MORPHOEA

Presenter -Aatish Tamta

Moderator-Dr Amit Tiwari Sir
 INTRODUCTION

• A group of related conditions characterized by varying degrees of sclerosis, fibrosis

& atrophy in the skin & subcutaneous tissues, sometimes extending deep into the

muscle, bone & brain

• Extracutaneous manifestations occur in 25% of cases

• No internal organ fibrosis & vascular changes exists

• Antinuclear antibody positivity is common

 CLASSIFICATION(PETERSON ET AL.)
• Plaque morphea –
• Morphea en plaque
• Guttate morphea
• Atrophoderma of pasini & pierini
• Lichen sclerosus
• Keloidal morphea
• Linear morphea –
• Linear morphea of the limbs & trunk
• En coup de sabre morphea
• Progressive hemifacial atrophy / Parry Romberg Syndrome
• Deep morphea -
• Subcutaneous morphea
• Morphea profunda
• eosinophilic fasciitis
• Disabling pansclerotic morphea
• Bullous morphea
• Generalised morphea
The classification remains controversial.

• It included atrophoderma of Pasini and Pierni, Lichen sclerosus and eosinophilic

fasciitis.
• It does not include mixed subtype.
 LAXER AND ZULIAN
• CIRCUMSCRIBED MORPHOEA
Superficial
Deep

• GENERALIZED MORPHOEA

• LINEAR MORPHOEA
Trunk/limb variant
Head variant

• PANSCLEROTIC MORPHOEA

• MIXED
 KREUTER ET.AL.
• Limited type
• Morphea( plaque type)
• Guttate morphea
• Atrophoderma of pasini & pierini
• Generalised type
• Generalised localized type
• Disabling pansclerotic type
• Eosinophilic fasciitis
• Linear type
• Linear localised scleroderma
• En coup de sabre type
• Progressive hemifacial atrophy
• Deep type
MODIFIED CLASSIFICATION OF MORPHEA
 EPIDEMIOLOGY
• Incidence – 4 to 27 per million per year

• Prevelance – 0.05% at age 18 years & 0.22% at age 80

• Mc in child - Linear>Plaque> generalized> deep

• Mc in adult – Plaque> generalized> linear

• Age- 75% of plaque disease occur b/w 40 & 50 years

75% of linear disease occur b/w 2 &14 years

• Sex- common in women

• Adult pansclerotic morphea is more common in men

• Ethnicity- affects all races

Associated diseases

• mostly with generalized morphoea

• AICTDs
• AITD
• Vitiligo
• Diabetes mellitus
• Psoriasis
• Multiple sclerosis
• IBD
• Lichen sclerosus
 PATHOPHYSIOLOGY
• Predisposing factors
• Genetics
• Trauma
• Radiation
• Infections
• Drugs
• GENETICS

• HLA-DRB1*O4:04 and HLA-B*37 (genralised and linear morphoea)

• family history is more likely in generalised form.

• INFECTIONS
• Borrelia burgdorferi sensu stricto (USA) and B.afzelii (Eurasia)
• But no conclusive evidence.

• RADIATIONS
• Especially in case of Ca breast -1/500
• Trauma
• Accidental trauma, surgery, insect bite reactions ,vaccinations,injections. (more
in linear and deep morphoea)
• Vaccination- Hep b, MMR,DPT, BCG, pneumococcal vaccine.
• Injectins- vit B12, vit K
• Mechanical trauma -
• Isotopic- ie morphea at site of healed lesion seen in 6%
• isomorphic- ie lesions developing at site of repeated trauma in 9%
Drugs
• mechanism- development of drug specific lymphocyte response and
autoantibody production causing endothelial damage and inflammation.
• eg-bleomycin, pentazocine,progestin, vitB12, vit k , cocaine, D- penicillamine,
paclitaxel, ibuprofen, gemcitabine, bromocriptine, bisoprolol, mitomycin C,
balicatib.
• Autoimmunity – supported by increased serum levels of B- Cell activating factor &variety of
antibodies

• ANA positivity

• SS- DNA antibody

• Antihistone antibody – 12% cases (linear subtype),

SPECIFIC associated
TO SCLEROTIC SKINwith more extensive disease
DISEASE
• Antifibrillin -1 antibody

• Antibody to MMP-1

• Antitopoisomerase antibody- 3.2% pts

• Anticentromere antibody- 1.7% pts

• Antids DNA antibody -2.3 to 14% cases

Pathogenesis
• Three major components
• Vascular damage
• activation of T cells
• Altered connective tissue formation by fibroblasts.

• Role of miRNA
• Downregulation of miR-7 and miRNA-19A
• IMMUNOPATHOLOGY

• INFLAMMATORY PHASE- Th1/TH17 response

• FIBROTIC PHASE- Th2 response

• Increased collagen deposition, decreased collagen degradation

• Pro –fibrogenic factors line IL-3, 4 , 6, 10, TGF-β , CTGF, PDGF increased

• Vascular injury leading to increased expression of VCAM & ICAM

TRANSITION FROM Th1/Th17 in the early stage to Th2 in later stages
 HISTOPATHOLOGY

• Early inflammatory stage- pronounced lymphocytic infiltrate present in lower dermis and
subcutaneous fat
• Large areas replaced by newly formed collagen fibrils, swollen, parallel to skin surface
• Occasionally mast cells & eosinophils detected

• Vascular changes mild in dermis & subcutis, mainly endothelial swelling & oedema of vessel
wall
• Sclerotic stage- inflammatory phase disappears

• Collagen consists of thick closely packed , hyalinized bundles with few fibroblasts

• Eccrine glands are atrophic & tightly bound down by the newly formed collagen
 Clinical features

• Onset and progression- slow & insidious

• Lesions begin with bruise like appearance

• F/b central sclerosis associated with change in skin colour and texture to thickened, waxy, yellowish

white

• Central sclerosis surroubded by erythematous to violaceous ‘ lilac ring ‘ reflecting disease activity
 LIMITED TYPE
• LIMITED PLAQUE MORPHEA

• Round to oval lesions>1 cm in upto 2 out of 7 anatomical sites

• Plaques located mostly on trunk, can occur anywhere

• Breasts often involved , nipples & areola spared

• Histopathological changes limited to epidermis & dermis

• GUTTATE MORPHEA
• Rare variant

• Multiple, small ( <1cm ), erythematous to yellowish white, mildly

indurated lesions

• Most frequent on trunk

• Lesions are superficial , crinkled shiny surface resembling extragenital

lichen sclerosus
• ATROPHODERMA OF PASINI AND PIERNI

• Rare

• 0.1% of childhood morphea

• Primarily superficial and atrophic variant

• Symmetrical distributed truncal lesions – most common,

• Single lesions and zosteriform distribution can also be present

• Non indurated , blue grey to brown , hyperpigmented , sharply demarcated

depressed patches with cliff drop border

KELOIDAL / NODULAR MORPHOEA

• Characterized by the presence of keloid like nodules in patients with previous or

coexistent morphoea.

• clinically keloidal or nodular lesions arising from sclerodermatous skin.

• histological appearace typical of either keloid or morphoea is seen

• homogenization and thickening of collagen bundles with increase mucin

• Limited deep morphea
• Aka morphea profunda

• Inflammation and sclerosis found in deep dermis, panniculus, fascia

& muscle

• Diffuse , taut , bound down skin,

• HP Features- Deep cutaneous sclerosis, hyalinization & thickening of

collagen bundles in deep dermis, in septa of subcutenous fat and

fascia

• Solitary lesions can also be present

 GENERALISED TYPE

• Involve 3 or more anatomical sites

• 7 to 9% of childhood morphea

• 13 to 52% of adult cases

• Extracutaneous features like myalgia , arthralgia, fatigue common

• DISSEMINATED PLAQUE MORPHEA
• Multiple , often symmetrically distributed plaques of morphea

• plaques may occur in different stages of evolution.

• Can present at several anatomical sites, some of which may coalesce

• Develop in an isomorphic pattern

• Minor trauma from clothing around waistband, under breasts and groins
• Pansclerotic morphea
• Rare presentation

• Extensive , circumferential involvement of majority of body surface

areas

• Sparing of fingers & toes

• Complicated by severe contractures , chronic ulceration &

development of squamous cell ca

 Eosinophilic fascitis

• Usually extensive , involves deep tissues

• Symmetrically involves extremities(LL), but spares
fingers and face
• Severe exercise precede onset of diasease
• Early stage- painful burning erythema with pitting
oedema over limbs
• Later on –induration and fibrosis , peau d’ orange
appearance, with tethering around blood vessels,
producing groove sign
• Eosinophilic infilterate in panniculus and deep fascia
• Can result in severe joint contractures
 LINEAR TYPE

• More common in children

• Sub devided into limb / trunk variant (mc)

• Head & neck variant

• Appears to follow blashko lines, suggesting genetic mosaicism

 HEAD & NECK VARIANT

• MORPHOEA EN COUP DE SABRE

• Usually begins in childhood

• Involves frontoparietal area of face and scalp in paramedian

distribution
• Follows blashko’s lines

• Sclerosis involves skin & subcutis first later on fascia and bone

• Scarring alopecia

• Neurological , ocular , auditory complications well recognised

• Progressive hemifacial atrophy

• Aka Perry Romberg syndrome

• Blashkoid lesions in territory of trigeminal nerve

• Unilateral , progressive, primary atrophic disease of the skin ,

subcutaneous tissue, cartilage & bone

• Altered pigmentation

• Gradual loss of fat & muscle , atrophy of frontal, maxillary &

mandibular bones

• Occular and neurological complications

 TRUNK/LIMB VARIANT

• Linear sclerotic bands present

• Coexistent or preceding plaque morphea on trunk is common

• Dermis, subcutis, underlying muscle & bone may be involved

• Lesions across joints result in flexion contractures

• Limb length discripancies

• LINEAR ATROPHODERMA OF MOULIN
• Unilateral , depressed , hyperpigmented blashkoid plaques on trunk & limbs

• Onset b/w 6 and 20 years of age

• On histology normal dermis and collagen present

• Depression due to atrophy of subcutenous tissue

Linear deep atrophic morphoea

• Three cases with no preceding clinical inflammation or sclerosis, involving the

subcutis and deep dermis are reported.

• similar to progressive hemifacial atrophy.

EXTRACUTANEOUS MANIFESTATION
• OCCURS IN 20-25% CASES

• Neurological(31%)- headache,migraine,seizures, peripheral neuropathy.

• ophthalmological(8%)-episcleritis, ant uveitis, keratitis.

• oral-malocclusion, tonguehemiatrophy, TMJ involvement.

• arthritisan joint involvement

• vascular- raynaud’s phenomenon

• GI-esophagitis, GERD.

• Respiratory-dyspnea more likely due to severe skin immobility.

• COURSE AND PROGNOSIS

• progresses over 3-5 years, then stabilizes and eventually resolves

spontaneously.

• residual atrophy and dyspigmentation

• older age of initial onset, ANA positivity are potential risk for relapse

• 30-50% linear morphoea have osteoarticular complications.

• linear moephoea - SSc in 0.9- 1.3"%

 DIFFERENTIAL DIAGNOSIS

• Systemic sclerosis
• Scleredema
• Scleromyxoedema
• Granuloma annulare
• Extragenital lichen sclerosus
• FDE
• Necrobiosis lipoidica
• PIH
• Actinic L.P
• Steroid induced atrophy
• lyme disease- erythema migrans.
 Classification of severity
• Age at onset

• Extent and depth of disease

• Bony , joint or CNS involvement

• Assessment

• LoSCAT (localized scleroderma cutaneous assessment tool)

• High severity- genealized /pansclerotic morphoea, craniofacial linear morphoea, CNS involvement , limb
shortening
• Moderate severity- limited deep morphoea or linear morphoea of trunk or limb without evidence of high
morbidity
• Low severity- superficial circumscribed plaque morphoea
 ASSESSMENT OF
PATIENT
• CLINICAL ASSESSMENT INVESTIGATION
• Are lesions symptomatic Measure LosCAT score
• Are lesions extending? Photography+/-thermography+/- USG
• Are these extracutaneous manifestation? Skin biopsy : deep incisional ellipse
• Full skin examination to determine extent MRI ( Depth of extent on limbs ), CT
& activity of lesions
• Examine for genital lichen sclerosus EEG
CK & aldolase( muscle)
Full blood count eosinophils,immunoglobulins
TFT, ESR, CRP
ANA, ENA, RF
Borrelia serology
• DISEASE ACTIVITY AND DAMAGE
• early and active disease is most resposive to therapy .
• increase in size, new lesion, erythema and or induration at advancing edge of the lesions.
•
• DEPTH OF INVOLVEMENT
• Superficial lesions can be treated with topical therapy whereas lesions beyond deep dermis should
be treated systemically.

• DISEASE PROGRESSION
• many patients initially diagnosed with limited morphea later progress to more extensive form, so
they should be followed up.

• SYSTEMIC INVOLVEMENT
• indication for systemic immunosuppression.
 Active diasease
New lesions, extending lesions, inflammation, sclerotic
stage

LIMITED DISSEMINATED PLAQUE PANSCLEROTIC LINEAR MORPHOEA

MORPHOEA MORPHOEA MORPHOEA
Ultrapotent
Topical Methotrexate
topical steroid
therapy+/- Child- 1mg/kg/weeks s.c , max 25mg /week* 12 months
Tacrolimus 0.1%
phototherapy Adult -15 to 25mg/week oral /s.c* 12 to 36 months
Imiquimod 5%
+/-Prednisolone
Child- 2mg/kg/day max 60mg for 2 to 4 weeks, tapered to
Calcipotriol Psychological 50%at 8 weeks, 25% at 16 weeks, 12.5% at 24 weeks,
Calcipotriol- support, NR stopped at 48 weeks
betamethasone physiotherapy,MLD Adult – 0.5 to 1 mg/kg/ day
Mycophenolate mofetil titrated upto 1-1.5g
Calcipotriol+ Inactive disease Combination therapies
low dose UV-A Mtx+MMF+/-Phototherapy
NR
PhototherapyUV Autologous fat Or
A-1, NB- transfer, dermal Ciclosporin+/_ combination therapy
UVB,UVA,PUV fillers,surgical Or
A correction Abatacept
 Treatment algorithm
LIMITED PLAQUE MORPHEA LINEAR MORPHEA (FACE & CROSSING JOINTS

Topical tacrolimus Methotrexate and systemic steroids

NR* 8 weeks
NR* 8 weeks

Phototherapy Occluded Calcipotriol-

Topical
calcipotriene imiquimod betamethaso Phototherapy Change therapy to
ne
MMF
GENERALISED MORPHEA WITHOUT JOINT CONTRACTURES

Phototherapy ( Better side effect profile)

NR* 8 weeks

Methotrexate & systemic steroids

NR* 8 weeks
Change therapy to MMF
EMERGING THERAPIES
• Imatinib
• tyrosine kinase inhibitor blocks c-kit, c-Abl, PDGF receptor

• ILOPROST
• prostaglandin analogue used in SSc pt for treatment of raynauds
• supress the secretion of CTGF

• TOCILIZUMAB
• IL-6 inhibitor blocks inflammatory and profibrptic effect of il-6.

• Abatacept
• CTLA-4 recombinant protein inbiting t cell activation.
THANK YOU