Rheumatoid Arthritis

Overview

• Systemic disorder of unclear aetiology (Genetic and Environmental factors play a part)
• Chronic inflammation leads to joint destruction and deformity
• Early recognition and treatment crucial to limit progression as above
• Prevalence of 1% in whet populations, predominantly females in age 30-55 years
• Increased risk of CAD 

Genetic Factors:
Account for 50-65% of risk of developing RA
Shared Epitopes: HLA-DRB (DR4, DR14, DR1) are strong RFs
Polymorphisms including TNF alpha promoter PTPN22 and STAT 4

Hormonal Influence:

Risk reduced in women who have had children 

Further reduced by those who breast feed for a year or so

Disease activity subsides during pregnancy

Men have lower levels of androgenic hormones and higher level of estradiol

Environmental factors:

Smoking

Miners and Construction workers (?dust related)

Lower socio-economic groups

Diagnosis:

• Clinically a symmetrical polyarthropathy affecting small joints (MCP and PIP joints)
• Can be asymmetric and oligoarthritis 
• Associated Morning stiffness (>60mins)
• DIP and Lumbar spine spared usually
• Examination reveals soft boggy or fluctuant swelling and tenderness, with warmth and redness
• Reduced active and passive movement with active arthritis

Laboratory:

• Active inflammation: High CRP and ESR, Anaemia of chronic disease, High Plts, low albumin
• Synovial fluid analysis: High leucs (predominant neuts)
• RF present in 70% of patients
• Anti CCP present in 60% of patients
• ANA positive in 40% (non specific)
• Specificity of Anti CCP for RA is 95% when compared to RF which is 80%

Imaging:

• Xray reveals: Periarticular osteopenia, erosions, and symmetric joint space narrowing
• MRI shows bone marrow oedema and synovial proliferation as precursors to erosions

Extra-Articular manifestations:

• Constitutional: Fatigue, Weight loss
• Dermatologic: Rheum nodules, Ulcers, Vasculitis
• Opthalmolgic: Episcleritis, Scleritis, Keratoconjunctivitis sicca
• Haematologic: Aneamia of chronic disease, Thrombocytosis, Pancytopenia + splenomegally (Feltys), large granular lymphocyte syndrome
• Cardiovascular: premature CAD, chronic heart failure, pericarditis, secondary amyloidosis
• Pulmonary: Exudative Pleural effusion, Fibrosis, pulmonary nodules, BOOP, brochiectasis, cricoarytenoid disease producing stridor
• GI: Dry mouth
• Renal: Secondary amyloidosis
• Neuro: c1-c2 subluxation, Mononeuritis mulitplex, peripheral neuropathy

Treatment:

Aims are to reduce inflammation, maintain remission and preserve function

At each visit disease activity and damage needs assessing with questions about fatigue, weight loss, morning stiffness, joint pain, functional status and quantification with a scoring system, measurement of CRP/ESR, and imaging.

NSAIDs and Steroids Provide symptomatic relief but do not alter disease course.  Used PO and intrarticular DMARDs MTX Hydroxychloroquine Sulfasalazine Leflunomide Azathioprine Cyclophosphamide MMF Cyclosporine Immunosuppressive agents that slow and block autoimmune damage to joints. First line is MTX  Add on therapy of Hydroxy/sulfa in poorly controlled RA patients Biologic agents TNF alpha inhibitors (Etanercept, infliximab, adalimumab, golimumab, certolizumba pegol) T cell costimulation (Abatacept) Anti CD20 B cell depleting (Rituximab)  IL 6 receptor antagonist (Tocilizumab) Used if above therapies have failed. Prior to using all pts require: -       CXR -       Anti viral screen (HIV/Hep) -       TB screen -       Monitor for infections during treatment Live vaccines should be avoided in these patients Concurrent use of 2 or more biologics is not recommended Surgical Intervention Synovectomy Repair or tendon rupture Osteotomy for realignment  Joint fusion for stabilisation  Joint arthorplasty Specific concerns for RA patients: Pre op optimisation of FBC C Spine imaging  Risk of infection and bleeding post op Balancing risk of infection with immunosuppressive therapy and healing time Non pharmacological treatment: Patient education MDT approach: Phsyio/OT/Dietician Smoking cessation Yearly flu vaccine

Pericarditis

Classic findings:

1. Chest pain (sharp and severe) with pleuritic component
2. Pericardial Friction Rub hear on auscultation
3. Diffuse concave ST segment elevation on ECG, with PR segment depression
4. Pericardial effusion (present in 60% of patients)
5. Fever and elevated inflammatory markers

Worse in recumbent position

Differentials to consider: Acute MI, PE, Aortic dissection

Causes:

Idiopathic
- Presumed viral or autoimmune - 40% of all cases 

Infection
- Post viral: Coxsackie A and B, Echovirus, Adenovirus HIS, Hep B+C
- Bacterial - Staph, Strep, Haemophilus, pneumococcus
- Mycobacterium TB
- Fungi: Histoplasma, Aspergillus, Candida

Autoimmune
- Rheumatic disease: SLE, RA, scleroderma
- Others: UC, GCA, PAN

Radiation
- Thoracic radiation: occurs 5 months post exposure usually

Myocardial Infarction Related
- Acute MI - 1-3 days post acute MI (usually ST elevation type)
- Dressler Syndrome - occurs several weeks/months post MI

Neoplasm
- Lung/breast/lymphoma, leukaemia

Cardiac Injury
- After blunt and penetrating trauma: may develop tamponade
- Post pericardiotomy
- Iatrogenic: post catheter insertion

Medications
- Antiarrhythmics: Procainamide, amiodarone
- Antihypertensives: hydralazine
- Antibiotics: Penicillin
- Chemo: Doxorubicin, daunorubicin

Metabolic disorders
- Uraemic

Aortic disease
- Thoracic aortic pathology causing leaking or rupture into pericardial space

Other
- Radiofrequency catheter ablation of atrial fibrillation
- Takotsubo CM

Myopericarditis

• Occurs in 15% of patients with pericarditis
• ECG shows regional concave downward ST segment elevation
• ECHO shows new segmental or global left ventricular dysfunction
• Elevated cardiac markers

Treatment:

Identify and treat underlying cause if possible

Pain relief

Prevention of tamponade and constrictive pericarditis and recurrence

1) Aspirin or NSAIDs + PPI protection - Caution post MI (use aspirin as NSAIDs promote ventricular rupture). 

2) Colchicine added in refractory cases (COPE trial supports concurrent use with above from start)

3) Steroids

Cardiac Tumours

Primary

• 75% are benign; 25% are malignant
• Myxoma is the most common and 80% originate in the left atrium
• Other benign tumours include papillary fibroelastoma and lipoma
• Malignant tumours are sarcomas

Secondary

• Secondary tumours reach the heart by metastasis (primary usually lung and breast) or direct extension and are 20 times more common than primary tumours. 
• Renal, adrenal and liver cancers can invade via the IVC

Presentation
Usually vague with constitutional symptoms but can be dramatic including syncope, CVA, HB, VT and sudden death.

Investigations

TTE and TOE

CT and Cardiac MRI

Biopsy and surgically derived tissue for histology

Management

Myxoma should be surgically removed to reduce embolic events

Fibroelastomas should be excised is highly mobile

If surgical risk is high anti platelet or anticoagulation should be considered

Malignant tumours are not amenable to curative surgical excision

Heart Failure

Clinical syndrome characterised by dyspnea, effort intolerance, orthopnea, PND, nocturnal cough and oedema. Other symptoms include early satiety, N+V, abdo discomfort, wheezing, coughing, fatigue.

Signs:
- Elevated cardiac filling pressures and fluid overload
- Cardiac enlargement
- Reduced cardiac output
- Arrhythmia

NYHA classification
Class I                 No limitation on physical activity
Class II                Slight limitation on physical activity
Class III               Marked limitation on physical activity
- IIIa - symptoms with less than ordinary activity
- IIIb - symptoms with minimal exertion
Class IV              Unable to carry on any physical activity without symptoms

Medical Rx:

• ACE inhibitors
• Angiotensin receptor blockers
• Beta blockers
• Aldosterone antagonists
• Other vasodilators - hydralazine and isosorbide dinitrate

HF with preserved Ejection Fraction (HFPEF)
Often associated with uncontrolled HTN
RFs include older age, female, HTN, obesity, DM, CAD, CKD
Rx: ACE (perindopril), Beta blockers (Nebivolol), ARB (Candesartan, Irbesartan)

Biventricular Pacing (CRT) indications:
All of the following:

• NYHA class III or IV
• EF <= 35%
• Ventricular dyssynchroniy (QRS>= 120msec)

Aim is to restore myocardial electromechanical coupling and effective ventricular contraction
Combined ICD and CRT devices can be placed

Autoantibodies in Rheumatology

Autoantibody	Condition	Comments
ANA	SLE	Screening tool for Autoimmunity
Anti DS DNA	SLE	Correlates with Lupus disease activity esp kidney disease
Anti Smith	SLE	Most speicifc for SLE
Anti U1 RNP	MCTD, SLE	Higher titre seen in MCTD
Anti Ro/SSA, Anti LA/SSB	Sjogrens, RA, SLE, PSS	SICCA symptoms in SLE, associated with neonatal lupus
Anti SCL 70	Diffuse PSS	Pulmonary fibrosis more common
Anti centromere	Limited PSS (CREST)	Pulmonary HTN
c-ANCA (antiproteinase-3)	GPA
p-ANCA (antimyeloperoxidase)	MPA/ Churg strauss	Atypical p-ANCA seen in IBD
Anti Jo1	Myositis	ILD
RF	RA, Sjogrens, Cryoglobulinaemia	Antibody to Ig hence many false positives
Anti CCP	RA	Positive in 1/3rd RF negative patients
Anti histones	Drug induced SLE	Also seen in Native Lupus
Cryoglobulins	Vasculitis, hep C, myeloma, SLE, RA	Type 2 seen in cryoglobulinemic vasculitis