Transcript Document

Mucinoses, Lichen
Planus and Related
Conditions
Kristy P. Gilbert, D.O.
January 24, 2006
What is Mucin?
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Fibrillar matrix in dermis called ground
substance, created by fibroblasts.
Ground Substance= acid glycosaminoglycans
and proteoglycans (formerly called acid
mucopolysaccharides) that bind 1000 times their
own volume in water
Adding sulfates to the acid GAGs creates
chondroitin sulfate and dermatan sulfate, the 2
primary dermal mucins
Classification
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Primary mucinoses
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Mucin deposition is the main histologic feature
Secondary mucinoses
Mucin deposition is an additional finding
 Examples include: LE, Dermatomyositis, Degos’,
GA, cutaneous tumors, or after therapies such as
PUVA or retinoids
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H&E: GA: Wispy bluish, feathery
material between collagen bundles
Colloidal Iron Staining: GA
Mucin – “wispy, feathery”
Mucin Stains
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Colloidal Iron
Alcian Blue
Toluidine Blue
Incubation of tissue in hyaluronidase eliminates
the staining, confirming the presence of mucin
Lichen Myxedematosus
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Aka Papular Mucinosis
Generalized = Scleromyxedema
Onset age 30-80
Multiple waxy 2-4mm dome shaped or flat topped
papules, usually linear array
Acral: dorsal hands, face, elbows, and extensor
extremities
Five localized forms recognized. Characterized by a
lack of monoclonal antibody and systemic disease.
Lichen Myxedematosus
Discrete Papular Lichen
Myxedematosus
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Waxy 2-5mm firm flesh colored papules, usually
confined to the limbs or trunk
May have erythematous or yellow hue, and
coalesce into nodules or plaques
Slow accumulation of papules over time is the
usual course
Papular Mucinosis and AIDS
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Widespread
Not associated with a paraprotein
Always seen in advanced HIV disease
If associated with eczematous dermatitis, usually
clears when eczema clears
May respond to oral retinoids
Histopathology of lichen myxedematosus (discrete type).
Mucin deposits splay collagen bundles in the dermis,
but there is only slight fibroblast proliferation and no
sclerosis.
Lichen myxedematosus of the discrete type
demonstrating mucin accumulation in the
dermis. Alcian blue stain (pH 2.5).
Acral Persistent Papular Mucinosis
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Subtype of localized LM
Usually women- F:M ratio is 5:1
Few to 100 bilaterally symmetrical 2 to 5mm, flesh
colored papules
Almost always on hands and wrists.
Rarely elbows, calves, or knees
No paraprotein, no systemic disease
H&E: Increased dermal mucin, but not fibroblasts
Self-healing Juvenile Cutaneous
Mucinosis
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Sudden onset, age 5 to 15
Skin lesions and polyarthritis x a few months.
Ivory white papules head, neck, trunk and
periarticular; also can be deep nodules on the
face and periarticular regions
Hard edema of periorbital area/face
Acute arthritis affects the knees, elbows and
hand joints
TSH, IgG normal
H&E dermal mucin
Self-Healing Papular Mucinosis
Adult form:
 Usually without the associated joint
symptoms
 Prognosis of both forms is excellent with
spontaneous resolution without sequelae
over several months
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Cutaneous Mucinosis of Infancy
AKA Papular Mucinosis of Infancy
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Subtype of localized LM
3 cases, onset birth-3 months of age
2-8mm skin-colored or translucent papules on trunk,
extremities, especially backs of hands
TSH, Paraprotein negative
There are neither systemic symptoms nor spontaneous
resolution as existing lesions remain static
H&E: papillary dermal mucin, no fibroblast
proliferation
Generalized Lichen Myxedematosus
Scleromyxedema
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Chronic and progressive; affects adults of both sexes
usually from ages 30-80.
Widespread eruption of 2-4 mm, firm, waxy, closely
spaced dome-shaped or flat topped papules
Papules often arranged in a linear array and may
coalesce into plaques
Surrounding skin is shiny and indurated(sclerodermoid)
“Doughnut sign” = central depression surrounded by
an elevated rim (due to skin thickening) is seen on the
PIP joints.
Scleromyxedema
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Woody, fibrous sclerosis
of skin
Lesions coalesce to
form leonine facies
Decreased ROM of
hands, lips and
extremities
Dysphagia is most
common GI symptom
Scleromyxedema: Systemic
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Pulmonary
Proximal Muscle
weakness
Arthralgias and
inflammatory arthritis
Carpal Tunnel Syndrome
Peripheral Neuropathy
Raynaud’s
IgG lambda
paraproteinemia
Myeloma
Scleromyxedema: Histopathology
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Triad
Diffuse deposit of mucin in the upper and midreticular dermis
 Increase in collagen deposition
 Marked proliferation of irregularly arranged
fibroblasts
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Increased fibroblasts and mucin in
the reticular dermis
Differential diagnosis
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Granuloma annulare
Lichen amyloidosis
Lichen planus
Eruptive collagenoma
Systemic scleroderma
Scleredema
Treatment
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Oral retinoids
Systemic corticosteroids- low doses not usually helpful but high
doses may temporarily arrest progressive visceral disease
Extracorporeal photochemotherapy
Melaphan
Topical and intralesional hyaluronidase
Electron-beam radiation
Plasmapharesis
PUVA
Dermabrasion
Topical DMSO
Overall prognosis is poor.
UVB and IFN alpha have exacerbated scleromyxedema
Scleredema
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Stiffening and hardening of the subcutaneous
tissues as if they were infiltrated with paraffin.
With DM II (men); without DM II (women)
Begins on the neck, may spread symmetrically to
arms, shoulders and back- distal extremities
spared
Skin waxy, wood-like.
Demarcation poor if no DM, good if DM
Scleredema without DM II
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F>M 2:1, Poorly demarcated edges
25% Streptococcal infection
Paraproteinemia usually IgG, Myeloma
Cardiac arrhythmias.
Upper GI dysphagia, tongue involvement
Pleural, pericardial or peritoneal effusion
If infection precedes it, 50% resolve 2-3 yrs.
Cyclosporin, UVA1, pulsed dexamethasone, and
extracorporeal photophoresis have been
reported to be beneficial
Scleredema with DM II
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Most common, well demarcated edges
Associated with late-onset, insulin dependent diabetes
M>F 10:1, usually obese
Lesions insidious onset and long duration- MC mid
upper back, neck and shoulders
Sharp step off at lesion edge
Persistent erythema & folliculitis possible
Controlling DM II has no effect on skin
No visceral disease or paraprotein
Scleredema Clinical Photo
Treatment
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PUVA
Pulse therapy with cyclophosphamide and
corticosteroids
Electron-beam therapy
Cyclosporine
Therapy has little benefit, however
Systemic and intralesional steroids, intralesional
hyaluronidase, MTX, antibiotics, and penicillamine have
not proved helpful
REM Syndrome
Reticular Erythematous Mucinosis
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Aka Plaque-like Cutaneous Mucinosis
Women, 3rd -4th decades of life
Frequently follows intense sun exposure, and
often pregnancy, OCPs, menses
DIF, ANA negative
MC midline chest & back
Reticulate or plaque-like appearance
Antimalarials often helpful
REM SYNDROME
Cutaneous Focal Mucinosis
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Benign, symptomless, skin colored solitary lesions less
than 1 cm
Resemble neurofibromas, cyst, BCC, and angiomyxoma
Can occur anywhere on the the body, except over the
joints of the hands and feet
Adulthood
Histopathology: mucin throughout upper and middermis sparing subQ fat. Cleft like spaces, but no cysts,
are seen. Numerous vimentin-positive dendritic shaped
fibroblasts are seen
Treatment: Surgical excision
Follicular Mucinosis
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Aka Alopecia Mucinosa, 3 groups
MC young; Occurs on the head, neck arms;
resolves in 2 months to 2 years
2nd group, larger more numerous lesions, takes
several years to resolve
3rd group, older, CTLC or lymphoma
30% of FM patients have MF
Any patient >30 yo with FM, look for MF
Follicular
papules
merging
into a
scaly
plaque
with
alopecia
MF associated follicular mucinosis
H&E: asterisks mark large
collections of mucin within cells of
the sebaceous gland and outer root
sheath with mixed dermal infiltrate
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Treatments for Follicular Mucinosis after
you have ruled out MF:
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Topical or oral corticosteroids
Dapsone
PUVA, Radiation therapy
Interferon alfa-2b
Mepacrine
Indomethacin
Minocycline
Oral isotretinoin
Spontaneous involution may occur, especially in young
children
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Myxoid Cysts
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MC terminal dorsal or lateral fingers
Solitary 5-7mm opalescent or skin colored
asymptomatic swellings of proximal nail fold or DIP
NO CYSTIC LINING, not a true cyst
Synovial origin still debated
TX: I&D, Cryo, IL steroids, fulguration of the base
after draining, CO2 laser ablation.
Recently recognized association of multiple myxoid
cysts with connective tissue disease i.e. JRA and
systemic sclerosis.
•Groove of nail plate
secondary to lesional
pressure to the nail
matrix
Case of dermatomyositis presenting with cutaneous
mucinosis as the sole manifestation. A malignancy screen
revealed an underlying nasopharyngeal carcinoma.
(J Am Acad Dermatol 2003;48:S41-2.)
Lichen Planus and
Related Conditions
Lichen Planus
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A disease of the skin, nails, hair follicles and
mucous membranes.
Mnemonic the 5 P’s
Wickham’s Striae, flat topped papules
Pruritis is paroxysmal, rubbing > scratching
Flexor wrists, trunk, medial thighs, shins, dorsal
hands, glans penis
Plentiful
Purple
Pruritic
Polygonal
Papules
Wickham’s
striae: gray
or white
puncta or
streaks that
cross the
lesion
5-10% of LP cases have nail changes including pterygium,
longitudinal grooving, onycholysis, splitting and peculiar
midline fissure
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Oral LP
75% of pts are women
15% also have skin
lesions
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Ulcerative
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Reticulate
Atrophic
MC on buccal mucosa
Risk of SCC
1/200 cutaneous LP pts
develop oral SCC
MC in ulcerative or
erythematous lesions
Mouth, anus are risk
areas too.
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A - Annular LP – most
commonly found on
lips or penis. Central
hyperpigmentation is
characteristic
Bullous LP
Usually shins,
as individual
lesions merge,
they vesiculate
centrally.
Often resolves
spontaneously
Lichen Planus Pemphigoides
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Rare
Typical LP patients who experience bullae on
top of their LP plaques
Pruritis may be severe
Triggered by medications and PUVA
DIF positive for 180kd BPAg2 antigen
Treat like Bullous Pemphigoid- potent topical or
systemic steroids, TCN, Nicotinamide, IVIG,
immunosuppressives
Hypertrophic LP
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AKA: LP verrucosus
Extremely pruritic
Usually symmetric, MC on shins
Chronic venous stasis frequently contributes to
this condition, making lesions refractory
SCC, which must be distinguished from
pseudoepitheliomatous hyperplasia, has been
reported to arise within these lesions
Hypertrophic LP
Linear LP –
Aka Zosteriform
1% of LP cases
Blaschko’s
lines, not
dermatomal
MC in children
Hepatitis C
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Prevalence in LP pts between 4% and 38%
Japan: Hep C = 8%, LP w/ HepC = 60%
LP patients with Hep C are more likely to have
erosive mucous membrane dz.
TX of Hep C w/ Alpha INF may induce LP.
Primary biliary cirrhosis & LP may coexist; ↑
risk of lichenoid rxn to D-Penicillamine
HBV immunization also associated- more than
30 cases reported
Lichen Planopilaris - scalp only
Graham-Little-Picardi-Lasseur
Syndrome - scalp & hairbearing body sites
Females > Males 4:1
Tufts of normal hair appear in
cicatricial areas of alopecia
Perifollicular erythema and
keratotic spiny papules
Tx: Difficult, IL or oral steroids,
antimalarials.
Interface dermatitis with “saw-tooth” pattern of epidermal hyperplasia
together with orthokeratosis and hyper-granulosis. Basal layer is lost or
“squamatized” with vacuolar interface change, necrotic keratinocytes.
“Band-like” infiltrate in the papillary dermis. “Civatte bodies” are necrotic
keratinocytes in the dermis
Hyperkeratosis, irregular (saw-tooth) acanthosis, dyskeratosis, basal
vacuolization, and a band-like infiltrate of mononuclear cells
Hyperkeratosis, focal increase in the granular layer, saw toothing of the
epidermis and a lichenoid infiltrate.
LICHEN PLANOPILARIS
LP Pathology
 Hypertrophic
LP = LP + LSC
 LPP and GLPL = LP histology
centered on follicular epithelium
 Civatte bodies reveal IgM on DIF
 Lichenoid drug reaction may mimic
LP. Look for eosinophils,
photodistribution to distinguish.
Lichen Planus Treatment
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Prednisone, Isotretinoin
PUVA, LMW Heparin, Cyclosporin
Oral: potent topical steroids in Orabase w/ vinyl dental tray TID
and 20 mins qHS
Plaquenil 400mg daily
Inhaled forms of corticosteroid are sometimes helpful for oral
LP
Vaginal: mix steroids with Replens (bioadhesive moisurizer)
Hydroxychloroquine, thalidomide have also been used
Mycophenolate mofetil and cyclosporin for refractory cases.
Lichen Planus Actinicus
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MC Africa, Middle East, Indian, Asians
MC Spring, Summer, Quiescent in Winter
Photodistributed
Mild or no pruritis
Hyperpigmented macules or plaques with the
blue-gray tinge of dermal melanin
May resemble Melasma
Erythema Dyschromicum Perstans
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Onset before age 40.
Chronic generalized, symmetrical
Various sizes & shapes, ashy-gray macules,
sometimes with a palpable non-scaling border.
Feels “like a small cord”
Pruritus is not reported
Nail and mucosal involvement is not found
Erythema Dyschromicum Perstans
Erythema dyschromicum perstans
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Occasionally there is a peripheral rim of
erythema
As in pityriasis rosea, the long axis of oval
lesions can follow skin cleavage lines
Histology: lichenoid infiltrate with pigment
laden macrophages in the dermis
EDP Treatment
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Sun protection
Topical retinoids
Topical vitamin C
Chemical peels
Oral antibiotics
Oral vitamin A
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Dapsone
Antimalarials
Griseofulvin
Anecdotal report with
clofazamine
Systemic and topical
steroids
Lichenoid Contact Dermatitis
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Dorsal hands - Paraphenylenediamine (color
film)
Oral due to Amalgan fillings
Patch testing recommended
Keratosis Lichenoides Chronica
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Rare, acral & buttocks, onset childhood
Violaceous papulonodular, hyperkeratotic lesions
covered with gray scales; discrete or may coalesce to
form reticulate or linear arrays, keratotic plugs and
prominent telangiectasias
Associated facial “seb derm” pattern
Nail thickening, longitudinal ridging, onycholysis, warty
periungual lesions
Painful oral apthae, keratoconjunctivitis
Tx: symptomatic; usually unsatisfactory
Keratosis Lichenoides Chronica
Lichen Nitidus
Minute, shiny, flat-topped, pale,
exquisitely discrete, uniform
papules
Lichen Nitidus – H&E
CHARACTERISTIC PATH: EPIDERMIS
GRASPS LYMPHOHISTIOCYTIC
INFILTRATE WITH “CLAW-LIKE
COLLARETTE
LICHEN
NITIDUS
Lichen Nitidus
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Linear Koebnerization
Lower abdomen and penis, inner thighs, flexor
wrists and forearms
Actinic Lichen Nitidis in black, Middle Eastern
and Indian subcontinent
Slowly progressive with tendency to remissions
Tx: Top. Steroids, PUVA, DNCB, Oral Retinoids
Lichen Striatus
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Common, Linear, erythematous or
hypopigmented papules, scaly, asymptomatic,
follow Blaschko’s lines, nails may be involved
Children age 3, females > males
Active lesions last for months, then resolve
Histology varies, lichenoid or spongiotic,
possibly even granulomatous. Dense eccrine
infiltrate helps differentiate from LP
Lichen Sclerosis et Atrophicus
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Females > Males, Itching may be severe
Anogenital “hourglass” or “figure eight” with
dyspareunia
Glans penis (balanitis xerotica obliterans)
Chest, breasts, back, oral mucosa, tongue
Histology may have features of morphea
Genital SCC risk higher than general population,
but lifetime risk is < 5%
LS&A IN A PERIUMBILICAL SKIN FOLD
LS&A Etiology
 Unknown.
 Borrelia
burgdorferi assoc. Japan, Europe
 20% of pts have autoimmune disease,
usually vitiligo, alopecia areata or
thyroid
LS&A Treatment
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Steroids (clobetasol)
Topical testosterone (emollient)
Topical retinoids
CO2 laser ablation
Excisional bx
Oral calcitriol (used in morphea and scleroderma)
Pimecrolimus/tacrolimus
PDT
Topical estrogens
Childhood LS&A
Childhood onset in 10-15%, usually genital
 Boys present with phimosis, circumcision
may improve/resolve
 Girls present with pain with defecation,
dysuria and 50% have spontaneous
resolution
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LS&A Histology
LATE LS&A: RETE
RIDGES EFFACED,
EDEMA “FADED,
WASHED OUT LOOK”,
TELANGIECTATIC
VESSELS
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JAAD, Volume 48, Number 6: Pages 935-937, June 2003
Tacrolimus ointment for the treatment of vulvar lichen sclerosis.
Assmann T, Becker-Wegerich P, Grewe M, Megahed M, Ruzicka T.
Department of Dermatology,
Heinrich-Heine-University,
Düsseldorf, Germany.
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The treatment of vulvar lichen sclerosus is generally considered difficult.
Ultrapotent corticosteroids represent the most effective topical
treatment, but carry the risk of side effects such as skin atrophy. We
describe a 71-year-old woman with long-standing vulvar lichen sclerosus
refractory to conventional treatment. After 6 consecutive weeks of
treatment with tacrolimus ointment 0.1% (Protopic) twice daily, signs
and symptoms of lichen sclerosus resolved. To our knowledge, this is
the first report of the use of topical tacrolimus, which does not induce
skin atrophy, in the treatment of vulvar lichen sclerosus.
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PMID: 12789187 [PubMed - indexed for MEDLINE]
The End