Metabolic and depositional diseases | Figure 3.18 Lichen amyloidosis
(Courtesy of Dr. Paul Getz) |
- Refers to several diseases sharing common feature of abnormal deposition of eosinophilic amyloid protein in various tissues
- Amyloid properties: insoluble fibril protein aggregates with β-pleated sheet configuration
- Classified into systemic and organ-limited amyloidosis, with the former being associated with ↑ morbidity and mortality (unlike the cutaneous counterpart)
- Histology: deposits of eosinophilic, homogenous and amorphous material limited to papillary dermis with melanin incontinence in lichen/macular amyloidosis; waxy eosinophilic fissured nodules involving dermis in nodular amyloidosis; characteristic staining pattern showing green birefringence under polarized light with Congo red stain; other stains include methyl violet, crystal violet, PAS + (diastase resistant), Sirius red, pagoda red 9, scarlet red (RIT), and thioflavin T
| | | | | | | Table 3-11 Types of Cutaneous Amyloidosis | | | Type | | Description | | Protein | | | Macular amyloidosis | | Presents with hyperpigmented small firm papules in rippled appearance coalescing into thin plaques, typically over interscapular region; asymptomatic or moderately pruritic; ± associated notalgia paresthetica
Treatment: potent topical corticosteroid, topical capsaicin | | Keratinocyte-derived
{Seen in MEN type 2A} | | | Lichen amyloidosis | | Presents with small, flat-topped shiny papules typically over shins, highly pruritic
Treatment: reduce friction, potent topical corticosteroid ± occlusion or IL corticosteroid, phototherapy | | Keratinocyte-derived
{Seen in MEN type 2A} | | | Nodular amyloidosis | | Presents with single or multiple waxy nodules ± purpura on limbs or trunk
Can progress to systemic involvement in about 7% cases → long term follow up needed
Treatment : excision or laser ablation if few lesions | | AL (immunoglobulin light chains, typically λ) | | | Secondary amyloidosis | | Amyloid deposits seen both in benign and malignant cutaneous tumors | | Keratinocyte-derived | | | | | | | | | |
| | | | | | | | | Multiple endocrine neoplasia (MEN) type 2A (Sipple syndrome): RET gene, AD
Medullary thyroid carcinoma, pheochromocytoma, hyperparathyroidism, ± lichen or macular amyloidosis
Of note, MEN type 1 (Wermer syndrome) associated with facial angiofibromas, collagenomas and lipomas
Type 2B (aka type 3) associated with mucosal neuromas | | | | | | | | |
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| | | | | | | Table 3-12 Types of Systemic Amyloidosis | | | Type | | Description / Treatment | | Protein | | | Primary systemic
amyloidosis | | Usually associated with underlying plasma cell dyscrasia; up to 50% may have mucocutaneous lesions including macroglossia (± indentation of teeth), difficulty swallowing, ecchymosis and ‘pinch’ purpura due to vessel fragility from perivascular amyloid deposition (‘raccoon eyes’), waxy nodules and plaques, bullous lesions (especially hemorrhagic); hoarseness; other non-cutaneous involvement include carpal tunnel syndrome, RA-like arthropathy, shoulder pad sign (amyloid infiltration around periarticular soft tissue), cardiac arrhythmias, heart failure, restrictive cardiomyopathy; may be associated with multiple myeloma; confirmation of diagnosis in absence of cutaneous findings with aspiration of abdominal fat to detect amyloid deposits (fat pad aspiration) | | AL (light chain) | | | Secondary systemic
amyloidosis | | Amyloid deposition in organs due to underlying chronic inflammatory or infectious process (i.e. rheumatoid arthritis, tuberculosis, chronic abscess, periodic fever syndromes such as familial Mediterranean fever, TRAPS and Muckle-Wells syndrome – see below); skin typically not involved | | AA (non-immunoglobulin protein: amyloidassociated) | | | Hemodialysis-associated
amyloidosis | | Due to ↑ secretion of β2-microglobulin in patients with long-term hemodialysis; deposition in synovial membranes resulting in carpal tunnel syndrome and spondyloarthropathy | | Aβ2M
(β2-microglobulin) | | | Familial amyloidosis | | Includes familial amyloidotic polyneuropathy, AD inheritance; findings include peripheral and autonomic neuropathy; treatment: orthotopic liver transplantation (remove major source of TTR)
{TTR transports thyroxine and retinol} | | ATTR
(TTR or transthyretin) | | | Senile systemic
amyloidosis | | Late-onset disease seen in elderly patients due to deposition of TTR-derived amyloid fibrils in heart causing CHF, cardiomyopathy | | ATTR
(transthyretin or TTR) | | | | | | | | | |
| | | | | | | | | Muckle-Wells syndrome (MWS): CIAS1 mutation (encodes cryopyrin), AD → urticaria, deafness, renal amyloidosis, acute attacks of fever, abdominal pain, myalgias, arthralgias, and conjunctivitis; treat w/ glucocorticoids or anakinra (recombinant human IL-1 receptor antagonist)
Familial Mediterranean fever (FMF): MEFV mutation (encodes pyrin, also known as marenostrin), AR → recurrent episodes of polyserositis, fever, erysipelas-like erythema (legs); treat w/ colchicine (prophylaxis)
TNF receptor associated periodic syndrome (TRAPS): TNFR1 mutation, AD → high fever, erythematous annular or serpiginous patches/plaques on extremities, abdominal pain, arthralgias/myalgias; treat w/ TNF inhibitors or glucocorticoids | | | | | | | | |
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