Connective tissue disease Flashcards
What is the main chemokine / cytokine involved in SLE?
Type 1 interferon
Person with negative ANA and clinical features of lupus. Can you make a lupus Dx without ANA?
No
What are teh cutaneous manifestations of SLE?
Acute cutaneous lupus causing a photosensitive rash the is nasolabial sparing
- Can also get facial discoid lupus that looks like a malar rash but has an area of central scaring
Subacute cutaneous lupus
- Rash that looks like psoriasis or piteraiasis
Bulus SLE
Discoid SLE
Perniosis (chillblains lupus)
Urticarial rash
Panniculitis
Allopecia
DO all pts with cutaneous manifestations of SLE have SLE?
No, some pts have isolated cutaneous manifestations
- For example only 50% of pts with subacute cut lupus have SLE.
- Only 25% of pts with discoid lupus have SLE
What antibody is cutaneous SLE associated with?
Anti-ro antibodies
What is the aponymous name and the features of SLE associaed small joint arthropathy?
Jacouds arthropathy
Deforming but non errosive small joint polyarthropathy (XR looks normal)
Nil swelling as with RA
In acute SLE flare, what do the ESR and CRP do? What is the exception
CRP is almost never elevated in SLE, even an acute flare
ESR will be elevated
The exception is serositis - CRP will be elevated
What is serositis in SLE?
Pleural effusion and pericarditis (inflammation of the thorasic linings)
What are the two differentials of raised CRP in SLE?
Infection is main one
Serositis
Pt comes in breathless with SLE. What is the main Dx (lung manifestation of lupus)?
Acute pneumonitis
Could be a PE associated with APLS (strong association with SLE)
Other less common lung manifestations inc:
- Pul HTN
- Pul haemorhage
- Shrinking lung syndroem
SLE rarely causes ILD
Vascular manifestations of Lupus? Cardio manifestations of lupus?
Vascular manifestations:
Capileritis (small vessel inflammation)
- Kayen pepper spots
Hypersensitivity vasculitis (inflam or larger vessel, often complex deposition)
- larger lesions and ulcers
Urticarial rash
- Wheel like lesions
Cardio manifestations:
- Libman sacks endocarditis (sterile endocarditis)
- Lupuis myocarditis
- Pericarditis
What is the most likely cardio complication of lupus?
Premature cardiovascular disease
(much more likely than the other more specific cardio manifestations ie pericarditis etc)
Haem manifestations of SLE?
Anaemia (often multifactorial)
- IDA, AoCD, AIHA
Leukopenia
-Most often lymphopenia, but also neutropenia
THrombocytopenia
- Large phenotypical overlap with ITP but different abs to pure ITP
MAHA (mainly TTP)
Myelofibrosis, HLH
What is the most important acute haem manifestation of SLE to recognize?
MAHA, this is an emergency
Neurological conditions?
CNS lupus
Peripheral nerve involvement:
- peripheral nerve sensory motor axonal nephropathy
Pt comes in with CNS manifestations, b/g SLE. What are the main 2 differentials to consider?
Catastrophic APLS
- If ruled out this then consider CNS lupus
What ab associated with CNS lupus?
Ribosomal P antibodies = CNS lupus
AUtoantibodies and specific blood findings in Lupus?
Raised ESR:CRP ratio
All are ANA positive (most sensitive)
Anti Smith (most specific)
Anti dsDNA
Anti SSA (anti ro), Anit SSB (la) can be positive, mostly associated weith sjogrens syndrome
Anti U1RNP - most often associated with MCTD but can be positive in Lupus
Anti ribosomal P - mostly with renal and CNS lupus
COngenital heart block is associated with which connective tissue disease?
SLE
What autoantibody associated with development of congenital heart block?
Anti SSA (anti ro52)
- Also anti SSB (anti la)
What is a neonatal cuteneous complications of lupus?
… neonatal cutaneous lupus lol
- due to autoantibodies that cross the placental and cause manifestations on the baby. Rarely severe disease, usually resolves
Rx of Lupus?
Non pharm:
- UV protection
- Smoking ceasation
Pharm:
- Hydroxychloroquine (backbone)
- Steroids (acute flares)
- Mycophenylate (renal lupus)
- Cyclosporin, tac (renal lupus)
- MTX, AZA, Leflunamide
- Cyclophosphamide
What drug should all lupus pts be on (similar to MTX in RA)?
Hydroxychloroquine
What is the main side effect of long term hydroxychloroquine? what other similar drugs can cause this same manifestation?
Who is most at risk of this complication? How is it monitored?
Retinopathy
- 304% for pts on HCQ >20 years
Mainly recognized in use of chloroquine for malaria. HCQ is a similar but different medication
Most at risk - elederly, renal impariment
Monitoring - HCQ >5 years needs annual eye checks to monitor. This is because it is slowly progressive and reversible in early stages
What is Belimumab? what does it target?
This is a mab to BLySS/BAFF pathway in SLE
- Not PBS approved but TGA approved
What is anifrolumab?
Anifrolumab is a mab directed at the subunit of the INF alpha receptor
- Not PBS approved but TGA approved for SLE
Pt with SLE, presents with GN and PE. APLS negative. WHy do they have a PE?
GN associated with hypercoagulability, especcially nephrotic syndromes (Lupus nephritis class V (membranous nephritis)
What is the classic cutaneous sign of APLS?
Livedo reticularis
What are the three tests in APLS?
Anti beta 2 glycoprotein
Anti cardiolipin
Check IgG and IgM of both the above, IgG is more relevant, therefore if have high IgG titre then this will be worse
Lupus anticoagulent (not an actual antibody, this is a functional test)
- contributes to thrombosis risk in vivo, but is an anticoagulent in vitro
What antibody / test in APLS is most associated with thrombosis?
Lupus anticoagulant
Young person with prolongued APTT? what is an important differential to consider that could solely manifest as prologue APTT on routine bloods?
APLS
How is APLS treated?
Primary prevention
- ? low dose aspirin or HCQ (somewhat contentious)
Secondary prevention (ie they have already had a clot / preg event)
- Warfarin INR 2-3 Indefinitley
- NOACs dont work
Management in pregnancy
- Prior thrombosis: therapeutic LMWH and aspirin
- Prior preg loss: proph LMWH and aspirin
Skin features of dermatomyositis?
Gotrons papules, and gotrons sign (rash of elbows or knees)
Shawl sign
What are the essential features of antisynthetase syndrome?
This is a specific subtype of myositis (usually dermato or polymyositis)
Key features:
- Myositis (ie elevated CK, may have clinica signs)
- ILD
- Mechanics hands - hyperkeratiosis and fisuring of the fingers and thumb
- Raynauds - not common with other forms of myositis
- Inflammatory polyarthritis
- Oesophageal dysmotility - dysphagia
What is the main auto-antibody in antisynthetase syndrome?
Anti Jo1
Pt with myositis has anti-HMGCR? what condition?
Immune mediated necrotising myositis, probably statin associated but not always
What HLA is IMNM associated with?
HLADRB1 11*01
Pt with dermatomyositis has MDA5+. What are they most at risk of developing?
ILD
What are the features of clinically amyopathic dermatomyositis (MDA5+ dermatomyositis)?
Often nil muscle involvement clinically (clinically amyopathic)
- Associated with rapidly progressive ILD and high mortality
- therefore need aggressive immunosupression
- Cutaneous ulcerations
- Inverse gottrens papules (palmer aspect rather than dorsal surface
- Pneumomediastinum
What are the three areas of pathophysiology in systemic sclerosis?
Vascular damage
Autoimmunity
Tissue fibrosis
Pt presents with PHTN and finger tip ulcers. What condition?
scleroderma
- very important cause of PHTN, often the first presentation of the disease
Autoantibodies in SSc?
Anti centromere
- limited cutaneous systemic sclerosis, therefore main complicaiton is PHTN
Anti-topoisomerase 1(anti SCL70)
- associated with difuse SSc. therefore main complication is associated ILD
Anti RNA polymerase III
- severe renal involvement
What is the pattern of skin involvement in limited cutaneous SSc?
Distal skin thickening (below elbows)
- therefore if pt has diffuse skin thickening with proximal arm or face/trunk affected then this is diffuse
What is a key feature that almost all pts with SSc have, often before they receive the diagnosis?
Raynauds
- would be very unusual to get SSc without raynauds. IN limited disease, often have long Hx raynauds before present, as opposed to diffuse disease where the Hx of raynauds is typically much shorter
Explain CREST?
Calcinosis
Raynauds
Esophageal inv
Sclerodactyly
Telangioectasia
What is systemic sclerosis sine scleroderma?
THis is systemic sclerosis with nil skin involvment
- Ie pt has ILD due to SSc, but nil skin involvement
Pts with SSc can get cardiac involvment. What is an important manifestation of cardiac involvment?
Conduction disease due to cardiac fibrosis
What is the scleroderma renal crisis presentation?
This manifests as an accelerated hypertension type phenotype
HTN may be asymptomatic of symptomatic. Symptoms/signs including:
- Headache, visual change
- Papiloedema
- Cardiac failure
Pt with systemic sclerosis has HP 110/80. Comes back 1 month later for routine check, now BP 150/95. What should you be concerned about
Developing scleroderma renal crisis
Often will develop accelerated HTN, then the renal crisis
What medication should be avoided in SRC?
Corticosteroids
What is the main treatment for SRC?
ACEI/ARB
When I move my ankle creaks. Exam shows tendon crepitus. What condition
Systemic SSc, this is tendon involvement (tendon rub)
Indicator of bad prognosis
What are the GI abn in SSc?
CREST is obvs associated with oesophageal involvment
however any part of the GIT can be affected
Other GIT manifestations inc:
- GAVE (watermelon stomach on G scope), delayed gastric emptying
- Small bowel overgrowth
- Faceal loading and secondary incont, or bowel obstruction
What are the phases of raynauds?
White, blue/purple, red
What distinguishes primary raynauds to secondary?
Secondary
- painful raynauds (most raynauds in uncomfortable but not painful)
- Other manifestation ie skin etc
Adult 40yo with new raynauds. Should you be concerned?
Every cause of new onset raynauds in adulthood has an important cause, needs to be investigated
- Primary raynauds begins in teenage years, secondary raynauds usually onsets in adulthood
Abnormal nail fold capilioscopy is usually assoicated with which connective tissue disease?
systemic sclerosis
What is a complication of raynauds? how does it manifest and time course?
Digital ulcers
- Extremely tender, last for several weeks to months
- Can be very debilitating
What is the main risk during preganncy for systemic sclerosis?
Increased risk of Preeclapsia and ecclampsia
Typical treatment regime for SSc ILD?
Nintedanib (antifibrotic) and mycophenylate
What is mixed connective tissue disease?
Currently this is a distinct entity however the phenotypes is that of a SLE and scleroderma overlap
Pt with puff hands. What disease?
MCTD
What is the commonest cause of death (therefore the most important complication) of MCTD?
Pul HTN
Characteristic lab findings in MCTD? How to tell between lupus and MCTD with antibodies?
Positive ANA, speckled pattern
Anti U1RNP (high titre), anti SSA (anti ro) often positive
There is often overlap between antibodies in SLE and MCTD. However if pt has pos Anit-sm, anti-dsDNA, or anti ribosomal P antibodies then it is lupus
Almost all MCTD have pos RF, but negative anti CCP. If pt has positive anti CCP then this is RA
Sjogrens syndrome can be thought of as a disease of the … ?
Exocrine organs
What are the main symptoms of SS? what is the pathological cause of these symptoms?
Sicca symptoms (xerostomia, xeropthalmous of the eye, dry vagina)
- Due to lymphocytic infiltration of the exocrine glands
Gladular enlargment
Circulating antibodies
What are some DDx of parotid enlargment?
Infections
- Viral: mumps, EBV, HCV, HIV
- Bacterial: acute bacterial parotitis, TB
Autoimmiune
- Sjogrens syndrome, GPA
Inflamatory:
- IgG4 disease
Metabolic:
- Diabetes, Bulimia, alcoholism
Cancer:
- Lymphoma, leukameia
Granulomatous
- sarcoidosis
Palpable purpura. Dx?
Sjogrens disease
Pt with Sjogrens syndrome has thin walled cystic leions on HRCT. What is the Dx?
Lymphocytic interstitial pneumonia
Pt has lymphocytic intersitial pneumonia, what primary condition do they most likely have?
Sjogrens syndrome
Pt with NAGMA and Sjogrens, what is teh Dx?
Type 1 RTA
What is teh main renal manifestation of Sjogrens syndrome?
TYpe 1 RTA
Pt has mixed cryoglobulinaemia, which connective tissue disease do they have? What would be the most likely infection associated with this?
Sjogrens syndrome
Hep C virus
What is a characteristic but uncommon neurological manifestation of Sjogrens syndrome? How does it manifest?
Sensory ganglionopathy that manifests as pseudoathetosis due to lack of proprioception in the affected limb
What cancer is Sjogrens syndrome most associated with?
Lymphoma (NHL, most common is MALT)
Autoantibodies in Sjogrens syndrome?
Most common:
- anti SSA (anti Ro60), Anti SSB (anti La)
Often have RF positive, CCP will be negative
Often have polyclonal hypergammaglobulinaemia -30%
Sometimes have cryoglobulins 15%
What is the antibody associated with neuromyelitis optica?
AQP4 IgG ab positive
What are the cardinal features of Behcets disease?
Relapsing oral and genital ulcers with bilateral posterior or panuveitis (hypopyona in anterior uveitis)
- often in a pt from the silk road demographic
Other features:
- pustulopapular rash (mucosal and non mucosal)
- non errosive mono or oligo arthritis
- Pathergy (abnormal reaction that occurs after tissue damage ie venepuncture)
- Pan vasculitis
What HLA in Behcets disease?
HLA B 51
What pathological description is characteristic of sarcoidosis?
Non caseating greanulomatous inflamation
Lupus pernio. What condition?
Sarcoidosis?
What are some key rheum features of sarcoidosis? What is lofgrens syundrome?
Lupus pernio
Errythema nodosum
Isolated ankle arthritis
Lofgrens syndrome is a clinical triad of sarcoidosis:
- Fever
- EN
- bilateral hilar Lymphadenopathy
Pt has painful ears. What condition?
Relapsing polychondritis
What is teh main malignant associated of relapsing polychondritis?
Myelodysplasia
What is teh pathopneumonic histo for IgG4 disease?
Lymphocytic infiltrate
Storiform fibrosis
What are the most common / important manifestation of IgG4 disease?
- Retroperitoneal fibrosis
- Periaortitis, periarteritis (manifesting as vascular complications)
- renal ionvolment
