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Psoriasis is a disorder of keratinization- hyperproliferation & abnormal differentiation of

epidermal keratinocytes , lymphocyte infiltration(T cells), endothelial vascular changes in


dermis .Clinically presents as chronic, symmetrical, erythematous, well-defined, dry, red, scaly
papules & plaques
Usually with spontaneous remissions & exacerbations.Course & progress- unpredictable.
Lack of a curative drug.Topical & systemic drugs may give symptomatic relief & prolong
remission
Goals of therapy
Early & rapid control of disease process.
Achieve a longer duration of remission.
Provide a better quality of life to patient by reducing the severity of disease & minimize the
side effects.
Modalities of treatment
1. Topical treatment
2. Phototherapy & Photochemotherapy.
3. Systemic therapy.
Other forms of therapy
Pathogenisis
Both innate & acquired immune responses.Innate- neutrophils,natural killer cells, DCs
Acquired TH 1 response IL-2, TNF-alpha, INF- gamma.
Topical therapy
Most of the patients with mild psoriasis can be adequately controlled with topicals
1. Emollients 2)Tar 3)Dithranol 4)Topical corticosteroids
5)Topical calcinuerin inhibitors 6)Vit D & its analogues 7)Vit A 8)Keratolytics
9)Occlusive dressings alone
Emollients
Liquid paraffin & White soft paraffin.
Hydrate stratum corneum
Reduce dryness- relieve itching, decrease scaling & limit painful fissuring
Immediately after bath & as frequently as required
Addition of urea may improve hydration & decrease scaling
Tars
Dry distillation product of organic matter heated in the absence of oxygen.
Crude coal tar- 48%hydrocarbons, 42%carbon and 10% water
Isoquinoline
Depresses epidermal DNA synthesis, reduces mitotic activity in basal layers of epidermis.
Antipsoriatic activity boosted by combining with UVR & anthralin.
2 to 5% salicycilic acid is added to increase its absorption
Goeckerman regimen:
Daily application of 2-5% crude coal tar was combined with tar bath & UV light.
In-patient treatment-stable plaque psoriasis
3 to 6 weeks- 80% of pts
Modern derivatives-alcoholic extracts of tar in cream / ointment base, tar gels, that are
cosmetically more acceptable & easy to apply but less effective than crude coal tar
1. Bad smell
2. Staining of clothes
Also used in Ingram regimen- anthralin, coal tar bath & UVR
Side effects-
1. Irritation-face, genitalia, flexures, unstable psoriasis
2. Allergic reactions
3. Folliculitis
4. Risk of skin cancer- avoid prolonged exposure over genitalia esp when combined with UVR,
continued surveillance for early detection of cancers
Contraindications
1. Erythrodermic psoriasis 2)Generalised pustular psoriasis 3)Preexisting folliculitis
2. Severe acne
Dithranol
Chrysarobin is a tree bark extract, accidentally found to be useful in treating psoriasis.
Dithranol (Anthralin)- 1,8-dihydroxy anthrone is a synthetic derivative of antracene & closely
related to chrysarobin.
Mechanism of action-
1. Inhibiting DNA synthesis of epidermal cells
2. Binds mitochondrial DNA & inhibits enzymes
3. Initiates generation of reactive oxidants by PMNL - immunosupressive
Ingram regimen
Used in chronic plaque psoriasis for over half a century
After a tar bath in which scales are removed suberythemogenic doses of UVB given & lesions
are then precisely covered with anthralin in Lassars paste (initially 0.05 to 0.1% used, may be
increased to 4%) Paste is kept in position with
tubular gauge
After 18 to 22 hrs cycle is repeated
Clearance of lesions seen in 3weeks, deep brown staining of treated skin.
Side effects:
1. Irritation & burning- (oxidation of skin to form anthraquinone) esp over head, neck, genitaia &
flexures
2. Staining
3. Stiff paste-difficult to apply & remove
Low strength formulations-0.01 to 0.1% dithranol in petrolatum or zinc paste, applied once
daily
Salicylic acid 1 to 2% added to prevent oxidation
Micanol microcrystalline formulation of 1% D less staining of fabrics but not skin.
Short contact therapy-
A high conc of dithranol 2 to 4% applied to skin lesions for 1hr & washed off
Out-patient basis, patient compliance
Aqueous creams -easy to apply & remove; can be rubbed into skin until absorbed, so less
staining & irritation
Equally or more effective to Ingram regimen
Other combinations-
With steroids-D in 0.0125% clobetasol propionate or D with flucinoide less irritation & rapid
initial clearance but total clearance time is the same(more rapid relapse rate)
Topical steroids
Mild to moderate psoriasis
If tar or dithranol have failed
Mechanism of action- anti inflammatory, antiproliferative, immunosuppressive &
vasoconstrictive effects
Advantages- effective, well tolerated, easy to apply & remove, relatively rapid action, less
irritation & lack of staining of clothes & skin
Indications
1. Mild to moderate psoriasis affecting <20% of the body surface area
2. Mod to severe P-during maintenance therapy after clearance with topical or systemic therapy
3. While awaiting the onset of systemic drugs
4. Unwilling to use systemic drugs
Low potency- face, groin, axilla, areas with thin skin & in infants
Mid potency- other areas & adults
Higher potency- thick chronic plaques resistant to lower potency agents
Clobetasol 0.05%- superior to flucinonide, Halcinonide & Betamethasone dipropionate
Begin with daily applications- improvement is seen in 2 to 4wks, then tapered to twice weekly
with a lower potency agent.
Betamethasone dipropionate- 3times over 24hr period each week,(weekend therapy)
Side effects-
Atrophy or thinning of skin, telangiectases, striae, acneiform eruption, rosacea, CD, side
effects secondary to systemic absorption.
Intralesional steroids-
Solitary resistant plaques & nail lesions
Triamcinolone hexacetonide5mg/ml or Triamcinolone acetonide 10mg/ml
Under occlusion by hydrocolloid dressings over recalcitrant plaques
Foam preprarations- scalp
Used in combination with various topical & systemic agents
A combination of topical clobetasol propionate, dithronal, UVB found to be superior to UVB &
dithronal alone in clearing psoriasis
Topical calcineurin inhibitors
Tacrolimus & Pimecrolimus- inhibit Calcineurin, an intracellular enzyme involved in regulation of
gene transcription in T-cells
Immunosuppressants- inhibit activation & maturation of Tcells & release of cytokines
Tacrolimus 0.1% ointment- face, intertriginous areas, in children.
Pimecrolimus 1% cream
Intermittent rescue therapy
Advantages-
1. Selective action
2. Not absorbed systemically
No skin atrophy-long term use
Vitamin d & its analogues
Naturally occuring active metabolite of vitD3 calcitriol(1,25, dihydroxy vitd3)
3 synthetic analogues-
1. Calcipotriol(calcipotriene)
2. Tacalcitol (1,24,DH VitD3) 3)Maxacalcitol (1,25,DH VitD3)
Mechanism of action-
1. Reduses keratinocyte proliferation 2)Enhances differentiation in lesional skin
3)Shifting TH1 cytokine profile towards TH2
Calcipotriol 50 microgm/gm-(0.005%) cream or ointment- stable plaque psoriasis
& 0.005% solution in chronic mod to severe scalp psoriasis
Cream & solution-twice daily . Ointment- once /twice daily .Effectiveness- 6 to 8 weeks
Advantages- more effective than anthraline, no atrophy, safe in children( upto 45gm/wk), does
not lead tachyphylaxis
Disadvantages- may cause irritation, only for stable & less severe cases,hypercalcemia if max
dose of 100 to 120gm/wk is exceeded
Monotherapy or in combination with topical steroids, UVB, PUVA, Acitretin, Methotrexate,
Cyclosporine
Increases immunosuppressive effects of cyclosporine on IL-2; reduses cumulative dose of
acitretin.
Study calcipotriol in morning + Halobetasole oint in evening for 2wks, superior to either drug
alone.
A stable oint formulation of Cal50mgm/gm + beta dipro 0.5mgm/gm twice daily.
Calcitriol 3mgm/gm- same effect,
better tolerated on face & flexures
no significant change in calcium levels
Tacalcitol 4mgm/m od- less effective,
well tolerated,
Maxacalcitol 25mgm/gm od- 8 wks
Vitamin a analogues
Tazarotene- topical synthetic retinoid, binds to RARs beta & gamma
Mechanism of action- 1.Downregulates markers of keratinocyte
differentiation, proliferation & inflammation
2.Upregulates transcription of genes TIG 1,2,3 in keratinocytes antiproliferative effects
Available as 0.05% cream, 0.1% gel
Thick recalcitrant plaques
Advantages-
1. Potency comparable to mid to high potency steroids
2. Rapid onset of action
3. Sustained beneficial effects upto 12wks after cessation of therapy
Efficacy increased by combining with topical steroids or UVB
Study- tazarotene 0.1% gel + mometasone furate 0.1% cream more effective than Mometasone
bd or Calcipotriol oint bd
Occlusive dressings alone
Prolonged application of adhesive hydrocolloid occlusion over limited psoriasis
Hyperpigmentation, pain while removing
Phototherapy &
photo chemotherapy
UVB Phototherapy Excimer laser Photochemotherapy
Uvb phototherapy
Sun light has beneficial role in psoriasis & the therapeutic wavelengths belong to middle & long
wave UVB 300 TO 313nm.
Shorter wavelengths- not effective, risk of acute & chronic phototoxicity.
Second line therapy
Expensive
Mechanism of action-
1. Depletion of T-cells in epidermis by apoptosis
Shift from TH1 to TH2 response in lesions
Narrow band UVB- selective UVB rays in a narrow band btw 311 to 313nm are used from Philips
TL-01 fluorescent lamp.
More effective than broad band, longer remissions
Minimizes irritation, phototoxicity, skin cancer
Stable plaque, guttate P with >20% body area effected- if they fail to respond to topical
therapies
Lighter skin types except type1 respond better
Schedule- suberythemogeic doses of UVB, thrice weekly
90% clearance in 80% of pts over 20 to 30 sittings.
Gradually reduced to once a week over the next 2 to 3 months
Initial dose should be 80% of the MED with 20% increment in each exposure if no erythema is
seen.
Advantages over PUVA- psoralen side effects are avoided, duration of exposure is reduced, less
carcinogenic
Dis advantages-
1. Thick lesions over elbows, knees, palms, soles respond poorly(petrolatum rubbed before )
2. Scalp & genitalia shielded hence are resistant
CI-
1. Pts with photosensitivity 2)Pts on phototoxic or photosensitive drugs
3)Unstable, erythrodermic & pustular psoriasis 4) H/O skin cancer
5) Skin type1
Combinations-
1. Prior application of coal tar- total UVB doses needed for clearance are less
2. With Acitretin- less no of exposures bt more relapse rates
Excimer laser
308nm excimer laser emits monochromatic & coherent beam in UVB spectrum, selectively to a
lesion, sparing the surrounding skin
Stable & recalcitrant limited psoriasis on elbows & knees
Average of 6 treatments given twice weekly- 75% improvement in most of the pts
Photochemo therapy
Psoralens are naturally occuring furocoumarins 8-methoxy psoralen(8-MOP); 5-methoxy
psoralen
(5-mop); 4,5,8 trimethoxy psoralen.
Administration of psoralens & subsequent longwave UVA radiation PUVA.
Mechnism of action-
1. Interferes with DNA synthesis, cellular proliferation
2. Apoptosis of cut lymphocytes-localized immunosuppression
3. Inhibits angiogenisis invitro.
Mc used regimen-
8-MOP 0.6mg/kg body wt on alternate days followed 2hrs later by exposure to UV rays
High intensity fluorescent UVA tubes
Smaller doses of UVA, increments of 0.5 to 1.5J/cm2
90% clearance after 15 to 25 treatments with a total UVA dose of 100 to 200 J/cm2
Maintenance-once in 1 to 4 weeks,(last UVA dose in clearance phase)
Indications-
1. Elders >55yrs with atleast 20% of body surface involved who cannot be controled by
conventional topical therapies
2. Generalised pustular P, erythrodermic P, palmoplantar pustulosis, nail P
Contraindications-
1. Pregnancy
2. Children <18yrs
3. (Relative) previous exposure to inorganic arsenic/ radiotherapy/ History of skin cancer
Liquid 8-MOP- rapidly absorbed ,high plasma concentration leading to good results
5-MOP- better GI tolerance, low incidence of phototoxic reactions
Side effects-
1. Nausea, vomiting 2)Headache, vertigo
3)Erythema, pruritus, blistering, koebner phenomena, lentigines, hypertrichosis, seborrheic
dermatitis on face, Lp, lichenoid eruption, Ocular complications
4) SLE,skin cancers
Topical psoralens-
8-MOP 0.15% in oil base & 1% oint
Intervening areas of skin spared from phototoxic damage
Nail P
PUVA Bath-
Trimethylpsoralen 50mg in 100ml ethanol is added to a 150 litre bath
Pt allowed to bath for 15mins, immediately exposed to UVA
Response & relapse rates are same but UVA exposure is less
Side effects of oral PUVA are less
A combination of PUVA, Methotrexate, UVB more efficacious than PUVA or UVB alone
RE-PUVA- Etretinate + PUVA faster clearing, less side effects
Systemic therapy
1. Oral retinoids (Acitretin)
2. Antimetabolites like Methotrexate, Mycophenolat mofetil, Hydroxyurea, Azathiorine
3. Cyclosporine
4. Biological therapies
5. Corticosteroids
6. Other forms of therapy
Retinoids
Acitretin only retinoid used in psoriasis
2
nd
generation monoaromatic retinoid- the active metabolite of etretinate
Less lipophilic, equally effective
Half life of 50 to 60 hrs
Mechanism of action-
1. Interaction with RARs & regulation of gene transcription
2. Decreases inflammation in epidermis & dermis by interfering with cytokines
3. Modulates differentiation-decreases scaling, erythema
Indications-
1. Drug of choice for erythrodermic, generalised pustular psoriasis
2. Modestly effective in plaque P
3. In HIV infected psoriatic pts
Dose- 10 to 25mg once daily with meals
Initial response in 12 to 16 wks, peak response in 3 to 6months
Relapse within 2m of stopping treatment
RE-PUVA- acitretin combined with PUVA,reduses cumulative dos of UVA
Contraindications-
1. Pregnancy, breast feeding
2. Severe liver & renal impairment
3. Caution- diabetics, alcoholics & obese
Drug interactions-
1. Tetracycline- increased phototoxicity, pseudotumor cerebri
2. Minocycline-pseudotumor cerebri
3. Alcohol,Mtx -hepatotoxicity
4. Other retinoids or Vit A suppliments-
5. Corticosteroids- hyperliidemia
6. Antidiabetic drugs- alterations in blood glucose
Side effects-
1. Cheilitis in 75%
2. Xerosis, skin fragility, pruritus, desquamation on palms & soles
3. Hair loss
4. Conjunctivitis & ocular irritation
5. GIT-
6. Hyperlipidemia
7. Skeletal hyperostosis, premature fusion of epiphyses
Methotrexate
Anti-metabolite
Synthetic analogue of folic acid
Mechanism of action-
1. Anti-proliferative binds to Dihydrofolate reductase, inhibits DNA synthesis in S-phase of cell
cycle-inhibits epi hyperproliferation
2. Anti-inflammatory-inhibits AICART(5-aminoimadazole carboxamide ribonucleoside
transformylase) involved in purine synthesisaccumulation of AICAR, release of Adenosine.
Indications-
1. Disabling or wide spread psoriasis (>20%)
2. Pustular psoriasis (Von Zumbusch type)
3. Erythrodermic psoriasis
4. Moderate to severe psoriatic arthritis not controlled with NSAIDs
5. Lack of response to PUVA, Retinoids or phototherapy
Test dose-
5mg blood count stable after 7 days
Gradually increased in steps of 2.5 to 7.5 mg
Dosage-
Single oral or im dose of 10 to 25mg once a wk
OR 7.5 to 22.5mg/wk in three equal divided doses at 12hrs interval
Response is rapid-72hrs with near complete clearance in 8 to 12 wks
Maximum weekly dose should not exceed 30mg
Withdrawn if no response after 6 to 8wks
Monitoring
Baseline investigatins:
1. Complete physical examination, CBC & platelet count ,LFT, RFT, X-ray chest, HIV in at risk
patient
Follow up:
For first 3months- every 2wks RBC, WBC, Plateletcounts
After 3months-monthly:CBC,plateletcount every 3months: LFT, RFT
CONTRAINDICATIONS:
Absolute-pregnancy , desire to get pregnant , severe hepatic/renal compromise, blood
dyscrasias , active peptic ulcer disease
Relative chronic alcoholism, mild to moderate renal impairmen, h/o recent hepatitis, past h/o
internal/skin malignancy, active infectious disease, h/o Mtx toxicity, elderly at risk of acute
dehydration
Side effects & Toxicity:
Acute toxicity- bone marrow suppression & oral ulceration. Folinic acid/Leucovorin given iv
immediately, atleast 20mg or as high as the last dose of MTX.
subsequent doses given at 6hr interval until serum Mtx <0.01mmol/L
adequate hydration
GIT- Nausea,vomiting, diarrhoea, stomatitis
nausea reduced by 5mg folic acid daily
Dividing total weekly dose into 3 doses at 12hr interval & taking Mtx with evening meal
Cytopenia- 10 to 20% patients on long term therapy (> 6weeks)
leukopenia (<3500/mm3), thrombocytopenia (platelets<1,00,000/mm3, or pancytopenia
Sore throat, fever, purpura .
risk factors-renal insufficiency ,oldage,
concomitant use of cotrimoxazole/NSAIDs
if it persists for >1wk- dose reduction/ discontinuation of Mtx

Macrocytosis:
On long term use
Folic acid supplementation on the 6 days of week when Mtx is not take
Hepatotoxicity:
7% overall risk of severe fibrosis/cirrhosis
Accumulation of polyglutamated form of metabolite of Mtx in hepatic cells- deficient nucleotide
synthesis- hepatocyte injury
Risk factors- age,weekly dose >20mg, high cumulative dose of >2.5gm,Increased frequency of
intake ,concomitent retinoid therapy, past h/o hepatitis B/C infection, obesity, DM, daily
dosage of Mtx
Liver biopsy- after a cumulative dose of 1.5g if liver chemistry is consistently abnormal
current guidelines- 4g
P3NP Essay- it is amino-terminal propeptide of type3 collagen that is cleaved during
collagen synthesis & upregulated in active fibrosis, 3 monthly.
If persistantly abnormal then go for biopsy.
HMRS- Proton magnetic resonance spectroscopy, measures liver fat content noninvasively

PMRS- estimates cell membrane turnover & fibrosis
Squamous cell carcinoma
Known abortifacient & teratogen
May affect spermatogenesis
Anaphylactoid reactions(low dose, during initial exposure)
Painful erosions of psoriatic plaques
Alopecia, hyperpigmentation, TEN
Headache,dizziness, mood alterations
Stress fractures
Erythema recall/UV burn recall-on plaques if Mtx begun within 1 to 2wks of stoping PUVA
MYCOPHENOLATE MOFETIL
Mycophenolic acid ,the active moiety inhibits guanin synthesis (inosine monophoshate
dehydrogenase)
This blocks DNA synthesis blocks proliferation of T & B lymphocytes
Inhibits leukotactic factors,LT B4 & 12-hydroxyeicosatetraenoic acid
Side effects- GI intolerance, frequency of micturition (dividing the doses)
HYDROXYUREA
Antimetabolite
Acts on ribonucleoside diphosphate reductase that prevents conversion of ribonucleotides to
deoxyribonucleotides . 1 to 2g daily orally.Fewer side effects than Mtx but less effective
Bone marrow depression, renal toxicity, flu-like syndrome
Cyclosporine
Immunosuppressant
Impairs release of IL-1 & IL-2
Indications-
1. Erythrodermic psoriasis
2. Generalised/localised pustular psoriasis
3. In patients who suddenly need to terminate another systemic therapy
4. As rotational therapy
Used either as a maintenance treatment or a short course of 4 to 12 weeks to induce remission.
Dose- 2.5 to 5mg/kg body wt/day
If no response after 2wks increase by 0.5 to 1mg/kg/day at fortnightly intervals
Adequate response-
stopped & maintained on alternate therapy
Or
maintained at lowest possible dose.
Renal toxicity & hypertention
Corticosteroids
Decrease the mitotic index in epidermis
Not used in routine care
Only short term efectiveness-
1. Severe forms- erythrodermic & generalised pustular types(life saving)
2. Acute exacerbations-waiting for other drugs to take effect
Flourinated forms-Triamcinolone-12to20mg/day
Betamethasone.
Other forms of therapy
Treatment of psychological factors, Surgical shaving , Daily sun bathing, sea bathing, Diet- fish oil
Photodynamic therapy- photosensitizing drug and light (topical 5-aminolevulinic acid + laser).
Combination therapy
A combination of two drugs at lower doses
After clearance one agent is discontinued & safer of the two is used as maintenance therapy
Indications-
1. Failure of monotherapy
2. Toxicity to a single agent
3. While tapering a patient from an individual drug.
Rotational therapy
Different treatment regimes are rotated before significant toxicity to individual drug develops.
Also decreases resistance to the drug
Allows long term treatment
Squential therapy
Clearance phase- rapidly acting (more toxic) drug at maximum dose, to clear psoriasis
Transition phase- a weaker less toxic agent is introduced while gradually tapering the initial drug
to maintain clearance
Maintenance phase- only the maintenance drug continued as long as required with or without
UVB/PUVA