Antibodies associated in scleroderma and their significance
- Anti-centromere: CREST, increased risk of calcinosis, raynauds, pulmonary hypertension
PROTECTIVE against ILD
- SCL70: diffuse disease Tendon friction rubs ILD (NSIP > UIP) Cardiac involvement Renal crisis
- Anti RNA polymerase III: diffuse disease
Extensive skin
Tension friction rubs
Renal crisis (highest risk for renal crisis)
GAVE
Malignancy
-To/T1
Poor outcome
Pulmonary HTN
ILD
Summary of treatment for Scleroderma
- Lung: MMF > Cyclophosphamide MMF improves DLCO + FVC - Skin: MMF > MTX > Cyclophosphamide - Raynauds and digital ulcers (threatening) --> iloprost Ulcer healing: bosentan, statin - Mild Raynauds: CCB, Sildenafil - Pulmonary HTN: bosentan, sildenafil - Renal crisis: captopril
Severe:
- Autologous SCT
- Heart/lung transplant
Subtypes of scleroderma
Diffuse scleroderma: anti SCL 70, anti RNA pol III
- Has both distal and proximal skin thickening
- Worse prognosis and rapid progress
- At risk of early pulmonary fibrosis and acute renal involvement
In scleroderma, the renal issue is a renovascular issue there they don’t have proteinuria but very severe htn - obliterative vasculopathy.
Limited scleroderma: anti centromere
- Long term prognosis better than diffuse but:
Pulmonary hypertension - 10-15% develop without ILD
ILD
Hypothyroidism
Primary biliary cirrhosis
- Sine scleroderma: Raynaud phenomenon and organ fibrosis in the absence of skin thickening.
ANA pattern, associated disease and associated autoantibodies
- Centromere: CREST/limited scleroderma, anti-centromere
- Diffuse (homogenous): RA/SLE/drug induced lupus
Anti dsDNA
Anti histone
Anti nucelosome - Nucleolar: SLE, systemic sclerosis
anti-nucleolar
anti-SCL70 - Peripheral: SLE, anti-dsDNA
- Speckled:
SLE, systemic sclerosis, CREST, sjogrens, mixed connective tissue disease, DM/PM
anti-smith, RNP, Ro, La, Mi2, jo1, SCL70
Ab in SLE
- ds DNA: disease activity, increased risk of nephritis, vasculitis, TNFi-induced SLE
- anti-smith: increased risk of nephritis, cerebral lupus, more severe disease
- Ribosomal-P: neuropsychiatric SLE, cerebral vasculitis
- Ro/La: cutaneous, neonatal SLE, congenital cardiomyopathy, congenital HB
- La: Sjogren’s syndrome, neonatal lupus
- Ro: neonatal lupus, lymphopenia, photosensitivity, C2 deficiency, subacute cutaneous lupus, Sjogrens
- RNP: crossover MCTD, myositis, raynauds
- Anti neuronals: cerebral Lupus/organic brain syndrome
- Anti histone: drug induced
Classes of lupus nephritis
6 lupus nephritis classes
Biopsy if 24 hour urine protein > 0.5
Must check for new haematuria/proteinuria
Class I/II: normally not seen
Class III/IV: highest prognosis, immunosuppression
Class V/VI: dialysis/transplant
Normally only class II, III, IV treated
Induce with IV methylpred for 3 days and MMF/CYC
- Maintain: MMF/ PO Cyclophosphamide, MMF >AZA
- Rapidly progressive: IV cyclophosphamide
- If refractory: Rituximab / Tacrolimus
Markers of disease activity in SLE
Elevated dsDNA Low C3,C4 Anaemia Neutropenia Lymphopenia Urine RCC, casts, protein, creatinine
Management of SLE
- Hydroxychloroquine mainstay management
- Corticosteroids: mainstay of SLE
- Doesn’t respond too well with steroid sparing agents but other immunosuppression include:
Mycophenolate
Azathioprine
Methotrexate
Cyclosporine, tacrolimus
Cyclophosphamide
Targeted therapy
- Rituximab: but takes 3 months to work
- Belimumab: anti B cell activating factor
- Anifrolumab: interferon y inhibitor inhibiting IgG1κ
Complications of SLE
- Infections
- Atherosclerosis: increased risk of CHD by 5x
- Osteoporosis
- Malignancies - non hodgkins lymphoma especially DLBCL
Treatment for PMR vs fibromyalgia
PMR - low dose steroids
Fibromyalgia: TCA (amitriptyline), SSRI (duloxetine), anticonvulsants (pregablin)
Lab hallmark of cryoglobulinaemia
Laboratory Hallmark: cryoglobulin (cryocrit), low C4 (marker of disease activity)
Hallmark of calcium phosphate deposition disease
Leads to Milwaukee shoulder syndrome characterised by symptoms of pain, stiffness and swelling that tend to occur overtime often with a preceding trauma or history of overuse on the affected side, common in F >70yo
Crystals can be visualised by alizarin red staining
Characteristics of sarcoidosis
Multisystem disease that is characterised by non-caseating granulomas that form in tissues, most commonly affecting the lungs.
Characteristics of primary angiitis of the CNS
- Median age of onset: 50y, M>F
- Necrotising granulomatous vasculitis of the intracerebral vessels, systemic vasculitis is absent
Clinical Features
- Recurrent headaches
- Progressive encephalopathy
- Inflammatory markers not elevated
Diagnosis
- Gold standard: brain biopsy: granulomatous vasculitis, as the vascular involvement is patchy it can lead to false negative
- LP: lymphocytosis and elevated protein
- MRI: multiple diffuse and focal abnormalities (non-specific)
- Cerebral angiography: ectasia and stenosis
Mx: Steroids + cyclophosphamide
Lead to cognitive decline, dementia, death
Low levels of which one of the following types of complement are associated with the development of systemic lupus erythematous?
C4 C5 C6 C7 C8
SLE: complement levels are usually low during active disease - may be used to monitor flares
Low levels of C4a and C4b have been shown to be associated with an increased risk of developing systemic lupus erythematous
Osteomalacia
Paget’s Disease
Osteomalacia
low: calcium, phosphate, associated with vit D deficiency
raised: alkaline phosphatase
Paget’s Disease
Normal CMP
Isolated ALP
Poor prognostic factors in RA
- Positive RF
- Positive anti CCP
- Early erosions on Xray
- HLA DR4
- Extra-articular features, eg: nodules
- Elevated ESR/CRP
