125: Amyloidosis Flashcards
(145 cards)
1
Q
What characterizes amyloidosis in terms of its material composition?
A
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.
2
Q
How can amyloid deposits be identified in tissue sections?
A
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.
3
Q
What are the main constituents of amyloid deposits?
A
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.
4
Q
What are some amyloid diseases relevant to dermatology?
A
Some amyloid diseases relevant to dermatology include high-density lipoprotein-associated serum amyloid A (apoSAA) and B2-microglobulin (AB2m).
5
Q
What staining method yields apple-green birefringence in amyloidosis diagnosis?
A
Staining with Congo red followed by polarizing microscopy.
6
Q
What is the role of serum amyloid P-component (SAP) in amyloid deposits?
A
It is a second feature present in all amyloid deposits.
7
Q
Which apolipoproteins are notably included in amyloid diseases relevant to dermatology?
A
ApoE, apoJ, and apoA4.
8
Q
What is the significance of high-density lipoprotein-associated serum amyloid A (apoSAA)?
A
It is an acute-phase reactant that forms amyloid in secondary (AA) amyloidosis.
9
Q
What color changes are observed with Congo red dye in amyloidosis?
A
Congo red appears orange in solution and yields apple-green birefringence.
10
Q
What is the typical fluorescence observed after staining with thioflavin T in amyloidosis?
A
Typical yellow-green fluorescence.
11
Q
What are the diagnostic stains used for amyloidosis, and what are their characteristic appearances?
A
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).
12
Q
What cellular factors contribute to protein misfolding in amyloidosis?
A
Cellular factors include membrane interactions, altered cell chemistry, posttranslational modifications, crowding, pathogenic mutations, acidification, temperature, protein concentration, and oxidative stress.
13
Q
What are the systemic forms of amyloidosis most commonly seen in patients?
A
The most common systemic forms of amyloidosis are AL (light chain amyloidosis), AA (secondary amyloidosis), and ATTR (transthyretin amyloidosis).
14
Q
What is the significance of elevated levels of SAA in AL amyloidosis?
A
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.
15
Q
How does the ‘sink’ effect relate to ATTR amyloidosis?
A
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.
16
Q
What organ systems are commonly involved in AL amyloidosis?
A
Organ system involvement in AL amyloidosis is clinically diverse, with significant impacts on the cardiac system, renal system, and neurologic system.
17
Q
What is the prognosis for patients with AL amyloidosis and cardiac involvement?
A
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.
18
Q
What skin manifestations are associated with systemic amyloidosis?
A
Skin manifestations can include occult or overt cutaneous involvement, pinch and periorbital purpura, macroglossia, lingual nodules, and fissured masses in the dermis.
19
Q
How does AA amyloidosis typically present in patients?
A
In AA amyloidosis, most patients present with glomerular disease, which manifests as proteinuria/nephrotic syndrome.
20
Q
What are the common clinical presentations of ATTR amyloidosis?
A
ATTR amyloidosis may present as overlapping syndromes including neuropathy, cardiomyopathy, gastrointestinal issues, vitreous involvement, and occasional leptomeningeal amyloidosis.
21
Q
What are the less-common forms of systemic amyloidosis associated with nephropathic amyloidosis?
A
They include several heredofamilial syndromes associated with apoA2, apoCII, apoCIII, fibrinogen, lysozyme, and others.
22
Q
What are the dermatologic signs of systemic amyloidosis, and which are unique to AL amyloidosis?
A
Signs include pinch purpura, macroglossia, and lingual nodules. Macroglossia and lingual nodules are unique to AL amyloidosis.
23
Q
What types of proteins may adopt configurations leading to amyloid fibril formation?
A
Precursor proteins that form amorphous aggregates, oligomers, and other intermediates.
24
Q
What is a common neurological presentation of WT and mutant ATTR amyloidosis?
A
They may present as carpal tunnel syndrome with amyloid retrievable from the flexor retinaculum.
25
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.
26
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.
27
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.
28
What vascular manifestations may occur in cutaneous amyloidosis?
Vascular involvement may present as congophilic angiopathy, petechiae, purpura, or ecchymoses.
29
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%).
30
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.
31
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.
32
What are the initial symptoms of lichen amyloidosis?
The initial symptoms include pruritus and the appearance of papules.
33
What is the appearance of macular amyloidosis?
Characterized by a rippled salt-and-pepper appearance with alternating hyperpigmentation and hypopigmentation.
34
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.
35
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.
36
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.
37
What are the three major types of primary cutaneous amyloidosis?
Macular (~35%), papular/lichen (~35%), and mixed/biphasic (~15%).
38
Where does macular amyloidosis commonly present on the body?
In the interscapular region as a pigmented patch.
39
In which demographic is macular amyloidosis more common?
It is more common in women and patients with a darker complexion.
40
What is the initial symptom of lichen amyloidosis?
Intense pruritus that may improve with sun exposure and worsen during periods of stress.
41
What is biphasic cutaneous amyloidosis?
The concurrent presence of macular amyloidosis and lichen amyloidosis.
42
What can biphasic cutaneous amyloidosis exist in combination with?
Blisters and poikilodermic skin lesions.
43
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.
44
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.
45
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.
46
What is the presumed cause of hyperpigmented lesions in a patient with lichen amyloidosis?
The hyperpigmentation is presumed to be secondary to scratching.
47
What are the clinical features of macular amyloidosis?
Features include pigmented patches with a rippled appearance, most common in women with darker complexions.
48
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.
49
What are the clinical features of biphasic cutaneous amyloidosis?
It presents with macular and lichen amyloidosis concurrently, sometimes with blisters and poikilodermic lesions.
50
What are the target organs affected by AL amyloidosis?
All except CNS.
51
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.
52
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.
53
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.
54
What is the common clinical appearance of macular amyloidosis?
Salt-and-pepper appearance with alternating hyper- and hypopigmentation.
55
Which type of amyloidosis is most common and affects the interscapular region?
Macular amyloidosis.
56
What is a characteristic feature of lichen amyloidosis?
Linear rows of firm, pigmented, grouped, hyper-keratotic papules.
57
What is the prevalence of biphasic cutaneous amyloidosis?
~15% of cases.
58
What is the pathologic feature of macular amyloidosis?
Mild epidermal hyperkeratosis and collections of amyloid 'corpuscles' within papillary dermis.
59
What are the common affected sites for lichen amyloidosis?
Shins and forearms, occasionally upper back.
60
What is the clinical manifestation of AA amyloidosis?
Fat pad aspiration/biopsy.
61
What is the target organ for transthyretin (ATTR) amyloidosis?
Nervous system; heart; vitreous.
62
What is towel-associated amyloidosis and what causes it?
Towel-associated amyloidosis is induced by prolonged contact with nylon towels.
63
What characterizes anosacral amyloidosis and its common associations?
Anosacral amyloidosis is characterized by brownish patches of plaques in the anosacral region, often associated with lichenification and pruritus, with amyloid deposits found in the papillary dermis.
64
What is notalgia paresthetica amyloidosis and its potential cause?
Notalgia paresthetica amyloidosis is an isolated sensory neuropathy that typically occurs on the back and may be associated with amyloid, likely resulting from prolonged pruritus and scratching.
65
What is the significance of friction melanosis or amyloidosis?
Friction melanosis or amyloidosis is associated with prolonged contact with sponges, towels, plant sticks, and leaves, likely representing variants of macular or lichen amyloidosis.
66
What are the characteristics of nodular amyloidosis?
Nodular amyloidosis presents with one or more deep-seated lesions that have a waxy or nodular appearance, can appear as papules, nodules, or plaques, and commonly occurs on the feet and trunk.
67
What is the relationship between nodular amyloidosis and primary Sjögren syndrome?
Up to 25% of nodular amyloidosis cases may be associated with primary Sjögren syndrome.
68
What is the prevalence of amyloid deposits in basal cell carcinomas?
Between 66% and 77% of basal cell carcinomas, particularly the nodular type, have been reported to have amyloid deposits within the tumor stroma.
69
What types of tumors are commonly associated with amyloid deposits?
Amyloid deposits are commonly found adjacent to keratocytic tumors such as basal cell carcinoma, Bowen disease, squamous cell carcinoma, and benign lesions like seborrheic or actinic keratoses.
70
What is the occurrence of amyloid adjacent to tumors?
It is common to find collections of amyloid adjacent to keratocytic tumors such as basal cell carcinoma and squamous cell carcinoma.
71
What percentage of basal cell carcinomas have been reported to have amyloid deposits?
Between 66% and 77% of basal cell carcinomas, particularly the nodular type, have been reported to have amyloid deposits within the tumor stroma.
72
What is the diagnosis for a patient with anosacral brownish patches and plaques associated with pruritus?
The diagnosis is anosacral amyloidosis, most common in Chinese and Japanese populations.
73
Describe the clinical presentation and pathology of nodular amyloidosis.
Nodular amyloidosis presents as waxy or nodular lesions, often on the feet and trunk. Pathology shows AL amyloid deposits, with vascular involvement common.
74
What are the common sites and clinical features of lichen amyloidosis of the auricular concha?
It presents as hyperpigmentation of the bowl of the ear, likely a variant of lichen amyloidosis.
75
What are the histological findings in amyloid deposits adjacent to keratocytic tumors?
Amyloid deposits are found within the tumor stroma, particularly in basal cell carcinomas.
76
What are the clinical features of towel-associated amyloidosis?
It presents as amyloid deposits in the papillary dermis, induced by prolonged contact with nylon towels.
77
What are the clinical features of friction melanosis or amyloidosis?
It presents as pigmentation changes due to prolonged contact with sponges or towels, likely a variant of macular or lichen amyloidosis.
78
What are the clinical features of notalgia paresthetica amyloidosis?
It presents as isolated sensory neuropathy on the back, likely caused by prolonged pruritus and scratching.
79
What are the clinical features of anosacral amyloidosis?
Features include brownish patches and plaques in the anosacral region. Histology shows amyloid deposits in the papillary dermis.
80
What are the clinical features of nodular amyloidosis?
Features include waxy nodules on the feet and trunk. Follow-up is recommended for plasma cell dyscrasia or lymphoproliferative disease.
81
What is Cutis Laxa and how is it related to familial amyloid caused by mutant gelsolin?
Cutis Laxa, originally described as Meretoja syndrome, is characterized by a worldwide distribution and manifests as lattice corneal dystrophy, Type 4, cranial and peripheral neuropathies, and prominent renal involvement.
82
What are the common manifestations of Cutis Laxa in familial amyloid?
It manifests as lattice corneal dystrophy, Type 4, cranial and peripheral neuropathies, and prominent renal involvement.
83
What are the consequences of skin atrophy in Cutis Laxa?
Consequences may include xerosis, easy bruising, loss of body and scalp hair, and occasional lichen amyloidosis.
84
Where does gelsolin amyloid tend to deposit in the skin?
Gelsolin amyloid tends to deposit adjacent to basement structures, including the subdermis, eccrine sweat glands, dermal blood vessels, and between collagen and elastic fibers.
85
What is Transthyretin Amyloidosis and where can amyloid be found?
Transthyretin Amyloidosis is characterized by amyloid found in the walls of small blood vessels, freely in the dermis, and diffusely in adipose tissue between adipocytes.
86
What is Injection-Site Amyloidosis and its association with enfuvirtide?
Injection-Site Amyloidosis refers to localized forms of amyloid that result from therapeutics with amyloidogenic propensity, such as insulin pumps and enfuvirtide (Fuzeon).
87
What is Amyloidosis Cutis Dyschromica and its clinical features?
Amyloidosis cutis dyschromica is a rare condition where patients develop progressive diffuse hyperpigmentation, hypopigmentation, and atrophy.
88
What are Injection-Site Amyloidoses and their association with insulin?
Injection-Site Amyloidoses are localized forms of amyloid resulting from therapeutics with amyloidogenic propensity, found in association with insulin pumps and enfuvirtide.
89
What is Amyloidosis Cutis Dyschromica?
Amyloidosis Cutis Dyschromica is a rare condition where patients develop progressive diffuse hyperpigmentation, hypopigmentation, and atrophy.
90
What is the pathogenesis of Amyloidosis Cutis Dyschromica?
The pathogenesis is unknown, although photosensitivity has been implicated.
91
How is amyloid characterized in patients with Amyloidosis Cutis Dyschromica?
Amyloid is usually localized within the papillary dermis and stains with antikeratin antibodies.
92
What are the clinical features of cutis laxa in familial amyloidosis caused by mutant gelsolin?
Features include premature aging, xerosis, easy bruising, loss of hair, and occasional lichen amyloidosis.
93
What are the clinical and histological features of amyloidosis cutis dyschromica?
Clinically, it presents as progressive diffuse hyperpigmentation and hypopigmentation with atrophy. Histologically, amyloid is localized in the papillary dermis.
94
What are the clinical features of transthyretin amyloidosis in the skin?
Features include amyloid in small blood vessel walls, fissured collections in the dermis, and diffuse deposits in adipose tissue.
95
What are the clinical features of injection-site amyloidosis, and which therapeutic agents are implicated?
Features include red-yellow subcutaneous nodules. Implicated agents include insulin and enfuvirtide.
96
What are the clinical features of familial amyloidosis caused by mutant gelsolin, and where does the amyloid deposit?
Features include cutis laxa, cranial neuropathies, and renal involvement. Amyloid deposits adjacent to basement structures and dermal blood vessels.
97
What are the clinical features of amyloidosis cutis dyschromica, and what is its pathogenesis?
Features include diffuse hyperpigmentation and hypopigmentation with atrophy. Pathogenesis is unknown but may involve photosensitivity.
98
What is the significance of female predominance in cutaneous amyloidoses?
Female predominance in cutaneous amyloidoses is significant as it suggests a potential genetic or hormonal influence on the disease. Familial cases account for up to 10% of overall cases, indicating a hereditary component that may involve specific gene defects such as mutations in the oncostatin M receptor (OSMR), interleukin-31 receptor A (IL31RA), and the RET protooncogene.
99
What are the associated conditions with cutaneous lichen amyloidosis?
Cutaneous lichen amyloidosis is primarily associated with multiple endocrine neoplasia 2A syndrome, which is linked to medullary thyroid cancer (MTC) in approximately 95% of cases. It is also less commonly associated with pheochromocytoma (30% to 50%) and primary hyperparathyroidism (20% to 30%).
100
What receptors have been identified in skin related to pruritus in cutaneous amyloidosis?
Recent studies have identified several receptors in the skin related to pruritus, including: Mas-related G-protein–coupled receptors and Transient receptor potential vanilloid Type 1.
101
What is the role of IL-31 in cutaneous amyloidosis?
IL-31 has been implicated in pruritus associated with various skin conditions, including atopic dermatitis, prurigo nodularis, and cutaneous T-cell lymphoma (Sézary syndrome). It is associated with increased epidermal expression of IL-31 receptors and elevated tissue/serum IL-31 levels in lesional skin.
102
What initial evaluations should be included in the diagnosis of cutaneous amyloidosis?
The initial evaluation for diagnosing cutaneous amyloidosis should include: Cataloging comorbid medical conditions (e.g., carpal tunnel syndrome, neuropathy), Inquiry about easy bruising, petechial rash, or ecchymoses, Examination for localized areas of pruritus on the upper back or shins, Search for multiple lesions, pinch or periorbital purpura, Evaluation for macroglossia or lateral ridging of the tongue.
103
What is the estimated percentage of familial cases in cutaneous amyloidoses?
Up to 10%.
104
Which gene defects are associated with cutaneous amyloidoses?
Mutations in the oncostatin M receptor (OSMR), interleukin-31 receptor A (IL31RA), and the RET protooncogene.
105
What variant of multiple endocrine neoplasia 2A syndrome is associated with cutaneous lichen amyloidosis?
It is primarily associated with medullary thyroid cancer (MTC).
106
What role does IL-31 play in cutaneous amyloidosis?
It has been implicated in pruritus associated with atopic dermatitis, prurigo nodularis, and cutaneous T-cell lymphoma.
107
What laboratory tests are included for both systemic and localized AL amyloidosis?
For both systemic and localized AL amyloidosis, laboratory tests include: Measurement of quantitative immunoglobulins (IgG, IgA, IgM isotypes), Serum and urine immunofixation, Measurement of serum κ and λ free light chains to identify clonal populations of immunoglobulin light chains in more than 95% of patients with systemic AL disease.
108
What laboratory findings are indicative of AA amyloidosis?
For AA amyloidosis, an elevated erythrocyte sedimentation rate and specific acute-phase reactants such as C-reactive protein and fibrinogen serve as surrogates for elevated levels of SAA protein.
109
What tests are recommended for suspected ATTR amyloidosis?
For suspected ATTR amyloidosis, an assay for serum TTR levels and TTR gene-sequence analysis may help identify specific mutations. It is noted that up to 25% of patients may also have monoclonal immunoglobulins as an incidental finding.
110
What should macular or papular lesions be examined for in relation to amyloidosis?
A waxy appearance suggestive of amyloidosis.
111
What does an elevated erythrocyte sedimentation rate indicate in the context of AA amyloidosis?
It serves as a surrogate for elevated levels of SAA protein.
112
What is the significance of measuring serum TTR levels in suspected ATTR amyloidosis?
It may help identify specific mutations related to the condition.
113
What percentage of patients with suspected ATTR may also have incidental findings of monoclonal immunoglobulins?
Up to 25%.
114
What are the laboratory tests for diagnosing systemic AL amyloidosis, and what do they detect?
Tests include serum and urine immunofixation and free light chain measurement, detecting clonal immunoglobulin light chains.
115
What is the significance of Congo red binding in the diagnosis of cutaneous amyloid?
Congo red binding to several forms of cutaneous amyloid may be weak and inferior to the use of thioflavin T or Pagoda red as diagnostic reagents. A modified Congo Red immunohistochemical overlay has been suggested to improve diagnosis.
116
What role do cytokeratins play in the pathology of cutaneous amyloidoses?
Cytokeratin (CK)-5 is identified as a major constituent of amyloid deposits in organ-limited cutaneous amyloidoses, suggesting a role of keratinocyte apoptosis in pathogenesis. Other cytokeratins show varying degrees of positivity in lichen amyloidosis and cutaneous amyloidosis associated with tumors and keratoses.
117
How can aspiration and biopsy be utilized in the evaluation of amyloid?
Aspiration can be used to screen for Congo red-positive material among fat globules, while biopsy can assess the morphology of amyloid in subcutaneous fat, aiding in immunohistochemistry and the isolation and sequencing of amyloid proteins by mass spectroscopy.
118
What treatment strategies are effective for systemic amyloidoses?
Effective treatment strategies for systemic amyloidoses include: Lowering precursor protein levels correlates with clinical improvement and regression of amyloid, Use of anti-IL-6 for AA amyloidosis, High-dose dexamethasone, melphalan, thalidomide analogs, proteasome inhibitors, and anti-CD38 monoclonal antibodies for AL amyloid, Ongoing trials with silencing RNAs and antisense oligonucleotides to reduce mutant and wildtype TTR levels in blood.
119
What has been developed to improve the selectivity and sensitivity of Congo red immunohistochemical diagnosis?
A modified Congo Red immunohistochemical overlay and a luminescent conjugated oligothiophene, h-FTAA.
120
What is the significance of cytokeratin (CK)-5 in cutaneous amyloidoses?
CK-5 is a major constituent of amyloid deposits and suggests a role of keratinocyte apoptosis in pathogenesis.
121
What is the efficacy of using anti-IL-6 in treating AA amyloidosis?
It has proven effective in reducing Ig light chain production by aberrant plasmablasts in AL amyloid.
122
What is the outcome of using chemotherapies adapted from evolving myeloma protocols for systemic amyloidoses?
It correlates with clinical improvement and even regression of amyloid for SAA and AL.
123
What techniques are used to diagnose AL and AA amyloidosis?
Mass spectroscopy can isolate and sequence amyloid proteins, establishing diagnosis in 80% to 90% of cases for AL and 75% to 80% for AA.
124
What ongoing trials are assessing in relation to TTR levels?
They are assessing the efficacy of silencing RNAs and antisense oligonucleotides to knock down mutant and wildtype TTR levels in blood.
125
Describe the role of cytokeratins in the pathology of lichen amyloidosis.
Cytokeratins, particularly CK-5, are major constituents of amyloid deposits in lichen amyloidosis, suggesting a role of keratinocyte apoptosis in pathogenesis.
126
What are the biochemical techniques used to diagnose systemic AL amyloidosis, and what is their diagnostic yield?
Techniques include biopsy for immunohistochemistry and mass spectroscopy. The diagnostic yield is 80-90% for AL amyloidosis.
127
A patient with systemic amyloidosis is treated with anti-IL-6 therapy. What type of amyloidosis is being treated, and what is the rationale for this therapy?
The patient likely has AA amyloidosis. Anti-IL-6 therapy reduces proinflammatory cytokines, lowering SAA levels and amyloid deposition.
128
A patient with ATTR amyloidosis has cardiomyopathy. What are the ongoing therapeutic trials targeting this condition?
Trials involve silencing RNAs and antisense oligonucleotides to reduce mutant and wild-type TTR levels.
129
What are the diagnostic challenges in using Congo red for cutaneous amyloidosis, and what alternatives are suggested?
Congo red binding may be weak. Alternatives include thioflavin T, Pagoda red, and h-FTAA for improved sensitivity.
130
What are some agents that may act as fibril disrupters in the treatment of amyloidosis?
Agents that may be active as fibril disrupters include: Doxycycline (ATTR, AL, Aβ2m): Disrupts fibril formation and mature fibrils, inhibits matrix metalloproteinase (MMP)-9, Epigallocatechin-3-gallate (green tea) (ATTR, Aβ-Alzheimer disease): Disrupts mature fibrils and suppresses oxidative stress markers, Curcumin (ATTR; Aβ): Induces oligomerization to a nontoxic 'off pathway.'
131
What is the significance of dimethylsulfoxide (DMSO) in the treatment of cutaneous amyloidoses?
DMSO was used in early studies for its potential to disaggregate AL fibrils and its possible anti-inflammatory effects. However, its general applicability was limited due to its acrid smell and difficulty in obtaining contaminant-free preparations.
132
How is treatment determined for cutaneous nodules in the absence of systemic AL?
In the absence of systemic AL, treatment is determined by: Size of the cutaneous nodules, Location of the nodules (e.g., foot or temple), Multiplicity of the nodules. Effective treatments include curettage, excision, and intralesional methotrexate or ablative laser therapy.
133
What are common treatments for localized cutaneous amyloidoses?
Common treatments for localized cutaneous amyloidoses include: Topical and intralesional steroids, Topical calcineurin inhibitors, Low-dose oral cyclophosphamide, Dermabrasion, Cyclosporine, Carbon dioxide resurfacing surgical laser, Yttrium-aluminum-garnet laser, Narrowband ultraviolet B light therapy, Combination of psoralen and ultraviolet A with acitretin.
134
Why are antihistamines ineffective for treating pruritus in cutaneous amyloidoses?
Antihistamines are ineffective for treating pruritus in cutaneous amyloidoses likely due to the lack of generation of histamine or involvement of histamine receptors in this disorder.
135
What role does topical capsaicin play in the treatment of cutaneous amyloidoses?
Topical capsaicin 0.025% is used in the treatment of cutaneous amyloidoses as it releases neuropeptides from C-fibers, preventing their deposition and potentially alleviating symptoms.
136
Why are antihistamines ineffective for treating pruritus in cutaneous amyloidoses?
Due to the lack of generation of histamine or involvement of histamine receptors.
137
What agents are being tested as fibril disrupters for amyloidosis?
Doxycycline, epigallocatechin-3-gallate, and curcumin.
138
What was the purpose of using dimethylsulfoxide (DMSO) in early studies for cutaneous amyloidoses?
To disaggregate AL fibrils and provide anti-inflammatory effects.
139
What is a major concern regarding nodular amyloid?
The potential for progression to systemic AL.
140
How is treatment determined for cutaneous nodules in the absence of systemic AL?
By the size, location, and multiplicity of the nodules.
141
What are common treatments for localized cutaneous amyloidoses?
Topical steroids, calcineurin inhibitors, and low-dose oral cyclophosphamide.
142
What topical treatment can help with pruritus in cutaneous amyloidoses?
Topical capsaicin 0.025%.
143
What surgical methods can be used to treat cutaneous amyloidoses?
Curettage, excision, and intralesional methotrexate or ablative laser therapy.
144
What are the systemic treatments for nodular amyloidosis, and when are they indicated?
Systemic treatments include DMARDs like hydroxychloroquine or methotrexate, indicated when there is potential progression to systemic AL amyloidosis.
145
What are the therapeutic agents under clinical testing for fibril disruption in amyloidosis, and what are their mechanisms?
Agents include doxycycline (disrupts fibril formation), epigallocatechin-3-gallate (suppresses oxidative stress), and curcumin (induces nontoxic oligomerization).
