Amyloidosis Flashcards

Question

What is the pathogenesis of systemic amyloidosis?

Answer 1

substitution of amino acids at specific positions within the variable region of the immunoglobulin light chain likely destabilizes these chains thereby increasing the likelihood of their conversion to amyloid fibrils and resulting in deposition within the tissue

Answer 2

* On H+E amyloid appears as amorphous, homogenous, hyaline, eosinophilic deposits *Crystal violet metachromasia * By electron microscopy, amyloid appears as 7 to 10 nm wide, non-branching, non-anastomosing fibrils * X-ray crystal- lography and infrared spectroscopy reveal a characteristic cross-β- pleated sheet conformation. * Congo red stain: amyloid has an orange–red color on routine light microscopy, whereas under polarized light it exhibits green birefringence

Answer 3

Can help differentiate the type of amyloid - immunoglobulin light chains - Transthyretin - keratin - AA protein etc

Answer 4

* Pruritic * Hyperpigmented macules, coaesling into patches * often with a **rippled **pattern apparent on stretching the skin * Common sites = upper back over the scapula, extensor surfaces of the extremities *In biphasic = papules are superimposed on the hyperpigmentation

Answer 5

* Persistent, prurtic plaques * normally on the shins or extensor surfaces * Starts as discrete firm, scaly, skin coloured or hyperpigmented papules, coalesce into plaques * Often have rippled or ridged pattern * Start unilateral but become bilateral with time

Answer 6

1. AICTD - systemic sclerosis - SLE - DM 2. Primary bilary cirrhosis 3. pachyonychia congenita, 4. dyskeratosis congenita 5. familial palmoplantar keratoderma 6. MEN 2A 7. Sipple syndrome At sites of injection of several medications, e.g. insulin, cutaneous amyloid deposits can develop

Answer 7

* Single or multiple waxy, nodules or infiltrative plaques * Most often on the tunk or extremities

Answer 8

False - previously reported at 50%, but newer studies suggest it is much lower (~7%)

Answer 9

Amyloid = amorphous, homogenous eosinophillic material in the dermis, subcutis and vessels Perivascular infiltrate of plasma cells Immunostaining of light chains is mnodmally positive.

Answer 10

Macular: * Notalgia paresthetica * Pit versicolour * Atrophic lichen planus * drug induced hyperpigmentation * Post inflammatory hyperpigmentation * Erythema dyschromicum perstans Lichen amyloidosis: * LSC * Hypertrophic LP * Eczema / Psoriasis * papular mucinosis * pemphigoid nodularis * Pretibial myxoedema

Answer 11

Systemic amyloidosis B-cell lymphoma Tumoour stage MF Cutaneous lymphoid hyperplasia Sarcoidosis Colloid millium

Answer 12

Aim: break the itch scratch cycle. General measures: avoid irritants, moisturise **Topicals ** * Potent topical steroids +/- under occlusion * Intralesional triamcinalone * Topical calcinurin inhibitors * Occlusive dressing - e.g Zinc impregnanted crepe bandages **Physical ** * UVB * PUVA * Dermabrasian * CO2 laser * Erbium YAG laser **Systemics** * Systemic retinoids * Dupilimab * Low dose cyclophosphamide * Thalidomide * Nemolizumab (IL 31RA)

Answer 13

Refers to amyloid deposits that are inapparent clinically but can be detected histopathologically within skin lesions Most commonly occurs in: - seb Ks - BCCs - Ds - intradermal melanocytic naevi - pilomatricoma - trichoepithelioma - sweat gland tumour - bowens - porokeratosis

Answer 14

uncommon autosomal dominant disorder regarded as a particular form of secondary cutaneous amyloidosis. Patients have normal hair at birth, but progressively lose most scalp hair by the third decade. Eyebrows, beard and axillary hair, nails, and teeth develop normally

Answer 15

Constitutional Sx: - Fatigue - weight loss Organ specifc: - paresthesias (nerves) - syncopal episodes (autonomic nerves) - gastric dysmotility (autonomic nerve invovlement) - dyspnoea (cardiac) - signs of heart failure (pedal oedema etc) - frothy urine (proteinuria) - oedema (due to proteinuria) - hepatomegaly Cutanoues features (~25%) - oral mucosal rubbery swellings - macroglossia +/- papules, plaques, blisters - petichiae / purpura / echymosis including racoon eyes - waxy, indurated papules / nodules / plaques - smooth, erythematous, waxy infiltration with scattered superimposed papules can appear on the palms and volar aspect of the fingertips - bullous lesions - scleradermoid appearance

Answer 16

Bloods: - SPEP - Serum free light chians - FBC - UEC - LFTs (inc albumin) Urine: - Protein electrophoresis - Urinalysis Tissue: - skin biopsy - abdominal fat aspirate - rectal mucosa biopsy Organ specific: - BNP, troponin, echo, ecg, cardiac MRI - Liver USS - nerve conduction studies

Answer 17

High mortality without treatment Guided by haematology Melphalan Systmemic corticosteroids Cyclophsophamide Bortezomib Daratumumab HSCT Organ sepcific supportive therapy

Answer 18

1. IL-31 receptor-associated amyloidosis - causes a pirmary cutanoeus amyloidsosis (PLCA1 and PLCA2) - gene: OSMR, IL31RA 2. Dyschromic amyloidosis - PLCA3 - unusual variant in which a guttate leuko-derma is superimposed upon a background of hyperpigmentation and admixed with characteristic lesions of macular and lichen amyloidosis - gene: GPNNB 3. Multiple endocrine neoplasia (MEN) type 2 A - associated with pruritic areas of hyperpigmentation on the upper back. - The lesions have been described as notalgia paresthetica, macular amyloidosis, and lichen amyloidosis at an early age 4. Sipple syndrome - an autosomal dominant disorder - triad of medullary carcinoma of the thyroid, pheochromocytomas, and hyper-parathyroidism 5. X-linked reticulate pigmentary disorder (Partington amyloidosis) - In women, involvement was limited to the skin - in male patients, recurrent respiratory infections, corneal dystrophy, and photophobia were seen 6. Familial Amyloidosis, Finnish Type (AGel Amyloidosis) - characteristic triad of corneal lattice dystrophy, cranial neuropathies, and skin findings including cutis laxa-like changes and skin fragility 7. Transthyretin Amyloidosis (ATTRwt/ATTRv Amyloidosis)