10 - 64 - MORPHEA AND LICHEN SCLEROSUS - HIGH YIELD

Question 1

What subtype predominates in children

Answer 1

Linear Morphea

Question 2

What subtype predominates in aduts?

Answer 2

Circumscribed and generalized

Question 3

how do you differentiate morphea from scleroderma

Answer 3

lack of acrosclerosis / sclerodactyly

Question 4

What are the stages of morphea

Answer 4

1. 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.
2. Sclerotic stage
   - Sclerosis develops centrally, has a shiny white color with surrounding hyperpigmentation
3. Atrophic stage
   - Over months to years, the sclerotic plaque softens and becomes atrophic with hypopigmentation or hyperpigmentation

Question 5

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)

Answer 5

Atrophic stage

Question 6

presents as oval to round lesions that are of limited cutaneous distribution so do not meet criteria for generalized disease

Answer 6

Circumscribed Morphea

Patients with circumscribed morphea should be closely followed, as both linear and generalized morphea may begin with circumscribed lesions.

Question 7

Generalized morphea is characterized by more than or equal to how many lesions on how many anatomic sites?

Answer 7

more than or equal to 4 lesions on at least 2 of 7 different anatomic sites

Question 8

3 variants of genaralized morphea

Answer 8

(a) isomorphic,
(b) symmetric, and
(c) pansclerotic

Question 9

where do lesions of generalized morphea begin?

Answer 9

lesions frequently begin on the trunk and spread acrally, sparing the fingers and toes

Question 10

Linear morphea usually affects what areas

Answer 10

extremities and face, but it can occur on the trunk

Question 11

Classification of Morphea Subtypes

Answer 11

Question 12

may present as an atrophic linear plaque on the forehead), extending to the scalp (where cicatricial alopecia occurs), brow, nose, and lip.

Answer 12

En coup de sabre (“cut of the sword”)

Question 13

involves the deep dermis, subcutaneous tissue, fascia, and muscle

The skin feels thickened and bound down to the underlying fascia and muscle.

Answer 13

Deep morphea, or morphea profunda

Question 14

5 subtypes of morphea

Answer 14

1. Circumscribed Morphea
2. GeneralizedMorphea
3. Linear Morphea
4. Deep Morphea
5. Mixed Morphea

Question 15

most common extracutaneous manifestation of morphea

Answer 15

Musculoskeletal involvement: arthritis, myalgias, neuropathies, and carpal tunnel syndrome

Question 16

• 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

Answer 16

Eosinophilic fasciitis, or Shulman syndrome

Question 17

En coup de sabre is associated with what complications

Answer 17

neurologic and ocular complications (3.6%) including seizures, headaches, adnexal abnormalities (eyelids, eyelashes), uveitis, and episcleritis

Question 18

this type of morphea is associated with an increased risk of squamous cell carcinoma caused by chronic ulcers

Answer 18

pansclerotic morphea

Question 19

What HLA confer an increased risk for morphea

Answer 19

HLADRB1 ∗ 04:04 and HLA-B37

Question 20

only in the subset of linear morphea, __________ antibodies were associated with functional limitation

Answer 20

antihistone

Question 21

only in the subset of linear morphea, ______ was associated with extensive body surface area involvement

Answer 21

ANA

Question 22

Where should biopsy be taken in morphea?

Answer 22

inflammatory or indurated border when present or sclerotic center and include subcutaneous fat

Question 23

Histopath findings of Inflammatory phase of morphea

Answer 23

• 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

Question 24

histopath findings of sclerotic phase of morphea

Answer 24

• **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

Question 25

A higher risk of recurrence (31% of patients) has been reported for what type of morphea as compared to other subtypes

Answer 25

linear morphea of the extremities

Question 26

define Therapeutic success in morphea management

Answer 26

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.

Question 27

T/F. In general, active lesions are most amenable to treatment.

Answer 27

True

Question 28

morphea-specific outcome measure

Answer 28

localized scleroderma cutaneous assessment tool (LoSCAT) consists of 2 scores: LoSSI (localized scleroderma severity index) and LoSDI (localized scleroderma damage index) ## Footnote * useful for monitoring disease activity and damage, respectively, especially in clinical trials and research. * Serial photography is helpful in clinical practice

Question 29

In determining which therapy is appropriate for morphea, what factors must be considered?

Answer 29

**■ 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.

Question 30

Indicators of active morphea disease

Answer 30

- 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

Question 31

what are examples of disease damage in morphea

Answer 31

- (reversible or irreversible) includes pigmentary change, - sclerosis of the lesion center, - atrophy (dermal, subcutaneous, muscle), - contracture, - limb-length discrepancy, and - scarring alopecia ## Footnote * 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).

Question 32

Question 33

Question 34

in morphea, define superficial involvement

Answer 34

defined by histologic evidence of papillary dermal involvement

Question 35

in morphea, define deep involvement

Answer 35

defined as sclerosis or inflammation of the deep dermis, subcutis, fascia, or muscle

Question 36

considered a first-line systemic treatment for morphea, especially for deep morphea and rapidly progressive or disabling morphea

Answer 36

Methotrexate

Question 37

Vulvar lichen sclerosus is associated with an increased risk of

Answer 37

SCC

Question 38

Lichen sclerosus is predominant in what age group and gender

Answer 38

5th to 6th decade of life and children younger than 10 years F>M (5:1)

Question 39

this subtype is associated with an increased rate of autoimmune disease

Answer 39

generalized morphea

Question 40

may potentially serve as a useful biomarker in morphea

Answer 40

CXCL-9 ## Footnote * 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

Question 41

histopath findings of atrophic phase of morphea

Answer 41

* l**oss of inflammatory cell infiltrate**, lessening of sclerosis, and a**bsence of appendageal structures. ** * Telangiectasia may occur

Question 42

Morpheaform reactions can also develop secondary to what medications?

Answer 42

vitamin K1injections, taxanes, IFN-β1a, and balicatib

Question 43

this subtype has a higher risk of recurrence as compared to other subtypes

Answer 43

linear morphea of the extremities (31% of patients)

Question 44

most responsive to therapy

Answer 44

early, active disease

Question 45

why is it important to know the depth of morphea involvement?

Answer 45

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.

Question 46

# 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

Answer 46

Mycophenolate Mofetil

Question 47

lichen sclerosus occurs predominantly in what sex and age group?

Answer 47

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.**

Question 48

Vulvar lichen sclerosus is associated with an increased risk of what malignancy

Answer 48

SCC

Question 49

Male genital lichen sclerosus (also known as balanitis xerotica obliterans) is usually confined to what areas?

Answer 49

**glans penis, prepuce, or foreskin remnants** ## Footnote * Penile shaft involvement is less common, whereas scrotal involvement is rare

Question 50

Extragenital LS typically affects what areas?

Answer 50

thighs, neck, trunk, and lips; ## Footnote lesions are associated with pruritus, burning, or maybe asymptomatic

Question 51

disease associations of lichen sclerosus

Answer 51

autoimmune thyroid disease, alopecia areata, pernicious anemia, morphea, and vitiligo

Question 52

lifetime risk of developing squamous cell carcinoma as a complication of longstanding LS has been estimated in the order of what %?

Answer 52

4% to 6%

Question 53

significant risk factors for developing SCC in vulvar LS

Answer 53

Age, long duration of LS, human papillomavirus infection, and evidence of hyperplastic changes

Question 54

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

Answer 54

IRF6

Question 55

most frequent complications of lichen sclerosus in men

Answer 55

painful erections and urinary obstruction

Question 56

histopathologic findings in lichen sclerosus

Answer 56

* **atrophic epidermis** and a l**ichenoid 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 ## Footnote * 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.

Question 57

common complication in children with anogenital lichen sclerosus

Answer 57

Constipation

Question 58

clinical course of lichen sclerosus

Answer 58

**chronic, relapsing** condition with possibility of **long-term functional and anatomic impairment** if left untreated

Question 59

prognosis of lichen sclerosus

Answer 59

* 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

Question 60

complications of lichen sclerosus

Answer 60

* 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