Mucinosis Flashcards
What are the two major groups of mucinosis?
- 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
What cell produces mucin?
Fibroblasts
What are the two major divisions of types of mucin in the dermis?
- Attached: glycosaminoglycans attached to a protein core (proteoglycan monomer). Dermatan sulfate, chondroitin sulfate
- Free: Hyaluronic Acid
What are the two major “attached” types of mucin?
Dermatan sulfate and chondroitin sulfate
What is the major “free” form of mucin in the dermis?
Hyaluronic acid
What are the two most common glycosaminoglycans in the dermis?
Chondroitin sulfate and hyaluronic acid (HA most important)
What condition is scleromyxedema associated with?
Paraproteniemia is almost always present and is IgGlambda (as compared to scleredema and NXG which are IgGk)
What is the clinical appearance of scleromyxedema?
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
What level of facial involvement can be seen with scleromyxedema?
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
What is the Dermato-neuro syndrome sometimes seen in scleromyxedema?
Potentially life-threatening encephalopathy; abrupt worsening of skin lesions, flu-like prodrome, fever/seizure, unexplained coma
What are some of the systemic manifestations of scleromyxedema?
Proximal muscle weakness, dysphagia, coma, sensory peripheral neuropathy (older men), arthropathies, scleroderma-like renal dz, carpal tunnel syn, restrictive or obstructive lung dz.
What are the most common sites of visceral involvement of scleromyxedema?
1 = GI/esophagus (ask about swallowing) and #2 Lung
What is the treatment for scleromyxedema?
No good tx for it.
- Most accepted currently is IVIg +/- thalidomide, CS, or therapies for MM (2nd line)
- 3rd line could be autologous BMT
What distinguished localized lichen myxedematosus from scleromyxedema?
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
What is the microscopic triad of scleromyxedema?
- Mucin deposition
- Fibroblast proliferation
- Fibrosis
What are the 4 types of localized lichen myxedematosus?
- Discrete papular form
- Acral persistent papular mucinosis
- Cutaneous mucinosis of infancy
- Nodular lichen myxedematosus
What is the clinical presentation of Discrete papular form of localized lichen myxedematosus?
- 2–5 mm papules on the extremities and trunk in a symmetrical pattern, face is spared
- No induration
- No systemic symptoms
What are the clinical features of the acral persistent papular mucinosis form of localized lichen myxedematosus?
- F:M = 3:1
- Ivory to skin-colored papules limited to dorsal hands and extensor forearms
- No systemic symptoms
Pathology findings of acral persistent papular mucinosis?
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
What are the important clinical features of cutaneous mucinosis of infancy?
- Firm opalescent papules on neck, upper arms, trunk
- No systemic symptoms or spontaneous resolution
Clinical presentation of pure nodular forms of localized lichen myxedematosus?
Multiple nodules on limbs and trunk with mild or absent papular component.
What are the pathology findings of localized lichen myxedemotosus?
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.
What are the clinical characteristics of self-healing cutaneous mucinosis?
- 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
What are the 3 types of scleredema?
I: Infection-related [Strep]
II: Monoclonal gammopathy associated
III: Diabetes associated (scleredema diabeticorum
Clinical features of type I scleredema?
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
What are the clinical features of the scleredema that is associated with monoclonal gammopathy?
Similar to those of type I but it is a much more gradual onset (years) and no associated illness
What are the clinical features of type III scleredema?
- 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)
If you treat the diabetes will the type III scleredema get better?
No
What is the histologic characteristics of scleredema?
- 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
Can you have systemic symptoms with scleredema?
Yes.
Serositis, myositis, cardiac abnormality, dysarthria, dysphagia, parotitis, ocular abnormalities.
What are the two types of thyroid dysfunction associated mucinosis?
Pre-tibial myxedema and generalized myxedema
In what situation does pre-tibial myxedema usually occur in?
- 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
What are the clinical features of pretibial myxedema?
Clinical features:
- Erythematous to skin-colored purple/brown or yellowish, waxy indurated nodules or plaques (peau d’ orange);
- Located on anterolateral lower legs & feet; painful & pruritic;
- Can present as a diffuse non-pitting edema of shins or feet that evolves into elephantiasis
- Rarely affects face, shoulders, UE, lower abd, scars or donor graft site.
- May also have hypertrichosis and hyperhidrosis confined to pre-tibial myxedematous skin
- May have foot drop/faulty dorsiflexion from entrapment of peroneal nerve
What are the histologic features of pretibial myxedema?
- Large quantities of mucin are deposited in reticular dermis
- Collagen bundles separate and dermis thickened
- May have a GRENZ zone
- Perivascular and periadnexal lymphocytic infiltrate w/ mast cells and large stellate fibroblasts
- Decreased elastic fibers
- Epidermis: hyperkeratosis, papillomatosis and epidermal hyperplasia
Treatment for pre-tibial myxedema?
Can try topical CS under occlusion or intralesional CS as first line.
Note that tx of the thyroid dysfunction will not improve skin, and indeed sometimes this precipitates pre-tibial myxedema.
In what setting does generalized myxedema occur?
This occurs w/ hypothyroidism
What is the pathophysiology of generalized myxedema?
Quantitative or functional deficiency of thyroxine leads to impaired degradation of mucin rather than increased synthesis
What types of hypothyroidism may precipitate generalized myxedema?
Congenital (cretinism), juvenile, or adult-onset hypothyroidism
What are the initial features of generalized myxedema?
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”
What are some clinical findings in congenital hypothyroidism?
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)
What is a distinctive feature of juvenile hypothyroidism?
Hypertrichosis
What things, when ingested, can lead to hypothyroidism?
Iodine uptake inhibitors: Raw Bok Choy
What is reticular erythematous mucinosis?
- 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
What is the clinical appearance of reticular erythematous mucinosis?
- 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
What is the treatment of reticular erythematous mucinosis?
Antimalarials (hydroxychloroquine) clears in 4-8 wks, sunscreens, topical & systemic corticosteroids
What is cutaneous lupus mucinosis?
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
Clinical findings of cutaneous lupus mucinosis?
- 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
What is primary follicular mucinosis?
An idiopathic, benign disease that occurs primarily in children and young adults
Differs from the follicular mucinoses associated w/ atopic derm or CTCL
Clinical of primary follicular mucinosis?
Presents as one to several pink plaques +/- scale limited to the face and scalp and associated w/ alopecia
Histology of primary follicular mucinosis?
Path shows mucin within follicular epi and sebaceous glands that causes acantholysis, later lesions may have cystic spaces w/ perifollicular lymphs, histiocytes, eo.
What is a mucinous nevus?
- Benign hamartoma which may be congenital or acquired
- Plaque in a unilateral nevoid pattern
What is the histology of mucinous nevus?
- 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
If you see an angiomyxoma in the external ear or eyelid what disease can this be associated with?
This is pathognomonic for Carney Simplex
What are the most common locations for angiomyxoma?
1-5 cm nodule on face, trunk or genitals
What are the cutaneous findings in generalized myxedema?
- 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
What are some internal organ issues that can occur in generalized myxedema?
Cardiomegaly, megacolon, bowel obstruction, serositis, carpal tunnel syndrome, CN7 paralysis, Alzheimer’s-like psychiatric symptoms (mucin deposits in the brain)
