Topical corticosteroids

hints about usage of topical corticosteroids for dermatologists

1. Topical Corticosteroids Quoted from original lecture of the same title of prof. dr zienab abdelaziem , staff member of dermatology department of Mansoura university – Egypt.

2. Introduction Topical corticosteroids are the most potent & effective anti-inflammatory agents. Introductoin of TS started with hydrocortisone in 1952. After that further derivatives were produced with enhanced activity. The basic steroid moiety consisted of 21 carbon atoms. New synthetic TS were introduced by manipulation of both ring structure & side chains of steroid skeleton.

3. Enhancement Addition of double bond between C1 &C2 Fluorination of C9 Esterefication at C17 Addition of methyl group at C16 Addition of various side chains e.g. valerate, acetonoides , butyrates & propionate particularly to C21

4. why These manipulations enhance activity of TS which results in: Better penetration through the skin Slower degradation by enzymes Greater affinity to cytosol receptors

5. Classification (potency) TS are assessed for potency on basis of 1- Vasoconstrictor assay 2- Atrophogenicity assay 3- Clinical trials A combination of these is used to produce a grouping of steroids of roughly equivalent potency Such groupings are clinically very helpful but can be regarded as only a rough guide

6. There are four categories of potency Mildly potent Moderately potent Potent Very potent

7. Mild TS Hydrocortisone base or acetate (Hydrocortisone, Alfacort ) Methyl prednisolone ( Medrol) Aclometasone dipropionate ( Perderm )

8. Moderate TS (2-25 times as potent as hydrocortisone) Flumethasone pivalate ( Locacortin ) Hydrocortisone 17 butyrate ( Locoid ) Clobetasone butyrate ( Eumovate ) Triamcinolone acetonoide ( Kenacort )

9. Potent TS (100-150 times as potent as hydrocortisone ) Betamethasone dipropionate ( Diprosone ) Betamethasone valerate ( Betaderm,Betaval,Betnovate ) Desoximetasone ( Esperson ) Diflucortolone valerate 0.1%( Nerisone ) Fluocinolone acetonoide ( Synalar ) Fluticasone propionate ( Cutivate ) Halometasone ( Sicortin ) Methylprednisolone aceponate (MPA) Mometasone furoate ( Elocom ) Prednicarbate ( Dermatop )

10. Very potent TS (Up to 600 times as potent as hydrocortisone) Clobetasol propionate ( Dermovate , clobex shampoo ) Diflucortolone valerate o.3% ( Nerisone forte ) Halcinonide ( Volog ) Ulobetasol ) Miracortin )

11. Percutaneous absorption of TS The effectiveness of TS is related to potency of the drug & its percutaneous absorption The rate of penetration into the st. corneum is greater the more hydrophilic the steroid On the other hand, penetration into the viable epidermis is greater with lipophilic steroid Receptor binding by the cytoplasm is also greater with increasing lipid solubility &clinical potency is related to high receptor binding

12. Percutaneous absorption of TS Receptor binding affinity is by: 1- Lipid soluble TS 2- Induction of double bond between C1 & C2 3- Flourination of C9 4- Esterification in C17

13. Percutaneous absorption of TS Other factors that enhance percutaneous absorption of TS: 1- Exposure to UVR 2- Inflamed skin e.g. atopic dermatitis & ED 3- Hydration of skin increase percutaneous absorption by 3-5 folds 4- Regional variation:TS is absorbed from scrotal skin (42 times) &check (13 times) more than forearm

14. Percutaneous absorption of TS 5- Vehicle: absorption of TS ointment is faster than TS cream 6- Occlusive dressing enhance percutaneous absorption by 10 folds 7- Age of patient: PA is increased in infant, small children & elderly

15. Mode of action 1- Anti-inflammatory 2- Antiproliferative 3- immunosuppressive

16. Anti-inflammatory Effect Prevent formation of prostaglandins & leukotriens V.C. Effect: due to inhibitory effect on prostaglandins, histamine & vasoactive kinins Mast cell depletion decrease No. of epidermal langerhans cells decrease lymphoid cells & antibody production

17. Antiinflammatory effect of TS Nucleus Cell TS TS+Cytosol receptor TS+Nuclear acceptor DNA mRNA Ribosomes Transcription Translation Protein synthesis (Lipocortin) Phospholipids Phospholipase A Arachidonic acid Prostaglandins Leukotreins DNA

18. Antiproliferative Effect TS inhibit DNA synthesis & thus mitotic activity This occurs following potent TS Hydrocortisone is ineffective in this regard

19. Immunosuppressive effect Decrease Lymphoid cells division Block access of lymphokines to target cells

20. Side effects of TS These vary from local effects up to systemic manifestations due to absorption of a potent TS or when it is applied on a large surface area. a direct relationship was found between unwanted effects & potency of TS Avoidance of these side effects can be achieved by relying on weaker TS or by acquiring a clear appreciation of how, when& where to use the more potent preparation

21. Side effects of TS 1. Epidermal effects: a- Atrophy of skin which becomes thin, fragile & transparent b- Melanocyte inhibition results in vitiligo like condition. This occurs more likely with TS under occlusion or with intracutaneous steroid injection

22. Atrophy of skin

23. Side effects of TS 2. Dermal effects: a- Reduction of collagen synthesis & ground substance with appearance of striae. 2- From poor support of dermal vasculature it will be easily ruptured on trauma leading to intradermal hemorrhage.

24. Striae and ID haemmorhage

25. Side effects of TS 3. Vascular effects: At first TS produce V.C. of superficial small vessels, followed by a phase of rebound V.D. which in later stages is fixed So , telangiectasia, rosacea- like eruption & exacerbation of rosacea may follow the use of & withdrawal of TS

26. Telangiectasia

27. Side effects of TS 4. Iatrogenic clinical syndromes: Tinea incognito Scabies incognito Infantile gluteal granuloma Results from TS on napkin area Charact . by oval dark brown or purplish nodules in napkin area An alteration of host response to candida under the influence of TS has been suggested After discontinuation of TS the nodules slowly disappear

28. Tinea incognito

29. Infantile gluteal granuloma

30. Side effects of TS Perioral dermatitis Results from prolonged use of fluorinated TS around the lips & eyes Appears in the form of papulopustular eruption Discontinuation of TS & administration of systemic tetracycline is effective

31. Periorificial dermatitis

32. Side effects of TS Glaucoma & cataract : if potent TS is applied around eyes Steroid acne: Comedones & pustules may be induced on face by TS Application of fluorinated TS to perianal skin results in comedones

33. Steroid acne

34. Side effects of TS Pustular psoriasis: Rebound phenomenon following withdrawal of TS may lead to pustular stage of psoriasis as a complication of treatment of chronic plaque psoriasis

35. Pustular psoraisis

36. Side effects of TS 5. Systemic side effects They are unlikely except after: Prolonged wide spread application of TS in child Use of TS under occlusion on a large area of skin Use of very potent TS e.g. clobetasol propionate at dosage > 50 gm/week or >100gm/week of potent TS

37. Side effects of TS 6. Contact sensitivity Extremely rare in relation to their use The reaction occurs to single or to closely related steroid configuration In many cases the responsible allergen is the vehicle of TS or preservative such as paraben or ethylene diamine How can we reach such a diagnosis ? The patient is presented with either chronic eczema non responsive to TS or with eruptions suggestive of contact dermatitis. Patch test confirmation is needed Ears, anogenital areas & lower legs are more prone to develop this complication

38. Side effects of TS 7. localized hypertrichosis 8. skin infections 9. delayed wound healing

39. Localised hypertrichosis

40. Indications

41. Indications of TS Eczema Atopic dermatitis Contact eczema Discoid eczema Xerotic eczema Pompholyx Psoriasis Lichen planus Lichen striatus

42. Indications of TS DLE PLE Intertrigo Alopecia areata Pemphigoid

43. Polymorphous Light Eruption

44. Bullous Pemphigoid

45. Fingertip unit The amount of cream squeezed out of its tube onto the end of finger

46. Contraindications of TS Skin manifestations resulting from vaccination Cut. TB & Syphilis Bacterial, viral & fungal infections Perioral dermatitis Hypersensitivity to any constituent

47. Guidelines for use of TS Use of very potent TS should be restricted to: Short term application (Dermovate can be used in less than 50gm/week for only 2 weeks in adult without side effects) Applied on small surface area ( not more than 10% of total body surface) Chronic plaque psoriasis NOT to be used with occlusive dressing

48. Guidelines for use of TS Potent TS may be used for: Intermediate duration (3-4 weeks) short period (1-2 weeks) on the face & in intertriginous areas Application on surface area Not more than 20% of total body surface for severe eczema, lichen planus, lichen simplex chronicus, psoriasis & DLE. Potent TS should be used in children Only if mild or moderately potent preparations do not yield the desired results. If essential , they should be used only for the first 1 - 2 weeks initial treatment & lower potency preparations should then be prescribed for maintenance treatment

49. Guidelines for use of TS Moderately potent TS should always be tried in eczema Mildly potent TS are: Safe for chronic application ( > 4weeks) Safest for use on the face & in intertriginous areas Safest for use in young children & infants

50. Guidelines for use of TS For treating patient with chronic eczema the step down ( in potency ) therapy is used to achieve optimum benefit with minimal adverse effects e.g. start with potent TS for 2-3 weeks then maintain with moderate potent TS for 3-4 weeks, then gradual withdrawal

51. Guidelines for use of TS Frequency of application: Most active preparations are usually applied just once or twice daily With flourinated TS because of their depot effect, it may be possible to reduce this to alternate days or less TS should be applied sparingly

52. Guidelines for use of TS Dilute or less potent TS can be used when larger areas of the body need to be covered . Dilution of TS is done by cetomacrogol base. However, manufactuer own diluent should be used because disturbance of the physicochemical composition of the vehicle will alter bioavailability of TS

53. Tachyphylaxis Repeated application of potent TS may result in a diminished effect of that preparation This may occur within one week of initial use, but the ability to fully respond returns within a week of stopping TS application This provides a reasonable basis for change of type of TS from time to time in the course of treatment Intermittent application may avoid tachyphylaxis Guidelines for use of TS

54. Guidelines for use of TS Occlusion & TS The use of plastic occlusive dressing may enhance the potency of TS by increasing hydration of st. corneum It can be used in treatment of chronic eczema (hyperkeratotic & lichenified type) However , wide spread occlusion should not be used to avoid systemic absorption of TS & other side effects such as : Disagreable odour Folliculitis & infection Miliaria Interference with heat exchange Reversible atrophy of adjacent skin

55. TS under occlusion

56. Folliculitis

57. Combinations

58. Combination of TS- Antimicrobial agents Used in treatment of eczema with 2ry infection, diaper dermatitis & intertrigo They should not be used except in small quantities & for short period

59. The antimicrobial agents used in combination with TS are : Vioform Triclosan Clotrimazole Miconazole Nystatin Gramicidin Neomycin Gentamycin Na Fusidate

60. Other combinations TS- Salicylic acid combination Salicylic acid has a keratolytic effect & enhance penetration of TS especially in hyperkeratotic conditions TS- Tar combination: Tar may disturb the pharmaceutical stability of the delicate Ts structure & such combination are best avoided If used the application of each should be separated in time

61. Other combinations TS – calcipotriol (vitamin d analogue) : e.g Daivobet ® ointment contains the active ingredients  calcipotriol (50 microgram/g)  betamethasone dipropionate (500 microgram/g).

62. Choice of vehicle It is preferable to use Ointment V. in chronic dry lichenified & hyperkeratotic lesion Cream V. in acute weeping dermatoses Cream, gel & alcoholic lotion in hairy regions