2. Psoriasis –epidemiology
Kanada
4,7%
USA 1,4-
4,6%
Indianie Płd
Am. 0%
Australia
2,6%
Aborygeni 0%
Szwecja
2,3%
Rosja
2,0%
Chiny
0,05-0,8%
Japonia
0,29%
Hiszpania
3,7%
Low incidence: West Africans, Japanese, very low: incidence or absence
in North and South American Indians
males = females
3. Psoriasis –epidemiology
Peak incidence - 22.5 years of age
Late onset (type II) ≈ age 55
Early onset (type I) predicts a more severe and
long- lasting disease, positive family history
4. Psoriasis - history
460-377 p.n.e – Hipokrates first description
129-99 p.n.e – Galen: term „psora” = pruritus
1841 - Ferdinand von Hebra: separated psoriasis from lepra
5. Psoriasis – genetic background
1963 r. Gunnar Lomhold
1972 r. – HLA: susceptibility
markers
1970 - 1990 –
twin studies
8. Genetics of psoriasis( GWAS, Genome wide association scans )
candidate genes
James T. Elder. Genes Immun, 2009, 10, 201.
9. Polygenic trait
one parent has psoriasis - 8% of offspring
develop psoriasis
both parents have psoriasis - 41% of
children develop psoriasis
Psoriasis - complex
disease
10. Physical trauma (Koebner phenomenon)
isomorphic sign - the psoriatic papules occur in the site of the mechanical trauma within a couple of days
Infections acute streptococcal infection - guttate psoriasis
Stress as high as 40% in adults and higher in children
Drugs systemic glucocorticoids, oral lithium, antimalarial drugs,
interferon, beta blockers (flares existing psoriasis or psoriasiform drug
eruption)
Alcohol ingestion, smoking, obesity
PSORIASIS - environmental factors
11. Nestle F. N Engl J Med, 2009, 361, 496.
Immunopathogenesis of psoriasis – history
1980’:immunological background
1990-2000’:
psoriasis - Th1 /Th17
mediated disease
1961r. van Scott epidermal
hiperproliferation
12. Immunopathogenesis of psoriasis
Nestle F. N Engl J Med, 2009, 361, 496.
Innate, adaptive immunity
Keratynocytes
Macrophages
Dendytic cells
Lymphocytes T
14. Clinical phenotypes
A. Localised forms B. Generalised forms
Psoriasis of folds Plaque
Seborhoic psoriasis Guttata
Psoriasis capitis Generalised plaque
Psoriasis palmo-plantaris (non-pustular)
Erytrodermia
Psoriasis plaque (limbs)
Psoriasis plaque (trunk)
Psoriasis – phenotype classification
International Psoriasis Council 2007
16. Auspitz sign - the appearance of bleeding spots when psoriasis scales are scraped off
The candle grease sign (the removal of the scale reveals the skin with a glossy grease-
like appearance
19. Sharply marginated, dull-red plaques
with loosely adherent, lamellar,
silvery-white scales
Plaques coalesce to form polycyclic,
geographic lesions and may partially
regress, resulting in annular,
serpiginous, and arciform patterns
Lamellar scaling can easily be
removed, or, when the lesion is
extremely chronic, it adheres tightly to
the underlying inflammatory and
infiltrated skin, resulting in
hyperkeratosis
Psoriasis -chronic stable type
20. Finger nails and toenails
frequently involved
(arthritis)
pitting
subungual
hyperkeratosis,
onycholysis
yellowish-brown spots
under the nail plate—
the oil spot
(pathognomonic)
Psoriasis – nails
21. One of the most common forms of the
disease-occurring in 50-80% of patients,
it is often the first clinical manifestation
of the dermatosis. They are usually
located at the border between the
glabrous skin and the hairy scalp,
forming the so called "psoriatic crown".
Plaques, sharply marginated, with thick
adherent scales Scattered discrete or
diffuse involvement of entire scalp,
Scalp psoriasis may be part of
generalized psoriasis or coexist with
isolated plaques, or the scalp may be
only site involved.
Psoriasis – scalp
23. not scaly but macerated, bright red and fissured
the sharp demarcation - distinction from intertrigo, candidiasis, contact dermatitis, tinea,
this form is seen rarely in clinical practice. It occurs in 3 to 6.8% of all patients with
psoriasis, and if it is the only clinical presentation it may cause difficulties in getting the
correct diagnosis. Scales are not found in the psoriasis of the skin folds, but maceration
and secondary infections are seen.
Chronic Psoriasis of the Perianal and Genital Regions and of the
Body Folds – Inverse Psoriasis
24. Acute Guttate Type
• Salmon-pink papules (guttate: Latin gutta, "drop"), 2.0 mm
to 1.0 cm with or without scales
• Scattered discrete lesions generally concentrated on the
trunk, less on the face and scalp, usually sparing palms and
soles
• Guttate lesions may resolve spontaneously within a few
weeks but usually become recurrent and may evolve into
chronic, stable psoriasis
27. Psoriasis palmo-plantaris
Palms and Soles
may be the only areas involved
massive silvery white or yellowish
hyperkeratosis and scaling not
easily removed
there may be cracking and painful
fissures and bleeding
29. Pustulosis palmo-plantaris (PPP)
Pustules in stages of
evolution, 2–5 mm, deep-
seated, yellow, develop into
dusky-red macules and
crusts; present in areas of
erythema and scaling or
normal skin
Limited to palms and soles,
may be only a localized patch
on the sole or hand, or
involve both hands and feet
33. Generalized Acute Pustular Psoriasis
(Von Zumbusch)
Fever, generalized weakness, severe malaise
Rare
The constellation of fiery-red erythema followed by formation of pustules
occurs over a period of less than 1 day
Patient frightened, "toxic.„
Nikolsky phenomenon - positive
Pustules are sterile
The eruption generalized
34. Psoriatic erytroderma
psoriasis is one of the most
common causes of
erythrodermia in adults, it can
arise anew or complicate
chronic plaque psoriasis (often
if the treatment is not
appropriate). Inflammation
with dandruff-like scaling
involving the whole skin
surface, accompanied by
elevated leukocyte count,
elevated ESR, and
lymphadenopathy
35. Psoriatic arthritis
seronegative spondyloarthropathies, which
include ankylosing spondylitis, enteropathic
arthritis, and reactive arthritis
Incidence is 5–8%. Rare before age 20
May be present (in 10% of individuals) without
any visible psoriasis; if so, search for a family
history !
36. Psoriatic arthritis
Types
"Distal"—seronegative, without subcutaneous
nodules, involving, asymmetrically, a few
distal interphalangeal joints of the hands and
feet: an asymmetric oligoarthritis.
Enthesitis—inflammation of ligament
insertion into bone.
Multilating psoriatic arthritis with bone
erosion and ultimately leading to osteolysis or
ankylosis.
"Axial"—especially involving the sacroiliac,
hip, and cervical areas with ankylosing
spondylitis.
37. Psoriatic arthritis
Skin symptoms and signs
Swelling, redness, tenderness of involved joints
or site of enthesitis (e.g., insertion of Achilles
tendon in calcaneus)
Dactylitis—sausage fingers, May or may not be
associated with psoriasis elsewhere.
Often psoriatic involvement of fingertips and
periungual skin. Massive nail involvement by
psoriasis is frequent
Arthritis may lead to arthritis mutilans:
destruction of interphalangeal joints results in
telescope fingers with mutilation of hand and
considerable functional impairment
39. CISD
I. Common ganetic background
II. Pathogenesis/efficacy of pathogenesis based
treatment
III. CVD risk
40. I. CISD – common genetic background
Gen Chromosom Skojarzone choroby
IL-12B 5q Łuszczyca, Ch. Crohna
IL-23R 1p Łuszczyca, Ch. Crohna,
ZZSK, łzs
CDKAL1 6p Łuszczyca, Ch. Crohna,
cukrzyca typu 1
PTPN22 18p Łuszczyca, RZS, SLE,
cukrzyca typu 2
Region genów rodziny IL-4
IL-13
5q Łuszczyca, Ch. Crohna
41. II. CISD -common pathogenesis
Th1/Th17 mediated immunological responce
Role of TNF-α
Role of DC
Endothelium dysfunction
Oxidative stres
Inflammatory markers in circulation
42. Psoriasis / atheromatosis – common pathogenesis
Spach F. Br J Dermatol 2008, 159, 10.
łuszczyca miażdżyca
44. Psoriasis comorbidities increasing risk of CVD
Metabolic syndrom
Associated with systemic inflammatory disease
Obestity
Diabetes
Hiperlipidemia
Hypertension
45. Psoriasis and obesity
Hamminga EA i inni. Med. Hypoth 2006, 67, 76.
Johnson A i inni. Br J Dermatol 2008, 159, 342.
Obesity 2x increases psoriasis risk
BMI correlates with psoriasis severity
46. Psoriasis and diabetes
Psoriatics have diabetes more often
Role of TNF-α in insuline resistence
Significant correlation of resistine in
blood with psoriasis severity
Cohen A. J Am Acad Dermatol, 2007, 56, 629.
47. Psoriasis and atherogenic dyslipidemia
Rocha-Pereira i inni. Clin Chim Acta 2001, 303, 33.
↑ LDL, VLDL, TG, cholesterol, ↓HDL in psoriatics
LDL correlates with psoriasis severity
Oxydative stres accelerates atherogenesis
Side effect of antipsoriatics drugs on lipide profile
49. Psychosocial impact of psoriasis
Stygmatisation
J Am Acad Dermatol. 1999 Sep;41(3 Pt 1):401-7.
50. Depression: 60 %
Suicidal tendency: 7,2 %
Psychosocial impact of psoriasis
Esposito M. Dermatology, 2006, 212,123. Gupta M. Br J Dermatol 1998, 139, 846.
51. thickening of the epidermis
(acanthosis) and thinning of
epidermis over elongated dermal
papillae
Increased mitosis of keratinocytes,
fibroblasts, and endothelial cells
Parakeratotic hyperkeratosis (nuclei
retained in the stratum corneum)
Inflammatory cells in the dermis
(lymphocytes and monocytes) and in
the epidermis (lymphocytes and
polymorphonuclear cells), forming
microabscesses of Munro in the
stratum corneum.
Psoriasis - laboratory examinations
dermatopathology
52. Psoriasis - laboratory examinations
Serology
Increased antistreptolysin titer in acute
guttate psoriasis with antecedent
streptococcal infection. Sudden onset
of psoriasis may be associated with HIV
infection
Culture
Throat culture for group A -hemolytic
streptococcus infection.
53. Psoriasis treatment – factors
selection of treatment
1.Age: childhood, adolescence, young adulthood, middle age, >60 years
2.Type of psoriasis: guttate, plaque, palmar and palmopustular,
generalized pustular psoriasis, erythrodermic psoriasis
3.Site and extent of involvement: localized to palms and soles, scalp,
anogenital area, scattered plaques but <5% involvement; generalized and
>30% involvement
4.Previous treatment: ionizing radiation, systemic glucocorticoids,
photochemotherapy (PUVA), cyclosporine (CS), methotrexate (MTX)
5.Associated medical disorders (e.g., HIV disease, CVD).
54. Psoriasis – local treatment
emolients and keratolytics
anthralin
vitamine D analogues
topical steroids
topical retinoids
56. Anthralin (dithranol)
usual concenrations 0.1-2%
efficacy- good in a short term
side efects: irritation
hypersensitivity, staining of
nails and hair
contraindication: acute or
actively inflamed psoriasis
57. Calcipotriene (vitamine D derivative)
benefit in mild to moderate psoriasis
combination of calcipotrene with topical steroids
provides better clearance and maintenance
may cause skin irritation
should not be used by patients with
hypercalcemia or vitamine D toxicity
58. Topical steroids
short period of up to 4 weeks for flexural
or facial psoriasis
long-term use must be avoided - side
effects:
- atrophy
- striae
-teleangiectasia
- skin fragility
- dyspigmentation
- systemic side effects
!
61. oral ingestion of 8-methoxypsoralen (8-MOP)
(0.6 mg 8-MOP per kilogram body weight) or, 5-
MOP (1.2 mg/kg body weight) and exposure to
doses of UVA that are adjusted to the sensitivity
of the patient.
three times a week.
most patients clear after 19 to 25 treatments,
and the amount of UVA needed ranges from 100
to 245 J/cm2.
Long-term side effects:
PUVA keratoses and squamous cell carcinomas
Oral PUVA Photochemotherapy
62. Oral retinoids in psoriasis
• Acitretin usual range 25-50mg/day very effective in inducing
desquamation but only moderately effective in suppressing
psoriatic plaques (an exception is pustular psoriasis
• They are highly effective when combined according to established
protocols with 311-nm UVB or PUVA (called Re-PUVA)
• Contraception is mandatory during treatment and for 2 years after
it is completed
• Combinations of oral retinoids and PUVA improve the efficacy of
each and permit a reduction of the dose and duration of each if
refractory to treatment
63. Psoriasis – retinoids- side effects
• teratogenic - women of childbearing age should use
contraception during and for two years after therapy!!!
• ro-dermatitis: eyes, ears, nose and throat: cheilitis, dry eyes
and nose, conjunctivitis
• abnormal liver function tests, hipertriglyceridemia,
hiperglycemia
• muscosceletal: arthralgia, myalgia
• central nervous system: dizziness, fatigue, headache
64. Psoriasis - retinoids - patient information
therapeutic effect after 2-4 week
avoid pregnancy for one month before and 2 years after treatment
avoid tetracycline
don’t donate blood one year (teratogenic effect)
avoid excessive sunlight
!
65. Cyclosporine in psoriasis
CS treatment is highly effective at a dose of
3–5 mg/kg per day. As the patient responds,
the dose is tapered to the lowest effective
maintenance dose. Monitoring blood
pressure and serum creatinine is mandatory
because of the known nephrotoxicity of the
drug. CS should be employed only in patients
without risk factors.
!
67. Methotrexate Therapy
Schedule of Methotrexate: the single-dose MTX once weekly
(12.5-25 mg/ week)
80% improvement but total clearing only in some, and higher
doses increase the risk of toxicity. Higher doses may be
needed in overweight patients
CBC, Liver Function
Contraindications:
anemia, thrombocytopenia or leukopenia
nursing mothers, pregnancy (avoid conception for 6 month after
stopping men and women)
gastric or duodenal ulcer
69. alkohol intake
abnormal liver parameters
liver disease in anamnesis
positive familial anamnesis into genetic liver diseases
diabetes
obesity
significant exposure into chemical substances
no folic acid suplemmentation
hiperlipidemia
Risk factors of liver damage in patients treated with mtx
70. Liver damage after Mtx in psoriatics
Fibrosis cirrhosis
Histological features of NAHS
(non-alkoholic hepatic steatosis)
71. Liver toxicity in patient treated with mtx – cumulative dose
Patients with risk factors
1,5 g Mtx
Patients with no risk
factors
3,5-4 g Mtx
74. Specifity
Short and long term efficacy
↓ organ toxicity
↓risk of drug interactions
Cardioprotective action
Biologics in psoriasis
75. Risk of infection
Risk of neoplasms ?
moAb antibodies
Long-term efficacy?
Costs
Biologics in psoriasis
76. Psoriasis - prevention
no effective preventive measures to be taken against the
development of psoriasis
flare-ups may be potentially reduced by modification
of risk factors – infections, stress, drugs, smoking, alkohol
interaction alert!
beta-blockers for hypertensives may cause the flare of psoriasis
77. Psoriasis prognosis
debilitating disease due to psychosocial impact
genaralized pustular psoriasis and erythrodermic
psoriasis may be life-threatening if untreated
course of disease is chronic and may be refractory to
treatment
5-8% of patients with psoriasis may develop psoriatic
arthropathy
78. Th1 i Th17 in psoriasis
pathogenesis
Psoriasis as a systemic disease
decreasing QL
81. Lichen planus – epidemiology
Worldwide occurrence; incidence < 1%, all races
Age of Onset: 30–60 years
Sex
Females > males
Hypertrophic LP more common in blacks
82. LP-onset
Acute (days) or insidious (over
weeks). Lesions last months to
years, asymptomatic or pruritic;
sometimes severe pruritus.
Mucous membrane lesions are
painful, especially when ulcerated
83. LP-etiology
Idiopathic in most cases but cell-mediated
immunity plays a major role. Majority of
lymphocytes in the infiltrate are CD8+ and
CD45Ro+ (memory) cells. Drugs, metals (gold,
mercury), or infection [hepatitis C virus (HCV)]
result in alteration in cell-mediated immunity.
There could be HLA-associated genetic
susceptibility that would explain a
predisposition in certain persons. Lichenoid
lesions of chronic graft-versus-host disease
(GVHD) of skin are indistinguishable from
those of LP
84. Lichen planus - distribution: predilection for flexural
aspects of arms and legs, can become generalized
85. LP – clinical manifestation
Papules, flat-topped, 1 to 10 mm, sharply
defined, shiny. Violaceous, with white lines
(Wickham striae), seen best with hand lens
after application of mineral oil. Polygonal or
oval. Grouped, annular, or disseminated
scattered discrete lesions when generalized. In
dark-skinned individuals, postinflammatory
hyperpigmentation is common. May present
on lips and in a linear arrangement after
trauma (Koebner or isomorphic
phenomenon).
86. LP - variants
Hypertrophic
Atrophic
Follicular
Individual keratotic-follicular papules and plaques that lead to cicatricial alopecia.
Spinous follicular lesions, typical skin and mucous membrane LP, and cicatricial
alopecia of the scalp are called Graham Little syndrome
Vesicular
Vesicular or bullous lesions may develop within LP patches or independent of them
within normal-appearing skin.
Pigmentosus
Hyperpigmented, dark-brown macules in sun-exposed areas and flexural folds. In
Latin Americans and other dark-skinned populations. Significant similarity with ashy
dermatosis
Actinicus
Papular LP lesions arise in sun-exposed sites, especially the dorsa of hands and arms
Ulcerative
LP may lead to therapy-resistant ulcers, particularly on the soles
87. LP - Mucous Membranes
Oral
40–60% of individuals with LP
Reticular LP
Reticulate (netlike) pattern of lacy white hyperkeratosis on
buccal mucosa lips, tongue, gingiva; the most common pattern
of oral LP
Erosive or Ulcerative LP
Superficial erosion with/without overlying fibrin clot; occurs
on tongue and buccal mucosa); shiny red painful erosion of
gingiva (desquamative gingivitis) or lips
Carcinoma may very rarely develop in mouth lesions.
Genitalia
Papular, annular, or erosive lesions arise on penis (especially
glans), scrotum, labia majora, labia minora, vagina.
89. LP-treatment
Cyclosporine
Oral prednisone is effective for individuals with
symptomatic pruritus, painful erosions, dysphagia, or
cosmetic disfigurement. A short, tapered course is
preferred
Systemic Retinoids (Acitretin)
1 mg/kg per day is helpful as adjunctive measure in severe
(oral, hypertrophic) cases, but usually additional topical
treatment is required.
PUVA Photochemotherapy
In individuals with generalized LP or cases resistant to
topical therapy.
Hinweis der Redaktion
łuszczyca jest prawdopodobnie jedna z najdłuzej znanych ludzkosci chorób
Pierwszy udokumentowany opis zmian skórnych odpowiadajacych łuszczycy odnaleziono w starym testamencie.
Z czasow starożytnych pochodzi łacińska nazwa choroby – psoriasis – od słowa psora oznaczający swiąd
Przez wieki łuszczyca traktowana była jako choroba nieczystych, schorzenie potencjalnie zakaźne i wynikajace z zaniedbań higienicznych. i bardzo często utozsamiana z trądem. Ten stereotyp funkcjonujacy czasem do dzisiaj został zerwany dzieki słynnum dermatologom Robert Willan jako pierwszy opisał łuszczycę jako odrebną jednostkęchorobowa zaś FV H ostatecznie oddzielił chorobę od tradu
Proces zapalny zarówno w łuszczycy jak i miażdżycy jest zależny od limfocytów Th1.
Kaskada zjawisk patogenetycznych w obu stanach wykazuje duży stopień podobieństwa.
APC aktywuja dziewicze LT na których dochodzi do ekspresji LFA-1
Aktywowane LT migruja do nn i przylegaja do sródbłonka i przedostaja się poza naczynia przy udziale LFA-1 i ICAM
Aktywowane LT wchodza w interakcje zKC, makrofagami KD i kkmgł
Reaktywowane TL wydzielają cytokiny i chemokiny tworzące zaplne srodowisko w którym tworzy się blaszka łuszczycowa i blaszka miazdzycowa
Zjawisko otyłości przybiera w krajach rozwiniętych skalę epidemii
Endotelina – 1peptyd wydzielany przez komórki sródbłonka ale też KC o silnych właściwosciach aterogennych zweza naczynia, działa proagregacyjnie
Zaburzenia depresyjne mogą mieć zróznicowany obraz od postaci poronnych po ciężkie zaburzenia przebiegające z myslami i tendencjami samobójczymi
