Dr. Kessel Aharon, Department of Allergy and Clinical Immunology Bnai-Zion,2007 CHRONIC AND ACUTE URTICARIA IN CHILDREN

Urticaria, is characterized by transient, itchy, elevated edematous wheals or red papules.

Wheal typical features # A central swelling, surrounded by erythema. # Itching or burning sensations # The wheal disappear usually within 1-24 h.

# Pronounced swelling of the lower dermis and subcutis. # Most often found in the lips, eyelids or genitalia. # Itching and sometimes pain. # Resolution can take up to 72h. # It is associated with urticaria in about 40% of cases. Angioedema

The histology of the lesions of chronic idiopathic urticaria Venule and capillary dilatation tissue edema –upper and mid dermis. predominantly perivascular cellular infiltrate – primarily mononuclear cells T cell are the predominant cell type (80%) Mild to moderate increase of mast Cell numbers

Clinical classification of urticaria and angioedema Ordinary urticaria- acute, chronic, episodic. Physical urticaria Angioedema Contact urticaria Urticarial vasculitis

Clinical classification of urticaria and angioedema Ordinary urticaria Acute- up to 6 weeks of continuous activity Chronic – 6 weeks or more of continuous Episodic (intermittent)

מה היא הסיבה השכיחה ביותר שניתן למצוא כגורמת לאורטיקריה חריפה ? 1.אלרגיה לתרופות 2.מחלות זיהומיות 3.עקיצות חרקים 4.חומרי ניגוד 5.אלרגיה למזון

57 children age range 1-36 months Presumptive cause Viral infection 18 cases (12 associated with drug intake) Adenovirus EBV Enterovirus RSV ROTA virus Varicella-Zoster virus BACTERIAL INFECTION 1 CASE– E.COLI FOOD -6 cases Probable cause (27 cases)– viral infections Mortureux P, et al Archives of dermatology 1998;143:

Acute urticaria I nfections - viral :herpes simplex, hepatitis B, coxsackie A and B, upper respiratory infections. Bacterial- associated with certain infectious foci: dental caries/abscesses, pharyngitis /tonsillitis, otitis media, occult abscesses, UTI. Parasitic : ascaris, strongyloides, echinococcus, toxocara, fasciola, filaria, schistosoma. Fungal?: candida

Acute urticaria Exposure to food allergens- milk, eggs, peanuts, sesame,soy wheat, shellfish, fish. Medications- β-lactam antibiotics, sulfonamides, aspirin. Radiocontrast media

האם מתן קורטיקוסטרואידים בנוסף לאנטיהיסטמיניקה עוזר בטיפול באורטיקריה חריפה ? ילדה בת 4 שנים מגיעה לחדר מיון עם אוטיקריה, היא מטופלת ע"י רופא מטפל באנטיהיסטמינקה למרות כך עדיין הפריחה קיימת.

Treatment of acute urticaria Short Outpatient management of acute urticaria: the role of prednisone. CONCLUSION: The addition of a prednisone burst improves the symptomatic and clinical response of acute urticaria to antihistamines. Patients' conditions improved more quickly and more completely when prednisone was administered, without any apparent adverse effects. Ann Emerg Med Nov;26(5):

ALGORITHM FOR ACUTE URTICARIA/ANGIOEDEMA DETAILED HISTORY : infection drug food physical triggers PHYSICAL EXAMINATION SPECIFIC EXAMINATION- CBC, URINE, ESR SKIN TESTS

IgE-dependent (type -1)

Skin Prick Test (SPT)

Positive reaction

Muckle-Wells syndrome Familial -dominantly inherited. urticaria progressive nerve deafness Limb pain arthritis Recurrent fever hypergammaglobulinemia amyloidosis SYNDROMYES THAT CAN BE ASSOCIATED WITH URTICARIA

Gleich's syndrome - the episodic angioedema with eosinophilia syndrome Schnitzler syndrome (SS), first reported in 1972, is characterized by chronic, nonpruritic urticaria in association with recurrent fever, bone pain, arthralgia or arthritis, and a monoclonal immunoglobulin M (IgM) gammopathy in a concentration that is usually less than 10 g/dL.

Chronic Urticaria – 6 weeks or more of continuous urticaria.

מה היא הסיבה השכיחה ביותר לאורטיקריה כרונית ? 1.אלרגיה לתרופות 2.גורמים זיהומיים 3.אידיופטי 4.מנגנון אוטואימוני 5.אלרגיה למזון 6.דלקת מפרקים של גיל הילדות

93 ילדים (52-זכרים, 41 נקבות, גיל ממצוע 7.8 שנים ) אורטיקריה-אידיופטית 31% אורטיקריה אוטואימונית 29% אורטיקריה עקב גורם זיהומי 15% אורטיקריה פיזיקאלית 12% אורטיקריה מולטיפקטוריאלית 11% אורטיקריה אלרגית – 2% Brunetti et al. J Allergy Clin Immunol 2004;114:922-7

In 1986 Grattan first described that: Autologous serum test produces a Wheal and Flare reaction In 30-50% of CIU cases Autoimmune urticaria

Autoimmune (autoantibodies against FcεRI or IgE) In 1993 M. Greaves first found the presence of autoantibodies in CIU. N Engl J Med 1993;328:

In vitro studies demonstrated that 75% of autoAb are IgG against FceR (causing in-vitro human basophil degranulation) 15% were IgG against IgE (cross-linking two IgEs on mast cells)

Autoimmune basis for CIU Thyroid autoimmunity in pts with CIU anti-thyroid Ab. in 14-20% increased / decreased thyroid function in 5-10%

B and T cell lymphocytes derived from active CU patients demonstrated an increase expression of bcl-2. Immune aberrations- basis for CIU Activated T cell express increased expression of CD40L Toubi et al. J Clin Immuno 2000;20:

Physical urticaria The physical urticarias are characterized by the development of wealing and itching promptly after application of the appropriate physical stimulus. Weals typically fade within minutes. The exception is delayed pressure urticaria when the weals take several hours to appear after sustained pressure and can last up to 48 hours.

Itchy, monomorphic pale or pink wheals on trunk, neck, and limbs – after exercise or a hot shower Physical urticaria-cholinergic Prevalence of 11% in the age group of years.

Physical urticaria-pressure Large painful or itchy red swelling at sites of pressure (soles, palms, or waist) lasting 24 hours or more- application of pressure perpendicular to skin produces red swelling after a latent period of 1 to 4 hours.

Physical urticaria- dermographic urticaria Itchy, linear wheals with surrounding bright-red flare at sites of scratching or rubbing.

Physical urticaria- dermographic urticaria # The most frequent form of physical urticaria. # Affecting mainly young adults # Mean duration 6.5 years

Physical urticaria- heat A rare form of urticaria. nduced by direct contact of the skin with warm objects or warm air. The eliciting temperature ranges from 38º C to more than 50 º C.

Physical urticaria- cold Itchy pale or red swelling at sites of contact with cold surfaces or fluids- ten minutes application of an ice pack causes a wheal within five minutes of the removal of ice.

More frequent in women than men. Majority is idiopathic, some can also occur as a result of infections, neoplasia or autoimmune diseases. Infectious: syphilis, measles hepatitis,mononucleosis, HIV. Physical urticaria- cold

Other forms of physical urticaria Solar Vibratory Adrenergic aquagenic

Role of nonallergic hypersensitivity reactions in children with chronic urticaria ~ 5 % Food –symptoms clears within 48 hours if relevant food allergens are eliminated. Food additives Elimination pseudoallergen diet - for at least 2-3 weeks before beneficial effect seen. Allergy 1998:53:1074-7

The prevalence in different studies ~ 5-10% Viruses- hepatitis B,C, EBV, CMV Bacteria- helicobacter pylori ? streptococci/staphylococci parasites -Anecdotal series of cases documented a link between parasites and chronic urticaria such as: toxocara canis, giaardia lamblia, strongyloides stercoralis and even blastocytis hominis.

Urticarial vasculitis

Do not have a predominantly physical trigger. Are not caused by underlying vasculitis. Are not caused by direct contact with the causative agent. This heterogeneous group includes: cases for which no cause can be identified. IDIOPATHIC URTICARIA

CU Duration ?? * Patients ask, how long CU will last ?? * More than 60% still visit the clinic after 6 months. * 40% of patients still suffer from CU after one year.

CU% Urticaria duration (months) Clinical and Laboratory Parameters in Predicting Chronic Urticaria Duration: A Prospective Study of 139 Patients Toubi et al Allergy: % 75% 52% 43% 14%

Rates of urticaria duration in relation to disease severity severity Rates of urticaria cure 12m* 24m 36m 60m p value mild (n = 23) moderate – severe (n = 116) 68% 0% % 59% 50% 32% <

TREATMENT OF CHRONIC URTICARIA Daily non-sedating antihistamine Combination of H1 and H2 receptors antagonists Corticosteroids

TREATMENT OF SEVERE UNREMITTING URTICARIA Plasmapheresis Intravenous immunoglobulin Cyclosporin A

Cyclosporine A cyclosporine on helper T-cells to inhibit T- cell receptor-activated induction of IL-2 gene. cyclosporine may also inhibit IgE- stimulated mast cell degranulation and stimulate TGF-  expression.

Low dose cyclosporin A in the treatment of severe chronic idiopathic urticaria. 2-3mg\kg of CsA, was shown to be beneficial AST Positivity could not predicted response to treatment. In some cases Prolonged treatment is needed Toubi et al Allergy 1997;52:

ANGIOEDEMA With weals Without weals All kinds of urticaria except dermographism Idiopathic DRUGS- NSAIDs,ACEIs C1 eterase deficiency

Complement-dependent (C1 esterase inh.Def.)

אנגיואדמה תורשתית סוג 1 C4 –decreased, C1 esterase-decreased אנגיואדמה תורשתית סוג 2 C4 –decreased, C1 esterase-normal אנגיואדמה אידיופטית C4 –normal, C1 esterase-normal

CONTACT URTICARIA Contact urticaria is an important manifestation of natural rubber latex allergy.

תאור מקרה ל.ע בת 16 שנים הופנתה עקב אורטיקריה מזה כחצי שנה. סקירה מערכתית : עליה במשקל של כ5 ק"ג בחצי שנה,עייפות. בדיקה גופנית אורטיקריה קלה בעיקר בבטן וגב – בולטת יותר באזורי לחץ.

בדיקות מעבדה : ס"ד, תפקודי כבד,כליה, שתן כללית,צואה לפרזיטים-ללא ממצא. טסט עורי למוצרי מזון- שלילי TSH- 50 ↑, נוגדנים לרקמת בלוטת התריס. - AUTOLOGUS SERUM TEST חיובי. טיפול – מתן אלטרוקסין לורסטין 10 מ"ג