SLE Flashcards

Question

Antiphospholipid Syndrome

Answer 1

Antiphospholipid syndrome is an acquired disorder characterised by a predisposition to both venous and arterial thromboses, recurrent fetal loss and thrombocytopenia. It may occur as a primary disorder or secondary to other conditions, most commonly systemic lupus erythematosus (SLE) A key point for the exam is to appreciate that antiphospholipid syndrome causes a paradoxical rise in the APTT. This is due to an ex-vivo reaction of the lupus anticoagulant autoantibodies with phospholipids involved in the coagulation cascade ``` Features venous/arterial thrombosis recurrent fetal loss livedo reticularis thrombocytopenia prolonged APTT other features: pre-eclampsia, pulmonary hypertension ``` Associations other than SLE other autoimmune disorders lymphoproliferative disorders phenothiazines (rare) Management - based on EULAR guidelines primary thromboprophylaxis low-dose aspirin secondary thromboprophylaxis initial venous thromboembolic events: lifelong warfarin with a target INR of 2-3 recurrent venous thromboembolic events: lifelong warfarin; if occurred whilst taking warfarin then consider adding low-dose aspirin, increase target INR to 3-4 arterial thrombosis should be treated with lifelong warfarin with target INR 2-3

Answer 2

Mixed connective tissue disease (MCTD, Sharp's syndrome) is a rare, heterogeneous, multi-system autoimmune disorder. It is a distinct clinical entity, but features of systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and myositis may all be present. It is associated with anti-U1 ribonucleoprotein (RNP) antibodies.* It is not to be confused with 'undifferentiated connective tissue disease'.** Epidemiology • Male:female ratio 1:3 • Average age of presentation 30-40, may present in children • Rare - incidence in adult population is estimated to be 2.1/million/year in one Norwegian study ``` Presentation: • Raynaud's phenomenon often precedes other symptoms and occurs in 90% of cases • Polyarthralgia/arthritis • Myalgia • 'Sausage fingers'(dactylitis) ``` Other clinically important features: • Dermatological: photosensitive rash, scleroderma-like changes, alopecia • Oesophageal dysfunction • Respiratory: pleuritis, pulmonary hypertension, interstitial lung disease • Haematological: anaemia, lymphadenopathy, splenomegaly, rarely TTP • Cardiac: pericarditis, pericardial effusion, accelerated coronary artery disease • Renal: glomerulonephritis (tends to be milder than SLE) • Neuropsychiatric: seizures, mood disturbance Investigations: • Exclude other connective tissue disease/vasculitis • Bloods FBC: anaemia, leucopenia, thrombocytopenia, U+E: renal impairment, CRP/ESR raised • ANA (usually) positive, anti Ds-DNA and scleroderma-specific antibodies (e.g. Anti-Scl70) are negative • Anti-U1 RNP (an extractable nuclear antigen, ENA), must be positive*. • Organ-specific investigations, e.g. ECG, echo, CT chest, MRI brain Management: • No large-scale trials - patients have been included in trials for SLE/SSc and show similar levels of response to immunosuppression/DMARDs • Calcium channel blockers may be used for the treatment of Raynaud's • Proton pump inhibitors for reflux disease • Endothelin receptor antagonists/prostacyclin analogues in pulmonary hypertension • Smoking cessation, moderate exercise Prognosis: • 1/3 long-term remission, 1/3 have chronic symptoms, 1/3 develop severe systemic involvement and premature death. * Note that anti-U1 RNP antibodies are not completely specific and may also be seen in definite SSc and SLE * *Undifferentiated connective tissue disease refers to syndromes in which features of one or more 'classical' connective tissue disease may be present, but do not meet diagnostic criteria. Anti-U1 RNP is absent.

Answer 3

In drug-induced lupus not all the typical features of systemic lupus erythematosus are seen, with renal and nervous system involvement being unusual. It usually resolves on stopping the drug. Features arthralgia myalgia skin (e.g. malar rash) and pulmonary involvement (e.g. pleurisy) are common

Answer 4

- In SLE, the CRP is not always elevated - If CRP is elevated, think serositis (pleuritis, pericarditis) - Think of other differentials, eg: infection

Answer 5

- Acute pneumonitis - Other ILD: organising pneumonia, NSIP - Pulmonary embolism - think ANTIPHOSPHOLIPID SYNDROME - Pulmonary HTN - Pulmonary haemorrhage - "Shrinking" lung syndrome

Answer 6

- Premature CV disease is the most likely - Vasculitis - Libman sacks endocarditis - Lupus myocarditis - Pericarditis

Answer 7

- Anaemia: often multifactorial iron deficiency anaemia, chronic disease, autoimmune (AIHA, DAT+), aplastic, anti EPO Ab - Leukopenia: peripheral destruction and suppressed production - Thrombocytopenia: common overlap with ITP - MAHA (TTP) - Myelofibrosis

Answer 8

- Brain fog is universal - CNS: headache, mood disorder, seizure, cognitive dysfunction, CVA, myelitis - PNS: present in up to 20%, sensorimotor axonal polyneuropathy is the most common - Consider catastrophic APLS - seizure, encephalopathy - Ribosomal P Abs = neurolupus

Answer 9

Mycophenolate mofetil is a prodrug of mycophenolic acid (MPA), an inhibitor of inosine-5'-monophosphate dehydrogenase. MPA depletes guanosine nucleotides preferentially in T and B lymphocytes and inhibits their proliferation, thereby suppressing cell-mediated immune responses and antibody formation.

Answer 10

Belimumab: against BAFF (B cell activating factor) Tibulizumab: against BAFF and IL17 Rituzimab, Veltuzumab: against B cells

Answer 11

Monoclonal ab directed at the subunit of the IFN-a receptor (Type 1 IFN)

Answer 12

- Primary or secondary - Thrombosis +/- obstetric complications - Also thrombocytopenia, cardiac valve abnormalities, livedo reticularis, renal microangiopathy, chorea, myelitis - Associated conditions: HELLP, pre-eclampsia, MAHA - "triple positive" at highest risk of thrombosis - lupus anticoagulant (most important), anticardiolipin IgG , B2 glycoprotein - Look out for prolonged APTT

Answer 13

- Asymptomatic/Primary Prevention (contentious): no treatment/low dose aspirin, HCQ - Secondary Prevention: WARFARIN DOACs are not recommended May require higher INR if recurrent/arterial Management in Pregnancy - Prior Thrombosis: therapeutic LMWH + aspirin - Prior Pregnancy Loss: low dose LMWH + aspirin

Answer 14

PASH - Prednisone - Azathioprine - Sulfasalazine - Hydroxychloroquine