Psoriasis Flashcards
Psoriasis epidemiology?
2% worldwide, bimodal peak @ 20-30 yrs and 50-60 yrs 75% onset before 40 -children plaque psoriasis mc then guttate -family hx in 35-90%
Rate of psoriatic arthritis
5-30%
Most common psoriatic susceptibility gene?
PSORS1 chormosome 6p contains HLA-Cw6 allele
what is the HLA affected in PSORS1?
HLA-Cw6
What cytokine is decreased in psoriasis?
IL-10
What antimicrobial proteins are secreted more in psoriasis?
hBD1-2, cathelicoidin LL37 and SLP1
What cytokine is responsible for the IL-23 response?
IL-6
What cytokine correlates w/ dz severity?
IL-22
Psoriasis triggers?
truama (Keobner phenomenon) [sunburn, morbillifrom drug eruptions etc], infection (strep pharyngitis –> guttate), HIV, hypocalcemia (genarlaized pustular psoriasis), pregnancy, stress, drugs (lithium, beta blockers, antimalrias, TNF alpha inhibitors and CS tapers (pustular))
Triggers of guttate psoriasis?
group A strep infection or URI
Which psoriasis is pregnancy related?
Impetigo herptetiformis –> begins in flexures then generalized w/ toxicity. Early delivery recommended
4 patterns of pustular psoriasis?
Von zumbusch, annular, exanthematic type, localized pattern
Describe the von zumbusch pattern of pusturlar psoriasis
Rapid and generalized, painful skin, fever, luekocytosis, hypoalbuminemia, and malaise; a/w hypocalcermia (risk factor)
What psoriasis disorder can be associated w/ bone lesions?
Palmoplantar pustulosis –> SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, osteitis). You get sterile inflammatory bone lesions.
What is acrodermatitis continua of Hallopeuau?
On fingers, lakes of puss, nail shedding and damage
What is the #1 cause of pityriasis aminatacea?
Psoriasis
What nails does psorasis affect most commonly
Fingernails>toenails
What are the nail findings in psoriasis?
- Proximal matrix involvement
- Distal matrix involvement
- Nail bed involvement
The proximal matrix primarily affects pits (small depressions in the nail surface).
The distal matrix is responsible for producing the dorsal surface of the nail, which explains why distal matrix involvement leads to leukonychia and other changes.
What percentage of pt’s can have nail findings w/o rash in psoraisis?
10-15%
What is the RF status of psoriatic arthritis?
RF negative
What are the 5 types of Psoriatic arthritis/patterns
- Oligoarthritis (most common)
- asymmetric DIP involvement
- Rheumatoid Arthirtis (can be RF+)
- Ankylosing Spondylitis
- Arthritis Mutilans
What comorbitities are decreased in psoriasis?
allergic disease and risk of superinfection is decreased
What are first-line topical therapies for children?
Vitamin D3 analogs (CS first line in adults)
What light therapy is more effective for guttate psoriasis?
broad band-UVB is more effective than narrow-band (NB) UVB
SE a/w cyclosporin use?
hypertrichosis, gingival hyperplasia, myalgia, paresthesia, tremos, malaise, hyperuricemia, hypomagnesmia, hyperkalemia
What IL-17 inhibitor is against the receptor?
Brodalimumab (Siliq)
(Brodalumab)
It uniquely targets IL-17 receptor A, blocking multiple IL-17 cytokines, unlike secukinumab and ixekizumab, which target IL-17A specifically. It is effective for moderate to severe plaque psoriasis but carries a boxed warning for potential suicidal ideation and behavior.
What is the tx choice for pustular (vonzumbusch)
Acitretin (>cyclosprin, MTX and biologic)
What genetic alteration is a/w early-onset psoriasis?
HLA-Cw6
What percent of people w/ early-onset psoriasis have HLA-Cw6?
90%
What chromosome is PSORS1 located on?
6p
What percent of psoriasis pt’s have PSORS1
50%
What psoriasis subtypes are a/w HLA-B27?
sacroiliitis-associated psoriasis, PsA, and pustular psoriasis
What HLA subtypes are a/w guttate and erythrodermic psoriasis?
HLA-B13 and B17
What HLA subtypes are a/w palmoplantar psoriasis?
HLA-B8, Bw35, Cw7, and DR3
What type of T-cell predominates in the epidermis in psoriasis lesions? Dermis?
CD8+ in the epidermis and a mix of CD4+/CD8+ T-cells in dermis.
What cytokines are increased in psoriasis?
Th1 cytokines (e.g., IFNgamma, IL-2) Also: IL-1, IL-6, TNF alpha
What cytokine is decreased in psoriasis?
IL-10
What cytokine from dendritic cells is key in the proliferation of keratinocytes in psoriasis and what is the progression?
IL-23 (from Dendritic Cells)–> Th17 cell stimulation–> IL-17 and IL-22 release –> dermal inflammation and keratinocyte replication
Which cytokine triggers neutrophil chemotaxis in psoriasis?
CXCL8
What antimicrobial peptides are increased in psoriasis?
hBD1-2, cathelicidin LL37, and SLP1
What cytokines are expressed by keratinocytes in psoriais?
IL-1, IL-6, IL-8, and TNF-alpha; also express TLRs
What is expressed in increased amounts in psoriasis that leads to blood vessel changes and the dilation seen in papilla on path and auspitz sign clincally?
VEGF
Triggering factors for psoriasis?
External vs internal triggers Extrenal= trauma (includes sunburn, drug eruption, viral exanthum etc) Internal=infections (strep #1), hypocalcemia, HIV, stress, drugs, alcohol, smoking obesity.
What forms of psoriasis is hypocalcemia a/w?
Pustular and pregnancy related impetigo herpetiformis
What drugs are implicated in psoriasis?
-Lithium, IFNs, Beta blockers, antimalarials, TNF alpha inhibitors, and CS tapers in (pustular psoriasis) -TNF alpha inhibitors may lead to plaque psoriasis and/or palmoplantar pustulosis
Which drugs are related to psoriasis with short, intermediate, or long-term latency?
Short: terbinafine, NSAIDs
Intermediate: antimalarials, ACE inhibitors
Long: Beta blockers, lithium
Most common type of psoriasis?
Chronic plaque form
What are the most common sites of chronic plaque form psoriasis?
Scalp, elbows, knees, pre-sacrum, hands, feet, genitalia (up to 45%)
What percent of guttate psoriasis patients go on to have the chronic plaque form of psoriasis?
40%
Most common location for guttate psoriasis?
Trunk and proximal extremities
Common trigger of guttate psoriasis?
Strep A infection/URI, usually 1-3 weeks prior to presentation. Note that this can be triggered from impetigo.
What titers might you check in guttate psoriasis?
Elevated antistreptolysin O, anti-DNaseB or streptozyme titer can be seen
Does treatment of a strep A infection improve guttate psoriasis?
No
What are the 4 distinct patterns of pustular psoriasis?
- Von Zumbusch pattern
- Annular pattern
- Exanthematic type
- Localized pattern
What is the presentation of Von Zumbusch pattern of pustular psoriasis?
Onset is rapid and generalized, painful skin, fever, leukocytosis, hypoalbuminemia, and malaise; a/w hypocalcemia (risk factor)
What is the presentation of the annular pattern of pustular psoriasis?
Annular lesions of erythema and scale with pustulation at advancing edge.
Presentation of exanthemic pustular psoriasis?
Acute eruption of small pustules, abrupt appearing and disappearing over few days. Usually following infection or meds. No systemic symptoms.
Presentation of the localized form of pustular psoriasis?
Pustules within or at edge of existing psoriatic plaques.
What is impetigo herpetiformis?
Pregnancy associated; begins in flexures then generalized w/ toxicity; early delivery recommended. Also a/w hypocalcemia.
Which disease can palmoplantar psoriasis be associated with? (hint, bone lesions)
SAPHO syndrome: Synovitis, acne, pustulosis, hyperostosis, osteitis
What is pustular psoriasis of pregnancy?
Impetigo herpetiformis is other name. This dz is important as it is associated with maternal and fetal morbidity. Onset is typically in the second or third trimester with erythematous plaques studded with pustules, favoring the flexural areas. It can be associated with hypocalcemia. Intrauterine fetal death and stillbirth have been associated with this condition
Treatment for pustular psoriasis of pregnancy?
Systemic corticosteroids are first line, however recently cyclosporine and infliximab have been added as first-line agents by the National Psoriasis Foundation.
What is the number one cause of pityriasis amiantacea?
Psoriasis!
What is annulus migrans and what type of psoriasis is it most common in?
It looks like geographic tongue and it is more common in pustular variants of psoriasis.
What is inverse psoriasis and how does it present?
Psoriasis that occurs in the body folds. Its appearance is unique due to the maceration and rubbing that occurs in these areas. It presents w/ shiny pink-red, well-defined plaques w/ fissuring.
M/c areas include: axillae, inguinal crease, intergluteal cleft, inframammary region and retroauricular folds.
What nails are most commonly affected by psoriasis and how is this different from onycomycosis?
Psoriasis most commonly affects the fingernails (onychomycosis most commonly affects the toenails).
What causes the pits in the nails seen in psoriasis?
Parakeratotic foci in the proximal matrix.
What findings arise from psoriasis involvement in the distal nail matrix?
leukonychia and loss of transparency and subungual hyperkeratosis
What findings arise from psoriatic involvement of the nail bed?
Oil spots, salmon patches (2/2 exocytosis of leukocytes beneath nail plate), Splinter hemorrhages (2/2 increased capillary fragility), Onycholysis, and subungual hyperkeratosis (2/2 parakeratosis of distal nail bed)
What nail findings occur in psoriasis and what parts of the nail anatomy are affected in each lesion?
- Pits (involvement of proximal nail matrix)
- Leukonychia and loss of transparency; subungual hyperkeratosis (distal nail matrix)
- Oil spots, salmon patches, Onycholysis, and subungual hyperkeratosis (Nail bed)
Is psoriatic arthritis seronegative or seropositive?
Seronegative
Most common presentation of psoriatic arthritis?
Morning joint stiffness lasting more than 1 hour, nail changes in the vast majority, involves the DIP’s and PIPs most commonly. Seronegative. B27 genetic alterations present in 50%
What are the 5 patterns of psoriatic arthritis?
- Oligoarthritis (60-70%)
- Asymmetric DIP involvement + nail changes (16%)
- Rheumatoid arthritis like (15%)
- Ankylosing spondylitis (5%)
- Arthritis mutilans (5%) (least common)
What is the presentation of oligoarthritis psoriatic arthritis?
Affects DIP +PIP joints of hand and feet (may lead to ”sausage digit”) +/- large joint involvement; spares MCP (unlike RA which favors these)
Presentation of Asymmetric DIP Involvement subtype of psoriatic arthritis?
exclusively affects DIP, leads to ”sausage digit” and nail damage
Presentation of Rhematoid Arthritis-Like psoriatic arthritis?
Symmetric polyarthritis of small and medium joints (PIP, MCP, wrist, ankle, and elbow); hard to distinguish from RA and may be RF+
Presentation of the Ankylosing Spondylitis subtype of psoriatic arthritis?
Axial arthritis +/- sacroiliac, knee, and peripheral joint involvement; M>F, usually HLA-B27+, a/w inflammatory bowel disease and uveitis
What is the presentation of Arthritis Mutilans presentation of psoriatic arthritis?
The least common subtype, most severe (osteolysis of phalanges/metacarpal leads to short, wide, and soft digits w/ “telescoping phenomenon”)
What is the effect on incidence of allergic dz due to psoriasis?
Incidence is decreased
Comorbidities of psoriasis?
Possible risk of lymphoma, increased risk of cardiovascular dz, HLD, HTN, DM, NASH, and metabolic syndrome
Asymmetric anterior uveitis (15% in juvenile psoriasis)
MOA for apremilast?
apremilast or Otezla is a PDE-4 inhibitor. Prevents cyclic AMP degredation within immune cells which decreases overall immune activation
Main S/E for apremilast?
Diarrhea and nausea, usually resolves in 4 weeks. No lab monitoring needed.
MOA for methotrexate?
Binds dihydrofolate reductase w/ greater affinity than folic acid. This prevents conversion of dihydrofolate to tetrahydrofolate which inhibits purine synthesis and thus ell division. This has a significant effect on lymphocytes because they do not have a purine salvage system.
At what cumulative dosage of methotrexate does the risk of hepatic fibrosis increase, and when should testing be considered?
1.5-4g
Major S/E’s for methotrexate?
Pancytopenia (occurs early, 4-6 weeks), GI, phototoxicity (including UV and radiation recall rxns).
How is methotrexate cleared?
It is renally cleared. Use w/ caution in pt’s with renal dz. This can increase the risk of idiosyncratic rxn’s like the pancytopenia.
When should methotrexate be stopped prior to trying to conceive?
3 months
What is the max time that cyclosporin should be used continuously?
1 year
Cyclosporin MOA?
Forms complex w/ cyclophilin, which inhibits calcineurin which reduces activity of NFAT-1 which transcribes various cytokines like IL-2. IL-2 reduction leads to decreased numbers of CD4 and CD8 cells.
Major S/E of cyclosporin?
Hypertrichosis, gigival hyperplasia, myalgia, hypertension, kidney disease, paresthesia, tremors, malise, hyperuricemia, hypomagnesemia, hyperkalemia.
BULK-up= Bilirubinemia, hyperUricemia, Lipds (hyperlipedemia), hyperKalemia, and these are all going UP.
What are the contraindications of Methotrexate
Pt’s that pregnant, have renal disease, active infections, or cytopenias.
What antibiotic should not be used in those taking methotrexate?
Bactrim –>displaces methotrexate from binding proteins increasing effective drug levels.
Screening labs for methotrexate?
CBC, CMP, hepatitis panel, pregnancy panel, HIV test, TB tests not required but you often do it in prep for a biologic later.
Monitoring labs for methotrexate?
CBC @ week 2 and 4, CMP done at week 1 and 2, repeat CBC and CMP every 3 months.
The standard starting dose for cyclosporin?
2.5mg/kg/day (ideal body weight) split into BID dosing
Contraindications for cyclosporin?
Impaired renal function, uncontrolled HTN, malignancy, serious infections
Screening labs for Cyclosporin?
CBC, CMP, hepatitis panel, pregnancy test, quant gold, magnesium, uric acid, fasting lipids, UA.
Monitoring labs for Cyclosporin?
You should repeat a CBC, CMP, lipid panel, UA, uric acid and magnesium levels and blood pressure readings, monthly for 2 months and then every 3 months after that.
Watch the creatinine. If this increases 30% over baseline you should decrease the dose and then monitor from there.
When is acitretin effective as monotherapy?
Pustular psoriasis (1mg/kg/day) or erythrodermic psoriasis (0.25mg/kg/day)
How long must contraception be used after discontinuing acitretin before conception?
3 years! They must use contraception for 3 years after stopping to prevent teratogenicity
How is acitretin used for plaque psoriasis?
combination w/ phototherapy (PUVA). Used at 0.5/mg/kg/day
Contraindications for acitretin?
Those who are pregnant or those who are of childbearing age who can’t guarantee contraception. Also, those with severe liver or kidney dz or alcohol use (this converts the acitretin to a byproduct which stays in the body for up to 3 years)
Major S/E of acitretin?
Dry eyes, decreased night vision, dry lips, elevated liver enzymes, and teratogenicity
Screening and monitoring labs for acitretin?
CBC, CMP, lipid panel, and a pregnancy test.
These labs can be repeated at 1 month of therapy and every 3 months thereafter.
Name 3 TNF-alpha inhibitors
infliximab (Remicade), etanercept (Enbrel), adalimumab (Humira)
Which TNF-alpha inhibitor is a/w infusion rxns?
infliximab (20%), it is from infliximab associated antidrug antibodies.
What diseases can the TNF-alpha inhibitors be a/w and should be screened for?
demyelinating dz , lymphomas, and worsening of CHF
Dosing of etanercept?
SubQ injections of 50mg twice weekly for 3 months and then weekly after that.
What is the TNF-alpha that is approved for kids with psoriasis >4y/o?
Etanercept
What is unique about the dosing of infliximab?
It is given IV. Rember the I at the first of infliximab reminds you of IV
Dosing of infliximab?
5mg/kg @ weeks 0,2,6 and then every 8 weeks after that
Dosing of adalimumab?
SubQ w/ 40mg syringes –> 80mg loading dose then a 40mg dose on day 8, and then 40mg every 2 weeks after that. (remember this dose is very different than that for HS)
Name 3 IL-17 inhibitors?
Secukinumab (Cosentyx), Brodalimumab (Siliq), and ixekizumab (Taltz)
What cells make IL-17? What does IL-17 do in psoriasis pathogenesis?
The Th17 T cells, leads to increased keratinocyte proliferation and inflammation
Which IL-17 inhibitor has its action against the IL-17 receptor?
Broadalumab (its against the receptor bro)
S/E profile of IL-17 inhibitors?
No risk of issue w/ neurologic dz or HF like TNF-alpha drugs but there is increased risk of nasopharyngitis and candidiasis
You do want to watch for signs of IBD worsening or occurrence as there have been reports of worsening of IBD w/ use of these meds.
Which IL-17 inhibitor has been associated with depression and suicidal ideation?
Broadalumab –> screen for these in this one
What is something unique about the clinical effect of IL-17 inhibitors?
They tend to work very quickly.
Dosing of IL-17 inhibitors?
All are given SubQ
-Talz (ixekizumab) –> 160mg loading dose and then 80mg q 2 weeks after that until week 12 and then every month after that.
Coseyntex (Secukinumab): 300mg per week for 5 weeks and then 300mg monthly afterward
Broadalumab (siliq): 210mg on weeks 0, 1 and 2, then every 2 weeks after that.
What is the role of IL-23 in psoriasis pathogenesis?
IL-23 stimulates the Th17 cells to make IL-17, IL-22, and TNFa
Name two agents that affect IL-23
Ustekinumab (Stelara) = IL-12 and IL-23
Guselkumab (Tremfya): IL-23 only
Why does ustekunumab (stelara) affect both IL-12 and IL-23?
It affects the p40 subunit on the protein that is common to both IL-12 and IL-23
What subunit of IL-23 does guselkumab (tremfya) block?
P19 subunit of IL-23
Dosing for Ustekinumab?
Weight-based: <100kg = 45mg for each dose those >100kg = 90mg at each dose.
Injections are received on day 1, 1 month later, and then every 3 months thereafter
Dosing for Guselkumab (tremfya)
100mg @ week 0,4, then every 8 weeks after that.
What is the overall pathogenesis of psoriasis in broad terms?
Inflammatory condition where certain triggers in genetically susceptible persons stress the keratinocytes and cause an abberant inflammatory reaction.
Explain the cytokines that trigger the Th1 and Th2 pathways and then what cytokines these Th1 and Th2 cells release
Th1 cells are stimulated by IL-12 and promote CD8 t-cells by making Interferon-gamma, and IL-2, IL-6, IL-8, and IL-12 all of which are overexpressed in psoriasis.
Th2 cells are stimulated by IL-4 and release IL-10 which inhibits the Th1 pathway.
Two big t-cell lines that are involved in psoriasis pathogenesis?
Th1 and Th17
What do the Th1 cytokines actually do in psoriasis pathogensis?
Interferon gamma activates macrophages to release TNFa, IL-23, and other inflammatory cytokines.
IL-2 activates cytotoxic t-cells and NK cells
IL-6 activates acute phase proteins
IL-8 recruits neutrophils
IL-12 activates even more Th1 cells
What are the Th17 cell cytokines and their role in psoriasis pathogenesis?
Th17 cells are stimulated by IL-12 and IL-23 (both blocked by stelara), when they are stimulated they release IL-17, IL-22, and TNFa
IL-17/IL-22: proinflammatory and lead to keratinocyte proliferation
TNFa: proinflammatory and released from keratinocytes, other Th1 cells and macrophages.
This is super high yield, all the biologics act on these
What are woronoff rings?
These are areas of clearing around lesions of psoriasis
