Morphoea Flashcards
Overview
Group of related diseases sharing acommon underlying patho-hysiology of increased collagen deposition in an autoimmune setting
Varying degrees of skin and subcut tissue sclerosis, fibrosis, atrophy
Sometimes extends deep into -
- Fascia
- Muscle
- Bone/Joints
- Eye
- Brain
PHASES OF LIMITED MORPHOEA
Early inflammatory active phase —> sclerotic phase —> hyperpigmented phase —> atrophic damage phase
Key to successful Rx = initiate Rx during active inflammatory phase before significant damage has occured
7 anatomical regions
- Head, neck
- Right UL
- Left UL
- Right LL
- Left LL
- Anterior trunk
- Posterior trunk
Limited = Up to 2 anatomical regions
Generalised = 3 or more anatomical regions
Occasional extracutaneous manifestations
- MSK
- Neurologixal
- Ocular
- Vascular incl. Raynauds phenomenon
- GIT
No internal organ fibrosis (unlike systemic sclerosis)
- heart, lungs (pulmonary fibrosis, pulmonary HTN)
- kidneys (hypertensive renal crisis)
- GIT (infiltration, fibrosis)
No vascular changes (unlike systemic sclerosis)
- nail fold capillary changes
- sclerodactyly
No increased mortality (unlike systemic sclerosis)
Autoantibodies may be found
- ANA positivity common
- Antihistone, anti-ssDNA may be present
Specific antibodies seen in systemic sclerosis rarely found
- Anti-topoisomerase (anti-Scl-70)
- Anti-centromere
- Anti-RNA polymerase
Protracted, relapsing-remitting course
Substantial morbidity d/t -
- Joint contractures
- Facial asymmetry
- Limb asymmetry
- Extracutaenous manifestations
- psychological impact
Classification
LIMITED TYPE (up to 2 anatomical regions)
Limited plaque morphoea - epidermis and dermis
Guttate morphoea - papillary and superficial dermis
Atrophoderma of Pasini-Pierini (controversial) - superficial reticular dermis
Keloidal/nodular morphoea
Limited deep morphoea - deep dermis and subcutis +/- fascia, muscle
GENERALISED TYPE (3 or more anatomical regions)
Disseminated plaque morphoea
- Isomorphic pattern
- Non-isomorphic pattern
Pansclerotic morphoea
Eosinophilic fascitis (controversial, ? Imtermediate condition between disseminated plaque and pansclerotic disease)
LINEAR TYPE
Head/neck variant
- Morphoea en coup de sabre
- Progressive hemifacial atrophy
Trunk/limb variant
- Linear morphoea
- Linear atrophoderma of Moulin (controversial)
- Linear deep atrophic morphoea
MIXED TYPE
LICHEN SCLEROSUS WITH MORPHOEA
Limited plaque morphoea (limited type)
Epidermis + dermis
Single or multiple
Round or oval lesions > 1cm diamater
Up to 2 anatomical regions
Usually trunk, esp breasts (but nipples and areola spared)
May be - - oedematous - erythematous to bruise-like - Yellowish white - Indurated \+/- lilac ring - Atrophic (late stage) - Pigmented (late stage)
Guttate morphoea (limited type)
Papillary, superficial dermis
Multiple small <1cm Erythematous to yellowish white Mildy indurated Round to oval lesions May have shiny crinkled surface Usually on trunk
clinically resembling extragenital LS
Difficult to distinguish guttate morphoea and extragenital LS based on climical and histological grounds
Lesions generally resolve leaving hyperpigmentation (in contrast with LS)
Atrophoderma of Pasinin-Pierini (limited type)
Superficial reticular dermis
Multiple Oval to round lesions Non-indurated Sharply demarcated Depressed patches “Cliff-drop” edge
Blue-grey to brown
Usually hyperpigmented
Symmetrically distirbuted truncal lesions (most common)
Also single lesions
Zosteriform lesions
Adolescent, young adults
Areas of induration may develop within existing lesions
May co-exist with plaque morphoea —> mixed type
Keloidal/nodular morphoea (limited type)
Keloid-like or nodular lesions
Arising from normal or sclerodermatous skin
Usually on trunk
May coalesce or occur in linear pattern
Past or co-existent hx of -
- Morphoea
- Systemic sclerosis
Limited deep morphoea (limited type)
Deep dermis + subcutis +/- fascia, muscle
Overlying skin may appear normal or puckered
@ morphoea profunda
Solitary or multiple lesions
Up to 2 anatomical sites
Poorly defined, thickened, skin tethered/bound down to underlying deep tissue
+/- cobblestone, peau d’orange appearance
DDX
Lipoatrophy
Disseminated plaque morphoea (generalised type)
The following may occur in All the subtypes of generalised morphoea -
- Extracutaneous symptoms i.e. myalgia, arthralgia, fatigue, dyspnoea, dysphagia
- Higher prevalence personal and family Hx autoimmune disease
Multiple plaques of morphoea
Plaques may be in different stages of evolution
3 or more anatomical regions
Most frequently trunk, lumbosacral area, thighs
ISOMORPHIC PATTERN Coalescing plaques - - Inframammary area, Bra-line - Waist band, Around the hips - Inguinal region at sites of repeated minor trauma from clothing
Middle aged F
NON-ISOMORPHIC PATTERN
Multple individual plaques +/- deep involvement
Symmetrical distribution
Trunk and limbs
Pansclerotic morphoea (generalised type)
Dermis, frequently subcutis +/- muscle, bone
Circumferential involvement
Majority body surface
Sparing of fingers, toes, nipples
No sclerodactyly, nail fold capillary changes, internal organ fibrosis (unlike systemic sclerosis)
Severe extensive skin sclerosis may cause -
- Restrictive picture on PFTs
- Dysphagia
- Hand oedema
DDX Systemic sclerosis Sclerodermoid GVHD Scleroedema Slceromyxoedema PCT Primary systemic amyloidosis Nephrogenic systemic fibrosis Carcinoid syndrome Drug-induced morphoea Chemical induced skin sclerosis - L-tryptophan —> Eosinophilia myalgia syndrome - Ingestion of rapeseed oil contaminated with aniline —> toxic oil syndrome - Gadolinium exposure on BG of renal failure, eGFR < 30 mL/min —> nephrogenic systemic fibrosis Occupational causes skin sclerosis - Vinyl chloride disease - Perchlorethylene - Trichlorethylene - Organic solvents - Pesticides - Epoxy resins - Silicone
Eosinophilic fascitis (generalised type)
Deep fascia + muscle
Dermis may be sclerotic or normal
May co-exist with plaque morphoea
Symmetrical involvement of extremities esp LL
+/- trunk (climical overlap with pansclerotic morphoea)
Spares fingers, face
Initial Painful burning erythema + pitting oedema of limbs —> subsequent peau d’orange appearance, guttering around vessels and tendons
Skin bound down to underlying structures
May result in severe joint contractures
BLOODS Raised ESR Raised CRP Eosinophilia Hypergammaglobulinaemia \+/- thrombocytopaenia \+/- aplastic anaemia \+/- leukaemia
TO CONFIRM DX
Deep biopsy showing inflammation and thickening of deep fascia
DDX Systemic sclerosis Sclerodermoid GVHD Scleroedema Slceromyxoedema PCT Primary systemic amyloidosis Nephrogenic systemic fibrosis Carcinoid syndrome Drug-induced morphoea Chemical induced skin sclerosis - L-tryptophan —> Eosinophilia myalgia syndrome - Ingestion of rapeseed oil contaminated with aniline —> toxic oil syndrome - Gadolinium exposure on BG of renal failure, eGFR < 30 mL/min —> nephrogenic systemic fibrosis Occupational causes skin sclerosis - Vinyl chloride disease - Perchlorethylene - Trichlorethylene - Organic solvents - Pesticides - Epoxy resins - Silicone
Morphoea en coup de sabre (linear type, head/neck variant)
May involve underlying muscle, bone, eye, brain
- sclerosis involves skin and subcutis first
- later extend to underlying fascia, bone
Usually begins in childhood
Occasional adult onset cases described
Blaschkoid linear induration —> suggests genetic mosaicism as a pathogenesis
Face and scalp —> frontoparietal area in a paramedian distribution
Varying degrees of sclerosis, hyperpigmentation, atrophy
Scarring alopecia of the eyelashes, eyebrows, scalp occur if involved in a band
Linear depressions in the skull bones common
Variety of abnormalities on CT and MRI
Bilateral lesions + concomitant linear trunk/limb morphoea + concomitant plaque morphoea may occur
HISTO
Vacuolar degeneration at DEJ
Perivascular and/or periappendageal lymphocytic infiltrate and vacuolar degenration of follicular epithelium in early disease —> suggests possible autoimmune attack of genetically dofferemt basal keratinocytes as a result of mosaicism
COMPLICATIONS
Neurological
Ocular
Auditory
COURSE/PROGNOSIS
Majority of cases onset insidious and progress slowly over many years
Occasionally sudden onset and rapidly progressive course
25% have another form of morphoea elsewhere i.e. mixed subtype (most often plaque morphoea)
May evolve into Progressive Hemifacial Atrophy
Progressive hemifacial atrophy (linear type, head/neck variant)
May involve dermis, subcut tissue, muscle, bone, eye, brain
Normal skin overlies atrophic depper structures
Unilateral, progressive, primary atrophic disease of -
- Skin
- Subcut tissue
- Muscle
- Underlying cartilage and bone
@ Parry-Romberg syndrome
Majority of cases begin in the 1st decade
Occasional adult onset cases described
Probable blaschkoid distribution —> suggests genetic mosaicism as a pathogenesis
Previously Traditionally described as affecting the area supplied by 1 or multiple branches of the trigeminal nerve
One side of face
Non-indurated skin
Altered pigmentation, usually a brownish or bruise-like change
Ocassional hypopigmentation described
Gradual underlying atrophy/loss of fat, muscle
Subsequent atrophy of frontal, maxillary, mandibular bones
Progressive facial asymmetry develops
Mouth and nose become deviated towards affected side
Enophthalmos (posterior displacement of the eyeball within the orbit) d/t combo of progressive fat atrophy, shrinkage of the eyeball, thinning of the extraocular muscles
COMPLICATIONS Ocular - choroidal and retinal folding - hyperopia - uveitis - retinal vasculitis - glaucoma - 3rd nerve palsies
Neurological
- Headaches
- Epilepsy
Dental malocclusion (consequence of mandibular and intraoral involvement)
Hemiatrophy of the tongue (consequence of mandibular and intraoral involvement)
COURSE/PROGNOSIS
Majority of cases onset is insidious and progress slowly over many years
Linear morphoea (linear type, trunk/limb variant)
Dermis, subcut tissue +/- muscle, bone
Blaschkoid linear induration
Limbs/trunk
Majority of unilateral
Bilateral lesions reported
Varying degress of erythema, sclerosis, atrophy, hyperpigmentation
Linear sclerotic bands may appear suddenly or insidiously —> then progress
Shiny, waxy appearance (Active inflammatory phase)
Progress to increased in sclerosis with peripheral erythema
Softened, atrophic, hyperpigmented (Late stage inactive disease)
May have coexistent or preceding plaque morphoea (most often on the trunk)
In limb lesions generalised arthralgias and oedema of the involved extremity may precede onset
COMPLICATIONS
Lesions extending across joints —> flexion contractures —> pain + significant functional limitation —> reduction QoL, psychosocial morbidity
Myopathic changes i.e. atrophy and weakness of involved and adjacent muscles —> pain + significant functional limitation —> reduction QoL, psychosocial morbidity
Limb girth asymmetry (adults)
Limb length discrepancies d/t Growth failure (children) —> pain + significant functional limitation —> reduction QoL, psychosocial morbidity
Linear atrophoderma of Moulin (linear type, trunk/limb variant)
Superficial dermis
Appears to lie within the morphoea spectrum
Akin to the linear Blaschkoid form of atrophoderma of Pasini-Pierini (limited mprhoea subtype)
Blaschkoid linear
hyperpigmented atrophic lesions
Limb/trunk
HISTO
Epidermal hyperpigmentation
Normal dermis
Normal collagen
Linear deep atrophic morphoea (linear type, trunk/limb variant)
Deep dermis + subcutis
Resembles Progressive Hemifacial Atrophy, but on a limb
Linear atrophic lesions
No preceding clinical inflammation or sclerosis
Progressive but Does not result in joint contractures
May occur with Progressive Hemifacial Atrophy
Mixed type
Combination of 2 or more subtypes
Often linear + plaque
Morphoea-lichen sclerosus overlap
Morphoea + extragenital lichen sclerosus lesions may occur at dame site or at different sites
Small patches of lichen sclerosus may arise within larger plaque of morphoea
Usually trunk
May be widespread
Need to chelc for genital lichen sclerosus
Associated diseases (Concomitant with morphoea)
Family Hx of Rheum or autoimmune disease in 1st or 2nd degree relatives significantly more likely in patients with generalised morphoea
AUTOIMMUNE DISEASES - commoner in adults than children with generalised morphoea * Psoriasis * Vitiligo * LS AA * SLE Antiphospholipid syndrome Mixed connective tissue disease * RA Autoimmune hepatitis Primary biliary cirrhosis IBD Coeliac disease * Type 1 DM * Autoimmune thyroid disease Multiple sclerosis
LICHEN SCLEROSUS-MORPHOEA OVERLAP - cases of genital, extragenital LS occuring in conjunction with morphoea esp plaque morphoea
Clinical Distinction between plaque morphoea and extragenital LS
Plaque morphoea
- Thicker, larger plaques
- Peripheral inflammatory lilac ring/border
LS
- Porcelain white papules and plaques
- Varying degress of hyperkeratosis, follicular plugging
- Erythema, telengiectasia, purpura
- Sclerosis, atrophy
Predisposing environmental factors/triggers
Aetiology poorly understood
Seems likely that an environmental trigger, on a background lf genetic susceptibility, triggers a sequence of events —> vascular activation, inflammation, subsequent fibrosis
POSSIBLE TRIGGERING EVENTS
Mechanical Trauma (particularly in linear morphoea)
- Accidental trauma
- Insect bite reactions
- Vaccinations
- Isotopic —> morphoea occurring in the same area as previously healed skin disease/injury (trauma occur at the site of the morphoea within 6 months of onset of morphoea) i.e. surgery, penetrating trauma, injection, herpes zoster/shingles, RTX
- Isomorphic (Koebner phenomenon) —> lesions exclusively in areas of friction in the bra-line, waistband area, inguinal creases
Vaccination —> Onset of morphoea in children at the site of or close temporal relationship to vaccination
- hep B
- MMR
- Diphtheria
- Tetanus
- pertussis
- Pneumococcus
- BCG
- vitamin B12 injection
- vitamin K injection
Post-Radiation
- mainly linked to RTX for breast CA
- prior Dx of sustemic sclerosis a risk factor
- mostly develop within 1 year of completing RTX, but delayed onset reported
Mostly within RTX field, but dam extend beyond RTX field
- DDx - chronic radiation dermatitis, post-irradiation recall dermatitis, cancer recurrence, cellulitis —> histo confirmation usually necessary to exclude cancer recurrence
Medications
- high dose balkcatib
- Onset 1-30 months post drug initiation
Infection (except Borrelia) —> No conclusive evidence to date that morphoea is caused by Borrelia infection
AUTOIMMUNITY
ANA positivity, predominatly speckled pattern (homogenous, nucleolar pattern also assoc)
- significance unclear
- ? Higher likelihood of extracutaneous manifestations
Antihistone antibodies
- mainly in linear moprhoea
- ? ANA positivity + antihistone antibodies —> ? more extensive disease, greater functional impairment
Anti-ssDNA
GENETIC FACTORS
Rare familial cases in linear and generalised morphoea
HLA-DRB104:04 (also assoc with systemic sclerosis)
HLA-B37
Predominance of F gender
Histo
Histo changes similar in all morphoea subtypes but vary in relation to depth of involvement
EARLY ACTIVE INFLAMMATORY PHASE
Epidermis may be
- normal
- flattened with loss of rete ridges
- acanthotic
Oedema + Dense predominantly perivascular Lymphocytic infiltrate in reticular +/- papillary dermis
variable plasma cells, eos, mast cells, macrophages
Inflammation may extend around eccrine glands in to the lower dermis, sub cut or deeper
Swollen collagen bundles running parallel to the skin surface in the reticular dermis
Subcut fat may ge replaced by thickened wavy fibres of newly formed collagem
Endothelial swelling, oedema of vessel walls
LATER FIBROTIC PHASE
Number of inflammatory cells reduce (little inflammation)
Collagen bundles thicken, closely packed, highly eosniphilic, orientated horizontally
Skin sclerosis increases
Dermal appendages and subcut fat progressively lost
Reduced number of eccrine glands + entrapped by collagen —> appear higher in the dermis
Fewer blood vessels within thickened hyalinised collagen
Fascia, striated muscles may show fibrosis, sclerosis
Grading of Disease severity
Age of onset
Extent of disease
Depth of disease
Extracutaneous involvement Bony, joint, CNS
LOW SEVERITY Superficial circumscribed (limited) plaque morphoea
MODERATE SEVERITY
Deep circumscribed (limited) moprhoea
Linear morphoea of the trunk and limb w/o high morbidity
HIGH SEVERITY
Generalised or pansclerotic morphoea
Craniofacial linear morphoea
CNS involvement
Limb shortening —> functional limitation
Joint contracture —> functional limitation
Complications - Extracutaneous manifestations
GENERALISED MORPHOEA Arthralgia Dysphagia Dypsnoea Raynauds phenomenon
LINEAR MORPHOEA
Neurological (related to affected site on face, scalp)
Ocular (related to affected site on face, scalp)
ORAL/DENTAL Malocclusion Overgrowth tendency lower 1/3 of face Abnormal mastication Dental anomalies Skeletal asymmetry Bone involvement TMJ involvement
OCULAR —> 25% cases unrelated to site of skin lesions Episcleritis Anterior uveitis Keratitis Glaucoma Xerophthalmia Strabismus Mydriasis Papilloedema
NEURO —> asymptomatic patients can have substantial CNS abnormalities on imaging —> ? Need for screening in patients with disease involving the head, neck Headache Seizures Cranial nerve palsies Hemiparesis Ipsilateral/contralateral bone thinning Cerebral atrophy White matter lesions Peripheral neuropathy CNS vasculitis
MSK
Arthritis
- unrelated to site in some cases —> systemic rather than local inflammatory process
- 30% had positive Rh factor
VASCULAR ABNORMALITIES Cutaneous vasculitis DVT Raynaud phenomenon Vascular malformations
GIT
Symptomatic GORD
RARE
Respiratory
Cardiac
Renal
Overall the extracutaneous manifestations suggest a more widespread inflammatory and/or autoimmune process —> need for more systematic multiorgan baseline investigation
Complications - Psychological manifestations
Anxiety/Depression
Psychological morbidity highest in patients with
- Generalised morphoea
- Eosinophilic fascitis
- More severe disease
- Pruritus
- Greater levels of pain
- Greater levels of fatigue
- Greater impact of disease on daily life
- Greater impact of disease on social support
DDx of early inflammatory phase
GA
Early extragenital LS
Lyme disease (erythema migrans)
MF
Cutaneous mastocytosis
Radiation dermatitis
Fixed drug eruption
DDx of sclerotic phase
NLD
Pretibial myxoedema
DDx of hyperpigmented phase
PIH
Actinic LP
CALM
DDx of atrophic phase
Lipodystrophy
Steroid-induced atrophy
Lupus profundus
Lyme disease (Acrodermatitis chronica atrophicans)
Late stage Panniculitis
