psoriasis

Presented by:
RANA AHMED
PSORIASIS:

• DEFINITION:
• Psoriasis is common immune mediated chronic noninfectious
inflammatory disease with a strong genetic basis that affect
mainly the skin but also have several systemic effects.
• affect 2-3% of the population worldwide
• male=female
• Precipitating factors:
• 1/trauma(kobner phenomenon):eg scratch,abarasion and surgical scar
• 2/infection:sterpococcal causing guttate psoriasis.
• 3/HIV
• 4/drugs:chloroquine,lithium,betablocker:propranolol,withdrawal from systemic steroid or
withdrawal from high potency topical steroid
• 5/weather: worse in winter
• 6/emotional stress
• 7/endocrinal factors:psoriasis may be exacerbated at puberty and menopause but usually
improves with pregnancy.
• 8/smoking and alchol
PATHOGENISIS

• Psoriasis is a Tcell mediated inflammatory process that leads to

epidermal hyperplasia
• 1-stimulation eg trauma,stress ,drugs,strept which activate
cells(APCS/MACROPHAGES),T helper,endothelial cells ,keratinocytes
• 2-secretion:of cytokines by activated cells eg IL1and IL8 from
keratinocyte ,TNFalpha,interferon gamma and IL2from activated
CD4
• 3-response which lead to:epidermal hyperproliferation,capillary
dilation in upper dermis and accumulation of inflammatory cells.
PATHOGENISIS
Clinical variant of psoriasis:

• MORPHOLOGIC VARIANT:
• Chronic plaque psoriasis(psoriasis vulgaris)
• Guttate psoriasis
• Pustular psoriasis
• Erythrodermic psoriasis
• Arthropathic psoriasis
• LOCATIONAL VARIANT:
• scalp psoriasis
• Palmoplantar psoriasis
• Nail psoriasis
• Inverse psoriasis
PSORIASIS VULGARIS:

• Type 1 and type2.

• Typical lesions are sharply demarcated erythematous papules and
plaques covered with nonadherent silvery scales
• GRATTAGE TEST:
• Scrapping of the psoriatic lesion with the edge of a glass slide
result in removal of scales layer after layer until a thin membrane
is left.
Auspitz sign
TYPE 1 PSORIASIS VULGARIS

• Early age 16-30

• Positive family history
• Associated with HLACW6,and possible B13 and B17
• More generalized
• Refractory or sever
TYPE 2 PSORIASIS VULGARIS

• Late onset.50 years

• Rarely associated with the family history
• HLA A2 and B27
• Localized
• Mild to moderate
GUTTATE PSORIASIS:

• Acute symmetric drop like lesion appears on the trunk and limbs
• Occurs in adolescent and young adult
• Often preceded by a history of sore throat /upper respiratory
infection usually strept 10days to 2 weeks before.
PUSTULAR PSORIASIS:

• 1/LOCALIZED PUSTULAR PSORIASIS:

• Palmoplantar pustulosis
• Pustular bacterid
• Acrodermatitis continua of hallopeau
• Circinate and annular pustular psoriasis
PALMOPLANTAR PUSTULOSIS

• Chronic relapsing disorder occurring on the palm and or sole

• Lesions : sterile pustule with yellow brown macule within areas of
extermities and scaling
• Sites :midpalm and thenar eminence of the hands and heels
• SAPHO syndrome : synovitis acne pustulosis hyperosteosis osteitis.
PUSTULAR BACTERID(ACUTE PALMOPLANTAR
PUSTULAR PSORIASIS)

• Symmetric itchy acute eruption of sterile pustule covering all the

palm and sole with relapsing and remission
ACRODERMATITIS CONTINUA OF
HALLOPEAU(ACROPUSTULOSIS)

• Chronic sterile pustular eruption affecting initially the tips of

fingers or teos and tend to extend proximally slowly over years
• Pustules may form beneath the nail plate leads to nail shedding
• Usually associated with oral mucosal lesion(annulus migrans)
• 2/GENERALIZED PUSTULAR PSORIASIS:
• Acute generalized pustular psoriasis(vonzumbusch)
• Generalized pustular psoriasis of pregnancy (impetigo
herpetiformis)
• Annular pustular psoriasis
GPP(VONZUMBUSCH)

• PRECIPITATING FACTORS:
• 1-irritating topicals eg tar,dithranol
• 2-infections
• 3-sunlight
• 4-pregnancy
• 5-hypocalcemia
• 6-drugs eg salicylates,iodides,progesterone and cortiocosteroid
withdrawal.
GPP

• The condition started with sensation of burning ,high fever and

sever malaise
• Sheet of erythema mainly on the flexures with tiny superficial
pustules that may become confluent(lake of pus)
• The nails become thickened or separated by subungal lakes of pus
• The buccal mucosa and tongue are involved
• EXANTHEMATOUS TYPE: active eruption of pustules that disappear
in few days,it follows infection or drugs as litium
• HISTOPATHOLOGY:SPONGIFORM PUSTULEV OF KOGOJ occurs as a
macropustule in all three variants of GPP and represent their
characteristic histologic lesion
Erythrodermic psoriasis

• It is precipitated by:infections,hypocalcemia,antimalarial,tar or
steroid withdrawal.
• Clues for diagnosis are nail changes and facial sparing
• CF:generalized erythema and scaling .90% skin surface affected
+or- leukocytosis,lymphadenopathy.
• May develop suddenly from guttate or stable psoriasis but typically
due to in appropriate treatment of the disease
Psoriatic arthritis

• Inflammatory arthritis with –ive rheumatoid factor,associated with

psoriasisin (5-30%) of patient with psoriasis
• Increase incidence of HLA B13,B17 AND CW6,B27 with ankylosing
spondylitis
• Nail affection occur more frequently(80-90%)
• CF:dactylitis, enthesitis, axial disease
• XRAY FINDING:pencile in cup deformity(distal head of bone
appearing sharpened like a point),fusiform tissue swelling (susage
digit) and joint space narrowing
Forms of psoriatic arthritis

• 1-Asymmetric oligoarticular form(70%)

• 2-symmetrical polyarthritis(RA like)15%
• 3-Asymmetrical DIParthritis 5-10%
• 4-spondylitis and sacroillitis 5%
• Arthritis mutilans 5%
• TREATMENT:
• NSAIDS
• Intraarticular steroids
• Methotrexate ,acitretin cyclosporin
• Biologics:etanercept,infliximab
Scalp psoriasis

• Discoid lesion or band like plaque along the anterior hair line,a telogen
effluvium may occur.
• Dd from seborrich dermatitis by dryness ,absence of itching or hair loss.

• Pityriasis amiantacea: soft patches with firmly adherent asbestos like scale,
• Causes:1-psoriasis(most common).
• 2-seborrheic dermatitis
• 3-secondarily infected atopic dermatitis.
• 4-tinea capitis
Psoriasis of the palm and soles

• 5 types:
• 1-typical silvery scaly patch.
• 2-thick fissured plaque.
• 3-pustulosis.
• 4-mixed form
• 5-rupiod on sole.
• Psoriasis of palm is differentiated from eczema by sharp
margination of the wrist.
Nail psoriasis

• Thimble pitting (most common)

• Onycholysis (separation of the distal end of the nail from the nail
bed)
• Oil drop or salmon colored spots
Flexural(inverse )psoriasis

• Affect axillary,submammary or groin

• Lesion are devoid of scales due to continuous friction and
moisture.
• Itching is the most common symptom
DD:
TREATMENT:

• Topical forms:
• 1-topical corticosteroid.
• 2-topical vitamin D
• 3-topical tar
• 4-topical calcineurin inhibitor(tacrolimus,pimecrolimus)
• 5-dithranol pulse.
Topical corticosteroid

• Moderately potent steroid eg betamethasone dipropionate.05 BD

• Creams are preferred to ointment
• SE:
• Lack of long term control
• Tachyphylaxis
• Dermal atrophy
• telangectesia
Topical vitamin D

• ACTION : through binding of vitamin d receptors;

• 1-reduces keratinocyte proliferation
• 2-decrease keratin 6,16,17 (marker of hyperproliferative activity)
• 3-induce normal keratinocyte differentiation
• 4-immunomodulatory effect
• 5-cosmetically acceptable oderless doesn’t burn or stain normal
skin
Calcipotriol cream or ointment(50 mcg/g):

• INDICATION:
• Mild to moderate plaque psoriasis
• 2-sever psoriasis :combination
• 3-vitiligo
• SIDE EFFECT:
• Sligth irritation avoid in the face and intertiginous area unless
combined with steroid
Topical tar

• Conc 2-3%
• Action :anti-inflammatory ,antipruritic.
• disadvantage: staining and unpleasant odor.
• SE:folliculitis ,acneform eruption,irritation
• GOECKER MAN TECHNIQUE:2-5% crude oil tar + UVB
• It may be combined with steroid(locacorten tar)
• Contraindication:
• Pustular psoriasis
• Erythrodermic psoriasis
• Pregnancy and lactation
Dithranol pulse

• Conc:.1-1% stielasan.
• 3% in short term contact therapy(5-30min)
• Action :antiproliferative effect and inhibit neutrophil chemotaxsis
• Indication:
• Mild to moderate or sever psoriasis
• INGRAM TECHNIQUE:tar bath +uv+dithranol paste
• CONTRAINDICATION:
• Unstable psoriasis
• Pustular psoriasis
• Erythrodermic psoriasis
• DISADVANTAGE:
• Irritation ,staining of clothes and normal skin
systemic treatment:

• 1-methotrexate
• 2-acitretin
• 3-cyclosporin
methotrexte

• Action : inhibit DNA synthesis during the s phase of the cell cycle
by competitive inhibition of folic acid reductase enzyme.
• Indication:
• Sever extensive psoriasis
• Erythrodermic psoriasis
• GPP
• Generalized intractable psoriasis of palm and sole
• Psoriatic arthropathy
methotrexate

• Dose:.2-.4 mg /kg .
• 1 tablet contain 2.5 mg
• Usually 7.5-25 mg are given in a divided weekly dose(3 doses each
every 12 hrs)
• Inj form contain 50mg ie ,25mg im every week
• Clinical response start in 7-14 days and complete in 4-8 weeks
• Note dialy adminsteration of methotrexate in small dose is
associated with toxcity
• Give with it folic acid
• Contraindication:
• Pregnancy or lactation
• Hepatic disease :alchol,hepatitis ,cirrhosis
• TB or any infection
• Peptic ulcer,leucopenia ,sever anemia
• Renal function abnormality
• SIDE EFFECTS:
• Stomatitis , bonemarrow suppression
• Hepatotoxicity
• Oligospermia , abortion , teratogenicity
• Dyspnea cough
Acitretin(neotigason)

• Action : correction of keratinocyte differentiation (decrease neutrophil

migration)

• Indication:
• Generalized pustular psoriasis,erythrodermic psoriasis as monotherapy
• Plaque psoriasis as combination regimen
• Dose: initial dose is 10-25 mg/kg then gradually increasing the dose
until the full response is achieved
• Optimal dose for monotherapy is 25-50mg/day for 3 to 6 months
• BLACK BOX WARNING:
• Teratogenic : avoid pregnancy 1 month before , during and 2 years after therapy
with acitretin
• Avoid drinking alchol
• Avoid vitamin A supplement
• Hepatotoxicty
• Other side effects:
• Hyperlipidemia
• Chelitis,skin peeling,rhinitis,dry skin ,alopecia
• Pseudotumor cerebri
Cyclosporin(cyA)

• Action:
• Inhibit keratinocyte proliferation
• Inhibit t cell activation by inhibiting the interaction between APCS(lcs
and macrophage) and t cell required for synthesis and release of
IL1,also inhibit the transcription and release of IL2 and the expression
of IL2receptors preventing T cell activation and IFN production
• Dose:2.5 mg/kg/day
• Check BP and serum creatinine every 2 weeks for the first 3 months
,then monthly there after
• Side effect:
• Nephrotoxic
• HTN
• Malignancy(lymphoma,Kaposi sarcoma,scc,bcc)
• Hypertrichosis (higher dose),gingival hypertrophy,acne ,folliculitis
• Contraindications:
• Abnormal renal function
• Uncontrolled HTN
Biologic therapy:

• Biologics:are proteins that bind to extracellular tagets(adhesion

proteins,receptors,cytokines) to block molecular activation in one
of the cellular pathways of T cell immune response.
• Classification of the biologics:
• 1-antibodies: mainly chimeric(fused segments of mouse and human
antibodies) and humanized (individual aminoacids in a human
backbone replaced with specific binding sequences derived from a
marine monoclonal)
• Eg antiCD11 a monoclonal antibody Efalizumab
• 2-fusion proteins:the receptor domain of human proteins is fused
to constant region sequences of human igG
• Eg alefacept,etanercept,infliximag
• 3-recombinant cytokines
Alefacept(Amevive)

• A fusion protein of human LFA3 and the Fc portion of human igG1 that
binds to surface CD2 on Tcells leads to apoptosis via the
perforn/granzyme system leads to depletion of activated T cells.
• Dose:7.5 mg iv or 15 mg im once weekly for 12 weeks.
• Repeated course may be given after 12 weeks rest period
• S/E:dose dependent decrease in CD4/CD8 cell count
• Increase the risk of infections and causes reactivation of latent infection
• Increase the risk of malignancy
• Hypersensitivity reaction(urticaria,angioedema)
Efalizumab(raptiva)

• A humanized monoclonal ab that binds to huaman lymphocyte

function associated antigen(LFA-1) and blocks LFA-1/ICAM-1
interaction leads to block both Tcell activation and trafficking into
skin but doesn’t deplete Tcells
• Dose:1 mg/kg sc once weekly for 11 weeks
Tumer necrosis factor alpha inhibitor

• 1-etanercept
• 2-infliximab
• 3-adalimumab
• S/E:increasing the risk ofseriouinfetions(TB,sepsis),histoplasmosis.
• Risk of hepatitis B virus activation
• Malignancies:eg lymphoma
• CHF
• Demylinating disease
• Anaphylaxsis
• Autoimmune hepatitis,cytopenia,lupus like syndrome.
Etanercept(Enbrel)

• Fusion protein of huam igG fc region+TNF alpha and beta in serum.

• Dose:25-50mg sc twice weekly for 12 months
Infliximab(Remicade)

• Monoclonal ab against TNFalpha that neutralize serum and

membrane boud TNF alpha
• Dose 3-5 mg/kg iv infusion over 2 hrs at week 0,2 and 6.
Adalimumab(Humira)

• Monoclonal ab against TNFalpha

• Dose:80 mg sc initial loadind dose followed by 40 mg on day 8,then
every 2 weeks 40 mg.
Ustekinumab(stelara)

• It’s a monoclonal ab that targets IL12and IL23

• Action:human igG1 monoclonal ab that binds with high affinity and
specificity to the P40 subunit that is shared by the heterodimeric
IL12and IL23 cytokines
• IL12has a critical role in the development of Th1 cells
• IL23 for the generation of TH17
• Dose:45 mg(if wt is<100 kg) or 90 mg (if wt is>100 mg) sc at weeks
0 and 4 then every 12 weeks
INV prior to treatment with biologics

• CBC
• PPD
• RFT
• LFT
• VIRAL SCREENING
CASE TIME