Chapter 64 :: Morphea

and Lichen Sclerosus

MORPHEA
 EPIDEMIOLOGY
 incidence: 2.7 /100,000, F:M= of 2-3:1
 More common in whites
 20-30% begins in childhood, can occur at any age.
 Linear morphea: most common pediatric subtype (25-87%)
 Limb or trunk (70%- 80%), en coup de sabre or progressive hemifacial
atrophy(Parry-Romberg syndrome)(22%-30%).
 circumscribed and generalized subtypes : adults
 Deep morphea/ morphea profunda (2% - 4%)
 Periods of disease activity :3 -6 years
 relapsing remitting course in some patients, recurrence : > 20%
 Others : chronic course persisting for decades.
 CLINICAL FEATURES

Pain or
itching

• No
loss of hair acrosclerosis/
follicles→alopecia sclerodactyly
• Lesions begin
on the trunk
and spread
acrally

cigarette paper wrinkling

,cliff drop or deep
indention
Deep morphea(morphea profunda)
• The skin feels thickened and bound down to
the underlying fascia and muscle.
• “groove sign” at the site of tendons and
ligaments.
• Esp. underlie linear and generalized subtype
Eosinophilic Fasciitis(Shulman syndrome)
• rapid onset of symmetric areas of pain
and poorly circumscribed indurated,
plaques on the extremities.
• With cutaneous lesions similar to
morphea(30%)
• Deep subcutaneous and fascial
involvement
• peripheral eosinophilia
 NONCUTANEOUS FINDINGS & COMPLICATIONS
 Musculoskeletal (most common,
12%) :arthritis, myalgias,
neuropathies, carpal tunnel
syndrome.
 En coup de sabre : neurologic and
ocular complications (3.6%)
 seizures, headaches, adnexal
abnormalities (eyelids,
eyelashes), uveitis, episcleritis,
CNS vasculitis
 Facial morphea: dental malocclusion,
altered dentition, gingivitis,
deviation of the uvula, and atrophy
of the tongue and salivary glands.
 involve the genitals: postmenopausal
women with generalized subtype, or
coexist with genital lichen sclerosus.
• linear morphea (45% - 56%) : limited range of
motion, limb-length discrepancy, joint deformity,
and contracture
• Children : effects on growth function, quality of
life, muscle weakness, behavioral changes,
learning disabilities, and seizure
• Disfigurement and physical symptoms (fatigue,
pain, itch) affect psychosocial development and
quality of life
• Pansclerotic morphea: increased risk of SCC
caused by chronic ulcers, contracture,
restrictive pulmonary defects and dysphagia.
• Circumferential sclerosis of the arms or legs:
compartment syndrome, bullae, and ulcers.
• generalized morphea is associated with an
increased rate of autoimmune disease: lichen
sclerosus, SLE, vitiligo, primary biliary sclerosis,
autoimmune hepatitis, Hashimoto thyroiditis,
myasthenia gravis.
 ETIOLOGY AND PATHOGENESIS
 HLA-DRB1 04:04 and HLA-B37 confer an increased risk
 local tissue trauma: chronic friction or surgery (60%), radiation, insect bites, intramuscular
injections.
 autoimmune-mediated inflammation early in the course :
 influx of large amounts of activated T lymphocytes, plasma cells, eosinophils
 elevated ANAs, cytokines, adhesion molecules (ICAM-1, VCAM-1, E-selectin)
 increased Th 1-associated cytokines and chemokines:IL-12, IL-2, IFN-γ,IFN-α2, CXCL-10, CXCL-9
 increased Macrophage cytokines and growth factors :GM-CSF and monocyte chemoattractant
protein-1
 positive correlation between CXCL-9, CXCL-10 levels and disease severity scores

 Elevation of Th2-related cytokines : IL-4 and IL-13→IL-4 upregulate TGF-β →induction of

connective tissue growth factor, PDGF, and matrix metalloproteinases→ increased
production of collagen and other extracellular matrix components
 inhibit IFN-γ (a suppressor of collagen synthesis).
 transition from a predominantly Th1 profile in the early inflammatory stage to a Th2 profile
in the later sclerotic stage.
 DIAGNOSIS
 the characteristic clinical appearance of the lesions.
 Histologic examination to exclude other disorders: lesions on the breast
(carcinoma of the breast)
 laboratory-based tests are not recommended in the absence of specific signs
and symptoms
 Serum Autoantibodies: ANA, anti–ssDNA, anti–ds DNA, antihistone,
antitopoisomerase II, antiphospholipid, anticentromere, anti–Scl-70,RF, MMP-1
 ANAs (34%- 80%) :more common in linear or generalized disease, speckled pattern
(81%)
 linear morphea: antihistone antibodies associated with functional limitation, ANA
associated with extensive body surface area involvement.
 Other Serum Abnormalities:
 active disease, particularly deep morphea :Peripheral eosinophilia,
hypergammaglobulinemia, increased ESR or CRP
 muscle involvement: elevation of CK and aldolase
 DIAGNOSIS
 PATHOLOGY ➢ IMAGING
 Biopsies should be taken from the inflammatory or indurated • MRI and ultrasonography :determination of
border or sclerotic center and include subcutaneous fat. lesion activity and depth( deep morphea )
 inflammatory phase : • MRI findings: fascial thickening and
 interstitial and perivascular inflammatory cell infiltrate enhancement, subcutaneous septal
in the dermis /subcutaneous tissue, mostly of thickening, articular synovitis,
lymphocytes and plasma cells tenosynovitis, perifascial enhancement,
 tissue edema, enlarged tortuous vessels, and thickened myositis, enthesitis, bone marrow
collagen bundles. involvement.
 sclerotic lesions • Ultrasonography: Disease activity correlate
 homogenization of the papillary dermis and sclerosis with hyperemia and echogenicity.
extending to the reticular dermis with thickened
collagen bundles.
 severe sclerosis: compression and loss of appendageal
structures.
 deep morphea: the deep reticular dermis, subcutis, and
fascia show similar changes.
 atrophic phase: loss of inflammatory cell infiltrate, lessening
of sclerosis, absence of appendageal structures.
Telangiectasia may occur.
DIFFERENTIAL DIAGNOSIS

acral sclerosis/sclerodactyly, nail-fold

capillary changes, Raynaud phenomenon,
internal organ involvement, hallmark
autoantibodies

vitamin K1, taxanes,

IFN-β1a, balicatib
 CLINICAL COURSE AND PROGNOSIS
 May be self-limited, but frequently remitting relapsing or chronic course
 Recurrences: 25%
 higher risk of recurrence (31% )for linear morphea of the extremities
 PATIENT EVALUATION
 Therapeutic success: resolution of
erythema(over 2 -3 months),
lesion softening(>12 months),
cessation of lesion growth, and no
new lesion development.
順從
 active lesions are most amenable
to treatment.
 localized scleroderma cutaneous
assessment tool (LoSCAT)
 LoSSI (localized scleroderma
severity index) and LoSDI
(localized scleroderma damage
index):
 Serial photography
 ◆ linear lesions, facial lesions, progressive
itch or tingling hemifacial atrophy, lesions crossing joint lines,
large body surface area involvement, rapid
progression→ aggressive therapy
** Phototherapy (phototherapy +/-systemic
無效 immunosuppressives).

NBUVB

* First line

(pulsed corticosteroids
and methotrexate)

sclerosis of the lesion

center, contracture, limb-
length discrepancy,
scarring alopecia.
LICHEN SCLEROSUS
• Incidence in males: 0.07%
• LS seems to be a prominent cause
of phimosis
• genital LS in males is almost
exclusively seen in uncircumcised
men
 CUTANEOUS FINDINGS
 Vulvar LS:
 porcelain-white atrophic papules coalescing into plaques on the labia minora and majora.
 Follicular plugging (early LS),fissures, erosions, telangiectasias, purpura, erythema,
hyperkeratosis, different degrees of sclerosis, bullae (occasionally hemorrhagic)
 classical figure-8 pattern of the vulva and anus
 intractable itching, soreness, dyspareunia, dysuria, discomfort with defecation, genital
bleeding, destructive scarring
 Gradual obliteration or synechiae of the labia minora and clitoris, burying of the clitoris,
stenosis of the introitus

 Male genital LS (balanitis xerotica obliterans):

 confined to the glans penis, prepuce, or foreskin remnants (Penile shaft, scrotal involvement
are rare)
 Many are simply diagnosed as phimosis.
 painful erections, urethral strictures with decreased urinary stream and difficulty voiding

 Extragenital LS: thighs, neck, trunk, and lips

 pruritus, burning, or asymptomatic
 a few millimeters to large portions of the trunk.
 lip involvement: asymptomatic vitiligo-like lesions, dermal sclerosis confined to the papillary
layer.
NONCUTANEOUS FINDINGS & COMPLICATIONS
 association with autoimmune thyroid disease, alopecia areata,
pernicious anemia, morphea, vitiligo
 In females:
 dyspareunia, urinary obstruction, constipation, secondary infection
related to ulceration, steroid use
 squamous cell carcinoma(4-6%)
 Risk factors: Age, long duration of LS, HPV infection, hyperplastic
changes
 IRF6 (tumor-suppressor gene) is downregulated in vulvar SCC
associated with LS
 In males: painful erections and urinary obstruction
 ETIOLOGY AND PATHOGENESIS
 The cause of LS is unknown: genetic predisposition, autoimmunity, local
factors
 high rate of familial LS cases(12%) : Vulvar cancer increased
 Local irritation and trauma (Koebner phenomenon)
 The disturbed function of fibroblasts with increased production of collagen
 Low-titer autoantibodies against the extracellular matrix protein-1(ECM-1)
and collagen XVII(67%)
 No infectious cause (acid-fast rods, spirochetes, or Borrelia)
 predominance of CD8 cytotoxic T cells
 upregulation of Th1 and Type I IFN-regulated cytokines and chemokines:
 Plasmacytoid dendritic cells product Type I IFN →regulate CXCL-9, CXCL-10, and
CXCL-11→migration of Th1 cells into tissues through binding to CXCR3.
 No upregulation of Th2 or Th17 pathways
 similar to pathogenesis of active inflammatory morphea
 DIAGNOSIS
 A skin punch biopsy of a mature lesion
 autoimmune workup(ANA, parietal cell antibody, vitamin
B12 levels, thyroid function tests) is not generally
recommended (relatively low occurrence)
 Borrelia antibody titers should not be analyzed
 serial biopsies to exclude SCC
 PATHOLOGY
 Classical LS : atrophic epidermis and a lichenoid infiltrate at
the DEJ.
 Papillary edema (early LS)→ fibrosis with homogenization of
collagen and acid mucopolysaccharides
 Epidermal hyperplasia and/or dysplasia on vulvar specimens
→increased risk of malignant transformation, eps. with
infection by high-risk HPV.

 IMAGING
 only needed in special situations(urinary obstruction secondary
to stenosing genital LS).
 High-resolution ultrasonography :document the depth of
sclerosis.
 CLINICAL COURSE AND PROGNOSIS
 chronic, relapsing condition with possibility of long-term functional
and anatomic impairment
 The prognosis is generally favorable: treated in the early nonscarring
stages with initial and maintenance therapy with topical
corticosteroids.
 childhood-onset vulvar LS does not always resolve at puberty and may
remain persistent.
 early aggressive treatment with ultrapotent corticosteroids
 Erosions and progressive scarring →severe dysfunction of urination,
sexual function, and defecation.
 resorption of the labia, alopecia, altered anatomic structure of the
vulva.
 MANAGEMENT
 TOPICAL TREATMENTS
 Ultrapotent topical corticosteroids (clobetasol propionate 0.05%): first-line
treatment for genital LS
 QD or BID until remission or QD for 4 weeks→ QOD for 4 weeks→ BIW for 4 weeks
 Ointments: less irritating and better tolerated
 Mometasone furoate 0.1% 與 clobetasol propionate 0.05% 效果相當
 Clobetasol 比 calcineurin inhibitors效果好
 topical androgens and progesterone 無效
 lower potency corticosteroid or calcineurin inhibitors: if cutaneous atrophy

 PHOTOTHERAPY AND SYSTEMIC TREATMENTS

 clobetasol was more effective than UVA-1 in relief of pruritus and quality of life.
 UVA-1 or photodynamic therapy: second-line treatment
 Systemic acitretin: effective for penile and severe vulvar LS

 ADJUNCTIVE TREATMENTS
 irritation from urinary and fecal incontinence exacerbates vulvar LS→ barrier
creams containing ZnO
 Referral to urogynecology and gastroenterology , pelvic floor therapists, counselors
 MANAGEMENT
 MAINTENANCE THERAPY
 topical corticosteroids 2-3 times/week, even with asymptomatic genital LS.

 TREATMENT OF MALE GENITAL LICHEN SCLEROSUS

 Circumcision will generally resolve male genital LS and the associated phimosis
 potent topical steroids may obviate the need for surgery.

 TREATMENT OF EXTRAGENITAL LICHEN SCLEROSUS

 the treatment modalities are similar to morphea.
 topical corticosteroids, topical calcineurin inhibitors,UVA-1 phototherapy,
methotrexate + prednisone.
 Limited surface area : clobetasol propionate
 generalized or resistance to topical steroids: UVA-1

 PREVENTION
 An interdisciplinary management team(gynecology, urology, pediatrics, pain
medicine) for the long-term control of LS.
45 關於Morphea的敘述，下列何者正確？
Morphea臨床上的進展可以分成inflammatory, sclerotic, atrophic三個階段
106 與Scleroderma的差異性在於morphea的病患會出現sclerodactyly的症狀
年 Morphea所造成的併發症包含肢體的contracture，骨骼的異常
成人型的morphea主要以linear subtype做為臨床上的表現

A.  B.  C.  D.  E. 
關於morphea，下列敘述何者錯誤？
Linear type的morphea好發於成人，而circumscribed and generalized好發於孩童。
33 引起morphea相關的血管變化(例如: adhesion molecules表現增加)的發炎主要是Th1
immune response相關的cytokine (如: interferon-γ)。

考古題
108 Morphea患者常合併acrosclerosis或sclerodactyly。
年 Morphea的病程可能為self-limited，疾病的活性約3~6年。

A.  B.  C.  D.  E. 

關於morphea的臨床特徵，下列敘述何者正確？
小孩及成年人都有可能發生
thickened sclerotic skin
21
包含inflammatory、sclerotic及atrophic phases
109 常合併acrosclerosis/sclerodactyly
年
A.  B.  C.  D.  E. 

02 有關於男性生殖器的皮膚病，下列何者可引起包莖 (phimosis)？
 Lichen sclerosis。
 Lichen planus。
103  Cicatritial pemphigoid。
年  Chronic penile lymphoedema。

A.  B.  C.  D.  E. 