兩本教科書同時大改版後，每天用凌晨的零碎時間熬夜趕工，終於將上課內容翻修改版終於完成！
 |
| 圖1：典型的結節型基底細胞癌，位於上嘴唇，上面會有一些黑色斑點，但往往不會擴及整個病灶，彷彿一個黑得不太完全的黑痣。 |
 |
| 圖2：結節型基底細胞癌發展到最後變成一個長久不癒的潰瘍，位於鼻翼外側臉頰。 |
 |
| 圖3：色素型基底細胞癌，位於髮際線，看起來很黑又有潰瘍，常被誤以為為是黑色素瘤。但本例整個全黑且邊緣相對隆起，並非黑色素瘤特徵。 |
 |
| 圖4：表淺型基底細胞癌，是一塊位於胸口，邊緣清楚的紅色斑塊，表面稍微粗糙類似濕疹但以濕疹方式治療無效。 |
 |
| 圖4：硬斑型基底細胞癌，看起來是一塊偏白稍硬的斑塊，常被誤認為是一個疤痕。 |
 |
圖5：鼻子上的基底細胞癌，在其他醫院確診後轉給筆者治療。經手術廣泛切除達到安全距離(safe margin)後，考量直接縫合張力過大，以皮瓣手術關閉傷口。半年之後除了膚色稍白尚未完全恢復外，疤痕相當輕微，幾乎看不出來。
|
 |
圖1 典型的鱗狀細胞癌原位癌：一塊紅色、邊界清楚、略為增厚、表面粗糙的皮膚
|
 |
圖2 頭頸部的鱗狀細胞癌原位癌：呈現紅色、粗糙的厚皮
|
 | ||
圖3 與圖2相同病人頭頸部另一處的鱗狀細胞癌原位癌：鱗狀細胞癌原位癌有時會有多處病灶，因為附近的皮膚往往也累積了相當程度的DNA突變。
|
 |
圖5 結痂的臨床細胞癌原位癌，呈現棕色與黃灰色的痂
|
 |
圖6 色素型的鱗狀細胞癌原位癌(pigmented squamous cell carcinoma in situ)，可能會被誤以為是老人斑。
|
 |
| 圖7 手術切除並轉皮瓣縫合是最能確保根治的作法 |
 |
| 圖8 手術切除得當，也可以兼顧美觀。本例是筆者幫106歲的人瑞切除額頭多年的鱗狀細胞癌，經過半年後回診追蹤，除了色素稍有不均之外，彷彿什麼事都沒發生過。 |
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 |
|
INTRODUCTION
|
|
|
What is the meaning of lichen planus(LP)?
|
Flat(planus) tree moss(lichen)
|
|
What is the involved tissue of LP?
|
Any ectodermal-derived tissue
|
|
What is the classification of LP?
|
Papulosquamous lesion (however, it just
has scant scales, not really “squamous”)
|
|
What is the four Ps of LP?
|
(1) purple, (2) polygonal, (3) pruritic,
& (4) papules
|
|
What is the histological feature of LP?
|
A brisk lymphocytic interface reaction
(lichenoid infiltration)
|
|
PATHOGENESIS
|
|
|
What contributing factors may cause LP?
|
Infectious, immune, metabolic, and
genetic causes
|
|
What is the main responder of LP?
|
Cell–mediated immunity(T cells). Immunoglobulins
(humoral immunity) is only secondary response.
|
|
What is the constitution of T cells in
LP? (Th or Tc?)
|
Dermis: CD4+ T-helper (CD4-Th)
Near basal keratinocytes: CD8+T-cytotoxic
(CD8-Tc)
|
|
What is the 4 stages of LP?
|
antigen recognition, lymphocyte
activation, keratinocyte apoptosis, resolution.
|
|
What is the pathogenesis of LP ?
|
Some antigen→Langerhans cell→↑MHC class II
receptors→↑CD4-Th (antigen recognition of HLA-DR(+) keratinocyte)→release
inflammatory cytokines (IFN-γ)→CD8-Tc oligoclonal expansion
|
|
What is the antigen of typical LP?
|
Unknown antigen
|
|
What is the antigen of lichenoid GVHD?
|
Alloantigens from the graft.
|
|
What is the antigen of oral LP?
|
MHC class I on keratinocytes (an
autoreactive peptide or an exogenous antigen?)
|
|
What are the exogenous antigen of LP?
|
1.
Inorganic mercury (dental
amalgam), gold (act as haptens)
2.
Syphilis, HSV 2, HIV,
amebiasis, chronic bladder infections, HCV, Helicobacter pylori, or HPV.
|
|
What are the cause of TNF- α associated lichenoid
tissue reactions(LTRs)?
|
TNF-α inhibitors (dysregulated cytokine) → upregulation of
type I IFN)
|
|
What is the major cytokine in LP?
|
IFN-γ (↑migration of lymphocytes to DEJ)
|
|
How does IFN-γ work in LP?
|
↑inflammatory
chemokines CXCL-9, 10, & 11→activate CXCR-3 on
CD4-Th
|
|
Why does peroxisome-proliferator-activated
receptor γ (PPARγ) stop scarring alopecia in LPP?
|
It inhibits CXCL-10 & 11
|
|
What is the mechanism of keratinocyte
apoptosis in LP?
|
CD8-Tc cells→granzyme B release,
TNF-α–TNF-α R1 receptor interaction, & Fas–Fas-L interaction
|
|
What is the mechanism of disruption of
the basement membrane in LP?
|
TNF-α→↑matrix metalloproteinase-9 (MMP-9), especially
in ulcerative lesions
|
|
What is the mechanism of the resolution
of LP?
|
1.
T-regulatory cells→↓Tc
2.
Fas-L, granzyme B, &
perforin on the keratinocytes: apoptosis of Tc
|
|
GENETIC AND EPIGENETIC REGULATION
|
|
|
What are the sites of gene polymorphisms
related to LP?
|
HLA,
immune signaling molecules & receptors (IFN-γ, TNF-α, TNF-α R2, IL-4,
IL-6, IL-18, NF-κB), PGE2, oxidative stress,
transglutaminase, thyroid hormone, & prothrombin.
|
|
What are miRNAs related to the epigenetic
regulation of LP?
|
micro-RNA (miRNA)-146a & -155
|
|
What are the most specific marker of LP?
|
CXCR-3 ligand & CXCL-9,
|
|
EPIDEMIOLOGY
|
|
|
How much is the prevalence of LP?
|
1% (0.1-4%), but not exact.
|
|
What is the age of most LP?
|
30-60 y/o (2/3 of all cases)
|
|
What is the peak onset of LP?
|
>55 y/o (elderly, earlier in women)
|
|
How much is the prevalence of childhood
LP?
|
1-5%, 20% in Pacific Indians. no sexual
predilection
|
|
What is the peak onset of childhood LP?
|
Between 8 & 12 years of age
|
|
What is the features of familial LP?
|
Family history(廢話), early onset, widespread & erosive/ulcerative disease,
mucosal involvement, & frequent relapses.
|
|
What is the HLA tendency in familial
& nonfamilial LP?
|
Familial: HLA-B27, Aw19, -B18, & -Cw8
Nonfamilial: HLA-A3, -A5, -A28, -B8,
-B16, & Bw35
|
|
What is the HLA tendency in oral & cutaneous
LP?
|
Oral: HLA-B8
Cutaneous: HLA-Bw35
|
|
CLINICAL FEATURES
|
|
|
Where is the locations of LP?
|
Skin, oral mucosa, any ectodermal-derived
tissue (hair, nails, internal & external genitalia, eyes, &
esophagus.)
|
|
How long is the development of typical
LP?
|
Over the course of weeks.
|
|
CUTANEOUS FINDINGS
|
|
|
What are the clinical featurs of LP?
|
1.
Well-marginated, dull
red-violet, flat-topped, polygonal papules. (4”Ps”)
2.
The grouped papules often
coalesce into plaques.
3.
Wickham striae, fine, white &
adherent reticulate scale (esp. in dermoscopy)
|
|
What is the meaning of Wickham striae?
|
1.
Characteristic features of LP
2.
Correlate with
orthokeratosis, epidermal thickening, & an ↑granular
layer.
|
|
Why does LP have dull red-violet hue?
|
Combination of vascular dilation &
pigment incontinence
|
|
Where are the typical locations of LP
lesions?
|
The flexural wrists, arms, legs, proximal
thighs, trunk, & neck, symmetrical distribution.
|
|
Where are the atypical locations of LP
lesions?
|
Face & palms
|
|
Where are the locations of inverse LP ?
|
Axillae, groin, & inframammary region
|
|
What is the most common symptom of LP?
|
Extreme pruritus (directly correlate with
the extent of involvement)
|
|
What type of LP affects limited areas but
has severe pruritus?
|
Hypertrophic LP (only lower extremities)
|
|
What is the name of trauma-induced
disease in acute LP?
|
Isomorphic (Koebner) phenomenon
|
|
What is the reason of isomorphic phenomenon?
|
Trauma→endogenous peptides (cathelicidin
LL-37) or antigens (DNA & RNA)→type I IFNs (-α
and -β) →LP
|
|
What is the common sequela of LP?
|
Postinflammatory hyperpigmentation, esp.
on darker skin. (hypopigmentation: other diagnosis)
|
|
What is the percentage of oral LP? (Adults
& children)
|
Adult: 42-60% (about 1/2)
Children: 17-30% (about 1/5)
|
|
What is the percentage of hair & nail
LP? (Adults & children)
|
Adult: 2-6% (about 1/20)
Children: 0-19% (about 1/10)
|
|
CLINICAL VARIANTS
|
|
|
How are LP variant categorized?
|
According to configuration, morphology,
& sites.
Configuration: annular LP, linear/ Blachkoid/
zosteriform LP
Morphologic appearance: hypertrophic LP,
atrophic LP
Site of involvements
|
|
What are the location of annular LP?
|
Penis & scrotum
|
|
What are the morphology of annular LP?
|
An arcuate grouping of individual papules→form a ring or
expand centrifugally with a central clearing & hyperpigmentation.
|
|
What is actinic LP
|
Annular LP in subtropical zones on
sun-exposed, dark-skinned young adults & children.
|
|
What is the cause of linear LP?
|
Trauma induces a row of LP papules.
|
|
What is the cause of Blaschkoid LP?
|
Postzygotic, somatic mutations in
susceptibility-associated genes
|
|
What is the cause of zosteriform LP?
|
A viral trigger of disease or an isotopic
response related to underlying resident memory cells.
|
|
What is the difference between linear
& zosteriform LP?
|
Linear LP does not follow dermatomal
lines.
Zosteriform LP follow dermatomal lines.
|
|
What are the differential diagnoses of
linear, Blaschkoid, zosteriform LP?
|
All segmental diseases: lichen striatus,
linear epidermal n., inflammatory linear & verrucal epidermal n., linear
psoriasis, & linear Darier dz.
|
|
Where are the locations of hypertrophic
LP?
|
Anterior shins & interphalangeal
joints.
|
|
What are the features of hypertrophic LP?
|
1.
Thickened, elevated,
purple-red, hyperkeratotic plaques & nodules, with follicular
accentuation & chalk-like scale.
2.
Highly pruritic, refractory
to treatment, & associated with relapse.
|
|
What are the differential diagnoses
verrucal lesions of hypertrophic LP?
|
Keratinocyte carcinomas, rupioid
psoriasis, rupioid syphilis, reactive arthropathy (Reiter's
syndrome), & cutaneous LE
|
|
What is the associated disease of
hypertrophic LP?
|
Chronic venous insufficiency
|
|
What are the features of atrophic LP?
|
Oligo-lesional, well-marginated,
blue-white papules or plaques with central atrophy.
|
|
Where are the locations of atrophic LP?
|
Proximal lower extremity & trunk
|
|
What are the differential diagnoses of
atrophic LP?
|
Lichen sclerosus et atrophicus &
mycosis fungoides
(MF)
|
|
What is the nature of atrophic LP?
|
Late-stage resolved disease of LP
|
|
What is the mechanism of vesiculobullous
LP?
|
Secondary to an exuberant inflammatory
response of LP (acute flares) & an exaggerated Max-Joseph space.
|
|
What are the features of LP pemphigoides?
|
1.
Classic LP + lesions of bullous
pemphigoid
2.
Bullous pemphigoid antibodies
(BP 180 and 230) & immunofluorescence.
|
|
What is the mechanism of LP pemphigoides?
|
LP→exposure of autoantigen→bullous pemphigoid antibody →BP lesions
|
|
Where are the locations of
vesiculobullous LP?
|
Lower extremities & oral cavity (became
erosion & ulcer).
|
|
What are the features of erosive &
ulcerative LP?
|
1.
Erosion & ulcer
2.
Significant pain &
scarring
3.
Other ectodermal involvement
(scarring alopecia & loss of the toenails)
4.
SCC in chronic lesions of
ulcerative oral LP.
|
|
Where are the locations of erosive &
ulcerative LP?
|
Feet & oral cavity
|
|
What are the 3 major variants of
follicular LP?
|
Lichen planopilaris (LPP), frontal
fibrosing alopecia(FFA), & Gram-Little-Piccardi-Lassueur syndrome (GLPLS)
|
|
What is the features of LP follicularis
tumidus (LPFT)?
|
Pruritic, red-violet pseudo-tumoral
facial & posterior auricular plaques + yellow cysts + LP elsewhere
|
|
What are the differential diagnoses of
LPFT?
|
Folliculotropic MF, & cutaneous lupus
erythematosus
|
|
What are the features of LP pigmentosus
(LPP)?
|
Hyperpigmented, dark-brown macules in
sun-exposed & flexural folds, usually in darker skinned individuals.
|
|
What is the relationship between LPP
& ashy dermatosis(erythema dyschromicum)?
|
A phenotypic spectrum based on genetic
&
environmental factors: they have
significant overlapping.
|
|
What are the features of actinic LP?
|
1.
Minimally symptomatic
2.
Annular, well-marginated,
hyperpigmented brown-violet, flat-topped, plaques with a slightly rolled
border
3.
Subtropical zones on
sun-exposed, dark-skinned young adults & children of Middle Eastern
descent
4.
In the spring & summer
months.
5.
Hx: a more brisk LTR relative to LP pigmentosus, vacuolar changes,
& pigment incontinence.
|
|
Where are the locations of actinic LP?
|
Face > the dorsal hands, arms, &
nape of the neck(sun-exposed skin)
|
|
Who predisposes LP of the scalp?
|
female
|
|
What are the 3 variants of LP of the scalp?
|
LPP, FFA, & GLPLS (the same as
follicular LP)
|
|
What are the features of classic LPP?
|
Individual perifollicular hyperkeratosis
+ diffuse livid erythema→plaques on the scalp→scarring alopecia
|
|
Where is the typical location of classic
LPP?
|
Vertex of the scalp
|
|
What are the features of LPP on the
dermoscope?
|
Absence of follicular opening, cicatricial
white patches, peripilar casts and perifollicular scale, blue-gray dots,
perifollicular erythema, & polytrichia (2 or 3 hairs)
|
|
What is the features of FFA?
|
1.
Progressive frontotemporal
recession (inflammatory)
2.
Loss of the eyebrows
(noninflammatory)
|
|
Who predisposes FFA?
|
Postmenopausal women (but can occur in
younger women)
|
|
What might be the cause of FFA?
|
Leave-on facial products, sun-screen,
& allergy to fragrances (positive patch test)
|
|
What are the features of GLPLS?
|
Cicatricial alopecia of the scalp,
nonscarring alopecia of the axilla & groin, & follicular papules on
the trunk & extremities.
|
|
What is the end stage of follicular LP?
|
Pseudopelade of Brocq (it can also be the
result of LE, pustular scarring forms of folliculitis, fungal infections,
scleroderma, & sarcoidosis.)
|
|
Where are the typical locations of
mucosal LP?
|
Mouth or genitalia
|
|
What are the types of oral LP?
|
Reticular(most common), plaque-like,
atrophic, papular, erosive or ulcerative, & bullous forms.
|
|
What are the locations & symptoms of
all the types of oral LP?
|
1.
Reticular: buccal >
tongue> gingiva (asymptomatic)
2.
Erosive & ulcerative:
tongue (extremely painful), gingiva (gingival stomatitis or desquamative
gingivitis)
|
|
What is the difference between oral LP
& oral lichenoid reactions (OLRs)
|
OLRs have an identifiable cause (They are
similar clinically & histologically)
|
|
Where is the common location or OLRs?
|
Buccal mucosa adjacent to amalgam dental
fillings
|
|
What is the result of patch test on the
patients with OLRs?
|
Positive reactions to mercury, gold,
& other metals→ negative after the removal of amalgams. (A special site irritant
reaction → koebnerization)
|
|
What are the features of oral LP on the
patients of HIV
|
1.
Bilateral reticular keratotic
or atrophic changes of the buccal mucosa
2.
Lichenoid atrophic patches
over the dorsal tongue
3.
Follows zidovudine or
ketoconazole intake (a unique drug hypersensitivity)
|
|
What is the features of esophageal LP?
|
1.
proximal esophagus (upper
1/3)
2.
middle-aged women
3.
preceding or concomitant oral
LP
4.
progressive dysphagia and
odynophagia
5.
lacy white papules, pinpoint
erosions, desquamation, pseudomembranes, & stenosis.
6.
Hx: parakeratosis (not in
skin LP), epithelial atrophy, & lack of hypergranulosis
|
|
What is the percentage of male genitalia
involvement of LP?
|
25% of all male cases
|
|
What is the most common pattern &
location of LP on male genitalia?
|
Annular lesions on glans penis
|
|
What are the features of anal LP?
|
Leukokeratosis, hyperkeratosis,
fissuring, & erosions
|
|
What are the features of vulvar &
vaginal LP?
|
1.
Combined with oral LP (in
25-60% oral LP cases)
2.
Patches of leukoplakia or
erythroplakia→erosive & atrophic disease→desquamative vaginitis
3.
Often asymptomatic→burning, itching,
painful erosion
|
|
What is vulvovaginal gingival syndrome
(VVGS)?
|
Triad of gingival/lingual erythema &
erosions, vulvar & vaginal desquamation & erosions. (Also involves skin/scalp/nails/esophagus
)
|
|
What are the significant long-term
sequelae of VVGS?
|
Fibrosis & stricture of vagina (needs
aggressive topical and systemic immunosuppression)
|
|
What are the HLA related to VVGS?
|
Class II HLA DBQ1∗0201 allele
|
|
What are the sequelae of conjunctival LP?
|
Cicatricial conjunctivitis.
|
|
What are the differential diagnoses of
conjunctival LP?
|
Paraneoplastic autoimmune multiorgan
syndrome
& paraneoplastic/cicatricial
pemphigoid
|
|
How to distinguish conjunctival LP with
other cicatricial conjunctivitis?
|
Direct immunofluorescence, indirect
immunofluorescence, & serologies for autoantibodies
|
|
What are the signs/symptoms of otic LP?
|
Otorrhea or external auditory canal
stenosis.
|
|
What is the long-term sequelae of otic
LP?
|
Progressive hearing loss(involvement of
external auditory canal & tympanic membrane)
|
|
What are the 3 major forms of nail LP?
|
Classic nail lichen planus , 20-nail
dystrophy, & idiopathic atrophy of the nails.
|
|
Which 2 forms of nail LP are common in
children?
|
20-nail dystrophy, & idiopathic
atrophy of the nails.
|
|
What are the common features of classic
nail LP?
|
Thinning, longitudinal ridging, distal
nail splitting (onychoschizia), onycholysis, longitudinal striation with a
“sandpaper-like quality” (onychorrhexis), subungual hyperkeratosis, &
atrophic or absent nail plates(anonychia)
|
|
What is the early finding of nail LP in
dermoscopy?
|
Nail pitting
|
|
What is the classic finding in nail LP involving
the matrix?
|
Pterygium or forward growth of the eponychia with adherence to the proximal
nail plate (irreversible, loss of nail plate)
|
|
What are the common features of 20-nail
dystrophy?
|
Trachyonychia (uniform roughness of the
20 nails), an indolent course.
|
|
What are the common features of idiopathic
atrophy of the nails?
|
Abrupt onset & rapidly progressive
thinning of the nails→subsequent loss & scarring ± dorsal pterygium
|
|
What are the differential diagnosis of
nail LP?
|
Psoriasis, alopecia areata, atopic
dermatitis, & rarely immunobullous diseases.
|
|
What are the features of inverse LP?
|
Red-brown,
discrete papules & flat-topped plaques at flexural areas
|
|
What are the locations of inverse LP?
|
Flexural areas: axillae, inframammary
region, & groin. (antecubital, popliteal, other ectodermal-derived
tissues are rare.)
|
|
What peoples predispose inverse LP?
|
Whites, Asians, & Tunisians
|
|
What are the differences of LP
pigmentosus & inverse LP?
|
LP pigmentosus inversus: flexural areas, no
involvement of sun-exposed areas
LP pigmentosus: flexural areas +
sun-exposed areas.
|
|
Where are the involved areas in those
with palmoplantar LP?
|
1.
Internal plantar arch of feet
2.
Thenar & hypothenar
eminence of hands.
3.
Anterior shin & malleoli
|
|
What are the features of palmoplantar LP?
|
Pruritic, red-purple, scaly plaques (a faint purple hue
& an inflammatory halo) ± callus-like, yellow,
compact keratotic papules/papulonodules on the lateral margins of the fingers
& hand surfaces.
No Wickham striae.
|
|
What are the 4 patterns of palmoplantar
LP?
|
Plaque type, punctate, diffuse
keratoderma, & ulcerated
|
|
What are the differential diagnoses of
palmoplantar LP?
|
Keratotic papules of palms & soles: psoriasis,
warts, calluses, porokeratosis, hyperkeratotic dermatitis, tinea, or
secondary syphilis.
|
|
What are the features of lichenoid drug
eruptions?
|
Localized or generalized with eczematous
papules & plaques with variable degree of desquamation
|
|
What are the cause of lichenoid drug
eruptions?
|
Ingestion
1.
Gold salts
2.
β-blackers
3.
Antimalarials
4.
Diuretics (thiazides,
furosemide, spironolactone)
5.
Penicillamine
6.
Immune checkpoint inhibotors (17%: pembrolizumab, nivolumab,
ipilimumab)
Contact or inhalation of certain
chemicals.
1.
Color film developers
2.
Dental restoration materials
(amalgams: Ag, Hg, Au)
3.
Musk ambrette (合成麝香)
4.
Nickel
5.
Gold
6.
Aminoglycosides
|
|
What are the features of lichenoid drug
eruptions?
|
1.
Often with hyperpigmentation
& alopecia
2.
Rare Wickham striae
3.
Often symmetrical on the
trunk & limbs, less flexural.
|
|
What are the common photo-inducer of LP
or lichenoid drug eruptions?
|
1.
5-FU
2.
Carbamazepine,
chlorpromazine, diazoxide
3.
Ethambutol
4.
Pyritinol (analog of vitamin B₆)
5.
Quinine (antimalaria )
6.
Quinidine (class I antiarrhythmic)
7.
Tetracycline
8.
Thiazide
9.
Furosemide
|
|
Why is lichenoid drug eruption hard to
diagnosed?
|
The latency period varies from months to
>1 year.
|
|
How long is the resolution of lichenoid drug eruption?
|
3-4 months(related to the severity &
extent), but may be years in gold-induced lesions.
|
|
What patients may have genetic
susceptibility of lichenoid drug eruption?
|
Recurrent cases and cases involving
immune-modulating drugs( INF-α, ipilimumab, pembrolizumab, & nivolumab=melanoma-related)
|
|
What are the features of LP-LE?
|
1.
Overlap of LP & LE
(clinical, histology, immunofluorescence)
2.
Red-violet, atrophic patches & plaques + hypopigmentation,
telangiectasia, & minimal scale.(The
bold is the features of LP)
3.
Some individuals→SLE.
4.
Weakly positive ANA.
5.
Prolonged course &
refractory to Tx.
|
|
Where are the locations of LE-LP?
|
The dorsal limbs, esp. hands &
nails(anonychia)
|
|
What are the features of lichen planus
pemphigoides?
|
1.
LP + BP (LP pemphigoides
blisters occur on the lichenoid lesions & normal skin)
2.
Younger age than typical BP
3.
Better prognosis than typical
LP
4.
Can be drug-induced.
|
|
What is the possible pathogenesis of LP
pemphigoides?
|
The brisk LTR→liquefactive
degeneration of keratinocytes→exposure of autoantigens→autoantibody
|
|
What is the antigen of LP pemphigoides?
|
Medical College of Wisconsin domain 4
(MCW-4) of BPAG180
|
|
What are the features of keratosis
lichenoides chronica (Nekam disease)?
|
1.
Lichenoid, keratotic papules
& plaques
2.
A seborrheic distribution,
palms & soles
3.
Folliculo- &
infundibulocentric
4.
Linear or reticulate pattern.
5.
Asymptomatic & refractory
to treatment
6.
A brisk LTR + parakeratosis +
Nφin
the crust
|
|
Lichenoid Graft versus Host Disease
|
|
|
What is the classic acute GVHD?
|
Transplant<100 days, a classic (folliculocentric)
maculopapular rash; GI s/s; &↑bilirubin (liver).
|
|
What is the classic chronic GVHD?
|
Transplant >100 days, dermatitic,
sclerodermoid, or lichenoid eruption
|
|
What is the new classification of GVHD?
|
1.
Acute GVHD: classic, persist,
recurrent, or late-onset (after 100 days)
2.
Classic chronic GVHD, and
overlap syndromes.
|
|
What are the driving cytokine of acute
& chronic GVHD ?
|
Acute: Th2 cytokines
Chronic: Th1/Th17 cytokines (IFN-γ– &
IL-17)
|
|
What are the features of lichenoid GVHD?
|
1.
Classic lichenoid papules
2.
Prominent follicular
involvement of the head & neck & oral involvement.
3.
Onycholysis & cicatricial
alopecia
|
|
What are the differences between GVHD
& LP?
|
Grossly similar, but GVHD has satellite
cell necrosis, plasma cells, & Eφ
|
|
What are the features of lichenoid
keratosis(LK)?
|
A single, nonpruritic, brown to red,
scaling flat-topped plaque on sun-exposed extremities.
|
|
What is the histological feature of LK?
|
LTRs + parakeratosis or a remnant
lentigo, seborrheic keratosis, or actinic keratosis.
|
|
What are the features of lichenoid
dermatitis?
|
Nonclassic LTRs + spongiosis ± granuloma
|
|
What are the differential diagnoses of
lichenoid dermatitis?
|
Dermatitis, drug eruption, lupus erythematosus,
lichen planus, & cutaneous T-cell lymphoma.
|
|
RELATED FINDINGS
|
|
|
What is the most common associations of
LP?
|
Liver diseases: autoimmune chronic active
hepatitis, primary biliary cirrhosis (PBC), & postviral chronic, active
hepatitis.
|
|
What
are the associated autoimmune dzs of LP?
|
SLE,
Sjögren syndrome, dermatomyositis, vitiligo,
&
alopecia areata (Taiwanese data)
|
|
What is the associated infection of oral
LP?
|
HCV in endemic regions (East &
Southeast Asia, South America, the Middle East, & Southern Europe)
|
|
Is there association between cutaneous LP
and HCV?
|
No
|
|
Is there association between LP &
HBV?
|
No
|
|
What is the related HLA of HCV-induced
oral LP?
|
HLA-DR6
|
|
What is the common laboratory abnormality
in LP?
|
1.
Dyslipidemia (higher risk of
cardiac dz & metabolic syndrome)
2.
Hypothyroidism (in 1/3 LPP)
|
|
What is the relationship between LP &
lichen sclerosus et atrophicus?
|
Oral LP→↑lichen sclerosus
et atrophicus
Lichen sclerosus et atrophicus: no risk
of oral LP.
|
|
What is the relationship between LP &
internal malignancies?
|
LP can be a manifestation of paraneoplastic
autoimmune multiorgan syndrome.
|
