CHRONIC AND ACUTE URTICARIA IN CHILDREN Dr Kessel

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

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.

Angioedema # 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 72 h. # It is associated with urticaria in about 40% of cases.

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)

57 children age range 1 -36 months Presumptive cause Viral infection 18 cases (12 associated with drug intake) Adenovirus ROTA virus EBV Enterovirus RSV 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: 319 -23.

Acute urticaria • Infections- 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

Treatment of acute urticaria Ann Emerg Med. 1995 Nov; 26(5): 547 -51. 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.

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

Ig. E-dependent (type -1)

Skin Prick Test (SPT)

Positive reaction

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

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 (Ig. M) gammopathy in a concentration that is usually less than 10 g/d. L.

Chronic Urticaria – 6 weeks or more of continuous urticaria.

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

Autoimmune (autoantibodies against FcεRI or Ig. E) In 1993 M. Greaves first found the presence of autoantibodies in CIU. N Engl J Med 1993; 328: 1599 -604

In vitro studies demonstrated that 75% of auto. Ab are Ig. G against Fce. R (causing in-vitro human basophil degranulation) 15% were Ig. G against Ig. E (cross-linking two Ig. Es 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%

Immune aberrations- basis for CIU Activated T cell express increased expression of CD 40 L B and T cell lymphocytes derived from active CU patients demonstrated an increase expression of bcl-2. Toubi et al. J Clin Immuno 2000; 20: 371 -378

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 30 -60 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.

Physical urticaria-cholinergic Itchy, monomorphic pale or pink wheals on trunk, neck, and limbs – after exercise or a hot shower Prevalence of 11% in the age group of 16 -35 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.

Physical urticaria- cold 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.

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

Urticarial vasculitis

IDIOPATHIC URTICARIA • 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.

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.

Clinical and Laboratory Parameters in Predicting Chronic Urticaria Duration: A Prospective Study of 139 Patients 94% 75% 43% CU% 52% 14% 60 36 24 12 Urticaria duration (months) Toubi et al Allergy: 2003 6

Rates of urticaria duration in relation to disease severity Rates of urticaria cure 12 m* mild 68% (n = 23) moderate – severe 86% (n = 116) 24 m 0% 59% 36 m 50% p value 60 m 32% < 0. 0001

TREATMENT OF CHRONIC URTICARIA • Daily non-sedating antihistamine • Combination of H 1 and H 2 receptors antagonists • Corticosteroids

TREATMENT OF SEVERE UNREMITTING URTICARIA • Plasmapheresis • Intravenous immunoglobulin • Cyclosporin A

Cyclosporine A • cyclosporine on helper T-cells to inhibit Tcell receptor- activated induction of IL-2 gene. • cyclosporine may also inhibit Ig. Estimulated mast cell degranulation and stimulate TGF- expression.

Low dose cyclosporin A in the treatment of severe chronic idiopathic urticaria. • 2 -3 mgkg of Cs. A, 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: 312 -316.

ANGIOEDEMA With weals All kinds of urticaria except dermographism Without weals Idiopathic DRUGS- NSAIDs , ACEIs C 1 eterase deficiency

Complement-dependent (C 1 esterase inh. Def. )

Complement-dependent (C 1 esterase inh. Def. )

1 אנגיואדמה תורשתית סוג C 4 –decreased , C 1 esterase-decreased 2 אנגיואדמה תורשתית סוג C 4 –decreased , C 1 esterase-normal אנגיואדמה אידיופטית C 4 –normal , C 1 esterase-normal

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