Amyloidosis

Question 1

What is amyloid?

Answer 1

Amyloid is fibril proteins that arrange in beta-sheets.

AA and AL are two common categories

Question 2

What is the histology of amyloid and what is the stain used to see it?

Answer 2

Appears as homogenous, pink, fissued areas (cotton candy) that stain with Congo Red stain and turn apple green (birefringence) w/ polarized light

Question 3

What stains stain amyloid?

Answer 3

Congo red (classic), crystal violet, PAS, and thioflavin T

Question 4

What causes AA amyloid to lose its affinity for Congo Red stain?

Answer 4

Exposure to potassium permanganate

Question 5

What are the 5 types of cutaneous amyloid?

Answer 5

Primary, secondary, genetic, hemodialysis-associated (Beta2 microglobulin), localized

Question 6

What are the 3 types of localized amyloidosis?

Answer 6

Macular, lichenoid, nodular

Question 7

What are the clinical characteristics of macular amyloidosis and where does it most commonly present?

Answer 7

Presents as a “salt and pepper” confluent or rippled pruritic, hyperpigmented patch.

• Most common location is the interscapular back

Question 8

What is the protein and the derivation of macular amyloid?

Answer 8

Protein: Aker

Derivation: Keratinocyte tonofilaments (usually keratin 5)

Question 9

What is the histology of macular amyloid?

Answer 9

Amyloid is noted in the papillary dermis

Question 10

What is the clinical appearance and most common location of lichen amyloid?

Answer 10

Rippled, hyperpigmented, pruritic papules/plaques on extensor surfaces. (most commonly the shins)

Question 11

What disorder can macular amyloid be commonly seen in?

Answer 11

Notalgia paraesthetica

Question 12

What is the protein and derivative for lichen amyloid?

Answer 12

Derivative: keratinocyte tonofilaments most commonly keratin 5

Protein: Aker

Question 13

What is the clinical appearance of nodular amyloid and what are the most common sites?

Answer 13

Pink to yellow waxy nodules (smooth) and/or plaques. These are most commonly seen on the face or acral surfaces

Question 14

What is the derivation and the protein for nodular amyloid?

Answer 14

Derivative: Ig light chains

Protein: AL

Note that this is the only localized primary amyloidosis that is not from keratin!

Question 15

In what groups is localized amyloidosis more commonly seen?

Answer 15

Asians, Hispanics, and Middle Easterners

Question 16

Treatment options for localized amyloidosis?

Answer 16

No great tx options. Can try topical corticosteroids, phototherapy/laser to surgery

Question 17

What is the protein and derivation of primary systemic amyloidosis?

Answer 17

Derivation: Ig light chains (usually kappa subtype)

Protein: AL

Question 18

What is the organ system carries the worst prognosis in primary systemic amyloidosis?

Answer 18

It can involve any number of organ systems, but cardiac carries the worst prognosis

Question 19

What percentage of patients with primary systemic amyloidosis have mucocutaneous findings?

Answer 19

One third

Question 20

What causes systemic primary amyloidosis?

Answer 20

Underlying plasma cell dyscrasia (15% with myeloma)

Question 21

What can be the clinical mucocutaneous findings in primary systemic amyloidosis?

Answer 21

Papules/nodules/plaques that are translucent, or purpuric. Ecchymosis/pinch purpura (eyelids, neck, anogenital, or axillary)[BIG FOR BOARDS]. Can see bullous amyloid

• Macroglossia (you can see teeth indentation on side of tongue
• carpal tunnel syndrome
• Can have sclerodermoid presentation w/ alopecia and cutis verticis gyrata-like scalp changes (these look like the folds of a shar-pei dog)

Question 22

What is the histology of systemic primary amyloidosis (cutaneous)

Answer 22

Amyloid throughout the dermis and subcutis, in sweat glands, and blood vessel walls

Question 23

What labs should be checked if there is evidence of primary systemic amyloidosis (cutaneous)

Answer 23

UPEP/SPEP, and immunofixation (IFE) (besides basic labs)

Question 24

What are some causes of secondary amyloidosis?

Answer 24

Ankylosing spondylitis, Tb, HA, dystrophic EB, scleroderma, and autoinflammatory syndromes like Muckle-Wells

Question 25

What is the protein in secondary systemic amyloidosis and how does it end up in the skin (or other organs)?

Answer 25

The protein is Serum amyloid A (SAA) which gets converted to AA amyloid in the tissues

Question 26

What organ systems are most commonly involved in secondary systemic amyloidosis?

Answer 26

Skin is rarely affected, usually involves kidneys, liver, spleen, adrenals, and heart

Amyloidosis in hemodialysis patients is made up often of beta 2 microglobulin (Abeta2microglobulin) usually no skin involvement but can have subcutaneous nodules on the lower back