CTD, Vasculitides, Sarcoidosis + Amyloidosis Flashcards
1
Q
What kind of disorder is SLE (Systemic Lupus Erythematosus)?
A
Systemic Autoimmune Connective Tissue Disease
2
Q
Which gene is associated with SLE?
A
HLA DR3
3
Q
What type of hypersensitivity reaction is seen in SLE?
A
Type 3
4
Q
What is/are the aetiologies of SLE?
A
Probably an unknown environmental trigger on someone with genetic susceptibility (e.g HLA DR3)
Can also be drug-Induced (e.g. Hydralazine)
5
Q
Which 5 drugs are most commonly associated with inducing SLE?
A
Procainamide, Hydralazine, Phenytoin, Isoniazid, Quinidine
6
Q
Who stereotypically presents with SLE?
What is the common presenting history?
A
Young AfroC. women
Malaise, anorexia, weight loss, PUO (pyrexia of unknown origin)
7
Q
Which type of autoantibody is seen in 95% of SLE cases?
What 2 subtypes of this autoantibody are most associated with (non drug induced) SLE?
Which is the most specific for SLE?
A
ANA (Anti-nuclear antibody)
Anti-ds DNA - most specific subtype
Anti-Smith
8
Q
Which autoantibody subtype is associated with drug induced SLE?
A
Anti-histone
9
Q
What is an LE cell? Can a histological finding of these be used to diagnose SLE?
A
Neutrophil or macrophage that has phagocytosed the denatured nuclear material of another cell.
No longer used for dx - only in 50=75% of SLE cases, and seen in many other CTDs
10
Q
Histologically, what is seen on an SLE skin biopsy?
A
Lymphocyte infiltration in upper dermis, vacuolization of the basal layer of epidermis, RBCs extravated into the upper dermis
11
Q
What would IF staining of a histological section of skin, from an SLE patient, show?
A
IgG antibody deposits in the epidermal basement membrane and within the nuclei of the epidermal cells
Anti ds DNA and Anti histone = homogenous staining pattern
Anti Sm = speckled coarse staining pattern
12
Q
What are the characteristic lesions seen on the spleen of an SLE patient?
A
Onion skin lesions
13
Q
What is the most common cardiac presentation of SLE? What would a biopsy of the cardiac tissue show?
A
Libman-Sack non infective endocarditis - vegetation on the valves
Strands of fibrin, neutrophils, lymphs and histiocytes
14
Q
What are the ACR criteria for defining SLE? How many of the criteria have to be present in order to make a diagnosis of SLE? (NB I think this is only used for dx in clinical trials)
A
Need 4/11 of ACR criteria (SOAP BRAIN MD): Serositis - pleurisy or pericarditis Oral Ulcers Arthritis - non errosive Photosensitivity Blood disorders (AIHA, ITP, leucopenia) Renal involvement ANA +ve Immune Phenomena (dsDNA, anti-Sm, Antiphopholipid) Neuro symptoms Malar rash Discoid Rash
15
Q
If a patient with SLE has a history of recurrent miscarriages and thrombosis, which autoantibody are they likely to have (subtype)?
A
Anti-phospholipid antibody
16
Q
What neurological symptoms can be seen in SLE?
What renal disorder is most commonly seen?
A
Seizures and Psychosis
Nephrosis (proteinuria, hypoalbuminaemia, oedema) - specifically Membranous Glomerular disease
17
Q
A patient with SLE has an increased incidence of getting other AI disorders. Which AID is it particularly associated with? What subtypes of ANA are seen in this disease?
A
Sjorgen’s syndrome
Anti-Ro
Anti-La
18
Q
What are the 2 types of scleroderma?
A
Limited Sceleroderma (CREST) Diffuse Sceleroderma
19
Q
Limited scleroderma used to be called CREST, which is helpfully a mneumonic of the symptoms seen in the disease. What does is stand for?
A
Calcinosis, Raynaud’s, Esophogeal dysmotility, Sclerodactyly, Telengiectasia
20
Q
What autoantibody is seen in Limited Scleroderma/CREST?
A
Anti-centromere
21
Q
What are the histological presentations of Limited SclerodermaCREST?
A
Increased collagen in skin anad organs
Onion skin
Intimal thickening of the arterioles
22
Q
What is Morphea?
A
An area of localised skin fibrosis and excess collagen
23
Q
What genes are associated with Scleroderma?
A
HLA DR5
Drw8
24
Q
Which subtype of scleroderma is associated with pulmonary fibrosis? and which with pulmonary hypertension?
A
Diffuse = fibrosis Limited = hypertension
25
Where are the skin changes in limited scleroderma?
Face and distal to elbow and knees
| If there are trunkal skin presentations, it has to be diffuse scleroderma!
26
Where do the skin changes in diffuse scleroderma present? Where else can it present?
Skin changes can occur anywhere
| Will also involve one or more internal organs, commonly the kidneys, oesophagus, lungs and heart
27
Which autoantibody is most commonly seen in Diffuse scleroderma?
What staining pattern, seen under IF, is associated with this autoantibody?
Anti Scl-70 (Anti Topoisomerase-1)
28
What is the gold standard test for diagnosing scleroderma?
There isn't one! It is predominantly a diagnosis of exclusion, but is defined as:
Symmetrical skin thickening with Raynauds phenomenon (70% of cases), nail fold capillary dilatation and ANAs (mainly Anti Scl-70 and Anti-centromere)
29
What is Polymyositis? and Dermatomyositis?
Polymyositis in an AI inflammatory disorder of muscle
DM is an AI inflammatory disorder of the muscle and skin
Both are commonly associated with underlying malignancy (if >50 years old at presentation)
30
Which Autoantibody (subtype) is seen in:
a) Polymyositis
b) Dermatomyositis?
What type of autoantibodies are these?
a) Anti Jo-1 (Anti-tRNA synthetase)
b) Anti Mi-2 (Anti Jo-1 is also seen in DM but not as common)
ANA
31
What are the main 2 cutaneous features of Dermatomyositis?
| What is a nail sign often seen in DM?
Heliotrope ('lilac') rash - violacious eruption on upper eyelids
Gottron papules - discrete rythematous papules on MCc and IP joint
Nail sign: Periungal telengiectasia
32
What is the main overlapping symptom seen in Polymyositis and Dermatomyositis?
Symmetrical proximal muscle weakness (pain may or may not be present, but in Juvenile DM it is normally very painful)
33
What investigations are used to diagnose Dermatomyositis?
| Which of these investigations is truly diagnostic?
Muscle biopsy, skin biopsy, EMG, bloods
| Muscle biopsy is truly diagnostic
34
On the muscle biopsy, what are the 2 classical histological findings of DM?
1. A mixed B- and T-cell perivascular inflammatory infiltrate
2. Perifascicular muscle fiber atrophy
'Drop out' of capillaries and myofibre damage?
35
What are the histological signs of DM on the skin biopsy?
Perivascular inflammation, hyperkeratosis in the stratum corneum, epidermal atrophy, follicular plugging, and interface dermatitis
36
How is Polymyositis diagnosed?
4 fold: History and physical examination, elevated CK, abnormal EMG, positive muscle biopsy
37
What are the hallmark clinical features of Polymyositis?
Main presentation is Proximal muscle weakness. Dysphagia and muscle pain also common.
25% of patients will also experience cardiac and pulmonary symptoms.
38
What does sclerosis mean?
Hardening of a body tissue
| Scleroderma therefore literally means hard skin
39
What is the most common systemic manifestation of DM and PM?
Interstitial lung disease (pulmonary fibrosis) and Cardiac disease (HF, conduction abnormalities)
40
What are the 3 ways used to classify Vasculitides?
Clinical Setting
Histopathological pattern
Vessel size (what we use from now on)
41
Name 2 large vessel vasculitides?
Takayasu's Arteritis
| Temporal Arteritis
42
What is Takayasu's arteritis often called, due to its clinical presentation?
What 2 other vascular symptoms are often seen?
Pulseless disease
| Vascular symptoms: absent pulse + bruits, claudication
43
Who stereotypically presents with Takayasu's arteritis?
Japanese women
44
What are the main symptoms of Temporal Arteritis?
With this clinical presentation, what sign (seen on blood test) would further solidify your diagnosis of TA?
What would you do next?
Symptoms: Scalp tenderness, temporal headache, pain on chewing/talking (jaw claudication), blurred vision
Sign: high ESR
Mgmt: Urgent biopsy!
45
What Ix is needed to give a definitive diagnosis of Temporal Arteritis (Gold Standard)?
What would a positive result show?
Temporal artery biopsy
| Granulomatous transmural inflammation, giant cells and skip lesions
46
What is another name for Temporal arteritis?
Giant Cell Arteritis
TA and GCA are now used interchangeably, though technically Temporal arteritis is GCA of the temporal artery (this is also called Horton's disease)
47
Who stereotypically presents with TA?
| Half of all cases of Temporal arteritis coexist with what other disease?
Elderly (>55yo), more often women
| Polymyalgia Rheumatica
48
What is the treatment for Temporal Arteritis?
High dose steroids
49
Name 3 medium vessel vasculitides?
Polyarteritis nodosa (PAN)
Kawasaki's Disease
Buerger's Disease (Thrombangitis obliterans)
50
Which 3 organs are most commonly affected in Polyarteritis Nodosa? How do each of these present?
Which organ is spared?
80% renal - haematuria , HTN
70% cardiac - HF, MI, pericarditis
50% GI (mesenteric arteries) - abdo pain
Lungs are spared
51
In Polyarteritis Nodosa, what characteristic sign is seen on angiography?
'Rosary' sign - Microaneurysms give a nodular appearnace, like beads on a rosary
52
Common symptoms of Polyarteritis Nodosa?
PUO, weight loss, neuropathy, haematuria, HTN, abdo pain, rash, livedo reticularis
53
Which disease is commonly associated with Polyarteritis Nodosa?
Hepatitis B (30%)
54
Where is the most common place to take a tissue biopsy in the diagnosis of Polyarteritis Nodosa?
What would a positive biopsy show?
Sural nerve
Necrotizing arteritis, focal and sharply demarcated, with areas of fibrosis (from healing). Infiltrates of polymorphs, lymphocytes, and eosinophils.
55
What is another name for Kawasaki's disease?
| Who is most commonly affected?
Microscopic Polyangitis
| Children (
56
Criteria for diagnosis of Kawasaki's Disease
Fever > 5 days associated with at least 4/5 of:
i) Bilateral non supportive conjunctivitis
ii) 1 + changes to URTI mucosal membrane (strawberry tongue, red lips)
iii) 1 + changed to arms and legs (swelling, redness, skin peeling around nails - desquamation)
iv) Polymorphous rash (normally truncal)
v) Cervical LNs
57
What is a potentially lethal complication of Kawasaki's disease?
MI - coronary artery involvement can lead to aneurysm formation and MI
58
Who commonly gets Buerger's disease?
Heavy smokers, usually men under 35
59
What is the common presentation of Buergers disease?
pain; ulceration of toes, feet, fingers
60
In Buerger's disease, what can be seen on an angiogram?
Corkscrew appearance from segmental occlusive lesions
61
Name 4 small vessel vasculitides?
Wegeners Granulomatosis
Churg Strauss Syndrome
Microscopic polyangitis
Henoch Schonlein Purpura
62
Which small vessel vasculitide(s) is/are associated with pANCA?
Which particular antibody is involved?
Churg Strauss Syndrome
Microscopic polyangitis
Anti-MPO (myeloperoxidase)
63
Which small vessel vasculitide(s) is/are associated with cANCA?
Which particular antibody is involved?
Wegener's Granulomatosis
Anti-PR3 (proteinase)
64
What are triad of symptoms seen in Wegener's granulomatosis?
1) Upper Resp Tract: sinusitis, epitaxis, saddle nose
2) Lower Resp tract: cavitation, pulmonary haemorrhage
3) Kidneys: crescentic glomerulonephritis (see renal histo)
65
What is another name for Wegener's Granulomatosis?
Granulomatosis with polyangitis
66
What is another name for Churg Strauss Syndrome?
Eosinophilic Granulomatosis with polyangitis
| or Allergic Granulomatosis
67
What are the 3 stages seen in the manifestation of Churg Strauss?
Is there any systemic involvement?
1 - Airway inflammation: asthma and allergic rhinitis
2 - Hypereosinophilia: tissue damage (mainly lungs and GI)
3 - Vasculitis: can lead to severe complications
Yes, happens later due to the last 2 stages
68
Who gets Churg Strauss?
People with a history of airway allergic hypersensitivity (atopy)
69
What are the diagnostic markers of CSS?
Eosinophil granulocytes and granulomas in affected tissue
| pANCA (anti-MPO) +ve
70
What does pANCA and cANCA stand for? What is the other form of ANCA?
What are they?/What is their function?
Perinuclear Anti-neutrophil cytoplasmic antibody
Cytoplasmic Anti-neutrophil cytoplasmic antibody
aANCA = atypical ANCA
Autoantibodies, mainly IgG, work against antigens in the cytoplasm of neutrophil granulocytes and monocytes.
71
What is the most serious complication of CSS? (accounts for 50% of deaths in CSS patients)
Heart disease: normally due to inflammation of the heart muscle (hypereosinophilia), sometimes due to inflammation of the arteries supplying the heart
72
What is microscopic polyangitis?
Ill-defined AID, characterized by a systemic, pauci-immune, necrotizing, small vessel vasculitis without clinical or pathological evidence of necrotizing granulomatous inflammation.
73
What does pauci-immune mean?
| Which small vessel vasculitides are considered to be Pauci-Immune?
Negative Immuno Flourescence: Form of vasculitis associated with minimal evidence of hypersensitivity upon IF (won't see anything on IF)
Wegener's, CSS, Microscopic Polyangitis are all Pauci-Immune
After a -ve IF result, an ANCA test should always be done to look for these vasculitides (especially in the presentation of Glomerulonephritis)
74
Who typically presents with Henoch Schonlein Purpura?
Children under 10, with a hx of URTI in the past few days
75
How does HSP commonly present?
Classic Triad:
1. Palpable purpuric rash (lower limb extensors and buttocks)
2. Colicky abdo pain
3. Arthritis (mainly ankles, knees, elbows)
Can also see: Glomerulonephritis (Type 2 RP Crescentric GN - see renal histo), Orchitis
76
How does Microscopic Polyangitis commonly present?
Pulmonary renal syndrome:
a) Pulmonary haemorrhage
b) Glomerulonephritis (RP Crescentric)
Can also get constitutional symptoms: fatigue, weight loss, anorexia, fever etc.
77
Immunostaining of a glomerular biopsy, from a patient with HS Nephritis, will show what characteristic feature?
IgA deposition
78
Typical signs on blood test for HSP?
High creatinine and urea (kidney involvement)
High IgA, CRP, ESR
May be high platelet count (useful in distinguishing from ITP and TTP)
79
How is HSP diagnosed?
Normally diagnosed on clinical presentation (quite specific combination of symptoms).
Blood tests and biopsy of skin lesions can also help aid diagnosis
80
What is the treatment and prognosis of HSP?
```
Symptom control (analgesia) is normally the only necessary treatment, as HSP should self resolve within several weeks.
Can relapse in 1/3 of cases and lead to severe kidney damage - treated with IV steroids
```
81
Fill in the gaps! (Esme is getting lazy...)
| Amyloidosis is a multisystem disorder caused by ? that are deposited as ? in ?, disrupting their normal function.
Amyloidosis is a multisystem disorder caused by ABNORMAL FOLDING OF PROTIENS that are deposited as FIBRILS in TISSUES, disrupting their normal function.
82
What protein (folding) structure is most commonly seen in Amyloidosis?
Beta-pleated sheets
83
Amyloidosis can be Primary or Secondary. What are the other names for these 2 forms of amyloidosis? (Full name, not just initials!)
```
Primary = AL Amyloidosis = Amyloid Light Chain
Secondary = AA Amyloidosis = (Serum) Amyloid A Amyloidosis
```
84
Which form of Amyloidosis is the most common?
AL Amyloidosis
85
For both AL and AA Amyloidosis: what is the amyloid derived from? (it's in the name!)
Primary: amyloid is derived from light chains (component of antibodies)
Secondary = amyloid derived from Serum Amyloid A (Acute phase protein)
86
Which form of Amyloid has 'Bence Jones protein' in their urine? What is Bence Jones Protein?
Primary
| Bence Jones protein is a term used to describe abnormal LIGHT CHAINS in the blood and urine.
87
What is Primary/AL Amyloidosis associated with?
Plasma Cell Dyscrasias and Paraproteins e.g Multiple Myeloma
N.B most people with Amyloid do not have MM!
88
What can AA Amyloidosis be secondary to?
| 3 categories; 2 examples for each.
The amyloid is formed from an acute phase protein, so, understandably, it is secondary to chronic infections/inflammation:
1. AID: RA, Ankylosing Spondylitis, IBD
2. Chronic Infections: TB Osteomyelitis, IVDU
3. Non-Immune: Renal Cell Carcinoma, Hodgkin's
89
What is the most common kind of Familial Amyloidosis?
Familial Mediterranean Fever (AR)
90
What is seen in Haemodialysis associated Amyloidosis?
Deposition of beta2-microglobulin
91
What form of amyloid is deposited in the kidneys in Familial Amyloidosis?
AA amyloid
92
What gene is associated with Familial Amyloidosis? What does this gene encode for?
TTR - encodes for pyrin
93
What are the clinical features of Amyloidosis? (Caused by amyloid deposits in various organs)
1. Kidney: nephrotic syndrome (most common presentation)
2. Heart: conduction defects, heart failure (restrictive cardiomyopathy)
3. Liver/Spleen: hepatosplenomegaly
4. Tongue: macroglossia (10%)
5. Neuropathies: incl carpal tunnel syndrome, autonomic neuropathy
94
Alzheimers Addociated Amyloidosis has deposition of which protein?
Abeta 2 protein
95
How is Amyloidosis diagnosed?
Tissue biopsy: most commonly viewed with Congo Red stain under polarized light - see Apple Green Birefringence
96
What form of Cardiomyopathy is associated with Amyloidosis?
RESTRICTIVE Cardiomyopathy
97
What happens (basic pathophysiology) in Familial Mediterranean Fever (form of Familial Amyloidosis)?
+++ production of IL-1,, casues attacks of fever and inflammation of serosal surfaces (pleura, peritoneum, synovium)
98
Fill in the Gaps:
| Sarcoidosis is a multisystem disease of ? causes, commonly affecting ?, characterized by ? in many ?.
Sarcoidosis is a multisystem disease of UNKNOWN causes, commonly affecting YOUNG ADULTS, characterized by NON-CASEATING GRANULOMAS in many TISSUES.
99
What might be seen in the blood results of a patient with Sarcoidosis? How might these blood signs present clinically (symptoms)?
High calcium (also Hypercalciuria): renal calculi + nephrocalcinosis
High ESR
High ACE
Low Hb: all signs of anaemia
100
What are the skin manifestations of Sarcoidosis?
Skin: erythema nodosum, lupus pernio, skin nodules
101
What are the joint manifestations of Sarcoidosis?
Joints: arthritis, bone cysts
102
What are the eye manifestations of Sarcoidosis?
| What is Uveoparotid fever?
Anterior uveitis - mistin gof vision and painful red eye
Posterior uveitis - progressive visual loss
Keratoconjunctivitis
Uveoparotid fever = bilateral uveitis, parotid enlargement +/- facial nerve palsy
103
What are the Cardiac manifestations of Sarcoidosis?
Cardiac: dysrhythmias, cardiomyopathy, conduction defects
CNS: meningitis, cranial nerve lesions
104
What are the CNS manifestations of Sarcoidosis?
CNS: meningitis, cranial nerve lesions
105
What might you notice on abdominal examination of a patient with Sarcoidosis
Painless, rubbery lymphadenopathy
| Hepatosplenomegaly
106
What organ is most commonly involver in Sarcoidosis?
Lung
107
What is commonly seen on a CXR of a patient with Sarcoidosis?
Bilateral Hilar Lymphadenopathy!!
| Fibrosis + fine nodular shadowing in mid zones (due to pulmonary infiltrates)
108
What are the DDx of a CXR with Bilateral Hilar Lymphadenopathy?
TB, Lymphoma, Bronchial Ca
109
What 2 groups of people are more at risk of having Sarcoidosis?
Female, Afro-Carribbean
110
Histopathology signs of Sarcoidosis?
Non-caseating granulomas = histiocytes, multinucleated giant cells of Langhans and lymphocytes
Schaumann bodies
Asteroid Bodies
111
What is the most common presentation of Sarcoidosis?
Insidious SOB, dry cough, chest pain, night sweats
| Often asymptomatic
