10 - 64 - MORPHEA AND LICHEN SCLEROSUS - HIGH YIELD Flashcards
What subtype predominates in children
Linear Morphea
What subtype predominates in aduts?
Circumscribed and generalized
how do you differentiate morphea from scleroderma
lack of acrosclerosis / sclerodactyly
What are the stages of morphea
- Inflammatory stage
- Morphea begins as erythematous plaques or patches, sometimes with a reticulated appearance. Later, hypopigmented sclerotic plaques develop at the center of the lesion, surrounded by an erythematous or violaceous border. - Sclerotic stage
- Sclerosis develops centrally, has a shiny white color with surrounding hyperpigmentation - Atrophic stage
- Over months to years, the sclerotic plaque softens and becomes atrophic with hypopigmentation or hyperpigmentation
This stage is associated with cigarette paper wrinkling (papillary dermis), cliff drop (dermal), or deep indentions altering the contour of the affected body part (subcutis or deeper atrophy)
Atrophic stage
presents as oval to round lesions that are of limited cutaneous distribution so do not meet criteria for generalized disease
Circumscribed Morphea
Patients with circumscribed morphea should be closely followed, as both linear and generalized morphea may begin with circumscribed lesions.
Generalized morphea is characterized by more than or equal to how many lesions on how many anatomic sites?
more than or equal to 4 lesions on at least 2 of 7 different anatomic sites
3 variants of genaralized morphea
(a) isomorphic,
(b) symmetric, and
(c) pansclerotic
where do lesions of generalized morphea begin?
lesions frequently begin on the trunk and spread acrally, sparing the fingers and toes
Linear morphea usually affects what areas
extremities and face, but it can occur on the trunk
Classification of Morphea Subtypes
may present as an atrophic linear plaque on the forehead), extending to the scalp (where cicatricial alopecia occurs), brow, nose, and lip.
En coup de sabre (“cut of the sword”)
involves the deep dermis, subcutaneous tissue, fascia, and muscle
The skin feels thickened and bound down to the underlying fascia and muscle.
Deep morphea, or morphea profunda
5 subtypes of morphea
- Circumscribed Morphea
- GeneralizedMorphea
- Linear Morphea
- Deep Morphea
- Mixed Morphea
most common extracutaneous manifestation of morphea
Musculoskeletal involvement: arthritis, myalgias, neuropathies, and carpal tunnel syndrome
- related disorder presenting with rapid onset of symmetric areas of pain and poorly circumscribed indurated, plaques, usually on the extremities
- may occur with cutaneous lesions similar to morphea in 30% of cases, or remain without skin involvement.
- Deep subcutaneous and fascial involvement and peripheral eosinophilia are common
Eosinophilic fasciitis, or Shulman syndrome
En coup de sabre is associated with what complications
neurologic and ocular complications (3.6%) including seizures, headaches, adnexal abnormalities (eyelids, eyelashes), uveitis, and episcleritis
this type of morphea is associated with an increased risk of squamous cell carcinoma caused by chronic ulcers
pansclerotic morphea
What HLA confer an increased risk for morphea
HLADRB1 ∗ 04:04 and HLA-B37
only in the subset of linear morphea, __________ antibodies were associated with functional limitation
antihistone
only in the subset of linear morphea, ______ was associated with extensive body surface area involvement
ANA
Where should biopsy be taken in morphea?
inflammatory or indurated border when present or sclerotic center and include subcutaneous fat
Histopath findings of Inflammatory phase of morphea
- interstitial and perivascular inflammatory cell infiltrate in the dermis and sometimes subcutaneous tissue, composed mostly of lymphocytes and plasma cells,
- eosinophils, mast cells, and macrophages also may be present
- tissue edema, enlarged tortuous vessels, and thickened collagen bundles
histopath findings of sclerotic phase of morphea
- **homogenization of the papillary dermis and sclerosis extending to the reticular dermis **(or beyond depending on depth of involvement) with thickened collagen bundles.
- With severe sclerosis there is compression and loss of appendageal structures.
- In deep morphea, the deep reticular dermis, subcutis, and fascia show similar changes
A higher risk of recurrence (31% of patients) has been reported for what type of morphea as compared to other subtypes
linear morphea of the extremities
define Therapeutic success in morphea management
Therapeutic success is defined by resolution of erythema, typically over 2 to 3 months, lesion softening, which can take 12 months or more, cessation of lesion growth, and no new lesion development.
T/F.
In general, active lesions are most amenable to treatment.
True
morphea-specific outcome measure
localized scleroderma cutaneous assessment tool (LoSCAT)
consists of 2 scores: LoSSI (localized scleroderma severity index) and LoSDI (localized scleroderma damage index)
- useful for monitoring disease activity and damage, respectively, especially in clinical trials and research.
- Serial photography is helpful in clinical practice
In determining which therapy is appropriate for morphea, what factors must be considered?
■ Disease activity and damage
- early, active disease is most responsive to therapy
- Disease damage is much more difficult to treat and therapy should be aimed at preventing disease damage
- patients with active disease at risk for significant damage (facial lesions, progressive hemifacial atrophy, lesions crossing joint lines, large body surface area involvement, rapid progression) likely need aggressive therapy (phototherapy and/or systemic immunosuppressives)
■ Depth of involvement
- Morphea involving the superficial to mid-dermis would logically be amenable to topical therapy or phototherapy; however, involvement of the deep dermis and beyond should be treated systemically.
- Deep involvement can occur in all subtypes of morphea, but is especially prominent among linear and some generalized patients, and is associated with functional impairment and pain
■ Disease progression
- Many generalized and linear morphea patients are initially diagnosed with circumscribed morphea, but progress to have much more extensive disease. 9
- Therefore, patients who initially present with 1 to 3 plaques (which may be amenable to localized therapy) should be closely followed.
- If these patients progress, therapy should then be aimed at preventing further progression (ie, phototherapy or systemic therapy).
■ Systemic involvement
- Systemic involvement is an indication for systemic immunosuppressive therapy
■ Disease subtype
- Patients with linear and generalized (particularly those with rapid onset of confluent plaques) are likely at risk for severe, extensive disease and should be treated aggressively either with phototherapy or systemic immunosuppressives depending on the depth of involvement.
Indicators of active morphea disease
- development of new lesions or extension of existing lesions (photographs are critical),
- erythema and/or induration of the advancing edge of the lesion, and
- patient-reported symptoms, such as itch or tingling
what are examples of disease damage in morphea
- (reversible or irreversible) includes pigmentary change,
- sclerosis of the lesion center,
- atrophy (dermal, subcutaneous, muscle),
- contracture,
- limb-length discrepancy, and
- scarring alopecia
- Disease damage is much more difficult to treat and therapy should be aimed at preventing disease damage
- Furthermore, patients with active disease at risk for significant damage (facial lesions, progressive hemifacial atrophy, lesions crossing joint lines, large body surface area involvement, rapid progression) likely need aggressive therapy (phototherapy and/or systemic immunosuppressives).
in morphea, define superficial involvement
defined by histologic evidence of papillary dermal involvement
in morphea, define deep involvement
defined as sclerosis or inflammation of the deep dermis, subcutis, fascia, or muscle
considered a first-line systemic treatment for morphea, especially for deep morphea and rapidly progressive or disabling morphea
Methotrexate
Vulvar lichen sclerosus is associated with an increased risk of
SCC
Lichen sclerosus is predominant in what age group and gender
5th to 6th decade of life and children younger than 10 years
F>M (5:1)
this subtype is associated with an increased rate of autoimmune disease
generalized morphea
may potentially serve as a useful biomarker in morphea
CXCL-9
- Interestingly, there is a positive correlation between CXCL-9 levels and disease severity scores in morphea, suggesting that CXCL-9 may potentially serve as a useful biomarker in morphea (unpublished data).
- CXCL-10 levels in serum also correlate with disease activity in morphea patients
histopath findings of atrophic phase of morphea
- loss of inflammatory cell infiltrate, lessening of sclerosis, and a**bsence of appendageal structures. **
- Telangiectasia may occur
Morpheaform reactions can also develop secondary to what medications?
vitamin K1injections, taxanes, IFN-β1a, and balicatib
this subtype has a higher risk of recurrence as compared to other subtypes
linear morphea of the extremities (31% of patients)
most responsive to therapy
early, active disease
why is it important to know the depth of morphea involvement?
depth is one factor that would determine the therapeutic intervention
Morphea involving the superficial to mid-dermis would logically be amenable to topical therapy or phototherapy; however, involvement of the deep dermis and beyond should be treated systemically.
mpr
be used as a second-line systemic treatment, and is effective for morphea refractory to methotrexate or patients with contraindications or intolerance of methotrexate
Mycophenolate Mofetil
lichen sclerosus occurs predominantly in what sex and age group?
Preferentially affects women in the **fifth or sixth decade **of life and children younger than age 10 years; the female-to-male ratio is 5:1.
Vulvar lichen sclerosus is associated with an increased risk of what malignancy
SCC
Male genital lichen sclerosus (also known as balanitis xerotica obliterans) is usually confined to what areas?
glans penis, prepuce, or foreskin remnants
- Penile shaft involvement is less common, whereas scrotal involvement is rare
Extragenital LS typically affects what areas?
thighs, neck, trunk, and lips;
lesions are associated with pruritus, burning, or maybe asymptomatic
disease associations of lichen sclerosus
autoimmune thyroid disease, alopecia areata, pernicious anemia, morphea, and vitiligo
lifetime risk of developing squamous cell carcinoma as a complication of longstanding LS has been estimated in the order of what %?
4% to 6%
significant risk factors for developing SCC in vulvar LS
Age, long duration of LS, human papillomavirus infection, and evidence of hyperplastic changes
a tumor-suppressor gene, is downregulated in vulvar squamous cell carcinoma associated with LS, and maybe involved in early carcinogenesis of squamous cell carcinoma in LS
IRF6
most frequent complications of lichen sclerosus in men
painful erections and urinary obstruction
histopathologic findings in lichen sclerosus
- atrophic epidermis and a lichenoid infiltrate at the dermal–epidermal junction.
- Papillary edema is usually seen in early LS, but is gradually replaced by fibrosis with homogenization of collagen and acid mucopolysaccharides as the lesion matures
- Epidermal hyperplasia and/or dysplasia associated with LS on vulvar specimens are associated with an increased risk of malignant transformation, especially in conjunction with infection by high-risk human papillomaviruses.
common complication in children with anogenital lichen sclerosus
Constipation
clinical course of lichen sclerosus
chronic, relapsing condition with possibility of long-term functional and anatomic impairment if left untreated
prognosis of lichen sclerosus
- prognosis of LS is generally favorable in patients who are diagnosed and treated in the early nonscarring stages, and in patients compliant with initial and maintenance therapy with topical corticosteroids.
- Importantly, childhood-onset vulvar LS does not always resolve at puberty and may remain persistent
- early aggressive treatment with ultrapotent corticosteroids enables the best clinical course of childhood LS
complications of lichen sclerosus
- Recalcitrant chronic LS that causes erosions and progressive scarring may result in severe dysfunction of urination, sexual function, and defecation.
- Furthermore, the scarring nature of advanced LS produces resorption of the labia, alopecia, and altered anatomic structure of the vulva
