Amyloid Sarcoid Flashcards
(48 cards)
Amyloid finding under light microscope & stain
Congo red stain → apple green birefringence
** Mech of amyloid deposition**
– High [ ] normal protein (eg serum amyloid A in chronic inflamm, and B2microglobulin in dialysis related amyloid)
– Prolonged exposure to normal [ ] of weakly amyloidogenic protein (eg amyloid B protein)
– Acquired prot w/ amyloidogenic structure (monoclonal IgG light chains in AL amyloid eg MM, Waldenstrom, NHL)
– Inherited variant protein w/ amyloidogenic structure (eg TTR)
Common symptoms in HD related amyloid
-CTS
-Arthralgia - shoulder pad sign, noninflamm joint effusion
-Paravertebral erosions, Intervertebral disc destruction
-Cystic bone changes (Advanced glycation end products stimulate OC)
HD related amyloid Tx
Renal transplant
Signs and symptoms AL amyloid
Constitutional: Fatigue, wt loss, adenopathy
HEENT:
- Macroglossia,
- submandibular enlargement
Heart
-CHF: SOBOE/edema
GI:
- Hepatomegaly
- Abdo pain,
Renal:
- Nephrotic syndrome
- Edema
MSK:
- Seronegative arthropathy
Neuro:
- CTS,
- Painful sensory polyneuropathy
- Autonomic neuropathy → orthostasis, syncope, impotence, gut dysmotility
Derm:
- Purpura (upper chest, neck, face, eyelid on pinch, periorbital),
- Bleeding,
- Nail dystrophy
** Syndromes that suggest AL amyloid**
-Nephrotic syndrome
-CHF
-CTS, peripheral and autonomic neuropathy (orthostatic hypotension, gastric atony)
-Hepatic disease
Clues of hepatic amyloid
Hepatomegaly (>15cm) w/ out of proportion LFT (⅓ normal), ALP > 1.5x ULN
-Howell jolly bodies on smear (splenic infiltration → hyposplenism)
-Proteinuria (high assoc w renal involvement)
Amyloid Cardiomyopathy investigation findings
NTproBNP: high (if normal = NO cardiac amyloid) - poor prognostic marker
-ECG - reduced voltage (amyloid replaced myocardium)
-TTE: sparkling echogneicity and increased septal thickness >6mm
-cMRI shows delayed subendocardial gad enhancement
How amyloid mimic rheum diseases
Vascular involvement → claudication (~GCA)
-Arthropathy ~RA but NO inflamm and frequent periarticular hip/shoulders infiltration→ enlarged pelvic/shoulder pad sign
-Muscle → weakness/pain ~polymyositis
-Abeta prot amyloid in Alzherimer deposits in cerebral blood vessels → stroke/bleed ~CNS vasculitis
How does amyloid cause bleeding/bruising
- Bruising: Deposit in vessels → weakening → bruising
- Bleeding: Factor X can bind fibrils → deficiency
** Clinical features of AA amyloid **
- Renal involvement: proteinuria, nephrotic syndrome
- Organ involvement: liver, thyroid, spleen
- GI dysfcn: bleeding, SIBO, decreased motility
- Increased ALP
-Less common: Cardiac and autonomic nerve involvement
** Disease assoc’d w/ AA amyloid **
Infxn:
- TB, HIV, IE, IVDU, Leprosy
- Chronic Pyelo, OM
- Bronchiectasis,
Cancer:
- Lymphoma (HL, NHL) , Leukemia
- Melanoma,
- GI/GU/Lung Ca, RCC
- Castleman
Autoimmune:
- RA, JIA
- Seronegative Spondyloarthropathy (PEAR)
- IBD (UC, CD)
- Rare: SLE, Sjogren’s, IgG4, GCA, TAK, PMR, Behcet, PAN, gout
Autoinflammatory:
- FMF, TRAPS, HIDS, CAPS, DADA2
Amyloid that occur more in elderly
Age related (senile ) amyloid - transthyretin amyloid deposition (ATTR)in M>F >70yo;
-MC = heart (restrictive CM), CTS
-A-beta protein amyloid (Alzheimers)
Mech of localized AL amyloid & MC organs
Focal infiltrate of monoclonal B cells producing amyloidogenic light chains → tumor deposits
Skin, Airway (lungs, larynx), eyes, bladder
Treatment for familial amyloid polyneuropathy
Liver transplant (replace variant TTR production and replace w/ normal TTR)
-Diflunisal and Tafamidis meglumine → binds/stabilizes TTR tetramer preventing fibril formation and amyloid deposition
-Paitisiran (RNA targeted therapies) interfere w/ hepatic TTR production
** How to diagnose Amyloid**
Screening biopsy
- In order of sensitivity: Fat pad, bone marrow, rectal mucosa, gingiva/labial salivary gland, skin
If negative: biopsy clinically involved site (kidney, carpal ligament, sural nerve, skin, liver) = +bleeding risk (ie do not bx enlarged liver)
Under light microscopy
- Unstained = amorphous, homogeneous hyaline extracellular material
- Congo red stained = apple green birefringence
** Investigations to order when working up amyloid**
-
SPEP/UPEP, immunoelectrophoresis, free light chains to r/o plasma cell dyscrasia as cause
– DNA analysis if consistent with hereditary
– Imaging (MRI/US) of joints
– Radiolabeled SAP scintigraphy(monitor response and see extent of dz)
AL amyloid Tx
Tx proliferating plasma cells: chemo, stem cell transplant
AA amyloid Tx
-Treat underlying (eg biologic)
-Surgery if Crohn’s
-Colchicine (1.2-1.8mg/d) for FMF
Sarcoid diagnosis
-Consistent clinical/radiographic presentation: asymptomatic bilateral hilar adenopathy, Lofgren, Heerfordt without another cause
OR
-Noncaseating granuloma WITHOUT other cause (eg TB, fungal, berylliosis, drugs, tumor/lymphoma)
Pathology of sarcoid
Noncaseating granuloma
Pathophys sarcoid
-Unknown Ag activates macrophage and DC, which serves as APC to CD4+ Th1 lymphocytes → IFNgamma, IL2, TNFa → recruits B cells, plasma cells, Th1/17 that contribute to granuloma formation
-Clonal expansion of CD4+ T lymphocytes → inflamm, noncaseating granuloma +/- fibrosis
Sarcoid clinical presentation
Asymptotic with AbN CXR (hilar adenopathy, pulm infiltrates)
-Pulm involvement
-Skin rash
-Ophthalmologic involvement
** Resp manifestations Sarcoid**
-Sinusitis, crusting, nasal bleeding
-Saddle nose deformity
-Laryngeal inflamm, stridor
-CP, SOB, dry cough
-Asymptomatic hilar adenopathy
-ILD w/ alveolitis
-pHTN
-RARE effusions, hemoptysis, clubbing
