Cutaneous amyloidosis

made as a part of residency programme in dermatology. includes latest classification.includes staining characteristics. good for revision. made from contents from Rooks and Bolognia

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 Localised cutaneous amyloidosis 1) Non hereditary Macular- 35% Papular-35% Nodular-15% SLCA( secondary localized cutaneous amyloidosis ) 2) Hereditary Familial PLCA

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

7. Hereditary – Transthyretin/ familial amyloid polyneuropathy Apo A1 amyloidosis Cystatin C amyloidosis Hereditary gelsolin amyloidosis

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

9. Clinical variants Biphasic,allotropic Poikilodermatous PLCA Amyloidosis cutis dyschromica Bullous amyloidosis

10. Pathophysiology (primary) Friction

11. Pathophysiology(secondary)

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

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

20. • 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

21. 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

22. 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

23. macular/papular nodular

24. Thioflavin staining under fluoresence microscopy

25. 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

26. Electron microscopy Definitive confirmation

27. management