count with differential, ESR, urinalysis, thyroid autoantibodies, and liver function tests. Further studies are warranted if the patient has fever, arthralgias, or elevated ESR (see Table 147-3 ). Hereditary angioedema, a potentially life-threatening form of angioedema associated with deficient C1 inhibitor activity, is the most important familial form of angioedema (see Chapter 133.3 ) but is not associated with typical urticaria. In patients with eosinophilia, stools for ova and parasites should be obtained because infection with helminthic parasites has been associated with urticaria. A syndrome of episodic angioedema/urticaria and fever with associated eosinophilia has been described in both adults and children. In contrast to other hypereosinophilic syndromes, this entity has a benign course. Skin biopsy for diagnosis of possible urticarial vasculitis is recommended for urticarial lesions that persist at the same location for >24 hr, those with pigmented or purpuric components, and those that burn more than itch. Collagen vascular diseases such as systemic lupus may manifest urticarial vasculitis as a presenting feature. The skin biopsy in urticarial vasculitis typically shows endothelial cell swelling of postcapillary venules with necrosis of the vessel wall, perivenular neutrophil infiltrate, diapedesis of red blood cells, and fibrin deposition associated with deposition of immune complexes. Mastocytosis is characterized by mast cell hyperplasia in the bone marrow, liver, spleen, lymph nodes, and skin. Clinical effects of mast cell activation are common, including pruritus, flushing, urtication, abdominal pain, nausea, and vomiting. The diagnosis is confirmed by a bone marrow biopsy containing increased numbers of spindle-shaped mast cells that express CD2 and CD25. Urticaria pigmentosa is the most common skin manifestation of mastocytosis and may occur as an isolated skin finding. It appears as small, yellow-tan to reddish-brown macules or raised papules that urticate on scratching (Darier sign). This sign can be masked by antihistamines. The diagnosis is confirmed by a skin biopsy that shows increased numbers of dermal mast cells. Physical urticaria should be considered in any patient with chronic urticaria (see Table 147-3 ). Papular urticaria commonly occurs in small children, generally on the extremities. It presents as

grouped or linear highly pruritic wheals or papules mainly on exposed skin at the sites of insect bites. Exercise-induced anaphylaxis presents as varying combinations of pruritus, urticaria, angioedema, wheezing, laryngeal obstruction, or hypotension after exercise (see Chapter 148 ). Cholinergic urticaria is differentiated by positive results on heat challenge tests and the rare occurrence of anaphylactic shock. The combination of ingestion of various food allergens (shrimp, celery, or wheat) and postprandial exercise has been associated with urticaria/angioedema and anaphylaxis. In such patients, food or exercise alone may not produce this reaction. Muckle-Wells syndrome and familial cold autoinflammatory syndrome (FCAS) are rare, dominantly inherited conditions associated with recurrent urticarial-like lesions. Muckle-Wells is characterized by arthritis and limb pain that usually appears in adolescence. It is associated with progressive nerve deafness, recurrent fever, elevated ESR, hypergammaglobulinemia, renal amyloidosis, and a poor prognosis. FCAS is characterized by a cold-induced rash that has urticarial features but is rarely pruritic. Cold exposure leads to additional symptoms such as conjunctivitis, sweating, headache, and nausea. Longevity is usually normal.
TREATMENT.

Acute urticaria is a self-limited illness requiring little treatment other than antihistamines. Hydroxyzine and diphenhydramine are sedating, but they are effective and commonly used for treatment of urticaria. Loratadine, fexofenadine, and cetirizine are also effective and are preferable because of reduced frequency of drowsiness ( Table 147-4 ). Epinephrine 1 : 1,000, 0.01 mL/kg (maximum: 0.3 mL) usually provides rapid relief of acute, severe urticaria/angioedema. A short burst of cortico-steroids should be given only for very severe episodes of urticaria and angioedema. TABLE 147-4 -- Treatment of Uticaria and Angioedema Class/drug Dose ANTIHISTAMINES, TYPE H1 (2ND GENERATION) Fexofenadine 611 yr: 30 mg; >12 yr: 60 mg Adult: 180 mg Loratadine Desloratadine 25 yr: 5 mg >6 yr: 10 mg 611 mo: 1 mg 15 yr: 1.25 mg 611 yr: 2.5 mg >12 yr: 5 mg qd Once daily qd bid

Frequency

Class/drug Cetirizine

Dose 624 mo: 2.5 mg 26 yr: 2.55 mg >6 yr: 510 mg

Frequency 612 mo: once daily 1224 mo: 12 daily 212 yr: once daily DIVIDED Q612 HR Divided q12 hr Divided q12 hr

ANTIHISTAMINES, TYPE H2 CIMETIDINE Ranitidine Famotidine INFANTS:1020 MG/KG/DAY; Children: 2040 mg/kg/day 1 mo16 yr: 510 mg/kg/day 312 mo: 1 mg/kg/day 116 yr: 12 mg/kg/day LEUKOTRIENE PATHWAY MODIFIERS Montelukast 12 mo5 yr: 4 mg 614 yr: 5 mg; >14 yr: 10 mg Zafirlukast Cyclosporine Sulfasalazine IVIG 511 yr: 10 mg 46 mg/kg/day >6 yr: 30 mg/kg/day 400 mg/kg/day bid Once daily Divided q6 hr[] 5 consecutive days IMMUNOMODULATORY DRUGS Once daily

Ophthalmologic examinations are required every 6 mo.

*

Monitor blood pressure, creatinine, potassium, and magnesium monthly.

Monitor complete blood count and liver function tests at baseline, every 2 wk for 3 mo, and then every 13 mo. IVIG,

intravenous immunoglobulin.

Most forms of physical urticaria respond to avoidance of triggering stimuli in combination with oral antihistamines. The exception is delayed pressure urticaria, which often requires oral corticosteroids. Cyproheptadine in divided doses is the drug of choice for cold-induced urticaria. Treatment of dermatographism consists of local skin care and antihistamines; for severe symptoms, high doses may be needed. The initial objective of therapy is to decrease pruritus so that the stimulation for scratching is diminished. A combination of antihistamines, sunscreens, and avoidance of sunlight are helpful for most patients. Chronic urticaria only rarely responds favorably to dietary manipulation. The combined use of H1- and H2-type antihistamines is sometimes helpful to control chronic urticaria when H1-type

antihistamines alone, even at higher than standard doses, do not work (see Table 147-4 ). Doxepin, an antagonist of both H1 and H2 receptors, can be helpful, but its usefulness is limited due to adverse effects. H2-type antihistamines alone may exacerbate urticaria. If hives persist after maximal H1- and/or H2-receptor blockade has been achieved, alternate-day therapy with cortico-steroids is the most effective treatment. In general, prednisone 20 mg orally as a single morning dose on alternate days is used, with the dosage decreased by 2.55.0 mg every 13 wk depending on the clinical response. The clinical goal is slow reduction of the use of this drug. Antileukotriene agents in combination with antihistamines may also be helpful. Treatment with cyclosporine 46 mg/kg/day has been effective in some adults with chronic urticaria, but is limited by hypertension and/or nephrotoxicity. Removal of urticarial aggravators, such as salicylates, alcohol, or -blockers, should be considered. Treatment of autoimmune chronic urticaria refractory to medical therapy includes intravenous immunoglobulin, plasmapheresis, or both. Nelson Textbook of Pediatrics [2007]

Urtikaria atau biduran adalah penyakit alergi yang sangat mengganggu dan membuat penderita atau dokter kadang frustasi. Frustasi karena pada keadaan tertentu gangguan ini sering hilang timbul tanpa dapat diketahui secara pasti penyebabnya. Kesulitan mencari penyebab ini terjadi karena faktor yang berpengaruh sangat banyak dan sulit dipastikan. Secara umum yang mendasari utama biasanya adalah penderita memang punya bakat alergi kulit yang didasari oleh alergi makanan dan dipicu oleh hilang timbulnya infeksi virus dalam tubuh (gejalanya demam, sumeng atau tanpa demam, pilek, badan pegal (sering dikira kecapekan), batuk atau gangguan saluran cerna). Bila dalam keadaan sehat pengaruh alergi makanan sangat ringan atau bila tidak cermat seperti tanpa gejala. Tetapi hal yang ringan bila tidak dikenali ditambah berbagai faktor resiko dan bila terjadi infeksi virus maka urtikaria baru akan timbul. Sayangnya alergi makanan sebagai penyakit mendasari ini tidak bisa dipastikan dengan tes alergi, karena tes alergi spesifitasnya rendah bila untuk mencari penyebab alergi makanan. Hal inilah yang membuat penanganan urtikaria lebih sulit lagi, khususnya dalam mencari penyebabnya. Pemberian obat jangka panjang adalah bentuk kegagalan mencari penyebabnya. Bila urtikaria ini sudah terjadi jangka panjang maka bila penderita mengalami serangan flu atau infeksi virus ringan saja akan dapat memicu kekambuhannya. Urtikaria
y y

Urtikaria merupakan penyakit yang sering ditemukan, diperkirakan 3,2-12,8% dari populasi pernah mengalami urtikaria. Urtikaria adalah erupsi pada kulit yang berbatas tegas dan menimbul (bentol), berwarna merah, memutih bila ditekan, dan disertai rasa gatal. Urtikaria dapat berlangsung secara akut, kronik, atau berulang.

Urtikaria akut biasanya berlangsung beberapa jam sampai beberapa hari (kurang dari 6 minggu) dan umumnya penyebabnya dapat diketahui. Urtikaria kronik, yaitu urtikaria yang berlangsung lebih dari 6 minggu, dan urtikaria berulang biasanya tidak diketahui pencetusnya dan dapat berlangsung sampai beberapa tahun. Urtikaria kronik umumnya ditemukan pada orang dewasa. Urtikaria juga dapat diklasifikasikan berdasarkan etiologi, yaitu imunologi, anafilaktoid dan penyebab fisik. Reaksi imunologi dapat diperantarai melalui reaksi hipersensitivitas tipe I, tipe II atau III. Sedangkan reaksi anafilaktoid dapat disebabkan oleh angioedema herediter, aspirin, zat yang menyebabkan lepasnya histamin seperti zat kontras, opiat, pelemas otot, obat vasoaktif dan makanan (putih telur, tomat, lobster). Secara fisik, urtikaria dapat berupa dermatografia, cold urticaria, heat urticaria, solar urticaria, pressure urticaria, vibratory angioedema, urtikaria akuagenik dan urtikaria kolinergik.

Urticaria pada penderita dengan infeksi virus MEKANISME TERJADINYA PENYAKIT

y

Pada gangguan urtikaria menunjukkan adanya dilatasi pembuluh darah dermal di bawah kulit dan edema (pembengkakan) dengan sedikit infiltrasi sel perivaskular, di antaranya yang paling dominan adalah eosinofil. Kelainan ini disebabkan oleh mediator yang lepas, terutama histamin, akibat degranulasi sel mast kutan atau subkutan, dan juga leukotrien dapat berperan. Histamin akan menyebabkan dilatasi pembuluh darah di bawah kulit sehingga kulit berwarna merah (eritema). Histamin juga menyebabkan peningkatan permeabilitas pembuluh darah sehingga cairan dan sel, terutama eosinofil, keluar dari pembuluh darah dan mengakibatkan pembengkakan kulit lokal. Cairan serta sel yang keluar akan merangsang ujung saraf perifer kulit sehingga timbul rasa gatal. Terjadilah bentol merah yang gatal. Bila pembuluh darah yang terangsang adalah pembuluh darah jaringan subkutan, biasanya jaringan subkutan longgar, maka edema yang terjadi tidak berbatas tegas dan tidak gatal karena jaringan subkutan mengandung sedikit ujung saraf perifer, dinamakan angioedema. Daerah yang terkena biasanya muka (periorbita dan

perioral). Urtikaria disebabkan karena adanya degranulasi sel mast yang dapat terjadi melalui mekanisme imun atau nonimun. Degranulasi sel mast dikatakan melalui mekanisme imun bila terdapat antigen (alergen) dengan pembentukan antibodi atau sel yang tersensitisasi. Degranulasi sel mast melalui mekanisme imun dapat melalui reaksi hipersensitivitas tipe I atau melalui aktivasi komplemen jalur klasik. Faktor infeksi pada tubuh diantaranya infeksi viru (demam, batuk dan pilek) merupakan faktor pemicu pada urtikaria yang paling sering terjadi namun sering diabaikan Beberapa macam obat, makanan, atau zat kimia dapat langsung menginduksi degranulasi sel mast. Zat ini dinamakan liberator histamin, contohnya kodein, morfin, polimiksin, zat kimia, tiamin, buah murbei, tomat, dan lain-lain. Masih belum jelas mengapa zat tersebut hanya merangsang degranulasi sel mast pada sebagian orang saja, tidak pada semua orang. Faktor fisik seperti cahaya (urtikaria solar), dingin (urtikaria dingin), gesekan atau tekanan (dermografisme), panas (urtikaria panas), dan getaran (vibrasi) dapat langsung menginduksi degranulasi sel mast. Latihan jasmani (exercise) pada seseorang dapat pula menimbulkan urtikaria yang dinamakan juga urtikaria kolinergik. Bentuknya khas, kecil-kecil dengan diameter 1-3 mm dan sekitarnya berwarna merah, terdapat di tempat yang berkeringat. Diperkirakan yang memegang peranan adalah asetilkolin yang terbentuk, yang bersifat langsung dapat menginduksi degranulasi sel mast. Faktor psikis atau stres pada seseorang dapat juga menimbulkan urtikaria. Bagaimana mekanismenya belum jelas.

MANIFESTASI KLINIS
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y y

Klinis tampak bentol (plaques edemateus) multipel yang berbatas tegas, berwarna merah dan gatal. Bentol dapat pula berwarna putih di tengah yang dikelilingi warna merah. Warna merah bila ditekan akan memutih. Ukuran tiap lesi bervariasi dari diameter beberapa milimeter sampai beberapa sentimeter, berbentuk sirkular atau serpiginosa (merambat). Tiap lesi akan menghilang setelah 1 sampai 48 jam, tetapi dapat timbul lesi baru. Pada dermografisme lesi sering berbentuk linear, pada urtikaria solar lesi terdapat pada bagian tubuh yang terbuka. Pada urtikaria dingin dan panas lesi akan terlihat pada daerah yang terkena dingin atau panas. Lesi urtikaria kolinergik adalah kecilkecil dengan diameter 1-3 milimeter dikelilingi daerah warna merah dan terdapat di daerah yang berkeringat. Secara klinis urtikaria kadang-kadang disertai angioedema yaitu pembengkakan difus yang tidak gatal dan tidak pitting dengan predileksi di muka, daerah periorbita dan perioral, kadang-kadang di genitalia. Kadang-kadang pembengkakan dapat juga terjadi di faring atau laring sehingga dapat mengancam jiwa.

Udara dingin dan debu bukan penyebab

Selama ini penderita menganggap bahwa penyebab urtikaria adalah udara dingin dan debu. Padahal udara dingin hanya sebagai faktor yang memperberat. Sedangkan debu bisa mengganggu kulit dengan bentuk yang berbeda, bila penyebabnya debu hanya timbul 2-6 jam setelah itu menghilang. Debu sebagai penyebab hanya dalam jumlah banyak seperti rumah yang tidak ditinggali lebih dari seminggu, bila bongkar-bongkar kamar, bila terdapat karpet tebal yang permanen, bila masuk gudang, boneka atau baju yang lama disimpan dallam gudang atau lemari. Faktor Resiko Yang memperberat Urtikaria :
y y y y y y

INFEKSI (panas, batuk, pilek) AKTIFITAS MENINGKAT (menangis, berlari, tertawa keras) UDARA DINGIN UDARA PANAS STRES GANGGUAN HORMONAL: (kehamilan, menstruasi)

Faktor pemicu tidak akan berpengaruh bila penyebab utama alergi tidak ada. Artinya, bila penyebabnya alergi makanan tidak ada atau dikendalikan maka udara dingin, udara panas, stres, infeksi virus, dan lain sebagainya tidak akan berpengaruh. Jadi, udara dingin dan faktor pemicu lainnya hanya memperberat bukan penyebab utama. DIAGNOSIS
y

Diagnosis ditegakkan secara klinis berdasarkan inspeksi kulit yaitu adanya lesi khas berupa bentol berwarna merah, berbatas tegas, gatal, memutih bila ditekan. Yang sulit adalah mencari etiologinya. Untuk menemukan etiologi perlu dilakukan anamnesis yang teliti dan terinci serta pemeriksaan fisis lengkap. Anamnesis terhadap faktor lingkungan seperti debu, tungau debu rumah, binatang peliharaan, tumbuh-tumbuhan, karpet, sengatan binatang, serta faktor makanan termasuk zat warna, zat pengawet, obat-obatan, faktor fisik seperti dingin, panas, cahaya dan sebagainya perlu ditelusuri. Pemeriksaan fisis yang menunjukkan bentuk khas dapat diduga penyebabnya seperti lesi linear, lesi kecil-kecil di daerah berkeringat, dan lesi hanya pada bagian tubuh yang terbuka. Bila dari anamnesis dan pemeriksaan fisis belum dapat ditegakkan etiologinya, dapat dilakukan beberapa pemeriksaan penunjang.

Bagaimana mendeteksi bahwa Makanan berperanan dalam urtikaria Alergi makanan dapat dicurigai ikut berperanan dalam gangguan urtikaria bila terdapat gangguan saluran cerna. Gangguan saluran cerna yang terjadi adalah :
y

Pada Bayi : bayi mengalami Gastrooesepageal Refluks, Sering MUNTAH/gumoh, kembung,cegukan, buang angin keras dan sering, sering rewel gelisah (kolik) terutama malam hari, BAB > 3 kali perhari, BAB tidak tiap hari. Feses warna hijau,hitam dan

berbau. Sering ngeden & beresiko Hernia Umbilikalis (pusar), Scrotalis, inguinalis. Air liur berlebihan. Lidah/mulut sering timbul putih, bibir kering Pada Anak dan dewasa : Keluhan muntah sejak bayi berkurang tetapi masih ada. Pada usia dewasa masih sering mengalami mudah muntah bila menangis, berlari atau makan banyak atau bila naik kendaran bermotor, pesawat atau kapal. MUAL pagi hari bila hendak gosok gigi atau sedang disuap makanan. Sering Buang Air Besar (BAB) 3 kali/hari atau lebih, sulit BAB (obstipasi), kotoran bulat kecil hitam seperti kotoran kambing, keras, sering buang angin, berak di celana. Sering KEMBUNG, sering buang angin dan buang angin bau tajam. Sering NYERI PERUT. Pada penderita dewasa sering megalami gejala penyakit Maag.

DIAGNOSIS BANDING
y

y y

Angioedema herediter Kelainan ini merupakan kelainan yang jarang tidak disertai urtikaria. Pada kelainan ini terdapat edema subkutan atau submukosa periodik disertai rasa sakit dan terkadang disertai edema laring. Edema biasanya mengenai ekstremitas dan mukosa gastrointestinalis yang sembuh setelah 1 sampai 4 hari. Pada keluarga terdapat riwayat penyakit yang serupa. Diagnosis ditegakkan dengan menemukan kadar komplemen C4 dan C2 yang menurun dan tidak adanya inhibitor C1-esterase dalam serum. Sengatan serangga multipel Pada sengatan serangga akan terlihat titik di tengah bentol, yang merupakan bekas sengatan serangga. sengatan serangga.

Pressure urticaria

Urticaria pigmentosa (Darier sign).

Urticaria pigmentosa. PENGOBATAN

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Pengobatan yang palin utama adalah ditujukan pada penghindaran faktor penyebab dan pengobatan simtomatik. Pada urtikaria akut generalisata dan disertai gejala distres pernafasan, asma atau edema laring, mula-mula diberi larutan adrenalin 1% dengan dosis 0,01 ml/kgBB subkutan (maksimum 0,3 ml), dilanjutkan dengan pemberian antihistamin penghambat H1 (lihat bab tentang medikamentosa). Bila belum memadai dapat ditambahkan kortikosteroid. Pada urtikaria akut lokalisata cukup dengan antihistamin penghambat H1.

Urtikaria kronik biasanya lebih sukar diatasi. Idealnya adalah tetap identifikasi dan menghilangkan faktor penyebab, namun hal ini juga sulit dilakukan. Untuk ini selain antihistamin penghambat H1 dapat dicoba menambahkan antihistamin penghambat H2. Kombinasi lain yang dapat diberikan adalah antihistamin penghambat H1 non sedasi dan sedasi (pada malam hari) atau antihistamin penghambat H1 dengan antidepresan trisiklik. Pada kasus berat dapat diberikan antihistamin penghambat H1 dengan kortikosteroid jangka pendek. Bila pada penderita terjadi gangguan saluran cerna (seperti gejala yang tersebut di atas) maka sangat mungkin alergi makanan ikut berperanan memperberat gangguan urtikaria yang ada. Untuk menanganinya lakukan eliminasi makanan beresiko (lihat topik mencari penyebab alergi makanan) dalam waktu 3 minggu secara ketat dan dilakukan evaluasi

PROGNOSIS
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Pada umumnya prognosis urtikaria adalah baik, dapat sembuh spontan atau dengan obat. Tetapi karena urtikaria merupakan bentuk kutan anafilaksis sistemik, dapat saja terjadi obstruksi jalan nafas karena adanya edema laring atau jaringan sekitarnya, atau anafilaksis sistemik yang dapat mengancam jiwa.

DAFTAR PUSTAKA
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