Mucinosis

Question 1

What are the two major groups of mucinosis?

Answer 1

• Primary cutaneous mucinoses (mucin deposition leads to clinical lesions and is the primary histologic feature)
• Secondary mucinosis: mucin deposition is an associated finding but not the primary process

Question 2

What cell produces mucin?

Answer 2

Fibroblasts

Question 3

What are the two major divisions of types of mucin in the dermis?

Answer 3

• Attached: glycosaminoglycans attached to a protein core (proteoglycan monomer). Dermatan sulfate, chondroitin sulfate
• Free: Hyaluronic Acid

Question 4

What are the two major “attached” types of mucin?

Answer 4

Dermatan sulfate and chondroitin sulfate

Question 5

What is the major “free” form of mucin in the dermis?

Answer 5

Hyaluronic acid

Question 6

What are the two most common glycosaminoglycans in the dermis?

Answer 6

Chondroitin sulfate and hyaluronic acid (HA most important)

Question 7

What condition is scleromyxedema associated with?

Answer 7

Paraproteniemia is almost always present and is IgGlambda (as compared to scleredema and NXG which are IgGk)

Question 8

What is the clinical appearance of scleromyxedema?

Answer 8

Numerous firm waxy 2-3 mm closely aligned papules form in a widespread symmetrical pattern.

• Most common sites of involvement are the head and neck as well as upper trunk, hands, forearms, and thighs

The strikingly linear array often seen of the papules

Question 9

What level of facial involvement can be seen with scleromyxedema?

Answer 9

Severe involvement can lead to leonine facies, however less robust involvement can occur near the glabella with furrowing.

note there is mucous membrane and scalp sparing

Question 10

What is the Dermato-neuro syndrome sometimes seen in scleromyxedema?

Answer 10

Potentially life-threatening encephalopathy; abrupt worsening of skin lesions, flu-like prodrome, fever/seizure, unexplained coma

Question 11

What are some of the systemic manifestations of scleromyxedema?

Answer 11

Proximal muscle weakness, dysphagia, coma, sensory peripheral neuropathy (older men), arthropathies, scleroderma-like renal dz, carpal tunnel syn, restrictive or obstructive lung dz.

Question 12

What are the most common sites of visceral involvement of scleromyxedema?

Answer 12

1 = GI/esophagus (ask about swallowing) and #2 Lung

Question 13

What is the treatment for scleromyxedema?

Answer 13

No good tx for it.

• Most accepted currently is IVIg +/- thalidomide, CS, or therapies for MM (2nd line)
• 3rd line could be autologous BMT

Question 14

What distinguished localized lichen myxedematosus from scleromyxedema?

Answer 14

Lesions in localized lichen myxedematosus are localized to only the skin, localized the upper and lower extremities, sometimes trunk

• The pathology triad is not present, only mucin deposition with variable fibroblast proliferation
• There is no monoclonal gammopathy

Question 15

What is the microscopic triad of scleromyxedema?

Answer 15

1. Mucin deposition
2. Fibroblast proliferation
3. Fibrosis

Question 16

What are the 4 types of localized lichen myxedematosus?

Answer 16

1. Discrete papular form
2. Acral persistent papular mucinosis
3. Cutaneous mucinosis of infancy
4. Nodular lichen myxedematosus

Question 17

What is the clinical presentation of Discrete papular form of localized lichen myxedematosus?

Answer 17

• 2–5 mm papules on the extremities and trunk in a symmetrical pattern, face is spared
• No induration
• No systemic symptoms

Question 18

What are the clinical features of the acral persistent papular mucinosis form of localized lichen myxedematosus?

Answer 18

1. F:M = 3:1
2. Ivory to skin-colored papules limited to dorsal hands and extensor forearms
3. No systemic symptoms

Question 19

Pathology findings of acral persistent papular mucinosis?

Answer 19

Discrete papule shape, collarette of scale, and then well-circumscribed deposits of abundant acid mucopolysaccharide between collage in the superficial dermis. Stains + with alcian blue, colloidal iron, or toluidine blue stains.

• Increased mast cells

Question 20

What are the important clinical features of cutaneous mucinosis of infancy?

Answer 20

1. Firm opalescent papules on neck, upper arms, trunk
2. No systemic symptoms or spontaneous resolution

Question 21

Clinical presentation of pure nodular forms of localized lichen myxedematosus?

Answer 21

Multiple nodules on limbs and trunk with mild or absent papular component.

Question 22

What are the pathology findings of localized lichen myxedemotosus?

Answer 22

Mucin in the upper and mid reticular dermis, fibroblast proliferation is variable, fibrosis is not marked or absent.

• In the acral persistent form the mucin is more superficial and in the cutaneous mucinosis of infancy, the mucin is very superficial and can look enclosed by the epidermis.

Question 23

What are the clinical characteristics of self-healing cutaneous mucinosis?

Answer 23

• Occurs in children ages 1-15
• Acute eruption of papules, sometimes coalescing into linear infiltrated plaques, commonly on the face, neck, scalp, abdomen, and thighs
• Mucinous subcutaneous nodules in periarticular areas and on face w/ periorbital swelling
• Can have systemic sx’s like fever, arthralgias, muscle tenderness

No paraproteinemia, bone marrow plasmacytosis or thyroid dysfunction.

SPONTANEOUSLY RESOLVES IN 1-8 MONTHS

Question 24

What are the 3 types of scleredema?

Answer 24

I: Infection-related [Strep]

II: Monoclonal gammopathy associated

III: Diabetes associated (scleredema diabeticorum

Question 25

Clinical features of type I scleredema?

Answer 25

Affects children and middle-aged adults (often women). Preceded by sx's of infxn or respiratory tract The skin of the cervicofacial region **suddenly** hardens w/ extension to the trunk and proximal upper limbs. - The face is expressionless and opening the mouth and swallowing are difficult because of involvement of tongue and pharynx - Resolves spontaneously

Question 26

What are the clinical features of the scleredema that is associated with monoclonal gammopathy?

Answer 26

Similar to those of type I but it is a much more gradual onset (years) and no associated illness

Question 27

What are the clinical features of type III scleredema?

Answer 27

* Subtle onset * Persistent involvement * Erythema & induration of posterior neck & back (peau d’ orange), sharp cutoff * Excess stimulation by insulin, microvascular damage & hypoxia may ↑ synthesis of collagen & mucin * Occasionally fatal (if internal involvement)

Question 28

If you treat the diabetes will the type III scleredema get better?

Answer 28

No

Question 29

What is the histologic characteristics of scleredema?

Answer 29

* Thickened reticular dermis * Large collagen bundles separated by clear spaces filled w/ mucin resulting in a fenestrated appearance * Decreased elastic fibers * Sparse perivascular lymphocytic infiltrate * Mucin also accumulates in muscle & heart

Question 30

Can you have systemic symptoms with scleredema?

Answer 30

Yes. Serositis, myositis, cardiac abnormality, dysarthria, dysphagia, parotitis, ocular abnormalities.

Question 31

What are the two types of thyroid dysfunction associated mucinosis?

Answer 31

Pre-tibial myxedema and generalized myxedema

Question 32

In what situation does pre-tibial myxedema usually occur in?

Answer 32

- A/w with HYPERthyroidism (GRAVES [1-5%] most commonly vs tx of hypothyroid) - Also: goiter, thyroid acropachy (subperiosteal new bone), exophthalmos (pretibial myxedema in 25% w/ exophthalmos), thyroid-stimulating immunoglobins recognizing TSH

Question 33

What are the clinical features of pretibial myxedema?

Answer 33

Clinical features: 1. Erythematous to skin-colored purple/brown or yellowish, waxy indurated nodules or plaques (peau d’ orange); 2. Located on anterolateral lower legs & feet; painful & pruritic; 3. Can present as a diffuse non-pitting edema of shins or feet that evolves into elephantiasis 4. Rarely affects face, shoulders, UE, lower abd, scars or donor graft site. 5. May also have hypertrichosis and hyperhidrosis confined to pre-tibial myxedematous skin 6. May have foot drop/faulty dorsiflexion from entrapment of peroneal nerve

Question 34

What are the histologic features of pretibial myxedema?

Answer 34

1. Large quantities of mucin are deposited in reticular dermis 2. Collagen bundles separate and dermis thickened 3. May have a GRENZ zone 4. Perivascular and periadnexal lymphocytic infiltrate w/ mast cells and large stellate fibroblasts 5. Decreased elastic fibers 6. Epidermis: hyperkeratosis, papillomatosis and epidermal hyperplasia

Question 35

Treatment for pre-tibial myxedema?

Answer 35

Can try topical CS under occlusion or intralesional CS as first line. ## Footnote *Note that tx of the thyroid dysfunction will not improve skin, and indeed sometimes this precipitates pre-tibial myxedema.*

Question 36

In what setting does generalized myxedema occur?

Answer 36

This occurs w/ hypothyroidism

Question 37

What is the pathophysiology of generalized myxedema?

Answer 37

Quantitative or functional deficiency of thyroxine leads to impaired degradation of mucin rather than increased synthesis

Question 38

What types of hypothyroidism may precipitate generalized myxedema?

Answer 38

Congenital (cretinism), juvenile, or adult-onset hypothyroidism

Question 39

What are the initial features of generalized myxedema?

Answer 39

Initial symptoms include mental and physical sluggishness, wt gain, leg cramps, constipation, loss of appetite, cold intolerance, dull facial expression; can lead to death if un-treated secondary to “myxedema coma”

Question 40

What are some clinical findings in congenital hypothyroidism?

Answer 40

Dwarfism, mental retardation, somnolence, constipation, poor muscle tone, the persistence of jaundice, respiratory problems; - 1/3 of patients asymptomatic - Skin is dry cold pale, nails and hair are dry/brittle - **Presence of a clavicular pad is diagnostic** (RECALL - shoulder pad sign = amyloid)

Question 41

What is a distinctive feature of juvenile hypothyroidism?

Answer 41

Hypertrichosis

Question 42

What things, when ingested, can lead to hypothyroidism?

Answer 42

Iodine uptake inhibitors: Raw Bok Choy

Question 43

What is reticular erythematous mucinosis?

Answer 43

* Rare disorder, mostly middle aged women [hx of tanning bed use], but can occur in men and children * Persistent photoaggravated eruption (back or chest, sometimes abdomen) [UVA and UVB mediated * Could be on the spectrum of tumid LE

Question 44

What is the clinical appearance of reticular erythematous mucinosis?

Answer 44

* Reddish macules & papules coalesce into reticulated or net-like annular patterns or plaque-like lesions on central chest * Slightly pruritic. * Generally NOT associated w/ systemic disease or abnormal lab tests

Question 45

What is the treatment of reticular erythematous mucinosis?

Answer 45

Antimalarials (hydroxychloroquine) clears in 4-8 wks, sunscreens, topical & systemic corticosteroids

Question 46

What is cutaneous lupus mucinosis?

Answer 46

Lesions that can accompany or precede CTD, most often LE. * Occurs in 1.5% of pts with LE * Is associated with systemic sx's in 75% of cases of LE * Is not UV sensitive

Question 47

Clinical findings of cutaneous lupus mucinosis?

Answer 47

* Characterized by asymptomatic, skin-colored papules or nodules on back, V of chest, or arms * Tangential illumination may enhance detection of lesions * UV doesn’t flare lesions

Question 48

What is primary follicular mucinosis?

Answer 48

An idiopathic, benign disease that occurs primarily in children and young adults Differs from the follicular mucinoses associated w/ atopic derm or CTCL

Question 49

Clinical of primary follicular mucinosis?

Answer 49

Presents as one to several pink plaques +/- scale limited to the face and scalp and associated w/ alopecia

Question 50

Histology of primary follicular mucinosis?

Answer 50

Path shows mucin within follicular epi and sebaceous glands that causes acantholysis, later lesions may have cystic spaces w/ perifollicular lymphs, histiocytes, eo.

Question 51

What is a mucinous nevus?

Answer 51

- Benign hamartoma which may be congenital or acquired - Plaque in a unilateral nevoid pattern

Question 52

What is the histology of mucinous nevus?

Answer 52

* Path shows diffuse mucin in the upper dermis w/ absent collagen and elastic fibers in the mucinous area * Fibroblasts are CD34+ * If the epidermis is acanthotic & hyperkeratotic, then may be a combined hamartoma mucinous + epidermal nevus

Question 53

If you see an angiomyxoma in the external ear or eyelid what disease can this be associated with?

Answer 53

This is pathognomonic for Carney Simplex

Question 54

What are the most common locations for angiomyxoma?

Answer 54

1-5 cm nodule on face, trunk or genitals

Question 55

What are the cutaneous findings in generalized myxedema?

Answer 55

* Skin is pale, cool, waxy, and dry; absence of sweating leads to acquired ichthyosis or eczema craquele * Eyelids, lips, tongue and hands are puffy; nose is broad * Hair & Nails are dry and brittle; non-scarring alopecia; alopecia of lateral third of eyebrows * Purpura of the extremities, blue telangiectatic fingertips, delayed wound healing, xanthomas

Question 56

What are some internal organ issues that can occur in generalized myxedema?

Answer 56

Cardiomegaly, megacolon, bowel obstruction, serositis, carpal tunnel syndrome, CN7 paralysis, Alzheimer’s-like psychiatric symptoms (mucin deposits in the brain)