Term
|
Definition
a chronic, T lymphocyte mediated, recurrent inflammatory disease of the keratin synthesis that is characterized by well circumscribed, dry, thickened, silvery, scaling papules and plaques
periods of exacerbations and remissions
lesions commonly occur on the back, buttocks, extensor surfaces of the extremities, and the scalp
severe manifestations of the disease can be physically and emotionally debilitating
not contagious |
|
|
Term
| epidemiology of psoriasis |
|
Definition
psoriasis occurs in 7.5 million Americans
estimated occurrence in Americans 2-4%
more prevalent in Caucasians 1.5-3%
blacks 0.4-0.7%
equal distribution between males and females
age onset: can occur at any age
most common between 20-30 years with a smaller peak at age 50-60
although rarely life threatening, adverse physical and emotional impact on quality of life
co morbidities:
psoriatic arthritis occurs in 10-30% of patients with psoriasis
clinical depression present in up to 60% of patients with psoriasis
atherosclerosis
anxiety
inflammatory bowel disease
poor self esteem
diabetes
CV disease
metabolic syndrome - risk factors include abdominal obesity, artherogenic dyslipidemia, hypertension, insulin resistance or glucose intolerance, prothrombotic state, and pro-inflammatory state
obesity |
|
|
Term
|
Definition
complex, multi factorial disease
antigens most likely infolved
genetic factors:
most patients have at least one immediate relative with the disorder
30-50% of genetic contribution of psoriasis is through loci PSORS1 (other genes include PSOR2, PSORS3, and PSOR4)
shows psoriasis is a heterogeneous disease with different genetic causes
HLA-Cw6 increases the likelihood of having psoriasis by 9-15 x normal
environmental factors:
climate - worse outcomes in colder weather reported in 90% of patients
stress - worsen psoriasis in 40% of patients
alcohol - worsen psoriasis progression more commonly in men
smoking - worsens psoriasis more often in women
trauma - can trigger a Koebner response (psoriatic lesions that develop at the site of injury of normally appearing skin); development can occur from days to weeks from initial injury
infection - guttate (small drop like plaques) have been associated with group A beta hemolytic streptococci due to endotoxin production
drugs - beta blockers, antimalarial agnets, NSAIDs, lithium, and tetracyclines can exacerbate psoriasiform lesions |
|
|
Term
| pathophysiology of psoriasis |
|
Definition
too many keratinocytes located on the epidermis layer of the skin
normal skin matures and fallos off in 28-30 days
in psoriatic lesions, the skin matures in 3-4 days and piles on itself to form a lesion instead of falling off
cell mediated immune mechanisms of psoriasis: activated T lymphocytes
causes cells to proliferate 7-8 x faster than normal cells forming a plaque
2 signals required to activate psoriasis:
1. interaction of T cell receptor with the APC
2. co stimulation mediated through various surface interactions
T cells then become activated and migrate from lymph nodes and circulate into the skin
T cells can enter the epidermis in psoriatic lesions with the help of selectins, integrins, and other adhesion molecules
cytokine release:
once the T cell is in the epidermis, it can release cytokines which are proteins secreted by the immune cells that bind to very specific receptors on the cell surface influencing keratinocytes and other cells to cause psoriasis
cytokines cause T helper cell type 1 response, which produces interferon gamma, TNFa, and IL2
keratinocytes, dendritic cells, and local neutrophils can also produce cytokines which can potentially become targets for drug therapy
defects in the epidermal cell cycle:
T cell production and proliferation causes psoriatic epidermal cells to proliferate 7 x faster than normal epidermal cells
the epidermal cell cycle is 8 x faster than for normal skin
skin with no lesions also has elevated proliferation
drug targets: block T cell activation, migration, and/or cytokine secretion |
|
|
Term
| symptoms and diagnosis of psoriasis |
|
Definition
normally asymptomatic lesions
biggest complaint is pruritus in 25% of patients
lesions are sharply demarcated, erythematous papules and plaques often covered with silver white scales
papules will enlarge over time
under silver scale there is an erythematous salmon pink lesion with possible pinpoint bleeding from prominent dermal capillaries (Auspitz sign)
removing the layer of silver scales under the epidermis are numerous twisted capillaries close to the surface which can cause seepage of blood from the capillaries
cracked skin and bleeding on flexture
fever and chills
arthritis (potential)
skin infection (secondary)
diagnosis is the recognition of the characteristics of a psoriatic lesion |
|
|
Term
|
Definition
psoriasis vulgaris is the most common type of psoriasis
scalp involvement from scales to thickened plaques with exudation, microabscesses, and fissures |
|
|
Term
| guttate psoriasis (small drop like plaques) |
|
Definition
more common for this type to start in child or young adulthood
an infection (especially streptococcal) or stress can bring this type of psoriasis on quickly |
|
|
Term
|
Definition
| located in the skin folds such as under arms, behind knees, buttocks, under breasts, and fat folds |
|
|
Term
|
Definition
white blisters of noninfectious pus (consisting of white blood cells) surrounded by red skin
3 types of pustular psoriasis
may be an acute emergency requiring systemic therapy |
|
|
Term
|
Definition
most severe form
erythema, desquamation, and edema which may require life support measures and systemic therapy |
|
|
Term
|
Definition
| most common type of psoriasis in children under 2 yo |
|
|
Term
| general psoriasis treatment strategies |
|
Definition
stress reduction
oatmeal baths in water that feels best
non medicated moisturizers
avoid chemical irritants, detergents
avoid skin trauma, sunburns - wear sunscreen, scratching
use ice packs if needed
Koebner response - psoriatic lesions that develop at the site of injury of normally appearing skin
development can occur from days to weeks from initial injury |
|
|
Term
| emollients (petrolatum jelly, Aquaphor, Bag Balm, Vasoline) |
|
Definition
help to minimize dryness that can lead to early recurrence during therapy free periods
BENEFITS:
hydration
minimize cutaneous transepidermal water loss (evaporation)
enhance desquamations
minimize scaling
anti-pruritic
mild vasoconstictor activity
DIRECTIONS:
apply QID to lesions to achieve beneficial response
ADRs:
folliculitis and allergic or irritant contact dermatitis (alcohols) |
|
|
Term
| balneotherapy (climatotherapy) |
|
Definition
bathing in water with high salt content
reduce activated T cells in the epidermis
ADRs:
tough to get time off
expensive |
|
|
Term
| ultraviolet B phototherapy (UVB) and psoralens (methoxsalen or trioxsalen) + ultraviolet A (PUVA) |
|
Definition
most effective narrow band UVB 310-315nm
plaque type
saliylic acid blocks UVB
can be used with emollients just prior to treatment to enhance efficacy
coal tar, anthralin, methotrexate, and oral retinoids can all be used to enhance UVB therapy
tazarotene and calcipotriene are inactivated by UVB light and should be applied 2 hours before or after treatment
ADRs:
potential for ocular damage
N/V with oral psoralens - take with food or milk to minimize |
|
|
Term
| treatment of mild to moderate psoriasis |
|
Definition
1. topical agents
2. topical agents plus phototherapy
3. topical agents plus systemic therapy
plus moisturizers ad lib. |
|
|
Term
| first line topical agents |
|
Definition
keratolytics (salicylic acid)
corticosteroids
vitamin D analogues
retinoids (tazarotene) |
|
|
Term
|
Definition
drug: salicylic acid 2-10%
MOA:
removes scales, smoothes the skin, and decreases hyperkeratosis
enhances penetration of topical corticosteroids when used concurrently
ADRs:
salicylate poisoning (N/V, tinnitus, hyperventilation, anion gap) |
|
|
Term
|
Definition
most widely used
MOA:
anti-inflammatory, anti-proliferative, immunosuppressive, and vasoconstirctive
bind to intracellular corticosteroid receptors and regulation of gene transcription that codes for inflammatory cytokines
vasoconstriction potency:
high potency = clobetasol propionate, halobetasol propionate, and betamethasone dipropionate
mild potency = betamethasone valerate
lowest vasoconstriction potency = hydrocortisone 1%
USE:
high potency agents
thick, chronic psoriatic plaques
use for short duration 2-4 weeks on smaller body surface areas
low potency
decreases erythema, sclaling, and pruritus
weak inflammatory effect
safe for long term application
can use on infants, face, and intertriginous areas (2 skin areas that may rub together)
avoid abrupt discontinuation of drug to avoid disease flare with chronic steroid use
ADRs:
local tissue atrophy with chronic use
epidermal and dermal degeneration
reversed if stop drug early but if not, can lead to atrophic changes that are long lasting (high potency agents)
telagniectasias (visible capillaries) and purpura can be caused by thinning of epidermia
acneiform eruptions and masking bacterial or fungal infection
tachyphylaxis
striae
MONITOR:
systemic ADRs with chronic topical use:
HPA axis suppression
hyperglycemia
Cushingoid features
DOSAGE FORMS:
best = ointment
oil phase that causes a hydrating effect
liphophilicity allows steroid to penetrate better causing increased vasoconstriction
use creams in the axilla, groin, or other areas where folliculitis can develop
DIRECTIONS:
low potency agents can be used on the face and intertriginous areas and infancts |
|
|
Term
| vitamin D analogues (calcipotriene) |
|
Definition
MOA:
inhibits keratinocytes differentiation and proliferation - mechanisms involves cytokines, chemokines, NFkB
ADRs:
hypercalcemia - calcipotriene binds to vitamin D receptors but is 100 x less active on systemic calcium metabolism b/c of its rapid local metabolism
lesional and perilesional irritation in 10% of patients causing mmild burning and stinging
DIRECTIONS:
takes 4-6 weeks to clear lesions
inactivated by UVA light so apply after exposure |
|
|
Term
|
Definition
synthetic retinoid, prodrug to tazarotenic acid
MOA:
modulates keratinocyte proliferation and differentiation
ADRs:
mild to moderate pruritus, burning, stinging, or erythema that are dose and frequency related
can use in combo with topical corticosteroids to decrease local ADRs and increase efficacy
do not cover > 20% of BSA due to systemic absorption
PREGNANCY CATEGORY X - women of child bearing age need to prove a negative pregnancy test prior to starting therapy and using contraceptives |
|
|
Term
| second line topical agents |
|
Definition
|
|
Term
|
Definition
MOA:
keratolytic, antiproliferative, anti-inflammatory
cytostatic effect with epidermal thinning
can be used with UVB light where activated coal tar forms photo adducts with epidermal DNA and inhibits DNA synthesis and reduces epithelial growth rate
ADRs:
local irritation, unpleasant odor, staining of skin and clothing, and increased sensitivity to UV light
very high concentrations increased risk of cancer |
|
|
Term
|
Definition
MOA:
possesses antiproliferative activity on human keratinocytes, inhibiting DNA synthesis
can induce proinflammatory cytokines via NFkB induction in keratinocytes, which can give it an irritant effect
may have direct effect on the mitochondria and reduce mitotic activity
plaque type and guttate psoriasis respond better
sometimes used with UVB light
ADRs:
irritation
staining - disappears within 1-2 weeks of stopping the drug; staining is a positive response sign b/c it shows that cell turnover has slowed enough to take up the stain |
|
|
Term
| treatment for moderate to severe psoriasis |
|
Definition
1. systemic agent - if needed, add topical agent or phototherapy
2. more potent systemic agent, or 2 systemic agents in rotation plus a topical agent
3. biologic response modifier |
|
|
Term
| systemic therapy - first line agents |
|
Definition
inflximab
etanercept
adalimumab
alefacept
ustekinumab |
|
|
Term
| 3 categories of biologic agents |
|
Definition
recombinant human cytokines
humanized monoclonal antibodies
molecular receptors that can bind target molecules |
|
|
Term
|
Definition
chimeric human/murine monoclonal antibody directed against TNFa; TNFa inhibitor
median time to response is 4 weeks
ADRs:
HA, fever, diarrhea, pharyngitis, infection, hypersensitivity reactions, and lymphoproliferative disorders
BBW: tuberculosis and other serious opportunistic infections, including histoplasmosis, listeriosis, and pneumocystosis have been reported in both the clinical research and post marketing surveillance settings
BBW: increased risk for malignancy and lymphoma
BBW: new onset psoriasis
demyelinating disorders have been associated with TNF inhibitors
rare cases of pancytopenia, aplastic anemia, and hepatotoxicity
new or worsening heart failure
patients should not receive live vaccinations while on infliximab
pregnancy category B
MONITOR:
PPD test prior to treatment and s/sx of TB while on treatment
LFTs periodically (if levels 5 x ULN, hold dose until LFTs are lower)
CBC
infusion site effects |
|
|
Term
|
Definition
fully humanized, fusion protein that binds and inactivates TNFa
indicated for plaque psoriasis with psoriatic arthritis
ADRs:
injection site reactions, respiratory tract and GI infections, abdominal pain, N/V, HA, and rash
BBW: increased rate of opportunistic fungal infections and TB
BBW: increased risk of malignancy (lymphoma and leukemia in children)
BBW: increased risk of new onset psoriasis in all patients
demyelinating disorders associated with TNF inhibitors
new onset or worsening heart failure
pregnancy category B
avoid live vaccines
MONITOR:
baseline PPD test, then yearly PPD test (watch for latent TB)
s/sx of infection
periodic CBC, LFTs |
|
|
Term
|
Definition
human IgG1 monoclonal TNFa inhibitor
approved for moderate to severe plaque psoriasis and psoriasis with arthropathy
ADRs:
BBW: tuberculosis and other serious opportunistic infections, including histoplasmosis, listeriosis, and pneumocystosis, have been reported in both the clinical research and post marketing surveillance settings
BBW: increased risk for malignancy and lymphoma
BBW: new onset psoriasis
rhinitis, upper respiratory tract infections, nausea, flu-like syndrome, HA, and injection site reaction
heart failure
increased risk of lymphoma
possible antibody formation to adalimumab
pregnancy category B
MONITOR:
PPD test prior to initiation and monitor for signs of latent TB
CBC
signs of infection, bleeding, or bruising |
|
|
Term
|
Definition
a dimeric human fusion protein T cell activation inhibitor
selectively depletes activated T cells and interacts with NKCs
for moderate to severe plaque psoriasis and psoriatic arthritis
well tolerated ADRs
ADRs:
lymphopenia, myalgia, chills, pharyngitis, cough, nausea
MONITOR:
CD4 T cell count every 2 WEEKS while receiving treatment
hold dose if CD4 count falls below 250 cells/microliter
discontinue if CD4 levels fall < 250 cells/microliter for 1 month
s/sx of infection and malignancy
pregnancy category B
do not give live vaccines while treating with alefacept |
|
|
Term
|
Definition
MOA:
monoclonal antibody that targets proteins IL12 and IL23 to decrease skin cell growth
ADRs:
upper respiratory infections, HA, tiredness
serious effects similar to other biological response modifiers including serious tubercular, fungal, viral infections, and malignancy
reversible posterior leukoencephalopathy syndrome has also been reported
MONITOR:
PPD prior to initiating therapy
s/sx of infection
CBC
ustekinumab antibody formation |
|
|
Term
| systemic therapy second line agents |
|
Definition
acitretin
cyclosporine
methotrexate |
|
|
Term
|
Definition
oral retinoid, active metabolite of etretinate (fewer ADRs)
best as adjuncti for plaque type
can be used for erythrodermmic and pustular
adsorption enhanced with food
alcohol converts acitretin to etretinate, which has a longer half life
do not drink alcohol during treatment and 2 months after stopping treatment
onset slower than cyclosporine or methotrexate
acitretin and PUVA reported to be highly effective
ADRs:
hypertriglyceridemia, increased transaminases in 1/3 of patients, mucocutaneous ADRs
pregnancy category X - KNOWN TERATOGEN
contraindicated in females who are pregnant/planning within 3 years after stopping
ALL patients must be provided a medication guide each time medication is dispensed
female patients must sign informed consent prior to therapy
MONITOR:
lipid profile and TGs at baseline; monitor every 2-4 weeks until stable, every 3-6 months after that (consider adding hyperlipidemia agent if needed
liver function tests at baseline and at 1-2 week intervals until stable, then as clinically indicated |
|
|
Term
|
Definition
inhibits T cell activation and inhibits the release of inflammatory mediators
treats cutaneous and arthritic manifestations of severe psoriasis
ADRs:
nephrotoxicity
hypertension
hypertriglyceridemia
potential risk for malignancy
MONITOR:
electrolyte panel, renal panel (Ca, Phos, Mag, BUN, SCr), uric acid, TGs, CBC, and blood pressure at baseline and every 2 weeks for 12 weeks, then monthly thereafter
dental exam yearly for gingival hyperplasia risk
contraindications: abnormal renal function, uncontrolled hypertension, uncontrolled infection |
|
|
Term
|
Definition
antimetabolite that inhibits the replication and function of T anc B cells and suppresses secretion of various cytokines; suppresses epidermal cell division
beneficial for patients with psoriatic arthritis and moderate to severe psoriasis
avoid in patients with active infections due to its immunosuppressive activity
ADRs:
hepatotoxicity
bone marrow toxicity
GI ADRs - divide doses 12 hours apart
pneumonitis
pulmonary fibrosis
pregnancy category X - contraindicated in pregnancy
MONITOR:
CBC with differential and platelets at baseline, 7-14 days after initiating therapy or dose increase, every 2-4 weeks for the first few months, then every 1-3 months
LFTs at baseline, monthly for the first 6 months, then every 1-2 months
liver biopsy for patients with risk factors for hepatotoxicity at baseline and with each 1.5 g cumulative dose interval
BUN, SCr at baseline and every 2-3 months
baseline PPD for latent TB screening
chest X ray for baseline underlying disease |
|
|
Term
|
Definition
UVA light with oral or topical psoralen
usually methoxypsoralen
take oral dose with milk or food to minimize N/V
can be added to bath water - minimizes ADRs and light exposure time
avoid tanning beds due to risk of severe burns
use caution with administering other photosensitive drugs such as quinolones
MONITOR:
minimize exposure to the sun
skin cancer |
|
|
