Psoriasis Lianjun Chen Huashan Hospital

WHAT IS PSORIASIS? l A common, life-long, genetic, autoimmune skin disease l Characterized by well circumscribed areas of thick, red, scaly skin From the Greek “ psoros ” meaning “ rough, scabby ” From the Greek “ psoros ” meaning “ rough, scabby ” Term first used (along with “ lepra ” ) by Hippocrates ( B.C.) in Corpus Hippocraticum Term first used (along with “ lepra ” ) by Hippocrates ( B.C.) in Corpus Hippocraticum l von Hebra first to distinguish psoriasis from leprosy in 1841

Morbidity rate l Natural population: 0.1%~3%. Estimated 1.25 hundred million patients in the world l China(1984): 0.123%. European country: 1.5%-3%. European country: 1.5%-3%. America: 2.6%. America: 2.6%. Hongkong:0.3%(2005 ) Hongkong:0.3%(2005 )

Prevalence l Equal frequency in males and females l May occur at any age from infancy to the 10 th decade of life l First signs of psoriasis –Females mean age of 27 years –Males mean age of 29 years

Prevalence l Two Peaks of Occurrence –One at years –One at years l Psoriasis in children –Low – between 0.5 and 1.1% in children 16 years old and younger –Mean age of onset - between 8 and 12.5 years

Etiopathogenisis 1.Theory of heredity Family positive of psoriasis is 4~91 ％, Family positive of psoriasis is 4~91 ％, 11.9~32% in china 11.9~32% in china Concordance rate in twins: Concordance rate in twins: monozygotic twins> binovular twins monozygotic twins> binovular twins High frequency in HLA-A1,B17,Cw6,DR7, High frequency in HLA-A1,B17,Cw6,DR7, a multifactorial inheritance disease a multifactorial inheritance disease

l PSORS9 4q31-q32 zhang Xuejun,2002

Psoriasis, an inherited disease If you have psoriasis, what is the risk to: l Your unrelated neighbor? About 2% l Your sibling? 15-20% l Your identical twin? 65-70% l Your child?25%-50%

银屑病的发病机制 罹患银屑病的危险系数： 罹患银屑病的危险系数：  60% of 有一或两个双亲为银屑病  父母同时患病，子女的风险为 50%  单亲患病者，子女的风险为 16%  父母均非银屑病，但有一子女患病，其同胞患病的风险为 15-20%  同卵双生同时发病率为 73%  异卵双生同时发病率为 20%

Etiopathogenisis 2.Theory of infection bacterial infection(esp.streptococcus) bacterial infection(esp.streptococcus) fungal infection fungal infection bacteria fungi bacteria fungi (streptococcus 、 superantigen) (yeast fungus) (streptococcus 、 superantigen) (yeast fungus) lymphocytes activated alternative lymphocytes activated alternative complement complement pathway pathway clonal proliferation clonal proliferation functional disorder of immune system functional disorder of immune system

Etiopathogenisis 3.Abnormal immune function : cellular immunity function reduce partly cellular immunity function reduce partly early skin lesions are infiltrated predominantly by early skin lesions are infiltrated predominantly by lymphocytes lymphocytes autoantibody deposit in the horny layer autoantibody deposit in the horny layer Th1/Th2 disequilibrium theory(Th1 dominant Th1/Th2 disequilibrium theory(Th1 dominant skin disease) skin disease)

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Etiopathogenisis 4.Dysmetabolism: cAMPmetabolic block of arachidonic acid 、 cGMP polyamines shortened epidermal cell transit time, hyperplasia 5.others: psychosis,neuroendocrine,climate,medicine, et al may induce or aggravate the disease.

Clinical Presentation l Erythematous papules/patches/plaques with silvery scales l Symmetric l Pruritic/ Painful （ sometimes ） l Pitting Nails l Arthritis in 10-20% of patients l Exacerbate in winter,improve in summer

Clinical Types l Psoriasis Vulgaris l Psoriasis Arthropathica l Psoriasis Pustulosa l Psoriasis Erythrodermica

Psoriasis Vulgaris red papule/plaque silvery white scales film phenomenon pinpoint bleeding Auspitz’s sign

20 DERMIS STRATUM BASALE STRATUM SPINOSUM STRATUM GRANULOSUM STRATUM CORNEUM Proliferation Immaturity Neutrophil accumulation Disorganized NORMALNORMAL PSORIASISPSORIASIS

Predilection site

CLASSIC ANATOMIC LOCATIONS FOR PSORIASIS Scalp (80%) Scalp (80%) Elbows (78%) Elbows (78%) Legs (74%) Legs (74%) Knees (57%) Knees (57%) Nails (10-55%) Nails (10-55%) Gluteal cleft Gluteal cleft Palms/soles (12%) Palms/soles (12%)

Guttate Psoriasis l Characterized by numerous 0.5 to 1.5 cm papules and plaques l Early age of onset l Most common form in children l Streptococcal throat infection often a trigger l Spontaneous remissions in children l Often chronic in adults

Psoriasis guttata

Chronic Plaque Psoriasis

30 Psoriatic Plaque

Geographic Psoriasis

Rhagades and thickness scales in palms and soles

Fascicle-like hair

Psoriasis of genitalia scantiness of scale

Flexural psoriasis (Psoriasis of vulvae,red plaque with little scaling)

PSORIATIC NAIL CHANGES l Onycholysis l “Oil drops” l “Salmon patches” l Pitting l Subungual debris l Onychodystrophy l Splinter hemorrhages

Thimble pitting in nails

TRIGGERS FOR PSORIASIS Direct skin injury (Koebner phenomenon) Direct skin injury (Koebner phenomenon) Discontinuation of systemic corticosteroids Discontinuation of systemic corticosteroids Cold weather Cold weather Streptococcal pharyngitis Streptococcal pharyngitis Emotional stress Emotional stress Alcohol intake Alcohol intake Smoking Smoking HIV HIV Medications Medications

DRUGS THAT CAN EXACERBATE PSORIASIS * Beta blockers * Beta blockers *Lithium *Lithium *IFN-alpha *IFN-alpha Antimalarials Antimalarials ACE inhibitors ACE inhibitors *Rebound with withdraw of prednisone and cyclosporine *Rebound with withdraw of prednisone and cyclosporine

STAGE OF PSORIASIS Active stage: large amounts of new lesions,red and pruritus Active stage: large amounts of new lesions,red and pruritus Resting stage: dark red lesions without new eruption Resting stage: dark red lesions without new eruption Regression stage: erythema fade, flatten and disappear Regression stage: erythema fade, flatten and disappear

Koebner Phenomenon Mechanical injury,insect bite,cold injury, sun shine et al Mechanical injury,insect bite,cold injury, sun shine et al Normal skin of patients in active stage express typical new lesions Normal skin of patients in active stage express typical new lesions Clinical significance: suggest disease in active stage Clinical significance: suggest disease in active stage

Course of psoriasis l exacerbate in winter,improve in summer l chronic and persistent l clear spontaneously, recur frequently

Diagnosis and differential diagnosis l Diagnosis: lesions,types and stages l Differential diagnosis: –pityriasis rosea –secondary syphilis –Seborrheic dermatitis –chronic eczema

Generalized Pustular Psoriasis l Unusual manifestation of psoriasis l Can have a gradual or an acute onset l Characterized by waves of pustules on erythematous skin often after short episodes of fever of 39˚ to 40˚C l Weight loss l Muscle Weakness l Hypocalcemia l Leukocytosis l Elevated ESR

Generalized Pustular Psoriasis l Cause is obscure l Triggering Factors –Infection –Pregnancy –Lithium –Hypocalcemia secondary to hypoalbuminemia –Irritant contact dermatitis –Withdrawal of glucocorticosteroids, primarily systemic

54 Generalized Pustular Psoriasis

Erythrodermic Psoriasis l Classic lesion is lost l Entire skin surface becomes markedly erythematous with desquamative scaling. l Often only clues to underlying psoriasis are the nail changes and usually facial sparing

Erythrodermic Psoriasis l Triggering Factors –Systemic Infection –Withdrawal of high potency topical or oral steroids –Withdrawal of Methotrexate –Phototoxicity –Irritant contact dermatitis

Erythrodermic Psoriasis

Psoriatic Arthropthy l Develops in approximately % of those with psoriasis l In approximately 50% of those affected arthritis appears one decade after the onset of psoriasis, whereas in the remainder the onset occurs with the disease or precedes it l HLA-B27 positive

The most distinctive features of psoriatic arthritis are The most distinctive features of psoriatic arthritis are l Distal interphalangeal joint arthritis l Dactylitis

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

Step 2 Step 3 Supplementary Tx Step 4 Treatment Step 1

Topical Treatment Emollients Emollients Topical corticosteroids Topical corticosteroids Keratoplastics: Tar, Salicylic acid, Dithranol Keratoplastics: Tar, Salicylic acid, Dithranol Vitamin-D analogues: Calcipotriene, Tacalcitol Vitamin-D analogues: Calcipotriene, Tacalcitol Retinoids ： retinoid acid, Tazarotene Retinoids ： retinoid acid, Tazarotene Calcineurin inhibitors ： Tacrolimus, Pimecrolimus Calcineurin inhibitors ： Tacrolimus, Pimecrolimus Anti IL-8 monoclonal antibody Anti IL-8 monoclonal antibody Others ： sunlight, bath solution, pyrithione zinc aerosol Others ： sunlight, bath solution, pyrithione zinc aerosol

Photo(chemo)therapy l Two types of phototherapy –Ultraviolet B (UVB) –Ultraviolet A + psoralen (PUVA)

UVB l Two types –Broadband UVB ( nm) –Narrowband UVB ( nm) l Treatment is time consuming –2-3 visits/week for several months l Side effect – possibility of experiencing an acute sunburn reaction

PUVA l Consists of ingestion of or topical treatment with a psoralen followed by UVA l Usually reserved for severe, recalcitrant, disabling psoriasis l Time consuming – 2-3 visits/wk; at least 6 weeks l Precautions –Patients must be protected from further UV light for 24 hours post treatment –With oral psoralen, wrap around UV-blocking glasses must be worn for 24 hours post treatment

PUVA l Side effects with oral psoralen –Nausea –Dizziness –Headache l Side effects with PUVA –Early l Pruritus –Late l Skin damage l Increased risk for skin cancer, particularly squamous cell (SCC) and after treatments, increased risk for melanoma

Contraindications to PUVA l Patients less than 12 years of age l Patients with a history of light sensitive disease states l Patients with, or with a history of melanoma l Patients with invasive SCC l Patients with aphakia

Systemic Therapies l Corticosteroids l Antibiotics l Retinoids (acitretin) l Methotrexate l Cyclosporine l Hydroxyurea l Biologic agents

Acitretin l Oral retinoid approved for the treatment of severe psoriasis in adults l Significant improvement can be achieved with 8 weeks of therapy

Acitretin - Contraindications l Patients with severely impaired liver or kidney function l Patients with chronic abnormally elevated blood lipid values l Patients who are taking methotrexate l Ethanol use when on therapy and for 2 months following therapy in female patients

Acitretin l Pregnancy Category X drug product as it is a human teratogen l Contraindicated in pregnant females or those who intend to become pregnant during therapy or any time up to three years post therapy

Acitretin – Side Effects l Those associated with retinoid therapy –Cheilitis –Alopecia –Skin peeling –Dry skin –Pruritus –Rhinitis –Xerophthalmia –Arthralgia

Acitretin– Side Effects l Laboratory Abnormalities –Hypertriglyceridemia (66%) –Decreased HDL (40%) –Hypercholesterolemia (33%) –Elevated liver function tests (33%) –Elevated alkaline phosphatase (10-25%) –Hyperglycemia (10-25%) –Elevated CPK (10-25%) l Hepatitis and jaundice occurred in < 1% of patients in clinical trials on Soriatane

75 Methotrexate l Folic acid antagonist l Usually reserved for severe, recalcitrant, disabling psoriasis l Maximum improvement can be expected after weeks

76 Contraindications - Methotrexate l Nursing mothers l Patients with alcoholism l Alcoholic liver disease l Other chronic liver disease l Patients with overt or laboratory evidence of immunodeficiency syndromes l Patients who have preexisting blood dyscrasias

77 Methotrexate l Pregnancy Category X drug product –Contraindicated in pregnant women with psoriasis –Pregnancy must be excluded in women of childbearing potential –Pregnancy should be avoided if either partner is receiving MTX during and for a minimum of 3 months after therapy for male patients and for at least one ovulatory cycle after therapy for female patients

78 Methotrexate – Side Effects l Acute or chronic hepatotoxicity l Hepatic cirrhosis l Leukopenia l Thrombocytopenia l Anemia, including aplastic anemia l Rarely, interstitial pneumonitis l Stomatitis l Nausea/vomiting l Alopecia l Photosensitivity l Burning of skin lesions

79 Methotrexate l Multiple prescreening tests necessary l Recommendations for hepatic monitoring –Periodic LFTs including serum albumin –Liver biopsy l Pretherapy or shortly thereafter l Cumulative dose of 1.5 grams l After each additional 1.0 to 1.5 grams

80 Cyclosporine l Potent Immunosuppressive l Adult, non-immunocompromised patients with severe, recalcitrant plaque psoriasis l Maximum efficacy achieved at 16 weeks of therapy

81 Contraindications - Cyclosporine l Concomitant PUVA or UVB therapy l Methotrexate or other immunosuppressive agents l Coal tar or radiation therapy l Patients with abnormal renal function l Patients with uncontrolled hypertension l Patients with malignancies l Nursing mothers

82 Cyclosporine– Side Effects l Possibility of Irreversible renal damage l Hypertension l Headache l Hypertriglyceridemia l Hirsutism/hypertrichosis l Paresthesia/hyperesthesia l Influenza-like symptoms l Nausea/vomiting l Diarrhea l Lethargy l Arthralgia

83 Cyclosporine l Multiple prescreening tests must be obtained l Continued monitoring throughout therapy necessary with possible dosage adjustment to prevent end-organ damage

Treatment procaine vein blockage procaine vein blockage Photochemotherapy:UVB, PUVA(8-mop) Photochemotherapy:UVB, PUVA(8-mop) light quantum therapy light quantum therapy