PSORIASIS- A BRIEF OUTLOOKBY: VISHNU.R.NAIRTHIRD YEAR PHARM.DNATIONAL COLLEGE OF PHARMACYKERALA UNIVERSITY OF HEALTH SCIENCES (KUHS),KERALA STATE

A. GENERAL INTRODUCTION:• Chronic, non-contagious, multi-system, inflammatory disorder• Characterized by defects in normal cycle of EPIDERMAL

DEVELOPMENT, that leads to epidermal hyper-proliferation, altered skin maturation, inflammation and vascular alterations• Aforesaid characteristics often manifest as areas of dry, thickened,

scaling, silvery white and reddened skin• Psoriatic lesions may hurt, itch and bleed• Extent of disease can range from a few small plaques to generalized

lesions• Manifests on the skin of elbows, knees, scalp, genitals, lumbo-sacral

areas, etc.• In 30% of patients, psoriasis also affects joints………………….

B. EPIDEMIOLOGY:• According to the National Institute of Health (NIH), approximately 2.2%

of US population has psoriasis• Can begin in any age• 2-3% of people are affected worldwide• 10-15% of new cases begin in children younger than 10 years• Slightly more common in women than in men• Psoriasis incidence depends on climate and genetic heritage of

population• Less common in tropics and in dark-skinned people• Psoriasis prevalence in African Americans is 1.3% compared to 2.5% in

Whites……………………………………..

C. CLASSIFICATION OF PSORIASIS:• PSORIASIS can be classified into 11 types:1. Chronic stationary psoriasis2. Plaque psoriasis3. Guttate psoriasis4. Inverse psoriasis5. Pustular psoriasis6. Erythrodermic psoriasis7. Scalp psoriasis8. Nail psoriasis9. Psoriatic arthritis10. Oral psoriasis11. Eruptive psoriasis………………………

CONTINUED……………………………1. CHRONIC STATIONARY PSORIASIS:

- Also known as “PSORIASIS VULGARIS”- Most common type- Occurs in: a. Scalpb. Extensor surfacesc. Genitalsd. Umbilicuse. Lumbosacral regionsf. Retro-auricular regions2. PLAQUE PSORIASIS:- Dry scaling patches- Occurs in:a. Kneesb. Elbowsc. Scalpd. Trunk

CONTINUED………………………………

3. GUTATTE PSORIASIS:- Occurs as drop-like dots- Mainly the aftermath of streptococcal or viral infections (especially Group A beta hemolytic streptococci)- Occurs in trunk4. INVERSE PSORIASIS:- Occurs as smooth, inflamed lesions- Occurs in:a. Flexural surfacesb. Armpitsc. Groind. Skin folds5. PUSTULAR PSORIASIS:- Pus like blisters occur- Non-infectious- Fluid contains WBCs- Present on palms and soles

CONTINUED……………………………..6. ERYTHRODERMIC PSORIASIS:

- Exfoliation of fine scales occurs- Widespread- Accompanied with severe infection and pain- Encompasses nearly entire body surface area7. SCALP PSORIASIS:- Plaque type lesion occurs- Affects approximately 50% of patients8. NAIL PSORIASIS:- Starts as numerous pits- May progress to yellowing, crumbling, and thickened nail- May get sloughed off9. PSORIATIC ARTHRITIS:- Inflammation, swelling and joint destruction may occur- Affects approx. 10-30% of those with skin symptoms

CONTINUED……………………………..10. ORAL PSORIASIS:

- May present as severe CHEILOSIS (inflammation of 1/ both mouth corners)- Extends onto surrounding skin11. ERUPTIVE PSORIASIS:- Involves upper trunk and extremities- Mostly seen in younger patients……………………………….

D. ETIOLOGY OF PSORIASIS:1. ENVIRONMENTAL FACTORS:Include:- Cold- Trauma- Stress increases concentration of neurotransmitters in psoriatic plaques- Infections:a. HIVb. Streptococcalc. Staphylococcal- Alcohol- Drugs:a. Iodidesb. Steroid withdrawalc. Aspirind. Lithiume. Beta-blockersf. Botulinum-Ag. Anti-malarials

CONTINUED……………………………

- Chronic gingivitis increases risk of psoriasis2. GENETIC FACTORS:- Genetic pre-disposition to obesity- HLA alleles HLA-Cw6- Deletion of LCE (Late cornified envelope) genes LCE3C, LCE3B increases

susceptibility for psoriasis3. IMMUNOLOGIC FACTORS:- Increased TNF-alpha activity- Increased T-cell activity in underlying skin- For HIV patients decrease in CD4 T cells causes over-activity of CD8 T cells

worsening of psoriasis4. KOEBNER PHENOMENON:- Refers to psoriatic lesions, that occur at sites of injury to the skin (cut, burn, scratch/ surgical scar)…………………………………..

E. PATHOGENESIS OF PSORIASIS:• Main function of the skin is protection that is offered by an intact epidermal layer• Epidermis consists of 5 layers (from DEEPEST to most SUPERFICIAL):- STRATUM BASALE- STRATUM SPINOSUM- STRATUM GRANULOSUM- STRATUM LUCIDUM- STRATUM CORNEUM• 4 types of cells compose the above layers:- Keratinocytes (90%)- Melanocytes (8%)- Langerhans cells- Tactile menisci (Merkel cells)

CONTINUED………………………….......• During epidermal cell cycle new cells formed in stratum basale migrate towards

stratum corneum• As cells move towards surface they accumulate keratin organelles disappear• By the time, the cells reach stratum corneum cells are dead and completely filled

with keratin this smooth , keratinous layer offers skin its protection surface cells slough off (exfoliation) and are replaced by underlying cells• Keratinocytes in basal layer divide approx. once every 2 weeks (in normal

conditions)• In psoriatic skin epidermal cell cycle is accelerated cell division in basal layer

occurs every 1.5 days migration of keratinocytes to stratum corneum occurs within just 4 days or so rapid movement of cells towards surface lack of proper maturations and differentiation of cells stratum corneum is not fully keratinized epidermal cells build up abnormally and become scaly epidermal in psoriatic lesions is 3-5 times thicker than normal blood vessels in dermal papillary layer dilate inflammatory cells (neutrophils) infiltrate epidermis………………………………..

F. PATHOLOGY ASSOCIATED WITH PSORIASIS:• Keratinocyte activity becomes abnormal• Lymphocyte infiltration occurs• The following markers of epidermal proliferation are increased in psoriasis:- Keratins (K6, K10, K16, K17)- Epidermal growth factor receptor- Ornithine decarboxylase• The following biochemical markers are associated with differentiation:- Keratinocyte transglutamase- Migration inhibitory factor related protein- Skin derived anti- leukoproteinase- Involucrin• Decreased levels of FILAGGRIN (essential for development of stratum corneum is observed)• Decrease in differentiation related keratins (K1, K2)• Keratinocytes also contain a variety of immuno-modulatory cytokines like Interleukins 1,6,8 and

TNF (Tumor necrosis factor), that are expressed in different ways in psoriasis…………..

G. SIGNS AND SYMPTOMS:• Worsening of a long term erythematous scaly area• Sudden onset of many small areas of scaly redness• Pain, especially in cases of:- Erythrodermic psoriasis- Traumatized plaques- Joints affected by psoriatic arthritis• Pruritus , especially in the case of:- Eruptive psoriasis- Guttate psoriasis• Afebrile state, except in cases of:- Pustular psoriasis- Erythrodermic psoriasis• Dystrophic nails• Long term rash, with recent presentation of joint pain• Stiffness, pain, throbbing, swelling/tenderness of joints

CONTINUED……………………………….• OCULAR MANIFESTATIONS:- Corneal dryness- Blepharitis (eyelid inflammation)- Chronic non-specific conjunctivitis- Keratoconjunctivitis sicca (inflammation of cornea and conjunctiva)

………………………………….

H. COMPLICATIONS:• Secondary infections• Possible increased lymphoma risk• Possible increased risk of cardiovascular and Ischemic heart disease• Psoriatic arthritis• Mitral valve prolapse……………………………….

I . DIAGNOSIS:1. LAB STUDIES:- Normal ESR (Erythrocyte sedimentation rate) , except in conditions of:a. Pustular psoriasisb. Erythrodermic psoriasis- Increased uric acid levels, especially in pustular psoriasis- Fluid from pustules is sterile, with neutrophilic infiltrate- Perform fungal studies:Important in cases of hand and foot psoriasis, that seem to be worsening with the use of topical steroids- CBC (Complete blood counts)

CONTINUED………………………………2. OTHER TESTS:

a. Dermatologic biopsy:- Biopsy of skin lesion may reveal:• Basal cell hyperplasia• Proliferation of sub-epidermal vasculature• Absence of normal cell maturation• Keratinizationb. Joint X-Ray:- Facilitates psoriatic arthritis diagnosisc. Bone scan:- Helps in early joint identificationd. Conjunctival impression cytology:- May reveal squamous metaplasia, neutrophil clumping, or snake-like chromatine. AUZPITZ sign:Scales on being removed small blood droplets appear within a few seconds……………………….

J. MANAGEMENT OF PSORIASIS:Here, we will discuss:• GOALS OF THERAPY• TREATMENT PLAN• PHARMACOTHERAPY• NON-PHARMACOTHERAPY (PATIENT COUNSELLING TIPS)

………………………………………..

A. GOALS OF THERAPY:- To alleviate signs and symptoms- To reduce irritations, pain and discomfort - To focus on strict drug regimen and medication adherence- To avoid progression into complications- To improve QOL (Quality of Life)…………………………..

B. TREATMENT PLAN :- Psoriasis is a chronic problem- Consultation for follow-up with a dermatologist/ rheumatologist is appropriate- Severity of psoriasis can be classified as follows :a. Mild: less than 2% of body surface area (BSA) affectedb. Moderate : 2-10 % of BSA affectedc. Severe: >10% of BSA affected (Remember : Palm of patient’s hand= 1% of BSA)- Treatments for more advanced psoriasis include:a. Narrow band UV ‘B’ lightb. Psoralen with UV ‘A’c. Light retinoids : Isotretinoin (ACCUTANE), Acitretin (SORIATANE)d. MTX (Methotrexate)e. Cyclosporinef. Infliximab , etc……………………- According to American Association of Dermatology (AAD) guidelines:Recommend treatment with MTX, cyclosporine, and Acitretin, considering their contraindications and drug interactions with other medications, as will be discussed………………………

C. PHARMACOTHERAPY:1. TOPICAL CORTICOSTEROIDS;- Decreases plaque formation- Possess anti-inflammatory activities- Cause profound and varied metabolic activities- Modify body’s response to diverse stimuli- Available in various strengths- Application regimen: 2-4 times daily for maintenance- ADRs:a. Local tissue atrophyb. Hypopigmentationc. Fine hair growthd. Contact dermatitise. Adrenal suppression

CONTINUED………………………………- Drugs:

a. TRIAMCINOLONE ACETONIDE (TRIDERM, PEDIADERM):• Treats inflammatory dermatosis responsive to steroids• Drug, has 2 anti-inflammatory actions:i. Suppresses PML (poly- morphonuclear leucocytes) ii. Reverses capillary permeability* Mild potency• First drug of choice for most patientsb. BETAMETHASONE (DIPROLENE , ALPHA TREX):• Same actions as in (a)• Drug of choice if psoriasis is resistant to milder

forms………………………………

CONTINUED………………………………

2. OPHTHALMIC CORTICOSTEROIDS:- Control conjunctival, corneal and anterior chamber inflammation- Delay vascularization- Drugs include:a. PREDNISOLONE ACETATE OPHTHALMIC ( OMNIPRED, PRED

FORTE):• Same actions as that of topical ones• In case of bacterial infections use along with anti-infective agents• Dosing may be reduced• Do not prematurely discontinue therapyb. DEXAMETHASONE OPHTHALMIC (MAXIDEX, OZURDEX):• Same action…………………..

CONTINUED……………………………….3. COAL TAR ( DHS-TAR, THERAPLEX T):

- Inexpensive- Use as 0.5-33%- Available as OTC , in the form of shampoos, lotions, creams, foams- Mainly useful in hair-bearing areas- 1% conc. Can also be used to control lesions- Mainly useful when used in combination with topical corticosteroids- ADRs:a. Staining potentialb. Skin irritationc. Photosensitivity- Application regimen: a. Apply at bedtimeb. Allow to remain as such until morning- Anti-pruritic- Anti-bacterial- Inhibits deregulated epidermal proliferation and dermal infiltration

CONTINUED……………………………….- Does not injure normal skin when applied widely

- Increases usefulness of phototherapy- Generally used as 2nd line drug therapy, due to messy application (except

shampoos)……………………………

CONTINUED……………………………..4. KERATOLYTIC AGENTS:

- Remove scales- Smoothen skin- Treat hyperkeratosis- Drug removes thick scale allows topical corticosteroids and other

medications to better reach target tissues better results achieved- Mainly effective on scalp- Many OTC preparations can be used for this, most of which contain

SALICYLIC ACID- Lactic acid, ammonium lactate and urea are the other ingredients that may be

applied too- Urea preparations stronger than 30% require a prescription- Anthralin is also considered to be in the anti-psoriatic therapeutic class

CONTINUED……………………………….- ADRs:

a. Skin irritationb. Salicylism (with salicylic acid)c. Staining potentiald. Inflammation- Strength : 0.1-1.0%- Application regimen: same as that of COAL TARANTHRALIN (DRITHO-CRÈME, ZITHRANOL):- Decreases cell proliferation rate- Drug possesses chemically reducing properties upsets oxidative

metabolic processes decreased epidermal mitosis………………………

CONTINUED…………………………….5. VITAMIN D ANALOGS:- Used in the following patients:a. Lesions resistant to topical therapyb. Lesions on facec. Exposed areas, where skin thinning can cause cosmetic problems- Used as ointments, solutions and foams- Mainly used for scalp treatments- Strength: 0.005%- Application regimen:a. Once or twice dailyb. Not more than 100g of vehicle base/week (for 8 weeks)- ADRs:a. Skin irritationb. Hypercalcemia risk

CONTINUED………………………………- Drugs:a. CALCITRIOL OINTMENT (VECTICAL):• Less irritatingb. CALCIPOTRIENE (DOVONEX, CALCITRENE):• Synthetic Vitamin D3 analog• Regulates skin cell production and development• Used in treatment of moderate plaque psoriasis• No long term skin thinning/ systemic effects• Also used in combination with BETAMETHASONE as topical ointment,

foam, / solution ,asa. Calcipotriene: 0.005%b. Betamethasone : 0.064%• Expensive therapy………………………………….

CONTINUED……………………………….6. TOPICAL RETINOIDS:

- Odorless and colorless aqueous gel formulations- No long term skin damage- No withdrawal symptoms- Avoid in pregnancy- TAZAROTENE ( TAZORAC FABIOR, AVAGE):• Retinoid prodrug enters body converted to active form modifies differentiation and proliferation

of epithelial tissue• Anti-inflammatory• Immuno-modulatory• Strength: 0.05, 0.1%• Application regimen: Once or twice daily, up to 12 weeks• ADRs:a. Pruritusb. Burningc. Erythema……………………………

CONTINUED……………………………….7. ANTI-METABOLITES:

- Inhibit cell growth and proliferation- METHOTREXATE (TREXALL, RHEUMATREX):a. Drug inhibits dihydrofolate reductase enzyme DHFA wont be converted to THFA Nucleotides and thymidylate synthesis wont occur DNA synthesis, repair and cellular replication obstructedb. Mainly effective against actively proliferating tissuesc. Used in people who are non-responsive to the above drugsd. Contraindicated in pregnancy, liver, and renal problems.e. ADRs:• Bone marrow toxicity• Hepatotoxicityf. Dose: 2.5-5 mg orally BID, thrice weekly……………….

CONTINUED……………………………….

8. IMMUNOMODULATORS:• Regulate key factors responsible for inflammatory response• Drugs include:a. TACROLIMUS TOPICAL 0.1% (PROTOPIC):- Used for psoriasis affecting face- Less effective than steroids- More ADRs associated with it, thus less used- Interferes with IL-2, and IL-8 production- Dose: 0.05-0.1 mg/kg/day - ADRs:i. Paresthesiaii. Tremoriii. Palpitationsb. CYCLOSPORINE (SANDIMMUNE):- 11-amino acid cyclic peptide- Natural fungi product

CONTINUED……………………………….

- drug inhibits Helper T-cell formation depresses cell mediated immune responses- Drug binds to cyclophilin (intracellular protein) prevents formation of IL-2 Prevents

recruitment of activated T-cells- Dose: 3mg/kg/day (maintenance therapy)- ADRs:i. Paresthesiaii. Musculoskeletal painiii. Nephrotoxicity c. ALEFACEPT ( AMEVIVE):- Recombinant dimeric fusion protein- Drug binds to CD2 on memory effector T-lymphocytes inhibits activation of these cells

decreases number of these cells- Mainly used for moderate-severe psoriasis- Given i.m- ADR: Lymphopenia, injection site reactions- Dose: 15 mg i.m every week, for 12 weeks…………………………..

CONTINUED…………………………….9. TNF INHIBITORS:- Neutralize TNF-alpha effects- Drugs include:1. INFLIXIMAB (REMICADE):- Chimeric antibody- Drug binds to both soluble and transmembrane TNF-alpha molecules neutralizes

TNF-Alpha effects- Used for chronic severe plaque psoriasis and for psoriatic arthritis- Dose: 5mg/kg i.v infusion (every 8 weeks)2. ETANERCEPT (ENBREL):- Recombinant human TNF-Alpha receptor protein, fused with Fc portion of IgG1- Same MOA as that of infliximab- ADR: injection site reactions- Dose: 25 mg twice weekly (s.c)

CONTINUED……………………………

3. ADALIMUMAB (HUMIRA):- Fully human anti-TNF alpha monoclonal antibody- Same MOA and ADR as that of infliximab and etanercept- Dose: 80 mg s.c……………………………………….

CONTINUED………………………………10. PHOSPHODIESTERASE-4-ENZYME

INHIBITORS:APREMILAST (OTEZLA):- Drug inhibits phosphodiesterase-4-enzyme increases cyclic AMP

levels affects cytokines and chemokine synthesis anti-inflammatory effects- Mainly used for moderate-severe plaque psoriasis- Dose: 30 mg PO BID- ADRs:a. Upper respiratory tract infectionsb. Headache…………………………….

CONTINUED……………………………11. INTERLEUKIN INHIBITORS:- IL-17 Plays key role in the pathogenesis of plaque psoriasis- SECUKINUMAB (COSENTYX):• Human IgG1 monoclonal antibody• Selectively binds to and neutralizes pro-inflammatory cytokine 17-A• Mainly used in severe plaque psoriasis• Given s.c• Dose: 300 mg s.c once monthly• ADRs:a. Infectionsb. Nasopharyngitis……………………….

CONTINUED……………………………..12. ANTI-PSORIATIC AGENT, SYSTEMIC:USTEKINUMAB (STELARA):-Human monoclonal antibody- Drug acts against IL-12 and IL-23 Interferes with T-cell differentiation

and activation blocks cytokine cascades- Given for moderate to severe plaque psoriasis- Newest available biologic agent- Dose: 45 mg s.c at 0, 4, 12 weeks- ADRs:a. Upper respiratory infectionb. Nasopharyngitis c. Injection site erythema…………………………..

CONTINUED………………………………13. OPHTHALMIC AGENTS, MISCELLANEOUS:ARTIFICIAL TEARS (HYPO TEARS, MURINE TEARS):- Used to treat dry eye irritation- Different types available OTC- Classified into:a. Preserved tears:• Used in mild cases• Include: GenTeal, Refresh Tears, Tears Naturale IIb. Non- preserved tears:• Used in severe cases• Include: Refresh, Refresh Plus, Hypo Tears PF- Contain equivalent to 0.9% NaCl- Used to maintain ocular tonicity- Stabilize and thicken pre-corneal tear film- Prolong tear film break up time- ADRs: Blurred vision, eye pain, headache……………

CONTINUED……………………………..14. INJECTABLE CORTICOSTEROIDS:- i.m route not preferred for corticosteroids since increased risk of

flares upon withdrawal- Used for isolated plaques (psoriatic nails)- Injected intra- lesionally / in nail/ matrixTRIAMCINOLONE (KENALOG, ARISTOSPAN):- Same corticosteroid action- Long lasting result- Dose: 0.4 ml injected into nail bed and matrix- Used to improve psoriatic dystrophy……………………..

CONTINUED………………………………15. LIGHT THERAPY (PHOTOTHERAPY):PUVA (PSORALENS + UVA LIGHT):- Valuable role in treatment of stable moderate- severe psoriasis- Psoralens:. Drugs activated by long wavelength UV light (320-400 nm) interferes with DNA synthesis decreases epidermal turnover. Include :• 8-MOP (Methoxy psoralen)• 5-MOP. Taken orally 2 hour before UVA light exposure. Eyes are protected due to cataract risks. Patients are given sunglasses to wear for 12 hours after treatment. Given twice a week, for 6 week period. ADR:- Nausea- Long term cutaneous malignancy………………………………….

D. NON-PHARMACOTHERAPY AND PATIENT COUNSELLING TIPS:• Focus on medication adherence• Focus on follow-ups, or consultations, as advised by doctors• People who take methotrexate, should focus on takin folic acid supplements to

avoid risk of anemia• Stress reduction• CLIMATOTHERAPY:“ Relocation of a patient to a different climate, so as to aid recovery from / management of a condition”• Adequate sunshine exposure• Use of moisturizers• Patients, who are on corticosteroid therapy, should report about pigmentation if

noted………………………..

BIBLIOGRAPHY:• CLINICAL PHARMACY AND THERAPEUTICS by ROGER WALKER• MEDSCAPE• PATHOPHYSIOLOGY AND TREATMENT OF PSORIASIS BY BRYAN ADAMS

(PHARM.D)• www.healthline.com• www.drugs.com

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