This document discusses cutaneous amyloidosis, which is a condition where abnormal protein deposits in the skin, changing its structure and function. It defines amyloidosis and describes the classification of primary localized, hereditary, and secondary systemic forms associated with other diseases. Key clinical features include yellowish macules and papules in localized forms, and petechiae, ecchymosis, and bleeding in secondary forms. Investigations include histology with amyloid stains like Congo red, immunohistochemistry to identify the amyloid precursor protein, and electron microscopy for definitive confirmation.

1. DR. SABHA TALIB NEAZEE
CUTANEOUS AMYLOIDOSIS

2. DEFINITION
 AMYLOID= STARCH LIKE (LATIN)
 AMYLOIDOSIS IS A CONDITION IN WHICH
THERE IS EXTRACELLULAR DEPOSITION
OF ANY OF GROUP OF AUTOLOGOUS
PROTEINS LEADING TO CHANGES IN
TISSUE ARCHITECTURE AND FUNCTION

3.  7.5-10 nm wide, linear, non branching
tubular fibrils loosely arranged in meshwork.
 Alpha and beta pleated sheet form.
 Distinction between primary and secondary
– Tt with KmnO4 prior to staining with congo
red.
 Primary amyloid retains its affinity for the dye
and green birefringence under polarized light
, whereas secondary loses both
characteristics

4. ETIOLOGIC FACTORS
 Racial susceptibility
 Chronic rubbing and friction
 Role of actinic radiation
 Familial cases with AD mode of inheritance
 Increased and reduced expression of various
pro or anti- apoptotic factors respectively

5. CLASSIFICATION
I. Localised cutaneous amyloidosis
1) Non hereditary
a) Macular- 35%
b) Papular-35%
c) Nodular-15%
d) SLCA( secondary localized cutaneous amyloidosis )
2) Hereditary
a) Familial PLCA

6. II. Cutaneous amyloidosis due to Systemic ds
–
1. Non hereditary-
a) Primary systemic and myeloma or plasmocytoma –
associated amyloidosis (AL)
b) Secondary systemic amyloidosis with inflammatory
tumour
c) Secondary hemodialysis associated ststemic
amyloidosis

7. 2. Hereditary –
a) Transthyretin/ familial amyloid polyneuropathy
b) Apo A1 amyloidosis
c) Cystatin C amyloidosis
d) Hereditary gelsolin amyloidosis

8. 3) Hereditary systemic ds with secondary
cutaneous amyloidosis
a) Muckle wells syndrome
b) TNF receptor 1 associated periodic fever
syndrome

9. CLINICAL VARIANTS
1) Biphasic,allotropic
2) Poikilodermatous PLCA
3) Amyloidosis cutis dyschromica
4) Bullous amyloidosis

10. PATHOPHYSIOLOGY (PRIMARY)
Friction
Friction
Apoptosis of basal keratinocytes
Release of cytokeratins
Covered with autoantibodies
Phagocytosed by macrophages
Degraded by enzymes to amyloid k

11. PATHOPHYSIOLOGY(SECONDARY)
Monoclonal plasma cell proliferation
Production of monoclonal immunoglobulin
Amyloid deposition in blood vessels
Fragile vessel walls
dermatorrhagia

12. CLINICAL FEATURES
 LCA- yellowish or brownish macules,
papules or plaques with pink to brownish
lichenoid glossiness ( amyloid deposition
exclusively in papillary dermis)
 Intense pruritus
 Predominantly on ventral surface of body

13. PAPULAR

14. MACULAR

15. NODULAR

16.  Secondary to systemic ds- petechiae,
ecchymosis and non healing ulcers.( amyloid
deposition in deeper skin layers and blood
vessels )
 Purpura –above nipple line.
 Bleeding in periorbital and intertriginous
areas
 Scleroderma amyloidosum Gottron-
scleroderma like changes by extensive
infiltration of dermis.

17.  Meretoja syndrome- massive cutis laxa,
extensive patechiae and haemorrhage,
hypotrichosis or alopecia seen in gelsolin
amyloidosis.
 TRAPS- prolong fever episodes, abdominal
pain, myalgias, migratory cutaneous
eryhtemas.

18. RACCOON EYES

22. INVESTIGATIONS
 • Histology
• Standard stainings: H&E, toluidin blue
and alkaline fuchsin
• Amyloid stainings: Congo red, thiofl avin
T, (crystal violet, methyl violet)
 • Immunohistochemistry

23.  • Electron microscopy
• From skin sample: for all kinds of
amyloidoses affecting the skin
• Abdominal fat or rectum biopsy: for all
suspected systemic amyloidoses and
nodular primary localized cutaneous

24. HISTOLOGY
 Papular macular- amyloid deposition
exclusively in papillary dermis.
 Epidermal acanthosis, hyperkeratosis
 Blood vessels remain unaffected
Nodular- diffuse infiltration of sub cutis and blood
vessels

25.  Staining properties-
 Congo red-green birefringence under polarized
light = DICHROMISM
 Methyl violet, cresyl violet- metachromatic
staining
 PAS staining
 Van geison`s stain- yellow brown color
 Pagoda red- more specific
 RIT scarlet No.5 – more specific

26. MACULAR/PAPULAR NODULAR

27. Thioflavin staining under fluoresence microscopy

28. IMMUNOHISTOCHEMISTRY
 For sub-classification of amyloid ppt.
Amyloid fibril precursor Amyloid fibril precursor
Papular, macular, SLCA Cytokeratin 5
Nodular, Immunoglobulin light chain.
Familial PLCA Apolipoprotein E4
Primary systemic Immunoglobulin light chain.
Secondary systemic
Muckle –wells syndrome
TRAPS
SAA( serum amyloid A )
Hemodialysis associated b 2 microglobulin
transthyretin amyloidosiis Transthyretin
Apo A1 amyloidosis Apolipoprotein A1
Cystatin amyloidosis Cystatin
Gelsolin A Gelsolin

29. ELECTRON MICROSCOPY
 Definitive confirmation

30. MANAGEMENT