PSORIASIS

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PSORIASIS:

PSORIASIS Etymology : Gk, psoriasis , itch Dr. Angelo Smith M.D WHPL

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Psoriasis is a disease which affects the skin is a disease which affects the skin and joints .

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It commonly causes red scaly patches to appear on the skin. The scaly patches caused by psoriasis, called psoriatic plaques, are areas of inflammation and excessive skin production. Skin rapidly accumulates at these sites and takes a silvery-white appearance. Plaques frequently occur on the skin of the elbows and knees, but can affect any area including the scalp and genitals.

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Psoriasis is an inflammatory skin disease in which skin cells replicate at an extremely rapid rate. New skin cells are produced about eight times faster than normal--over several days instead of a month--but the rate at which old cells slough off is unchanged. This causes cells to build up on the skin's surface, forming thick patches, or plaques, of red sores (lesions) covered with flaky, silvery-white dead skin cells (scales).

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The disorder is a chronic recurring condition which varies in severity from minor localized patches to complete body coverage. Fingernails and toenails are frequently affected ( psoriatic nail dystrophy ). Psoriasis can also cause inflammation of the joints, which is known as psoriatic arthritis .

Genetics:

Genetics Psoriasis was present in 73% of monozygotic twins compared with 20% in dizygotic twins . When both parents are affected by psoriasis, the rate in siblings is as high as 50%. When one parent is affected, the rate is 16.4% When neither parent has psoriasis, only 7.8% of siblings of probands are affected Other studies have shown that 36-71% of patients with psoriasis have one relative who is also affected by psoriasis

Exacerbating Factors:

Exacerbating Factors Local factors Trauma: e g, physical, chemical, electrical, surgical, infective, and inflammatory types of injury or even excessive scratching can aggravate or precipitate localized psoriasis (Koebner reaction) Sunlight: Most patients generally consider sunlight to be beneficial for their psoriasis. Most report a decrease in illness severity during the summer months or periods of increased sun exposure; however, a small minority find that their symptoms are aggravated by strong sunlight.

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Systemic factors Infection: Pharyngeal streptococcal infections have been shown to produce guttate psoriasis. Some evidence suggests that subclinical streptococcal colonization or overgrowth could be responsible for refractory plaque psoriasis. An increase in psoriasis activity was observed in HIV infected patients. Drugs: Some drugs cause an exacerbation of psoriasis. Lithium and withdrawal from systemic corticosteroids are well known to cause flares of disease. Beta-blockers, antimalarials, and nonsteroidal anti-inflammatory drugs (NSAIDs) have also been implicated.

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Psychogenic/emotional factors: Many patients report an increase in psoriasis severity with psychological stress. A clear cause-and-effect relationship between disease exacerbation and stress unfortunately has not been proven but, pruritus associated with increased anxiety or depression may promote scratching and a Koebner reaction.

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Smoking: An increased risk of chronic plaque psoriasis exists in smokers Alcohol: Alcohol is considered a risk factor for psoriasis Endocrine: 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 than worsen. In contrast, the disease is more likely to flare in the postpartum period

HYPOTHESIS:

HYPOTHESIS two main The first considers psoriasis as primarily a disorder of excessive growth and reproduction of skin cells. The problem is simply seen as a fault of the epidermis and its keratinocytes .

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The second hypothesis sees the disease as being an immune-mediated disorder The second hypothesis sees the disease as being an immune-mediated disorder in which the excessive reproduction of skin cells is secondary to factors produced by the immune system. T cells (which normally help protect the body against infection) become active, migrate to the dermis and trigger the release of cytokines (tumor necrosis factor-alpha TNFα, in particular) which cause inflammation and the rapid production of skin cells. It is not known what initiates the activation of the T cells. The immune-mediated model of psoriasis has been supported by the observation that immunosuppressant medications can clear psoriasis plaques.

Histopathology:

Histopathology T-cell mediated inflammatory Epidermal hyper proliferation (6 times over) 2 O to activation of immune system Altered maturation of skin - immature Inflammation Vascular changes – new angiogenesis

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16 DERMIS STRATUM BASALE STRATUM SPINOSUM STRATUM GRANULOSUM STRATUM CORNEUM Proliferation Immaturity Neutrophil accumulation Disorganized N O R M A L P S O R I A S I S

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CLINICAL PATTERNS

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Erythematous, raised patches with silvery scales Symmetric Pruritic/ Painful Pitting Nails Arthritis in 10-20% of patients

Psoriasis: Clinical Presentation :

21 Psoriasis: Clinical Presentation

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Plaque psoriasis (psoriasis vulgaris) is the most common form of psoriasis. It affects 80 to 90% of people with psoriasis. Plaque psoriasis typically appears as raised areas of inflamed skin covered with silvery white scaly skin. These areas are called plaques.

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Note: red ring surrounding the silvery plaque

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Guttate psoriasis is characterized by numerous small oval ( Gutta - teardrop-shaped ) spots. These numerous spots of psoriasis appear over large areas of the body, such as the trunk, limbs, and scalp. Guttate psoriasis is associated with streptococcal throat infection

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28 Guttate Psoriasis

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Erythrodermic psoriasis involves the widespread inflammation and exfoliation of the skin over most of the body surface. It may be accompanied by severe itching, swelling and pain. It is often the result of an exacerbation of unstable plaque psoriasis, particularly following the abrupt withdrawal of systemic treatment. This form of psoriasis can be fatal, as the extreme inflammation and exfoliation disrupt the body's ability to regulate temperature and for the skin to perform barrier functions.

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Pustular psoriasis appears as raised bumps that are filled with non-infectious pus (pustules). The skin under and surrounding pustules is red and tender. localized - hands and feet , generalized and randomly on any part of the body.

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Several clinical variants of pustular psoriasis exist: ِ A -generalized Pustular Psoriasis (Von Zumbusch Type) B -annular Pustular Psoriasis C -impetigo Herpetiformis D -acrodermatitis Continua Of Hallopeau

Generalized pustular psoriasis (von Zumbusch type):

Generalized pustular psoriasis (von Zumbusch type) It is usually preceded by other forms of the disease The disease occurs as attacks characterized by fever that lasts several days and a sudden generalized eruption of sterile pustules 2 to 3 mm in diameter

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The pustules are disseminated over the trunk and extremities, including the nail beds, palms, and soles The pustules usually arise on highly erythematous skin, first as patches and then becoming confluent as the disease becomes more severe

Annular Pustular Psoriasis:

Annular Pustular Psoriasis 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 on a ring-like erythema

Impetigo Herpetiformis:

Impetigo Herpetiformis lesions are identical to annular pustular psoriasis but occur during pregnancy Onset is usually early in the third trimester and persists until delivery It tends to develop earlier in subsequent pregnancies It is often associated with hypocalcemia There is usually no personal or family history of psoriasis

Acrodermatitis Continua of Hallopeau:

Acrodermatitis Continua of Hallopeau It is rare sterile, pustular eruption of the fingers or toes slowly extends proximally Continuous pustulation leads to nail destruction and atrophy of the distal phalanx

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38 Nail changes

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In 78% of psoriatic patients Fingernails>Toenails Six changes Onycholysis (= separation from nail bed) and crumbling of the nail Pitting* Subungual debris accumulation Color alterations Thickening of skin under the nails Beau’s Lines going across the nails *Pitting rules out a fungal infection

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42

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Flexural psoriasis (inverse psoriasis) appears as smooth inflamed patches of skin. It occurs in skin folds, particularly around the genitals (between the thigh and groin), the armpits, under an overweight stomach (pannus), and under the breasts (inframammary fold). It is aggravated by friction and sweat, and is vulnerable to fungal infections.

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Psoriatic arthritis involves joint and connective tissue inflammation . Psoriatic arthritis can affect any joint but is most common in the joints of the fingers and toes. This can result in a sausage-shaped swelling of the fingers and toes known as dactylitis. Psoriatic arthritis can also affect the hips, knees and spine (spondylitis). About 10-15% of people who have psoriasis also have psoriatic arthritis.

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In 10-20% of psoriasis patients Distal inter phalangeal joints No elevated serum levels of rheumatoid factors (as seen in rheumatoid arthritis, yet has all other features) Often seen in patients with nail and scalp psoriasis

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Enthesitis(inflammation of the insertion points of tendons and joints into bone) Periosteal new bone formation Asymmetric oligoarthritis & spondylitis 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

Sebopsoriasis:

Sebopsoriasis It is a common clinical entity It presents with erythematous plaques with greasy yellow scales localized to seborrheic areas (scalp, glabella, nasolabial folds, perioral and presternal areas, and intertriginous areas) In the absence of typical findings of psoriasis elsewhere, distinction from seborrheic dermatitis is difficult It may represent a modification of seborrheic dermatitis by the genetic background of psoriasis

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Elephantine psoriasis is an uncommon form characterized by thickly scaling, large plaques, usually on the lower extremities

Napkin psoriasis :

Napkin psoriasis Usually begins between the ages of 3 and 6 months First appears in the napkin areas as a confluent red area with appearance a few days later of small red papules on the trunk that may also involve the limbs These papules have the typical white scales of psoriasis

Geographic tongue:

Geographic tongue Presents as asymptomatic erythematous patches with serpiginous borders, resembling a map The lesions have a migratory character 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

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- Auspitz sign(Grattage test): Removing the scale reveals a smooth, red, glossy membrane with tiny punctate bleeding points. These points represent bleeding from enlarged dermal capillaries after removal of the overlying epithelium

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- 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

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GRADATION OF SEVERITY

PASI Score (Psoriasis Area and Severity Index):

PASI Score (Psoriasis Area and Severity Index) It is a method to estimate severity of psoriasis in order to evaluate the clinical efficacy of new treatments Psoriatic plaques are graded based on three criteria: redness (R) , thickness (T) , and scaliness (S) Severity is rated on a 0-4 scale (0 for no involvement up to 4 for severe involvement) The highest PASI score is 12; the lowest is 0

OLA Photonumeric Guidelines (overall lesion assessment):

58 OLA Photonumeric Guidelines (overall lesion assessment) 0 = none 5 = very severe 4 = severe 3 = moderate 1 = minimal 2 = mild

Psoriasis: Treatment :

Psoriasis: Treatment Lubrication Removal of scales Slow down lesion proliferation Pruritus management Prevent complications Lessen patient stress Season and climate

Topical treatment:

Topical treatment Salicylic acid Keratolytic agents, weak antifungals, antibacterial agents Remove accumulated scale, allow topical agents to pass through AE: irritation, salicylism (N&V, tinnitus)

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Coal Tar Prefered for limited or scalp psoriasis. In 1925, Goeckerman introduced “The Goekerman technique” which uses crude coal tar and UV light for the treatment of psoriasis Can be effective in widespread psoriasis Antimitotic, anti-pruritic No quick onset but longer remission Often combined with SA, UV light therapy 2 types: Crude coal tar and Liquor picis carbonis

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Coal tar, in concentrations 5- 20% can be compounded in creams, ointments, shampoos and and pastes It is often combined with salicylic acid (2-5% ), which by its keratolytic action leads to better absorption of the coal tar Disadvantages include : allergic reactions, folliculitis, it has an unwelcome smell and appearance and can stain clothing and other items. Coal tar is carcinogenic

Dithranol:

Dithranol May restore normal epidermal proliferation and keratinization Useful in thick plaque psoriasis Commonly used with SA 2 treatment approach: long contact and short contact Stains clothes, irritating to normal skin

Vitamin D Analogues:

Vitamin D Analogues Calcipotriene (calcipotriol)”Betdaivonex” Potent topical corticosteroids are superior to calcipotriene. But calcipotriene was more effective than coal tar or anthralin The efficacy of calcipotriene is not reduced with long-term treatment Calcipotriene is applied twice daily Salicylic acid inactivates calcipotriene It is often used in combination with or in rotation with topical corticosteroids in an effort to maximize therapeutic effectiveness while minimizing steroid-related skin atrophy. In view of their efficacy, cosmetic acceptability and relative safety, they may accepted as first-choice therapies in the topical treatment of mild to moderate psoriasis, although cost may be a problem

Topical CS:

Topical CS Anti-inflammatory, immunosuppressive Quick onset than coal tar and dithranol Tachyphylaxis can occur High potent agents used in severe cases, thick plaques AE local and systemic Should not be stopped abruptly – rebound psoriasis

Phototherapy:

Phototherapy UVA, UVB, PUVA UVB prefered Administered by lamp, sunlight exposure alone or in combo with another topical agent PUVA (methoxsalen) given PO 2 hours before UVA or lotion applied 30mins before exposure AE: itch, edema

Phototherapy:

Phototherapy

Determination of the minimal erythema dose (MED):

Determination of the minimal erythema dose (MED) 1-The patient wears a thick cotton shirt which has 10 small, vertical holes on its back 2-The patient is exposed to 50 mj of UV on the back while all the holes are opened

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3-The first hole is closed and another exposure is given By that time the skin under the first hole was exposed to 50 mj of UV while the skin under the second hole was exposed to 100 mj 4-The second hole is closed and the procedure is repeated in the same way (closing an hole and giving a dose) for all the holes 5-After 24-72 hours the skin of the back is examined and the first skin area showing well-defined erythema is determined and the amount of UV causing it is called "the minimal erythema dose"

Dosing:

Dosing Excimer laser PUVA NB-UVB 2-6 MED twice weekly Initial dose 0.5-2.0 J/cm 2 , depending on skin type followed by twice weekly Increase dose by 40% per week until erythema, then maximum 20% per week until a maximum of 15 J/cm 2 Initial dose at 50% of MED followed by 3 treatments /w Lubricate before ttt Increase dose by at least 10-20% of the MED NB-UVB=Narrow-band Ultraviolet B (Wave length 310-331 nm) PUVA=Psoralen +ultraviolet A (Wave length 315–380 nm) Excimer laser (Wave length 308 nm)

Efficacy :

Efficacy Excimer laser PUVA NB-UVB 75% improvement in 72% of patients in an average of 6.2 treatments Induces remission in 70%-90% of patients > 70% improvement study after 4 wk of treatment

Side Effects:

Side Effects Excimer laser PUVA NB-UVB Erythema, blisters, hyperpigmentation, and erosions Similar to NB-UVB but the risk is higher Photodamage Polymorphic light eruption Increased risk of skin aging and skin cancer

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Excimer laser PUVA NB-UVB As NB-UVB Absolute: Light-sensitizing disorder, lactation, melanoma Relative: Age < 10 yr, pregnancy, photosensitizing drugs, non-melanoma skin cancers Absolute: Photosensitivity disorders Relative: Photosensitizing drugs, melanoma, and nonmelanoma skin cancers Contraindications

Systemic Therapy:

Systemic Therapy Immunomodulators Cyclosporin, methotrexate commonly used Antibiotics in case of secondary bacterial infections

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Systemic agents are generally recommended for patients with moderate-to-severe disease. Moderate disease is defined as greater than 5% body-surface area involvement; severe disease is defined by greater than 10%

Efficacy:

Efficacy Acitretin Methotrexate Cyclosporin A Modestly effective as monotherapy May reduce the severity of psoriasis by at least 50% in more than 75% of patients Up to 90% of patients achieve clearance or marked improvement

Side effects:

Side effects Acitretin Methotrexate Cyclosporin A Hepatotoxicity Lipid abnormalities Fetal abnorma-lities or death Alopecia, mucocutaneous toxicity Hyperostosis Chronic use may lead to hepatic fibrosis Fetal abnorma-lities or death Myelosupp-ression Pulmonary fibrosis Nephrotoxicity Hypertension Immuno -suppression Neurotoxicity Increased risk of malignancy

Monitoring :

Monitoring Acitretin Methotrexate Cyclosporin A Baseline CBC and CMP Repeat laboratory tests weekly × 6 wk, then every 2 wk × 2 mo, and then monthly. Monitor BP Baseline CBC, CMP, LFTs Repeat baseline tests weekly during dose escalation, then every 2 wk. Hold if WBC ≤ 4.0 ×10 9 /L, platelet count is < 125 × 10 9 /L, or Hg < 110 g/L BP Baseline CBC CMP, Mg, uric acid, lipids, urinalysis Repeat tests every 2-4 wk , then every month along with BP Acitretin Methotrexate Cyclosporin A Baseline CBC and CMP Repeat laboratory tests weekly × 6 wk, then every 2 wk × 2 mo, and then monthly. Monitor BP Baseline CBC, CMP, LFTs Repeat baseline tests weekly during dose escalation, then every 2 wk. Hold if WBC ≤ 4.0 ×10 9 /L, platelet count is < 125 × 10 9 /L, or Hg < 110 g/L BP Baseline CBC CMP, Mg, uric acid, lipids, urinalysis Repeat tests every 2-4 wk , then every month along with BP

Contraindications :

Contraindications Acitretin Methotrexate Cyclosporin A Absolute: Severe infections Malignancy Absolute: Inherited deficiency of thiopurine methyltransferase enzyme due to increased risk of myelosuppression Liver toxicity Pregnancy Absolute: Prior bone marrow depression Pregnancy Lactation Relative: Renal abnormalities

Use in Pregnancy:

Use in Pregnancy Acitretin Methotrexate Cyclosporin A X category The drug is contraindicated in women who are or may become pregnant D category There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation) C category Studies on animals revealed teratogenic or embryocidal effects and there are no controlled studies in women It should be given only if the potential benefit justifies the potential risk to the fetus

Summary:

Psoriasis is a lifelong condition. There is currently no cure but various treatments can help to control the symptoms. Many of the most effective agents used to treat severe psoriasis carry an increased risk of significant morbidity including skin cancers, lymphoma and liver disease. Psoriasis does get worse over time but it is not possible to predict who will go on to develop extensive psoriasis or those in whom the disease may appear to vanish. Individuals will often experience flares and remissions throughout their lives. Controlling the signs and symptoms typically requires lifelong therapy. Summary

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