Transcript Document

Mucinoses, Lichen Planus
and Related Conditions
Adam Wray, D.O.
September 28, 2004
What is Mucin?
• Fibrillar matrix in dermis called ground
substance, created by fibroblasts.
• GS= acid glycosaminoglycans (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
• Primary mucinoses
– Mucin deposition is the main histologic feature
• Secondary mucinoses
– Mucin deposition is an additional finding
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
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, usu. linear array
• Acral: dorsal hands, face, elbows, and
extensor extremities
Acral Persistent Papular Mucinosis
• Subtype of localized LM
• Usually women
• Few to 100 bilaterally symmetrical 2 to
5mm, flesh colored papules
• Always on hands and wrists.
• Rarely elbows and knees
• No paraprotein, no systemic dz
• H&E: Increased mucin, but not fibroblasts
Cutaneous Mucinosis of Infancy
• Subtype of localized LM
• 3 cases, onset birth-3 months of age
• 2-8mm papules trunk, extremities, especially
backs of hands
• TSH, Paraprotein negative
• There are neither systemic symptoms nor
spontaneous resolution
• H&E: papillary dermal mucin, no fibroblasts
• 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).
Scleromyxedema
• 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
• Pulmonary
• Proximal Muscle
weakness
• Carpal Tunnel Synd.
• Peripheral Neurop.
• Raynauds
• IgG lambda
paraproteinemia
• Myeloma
Scleromyxedema
• Widespread eruption of 2-3 mm, firm,
waxy, closely spaced papules
• Papules often arranged in a linear array
• 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: Histopathology
• Triad
– Diffuse deposit of mucin in the upper and midreticular dermis
– Increase in collagen deposition
– Marked proliferation of irregularly arranged
fibroblasts
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
Extracorporeal photochemotherapy
Melaphan
Topical and intralesional hyaluronidase
Electron-beam radiation
Plasmapharesis
PUVA
Dermabrasion
Topical DMSO
Overall prognosis is poor.
Papular Mucinosis and AIDS
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Widespread
Not associated with a paraprotein
Always seen in advanced HIV disease
If assoc. with eczematoid dermatitis,
clears when eczema clears
• Oral retinoids
Scleredema
• 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
• 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.
Scleredema with DM II
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Most common, well demarcated edges
M>F 10:1, usually obese
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
• PUVA
• Pulse therapy with cyclophosphamide and
corticosteroids
• Electron-beam therapy
• Cyclosporine
• Therapy has little benefit, however
• Systemic and intralesional steroids, intralesional
hyaluronidase, MTX, antibx, and penicillamine
have not proved helpful
REM Syndrome
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Reticular Erythematous Mucinosis
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
• 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
• Histopath: mucin throughout upper and mid-dermis
sparing subQ fat. Cleft like spaces, but no cysts, are
seen. Numerous vimentin-positive dendritic shaped
fibroblasts are seen
• Tx: Surgical excision
Self-healing Juvenile Cutaneous
Mucinosis
• Sudden onset, age 5 to 15
• Skin lesions and polyarthritis x a few mos.
• Ivory white papules head, neck, trunk and
periarticular
• Hard edema of periorbital area/face
• TSH, IgG normal
• H&E dermal mucin
• Prognosis excellent
Follicular Mucinosis
• Aka Alopecia Mucinosa, 3 groups
• MC young, head, neck arms, resolves in 2
mos to 2 years
• 2nd group, larger more numerous lesions,
takes several years to resolve
• 3rd group, older, CTLC
• 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
• 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
Myxoid Cysts
• 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. Meticulous excision
including “stalk” by Salasche in 11 pts, no recur.
•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
• 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
Ulcerative
Reticulate
Atrophic
Risk of SCC
1/200 cutaneous
LP pts develop
oral SCC
• 1/100 oral LP pts
develop SCC over
3 year period
• Mouth, anus are
risk areas too.
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
• Rare
• Typical LP patients who experience bullae
on top of their LP plaques
• DIF positive for 180kd BPAg2 antigen
• Treat like Bullous Pemphigoid
Hypertrophic LP
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AKA LP verrucosus
Extremely pruritic
Usually symmetric
Chronic venous stasis frequently
contributes to this condition
• 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
Hepatitis C
• 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
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 hypergranulosis. Basal layer is lost or “squamatized” with
vacuolar interface change, necrotic keratinocytes. “Bandlike” 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
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
Lichen Planus Treatment
• Prednisone, Isotretinoin
• PUVA, LMW Heparin, Cyclosporine
• 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)
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
Erythema Dyschromicum Perstans
• Onset before age 40.
• Chronic generalized, symmetrical
• Various sizes & shapes, ashy-gray
macules, sometimes with a palpable nonscaling border. Feels “like a small cord”
• Pruritus is not reported
• Nail and mucosal involvement is not found
Erythema dyschromicum perstans
• 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 antibx
Oral vitamin A
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Dapsone
Antimalarials
Griseofulvin
Anecdotal report with
clofazamine
• Systemic and topical
steroids
Lichenoid Contact Dermatitis
• Dorsal hands - Paraphenylenediamine
(color film)
• Oral due to Amalgan fillings
• Patch testing recommended
Keratosis Lichenoides Chronica
• 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
• 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
• 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
• 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
LS&A Histology
LATE LS&A: RETE
RIDGES EFFACED,
EDEMA “FADED,
WASHED OUT LOOK”,
TELANGIECTATIC
VESSELS
• JAAD, Volume 48, Number 6: Pages 935-937,
June 2003
Tacrolimus ointment for the treatment of vulvar lichen
sclerosis.
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Assmann T, Becker-Wegerich P, Grewe M, Megahed M, Ruzicka T.
Department of Dermatology,
Heinrich-Heine-University,
Düsseldorf, Germany.
• 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.
• PMID: 12789187 [PubMed - indexed for MEDLINE]
The End