MALIGNANT TRANSFORMATION
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How about the risk of malignant
transformation in oral LP?
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Low risk (0.6-1.9%)
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What are the risk factors of malignant
transformation in oral LP?
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Long-standing dz, erosive or atrophic
types, tobacco use, esophageal involvement, oncogenic subtypes of HPV (type
16)
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What is the stage of malignant
transformation in oral LP?
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In situ carcinoma or with a microinvasive
pattern.
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Where is the common sites of malignant
transformation in oral LP?
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Tongue> buccal
mucosa>gingiva>>>lip
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What are the features of malignant
transformation in oral LP?
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Invasive SCC:
1.
Indurated, nonhealing ulcers
2.
Exophytic lesions with a
keratotic surface.
3.
Red atrophic plaques(correlate
with SCC in situ)
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What are the risk factors of SCC in LP ?
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1.
Hypertrophic or verrucous LP
2.
LP on the lower extremity
3.
A history of arsenic exposure
4.
A history of x-ray exposure
5.
Long-standing disease
(average, 12 ys)
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DIAGNOSIS
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What should you do for the vesiculobullous
disease or erosive disease of LP?
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Histopathology, DIF, IIF, & ELISA (to
differentiate from immunobullous dzs)
Laboratory testing is not required
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What laboratory testing should be
performed in LP?
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Tests for dyslipidemia
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What laboratory testing should be
performed in oral LP?
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Patch tests of mercury, gold, chromate,
flavoring agents, acrylate, & thimerosal
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What laboratory testing should be
performed in LLP?
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Testing for thyroid abnormalities: TSH,
antithyroid peroxidase antibodies, & anti-thyroglobulin antibodies.
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When should you check HCV in the case of
LP?
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Oral LP, risk factors for HCV (↑liver function, IV
drug use, blood transfusion
prior to 1992, & high risk sex), in
endemic areas (East and Southeast Asia,
South America, the Middle East, & Southern Europe)臺灣是流行區
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PATHOLOGY
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What are the major pathologic findings of
LP?
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Epidermis: hyperkeratosis, wedge-shaped
areas of hypergranulosis, & elongation of rete ridges (sawtooth)
l Basal epidermal keratinocyte damage (effacement of DEJ)
l A lichenoid-interface lymphocytic reaction: a dense, continuous,
& band-like lymphohistiocytic infiltrate at the DEJ
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What are the 2 absent features in LP?
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Parakeratosis & eosinophils
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What is the apoptotic cells at the papillary
dermis of LP ?
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Colloid-hyaline bodies=Civatte bodies=
eosinophilic bodies.
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What is the difference between lichenoid
drug eruptions & classic LP?
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Eosinophils (in 2/3 lichenoid drug
eruption)
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What is the difference between hypertrophic
LP & classic LP?
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Eosinophils (in 1/5 hypertrophic LP, thus
they are very itchy.)
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What is Max Joseph cleft formation in LP?
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Separation of the epidermis in small
clefts under severe inflammation of LP.
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What are the features of late disease of
LP?
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Scarring (an atrophic epidermis,
effacement of the rete ridges, dermal fibrosis), colloid bodies & melanophages.
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What is difference between late disease
of LP & poikiloderma?
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LP: colloid
bodies (+)
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What are the features of hypertrophic LP?
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Hyperkeratosis, acanthosis,
papillomatosis, thick-ened collagen bundles in the dermis, & Eφ.
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What are the differences between mucosal/genital
LP & cutaneous LP?
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Parakeratosis & an absent granular
layer, plasma cells.
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What are the features of LPP?
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A perifollicular, lymphohistiocytic
inflammation at only isthmus & infundibulum + scarring alopecia
(perifollicular fibrosis, scarring, & follicular atrophy)
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What is the features of DIF in LP?
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1.
IgM(±IgG, IgA) on the
apoptotic cells(colloid bodies) at the DEJ
2.
Shaggy deposition of
fibrinogen at the DEJ
3.
Multiple Ig conjugates(IgM,
IgG, IgA): consider LE
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What is the role of DIF in LP?
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1.
More important in oral LP
2.
Atypical disease
3.
Ulcerative and
vesiculobullous LP
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Where is the optimal location for biopsy
of cutaneous LP?
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1.
Proximal trunk
2.
Avoidance of the distal
extremities.
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How do you select optimal location for
biopsy of LPP & nail LP?
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With dermoscopy.
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Where is the proper location of biopsy of
nail LP?
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Surficial change (trachyonychia &
pitting): matrix
Change of plate(chromonychia, nail plate
fragmentation), subungual change(splinter hemorrhage, onycholysis, &
subungual debris): nail bed.
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Where are the proper locations of DIF of
LP ?
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1.
Mouth floor & ventral
tongue
2.
Can be 1 cm from the lesion
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DIFFERENTIAL DIAGNOSIS
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CLINICAL COURSE AND PROGNOSIS
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How long is the duration of most
cutaneous LP?
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Resolves within 1-2 years
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How much is the recurrence rate of LP?
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20%, common in generalized cutaneous
disease.
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What is the relationship between duration
& the extent/sites of LP?
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Short to Long: generalized cutaneous <
nongeneralized cutaneous < cutaneous & mucosal < mucosal <
hypertrophic <LPP
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What is the most common manifestation of
LP sequelae?
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Postinflammatory hypo-/hyperpigmentation
(in higher Fitzpatrick skin types)
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TREATMENT(challenging & discouraging)
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How can you decrease the severity of LP?
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Discontinue exacerbating drugs, minimize
trauma, & reduce microbial overgrowth
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What is most specific tx of lichenoid
dzs?
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Janus kinase (JAK) inhibitors (target
CD8-Tc cells, also works in DM, AA, & vitiligo)
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CUTANEOUS LICHEN PLANUS
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What are the choices of skin-directed Tx
of cutaneous LP?
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Topical: steroids(±occlusion), calcipotriene,
calcineurin inhibitors (esp. combination of steroids)
IL: steroids (5-10 mg/mL monthly ± topical steroids)
Phototherapy: NBUVB, BBUVB, UVA, PUVA
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What are the special applications of
hypertrophic LP?
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Occlusion of topical steroids, IL
steroids.
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What are the systemic Tx of LP?
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1st: oral steroids
2nd: sulfasalazine, metronidazole, acitretin, hydroxychloroquine/
chloroquine, methotrexate, mycophenolate mofetil (MMF), & azathioprine
3rd: cyclosporine
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How do you choose the systemic Tx of LP ?
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Refractory/ulcerative: target lymphocutes
(methotrexate, MMF,
and azathioprine)
Generalized/hypertrophic: indirectly on
lymphocytes (sulfasalazine & metronidazole) or cellular
differentiation (acitretin)
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How much is the dose of systemic prednisolone
for cutaneous LP?
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0.3-1 mg/kg/ day for 4-6 wks.
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Why is corticosteroid-sparing agents very
important for cutaneous LP therapies?
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Relapse is common after DC steroid
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What drug in 2nd line
therapies has highest efficacy for cutaneous LP?
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Sulfasalazine (1-2.5 g/day)
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What is adverse effects of sulfasalazine?
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Agranulocytosis & ↑liver function
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What is the role of metronidazole in the Tx
of cutaneous LP?
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1.
The first-line
nonimmunosuppressive systemic agent (250mg tid or 500mg bid)
2.
Effective in generalized
cutaneous LP.
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What is adverse effects of metronidazole?
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Sensory peripheral neuropathy
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What is the role of acitretin in the
therapies of cutaneous LP ?
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Highly effective for hypertrophic LP (30
mg/day)
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What is adverse effects of acitretin?
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Mucocutaneous side effects(xerosis,
scaling) and hyperlipidemia
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What is the role of antimalarials in the Tx
of cutaneous LP ?
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Chloroquine: cutaneous LP.
Hydroxychloroquine: LPP, & actinic
LP, favorable side effects
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What is the role of methotrexate in the Tx
of cutaneous LP ?
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Works for recalcitrant disease,
hypertrophic LP, & LPP
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What is drawbacks of MMF, azathioprine,
& cyclosporine?
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MMF: expensive, delayed response (needs
steroids)
Azathioprine: suppressive effects on T +
B lymphocytes & poor tolerability
Cyclosporine: expensive, frequent
relapses, long-term side effects (kidney insufficiency & lymphoma)
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ORAL LICHEN PLANUS
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What is the cornerstone of Tx in oral LP?
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Good oral hygiene with regular
professional dental cleanings
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How can patients minimize exacerbating
factors of oral LP?
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Avoiding contact allergens(removal of
amalgams, gold), DC drug, reducing oral microbes & trauma
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What are the skin-directed Tx of oral LP?
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1st: topical sterods in
orabase.(Stronger agents: clobetasol & fluocinonide + more occlusive
preparations + 2-6 times daily)
2nd: topical tacrolimus/
pimecrolimus
3rd: topical cyclosporine/tretinoin
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What is the major complication of topical
steroids?
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Fungal infection
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How can you manage the major complication
topical steroids?
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Oral chlorohexidine gluconate mouthwash,
topical anticandidal medications, oral fluconazole
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What is the side effect of topical
calcineurin inhibitors for oral LP?
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Transient burning (improved by combination
of topical steroids)
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What is the role of IL steroid in the Tx
of oral LP?
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Last line (after exhausting topical
therapies, 10-40mg/ml, Q 1-4 wks)
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What are the systemic Tx of oral LP?
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1st: oral steroids
2nd: acitretin,
hydroxychloroquine/ chloroquine, methotrexate, MMF
3rd: cyclosporine, azathioprine…
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How much is the dose of systemic prednisolone
for oral LP?
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1.5-2 mg/kg/ day for 4-6 wks.
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What are the concerns of systemic Tx in
oral LP? (2)
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1.
iatrogenic candida infections
2.
↑risk of oral SCC under erosive & refractory LP &
immunosuppression
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What drugs are preferred in oral LP? (4)
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Erosive LP
1.
MMF
2.
Hydroxychloroquine (less
immunosuppressive)
3.
Methotrexate (less immunosuppressive)
Hyperkeratotic/noneroded LP
4.
Acitretin (antiploliferative,
less immunosuppressive)
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How much is the dose of systemic steroids
for oral LP?
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Prednisolone: 1.5-2 mg/kg (higher than
skin, more side effects)
Betamethasone: 5 mg on 2 consecutive days
weekly (pulse tx: less side effects)
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What oral drugs can be considered in oral
LP?
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1.
Acitretin 30mg/day
2.
Alitretinoin 30mg/day (臺灣沒有)
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What are first choices of steroid-sparing
agents for oral LP? (2)
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1.
Methotrexate (10-15mg/wk)
2.
MMF (2-3g/day)
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Tx of LPP
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Why does LPP & FFA cause scarring
alopecia?
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Deficiency of PPARγ→loss of immune privilege→destruction of the
bulge
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What are the skin-directed Tx of LPP?
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1st: mid to high potency steroids(topical
or IL)
2nd: calcineurin inhibitors
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What are the systemic Tx of LPP?
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1st: prednisolone 1 mg/kg/day
2nd: Hydroxychloroquine (+
doxycycline, not monotherapy),
MMF, methotrexate
3rd: cyclosporine (monotherapy)
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Tx of FFA
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What are the skin-directed Tx of FFA?
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IL steroid, topical minoxidil (combine hydroxychloroquine
or others)
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What are the systemic Tx of FFA?
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1.
5 α-reductase inhibitors (finasteride
2-5mg/day or dutasteride 0.5mg every 1-7 days)
2.
Systemic steroids + MTX &
MMF
3.
Cyclosporine (monotherapy)
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NAIL LICHEN PLANUS
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What is the goal of the therapy of nail
LP?
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Stop the disease (prevent irreversible
pterygium), not reverse it.
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What is the therapies of nail LP?
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Ultrapotent topical & intralesional
steroids→syetemic steroids (for compromise of function & debilitating
pain) or hydroxychloroquine
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