125: Amyloidosis Flashcards
What characterizes amyloidosis in terms of its material composition?
Amyloidosis is characterized by the presence of mostly extracellular homogenous hyaline material that is typically metachromatic.
Color changes of dyes such as Congo red (orange in solution), Crystal Violet (deep red-purple color on a blue background), and Sodium sulfate Alcian blue (green color) are observed.
How can amyloid deposits be identified in tissue sections?
Amyloid deposits can be identified by yielding apple-green birefringence when stained with Congo red and viewed under polarizing microscopy, and by exhibiting typical yellow-green fluorescence after staining with thioflavin T.
What are the main constituents of amyloid deposits?
The main constituents of amyloid deposits are fibrils that are 10 to 15 nm in diameter, serum amyloid P-component (SAP), and several apolipoproteins, notably apoE, apoJ, and apoA4.
What are some amyloid diseases relevant to dermatology?
Some amyloid diseases relevant to dermatology include high-density lipoprotein-associated serum amyloid A (apoSAA) and B2-microglobulin (AB2m).
What staining method yields apple-green birefringence in amyloidosis diagnosis?
Staining with Congo red followed by polarizing microscopy.
What is the role of serum amyloid P-component (SAP) in amyloid deposits?
It is a second feature present in all amyloid deposits.
Which apolipoproteins are notably included in amyloid diseases relevant to dermatology?
ApoE, apoJ, and apoA4.
What is the significance of high-density lipoprotein-associated serum amyloid A (apoSAA)?
It is an acute-phase reactant that forms amyloid in secondary (AA) amyloidosis.
What color changes are observed with Congo red dye in amyloidosis?
Congo red appears orange in solution and yields apple-green birefringence.
What is the typical fluorescence observed after staining with thioflavin T in amyloidosis?
Typical yellow-green fluorescence.
What are the diagnostic stains used for amyloidosis, and what are their characteristic appearances?
Diagnostic stains include Congo red (apple-green birefringence under polarized light), Crystal Violet (deep red-purple on a blue background), and thioflavin T (yellow-green fluorescence).
What cellular factors contribute to protein misfolding in amyloidosis?
Cellular factors include membrane interactions, altered cell chemistry, posttranslational modifications, crowding, pathogenic mutations, acidification, temperature, protein concentration, and oxidative stress.
What are the systemic forms of amyloidosis most commonly seen in patients?
The most common systemic forms of amyloidosis are AL (light chain amyloidosis), AA (secondary amyloidosis), and ATTR (transthyretin amyloidosis).
What is the significance of elevated levels of SAA in AL amyloidosis?
Elevated levels of Serum Amyloid A (SAA) are triggered by proinflammatory cytokines, notably interleukin (IL)-6, and are associated with the production of monoclonal immunoglobulin light chains by aberrant plasma cell populations.
How does the ‘sink’ effect relate to ATTR amyloidosis?
In ATTR amyloidosis, the ‘sink’ effect refers to the conversion of circulating wild-type (WT) or mutant transthyretin (TTR) resulting in relatively low levels of precursor protein, as the precursor may deposit onto existing amyloid.
What organ systems are commonly involved in AL amyloidosis?
Organ system involvement in AL amyloidosis is clinically diverse, with significant impacts on the cardiac system, renal system, and neurologic system.
What is the prognosis for patients with AL amyloidosis and cardiac involvement?
Patients with AL amyloidosis and cardiac involvement have a 1-year mortality rate of approximately 45% and a median survival time of 6 to 14 months.
What skin manifestations are associated with systemic amyloidosis?
Skin manifestations can include occult or overt cutaneous involvement, pinch and periorbital purpura, macroglossia, lingual nodules, and fissured masses in the dermis.
How does AA amyloidosis typically present in patients?
In AA amyloidosis, most patients present with glomerular disease, which manifests as proteinuria/nephrotic syndrome.
What are the common clinical presentations of ATTR amyloidosis?
ATTR amyloidosis may present as overlapping syndromes including neuropathy, cardiomyopathy, gastrointestinal issues, vitreous involvement, and occasional leptomeningeal amyloidosis.
What are the less-common forms of systemic amyloidosis associated with nephropathic amyloidosis?
They include several heredofamilial syndromes associated with apoA2, apoCII, apoCIII, fibrinogen, lysozyme, and others.
What are the dermatologic signs of systemic amyloidosis, and which are unique to AL amyloidosis?
Signs include pinch purpura, macroglossia, and lingual nodules. Macroglossia and lingual nodules are unique to AL amyloidosis.
What types of proteins may adopt configurations leading to amyloid fibril formation?
Precursor proteins that form amorphous aggregates, oligomers, and other intermediates.
What is a common neurological presentation of WT and mutant ATTR amyloidosis?
They may present as carpal tunnel syndrome with amyloid retrievable from the flexor retinaculum.
What is the relationship between neuropathy and cardiomyopathy in mutant ATTR amyloidosis?
Approximately 50% of patients with mutant ATTR have cardiomyopathy, which may dominate the clinical presentation.
What are the symptoms associated with localized amyloidosis in specific organ systems?
Symptoms reflect the specific organ system, including hoarseness in laryngeal amyloid and gross hematuria in genitourinary amyloid.
What percentage of localized forms of amyloid account for localized amyloidosis, excluding CNS amyloid associated with neurodegenerative diseases?
Localized forms of amyloid account for approximately 10% of localized amyloidosis.
What vascular manifestations may occur in cutaneous amyloidosis?
Vascular involvement may present as congophilic angiopathy, petechiae, purpura, or ecchymoses.
What are the three major types of primary cutaneous amyloidosis?
The three major types are Macular Amyloidosis (~35%), Papular/Lichen Amyloidosis (~35%), and Mixed/Biphasic Amyloidosis (~15%).
What is the typical presentation of macular amyloidosis?
Macular amyloidosis typically presents as a pigmented patch of varying size, commonly in the interscapular region, characterized by a rippled salt-and-pepper appearance.
What is the most common type of cutaneous amyloidosis and its typical demographic?
The most common type is Lichen Amyloidosis, usually presenting later in life, predominantly in the fifth and sixth decades, more common in men.
What are the initial symptoms of lichen amyloidosis?
The initial symptoms include pruritus and the appearance of papules.
What is the appearance of macular amyloidosis?
Characterized by a rippled salt-and-pepper appearance with alternating hyperpigmentation and hypopigmentation.
What is the most common type of cutaneous amyloidosis and its typical demographic?
The most common type of cutaneous amyloidosis is Lichen Amyloidosis. It usually presents later in life, predominantly in the fifth and sixth decades, and is more common in men and patients with a higher Fitzpatrick skin type.
What are the initial symptoms of lichen amyloidosis?
The initial symptom of lichen amyloidosis is intense pruritus (itching) that may improve with sun exposure and worsen during periods of stress.
What does biphasic cutaneous amyloidosis refer to?
Biphasic cutaneous amyloidosis refers to the concurrent presence of macular amyloidosis and lichen amyloidosis. It may also exist in combination with blisters and poikilodermic skin lesions.
What are the three major types of primary cutaneous amyloidosis?
Macular (~35%), papular/lichen (~35%), and mixed/biphasic (~15%).
Where does macular amyloidosis commonly present on the body?
In the interscapular region as a pigmented patch.
In which demographic is macular amyloidosis more common?
It is more common in women and patients with a darker complexion.
What is the initial symptom of lichen amyloidosis?
Intense pruritus that may improve with sun exposure and worsen during periods of stress.
What is biphasic cutaneous amyloidosis?
The concurrent presence of macular amyloidosis and lichen amyloidosis.
What can biphasic cutaneous amyloidosis exist in combination with?
Blisters and poikilodermic skin lesions.
What is the likely diagnosis for a pigmented patch on the interscapular region with a rippled appearance?
The likely diagnosis is macular amyloidosis. Common sites of occurrence include the interscapular region, extensor surfaces of the arms, thighs, and shins.
What is the diagnosis for a 55-year-old man with linear rows of firm pigmented hyperkeratotic papules on his shins?
The diagnosis is lichen amyloidosis. The initial symptom is intense pruritus, which may improve with sun exposure and worsen during stress.
Describe the pathology and clinical presentation of biphasic cutaneous amyloidosis.
Biphasic cutaneous amyloidosis refers to the concurrent presence of macular amyloidosis and lichen amyloidosis. It may also present with blisters and poikilodermic skin lesions.
What is the presumed cause of hyperpigmented lesions in a patient with lichen amyloidosis?
The hyperpigmentation is presumed to be secondary to scratching.
What are the clinical features of macular amyloidosis?
Features include pigmented patches with a rippled appearance, most common in women with darker complexions.
What are the clinical features of lichen amyloidosis?
Features include hyperkeratotic papules on the shins and forearms, most common in men in their fifth and sixth decades.
What are the clinical features of biphasic cutaneous amyloidosis?
It presents with macular and lichen amyloidosis concurrently, sometimes with blisters and poikilodermic lesions.
What are the target organs affected by AL amyloidosis?
All except CNS.
What are the common clinical features of macular amyloidosis?
- Epidemiology: ~35% of cutaneous amyloidosis cases; more common in women of darker complexion.
- Commonly Affected Sites: Interscapular region, extensor surfaces of arms, thighs, and shins.
- Clinical Appearance: ‘Salt-and-pepper’ appearance with alternating hyper- and hypopigmentation.
- Pathologic Features: Mild epidermal hyperkeratosis; collections of amyloid ‘corpuscles’ within papillary dermis; melanin-containing histiocytes encircle the deposits.
What distinguishes lichen amyloidosis from macular amyloidosis in terms of clinical appearance?
- Lichen Amyloidosis:
- Commonly Affected Sites: Shins and forearms, occasionally upper back.
- Clinical Appearance: Linear rows of firm, pigmented, grouped, hyper-keratotic papules that can evolve into plaques.
- Macular Amyloidosis:
- Clinical Appearance: ‘Salt-and-pepper’ appearance with alternating hyper- and hypopigmentation.
What are the characteristics of biphasic cutaneous amyloidosis?
- Epidemiology: ~15% of cases.
- Clinical Features: Characteristics of both macular and lichen amyloidosis.
- Pathologic Features: Overlapping clinical features.
What is the common clinical appearance of macular amyloidosis?
Salt-and-pepper appearance with alternating hyper- and hypopigmentation.
Which type of amyloidosis is most common and affects the interscapular region?
Macular amyloidosis.
What is a characteristic feature of lichen amyloidosis?
Linear rows of firm, pigmented, grouped, hyper-keratotic papules.
What is the prevalence of biphasic cutaneous amyloidosis?
~15% of cases.
What is the pathologic feature of macular amyloidosis?
Mild epidermal hyperkeratosis and collections of amyloid ‘corpuscles’ within papillary dermis.
