[考生加油] Dermatological Recall: Chapter 32 Lichen Planus Part 2

口腔的扁平苔蘚除了造成疼痛，長期下來也有癌變的危險。扁平苔蘚不容易治療，常常需要另加上口服藥才能控制。很多位於頭皮、指甲的扁平苔蘚如果沒有及時治療，甚至可能造成不可逆的毛髮與指甲脫失。

Chapter 32 :: Lichen Planus Part 2

:: Aaron R. Mangold & Mark R. Pittelkow

鄭煜彬(20200329)

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