Rheumatology 1 - CTD and vasculitis Flashcards
What are the clinical diagnostic criteria for SLE?
Malar Rash Discoid Rash Photosensitivity Oral ulcers Arthritis Serositis Renal disorder Neurological disorder Immunological disorder
What are the Immunological criteria for SLE?
ANA dsDNA anti-Sm anti-phospholipid low complement DAT
What are the points required for Dx?
> =4/17 criteria, with at least one clinical and one immunological OR nephritis plus ANA/dsDNA
What is the difference in performance in the new criteria?
Improved Sn, lower Sp
What is the characteristic finding on lupus skin biopsy?
IgG deposition at dermoepidermal junction
What are characteristics of lupus arthritis?
symmetrical inflammatory polyarthritis - synovitis is a criterion, not arthralgia.
non-erosive, non deforming (except jaccoud’s - laxity of ligaments due to chronic inflammation of joint capsule)
What are the classes of lupus nephritis?
Class I - minimal change - mesangial w/o hypercellularity
Class II - mesangial with hypercellularity
Class III - focal proliferative
Class IV - diffuse proliferative
Class V membranous
Class VI - advanced sclerosing lesions
What are features of SLE CNS disease?
Seizure * Headache * Stroke syndromes * Transverse myelitis Coma Dementia Ataxia Rigidity, Tremor Chorea Aseptic meningitis Psychiatric disorders * SAH Hemiballismus Cranial neuropathy Peripheral neuropathy * Mononeuritis multiplex MS like disorder Guillain - Barre syndrome
What are features of reversible posterior leukoencephalopathy?
vasogenic oedema
DWI, different from stroke
HA, seizures and visual changes
Steroids as therapy
What are findings on LP in CNS lupus?
increased protein and lymphocytes, non-specific
CSF Ab not usually measured
normal LP does not exclude CNS lupus
What ethnicity is differently affected by SLE?
incr risk in hispanic and african americans
Asians have higher severity, prevalence, increased renal disease and increased autoantibodies
What is the relationship between Vit-D and SLE?
vit deficiency is common in SLE
steroid induced OP common in SLE
Vit D deficiency is associated with increased disease activity
Small RCT shows benefit in disease activity in SLE
When are antimalarials indicated in SLE treatment?
in skin and joint disease
chronic treatment reduces flares
When are glucocorticoids indicated in sle Rx?
low dose - 0.25mg/kg - skin, joints, musculocutaneous
medium dose - 0.5mg/kg - serosal, moderate haem (plt 20.50)
high dose - 1mg/kg - CNS, renal, significant haematologic disturbance
When is azathioprine used in SLE Rx?
useful for almost all lesions - steroid sparing
good for all GN other than IV
What is the feature of cyclophosphamide in the treatment of lupus nephritis?
Low dose IV cyclophosphamide followed by AZA is equally effective as long term high dose cyclophosphamide
What are features of mycophenolate mofetil in the treatment of lupus nephritis?
MMF is equivalent to IV cyclophosphamide in the treatment of class III/IV lupus nephritis.
MMF is the recommended therapy in class IV lupus GN unless significant renal impairment at start of therapy
What are features of MMF vs AZA in lupus nephritis?
AZA is inferior to MMF in maintenance after low dose IV cyclosporin.
What effect does rituximab have in the treatment of SLE?
Is not active in SLE! demonstrated in both lunar and explorer studies.
However some patients definitely respond - so it could be considered in refractory cases.
What is the agent of choice in cerebral lupus?
IV cyclophosphamide remains the treatment of choice in cerebral lupus
What are features of hydroxychloroquine in lupus?
improves outcomes across the spectrum of lupus
regarded as standard of care
ocular toxicity - cumulative dose is risk factor - most cases reported on >6.5mg/kg/day
annual review after 5 years of therapy
specific visual field challenging, fundo is insufficient
What is the safety of hydroxycholorquine in pregnancy?
Safe to continue during pregnancy! and SHOULD be continued.
What is the role if IFN in SLE?
IFN-a expressed by pDCs - TLRs and nucleic acid induction - results in activation of T and B cells
IFN-alpha therapy can induce ANA+ve CTDs
High IFN-alpha state associated with disease severity, renal disease but not with disease severity.
-> Hydroxychloroquine inhibits the production of IFN-a
What effect does HRT have in SLE?
increases minor flares, but no significant increase in major flares.
likewise, OCP is safe in SLE -with no increase in flares or damage UNLESS previous history of clots
What effect does lupus have on vaccination?
Has NO effect on vaccination effectiveness - esp hep B or influenza
What is the mechanism of action of belimumab?
anti-BAFF
BAFF is a B-cell stimulation cytokine, inhibition limits B-cell survival, activation.
Responders to anti-BAFF include those with high activity, ds-DNA and low complement
What is the OR of vascular deaths in SLE?
OR = 1.7
accellerated atheroma formation in SLE and higher coronary calcium scores
What is the predominant feature of myositis, and the associated features?
Presentation is WEAKNESS, not muscle pain. Associated features include: - arthritis - raynauds - interstitial lung disease
What is the purpose of MRI in myositis?
for guidance of biopsy, not for diagnosis or screening
What are histological differences between polymositis and dermatomyositis?
PM and IBM - endomysial, infiltrating muscle fibres, CD8>CD4
DM - perimysial and perivascular, not infiltrating, CD4>CD8
What are rashes associated with DM?
heliotrope
shawl
gottron’s papules
(the rash on hands in SLE is essentially a mirror image of gottron’s papules, with the joints spared!)
anti-Mi-2 is an associate antibody
What is the principle of treatment of DM?
initially start with prednisone, then can consider MTX, AZA, as steroidsparing agents
Hydroxychloroquine is useful in treatment of skin only disease.
Cyclosporin, cyclophosphamide and rituximab are options for resistant disease.
IVIg
What are features of antisynthetase syndrome?
Myositis ILD Arthropathy Fever Raynaud's Mechanic's hands
Anti-Jo-1 is an associated antibody
DDx - dermatomyositis, RA with ILD/NSIP
What are features of limited SSc?
limited disease is distal to elbow and knees - better prognosis than diffuse disease
~CREST
pulmonary hypertension is NOT a common long-term complication
What are features of Ab in systemic sclerosis?
ANA is sensitive and present in 95%
anti-centromere pattern is usually in limited subtype
Anti-topoisomerase1/SCL-70 is highly Sp 97% for SSc, and is associated with diffuse subtype and ILD
Anti-RNA-polymerase III - highly specific (>99%) - associated with diffuse subtype, rapid skin and renal crises
What part of the hand is tight first in SSc?
Between the PIP and DIPJ
What is the concern of oral telangiectasia in CREST?
indicative of telangiectasia throughout the whole GIT and assocaited with a risk of bleeding
What is the current treatment for pulmonary hypertension in SSc?
annual screening - PFTs and TTE
Bosentan improves 6MWT and reduced events
Ambrisentan improves exercise tolerance
Sildenafil - improves 6MWT and reduces pulm art pressure
(no good evidence of mortality benefit due to low prevalence of disease)
What treatment is available in digital ulcers and raynaud’s in SSc?
Bosentan reduces new ulcers however has no effect on healing.
Sildenafil reduces number of cumulative attacks in 4 weeks and reduces raynaud’s condition score.
What medications are available for the treatment of of skin disease and alveolitis in SSc?
cyclophosphamide
What is the benefit of cyclophosphamide in scleroderma lung disease?
Improved QoL
Significant improvements in lung function
reduces progression of skin disease (reduced skin score)
What is the risk of steroids in SSc?
no evidence of steroids in SSc
can precipitate renal crisis in doses >15mg/day
What are risk factors and treatment of Scleroderma renal crisis?
Increased in diffuse disease
increased risk with higher dose steroids
Treatment - captopril - commence at 6.25mg and double dose every 6 hours, until controlled.
no role for prophylaxis
What is the role of HRCT in CTD lung disease?
ground glass reflects inflammation, fibrotic patterns represent scarring - now thought to be unhelpful as not strong correlation with histology.
Instead, HRCT should be used to determine if there is progression on HRCT or PFTs - treat.
If severe disease, treat in any case
What is the value of BAL in CTD lung disease?
NONE! whilst % of PMN does predict mortality, this is lost when adjusted for lung function and presence of PHT
No prediction of treatment response
No value!
What is the use of prostacyclin in SSc?
PGI2 - vasodilatory - endothelial platelet interactions - short term infusions.
Can use inhaled therapy for PPHT and CTD-PHT
What are large vessel vasculitides?
Takayasu arteritis
Giant cell arteritis
What are medium vessel vasculitides?
Polyarteritis nodosa
Kawasaki disease
What are ANCA associated small vessel vasculitides?
Microscopic polyangiitis
Granulomatosis with polyangiitis
Eosinophilic granulomatosis with polyangiitis
What are immune complex small vessel vasculitides?
Cryoglobulinaemic vasculitis
IgA vasculitis (HSP)
Hypocomplementaemic urticarial vasculitis (Anti-C1q vasculitis)
What is a general rule for vasculitides?
Increased creatinine with nil proteinuria - medium vessel
Purpura - medium vessel
Petechiae - small vessel
What vasculitides are ANCA +ve?
MPA, GPA, EGPA
What ANCA +ve vasculitides involve granulomas?
GPA, EGPA
What ANCA +ve vasculitides involve eosinophilia?
EGPA
What ANCA +ve vasculitides have renal involvement?
MPA ++
GPA ++
EGPA +/-
What ANCA +ve vasculitidies have pulmonary involvement
MPA +
GPA +++
EGPA +++
What ANCA +ve vasculitidies have ENT involvement?
MPA NO
GPA ++
EGPA +/-
What ANCA +ve vasculitides have neurological involvment?
GPA + (ENT, kidney and lung)
EGPA ++ (mononeuritis multiplex)
what ANCA is associated with GPA?
c-ANCA-PR3 - SNP in HLA-DP
What ANCA is associated with MPA?
p-ANCA-MPO - SNP in HLA-DQ
What is the induction regime in ANCA associated vasculitides?
Likewise, Pred + IVCY x 2 + ritux vs Pred + IVCY x 6 + Aza - non inferior
Rituximab is equivalent to oral cyclophosphamide in the induction of Anca associated vasculitis. (Pred plus Ritux vs Pred + oral Cyclophosphamide -> AZA (60% remission rate at 6/12)
equivalent at 18/12 (rituximab vs cyc-aza)
What antibody is associated with increased relapses in ANCA associated vasculitis
anti-PR3 is associated with increased relapses
What is the effect of fixed dose interval rituximab therapy in ANCA vasculitis?
fixed dosing q6m rituximab 1g leads to lower rates of relapse vs. rituximab given at time of relapse
What are features of rituximab as maintenance therapy vs AZA in ANCA vasculitis?
rituximab is superior for remission maintenance vs AZA
also of benefit in renal disease
What are options if not using rituximab in patients with ANCA vasculitis?
azathioprine following cyclophosphamide is equivalent to more cyclophosphamide - hence AZA is preferred maintenance agent if not for rituximab
What is the role of infliximab in AAV?
none! anti-TNF has not been showed to reduce relapse,
What is the role of infliximab in GCA?
no role! doesn't improve remission. Tocilizumab however (anti-IL-6) has been shown to be effective in an RCT in september.
What are Dx options in GCA?
USS halo sign is only Sn/Sp 70%
MRI - may be useful, more data required.
Biopsy is still needed in majority of cases - 40% sensitive, but highly specific. (bilateral, >3cm needed)
