The role of corticosteroid therapy in dermatology.pptx

The role of corticosteroid therapy in dermatology

1. In The Name of God The role of corticosteroids in skin disease 1

2. Corticosteroid therapy in dermatology Nyaz K arwan O mer 4 th year General Medicine 2

3. Corticosteroids in dermatology 3 Topical CS therapy Intralesional injection Systemic CS therapy Oral IM (intramuscular) Intravenous (Pulse therapy)

4. Selected Indications of Topical Corticosteroids Topical corticosteroids play a major role in the treatment of many dermatologic conditions (effective for conditions involving hyper- proliferation , immunological , and inflammatory properties) . 4 Dermatitis/Papulosquamous Bullous Dermatoses Connective Tissue Diseases Neutrophilic Dermatoses Other Dermatologic Uses Alopecia areata / Acne keloidalis nuchae Chondrodermatitis nodularis helicis Cutaneous T-cell lymphoma, patch-stage Granuloma annulare /Jessner lymphocytic infiltrate Lichen planopilaris / Lichen sclerosis et atrophicus Morphea / Pruritic urticarial papules and plaques of pregnancy Sarcoidosis / Vitiligo / Well syndrome 1) Topical corticosteroid therapy

5. The potency of topical corticosteroids Topical corticosteroids are organized into classes based on their strength ( potency ), ranging from super high potency (class I) to low potency (class VII). The efficacy of any topical medication is related to: The active ingredient (inherent strength) Anatomic location The vehicle (the mode in which it is transported) The concentration of the medication 5

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7. Vehicles: Ointments : semiocclusive , greasy Useful for smooth ,non -hairy skin, dry or hyperkeratotic lesions. Creams : less greasy, not occlusive , may sting, could cause irritation Useful for intertriginous areas. Lotion : less greasy, less occlusive, may sting Helpful for acute exudative inflammation and on hairy areas 7

8. TCS Selection : Super high potency (class I) are used for severe dermatoses over non-facial and non-intertriginous areas Scalp, palms, soles, and thick plaques on extensor surfaces Medium to high potency steroids (classes II-V) are appropriate for mild to moderate non-facial and non-intertriginous areas Okay to use on flexural surfaces for limited periods Low potency steroids (classes VI, VII) can be used for large areas and thinner skin Face, eyelid, genital and intertriginous areas 8 Absorption : TCS are better absorbed through areas of inflammation and desquamation compared to normal skin. Anatomic regions with a thin epidermis are significantly (e.g., eyelid) more permeable then thick-skinned areas (e.g., palms). Ointments allow better percutaneous drug absorption and are therefore more potent than creams or lotions.

9. treatment Duration : In general: Super high potency: treat for <4 weeks High and Medium potency: <6-8 weeks Low potency: side effects are rare. Treat facial, intertriginous, and genital dermatoses for 1-2 week intervals to avoid skin atrophy, telangiectasia, and steroid-induced acne Longer-term management: use least-potent corticosteroid that is effective Intermittent therapy (Twice weekly application of TCS have been shown to reduce the risk of relapse in patients with atopic dermatitis Taper with gradual reduction of both potency and dosing frequency to avoid rebound/flares 9

10. Use during pregnancy or lactation : limited studies found an increased risk for orofacial cleft with topical corticosteroid use in the first trimester and low birth weight with high potency topical corticosteroid use during pregnancy. In contrast, the large, population-based studies and a Cochrane review have not shown an increased risk of malformations, including oral cleft palate, or preterm delivery, or stillbirth. However, Because fetal growth restriction has been reported with extensive use of potent corticosteroids, mild to moderate CS are recommended over potent CS. If potent CS are required, the treatment period should be limited in duration ( <300 grams ). No adverse effects have been noted in lactating women . The drugs should not be applied to the nipples prior to nursing. 10

11. Direct delivery of corticosteroids into skin lesions with limited distribution Indications: hypertrophic scarring/keloids, Psoriasis, lichen simplex chronicus, hypertrophic LP, cystic acne, Alopecia areata etc. Inject into dermis (Injecting into subcutis more likely to cause atrophy with minimal anti inflammatory effect Inject enough to cause blanching Avoid injecting lesions in the glabella 11 2) Intralesional corticosteroids

12. 3) Systemic corticosteroids : Oral corticosteroid therapy Intramuscular corticosteroid therapy Intravenous (IV) pulse therapy Oral mini-pulse therapy 12

13. Indications in dermatology : Bullous Dermatoses Autoimmune Connective Tissue Diseases Vasculitis Neutrophilic Dermatoses Dermatitis/Papulosquamous Dermatoses Other Dermatoses DRESS syndrome Sarcoidosis Sunburn or photodermatitis Urticaria/ angioedema (acute) Panniculitis Androgen excess (acne/hirsutism) Prevention of isotretinoin-induced acne fulminans Systemic steroids are best avoided in patients with psoriasis and chronic urticaria . 13

14. How do systemic steroids differ? Overall, the MC effect and duration of action are much more important factors in the choice of CS therapy than is the anti inflammatory potency of the product. 14

15. Oral corticosteroids Therapy 15 Most CS therapy is given as a single oral daily dose in the morning with an intermediate-duration CS such as prednisone ( similar to the body’s own diurnal variation of cortisol production) . Prednisone and prednisolone are equivalent and are the most commonly prescribed oral corticosteroids for inflammatory skin diseases (optimal duration of action for daily or alternate-day therapy). Divided doses , typically given twice daily, are reserved for acute therapy for severe, potentially life-threatening illnesses such as pemphigus vulgaris : greater therapeutic benefits greater risk of HPA-axis suppression and AE

16. What is the usual dose and duration of treatment? Physiologic CS therapy is 5 to 7.5 mg daily of prednisone or its equivalent; Pharmacologic dosage ranges Low dose, eg < 10mg/day of prednisone Medium dose, eg 10–20 mg/day of prednisone High dose, eg > 20mg/day of prednisone, sometimes more than 100 Short-term : Treatment for less than one month long-term : Treatment continuing for more than 3 months 16

17. Corticosteroid Baseline Monitoring (Long-term Therapy) Examination Blood pressure, weight Height and weight plotted on a growth curve (in children) Ophthalmoscopic examination for cataracts  Laboratory Tuberculosis screening—interferon-γ-releasing assay > tuberculin skin test, chest x-ray Strongly consider screening for hepatitis B, hepatitis C, HIV Consider screening for Strongyloides in endemic areas FBS, hemoglobin A1c, triglycerides; potassium level Baseline bone densitometry 17

18. Definitions for Disease Outcome Parameters Control of disease activity: start healing of previous lesions no new lesions formation End of consolidation phase: no new lesions have developed for a minimum of 2 weeks approximately 80% of lesions have healed. This is when most clinicians start to taper steroids.“ Decrease predniso(lo)ne by 25% every two weeks, until 20 mg per day . Once at 20 mg per day, decrease predniso(lo)ne by 2.5 mg a week; and then at 10 mg/day, decrease dose by 1 mg per day after that. 18

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20. Discontinuation of Treatment Discontinuation of systemic corticosteroids may be proposed in patients in complete remission on minimal therapy (prednisolone or equivalent at ≤10 mg/day). Discontinuation of treatment is primarily based on the clinical symptoms but may be also supported by the findings of Dsg ELISA , IIF and/or negative DIF microscopy of a skin biopsy . The adjuvants may be stopped 6–12 months after achieving complete remission on minimal therapy with adjuvants only. Complete remission on therapy: The absence of new or established lesions while the patient is receiving minimal therapy for at least 2 month 20

21. If relapse occurs: 21 (the appearance of ≥3 new lesions/month that do not heal spontaneously within 1 week, or there is extension of established lesions) go back to the second to last dose If disease control is still not reached,go back to initial dose . If oral corticosteroids are given alone: add an immunosuppressant • If oral corticosteroids are already combined with an immunosuppressant, consider a change in immunosuppressant

22. Tapering Principles : It is important from two points of view: undesirable flare-ups of the disease Adrenal recovery short-term therapy ≤ 3w →→→ Although it may help to prevent a disease rebound, tapering of the glucocorticoid dose is not usually necessary from an adrenal recovery standpoint . However, tapering to allow adrenal recovery is an important consideration when treatment is for longer than 3–4 weeks , especially at a dose ≥20 mg/day . Even in the absence of overt adrenal insufficiency, patients can develop a glucocorticoid withdrawal syndrome characterized by arthralgias, myalgias, mood changes, fatigue, headache, nausea, and anorexia. When this occurs, a return to the previous dose of glucocorticoid, followed by more gradual tapering, is recommended. 22

23. In general, the rate of prednisone tapering depends on both features of the dermatosis (e.g. type, activity, severity) and adrenal recovery issues. The prednisone dose can usually be tapered 20 mg →→ at doses greater than 60 mg/day, 10 mg →→ between 30 and 60 mg/day, 5 mg →→ between 30 mg and the physiologic dose range . Once the physiologic dose range of 5–7.5 mg/day of prednisone is reached, a more gradual reduction (e.g. in 1–2.5 mg increments) may be necessary to allow adrenal recovery. 23 Conversion to Alternate-Day Corticosteroid Therapy After compelete control of disease Start at dose 20-30 mg or less ( daily AM dose) Intermediate -acting steroids such as prednisolone

24. Systemic corticosteroid use during pregnancy : Prednisolone is the systemic corticosteroid of choice for dermatologic indications as it is largely inactivated in the placenta (placental enzyme, 11- hydroxysteroid dehydrogenase type 2) This enzyme has a limited ability to metabolize fluorinated glucocorticoids (e.g. betamethasone, dexamethasone), so greater amounts of these agents reach the fetus. During the first trimester , particularly between weeks 8 and 11, there is a possible (debated) slightly increased risk of cleft lip/cleft palate, especially if high doses prescribed and for >10 days (safe dosages for long-term are <10–15 mg daily with monitoring of fetal growth). Prednisone therapy is compatible with breastfeeding ; if possible, nursing should be delayed for ~4 hours after prednisone administration. 24

25. corticosteroid pulse therapy IV infusion treatment with more than 250 mg prednisone or its equivalent per day , for one or more days. “ Most commonly used corticosteroids in pulse therapies are methylprednisolone and dexamethasone : Methylprednisolone ) 20-30 mg/kg (500-1000 mg/m 2 ) per pulse up to a maximum dose of 1 g, for 3 to 5 consecutive days Dexamethasone ) 4-5 mg/kg (100-200 mg) per pulse. Rapid infusions are known to be associated with a higher risk of hemodynamic abnormalities ( infused IV, slowly over 2-3 h ). Advantage of Corticosteroid as a Pulse Therapy: An immediate anti-inflammatory effect and Faster clinical recovery No prolonged suppressive effect on the hypothalamic-pituitary axis. 25

26. Uses of Corticosteroid Pulse Therapy The dermatological disorders in which corticosteroid pulse therapy has been advocated are: Autoimmune blistering disorder (PV) Alopecia totalis Severe form vasculitis Generalized morphea Systemic lupus erythematosus Bullous dermatitis herpetiformis Infrequently used in : Severe Steven-Johnson syndrome (SJS) Pyoderma gangrenosum. Vitiligo with rapidly progressive disease Exfoliative dermatitis Systemic sclerosis 26

27. Contraindication in Pulse Therapy Systemic infections, fungal sepsis uncontrolled hypertension hypersensitivity to the steroid preparation ( Absolutely contraindicated ) in pregnant and lactating women Monitoring Careful Notable complication of IV pulse therapy: Sudden cardiac death ( due to Acute electrolyte shifts ) Atrial fibrillation anaphylaxis Pulse methylprednisolone is traditionally administered in an inpatient setting, with cardiac and electrolyte monitoring highly recommended. (potassium infusions may minimize the risk of serious cardiac AE) . Alternate-day CS or a nonsteroidal immunosuppressive (‘CS-sparing’) drug such azathioprine and cyclosporine is used to maintain the improvement from the pulse IV CS. 27

28. Mini Pulse Corticosteroid Therapy Oral betamethasone has been given at a dose of 10 mg weekly (5mg Betamethasone on two consecutive days for several weeks). oral prednisolone (30 mg daily for 3 consecutive days in a week for several months) It is used in following skin disease with variable success: Vitiligo (progressive) Alopecia areata Lichen planus Topical Corticosteroid Pulse Therapy Topical corticosteroid pulse therapy comprises of intermittent use of superpotent corticosteroids (maintenance of remissions and diminishing the side-effects) . Clobetasol propionate (0.05%), weekly topical treatment with three consecutive applications at 12 h intervals is used mainly in psoriasis. 37

29. Intramuscular Corticosteroid Administration HPA-axis suppression up to 3 to 4 weeks after each injection of triamcinolone acetonide. The interval between doses is a more important factor in HPA-axis suppression than the actual dose administered. Lowdose IM CS at 2 to 4-week intervals produced greater suppression than did higher doses at 6-week intervals. The evidence of HPA-axis suppression up to 10 months after treatment. Betamethasone and dexamethasone , which have a duration of action of less than 1 week, may be preferred in self-limited dermatoses. Longer-acting intramuscular agents that produce effects for about 3 weeks, such as triamcinolone acetonide and methylprednisolone acetate , should not be given more than about four to six times per year. 29

30. References : Stephen Wolverton, Jashin Wu - Comprehensive Dermatologic Drug Therapy- Elsevier (2020). Eroğlu, et al. Effective topical delivery systems for corticosteroids: dermatological and histological evaluations. Drug Delivery 2016, 23:5, 1502- 1513, DOI: 10.3109/10717544.2014.960981. Senyigit, et al. Corticosteroids for Skin Delivery: Challenges and New Formulation Opportunities. DOI: 10.5772/53909. Issa MC, et al. Transepidermal drug delivery: a new treatment option for areata alopecia? J Cosmet Laser Ther : official publication of the European Society for Laser Dermatology. 2015;17(1):37-40. Majid I, et al. Fractional carbon dioxide laser in combination with topical corticosteroid application in resistant alopecia areata: A case series. J Cutan Aesthet Surg. 2018;11(4):217. Gupta G, et al. Steroid pulse therapies in dermatology. Muller J Med Sci Res 2014;5:155-8. 30

31. Murrell D F , 31 et a l . Diagn o sis and Man a gement of P e m phigus: recommendations by an International Panel of Experts, Journal of the A m er i c a n Acade m y o f Der m a t o l o g y (201 8 ) , do i: 10.1016/j.jaad.2018.02.021. Haedersdal M, et al. Translational medicine in the field of ablative fractional laser (AFXL)-assisted drug delivery: A critical review from basics to current clinical status. J Am Acad Dermatol. 2016;74(5):981- 1004. Suran K, et al. Pulse therapy – A newer approach. Indian J Multidiscip Dent 2017;7:41-4. British association of dermatologists (BAD) patient information leaflets. produced August 2004, updated March 2010, March 2013, September 2016, May 2020. Review date May 2023. Christoph e r M Hul l , Op t imal use of t o pi c al and i n t r a l esional Utah, school corticosteroids. Department of Dermatology , university of of medicine.

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