Efi. Gelerstein 2011/12

Topic 1. Psoriasis

Chronic non-infectious inflammatory skin disorder, characterized by well-defined erythematous plaques bearing large adherent silvery scales.

Morbidity : 1-3% (white races). Black skin: rare Can start at any age but is rare < 10 years Appears most often b/w 15-40 years. Usually chronic with exacerbations and remissions.

Cause: Unknown Genetic predisposition Environmental trigger Abnormalities in psoriasis plaque:

- Hyper-proliferation of keratinocytes - Inflammatory reaction → neutrophils + Th1 infiltrate

Precipitating factors / Provocation:1. Physical factors → injury, UV, burning, scars.2. Chemical factors → toxic agents, antipsoriatic agents3. Inflammatory dermatoses → zooster, impetigo, candidosis4. Endogenous → infectious diseases, stress, alcohol, pregnancy, drugs (Lithium, β-blockers, NSAID)

“Köbner sign” → upon skin injury, redness will appear → 2 weeks after injury psoriasis will appear.

Histology The main changes are the following.

1. Parakeratosis (nuclei retained in the horny layer).2. Polymorphonuclear leukocyte micro-abscesses .3. Irregular thickening of the epidermis, but thinning over dermal papillae is apparent clinically when

bleeding is caused by scratching and the removal of scales (Auspitz’s sign).4. Dilated and tortuous capillary loops in the dermal papillae.5. T-lymphocyte infiltrate in upper dermis.

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Presentation:1. Plaque pattern (most common)

Lesions are well demarcated and range from a few mm to several cm in diameter Pink or red with large dry silvery-white polygonal scales Elbow, knees, lower back, scalp are sites of predilection

2. Guttate pattern Children and adolescents Often triggered by streptococcal tonsillitis Numerous small round red macules on the trunk → scaly

3. Napkin psoriasis A psoriasiform spread outside the napkin (nappy/ diaper) area may give the first clue to a

psoriatic tendency in an infant Clears quickly, ↑risk of ordinary psoriasis developing in later life.

4. Localized pustular psoriasis (palmo-plantar pustulosis) Recalcitrant, often painful condition It affects the palms and soles → studded with numerous sterile pustules, 3–10 mm in

diameter, lying on an erythematous base. The pustules change to brown macules or scales Generalized pustular psoriasis is a rare but serious condition, with fever and recurrent

episodes of pustulation within areas of erythema.5. Erythrodermic psoriasis

Rare, triggered by irritant (tar, drugs) The whole skin is involved ! The skin becomes universally and uniformly red with variable scaling Malaise is accompanied by shivering and the skin feels hot and uncomfortable

Preferred site: Scalp → often involved. Areas of scaling are interspersed with normal skin; their lumpiness is more

easily felt than seen. Frequently, the psoriasis overflows just beyond the scalp margin. Significant hair loss is rare.

Nails → commonly involve, with ‘thimble pitting’, onycholysis (nail separation from nail bed), and sometimes subungual hyperkeratosis. Yellowish-brown discoloration below nail plate → “oil point”

Flexures → Psoriasis of the sub-mammary, axillary and anogenital folds is not scaly although the glistening sharply demarcated red plaques, often with fissuring in the depth of the fold, are still readily recognizable.Flexural psoriasis is most common in women and in the elderly, and is more common among HIV-infected individuals than uninfected ones.

Palms and soles → Palmar psoriasis may be hard to recognize as its lesions are often poorly demarcated and barely erythematous. The fingers may develop painful fissures.

Efi. Gelerstein 2011/12

Differential diagnosis1. Discoid eczema

Lesions are less well defined and may be exudative or crusted, lack ‘candle grease’ scaling, and may be extremely itchy.

Lesions do not favors scalp, extensor aspects of elbows and knees but rather the trunk and proximal parts of the extremities.

2. Seborrhoeic eczema Scalp involvement is more diffuse and less lumpy. Intervening areas of normal scalp skin are unusual. Flexural plaques are less well defined and more exudative. There may be signs of Seborrheic eczema elsewhere, such as in the eyebrows, nasolabial folds

or on the chest.3. Pityriasis rosea

This may be confused with guttate psoriasis but the lesions, which are oval rather than round, tend to run along rib lines.

Scaling is of collarette type and a herald plaque may precede the rash. Lesions are usually confined to the upper trunk.

4. Secondary syphilis There is usually a history of a primary chancre. The scaly lesions are brownish and characteristically the palms and soles are involved. Oral changes, patchy alopecia, condylomata lata and lymphadenopathy complete the picture.

5. Cutaneous T-cell lymphoma The lesions, which tend to persist, are not in typical locations and are often annular, arcuate,

reniform or show bizarre outlines. Atrophy or poikiloderma may be present and individual lesions may vary in their thickness.

6. Tinea unguium This is often confused with nail psoriasis but is more asymmetrical and there may be obvious

tinea of neighbouring skin. Uninvolved nails are common. Pitting is not seen and nails tend to be crumbly and discoloured at their free edge.

PathogenesisEpidermal hyper-proliferation → More keratinocytes in the epidermis → thickening.Leukocyte infiltration → in dermis and epidermis

PMNL T-lymphocytes activated.

Early lesion: activated T-cells

The role of TNF-α in psoriasis:1. Induction of IL-1 and IL-8 production2. Induction of adhesion molecules3. Induction of keratinocytes proliferation

Psoriasis Treatment:

1st event

Innate immunity

Acquired immunity (T-cell)

PSORIASIS

TNF α

Efi. Gelerstein 2011/12

Local : Dithranol 0.1-8.0% → stains everything brown.

Mini treatment → skin is treated for a short time → washed out so it won’t stain the skin. It affects the mitochondria of the skin. Side effects: inflammation staining

Steroids → only topical corticosteroids, otherwise there will be a rebound. Vitamin D → affects the proliferations of Karetinocytes. Has a slow reaction time. Retinoids → vitamin A derivatives, we can use it for long term after using steroids in the beginning.

Phototherapy : BB-UVB → Broad band UV B-light. NB-UVB → Narrow band UVB (300nm) below 300nm no anti-inflammatory effect. PUVA → Psolaren (an ionic DNA binding drugs) UV light. Anti-proliferative effect. 308 nm laser → UVB light source.

Systemic: if phototherapy is not enough . Retinoids (ACITRETIN) → Influences the proliferation and differentiation of Karetinocytes.

Patients taking this drug must not be pregnant for the following 2 years due to its tetragenic effect. Male patients are not restricted in taking the drug.

Methotrexate → anti proliferated drug. SE: Hepatotoxicity effect and bone marrow suppression. Cyclosporine → check regularly renal function, creatinine level. Biological treatments for psoriasis

1. Biologicals targeting TNF-a - Etanercept: blocks TNF-α- Infliximab: Anti-TNF-a antibody- Adalimumab: Anti-TNF-a antibody

2. Biologicals targeting IL12/23 - Usztekinumab: blocks p40 common subunit of IL12/23

LOCAL Emolliens Keratolysis Dithranol Steroids Vitamin D Retinoids Kalcineurin inhibitors

PHOTOTHERAPY BB-UVB NB-UVB PUVA 308 nm laser

SYSTEMIC Retinoids Methotrexate Cyclosporine Biological treatments