Rheumatology

Rheumatological Diseases

Osteoarthritis

Introduction

  • Very common seen with increasing age
  • Affects the synovial joints with loss of cartilage
  • Commoner in whites and familial tendency
  • Strong heritability - polygenic

Joints affected

  • Hand, Knee
  • Hips, Spinal apophyseal joints

Aetiology

  • Not just "wear and tear" - there is destruction and loss of articular hyaline cartilage
  • There is sclerosis and cyst formation due to adjacent bone remodelling
  • Attempts at repair lead to osteophyte formation

Secondary OA may result from other causes

  • Trauma with previous fractures through the joint
  • Metabolic diseases, Haemochromatosis - check ferritin and Iron and transferrin saturation
  • Chondrocalcinosis, Acromegaly - Measure GH following OGTT
  • Ochronosis - see below
  • Systemic diseases : Haemophiliacs, Sickle cell disease, Joint damage, Rheumatoid arthritis, Gout, Seronegative arthropathies
  • Septic arthritis, Paget's disease, Avascular necrosis, Thiemann's disease
  • Osteochondrosis affecting the hands, Obesity, Previous fractures and trauma
  • Perthe's disease, Congenital dislocation of the hip

Clinical

  • Activities which worsen with activity and decrease on rest
  • Morning stiffness < 30 minutes
  • Age > 50
  • Crepitus on joint movement
  • Bony tenderness on examination
  • Bony enlargement on examination
  • No palpable warmth on examination
  • Hands : DIP and 1st MCP
  • Foot 1st MTP
  • Spine, hips and knees
  • Heberden's nodes at DIP
  • Bouchard's nodes at the IPJ
  • Knee - varus and valgus deformities +/- knee effusion
  • Baker's cyst behind knee

Investigations

  • ESR < 40 mm/hr
  • RF titre < 1:40
  • Radiology : Joint narrowing, sclerosis, osteophytes, localised osteoporosis, cyst formation
  • Arthroscopy may show cartilage destruction

Differentials

  • Age < 45 consider inflammatory arthritis, severe trauma, metabolic disease
  • Marked early morning stiffness > 1 hour - inflammatory arthritis
  • Unusual joints e.g. MCPs - Metabolic disease e.g. haemochromatosis
  • Multiple regional pains 'tender spots' - fibromyalgia
  • Joint locking or giving way - meniscal or ligamentous injury
  • Fever or systemic upset - consider joint sepsis
  • Warm and erythema - sepsis or crystals
  • Pain mainly at night - malignancy, osteonecrosis

Management

  • Rest and analgesia but careful exercise to maintain muscle bulk
  • Cardiovascular exercise, quadriceps strengthening
  • Weight loss to reduce body mass index
  • Heat therapy is useful, physiotherapy and OT
  • Correct use of walking stick can reduce hip loading by 1/5th
  • Paracetamol is first line agent but NSAIDs and weak Opiates may be needed
  • Glucosamine sulphate may be added
  • Topical NSAIDs or Capsaicin can help knee and had OA
  • Intra articular steroids can give approximately 4 to 6 weeks of pain relief. Sepsis is a very rare complication.
  • Surgery - joint replacement effective for Hip and Knee

Rheumatoid Arthritis

Introduction

  • Typically a chronic symmetrical deforming polyarthropathy involving large and small joints
  • Affects 1% of population and Females 3:1
  • The cardinal symptoms of RA are early morning stiffness > 60 mins
  • Duration of stiffness relates to disease activity

Aetiology

  • Increased HLA DR4+ve in over 60%
  • Increased Postpartum and increased with breast feeding
  • RF +ve have nodules

Pathology

  • The primary target of RA is the synovium - joints show synovitis and hyperplasia and pannus formation which leads to joint destruction
  • Synovial tissues proliferate in an uncontrolled fashion and this results in excess fluid production, destruction of cartilage, erosion of marginal bone, and damage to tendons and ligaments
  • Rheumatoid nodules Histology shows
    • Granulomas
    • Fibrinoid necrosis
    • Palisaded histiocyte
  • Joints affected - warm tender and some skin discolouration (not a red hot joint)
    • Proximal interphalangeal joints
    • Metacarpophalangeal joints
    • Wrists
    • Elbows
    • Knees
    • Metatarsophalangeal
    • Upper Cervical spine
  • Classical clinical joint deformities
    • Ulnar drift and ulnar deviation at the MCP joints
    • Boutonniere (button hole) with fixed flexion at PIP and extension at DIP
    • Swan Neck with flexion at DIP and hyperextension at PIP
    • Trigger finger finger locks on flexion and needs passively extended due to a narrowed tendon sheath with enlarged tendon
    • Z shaped deformity of the thumb - hyperextension at IP joints and flexion at MCP
    • Wasted intrinsic muscles of the hand
    • Palmar erythema, Nail bed infarcts, Subcutaneous nodules, Skin and muscle atrophy and extensor tendon rupture
    • Feet - subluxation of MTP joints means walking on heads of Metatarsals and pain and deformity
    • Damage to subtalar and ankle joint and development of flat feet due to rupture of the tibialis posterior tendon
    • Cervical - Care must be taken as patients are prone to atlantoaxial C1/2 subluxation. Caution with neck pain. Atlantoaxial dislocation (C1-C2) May be asymptomatic. It is a particular worry for anaesthesia and intubation. Preliminary full flexion and extension X-ray for patients undergoing intubation with severe RA.

    Clinical systemic

    • Symptoms should be present for more than 6 weeks
    • Systemic
      • Fatigue
      • Low grade fever
      • Weight loss
    • Dryness of mucous membranes
      • Mouth, Genital, Eyes
    • Haematology
      • Splenomegaly
      • Lymph node enlargement
      • Anaemia, splenomegaly, eosinophilia, thrombocytosis
      • Increased risk of infection
    • Lung
      • Caplan's syndrome (below)
      • Pulmonary nodules
      • Fibrosing alveolitis
      • pleural effusion (exudates with low glucose)
      • Bronchiolitis obliterans
    • Cardiac
      • endocarditis
      • pericarditis
      • myocarditis
      • rheumatoid nodules
      • pericardial effusion
      • coronary arteritis
      • aortitis
    • Dermatological
      • skin ulcers
      • pyoderma gangrenosum
    • CNS
      • Cervical cord compression
      • peripheral neuropathy
      • mononeuritis multiplex
      • compression neuropathies e.g. carpal tunnel syndrome, ulnar, lateral popliteal
    • Eyes
      • Scleritis (red painful eye with threat to sight. Steroids)
      • episcleritis
      • Scleromalacia (bilateral painless blue thinning)
      • keratoconjunctivitis sicca
      • Corneal melting - red painful eye serious needing urgent immunosuppression
    • Renal
      • Amyloidosis - nephrotic syndrome
    • Felty's syndrome seen in < 1%
      • RF +ve
      • Splenomegaly
      • Neutropenia
    • Caplan's syndrome
      • RA in Coal miners with pneumoconiosis

    Investigations

    FBC

    • Normochromic normocytic anaemia and Raised platelets,
    • Elevated ESR and Elevated CRP - WCC may be elevated or depressed in Felty's syndrome with splenomegaly

    U&E and urinalysis to detect renal disease

    LFT's to detect liver disease or drug side effects

    Rheumatoid factor is an IgM against the Fc portion of IgG1 and a titre greater than 1 in 320 is significant and related to disease activity, presence of rheumatoid nodules and extra-articular complications. RF is found in 80% of patients. Presence of RF however does point to increased frequency of certain complications.

    Anti cyclic citrullinated peptide is a sensitive and specific test for RA. Anti CCP in 70% but is highly specific. Anti CCP (Antibodies to cyclic citrullated peptides may be found) antibodies have both high sensitivity and specificity for RA and appear early in disease and may actually be part of the disease process

    X-Ray changes

    • Early on (< 6 months)
      • Soft tissue swelling
      • Periarticular demineralisation/osteoporosis
    • Later
      • Joint margin narrowing and erosions
    • Very late
      • atlantoaxial C1/2 subluxation
    • Joint aspiration - Increased WCC and protein
    • Atlantoaxial subluxation - Lateral X-rays in flexion and extension and MRI Syndromes
  • 1987 Criteria for the Classification of Acute Arthritis of Rheumatoid Arthritis Criterion Definition. A patient shall be said to have rheumatoid arthritis if he/she has satisfied at least 4 or these 7 criteria. Criteria 1 through 4 must have been present for at least 6 weeks. Patients with 2 clinical diagnoses are not excluded. Designation as classic, definite, or probable rheumatoid arthritis is not to be made.
  • Diagnostic Criteria
    • 1. Morning stiffness - Morning stiffness in and around the joints, lasting at least 1 hour before maximal improvement
    • 2. Arthritis of 3 or more joint areas - At least 3 joint areas simultaneously have had soft tissue swelling or fluid (not bony overgrowth alone) observed by a physician. The 14 possible areas are right or left PIP, MCP, wrist, elbow, knee, ankle, and MTP joints
    • 3. Arthritis of hand joints - At least 1 area swollen (as defined above) in a wrist, MCP, or PIP joint
    • 4. Symmetric arthritis - Simultaneous involvement of the same joint areas (as defined in 2) on both sides of the body (bilateral involvement of PIPs, MCPs, or MTPs is acceptable without absolute symmetry)
    • 5. Rheumatoid nodules - Subcutaneous nodules, over bony prominences, or extensor surfaces, or in juxta-articular regions, observed by a physician
    • 6. Serum rheumatoid factor - Demonstration of abnormal amounts of serum rheumatoid factor by any method for which the result has been positive in <5% of normal control subjects
    • 7. Radiographic changes - Radiographic changes typical of rheumatoid arthritis on postero-anterior hand and wrist radiographs, which must include erosions or unequivocal bony decalcification localised in or most marked adjacent to the involved joints (osteoarthritis changes alone do not qualify)
  • Baseline assessments
    • Functional status
    • Extent and degree of synovitis
    • Extra-articular disease
    • Radiographic damage
    • FBC,ESR,U&E,LFTs,RF,Urinalysis

    Management

    • The aim of treatment is to reduce and prevent synovitis and damage can occur early in disease so one must consider Rheumatology referral and initiation of DMARDs early.
    • Delays in starting appropriate therapy can cause long term differences in outcome.
    • Non medical
      • Rest, hot baths, passive movements and targeted anti inflammatory therapy
      • Physiotherapy and OT are important in maintaining activities of daily living (ADLs) and splinting and protecting joints
      • Home adaptations.
    • Medical
      • NSAIDs/paracetamol
        • reduce inflammation and pain and stiffness
        • Do not alter the course of the disease
      • DMARDs are Disease modifying anti rheumatic drugs (DMARDS)
        • Alter course of disease. Steroids, methotrexate, sulfasalazine and hydroxychloroquine and others below but not NSAIDs.
        • They should be started early to improve outcome.
        • Side effects shared by many DMARDs are Skin rash, mouth ulcers and Low Neutrophils, Low platelets and proteinuria Drugs (check all doses with BNF)
          • Sulfasalazine 1 g bd or tds benefit in 6-12 weeks
          • Methotrexate orally (or injectable) 7.5-30 mg weekly benefit in 6-12 weeks
          • Leflunomide 10-20 mg od orally
          • Prednisolone 7.5 mg od for 2 years can reduce radiological progression over 2 years
          • D-Penicillamine 250-750 mg/day orally
    • Surgery
      • Synovectomy, excision of distal ulnar head
      • Joint replacement are useful in preserving function and pain control and improving quality of life
    • Shared care
      • The GP and Specialist nurse often plays a pivotal role in management led by the rheumatologist
      • Patient education and support networks
  • Poorer Prognosis
    • Systemic disease
    • Insidious onset
    • RF titre > 1/512
    • Persistent activity > 12 months
    • Early bone erosions
    • White females
    • More than 20 involved joints
    • Rheumatoid nodules
  • DMARDS

    Name Action Side effects
    NSAIDs Useful anti-inflammatory and analgesics but do not alter disease progress
    Peptic ulcer disease
    Renal disease
    Fluid retention
    Corticosteroids (glucocorticoids) Inhibitory effects on a broad range of specific immune responses mediated by T cells and B cells as well as potent suppressive effects on the effector functions of monocytes and neutrophils Multiple side effects
    Methotrexate
  • Inhibits Dihydrofolate reductase
  • Given weekly at 5-25 mg per week
  • Folate reduces side effects without altering efficacy
  • raised transaminases, rash, CXR before treatment, bone marrow suppression and acute pneumonitis. Nausea, mouth ulcers, diarrhoea, Low Neutrophils, Low platelets, Pulmonary fibrosis, Deranged LFT's, Abnormal renal function. Given weekly orally
    Sulfasalazine Inhibits prostaglandin synthesis Bone marrow suppression and hepatitis and oligospermia. Check initial, fortnightly then 4 monthly FBC and LFT's as it potentially causes neutropenia, low platelets and deranged LFT's
    Leflunomide Inhibits pyrimidine synthesis Diarrhoea, raised BP, Hypertension, Abnormal LFT's
    D-Penicillamine Depresses circulating IgM rheumatoid factor, depresses T-cell but not B-cell activity metallic taste, skin rashes, proteinuria
    Hydroxychloroquine Inhibits neutrophils and eosinophil motility and function and complement-dependent antigen-antibody reactions Anti malarial, ocular toxicity more so with chloroquine. Retinopathy is the most serious side-effect but takes 5-6 years to develop
    Cyclophosphamide reserved to treat vasculitis
    Ciclosporin Targets calcineurin and thereby inhibit the production of interleukin-2 by activated T-lymphocytes. Gingival hyperplasia, tremor, hirsutism, renal impairment
    Azathioprine Similar to mercaptopurine and blocks purine metabolism and may inhibit synthesis of DNA, RNA, and proteins; may also interfere with cellular metabolism and inhibit mitosis. Bone marrow suppression or raised transaminases
    Gold therapy Possibly dissociates antigenic peptides from HLA-class II antigen presenting molecules Rashes, proteinuria, blood dyscrasia
    Etanercept A soluble p75 TNF receptor fusion protein that consists of two p75 TNF receptors bound to the Fc portion of IgG. Injection site reaction
    Infliximab anti-TNFa agents Always screen for TB
    Adalimumad anti-TNFa agents Always screen for TB
    Anakinra Human recombinant IL-1 receptor antagonist
    Tacrolimus Targets calcineurin and thereby inhibit the production of interleukin-2 by activated T-lymphocytes
    Mycophenolate mofetil Blocks the synthesis of purines

    Polymyalgia Rheumatica

    Introduction

    • A vasculitis affecting mainly extracranial arteries

      Causes systemic non specific symptoms

    • Related to Temporal arteritis which can cause blindness

    Aetiology

    • Possibly an immune response to an antigen of some sort
    • There is a Th1 cell mediated immune response with elevated IL-6
    • HLA DR4 association

    Clinical

    • Often vague e.g. Generalised aches, pains, Depression
    • Severe, symmetrical shoulder stiffness
    • Proximal weakness
    • Notable rapid response to steroids

    Investigations

    • Normocytic normochromic anaemia
    • ESR almost always > 50
    • Elevated CRP
    • Elevated ALP in 30%

    Management

    • Prednisolone 15 mg stat
    • Consider bone protection
    • Reduce dose over 18 months

    Psoriatic arthritis

    Introduction

    • A severe form of psoriatic arthritis is seen in HIV positive patients
    • Inflammatory arthritis associated with psoriasis. Affects women and men equally
    • The psoriatic rash may predate or follow the onset of the arthritis

    Clinical

    • Classical rash - scaling erythematous plaques on scalp and extensor surfaces also periumbilical / perineal
    • Nail pitting and onycholysis (lifting of nail from nail bed) and oil drop sign due to discolouration
    • Dactylitis - inflammation of the whole finger, red swollen tender "sausage digit"
    • Pulmonary fibrosis, Aortic regurgitation
    • Conjunctivitis and anterior uveitis usually in those with spinal involvement
    • Typically five joint involvement patterns
      • Distal interphalangeal form with nail changes
      • Asymmetrical mono/oligo arthritis - like a spondyloarthropathy
      • Symmetrical polyarticular arthritis - like rheumatoid
      • Arthritis mutilans (rare) with large and small joint destruction
      • Axial - sacroiliitis ( like ankylosing spondylitis)

    Investigations

    • FBC - anaemia
    • Elevated ESR, CRP
    • Rheumatoid factor negative
    • ANA negative
    • Radiology of hand - "Pencil in cup" appearance as proximal phalanx sits into distal phalanx

    Management

    • Analgesia with NSAIDs
    • Sulfasalazine, Methotrexate
    • Biological Anti-TNF agents
    • Splinting, Joint surgery and replacement

    Reactive arthritis

    Introduction

    • Previously known as Reiter's syndrome
    • Arthritis that occurs following an infectious disease either enteric or chlamydia
    • However the microorganism cannot be found in the joint
    • Usually have additional extraarticular features
    • Implicated pathogens - Salmonella, Yersinia, Campylobacter, Shigella, Chlamydia trachomatis

    Aetiology

    • Usually post infectious with the following clinical findings which resemble features seen in some of the spondyloarthropathies

    Clinical

    • Conjunctivitis, Uveitis (Like Ankylosing spondylitis)
    • Oral ulcers, Circinate balanitis, Keratoderma Blennorrhagica
    • Nail dystrophy (psoriasis)
    • Erythema nodosum (inflammatory bowel disease)
    • Aortitis (Ankylosing spondylitis) and conduction defects

    Investigations

    • Elevated CRP or ESR or WCC non specific
    • Stool cultures may identify a triggering pathogen
    • Screening for Chlamydia trachomatis
    • Rheumatoid factor negative

    Management

    • NSAIDs are the main treatment with analgesic and anti inflammatory properties
    • Sulfasalazine may be useful
    • Intra articular steroid injections may be tried
    • Anti TNF agents have been tried in those non responsive to other therapies
    • Antibiotic therapies for active chlamydial infection

    Relapsing polychondritis

    Introduction

    • Immune condition causing inflammation in cartilage structures with cartilage destruction
    • Antibodies to Type 2 Collagen are found which may be a clue to the underlying pathophysiology.
    • Commonest in middle age but other ages are not excluded including elderly and children.
    • Other diseases are associated in 30% of cases e.g. Behçet's syndrome, Inflammatory bowel disease, Systemic vasculitis, Rheumatoid arthritis, SLE, SS, PBC, Myelodysplasia.

    Clinical

    • Systemic symptoms of fever, malaise and lethargy are seen.
    • Auricular chondritis is the commonest presentation.
    • Destruction of cartilage involving the nasal, laryngeal, bronchial tract and pinna of the ear.
    • Heart valve may also be affected most commonly with AR or MR.
    • The eye is affected too - Episcleritis, Scleritis, Uveitis
    • Hearing loss also occurs as well as saddle nose
    • Arthritis and pulmonary disease also seen.

    Investigations

    • The ESR and CRP are elevated.
    • Mild WCC rise and normochromic normocytic anaemia.
    • Positive pANCA or cANCA in some cases.
    • Antibodies to Type 2 Collagen
  • Differential
    • Wegener's Granulomatosis.

    Management

    • Treatment is with high dose Prednisolone, Dapsone and Immunosuppression
  • Septic Arthritis

    Introduction

    • Septic arthritis is a medical/orthopaedic emergency
    • Delayed diagnosis can lead to significant joint damage at any age
    • The diagnosis must be considered whenever painful joint dysfunction is present
  • Infectious agents
    • Staphylococcus aureus is the commonest cause in all age groups
    • Streptococci
    • Pseudomonas
    • Pneumococci
    • Haemophilus Influenzae type b has fallen with vaccination
    • Candida albicans

    Aetiology

    • The infection is spread by blood perhaps from another infective source or skin
    • Relatively common in infancy and childhood and must not be missed
  • Risk factors in adults
    • Age greater than 80 years
    • Diabetes mellitus
    • Rheumatoid arthritis
    • Prosthetic joint
    • Recent joint surgery
    • Skin infection

    Investigations

    • Joint aspiration - Grey/white pus, The WBC count > 50,000 / ml with 80% neutrophils and Positive gram stain.
    • X-Ray - exclude a fracture
    • CT, MRI, Radionuclide scan, USS (except to show effusion) are entirely unhelpful
    • If a haemarthrosis is found always consider a bleeding disorder - haemophilia
  • Differential in a child
    • Transient synovitis - ? viral less raised inflammatory markers
    • Still's disease
    • Rheumatic fever- flitting
    • Lyme disease
    • Perthes disease
    • Differential in adult
    • Gout - crystals of monosodium urate
    • Pseudogout - crystals of calcium pyrophosphate dihydrate
    • Rheumatoid arthritis - erythema unusual
    • Reactive arthritis

    Management

    • Treat for 6 weeks - 1 st 2 weeks IV
    • Flucloxacillin 1-2 g 6 hourly iv + Oral Fusidic acid 500 mg 8 hourly
    • 3rd generation cephalosporins e.g. Ceftazidime (1 to 2 g IV every eight hours)
    • Orthopaedic involvement - needle aspiration, joint wash out
    • Immobilise acutely and then mobilise early
  • Still's disease

    Introduction

    • It is a systemic form of Juvenile Idiopathic arthritis

    Aetiology

    • Seen most commonly in children under the age of 5
    • Systemic illness affecting more than just joints.
    • Seen equally in males and female but very rarely seen in Adults

    Clinical

    • A high spiking pyrexia > 39 C usually appearing late evening
    • A widespread pink or salmon coloured maculopapular rash
    • Myocarditis, Pericarditis and Dry eyes and mouth
    • Pleurisy and Hepatosplenomegaly

    Investigations

    • Raised CRP and ESR
    • Markedly elevated concentrations of ferritin
    • Negative autoantibodies
    • A positive ANA > 1:100 or Rheumatoid factor > 1:80 excludes the diagnosis
    • Raised neutrophils and platelets

    Management

    • NSAIDs e.g. indomethacin (NO ASPIRIN IN CHILDREN)
    • Steroids for myocarditis or tamponade
    • Anti-tumour necrosis factor drugs may have a role
    • Methotrexate and other steroid sparing agents have been used
  • Aspirin should be avoided in all those under 12 because of the risk of Reye's syndrome

  • Systemic Lupus Erythematosus

    Introduction

    • Common chronic multisystem connective tissue disorder
    • Affects young females (F:M 9:1) Blacks > Whites (3:1)
    • Circulating Autoantibodies detectable.
    • Drugs can cause a lupus like syndrome (see Drug Induced lupus)

    Aetiology

    • Genetic : Identical twins show a 25% concordance
    • Autoantibodies are found to intracellular and nuclear components - a Autoimmune process
    • Hormones : Commoner in females and Klinefelter's syndrome ?oestrogen
    • Apoptosis: Studies suggest a defect in the apoptosis gene
  • Pathology
    • Immune complex deposition with damage
    • Other immunological dysfunction
    • Haematoxylin bodies seen in connective tissue. When ingested by neutrophils form LE cells
    • Fibrinoid necrosis is found in vessel walls
    • Onion skin lesions of splenic arteries
  • American College of Rheumatology (ACR) Criteria 4 out of 11 criteria is required to make the diagnosis
    • Malar rash usually spares nasolabial folds
    • Discoid rash
      • scaling
      • follicular plugging
    • Photosensitivity
    • Oral ulcers or nasal
    • Arthritis - non erosive usually tenderness, swelling, effusion
    • Serositis - pleuritis or pericarditis
    • Renal disorder
      • 3+ proteinuria or
      • Proteinuria > 0.5 g /24 hrs
    • CNS involvement - seizures or psychosis
    • Haematological
      • Thrombocytopenia < 100 x 10^9
      • Haemolytic anaemia
      • Leucopenia < 4.0 × 10^9/L on 2+ or more occasions
      • Lymphopenia < 1.5 × 10^9/L on 2+ or more occasions, )
    • Immunological
      • Raised anti native DNA antibody binding
      • Anti-Sm antibody
      • positive Anticardiolipin
      • Antinuclear antibody is raised titre seen in 95%

    Clinical

    • Systemic: Tiredness, Malaise, Fatigue, Fever
    • Dermatology: Classical facial butterfly rash may be seen. There is redness and erythema over cheeks and bridge of nose. Photosensitive skin rashes may be seen. Urticaria. Disease may be in part to immune complex deposition within dermoepidermal junctions. Discoid lupus with follicular plugging and hyperkeratosis. Scarring alopecia can be disfiguring. Livedo reticularis.
    • Secondary Raynaud's syndrome with hands turning white, blue, red and painful on exposure to cold.
    • Neurological disease may be partly due to APL with strokes etc or due to SLE with more neuropsychiatric disturbances such as acute psychotic episodes. Other manifestations include focal epilepsy, migrainous attacks, cerebellar signs and ataxia, aseptic meningitis and cranial nerve palsies. A polyneuropathy may be seen.
    • Renal : Lupus nephritis is the most serious form with a reduced life expectancy. SLE can cause all types of renal disease including nephrotic and nephritic syndrome. May cause interstitial nephritis. Mild and benign disease to rapidly progressive glomerulonephritis. Interestingly patients with ESRF their SLE seems to be less severe possibly as ESRF is an immunosuppressed state. Patients with SLE do relatively well with Dialysis and renal transplantation as the immunosuppression is good for the SLE too.
    • Haematology : Normochromic and normocytic anaemia, Low platelets, Low WCC, Raised ESR
    • Cardiac : Pericarditis and effusions may be seen. Myocarditis and aortic valve involvement. Risk of thrombosis in arterial and venous systems and vasculitis. Women appear to be at increased risk of IHD and premature atherosclerosis. Libman-Sacks endocarditis.
    • Pulmonary : Pleurisy and pleural exudative effusions. A restrictive lung defect rarely seen - "shrinking lung syndrome". Pneumonitis, pulmonary vasculitis. Secondary pulmonary hypertension also seen.
    • Joints :Symmetrical arthritis and arthralgia and generalised aches and even some morning stiffness. Jaccoud's arthropathy and generalised joint deformity with SLE is rare. Polyarthritis.

    Investigations

    • FBC - anaemia. Anaemic of chronic disease and rarely haemolytic.
    • Classically the ESR is raised but the CRP is normal
    • A raised CRP suggests that an additional process is going on e.g. infection
    • Antinuclear antibodies positive in 99%
    • Anti - dsDNA is found in approximately 50% and more specific
    • Low complement C3 and C4 levels
    • Elevated APTT suggests antiphospholipid syndrome
    • Rheumatoid factor 25%
    • Anaemia - normocytic normochromic may be seen
    • A low platelet count is seen
    • Antiphospholipid antibody should be checked especially in those with a history of fetal loss or thrombotic events
  • Renal disease
    • I : Minimal mesangial lupus nephritis
    • II :Mesangial proliferative lupus nephritis
    • III: Focal lupus nephritis
    • IV: Diffuse segmental or global lupus nephritis
    • V : Membranous lupus nephritis
    • VI Advanced sclerosing lupus nephritis

    Management

    • Low Dose steroid creams may be used for the skin complications
    • Simple analgesia and NSAIDs may be used for arthralgia and mild disease
    • Hydroxychloroquine is used for mild disease involving skin and joints.
    • Steroids may be used to treat transient rashes and synovitis or pleurisy keeping doses low and short. Higher dose steroids reserved to treat renal/neurological lesions. The typical steroid sparing agents such as azathioprine may also have a role.
    • Warfarin may be required to reduce thrombotic complications with Antiphospholipid syndrome
  • Gout

    Introduction

    • Acute joint pain in older male (M:F 10:1)
    • May result long term in renal failure
    • In young always consider enzyme defect
    • In elderly always consider drugs e.g. thiazides
    • NB. Urate levels may be normal in acute attack

    Aetiology

    • Deposition of monosodium urate crystals - strongly negative birefringent needle shaped crystals
    • Typically affects the first metatarsophalangeal joint - "podagra"
    • May be caused by diuretic therapy and low dose aspirin and cyclosporin
    • Other associations - Obesity, Alcohol intake, Hypertension

    Clinical

    • Attacks tend to occur in the early morning with severe localised pain, erythema and swelling
    • Chronic gout leads to formation of tophi
    • Urate crystal deposits usually on extensor surfaces of fingers, hands and elbows
    • 20% have renal colic due to urate stones in preceding years
    • The diuretic induced gout form occurs mainly in elderly rather than middle aged with early formation of tophi and lesser degree of acute attacks
    • Chronic Tophaceous gout can lead to a urate nephropathy and chronic kidney disease if untreated
    • Confirm hyperuricaemia on 2 fasting samples and can be falsely low during an acute attack

    Investigations

    • FBC, U&E (renal impairment) CRP elevated
    • Urate levels unhelpful - may be up down or normal
    • Joint aspiration needed to exclude septic arthritis
    • Microscopy - strongly negative birefringent needle shaped crystals
    • Radiology

    Management of acute attack of Gout

    • Ask yourself is this gout or a septic arthritis
    • NSAIDs if tolerated e.g. naproxen. Consider gastro protection with PPI
    • Oral colchicine for those who cannot take NSAIDs
    • A short course of steroids may be used in some cases either orally, IV or IM
    • Allopurinol is avoided for 3-4 weeks and then started with either colchicine or NSAID cover
  • Indications for commencing Allopurinol
    • Repeated acute attacks > 2 per year
    • Chronic Tophaceous gout
    • Renal disease/Stones
    • High uric acid
  • Prevention of Gout and its complications
    • Indicated in those > 2 attacks per year
    • Identify and treat any underlying cause - consider whether can stop low dose aspirin or thiazide, reduce alcohol intake and weight loss
    • Allopurinol - xanthine oxidase inhibitor however can provoke acute attack so should be combined with NSAID or low dose colchicine 0.5 mg bd about 3-4 weeks after an acute attack
    • Urinary alkalinisation and hydration
    • Losartan the ATII blocker is uricosuric and could be useful in hypertensive patients
  • Pseudogout (chondrocalcinosis)

    Introduction

    • Arthritis usually seen in those over 50 years of age unless there is an underlying predisposition
    • Can mimic gout, rheumatoid arthritis and osteoarthritis

    Aetiology

    • There is calcium pyrophosphate dihydrate (CPPD) crystal deposition in the cartilage

    Clinical

    • Acute red hot joint
    • Commonly involves the knee, haemarthrosis
  • Associations (common MRCP exam/Boards questions)
    • Hyperparathyroidism
    • Hereditary Haemochromatosis
    • Hypomagnesaemia
    • Myxoedematous hypothyroidism
    • Ochronosis
    • Wilson's disease
    • Dialysis-dependent renal failure
    • Acromegaly

    Investigations

    • Polarized light microscopy is essential to confirm the presence of positively birefringent Calcium pyrophosphate crystals

    Management

    • Treatment is joint aspiration, rest and analgesia
    • Rehabilitation
  • Sjögren?s syndrome

    • Notes
      • Primary Sjögren?s syndrome (PSS) autoimmune disease seen in middle aged older lady and 50% are RF positive
      • Secondary Sjogren's syndrome where the symptoms come on after the primary disease such as Rheumatoid arthritis SLE, Scleroderma and PBC have been present for a period. 95% RF positive
    • Primary Sjogren's syndrome
      • Autoimmune disease which presents with sicca symptoms dry mouth and dry eyes

      Clinical

      • Dry Mouth - dental caries, parotitis
      • Dry and gritty eyes - >Positive schirmer test
      • Vaginal dryness - dyspareunia
      • Arthritis, Vasculitis, Raynaud's phenomenon
      • Fatigue, Myalgia, Arthralgia

      Investigations

      • Typically RF and ANA positive as well as Anti-Ro/LA is typical (SS-A and SS-B)
      • Schirmer's test, performed without anaesthesia ( ?5 mm in 5 minutes )
      • Rose bengal score or other ocular dye score
      • A positive labial gland biopsy can aid the diagnosis and shows lymphocytic infiltration of the exocrine glands

      Management

      • Artificial tears, eye lubricant ointments
      • Pilocarpine
      • Cyclosporin eyedrops recently approved in US
      • Drinking plenty
      • Systemic disease - Hydroxychloroquine, Methotrexate and steroids for systemic problems

    Raynauds' Phenomenom

    Introduction

    • Spasm of distal arteries to the fingers and toes
    • May be primary or be secondary to another disease

    Clinical

    • Pallor with vasoconstriction
    • Blue due to Cyanosis
    • Red with reperfusion and hyperaemia - painful

    Management

  • Non pharmacological
    • Keep warm - gloves - central body core warmth and not just peripheries
    • Stop smoking and avoid sympathomimetics (cold remedies) and beta blockers
  • Pharmacological
    • Calcium channel blockers - acutely short acting oral nifedipine qds or slow release or long acting preparations of nifedipine or amlodipine. Most patients tolerate these well.
    • Nitrates would probably be second line but there are many new medications being assessed
    • Ketanserin, a selective antagonist of the S2-serotonergic receptor
    • Angiotensin converting enzyme [ACE] inhibitor or ARB2 - reduces angiotensin II
    • Infusion of CGRP has been evaluated as possible therapy
    • Sildenafil and other phosphodiesterase inhibitors
    • Prazosin has been reported to improve RP
    • Fluoxetine - SSRI
    • Infusions of Prostacyclin (PGI2)
    • Lumbar Sympathectomy for lower limb symptoms
  • Ankylosing spondyltis

    Introduction

    • Rheumatoid factor negative lower back pain and progressive stiffness
    • Age 15-40 years affects predominantly Males (M:F 4:1)
  • Pathology
    • There is gradual fusion of the spine (ankylosis)
    • Restriction of movement in three planes
    • There is also deterioration of chest expansion and inflammatory back pain

    Aetiology

    • Strong linkage with HLA B27 in over 90% of cases
    • Suggested infectious component or trigger - e.g. Klebsiella

    Clinical

    • Loss of lumbar lordosis and reduced spinal flexion (Schober test)
    • Eventually kyphosis with question mark posture
    • Usually young adults with Low back pain which improves with exercise but not with rest (spondylitis)
    • Morning stiffness > 1 hour
    • Alternating Buttock pain suggests sacroiliitis
    • Cardiac - Aortic Regurgitation and Conduction defects
    • Pulmonary - Apical fibrosis and restrictive lung pattern
    • Spinal - Fractures and Cauda equina lesion and Cord compression
    • Spinal rigidity makes them more prone to spinal fractures
    • Eye - iritis (Acute anterior uveitis is the commonest extra-articular complication)
    • Rarely a peripheral arthritis
    • Plantar fasciitis and achilles tendonitis
    • Secondary amyloidosis (AA) is rare
    • Cauda equina syndrome is rare
    • Aide-Memoire - the 9 A's
      • Ankylosis of spine
      • Acute anterior uveitis
      • Amyloidosis
      • Aortic incompetence
      • Aortitis
      • AV Block
      • Apical fibrosis
      • Achilles tendonitis
      • Anti-TNF alpha therapy
  • Formal Examination to demonstrate restricted spinal movements
    • There is limited flexion and extension as well as lateral flexion and rotation. These can be assessed clinically
    • Modified Schober test - Ventral: with the patient standing upright, a line is drawn across the lumbar spine connecting the two posterior superior iliac spines. Marks are made in the midline over the spine 10 cm cranial and 5 cm caudal to this horizontal line. The patient then bends with legs straight and the distance is measured again. It normally increases by more than 3 cm.
    • Lateral: the distance between the longest finger tip and the floor is measured in the upright position. This is repeated when the patient tries to flex laterally towards the ground as far as possible, normally moving by more than 10 cm.
    • Thoracic excursion. The circumference of the thorax is measured in the fourth intercostal space after maximal inspiration and expiration. It normally alters by more than 3 cm.
    • Occiput to wall distance. In the upright position the patient leans backwards against a wall, and should normally be able to touch the wall with their occiput.
    • Chin to sternum distance. The chin is maximally bent towards the sternum, and should normally be able to touch it.
    • Cervical rotation. The head is rotated to the left and right sides with the angles of rotation measured (normally more than 50°).
    • Intermalleolar distance. The patient tries to stand with their feet together: the malleoli should normally touch.

    Investigations

    • FBC - anaemia due to NSAID or AOC
    • Elevated ESR / CRP
    • RF and other autoantibodies classically negative
    • CXR - apical fibrosis
    • ECG - conduction defects
    • Lung function tests - restrictive pattern
    • HLA-typing not needed for diagnosis
    • Echocardiogram - if aortic regurgitation suspected
    • Radiology
    • AP and lateral of spine can show Bamboo spine - due to fusion of syndesmophyte which is a bony outgrowth that grows cranially from the ligament attachment point of the vertebra which can become squared below to fuse into the vertebrae above. In later stages there is calcification of the anterior and lateral spinal ligaments and formation of a "bamboo" spine
    • Sacroiliac joints - blurring of the joint margin, later erosions, sclerosis and fusion at the sacroiliac joint
    • Differential of sacroiliitis - Ankylosing spondylitis, Reiter's syndrome, Enteropathic arthropathy (with inflammatory bowel disease, Psoriatic arthropathy

    Management

    • Physical therapy and regular exercises to improve back flexibility
    • NSAIDs - can reduce symptoms
    • Sulphasalazine is a useful 2nd line agent
    • Intra-articular steroids can be considered for flare ups
    • Other Disease modifying agents - Sulphasalazine, Methotrexate (?) Gold (?)
    • Systemic steroids
    • New promising treatments - Anti TNF alpha therapy with etanercerpt
    • Thalidomide - may have a use