Immune-related multi-system diseases Flashcards
What are the diagnostic criteria/ clinical presenation of SLE?
4 of 11 ACR criteria (SOAP BRAIN MD)
* Serositis
* Oral ulcers
* Arthritis
* Photosensitivity
* Blood disorders (AIHA, ITP, leucopenia)
* Renal involvement ANA +ve
* Immune phenomena (dsDNA, anti-Sm, Antiphospholipid Ab)
* Neuro symptoms
* Malar rash
* Discoid rash
What antibody can be tested for if you suspectd drug-related SLE?
Anti-histone
What is the most specific antibody for diagnosis of SLE?
Anti-Sm (Anti-smith) antibodies
Only positive in 30% of patients but highly specific
What are the most sensitive antibodies for detection of SLE?
ANA (anti dsDNA)
Positive titers of ≥ 1:80 have ∼ 98% sensitivity for SLE
What are the findings on Histology for patients with SLE?
in
1. Bloods
2. Kidney
3. CNS
4. Skin
5.Cardiac
- LE test –> denaturated nucleus in neutrophils (not done anymore)
- Kidney –wire-loop appearance of glomeruli
- CNS : small vessel angiopathy
- Skin: antibodies on epidermal-dermo junction (picture)
- Spleen -. “onion skin” lesions
- Heart– Libman-Sack endocarditis (non-infective endocarditis)
What is the pathophysiology of systemic sclerosis
2 main things
1. Endothelial changes in blood vessels
2. increased collagen release –> firbrosis of tissue (due to inflammation)
What are the features of limited cutaneous sclerosis?
What are the associated antibodies?
CREST syndrome
1. Calcinosis
2. Raynauds
3. esophageal dysmobility
4. sclerodactily
5. telangiectasia
–> anti-centromere antibodies
What is the difference between limited and diffuse systemic sclerosis?
Limited cutaneous systemic sclerosis
- Starts at Skin of feet, lower legs, hands and forearm
- progresses centrally and can have organ involvement in 10-20 years after onset
- Anti-centromere antibodies
- Primary pulmonary hypertension
Diffuse cutaneous systemic sclerosis
- Rare
- Wide-spread skin involvement
- Early involvement of organ damage
- With interstitial lung disease (rarely pulmonary hypertension)
- Scleroderma kidney/renal disease –> renal hypertension due to fibrosis and microvascular –> renal hypoperfusion
- Anti scl70 staining (and others)
What are the histological finidings of limited systemic sclerosis?
↑collagen in skin and organs
* “Onion skin” thickening of arterioles [BUZZWORD]
What antibodies are used in diagnosis of limited systemic sclerosis?
Anti- centromere
–> speckled nuclear pattern
What antibodies are associated with the diagnosis of diffuse systemic sclerosis?
Anti- topoisomerase II (Scl-70)
What is polymyositis and dermatomyositis?
Skeletal muscle disorders characterised by progressive muscle weakness and inflammation on muscle biopsy (definitive diagnosis)
What is the aetiology/ association of dermatomyositis or polymyositis?
No clear cause but several associations
- Polymyositis (PM): cell-mediated cytotoxicity against unidentified skeletal muscle antigens, chiefly affecting the endomysium
- Dermatomyositis (DM): idiopathic or paraneoplastic antibody-mediated vasculopathy, associated with malignancies (non-Hodgkin lymphoma; lung, stomach, colorectal, or ovarian cancer )
What is the main clinical presentation of dermatomyositis and polymyositis?
- progressively worsening proximal myopathy
2. Cutaneous features in dermatomyositis
- Macular ‘lilac’ heliotrope rash on upper eyelids with periorbital oedema,
- ash on chest wall, neck (shawl signs) , elbows or knees
- Gottron’s papules (scaly erythematous raised/thickened plaques on finger joints)
What is sarcoidosis?
Multisystem, Connective tissue disease, can involve any organ system, most commonly lung and skin
- forms non-caseating granulomas.
What is the pathological hallmark of sarcoidosis?
non-caseating granulomas
What is the epidemiology of sarcoidosis?
- Average age of onset: 30–55 years [1][2]
- Sex: ♀ > ♂ (2:1)
Prevalence
* Highest in African American and Scandinavian populations
* 2–4 times higher in Black individuals than in non-Hispanic white individuals
Explain the changes in calcium seen with sarcoidosis
Calcium dysregulation
1. activated pulmonary alveolar macrophages →
2. ↑ 1-alpha hydroxylase expression and activity →
3. ↑ 1,25-dihydroxyvitamin D (calcitriol) →
4. hypervitaminosis D →
5. hyperphosphatemia, hypercalcemia, and, possibly, renal failure
What are the clinical signs and symptoms of sarcoidosis?
Can caus anythign
- Most commonly: lung –> chronic dry cough + hypercalaemia
- Night sweats, chest pain
Many many extra-pulmonary manifestations
- SKIN: erythema nodosum (tender red nodules on shins), lupus pernio (red/purple
lesions around nose), skin nodules - LNs: lymphadenopathy, painless and rubbery
- JOINTS: arthritis, bone cysts
- EYES: anterior uveitis → misting of vision and painful red eye; posterior Uveitis → progressive visual loss; uveoparotid fever = bilateral uveitis, parotid enlargement +/- facial nerve palsy (Heerfordt’s Syndrome); keratoconjunctivitis, lacrimal gland enlargement
- LIVER/SPLEEN: Hepatosplenomegaly
- BLOOD: Leukopaenia/ anaemia
- Hypercalcaemia/hypercalciuria → renal calculi + nephrocalcinosis
- HEART→ dysrhythmias, cardiomyopathy, conduction defects, pericarditis,
- valvular lesions
- CNS involvement
- CONSTITUTIONAL SX: malaise, fever, wt loss, night sweats
What are the investigations that should be done in a patient with suspeceted sarcoidosis?
- ↑Ca2+ (ectopic 1-alpha hydroxylase release by activated macrophages)
- ↑ESR,
- ↑ACE (due to pulmonary production)
- Transbronchial biopsy → non caseating granuloma
- Spirometry might show
How are vasculitides classified?
Classified by Vessle size
1. Large Vessle
2. Medium Vessle
3. Small Vessle
What are the 2 Large Vessel Vasculitides?
- Giant Cell Arteritis (Temporal arteritis)
- Takayasu’s arteritis
What are the histological findigns for GCA?
Remember to have ESR first
Granulomatous transmural inflammation + giant cells (fused cells) + skip lesions
and immediate treatment with high-dose Prednisolone
What are the 2 most important medim vessle Vasculitides?
- Kawasaki’s disease
- Polyarteritis nodosa
What is Polyarteritis nodosa?
Which organs are primarily involved?
Medium-vessle vasculitis, most commonly in middle- aged adults
- often associated with renal impirement
- Associated with Hepatits B (in 30%)
- can involve any organ, but lung-sparing
- presents with abdominal pain, muscle, joint pain
- fever malaise
- rash ulcers and **nodules (nodosa) **
What is the angiographic appearance of polyarterittis nodosa?
Microaneurysms on angiography (“string of pearls / rosary bead appearance”)
–> NODOSA = nodules = string of pearls
What are the most important Small-vessele vasculitides?
- cANCA: Granulomatosis with polyangitis (former Wagner’s)
- pANCA –> Eosinophic granulomatosis with polyangitis and
- pANCA –> Microscopic polyangitis
- Henoch Schönlein purpura
What is granulomatosis with polyangitis?
What are the organ systems mainly involved?
It is a small vessle vasculitis associaetd with cANCA antibodies
Triad of:
(1) Upper resp tract: sinusitis, epistaxis, saddle nose
(2) Lower resp tract: cavitation, pulmonary haemorrhage
(3) Kidneys: crescentic glomerulonephritis → haematuria & proteinuria
What is Eosinophilic granulomatosis with polyangitis?
pANCA associated small-vessle vasculitis
- asthma
- eosinophilia
- vasculitis
–>to remember: Eosinophils are associated with asthma –> Eosinophilic grnaulomatosis associated with asthma
What is amyloidosis?
A multi-system connective tissue disease characterised by deposition of misfolded amyloid proteins
What are the main sub-types of Amyloidosis?
- Primary (AL) Amyloidosis
- most common
- deposition of Ig light chains
- associated with multiple myeloma –> production of monoclonal Ig light chains
- Secondary (AA) amyloidosis –> chronic inflammation –> production of amyloid A (acute phase protein)
- e.g. autoimmune disease (60%), RA, ank spond, iBD
What are the main clinical/ histological features of amyloidosis?
● KIDNEY: nephrotic syndrome = most common presentation (especially seconary)
● HEART: restrictive cardiomyopathy, conduction defects, heart failure,
cardiomegaly
● LIVER/SPLEEN: hepatosplenomegaly
● TONGUE: macroglossia in 10%
● NEUROPATHIES: incl carpal tunnel
What histological stains are used to diagnose amyloidosis?
- Congo Red stain
2.Appear Apple green birefringence with Congo red stain under polarized light
What is Takayasu’s artierits?
What is the main clinical presentation of Takayasu’s arteritis?
- Affects branches of the aortic arch
- Inflammatory phase → FLAWS
- Pulseless phase → ”Pulseless” (discreprancy in BP between arms) , claudication, cold hands
- ↑ in Japanese women
What are the investigations that should be done in a patient with suspeceted sarcoidosis?
- ↑Ca2+ (ectopic 1-alpha hydroxylase release by activated macrophages)
- ↑ESR,
- ↑ACE (due to pulmonary production)
- Transbronchial biopsy → non caseating granuloma
- Spirometry might show
