Amyloidosis Flashcards
Descibe. This tissue has a toludine blue and alkaline fuchsin stain
This tissue has been stained with Thioflavin
Describe
Amorphous mass of eosinophillic material with the superficial dermis
Differenitation between nodular PCLA and systemic amyloidosis may require biopsies taken from the rectal submucosa or abdominal subcutaneous fat
True
What stains can you do if you suspect amyloidosis
Standard stains:
- H +E,
- toludine blue
- alkaline fuschsin
- PAS (positive)
Amyloid stains:
- Congo Red (apple green birefingrince under polarised light)
- Thioflavin T (positive immunoflurescence)
- Crystal violet or methyl violet (metachromasia)
Immunohistochemistry:
- Cytokeratin stains (pan or for 5, 1, 10 and 14)
- immunoglobulin light chain antibodies
Electronmicroscopy
Primary amyloidosis is commonly observed in west europeans
False - South east asians (singapore, taiwan, thailand)
and lichen amyloidosis in those of chinese descent, type 4 an 5 phototype
macular = central and south america
Other than stains, what else can you do with a skin sample suspicious for amyloidsosis?
Electron microscopy - can visualise amyloid fibrils and filaments ( 7.5 - 10 nm)
What the triggers for amyloidosis?
○ Chronic inflammation
○ Malignancy
○ Mutation
○ Pro-amyloidogenic peptides sequences
○ Microenvironmental changes
How do you classify amyloidsosis?
- Primary localised cutaneous amyloidosis (PLCA)
- Secondary localised cutaneous amyloidosis (SLCA)
- Systemic amyloidosis with cutaneous involvement
- Secondary cutaneous amyloidosis originating from other systemic disease
How do you investigate someone you suspect has primary cutaneous amyloidosis?
Biopsy for:
- HE, toluidine blue, alkaline fuchin
- congo RED, thioflavin T, crystal violet, methyl violet
- IF: cytokeratin, immunoglobulin light chians
- Electronmicroscopy
What are the investigations for systemic amyloidosis?
Baseline:
- FBC
- UEC
- Urinalysis
- Coagulation profile
- BNP
- Troponin
- ECG
Abdominal fat +/- direct tissue biopsy for all suspected systemic amyloidsosis systems
Immunotyping
SPEP, urine electophoresis
Describe and provide DDx
Describe
What are the subtypes of Localised cutaneous amyloidosis
Macular PLCA (35%)
Papular (lichenoid) PLCA (35%)
Biphasic
Nodular PLCA (1.5%)
Secondary localised cutaneous amyloidosis SLCA
Familial PLCA
Primary cutaneous amyloidosis affects women more than it affects men
True (2-3 -1)
Describe and DDx
Describe and Dx
Describe and DDx
Describe and Dx
Describe and Dx
Describe and Dx
Describe and DDx
Describe and Dx
what is the pathogenesis of Primary cutaneous amyloidosis?
Amyloid (which is normally soluable) undergoes changes that cause it to aggregate and deposit in the skin.
Exact reason for this is not not well understood
- combination of environmental, genetic factor and friction
What is the pathogenesis of systemic amyloidosis?
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
What are the key features of amyloid on histology?
- 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
Why do you do immunohistochemistry on amyloid?
Can help differentiate the type of amyloid
- immunoglobulin light chains
- Transthyretin
- keratin
- AA protein
etc
What are the key clinical features of Macular amyloidosis? and biphasic amyloidosis?
- 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
What are the clinical features of lichen amyloidosis?
- 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
What are the associations of macular and lichen amyloidosis?
- AICTD
- systemic sclerosis
- SLE
- DM - Primary bilary cirrhosis
- pachyonychia congenita,
- dyskeratosis congenita
- familial palmoplantar keratoderma
- MEN 2A
- Sipple syndrome
At sites of injection of several medications, e.g. insulin, cutaneous amyloid deposits can develop
What are the clinical features of nodular amyloidosis?
- Single or multiple waxy, nodules or infiltrative plaques
- Most often on the tunk or extremities
50% of patients with nodular amyloidosis progress to systemic invovlement
False - previously reported at 50%, but newer studies suggest it is much lower (~7%)
What would you see on histo for nodular amyloidosis?
Amyloid
= amorphous, homogenous eosinophillic material in the dermis, subcutis and vessels
Perivascular infiltrate of plasma cells
Immunostaining of light chains is mnodmally positive.
What is your DDx for macular or lichenoid amyloidsis?
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
What are your DDx for nodular amyloidosis?
Systemic amyloidosis
B-cell lymphoma
Tumoour stage MF
Cutaneous lymphoid hyperplasia
Sarcoidosis
Colloid millium
How is primary cutaneous amyloidosis treated?
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)
What is secondary cutaneous amyloidosis?
What lesions does it occur?
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
What is Hypotrichosis simplex of the scalp 1/hypotrichosis 2 (HYPT2)
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
How does systemic amyloidosis present?
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
How to investigate systemic amyloidosis?
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
Treatment of systemic amyloidosis?
High mortality without treatment
Guided by haematology
Melphalan
Systmemic corticosteroids
Cyclophsophamide
Bortezomib
Daratumumab
HSCT
Organ sepcific supportive therapy
What are the familial / inherited amyloidosis
- IL-31 receptor-associated amyloidosis
- causes a pirmary cutanoeus amyloidsosis (PLCA1 and PLCA2)
- gene: OSMR, IL31RA - 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 - 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 - Sipple syndrome
- an autosomal dominant disorder
- triad of medullary carcinoma of the thyroid, pheochromocytomas, and hyper-parathyroidism - 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 - 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 - Transthyretin Amyloidosis (ATTRwt/ATTRv Amyloidosis)
Describe and DDx
