• DEFINITION: It is a chronic immune-mediated systemic disorder results from a polygenic predisposition combined with environmental triggering factors.

• The word “psora” means a desquamative condition or itch.

• The characteristic lesion is a sharplydemarcated erythematous plaquewith micaceous scale, and the plaques may be localized or widespread in distribution.

• Natural history: chronic with intermittent remissions.

• Psoriasis is a systemic disease process in which up to 20–30%of the patients have or will develop psoriatic arthritis. In addition, in patients with moderate to severe psoriasis, there is an increased relative risk for metabolic syndrome and atherosclerotic cardiovascular disease.

• Psoriasis also has a significant impact on patients’ quality of life.

• 2% of the world’s population.

• Two-thirds of affected individuals were suffering from mild psoriasis, while one-third had more severeinvolvement.

• Psoriasis can first appear at any age, from infancy to the eighth decade of life. Two peaks in age of onset have been reported: one at 20–30 years of age and a second peak at 50–60 years.

• Age of onset is earlier in women than in men

• Are important in psoriasis also play a role in the clinical course of psoriasis.

• Positive family history has been reported by 35% to 90% of patients with psoriasis.

• If both parents had psoriasis, the risk of their childdeveloping psoriasis is 41%.

• There is a two- to three fold increased risk of psoriasis in monozygotic twins as compared to dizygotic twins.

• Psoriasis is associated with HLA-Cw6.

• HLA-Cw6 is strongly linked to the age of onset of psoriasis 90% of the patients with early-onset psoriasis, in 50% of those with late-onset psoriasis.

MHC genes resides on chromosome 6

• Classic genome-wide linkage analysis has identified at least nine psoriasis susceptibility regions (PSORS1–9)in different chromosomal locations.

• By far the most important genetic region is PSORS1 (on chromosome 6p), which is estimated to account for up to 50% of psoriasis risk.

• PSORS1 contains genes such as HLA-C (with the HLA-Cw6 risk allele) and corneodesmosin (CDSN).

• Most of the genes that have been implicated have immune-relatedfunctions, underscoring the importance of the innate and adaptiveimmune systems in the pathogenesis of psoriasis.

• Skin-derivedantimicrobial peptides: expressed at high levels inpsoriatic skin.

• Associated genes encode proteins with roles in particular immunologic and signaling pathways, especially those involving tumor necrosis factor (TNF), NF-κB, interferons (IFN) and interleukin (IL)-23/Th17 cells.

• In contrast, relatively few genes that encode skin-specific proteins have been associated with psoriasis.

• The ERAP1 gene encoding an aminopeptidase involved in MHC class I antigen processing is only associated with psoriasis risk in individualscarrying the HLA-Cw6 risk allele, providing evidence for the role of an MHC-restricted antigen and its presentation through HLA-C in the pathogenesis of psoriasis.

PSORIASIS CLASSIFICATION

• No one classification of psoriasis satisfies all the mentioned requirements. Usually, criteria are intermingled.

1. PSORIASIS VULGARIS (Most common subtype is chronic plaque psoriasis)

2. GUTTATE PSORIASIS.

3. ERYTHRODERMIC PSORIASIS.

4. PUSTULAR VARIANTS.

5. PSORIATIC ARTHRITIS

1. Scalp psoriasis & sepopsoriasis

2. Nail psoriasis

3. Palmoplantar psoriasis

4. Flexural psoriasis

5. Oral psoriasis

6. Napkin psoriasis

• Psoriasis can present with a spectrum of cutaneous manifestations. At any one point in time, different variants may coexist in a particular individual, but the skin lesions all share the same important hallmarks: erythema, thickening and scale.

SYMPTOMS

• The major symptom is disfigurement.

• Over 65% of patients complain of itching.

• Patients may report that their disease worsens in the winterand improves in the summer.

• The most common variant of psoriasis vulgaris.

• Characterized by sharplydemarcated and erythematouspapulosquamous lesions (Dry, thin, silvery-white scales).

• Irregular, discoid or oval in shape.

Relatively symmetric distribution.

• The scalp, elbows, knees and presacrum are sites of predilection, as are the hands and feet. The genitalia are involved in up to 45% of patient.

• Other sites of predilection include the umbilicus and the intergluteal cleft

• Plaques may persist for months to yearsat the same locations.

• Rich red color: often referred to as 'salmon pink‘. This quality of color is of special diagnostic value to differentiate psoriasis from eczema in lesions on the palms, soles and scalp.

• In the fair-skinned individual, the color is less rich and almost magenta pink.

• In dark-skinned races, the quality of the color is lost.

• Their highly characteristic sharp demarcation, psoriatic lesions are sometimes surrounded by a paleblanching ring, which is referred to as Woronoff’s ring.

• During exacerbations, psoriatic lesions often itch. Pinpoint papules surrounding existing psoriatic plaques indicate that the patient is in an unstable phase of the disease. In addition, expanding psoriatic lesions are characterized by an activeedge with a more intense erythema. Inflamed lesions may be slightly tender.

• The involution of a lesion usually starts in its center, resulting in annularpsoriatic lesions.

• Annular, well-demarcated, erythematous plaques with adherent, silvery-white scales and centralclearing. The elbows, knees, scalp, intergluteal region, lower back, periumbilical area, palms, and soles are often involved.

• The annular pattern occurs with plaque or pustular psoriasis.

• The isomorphic phenomenon (Koebner reaction): 38-76% of patients recognize that new lesionsappear at sites of injury 7-14 days after the skin has been injured

• In some patients, so-called reverse-Koebner reactions have also been noted in which preexisting psoriaticplaques actually clear after injuryor trauma to the skin.

• If the superficial silvery whitescales are removed via curettage (grattage method), a characteristic coherence is observed, as if one has scratched on a wax candle (“signe de la tache de bougie”).

• Subsequently, a surfacemembrane is seen, which will also come off as a whole.

• If the latter is removed, then a wet surface is seen with characteristic pinpoint bleeding. This finding, called Auspitz sign, is the clinical reflection of elongated vessels in the dermal papillae together with thinning of the suprapapillary epidermis.

Psoriasis geographica:The borders may resemble a land map

GENITAL PSORIASIS

It is a method to estimateseverity of psoriasis in order to evaluate the clinical efficacyof new treatments.

This is a single score calculated from the body surface area involved (utilizing a seven-point score for involvement in each of four anatomic areas –head, upper extremities, trunkand lower extremities 0 to 6).

• and from the scores for erythema, induration and scaling (each scored using a five-point score from 0 to 4).

• Total score ranges 0-72.

• Characterized by eruption of small (0.5 to 1.5 cm in diameter) papules over the upper trunk and proximal extremities.

• More commonly seen in children and adolescents and is frequently precededby an upper respiratory tract infection.

• In over half of the patients, an elevated antistreptolysin O, antiDNase B or streptozyme titer is found, indicating a recent streptococcal throat infection

• The disease affects all body sites.

• Erythema is the most prominent feature with superficial scaling.

• Patients with erythrodermic psoriasis loseexcessive heat because of generalizedvasodilatation, and this may cause hypothermia.

• Psoriatic skin is often hypohidrotic due to occlusion of the sweat ducts.

• There is an attendant risk of hyperthermia in warm climates.

• Lower extremity edema is common secondary to vasodilatation and loss of protein from the blood vessels into the tissues.

• High-output cardiac failure and impaired hepatic and renal function may also occur.

• Erythrodermic psoriasis may start from worsening of plaque psoriasis to involve most body areas or it may be a response to treatment as a generalized Koebner reaction.

• Onset can be gradual or acute.

• Clues to the diagnosis of psoriatic erythroderma include previous plaques in classic locations, characteristic nailchanges, and facial sparing.

A. Generalized pustular psoriasis: Generalized pustular psoriasis during pregnancy is also referred to as impetigo herpetiformis. Four distinct patterns of generalized pustular psoriasis can be seen

i. von Zumbusch Type.

ii. Annular pattern.

iii. Exanthematic type.

iv. “Localized” pattern.

B. Localized pustular psoriasis:

i. Pustulosis of the palms and soles (palmoplantar pustulosis.

ii. Acrodermatitis continua of Hallopeau.

• It is an unusual rare life-threatening manifestation of psoriasis, It is usually preceded by other forms of the disease.

• The disease occurs abruptly as attacks characterized by fever malaise, and leukocytosis that lasts several days and a sudden generalized eruption of sterilepustules 2 to 3 mm in diameter.

• Various provoking factors are known including:

1. Withdrawal of systemic corticosteroids

2. Other systemic therapies: lithium, aspirin, indomethacin, iodide and some beta-blockers

3. Infections

4. Irritating topical treatment: coal tar, dithranol

5. Hypocalcemia.

• The pustules are disseminated over the trunk & extremities, including nail beds, palms, & soles.

• The pustules usually arise on highly painful erythematous skin, first as patches and then becoming confluent as the disease becomes more severe disease & lead to erythroderma.

• After several days, the

pustules usually resolve and

extensive scaling is observed.

Sometimes, chronic plaques

of psoriasis, if present, can

resolve.

• Onycholysis and shedding of

nails; hair loss of the telogen

defluvium type, 2–3 months

later; circinate desquamation

of tongue

• It is a rare variant of pustular psoriasis.

• Lesions may appear at the onset of pustular psoriasis, with a tendency to spread and form enlarged rings, or they may develop during the course of generalized pustular psoriasis.

• The characteristic features are pustules in advancing edge on a ring-like erythema.

• Healing occurs centrally.

Annular pustular psoriasis. Multiple annular

inflammatory plaques studded with pustules.

As the lesions enlarge, there can be central

clearing, dry desquamation

• lesions are identical to annularpustular psoriasis but occur duringpregnancy.

• Onset is usually early in the thirdtrimester and persists until delivery.

• It tends to develop earlier in subsequent pregnancies.

• It is often associated with hypocalcaemia.

• There is usually no personal or familyhistory of psoriasis.

• This is an acute eruption of small pustules, abruptly appearingand disappearing over a few days.

• It usually follows an infection or may occur as a result of administration of specific medications, e.g. lithium.

• Systemic symptoms usually do not occur.

• There is overlap between this form of pustular psoriasis and pustular drug eruptions, also referred to as acute generalizedexanthematous pustulosis (AGEP)

• Sometimes pustules appear within or atthe edge of existing psoriatic plaques.

• This can be seen during the unstablephase of chronic plaque psoriasis and following the application of irritants, e.g. tars.

• Characterized by “sterile” pustules of the palmoplantar surfaces admixed with yellow–brown macules scalyerythematous plaques.

• A minority of patients have chronicplaque psoriasis elsewhere.

• In contrast to the natural history of generalized pustular psoriasis, the pustules remain localized to the palmoplantar surfaces and the course of this disease is chronic.

• Focal infections and stress have been reported as triggering factors and smoking may aggravate the condition.

• Pustulosis of the palms and soles is one of the entities most commonly associated with sterile inflammatorybone lesions, for which there are several names: chronic recurrent multifocalosteomyelitis, pustulotic arthro-osteitis, and SAPHO syndrome. Several neutrophilic dermatoses are associated with SAPHO.

• Synovitis, Acne, Pustulosis, Hyperostosis, and Osteomyelitis

• Acne fulminans, acne conglobata, pustular psoriasis, and palmoplantar pustulosis

• Chest wall is most site of musculoskeletal complaints

• It is rare sterile, pustular eruption distal portions of

fingers or sometimes toes slowly extends proximally.

• Often triggered by localized trauma or infection at

the distal phalanx (the tip of the digit).

• 80% begin in only one digit, most commonly thumb.

• During acute flare-ups, the skin of the distal phalanx becomes red and scaly

and develops small pustules.

• The pustules often join together and on bursting, reveal a painful, red and

glazed area where new pustules then develop.

• Pustulation of the nail bed and nail matrix can

result in onychodystrophy and anonychia (loss of

nail).

• Slowly, the disease can rarely spread proximally to

affect the hand, forearm and/or foot.

• There may be osteolysis resulting in a wasted and

tapered tip of finger or toe.

• Transition into other forms of psoriasis can occur

and may be accompanied by generalized

pustular psoriasis of the Zumbusch type and

annulus migrans of the tongue.

• Develops in approximately 10-30 %of those with psoriasis.

• In approximately 50% of those affected arthritis appears onedecade after the onset of psoriasis, whereas in the remainder the onset occurs with the disease or precedesit In a minority of patients .

• More prevalent among patients with relatively severe psoriasis.

• Inflammation of the interphalangeal joints – both distal (DIP mainly) and proximal (PIP) – of the hands and feetis the most common presentation of psoriatic arthritis.

• Involvement of the PIP or both the DIP and PIP joints of a single digit can result in the classic “sausage” digit.

CLASSIFICATION PSORIATIC ARTHRITIS (Five Types)

1. Mono- and asymmetric oligoarthritis.

2. Arthritis of the distal interphalangeal joints.

3. Rheumatoid arthritis-like presentation.

4. Arthritis mutilans.

5. Spondylitis and sacroiliitis.

• Early diagnosis of psoriatic arthritis is important, as disease progression often results in loss of function.

• There are no specific serologictests for establishing the diagnosisof psoriatic arthritis.

• X-Ray: Enthesitis (inflammation of the insertion points of tendons and joints into bone).Periostealnew bone formation.

•The blue arrow = a normal joint space.

• Red arrow = “cup and saucer” effect of the fourth metatarsal

bone being jammed into the base of the fourth toe.

•The yellow circle = “Pencil

appearance” destruction characteristic of the disease.

1. Scalp psoriasis & Sebopsoriasis

2. Nail psoriasis

3. Palmoplantar psoriasis

4. Flexural psoriasis

5. Oral psoriasis

6. Napkin psoriasis

• The scalp is one of the most common sites for psoriasis. Unless there is complete confluence, the individual lesions are discrete, in contrast to the less well-defined areas of involvement in seborrheic dermatitis.

• At times, however, it is not possible to distinguish seborrheic dermatitis from psoriasis, and the two disorders may coexist.

• In very severe cases there may be some temporary mild localised hair loss but scalp psoriasis does not cause permanent balding.

• The back of the head is a common

site for psoriasis, but multiple discrete

areas of the scalp or the whole scalp

may be affected.

• Scalp psoriasis is characterized by

thick silvery-white scale over well-

defined red thickened skin.

• Psoriasis may extend slightly beyond

the hairline (facial psoriasis).

• The lesions of psoriasis often advance onto the periphery of the face, the retroauricular areas and the upper neck.

• The scales sometimes have an asbestos-likeappearance and can be attached for some distance to the scalp hairs (pityriasis amiantacea).

• Pityriasis amiantacea can be seen in:

1. Scalp psoriasis is the most common cause

2. Seborrheic dermatitis

3. Secondarily infected atopic dermatitis

4. Tinea capitis (very rare)

• Is an overlap between psoriasis and seborrhoeic dermatitis.

• It is a common clinical entity.

• Localized to seborrheic areas (scalp, ears, glabella, nasolabial folds, perioral and presternal areas, and intertriginous areas).

• It presents with erythematous plaques with less silvery scale than psoriasis and more yellowish, greasy scale.

• But sebopsoriasis has a deeper red color, more defined margins and a thickerscale than typically seen in seborrhoeic dermatitis alone. It is also less likely to clear up with anti-dandruff shampoo.

• In the absence of typical findings of psoriasis elsewhere, distinction from seborrheic dermatitis is difficult.

• Reported in 10–80% of psoriatic patients.

• The fingernails are more affected than toenails.

• Psoriasis affects the nail matrix, nail bed and hyponychium.

• Nail pitting is the commonest feature occurs due to small parakeratotic foci in the proximal portion of the nail matrix.

• Leukonychia and loss of transparency (less common findings) are due to involvement of the mid portion of the matrix.

• If the whole nail matrix is involved, a whitish, crumbly, poorly adherent “nail” is seen.

• Psoriatic changes of the nail bed result in the “oil spot” or “oil drop” phenomenon, which reflects exocytosis of leukocytesbeneath the nail plate.

• Splinter hemorrhages are the result of increased capillary fragility.

• Subungual hyperkeratosis and distalonycholysis are due to parakeratosis of the distal nail bed. Vigorous removal of distal subungual debris may be an exacerbating factor.

STOP

• Subungualhyperkeratosis/ Splinter hemorrhages

• Thickening/ Transparency loss

• Oil spot /Onycholysis

• Pitting

Psoriasis may predominantly affect the

palms and soles in various ways:

1. Typical scaly, red patches similar to

psoriasis elsewhere (Chronic plaque

psoriasis).

2. Generalised thickening and scaling of

the palms and soles (psoriatic

keratoderma).

3. Sheets of tiny yellow-brown pustules

(palmoplantar Pustulosis).

• Palms and soles affected by

psoriasis tend to be partially or

completely red, dry and thickened,

less often deep painful fissures.

• It can be quite hard to differentiate

from hand dermatitis and other

forms of keratoderma, but signs of

psoriasis elsewhere may help make

a diagnosis.

• Characterized by shiny, smooth, pink to red, sharply demarcated thin plaques.

• Scaling is usually minimal or absent.

• Often a central fissure in the depth of the skin crease is seen.

• When flexural areas are the only sites of involvement, the term “INVERSE” psoriasis is sometimes used.

• Localized dermatophyte, candidal or bacterial infections can be a trigger for flexural psoriasis.

Common sites of flexural psoriasis are:

1. Axillae

2. Inguinal

3. Inframammary

4. Umbilicus

5. Penis

6. Vulva

7. Natal (intergluteal) cleft

8. Around the anus

9. Retroauricular

Complications of flexural psoriasis include:

1. Irritation from heat and sweat.

2. Secondary fungal infections particularly Candida albicans.

3. Lichenification from rubbing and scratching – this is a particular problem around the anus where faecal material irritates causing increased itching.

4. Sexual difficulties because of embarrassment and discomfort.

5. Atrophy of skin due to long term overuse of strong topical steroids.

• Relatively uncommon.

• It is more likely to develop in those with the more severe forms of psoriasis, especially pustular psoriasis.

There are several types of oral lesion:1. Irregular red patches with raised yellow or

white borders, similar to geographictongue. This is the most common.

2. Redness of the oral mucosa3. Ulcers4. Desquamative gingivitis5. Pustules (in pustular psoriasis)

• Migratory asymptomatic annular erythematouslesions with hydrated white scale (ANNULUS MIGRANS) have been observed in patients with acrodermatitis continua of Hallopeau and generalized pustular psoriasis.

• It has been postulated to be an oral variant of psoriasis, as these lesions show several histologic features of psoriasis.

• However, geographic tongue is a relatively common condition and is seen in many nonpsoriatic individuals.

• Usually begins between the ages of 3-6months.

• First appears in the napkin areas as a confluent persistent, well-circumscribed, symmetrical, shiny, red, scaly or maceratedplaques; other sites may be involved.

• It usually clears up after a few months to a year, but may later generalize into plaquepsoriasis on the trunk & limbs.

• Family history common.

• Patients with extensive BSA involvement often afraid to be in public or wearrevealing clothing.

• Some patients shed scale constantly onto clothing, furniture, floors, etc.

• Many patients eventually become depressed if disease poorly controlled.

• Patients often motivated to try anything that might be effective.

• Chronic plaque psoriasis is in most cases a lifelong disease, manifesting at unpredictable intervals.

• Spontaneous remissions, lasting for variable periods of time, may occur in the course of psoriasis in up to 50 % of patients.

• The duration of remission ranges from 1 year to severaldecades

• Guttate psoriasis is often a self-limited disease, lasting from 12 to 16 weeks without treatment. It has been estimated that one-third to two-thirds of these patients later develop the chronic plaque type.

• Erythrodermic and generalized pustular psoriasis have a poorer prognosis, with the disease tending to be severe and life threatening.

• Parakeratosis

• Orthokeratosis of normal basket-weave type

• Loss of granular layer

Dilated vessels in dermal papillae, perivascular cuffing with lymphocytes

• Munro micro-abscesses i.e. accumulation of neutrophil remnants in the stratum corneum, surrounded by parakeratosis

• Spongiform pustule of Kogoj: An infiltration of neutrophils into necrotic Malpighian layer in which the cell walls persist as a sponge-like

network

• Commonly seen in pustular psoriasis

• Test tube-like elongation of rete ridges

• Relatively thin suprapapillary plates

• Elongated club-shaped dermal papillae

Parakeratosis

Neutrophils

Hyperkeratosis

Mild Moderate Marked

Suprapapillary thinning

Mild Moderate Marked

Mild Moderate Marked

Capillary dilatation

• Guttate psoriasis. Superficial

perivascular, predominantly

lymphocytic infiltrate

• Minimal dermal edema.

• The overlying epidermis has

psoriasiform hyperplasia.

• Notice how the stratum

granulosum (on right) disappears

underneath the mound of

parakeratosis in the stratum

corneum (in center)

• Fully developed guttate lesion or the marginal zone of an enlarging psoriatic plaque is designated as an “active lesion”.

• Exaggerated spongiform pustules of Kogoj and microabscesses of Munro, the histologic hallmarks of “active” psoriasis, are seen also in pustular psoriasis.

• Neutrophils are typically prominent in active lesions and in the marginal zone of expanding plaques,

• Marked edema is seen, especially at the tops of the papillae in the active lesion.

• P: (Pink papules /Plaques /Pinpoint bleeding <Auspitz sign> /Physical injury <koebner phenomenon>/Pitting of nails)

• S: (Silver scale/Sharp margins)

• O: (Onycholysis/Oil spots)

• R: (Rete Ridges with Regular elongation)

• I: (Itching)

• A: (Arthritis/Abscesses <Munro-Kogoj>/Acanthosis)

• S: (Stratum cornium with retained nuclei <parakeratosis>)

• I: (Immunologic)

• S: (Stratum granulosum absent/Subungual hyperkeratosis/Splinter hemorrhages)

CAN BE DIVIDED INTO LOCAL (EXTERNAL) AND SYSTEMIC FACTORS:

I. Local factors1. Trauma to the skin

2. Sunlight

II. Systemic factors1. Infections

2. Endocrine factors

3. Psychogenic stress

4. Drugs

5. Alcohol consumption

6. Smoking

7. Obesity

8. Cold Weather

1. Trauma: • Physical, chemical, electrical, surgical, infective and

inflammatory types of injury or even excessive scratching can aggravate or precipitate localized psoriasis (Koebner phenomenon).

• KP is observed in ~25% of patients with psoriasis.

• A particular patient may be “Koebner -ve” at one point in time and later become “Koebner +ve”.

• The Koebner phenomenon suggests that psoriasis is a systemic disease that can be triggered locally in the skin.

• The lag time between the trauma and the appearance of skin lesions is usually 2–6 weeks.

2. Sunlight: • Most patients generally consider sunlight to be

beneficial for their psoriasis. Most report a decrease in illness severity during the summermonths or periods of increased sun exposure; however, a small minority find that their symptoms are aggravated by strong sunlight

1. Infections: • Pharyngeal streptococcal (most common)

infections have been shown to produce guttatepsoriasis.

• Streptococci can also be isolated from other sites, e.g. dental abscesses, perianal cellulitis, impetigo.

• An increase in psoriasis activity was observed in HIVinfected patients.

• Localized dermatophyte, candidal or bacterialinfections can be a trigger for flexural psoriasis.

2. Endocrine factors: • Psoriasis severity has been noted to fluctuate with

hormonal changes. Disease incidence peaks at puberty and during menopause.

• Pregnant patients' symptoms are more likely to improve(> 50% of the patients) than worsen (impetigo herpetiformis). In contrast, the disease is more likely to flare in the postpartum period.

• Hypocalcemia has been reported to be a triggering factor for generalized pustular psoriasis. Although active vitamin D3 analogues improve psoriasis, abnormal vitamin D3 levels have not been shown to induce psoriasis.

3. Psychogenic stress: • Psychogenic stress is a well-established

systemic triggering factor in psoriasis.

• It has been associated with initialpresentations of the disease as well as flares of pre-existing psoriasis.

• Pruritus associated with increased anxiety or depression may promote scratching and a Koebner reaction.

4. Drugs: • Several drugs have been incriminated as

inducers of psoriasis. Rapid taper of systemic corticosteroids can induce pustular psoriasis as well as flares of plaque psoriasis.

• LIMBS

1. L: Lithium

2. I: Interferon

3. M: anti-Malarials

4. B: Beta blockers

5. S: Steroids/NSAIDs

5. Alcohol consumption: • Alcohol consumption has been associated

with psoriasis.

6. Smoking: • An increased risk of chronic plaque psoriasis

exists in smokers

• Smoking have a role in the onset of psoriasis.

7. Obesity: • Obesity has been associated with psoriasis.

• Some studies have suggested that obesity appeared to be a consequence of psoriasis, whereas other studies have suggested that weight gain often proceeds the development of psoriasis.

8. Cold Weather: • Sudden exposure to cold weather can be a

trigger for a flare-up.

• In general, psoriasis symptoms appear morefrequently at high altitudes and in cold weatherclimates than in tropical ones.

• Psoriasis is regarded as a T-cell-driven disease.

• The role of lymphocyte subsets as well as cytokines involved in chemotaxis, homing and activation of inflammatory cells has been extensively investigated, culminating in the development of novel therapeutic approaches.

• Although some regard psoriasis as an autoimmune disease, to date no true auto-antigen has been definitively identified. It is considered immune mediated disease by both innate & adaptive immune responses.

EVIDENCES SUPPORTING INVOLVEMENT OF THE INNATE IMMUNE SYSTEM IN DEVELOPMENT OF PSORIASIS “6”:

1. DCs in both uninvolved and lesional psoriatic skin have potent immunostimulatory capacity, There is an increased number of dermal DCs in psoriatic skin, and they have an enhanced ability to activate T cells when compared to DCs from normal skin.

2. Natural killer (NK) cells are found in psoriatic skin lesions; they interact with CD1d on keratinocytes. The resulting production of IFN-γ could contribute to additional immune stimulation.

3. Neutrophils found in the epidermis, either in spongiform pustules of Kogoj or in microabscesses of Munro but they are not considered to be the primarycause of psoriasis.

4. The innate immune cytokines IL-1, IL-6 and TNF-α are upregulated in psoriatic skin. TNF-α is a particularly relevant cytokine and its importance is underscored by the therapeutic efficacy of TNF-α inhibitors.

5. Chemokines: Increased presence of several chemokines and their cognate receptors in psoriatic lesions.

6. AMP: such as (hBD1-2) and secretory leukocyte protease inhibitor (SLPI) and cathelicidin LL37 are highly expressed in lesional psoriatic skin.

EVIDENCES SUPPORTING INVOLVEMENT OF THE ADAPTIVE IMMUNE SYSTEM IN DEVELOPMENT OF PSORIASIS “6”:

1. The presence of specific T-cell subsets within the epidermis and dermis of lesional skin.

2. Disappearance or development of psoriasis following hematopoietic stem celltransplantation.

3. Number of drugs that affect T-cell function (e.g. by targeting the IL-2 receptor, CD2, CD11a and CD4) were found to result in clinical improvement of psoriasis.

4. Analysis of lesional T-cells has shown oligoclonality, possibly triggered by exogenous microbial or viral antigens or cross-reacting autoantigens, e.g. keratins,DNA, RNA.

5. The association of psoriasis with particular MHC alleles, such as HLA-Cw6, and (in individuals carrying such alleles) variants in the ERAP1 gene encoding an aminopeptidase involved in Ag processing.

6. The adaptive immune cytokines:i. Increased amounts of Th1 cytokines (TNF-α, IFN-γ and IL-2) are observed in psoriasis.

ii. The striking response of psoriasis to ustekinumab (a human monoclonal antibody against the p40 subunit of IL-12 and IL-23).

iii. Circulating levels of IL-22 (secreted by Th17 & Th22) correlate with disease severity.

PHASES OF IMMUNOPATHOGENESIS OF PSORIASIS

1. Initiation phase

2. Innate immune response

3. Adaptive immune response

4. Epidermal hyperproliferation

1. Initiation phase• In genetically predisposed individuals with

occurrence of triggering environmentalfactors complexes of self DNA or RNA(from stressed keratinocytes) plus antimicrobial peptide LL37.

• This leads to a breaking of tolerance to self nucleic acids and explains the start of the inflammatory cascade in psoriasis.

2. Innate immune response • Self DNA or RNA / LL37 complex trigger

IFN-α release by plasmacytoid dendriticcells (pDCs) via a Toll-like receptor 9 (TLR9)-dependent mechanism thereby activating dermal DCs (dDCs).

• Activated dDCs start migration to regional lymph node.

3. Adaptive immune response

• dDCs present an as-yet-unknown antigen (either of self or of microbialorigin) to naïve T cells and (via secretion of different types of cytokines by DCs) costimulatory signals are sent to the T cell as a result of several other interactions promote their differentiation into T helper 1 (Th1), Th17 and Th22 cells.

3. Adaptive immune response • Th1 cells expressing CLA, CXCR3 and CCR4.

• Th17 cells expressing CLA, CCR4 and CCR6.

• Th22 cells expressing CCR4 and CCR10.

• These cells migrate via lymphatic and blood vessels into psoriatic dermis, attracted by the keratinocyte-derived chemokines CCL20, CXCL9–11 and CCL17. CLA Expressed on their surface binds to E-selectin on vascular endothelium of the affected area of the skin.

3. Adaptive immune response • At the dermal–epidermal junction, memory CD8 +

cytotoxic T cells (Tc1) expressing very-late antigen-1 (VLA-1) bind to collagen IV, allowing entry into the epidermis and contributing to disease pathogenesis by releasing both Th1 and Th17 cytokines.

4. Epidermal hyperproliferation• Th1 cells release IFN-γ, TNF-α and IL-2 which amplify the

inflammatory cascade, acting on keratinocytes and dDCs.

• Th17 cells secrete IL-17A and IL-17F (and also IFN-γ and IL-

22), which stimulate keratinocyte proliferation and its

release of β-defensin 1/2, S100A7/8/9 and the neutrophil-

recruiting chemokines CXCL1, CXCL3, CXCL5 and CXCL8.

• Th22 cells secrete IL-22, which induces further release of

keratinocyte-derived T cell-recruiting chemokines.

• Keratinocytes also release vascular endothelial growth

factor (VEGF), basic fibroblast growth factor (bFGF), and

angiopoietin (Ang), thereby promoting neoangiogenesis.

4. Epidermal hyperproliferation• Neutrophils infiltrate the stratum corneum and

produce reactive oxygen species (ROS) and α-defensin with antimicrobial activity, as well as CXCL8, IL-6 and CCL20.

• Cross-talk between keratinocytes, producing TNF-α, IL-1β and transforming growth factor-β(TGF-β), and fibroblasts, which in turn release keratinocyte growth factor (KGF), epidermalgrowth factor EGF) and TGF-β, contribute to tissue reorganization and deposition of extracellular matrix (e.g. collagen, proteoglycans).

4. Epidermal hyperproliferation• Keratinocytes within psoriatic plaques express

STAT-3. STAT-3 induced the upregulation of a number of genes relevant for psoriasis, such as those encoding ICAM-1 and TGF-α; the latter has been shown to stimulate proliferation of keratinocytes in psoriasis via an autocrine loop.

• As STAT-3 is activated by a variety of cytokinesincluding IL-22 as well as IL-6, IL-20 and IFN-γ, this could represent a link between keratinocyte activation and immune cells in the development of the psoriatic lesion.

Hyperproliferation

of keratinocytes

Role of TNF-α in the pathogenesis of psoriasis:• Elevated concentration in lesional skin.

• Induces migration & maturation of DCs.

• Stimulates proinflammatory cytokines production.

• Induces proliferation of keratinocytes.

• Induces vascular proliferation.

• Psoriasis and psoriatic arthritis: Dr Arvind Kaul, Royal Free Hospital

• Bolognia 3rd ed

• http://dermnetnz.org

• Google images