MANAGEMENT OF URTICARIA

1. MANAGEMENT OF URTICARIA By Lamia Elgarhy Assistant lecturer

2. MANAGEMENT OF URTICARIAAm J Clin Dermatol. 2009

3. First-line Therapy

4. General measures • It include : • Avoidance of aggravating factors such as overheating, stress, and alcohol. • Avoidance of acetylsalicylic acid, NSAIDs, and ACE inhibitors may also be advisable. • Cooling antipruritic lotions such as 1% or 2% menthol in aqueous cream or calamine lotion may be helpful.

5. General measures • It is important to keep patients well informed about the disease, using both verbal and written information. Specifically, patients should be informed about the benign course of the disease, the lack of a cure, and the fact that a cause often can not be found.

6. Histamine H1 Receptor Antihistamines • The efficacy of antihistamines in alleviating pruritus and decreasing the number of hives is well established, although not all patients will respond. • Of patients treated with antihistamines , only 40% experienced complete clearing of their symptoms.

7. Histamine H1 Receptor Antihistamines • In some patients, antihistamines only reduce the severity of pruritus and decrease the number and duration of wheals. • However, it is important to not assume therapeutic failure if one particular antihistamine does not resolve the urticaria; more than one antihistamine should be tried since efficacy is patient specific. Antihistamines are most effective if taken daily rather than on an as-needed basis.

8. First-generation or classic H1 receptor antihistamines • They include hydroxyzine, diphenhydramine, cyproheptadine, and chlorpheniramine. • These antihistamines are rarely used as monotherapy because of their adverse effect profile, which includes sedating and anticholinergic effects.

9. First-generation or classic H1 receptor antihistamines • However, they can be valuable adjunctive therapy, especially for patients whose sleep is disturbed by symptoms of urticaria. • Many believe that the adverse effect profile in patients with significant urticaria is attenuated and becomes less apparent if the medication is used long term (daily for more than 1 week); however, to our knowledge, this has not been shown in any well conducted studies.

10. Second-generation H1 receptor antihistamines • These include: • cetirizine, • levocetirizine, • loratadine, • desloratadine, • fexofenadine, • ebastine, • mizolastine

11. Second-generation H1 receptor antihistamines • A major advantage of second-generation antihistamines is their lack of significant CNS and anticholinergic adverse effects. • Although antihistamines are often prescribed at doses higher than those recommended in the package insert in an attempt to achieve additional anti-allergenic and anti-inflammatory effects, there is no evidence to support this practice

12. Second-generation H1 receptor antihistamines • Desloratadine is an active metabolite of loratadine and has more potent antihistaminic and anti-inflammatory properties than loratadine. • Cetirizine is an active component of hydroxyzine with similar effects but less sedation. • Levocetirizine is the active enantiomer of cetirizine and is more potent than cetirizine. It has been shown to provide rapid relief of pruritus and wheals in patients with chronic urticaria.

13. H2 Receptor Antagonists • Because 15% of histamine receptors in the skin are of the H2 type, H2 receptor antihistamines have been shown to be a helpful addition to H1 receptor antihistamines in some patients with chronic urticaria. • However, H2 receptor antagonists should not be used alone since they have only minimal effects on pruritus.

14. H2 Receptor Antagonists • H2 receptor antagonists include cimetidine, ranitidine, nizatidine, and famotidine. • Overall, data supporting the efficacy of H2 receptor antagonists are limited.

15. Second-line Therapy

16. ANTIDEPRESSANTS • Doxepin may be especially useful in patients with chronic urticaria and coexisting depression. Although the dosage of doxepin for the treatment of depression may vary from 25 to 150 mg/day, only 10–30 mg/day is recommended for chronic urticaria. • Mirtazapine is an antidepressant that demonstrates significant effect on the H1 receptor and has antipruritic activity. It has been reported to be helpful in a few cases of physical urticariaand delayed-pressure urticariaat doses of 30 mg/day.

17. Corticosteroids • Short courses of systemic corticosteroids can be prescribed for severe urticarial symptoms when the patient needs rapid and complete disease control. • Clinicians should be aware that antihistamine dosages, particularly of first-generation antihistamines given up to four times daily, should be maximized in an attempt to avoid corticosteroid courses.

18. Leukotriene receptor antagonists • Such as montelukast, zafirlukast, and zileuton have been shown to be superior to placebo in the treatment of patients with chronic urticaria. • Leukotriene receptor antagonists such as montelukast may also be effective in controlling chronic urticaria in patients who are unresponsive to antihistamines alone.

19. Leukotriene receptor antagonists • There is also evidence that leukotriene receptor antagonists may prevent NSAID-induced exacerbations in patients with chronic urticaria • Despite these promising results, use of leukotriene receptor antagonists in the management of urticaria remains controversial and not all trials have shown a beneficial effect.

20. Nifedipine • Nifedipine has been reported to be effective in decreasing pruritus and whealing in patients with chronic urticaria when used alone or in combination with antihistamines. • The proposed mechanism of action is modification of calcium influx into cutaneous mast cells.

21. Nifedipine • A trial of nifedipine may be a reasonable option in patients with co-morbid hypertension.

22. Third-line Therapy

23. Third-line Therapy • Patients who require third-line therapy often have the autoimmune form of chronic urticaria. • Immunomodulatory agents, which include cyclosporine, tacrolimus, methotrexate, cyclophosphamide, mycophenolatemofetil, and intravenous immunoglobulins (IVIG).

24. Third-line Therapy • plasmapheresis, • colchicine, dapsone, albuterol (salbutamol), tranexamic acid, terbutaline, sulfasalazine, hydroxychloroquine, and warfarin.

25. Immunomodulatory Agents • Cyclosporine 3–5 mg/kg/day appears to benefit about two-thirds of patients with chronic urticaria (with +ve ASST) who do not respond to antihistamines. • Maintaining patients on long-term cyclosporine therapy should not be taken lightly because of the numerous adverse effects of the drug (e.g. hypertension, renal toxicity) and the potential for rebound after discontinuation

26. Immunomodulatory Agents • Experience with other immunomodulatory agents (tacrolimus, methotrexate, and cyclophosphamide) is more limited

27. The autologous serum skin test (ASST) • The autologous serum skin test (ASST) is currently the best in vivo clinical test for detection of in vitro basophil histamine-releasing activity. • it is performed in patients with chronic idiopathic urticaria to determine the incidence of autoimmune urticaria.

28. The autologous serum skin test (ASST) • The test was performed by injecting 0.05 ml of the patient's own serum intradermally into the left flexor forearm 2 inches below the antecubital crease and a saline control into the right forearm.

29. The autologous serum skin test (ASST) • A reading of the wheal was taken after 30 minutes. A wheal and flare of more than 1.5 mm diameter than that of the control was considered positive

30. IVIG • IVIG appear to be effective in the management of patients with severe refractory autoimmune chronic urticaria. • Although the mechanism of action involved is unclear, it has been proposed that IVIG may contain anti-idiotypic antibodies that compete with endogenous IgG for H1 receptors and block histamine release or enhance clearance of endogenous IgG

31. Plasmapheresis • Plasmapheresis has been reported to be beneficial in the management of treatment-resistant autoimmune chronic urticaria. • this approach can not be used long term or as monotherapy because of expense, potential morbidity, and early relapse of urticaria.

32. Plasmapheresis • Plasmapheresis alone is insufficient to prevent re-accumulation of histamine-releasing autoantibodies

33. OTHER DRUGS • Dapsoneand/or colchicinemay be beneficial in managing urticaria when predominantly neutrophilic infiltrates are seen histologically, but are probably most useful for urticarialvasculitis. • Limited experience suggests that sulfasalazine may be beneficial in managing both chronic idiopathic urticaria and delayed-pressure urticaria;however, many have not found this agent useful and it is probably best reserved for urticarialvasculitis.

34. OTHER DRUGS • Hydroxychloroquine has also shown promising results in the treatment of chronic idiopathic urticaria; and has been associated with a good response in hypocomplementemicurticarialvasculitis.

35. OTHER DRUGS • ß2-adrenoceptor agonist terbutaline has been evaluated for management of chronic urticaria, its use is generally not recommended because of adverse effects such as tachycardia, insomnia, and jitteriness that are not well tolerated by many patients

36. OTHER DRUGS • Warfarin produced a response in some patients with ASST-negative chronic urticaria and angioedema who were resistant to antihistamines. These results suggest that their symptoms were not histamine dependent but more related to coagulation-dependent mediators such as kinins.[74]

37. RECENT STUDY

38. Cutaneous biopsies of the urticaria lesions were taken

39. Treatment regimen

40. After12 weeks of treatment

41. Two years afterdiscontinuation

42. PAPULAR URTICARIAMay 12, 2010 • The use of insect repellents while outside and • the use of flea and tick control on indoor pets are necessary when treating papularurticaria. • For safety purposes, topical insecticides used on infants and children should be in accordance with their age.

43. Medication • Corticosteroids Triamcinolone 0.1% cream (Aristocort) Indicated for the treatment of dermatitis. Midpotency topical corticosteroid that inhibits cell proliferation. Has immunosuppressive and anti-inflammatory properties.

44. Medication • Prednisolone Decreases inflammatory reactions by suppressing migration of polymorphonuclear leukocytes and reducing capillary permeability. Adult 40-60 mg/d PO divided 1-2 doses/d Pediatric 0.5-2 mg/kg/d PO divided 2-4 doses/d

45. Medication • Antihistamines These agents are type 1 histamine receptor blockers. They are most effective when used prophylactically. Typically, the sedating antihistamines are stronger and have more anticholinergic adverse effects.

46. TREATMENT OF MASTOCYTOSIS • Many patients require a combination of H1 and H2 antihistamines • mast cell stabilizer: • Ketotifen • Disodium cromolyn • Psoralens and ultraviolet-A (PUVA) or corticosteroids to reduce pruritus and whealing.

47. TREATMENT OF MASTOCYTOSIS • Interferon alpha-2b (aggressive forms of mastocytosis). • Chemotherapy (aggressive systemic mastocytosis). • Local radiation for bone pain. • Splenectomy

48. TREATMENT OF MASTOCYTOSIS • Low-dose aspirin is helpful in some patients, because it causes continuous degranulation and prevents extreme peaks of histamine release from mast cells. Doses of 40 mg per day have been used, and this dose is increased gradually based on patient response.