urticaria skin disease dermatology ppt.pptx

Details understanding of urticaria disease

1. URTICARIA Moderator- Dr. Rajkumar Kothiwala Presenter- Dr. Abhinav Awasthi

2. URTICARIA Urticaria is defined as a skin lesion consisting of a wheal-and-flare reaction in which localized intracutaneous edema (wheal) is surrounded by an area of redness ( erythema ) that is typically pruritic . Short lived swellings of the skin due to transient leakage of plasma from small blood vessels into the surrounding connective tissue. Superficial swellings of the dermis are called WHEALS.

3. Wheals are lesions ranging from a few mms to several cms in diameter: round or irregular By confluence, larger plaques may occur. Individual wheals normally last less than 24 hours. Itching is a predominant feature of wheals. It is pricking or burning in quality.

4. Deeper swellings of the dermis, subcutaneous and sub-mucosal tissues are called ANGIOEDEMA. They are painful rather than pruritic and take longer to resolve. Wheals and angioedema often coexist in urticaria but may occur alone.

5. CLASSIFICATION OF URTICARIA ACUTE : Wheals < 6 weeks. CHRONIC : ≥ 6 weeks.

6. Classification

7. PATHOGENESIS HISTAMINE causes local increase in permeability of capillaries and venules. Degranulation of mast cells occurs due to non-immunological and immunological factors. Though it is not clear whether their number is increased or not, their mediator contents are released more easily.

8. Non- immunological stimuli Neuropeptides (substance P) Drugs (opiates, morphine, codeine) Vancomycin, polymyxin Radiocontrast media Foods

9. Immunological stimuli Linkage of 2 alpha subunits of high affinity IgE receptor Auto antibodies against IgE or alpha subunit of IgE receptor C3a and C5a

10. Immunological and non –immunological stimuli lead to activation of intracellular kinases and increase in intracellular Ca 2+ Degranulation of mast cells Release of preformed mediators hiatamine, tryptase, chymase.

11. All these lead to rapid onset of local increase in permeability of submucosal or subcutaneous capillaries and post capillary veneules. Local plasma extravasation Swellings

12. CELLULAR INVOLVEMENT IN CHRONIC URTICARIA Lymphocytes, neutrophils and eosinophils found in dermis release a number of cytokines with proinflammatory properties. These enhance whealing response.

13. Basophils number is reduced; they release less histamine in response to anti IgE stimulation. They contribute to prolongation of urticarial wheals by active recruitment from circulation.

14. CLASSIFICATION OF ANGIOEDEMA Acute allergic NSAID induced ACE inhibitors induced Hereditary angioedema Idiopathic angioedema Angioedema associated with autoimmune chronic urticaria with eosinophilia with infections and infestations With physical urticaria

15. ACUTE URTICARIA Idiopathic in >50% of patients. Can occur as a type I hypersensitivity reaction to food, wasp or bee stings. As an immunological response to blood products, infection or febrile illness. As an adverse effect of drug therapy by various mechanisms: Penicillin (type I), opiates, NSAIDS, ACE inhibitors.

16. CHRONIC URTICARIA Idiopathic Physical CIU is defined as daily or almost daily occurrence of wheals for > 6 weeks, where a predominant physical urticaria and urticarial vasculitis have been excluded

17. About 1/3 rd of patients with CIU have circulating functional autoantibodies to either a) High affinity IgE receptor OR b) IgE In some patients, CIU is aggravate by components of food such as salicylates, benzoates, nitrites etc. though mechanism unclear.

18. Symptomatic Dermographism Erythema & wheals on stroking 5% normal population - exaggerated physiological response 4.2% of general population develop wheals on minor stroking (accompanied by itching)- symptomatic dermographism Develop within min; subsides in 1 hr Delayed - up to 3 to 6 hours; lasts for 24-48 hours

19. Tests for Dermographism Patient off antihistamines for at least 24 hrs Methods Dermographometer : pen-like calibrated instrument with spring loaded stylus to set pressure at pre-determined value (Strike skin at pressure < 36 g/mm2 and observe for 10 min) Dermograder : striker & template that gives 4 different grades of pressure (Least pressure that elicits wheal is called the dermagrade of patient) A blunt instrument with moderate friction (Not more than 49 g/mm2)

20. PRESSURE URTICARIA Appears as erythematous, deep local swellings, often painful,associated with systemic symptoms   Arise from 30 min to 9 h after constant pressure has been applied to the skin May be associated with CIU Underlying mechanism is unclear

21. COLD URTICARIA Two types: Primary acquired cold urticaria (essential) Secondary acquired cold urticaria

22. PRIMARY ACQUIRED COLD URTICARIA Though occurs at any age, but most frequent in young adults. May be preceded by non specific upper respiratory tract infections, infectious mononucleosis or insect bites Itching and wheals occur on cold exposure within minutes and last up to 1h.

23. Cold winds are particularly effective stimuli Mouth and pharynx may swell after drinking cold liquids. Systemic symptoms include flushing, palpitations, headache, wheezing and loss of consciousness

24. In some patients, serum can passively transfer the cold urticarial response to recipients (auto antibody IgE or IgM) Antigen: a protein produced normally by cold exposure or less likely, an abnormal protein Histamine is the important mediator

25. PROVOCATION Application of melting ice cubes in a plastic bag to the skin for 20 minutes. This elicits a local rapid whealing within 15 min. usually during rewarming If ice cube test is negative, arm can be immersed in cold water at 5-10 °C for 10 minutes.

26. Cryostimulation test Apply base of cryostimulator on volar aspect of forearm for 2 min Allow skin to re-warm for 5 min & look for whealing

27. SECONDARY ACQUIRED COLD URTICARIA Cold urticaria due to presence of cryoglobulins is rare (1-5%). It is usually associated with Raynaud’s phenomenon, purpura or skin necrosis. Cryoglobulinaemia may be idiopathic or occur in collagen vascular disease, chronic lymphatic leukemia, myeloma and infectious diseases.

28. OTHER RARE FORMS OF COLD URTICARIA Delayed cold contact urticaria Localized cold contact urticaria Familial cold urticaria Acquired cold contact erythema Systemic cold urticaria (Widespread whealing in response to cooling of core body temperature; ice cube test negative)

29. CHOLINERGIC URTICARIA Hives precipitated by increase in core body temperature Accounts for about 5% of all cases of chronic urticaria Onset 2 nd or 3 rd decade. Both sexes affected equally.

30. Triggers : Exercise Hot baths or showers Ingestion of spicy or hot foods Strong emotional feelings All above factors lead to increase in sweating which may have some bearing on pathogenesis

31. CHOLINERGIC URTICARIA The eruption appears as Distinctive, pruritic, small, 1- to 2-mm wheals Surrounded by large areas of erythema Systemic features may include Dizziness, headache, wheezing, shortness of breath, nausea, vomiting, and diarrhea.

32. Test for Cholinergic urticaria Methods Raising core body temperature by 0.7-1°C (a) Taking hot water (42°C) bath x 15 min or (b) Exercising in hot environment x 15 min Intradermal inj of Methacholine 0.01mg in 0.1ml of normal saline

33. AQUAGENIC URTICARIA Urticaria arising from direct contact of skin with water Very rare; less than 50 cases; familial occurrence Lesions are small, punctuate (1-3 mm) perifollicular and resemble cholinergic urticaria .

34. Wheals appear rapidly within minutes of exposure to water; not influenced by temperature or pH of water; systemic symptoms rare.

35. CONFIRMATION By localized application of water at body temperature (gauze soaked in water at 37 ° C) to affected areas for 20 minutes Or After bathing in water at body temperature: WHEALS appear within minutes

36. SOLAR URTICARIA Wheals develop at site of exposure within minutes of exposure to visible, long or short wave ultraviolet radiation; usually fade within 2h; Uncommon PU Peak onset between 20 and 30 years; slight female preponderance.

37. Wheals confined to sunlight-exposed skin; occasionally patients experience erythema , wheal and flare under thin clothes that allows penetration of light. SU is considered to be an allergic Type I hypersensitivity response mediated by histamine Some patients have a circulating factor (photo allergen) which passively transfers the disease to normal individuals.

38. SOLAR URTICARIA

39. SU resolves spontaneously in approximately 50% of cases within 5 years Disease severity runs a fluctuating course with periods of improvement and remission.

40. VIBRATORY ANGIOEDEMA Pruritus and swelling after application of a vibratory stimulus to the skin within a few minutes. Very rare; familial cases have been reported. Symptoms peak at 4 to 6 hours and resolve by 24 hours.

41. Several triggers: riding of a bike, horse,clapping, walking, massaging; occupational mechanist, carpenter, metal grinder. Direct mast cell stimulation from vibration may lead to degranulation and local release of histamine. Diagnostic testing: By application of a vibratory stimulus in contact with skin

42. IMMUNE COMPLEX MEDIATED URTICARIA Serum sickness Urticarial vasculitis

43. SERUM SICKNESS Type III hypersensitivity reaction Originally defined as adverse reactions resulting from the administration of heterologous serum to humans

44. URTICARIAL VASCULITIS Cutaneous lesions resembles that of the urticaria but histological features are that of the vasculitis Type III hypersensitivity reaction Generally idiopathic but in few – Hepatitis B & C, EB virus & collagen vascular disease

45. Lesion persist more then 24 hr. Lesion are tender or painful and resolve with residual bruising or staining Angioedema is present in 40%of cases Rarely bullae may occur Systemic involvement is common

46. Differential Diagnosis Insect Bites (papular urticaria) Atopic dermatitis Erythema multiforme Urticaria pigmentosa Vasculitis Morbilliform drug eruptions Anaphylaxis Melkersson -Rosenthal syndrome Erysipelas Cellulitis Contact dermatitis Dermatitis herpetiformis Photodermatitis Familial cold autoinflammatory syndrome

47. Treatment/s Type of antihistamine : non-sedating / sedating Dose : Standard / Higher Response: Complete / Partial / Nil Adjuvant : Corticosteroids / immunomodulators Side effects

48. Drugs First line drugs Antihistamines H-1 receptor blockers: Conventional - Chlorpheniramine, Hydroxyzine, Promethazine, Diphenhydramine, Trimeprazine, Cyproheptadine etc. Newer - Cetrizine, Levocetrizine, Loratidine, Desloratidine, Fexofenadine, Mizolastine etc. H-2 receptor blockers: Cimetidine, Ranitidine etc.

49. Treatment is generally started with nonsedating antihistamine in the daytime and sedating antihistamine in the night. In the licenced dosage all antihistamines are equal in efficacy and there is little to chose between the different molecules. It is common to double or triple the dosage of nonsedating antihistamines if patients do not respond to standard dosage. H2 antihistamines can be added if patients complain of indigestion or acidity. Combination often helps the patient. 

50. Second line drugs Systemic corticosteroids: Betamethasone, Prednisolone: They should be used for only short periods due to the side effects. Prednisolone in the dose of 20-30 mg for three days is effective to control severe attacks of urticaria and angioedema Low dosage alternate day dosing may be used in patients with CU who do not respond to other therapies. Systemic corticosteroids act at multiple levels, they suppress the formation of antibodies, they have a strong anti-inflammatory effect, and in addition, are known to decrease the production of histamine-releasing factors.

51. Leukotriene inhibitors: Monteleukast (10 mg/d) Zafirleukast, Zileuton It works well for aspirin-sensitive urticaria. Daily dosage is 10 mg taken at bedtime. There are no important drug interactions. Tricyclic antidepressant: Doxepin : Dosage is 10-25 mg and may be increased to 50 mg. It works well when taken at night. Its main side effects are drowsiness, dry mouth, metallic taste, constipation, urinary retention, blurred vision, palpitation, and tachycardia.

52. Third line drugs Immunosuppressives / Immunomodulators Cyclosporine (3-5 mg/d) 3-5 mg/kg as a starting dose and reduced over three to four months. One study showed that prolonged treatment with cyclosporine is beneficial for maintaining remission in severe cases of CU. Sulfasalazine (2-4 g/d) - Efficacy and safety established

53. Cyclophosphamide, Azathioprine Methotrexate: A study found methotrexate effective in patients with autoimmune urticaria in a dose of 2.5 mg orally twice a day on Saturday and Sunday of every week. Plasmapheresis, Intravenous immunoglobulin , Dapsone, Hydroxychloroquine, Stanozolol, Tacrolimus (low-dose)

54. A utologous serum therapy (AST) for two groups of patients with CIU (ASST-positive and ASST-negative) and found it to be an effective therapeutic modality to reduce disease severity as well as antihistamine requirement. This also prevented relapse of symptoms for durations as long as two years.

55. Omalizumab, a recombinant humanized monoclonal antibody against immunoglobulin IgE, represents a unique therapeutic approach for the treatment of allergic diseases. This agent acts as a neutralizing antibody by binding IgE at the same site as the high-affinity receptor. There are reports of efficacy of omalizumab in CU

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