Buku Medicine

Acutely swollen joint

General principles

Septic arthritis is rare (incidence roughly 7 per 100,000) but should always be considered in patients presenting with an acutely swollen joint. It can be life-threatening (case fatality rate 11%) and needs to be assessed and treated as an emergency.

History and examination

Patients with a short history of hot, swollen painful joint should be investigated to exclude septic arthritis

Differential diagnosis

Septic arthritis:
- Signs of infection – fever (not always present), systemically unwell, marked restriction of range of joint movement
- Immunosuppression, pre-existing joint disease (as risk factors)
- Other site of active infection e.g cellulitis, ulcers as sources of haematogenous or direct seeding
Reactive arthritis:
- History of gastroenteritis, urethritis
- Ask specifically about possible sexually transmitted infections
Haemarthrosis:
- Recent trauma, anticoagulation
Gout:
- 1st MTPJ involvement - almost always due to gout
- Previous episodes of gout, renal impairment, alcohol excess
Pseudogout:
- Elderly, usually affects joints with pre-existing osteoarthritis
- Particularly affects wrists and knees
Pattern of joint involvement
- >1 joint involved – less likely to be septic
- Gout crystals form in cold so tends to affect peripheral joints - feet, ankles, wrists and knees

Specific considerations

Immunocompromised - can present atypically without fever or systemic upset

Investigations

Do not delay referral for investigations if clinical suspicion of septic arthritis. If suspected needs urgent assessment in secondary care for aspiration +/- antibiotics:
- Assess for sign of sepsis and follow sepsis guidelines for investigations
- Blood cultures critical
- Aspirate joint if trained and able to do so – call orthopaedics or rheumatology if needed. Aim to aspirate to dryness.
- Follow local microbiology guidelines and start antibiotics
- DO NOT attempt to aspirate a prosthetic joint – contact orthopaedics as this will need to be done in theatre

Blood tests:
- FBC, U&E, CRP, urate, INR if on warfarin
- Blood cultures
XR of affected joint ?trauma ?chondrocalcinosis
Depending on the situation consider:
- Urine/stool cultures
- Referral for STI screening including HIV in reactive arthritis
- Investigations for inflammatory arthritis (rheumatoid factor, anti-CCP antibodies) but note very unusual for rheumatoid arthritis to present acutely as monoarthritis
- Investigate other ports of infection:
  - Skin swab, echo

Differential diagnosis:

Reactive arthritis

Uncommon cause of acute arthritis. Infective precipitant can be difficult to identify.

Classical triad of oligoarthritis, uveitis and non-gonococcal urethritis not always present
May have history of recent or concurrent infection, particularly GI (gastroenteritis) or GU (urethritis, cervicitis)
Commonly presents with large joint mono/oligoarthritis affecting knees and ankles.
Ask about other involved areas: heel pain (Achilles tendonitis), sausage toes
Ask about eye involvement (conjunctivitis or uveitis) - consider referral to ophthalmology if so
Ask about back and buttock pain (sacroiliitis or spondyloarthritis)
Check for skin, oral and genital lesions
Investigations:
- Joint aspiration
- HLA-B27 (can help predict development of recurrent disease)
Treatment:
- Involve rheumatology - would generally be diagnosed and assessed in secondary care but can consider NSAIDs for acute symptoms.
- Often benefit from intra-articular or oral steroids
- Can resolve without recurrence but up to half of patients go on to have chronic reactive arthritis requiring long term treatment.

Gout

See gout module

Pseudogout

Common cause of acute monoarthritis. Like gout, it is episodic and can be severe. Generally affects the older population in joints with pre-existing osteoarthritis. Due to calcium pyrophosphate dihydrate (CPPD) crystals deposited in the joint, hence it is sometimes called CPPD disease or CPPD arthropathy

Commonly affects large joints (knee, wrist, ankle, elbow) but in contrast to gout can affect central joints (shoulder, hip)
Often a monoarthritis but can affect multiple joints
Can be triggered by illness, surgery or local trauma
Investigations
- Joint aspiration - specifically request crystal microscopy alongside Gram stain and culture and sensitivity
- X-rays - can see chondrocalcinosis (thin rim of calcified material in articular cartilage). Note that while this supports the diagnosis it is not specific (asymptomatic chondrocalcinosis is common, particularly in osteoarthritis)
Treatment
- Rest, ice, splinting - it will settle without treatment
- For symptomatic relief:
  - NSAIDS - use with caution in this patient population OR
  - Colchicine 250-500µg BD (advise patients this may cause diarrhoea and to reduce dose or stop if this occurs) until flare settles OR
  - Corticosteroids – avoid whilst co-existing infection. A course of prednisolone 15-20mg, reducing down over 2-4 weeks can be very effective
  - Intra-articular steroid injection
- Unlike gout, there are no long term treatments to prevent episodes of pseudogout. However, in problematic recurrent cases prophylaxis with colchicine or prednisolone have been used in similar doses and regimes as for gout.
When to refer
- If concerned about septic arthritis
- No role for rheumatology in long-term follow up as no preventative treatment, but can be involved for acute flares (for example - injection)
- Patients who are already in hospital for other medical problems and develop pseudogout often benefit from a rheumatology review, particularly when there is underlying infection precluding the use of corticosteroids

Haemarthrosis:

Bleeding into the joint is rare without a contributing cause such as haemophilia (or other genetic bleeding predisposition) or anticoagulation use.

Investigations:
- Check coagulation screen or INR and platelets
- Joint aspiration is generally safe if therapeutic INR and platelets > 50 if needed for diagnosis. If known bleeding disorder and haemarthrosis is probable diagnosis, aspiration can be avoided to reduce risk of introducing infection (unless concern of co-existing septic joint)
- Investigate further and consider involving haematology if no identified precipitant

New inflammatory arthritis

It is unlikely for inflammatory arthritis to present with an acute monoarthritis so consider alternative diagnoses. More likely in seronegative inflammatory arthritis so ask about personal or family history of:
- Psoriasis
- Inflammatory bowel disease
- Uveitis
See section on inflammatory arthritis

References

Rutherford AI, Subesinghe S, Bharucha T, Ibrahim F, Kleymann A, Galloway JB. A population study of the reported incidence of native joint septic arthritis in the United Kingdom between 1998 and 2013. Rheumatology (Oxford). 2016 Dec;55(12):2176-2180. doi: 10.1093/rheumatology/kew323. Epub 2016 Sep 16. PMID: 27638811.

https://dermnetnz.org/topics/reactive-arthropathy/

Carter JD. Treating reactive arthritis: insights for the clinician. Ther Adv Musculoskelet Dis. 2010;2(1):45-54. doi:10.1177/1759720X09357508

Macmullan P, McCarthy G. Treatment and management of pseudogout: insights for the clinician. Ther Adv Musculoskelet Dis. 2012;4(2):121-131. doi:10.1177/1759720X11432559

New polyarthritis

General principles

Early introduction of DMARDs in rheumatoid arthritis prevents joint damage and improves long-term outcomes. As such, NICE states that all adults with persistent synovitis of undetermined cause should be referred urgently if any of the following apply:

The small joints of the hands or feet are affected

More the one joint is affected

There has been a delay of ≥3 months between symptom onset and seeking medical advice

Referral pathways vary nationally but often Rheumatology departments will have an Early Arthritis Clinic service to see patients fulfilling these criteria urgently.

Useful investigations

Bloods

FBC, U&Es, LFTs (this is not only helpful in diagnosis and ruling out other causes, but is also useful to have when starting new medication in clinic)
Inflammatory markers – CRP and ESR
Autoantibodies – rheumatoid factor and anti CCP antibody (ACPA)
Others – consider urate if gout is possible

Imaging – often not needed in primary care and should not delay referral - patients with suspected inflammatory arthritis will get XRs of hands and feet as a baseline investigation and most will get a musculoskeletal ultrasound

Treatment (while awaiting rheumatology review)

Rest and ice
NSAIDs if not contraindicated (e.g. naproxen 250-500mg BD with PPI cover)
Discuss with local rheumatologist if this is not sufficient while waiting for review. Corticosteroids can be helpful but it is often better for rheumatology to assess the patient first

NICE (2018a) Rheumatoid arthritis in adults: management. National Institute for Health and Care Excellence. http://nice.org.uk [https://www.nice.org.uk/guidance/ng100]

Giant cell arteritis

General principles

GCA should be considered in older patients (>50 years, peak incidence 70-79 years) with a new headache and (in most cases) scalp tenderness. Ischaemic sequelae including visual loss can occur rapidly but can be prevented with prompt treatment so a high index of suspicion is important. If suspected it may be appropriate to start treatment with corticosteroids before assessment in secondary care, particularly out-of-hours, but it is important to check bloods including inflammatory markers first.

Liaise with rheumatology as soon as possible. Temporal artery ultrasound can avoid the need for biopsy but becomes less sensitive with steroid treatment.

Referral pathways vary nationally but BSR guidelines suggest patients ideally should be assessed by rheumatology next working day. Many local services have ‘fast-track’ pathways in place.

If there are visual symptoms (transient or permanent visual loss or diplopia) patients should be reviewed urgently by ophthalmology before rheumatology.

History and examination

Classical features:
- Headache and scalp tenderness (common but non-specific)
- Jaw or tongue claudication - discomfort that worsens during activity such as chewing or talking (specific but uncommon)
Temporal artery tenderness, nodularity, thickening or reduced pulsation
Visual changes (transient and permanent visual loss, diplopia, changes to colour vision)
Polymyalgia rheumatica as an associated disorder - shoulder and hip girdle pain and stiffness, worse in the mornings
Constitutional symptoms such as fever, weight loss, anorexia and fatigue

Specific considerations

GCA is vanishingly rare under 50 years of age. Consider alternative diagnoses in this group.

Investigations

Blood tests
- FBC, U&E, LFT, bone panel
- CRP - nearly always elevated (consider alternative diagnoses if not). ESR is often checked but is less specific. Important to check before starting steroids as can normalise rapidly following treatment.
- HbA1c and lipid profile- Diabetes, hyperlipidaemia and hypertension may be affected by treatment

Treatment

Liaise with local rheumatology and ophthalmology teams as early as possible for advice on steroid treatment. If this is not possible:
- If threatened visual loss (sustained or unilateral loss of vision or monocular diplopia) with suggestive history, start steroids IMMEDIATELY
- If high index of suspicious without threatened visual loss, start treatment after blood tests but before results returned
Initial treatment (in line with BSR guidelines):
- Headache, scalp tenderness - prednisolone 40mg OD
- Jaw claudication - prednisolone 60mg OD
- Intermittent visual loss - IV methylprednisolone 500mg-1g for three days
- Always start PPI cover alongside high dose steroids unless contraindicated –and document rationale

Ongoing management after diagnosis

Management is with a reducing course of prednisolone over 6-18 months, depending on severity
Half of patients will experience a flare over this time. Management of this will depend on features:
- Worsening headache, scalp tenderness - return to previous effective dose
- Jaw claudication - liaise with rheumatology and increase to prednisolone 60mg OD
- Visual disturbance - liaise with rheumatology and ophthalmology and consider need for further IV methylprednisolone
Vascular risk factors - these have an additive effect to the risk of ischaemic sequelae and deteriorate with steroid treatment so treatment should be optimised

Resources

British Society for Rheumatology guideline on diagnosis and treatment of Giant cell arteritis

Oxford Desk Reference Rheumatology

Gout

General principles

Gout is the commonest inflammatory arthritis, with a prevalence in the UK of 2.49% in 2012. Although the gold standard for diagnosis remains joint aspiration and identification of monosodium urate crystals, this is often not needed when the clinical picture is clear.

History and examination

Acute and severe pain
Few diseases cause episodic arthritis - gout is by far the commonest
Many rare causes but commonest risk factors are:
- Alcohol excess
- Renal impairment
- Diuretics/dehydration

Investigations

Joint aspiration
Urate – can be normal or even low in acute attacks so should be rechecked four weeks after acute attack
Vascular risk factors - BP and glucose/HbA1c
U&Es – renal impairment is a risk factor and affects potential treatments

Treatment

Acute attack
- Treat attack early, rest and ice. Patient education
- NSAID (or ‘-coxib’) + PPI OR
- Colchicine 250-500µg BD OR
- Corticosteroids (intra-articular or oral – e.g prednisolone 20-30mg reducing over 1-2 weeks)
Prophylaxis:
- Urate lowering therapy (ULT) should be offered to all patients with a diagnosis of gout and should be particularly advised to those with:
  - Recurring attacks (≥2 attacks in 12 months)
  - Tophi, gouty arthritis or joint damage
  - Renal impairment (eGFR < 60m/min)
  - History of urolithiasis
  - Diuretic use
  - Young age
Urate-lowering therapy
- Principles of urate lowering therapies (ULTs)
  - ULTs can provoke a flare so consider concomitant prophylaxis while titrating treatment with e.g NSAID + PPI OR colchicine 250-500µg OD or BD OR prednisolone 10-15mg OD with PPI
  - Recheck urate and U&Es every 4-6 weeks and titrate ULT as necessary to achieve serum urate < 300µmol/L
  - Once started, DO NOT STOP during acute attacks
- Allopurinol
  - Allopurinol is first line, starting at 100mg daily - though this initial dose should be reduced in the presence of renal impairment (see table - reproduced from BSR guidelines 2017) because of the increased risk of allopurinol drug reaction.
  - Allopurinol is well tolerated but is rarely associated with potentially life-threatening Severe Cutaneous Adverse Drug reactions (SCARS - 0.1-0.4%) so patients should be advised to stop it immediately and seek medical advice if they develop a skin rash
  - Increase by 100mg (50mg in presence of renal impairment) every 4 weeks while measuring urate levels, maximum dose 900mg OD. The same target urate can be used in the presence of renal impairment but maximum dose may be reduced or dosing interval altered - consult with renal team.

eGFR	Allopurinol starting dosage
<5	50mg/week
5-15	50mg twice weekly
16-30	50mg every two days
31-45	50mg OD
46-60	50mg/100mg alternate days
61-90	100mg OD

Febuxostat:
- Consider if unable to tolerate allopurinol
- Febuxostat is an option in patients with pre-existing cardiovascular disease - early studies suggested an increased risk of death but this has not been shown in recent follow-up studies (FAST, Lancet 2020)
Alternative options (secondary care)
- Benzbromarone - xanthine oxidase with small but significant risk of hepatic failure
- Anakinra - IL-1 receptor inhibitor

General points:

Review medications (especially diuretics)
Address cardiovascular risk factors (hypertension, diabetes, lipids)
Patient education (see below)

Patient education

There is still widespread belief that gout only affects older, overweight men and that it is a self-inflicted disease. Although lifestyle factors can impact on the risk of developing gout and having attacks, these beliefs can prevent patients seeking help early. The course of the disease should be explained to the patient, including the likelihood of flares during initiation of ULT

If overweight, the patient should be encouraged to lose weight through diet modification and exercise
Diet associated with gout – excessive meat, seafood, alcohol (especially beer and spirits), sugary soft drinks, fructose-containing foods
When starting ULT, patients should be warned about the risk of attacks and given a plan of how to manage them. ULT should not be stopped when an attack happens
Maintenance of serum urate levels at or below 300µmol/L will prevent urate crystals forming and over time will dissolve away existing crystals

Gout in renal failure

Colchicine
- Reduce dose to 500µg OD if eGFR 30-60ml/min/1.73m2
- Reduce to 500µg every 2-3 days if eGFR 10-30ml/min/1.73m2
- Avoid if eGFR < 10ml/min/1.73m2
Allopurinol
- Dose should be reduced in renal impairment to prevent to increased risk of severe cutaneous reactions. The BSR guidelines provides a guide to starting dose according to creatinine clearance (https://academic.oup.com/rheumatology/article/56/7/e1/3855179 - table 2)

When to refer to rheumatology

Chronic or tophaceous gout
Ongoing flares despite maximal allopurinol/febuxostat therapy (or unable to tolerate)
Diagnosis unclear

References

Stamp LK, Chapman PT, Barclay ML, et al. A randomised controlled trial of the efficacy and safety of allopurinol dose escalation to achieve target serum urate in people with gout. Annals of the Rheumatic Diseases 2017;76:1522-1528. Accessed at http://dx.doi.org/10.1136/annrheumdis-2016-210872 on 7/6/21.

Michelle Hui, Alison Carr, Stewart Cameron, Graham Davenport, Michael Doherty, Harry Forrester, Wendy Jenkins, Kelsey M. Jordan, Christian D. Mallen, Thomas M. McDonald, George Nuki, Anthony Pywell, Weiya Zhang, Edward Roddy, for the British Society for Rheumatology Standards, Audit and Guidelines Working Group, The British Society for Rheumatology Guideline for the Management of Gout, Rheumatology, Volume 56, Issue 7, July 2017, Pages e1–e20, https://doi.org/10.1093/rheumatology/kex156

Richette P, Doherty M, Pascual E, et al. 2016 updated EULAR evidence-based recommendations for the management of gout. Annals of the Rheumatic Diseases 2017;76:29-42.

American College of Rheumatology Guidelines May 2020: https://www.rheumatology.org/Portals/0/Files/Gout-Guideline-Early-View-2020.pdf

Polymyalgia rheumatica

Quick tip; Provide education to patients about long-term steroid therapy such as ‘sick days’ and the need to adhere to strict compliance to therapy

History and examination

>50 years old
Symptoms lasting > 2 weeks
Proximal pain or stiffness: Bilateral shoulder and/or hip girdle pain/ aching (more often the shoulders)
Morning stiffness > 45 minutes
Evidence of an acute phase response
Usually patients will have an acute phase response - consider referral if making a diagnosis to secondary care if absent

The following should be ruled out in the presence of raised inflammatory markers and malaise:

Infection
Cancer
Giant cell arteritis (GCA) - can co-exist and symptoms such as headache, scalp tenderness and jaw claudication should be recorded at baseline

Common alternative diagnoses are:

Osteoarthritis - peripheral involvement, longer onset, no systemic features
Shoulder pathology (rotator cuff syndrome, frozen shoulder)
Inflammatory arthritis

Patients with a typical history and prompt (1 week) and sustained response to initiating corticosteroids can be managed in primary care. Consider referral to secondary care if the following atypical clinical features are present:

Age <60 years
Chronic onset (>2 months)
Lack of shoulder involvement
Lack of inflammatory stiffness
Prominent systemic features, weight loss, night pain, neurological signs
Features of other rheumatic disease
Normal or extremely high acute-phase response
Incomplete or non-sustained response to steroids

GCA should always be managed in secondary care so refer these patients urgently (see separate section)

Similarly consider referral if the following are present with treatment.

Incomplete, poorly sustained or non-response to corticosteroids
Inability to reduce corticosteroids
Complications or contraindications to corticosteroid therapy
The need for prolonged corticosteroid therapy (>2 years)
More than 1 relapse of PMR symptoms

DMARDs such as methotrexate have been used in PMR as steroid sparing agents

Investigations :

Bloods:
FBC – normocytic anaemia, thrombocytosis are common
ESR – usually normalises within a month of commencing treatment
CRP - usually elevated and normalises before the ESR
Alternative causes:
- TSH
- Creatine kinase – should be normal in PMR, if elevated consider investigating for other causes and myopathy
- Immunoglobulins and protein electrophoresis- should be normal (myeloma and lymphoma can mimic PMR)
Baseline prior to steroid treatment:
HbA1c- baseline (steroids can induce diabetes or worsen blood sugar control)
Lipid profile- baseline (increased cardiovascular risk with steroid treatment)

Standard treatment

Corticosteroids (from 2009 BSR Guideline):
- Prednisolone 15mg OD for three weeks
- Then 12.5mg for three weeks
- Then 10mg for 4-6 weeks
- Then reduce by 1mg every 4-6 weeks
This standard protocol can be flexible - slower reductions may be necessary and if relapses occur, return to last effective dose. However, if treatment continues for >2 years then consider referral.
Patients should be given advice about chronic corticosteroid use (sick day rules, ensuring no gaps in treatment, steroid cards).
Early regular testing of blood sugars should be performed in new diagnoses in both diabetic and non-diabetic patients
If symptoms develop during steroid reduction without recurrence of PMR symptoms (e.g. malaise, mood change, lethargy, anorexia, poor motivation) consider glucocorticoid insufficiency - discuss with Rheumatology or Endocrinology, they may require a short synacthen test
Assess osteoporotic risk and treat as indicated e.g. by using a validated tool such as FRAX (https://www.sheffield.ac.uk/FRAX/ ) and treat as indicated. Note that FRAX is not applicable to patients under 40 yrs and tends to underestimate # risk with steroids (see the section from the NOGG Osteoporosis Guideline below on glucocorticoid-induced osteoporosis)
Annual influenza vaccine, 5 yearly pneumovax, recombinant zoster vaccine (killed)- see vaccine section within Buku Rheumatology

Relapses (not just unexplained rises in CRP/ ESR)

Clinical features of GCA (treat as new GCA/ medical emergency and refer – see GCA section)
Clinical features of PMR: increase prednisolone to previous higher dose
Second PMR relapse: referral to specialist to consider starting DMARD therapy

Monitoring:

Diabetes (worsening of blood sugars or new steroid induced diabetes)
Hypertension and cardiovascular disease (steroid induced cardiomyopathy)
Bone health

References

Bhaskar Dasgupta, Frances A. Borg, Nada Hassan, Kevin Barraclough, Brian Bourke, Joan Fulcher, Jane Hollywood, Andrew Hutchings, Valerie Kyle, Jennifer Nott, Michael Power, Ash Samanta, on behalf of the BSR and BHPR Standards, Guidelines and Audit Working Group, BSR and BHPR guidelines for the management of polymyalgia rheumatica, Rheumatology, Volume 49, Issue 1, January 2010, Pages 186–190, https://doi.org/10.1093/rheumatology/kep303a

https://www.sheffield.ac.uk/NOGG/NOGG%20Guideline%202017.pdf

https://expertconsult.inkling.com/read/west-rheumatology-secrets-4e/chapter-20/idiopathic-inflammatory

Rheumatology Secrets, chapter 20, Idiopathic Inflammatory Myopathies. Sterling G.West