18th January 2024

Rheumatological Emergencies

Giant Cell Arteritis

Background

Giant Cell Arteritis (or GCA) is a large vessel vasculitis causing granulomatous inflammation of the aorta and larger branches. Cranial GCA (or Temporal Arteritis) is the most common form and will be the focus of this section. 

GCA is more common in females (ratio 2:1) and in patients aged >50 years– presentation in younger age is extremely rare. Prompt recognition and treatment of GCA is vital given the risk of ophthalmic involvement, which can lead to permanent visual loss. 

Association with Polymyalgia Rheumatica

GCA is closely associated with Polymyalgia Rheumatica (PMR), another large vessel vasculitis; some consider the two conditions to be a spectrum of the same disease process with variable expression. Roughly half of patients with GCA have symptoms of PMR, and a fifth of patients with PMR have evidence of GCA. Genetic susceptibility to both conditions is found in those carrying the HLA DRB1*04 and DRB*01 genes. Those carrying this gene are at higher risk of complications and treatment resistance. 

Clinical presentation

GCA classically presents with the following, either acutely or sub-acutely: 

Symptoms

• Temporal headache – usually unilateral but can be bilateral
• Scalp tenderness
• Intermittent claudication to the jaw/tongue – pain on chewing, which resolves on rest
• Constitutional symptoms – fatigue, night sweats, weight loss, anorexia, low-grade fever
• Visual disturbance – flashers/floaters, diplopia, changes in colour vision and in severe cases visual loss
• Features of PMR – proximal muscle pain and stiffness
• Neurological features such as TIA or upper cranial nerve palsies

Signs

• Temporal artery tenderness, thickening, nodularity or ulceration
• Pallor and oedema of the optic disc on fundoscopy

Investigations

Confirming the diagnosis is vital, and the gold standard is currently temporal artery biopsy. Colour duplex ultrasonography has also been shown to be effective in diagnosing GCA and is gaining popularity due to being non-invasive and more easily available.

Other expected findings would be:

• Raised ESR/CRP 
• Normocytic, normochromic anaemia
• Thrombocytosis
• Deranged liver function tests, in particular, a raised ALP

Histology

Histology of the temporal artery shows an occlusive vasculopathy with intimal proliferation and a reduction in diameter of the lumen. Inflammation is patchy (skip lesions); therefore, a normal biopsy cannot rule out GCA. The inflammatory infiltrate is predominantly composed of macrophages and CD4 lymphocytes. Only half of positive histological samples demonstrate giant cells.

Management 

All patients with suspected GCA should be referred for urgent specialist assessment, but this should not delay initiation of treatment. 

Treatment involves steroids, as follows:

• 40mg Prednisolone daily, unless the patient has ischaemic symptoms
• 60mg Prednisolone daily in the presence of ischaemic symptoms, i.e. jaw claudication/visual loss
• Admission for IV Methylprednisolone may be indicated in the presence of visual symptoms (along with urgent ophthalmic assessment)

After resolution of symptoms, steroids can be tapered, and this is often a long and protracted process. Relapses are common and respond to increasing the dose back up to the last effective dose. If steroids are ineffective or not tolerated, methotrexate or tocilizumab (IL-6 inhibitor) may be considered by rheumatologists.

Complications

GCA is considered a medical emergency due to the risk of severe complications, particularly if it is not treated in a timely manner. The following complications may occur:

• Visual loss (due to anterior ischemic optic neuropathy)
• Dissections or aneurysms of the aorta or its branches
• Stroke

References

• Tidy C. Giant cell arteritis (temporal arteritis) [Internet]. Patient.info. 2022 [cited 2023 Feb14]. Available from: https://patient.info/doctor/giant-cell-arteritis-pro
• Hernández-Rodríguez J, Murgia G, Villar I, Campo E, Mackie SL, Chakrabarty A, et al. Description and validation of histological patterns and proposal of a dynamic model of inflammatory infiltration in giant-cell arteritis. Medicine. 2016;95(8).

Septic Arthritis

Background

The acute hot joint is a common clinical presentation with a wide differential diagnosis, of which septic arthritis confers the highest morbidity and mortality. The British Society for Rheumatology (BSR) guidelines on management of the hot swollen joint state that:

“Patients with a short history of a hot, swollen and tender joint (or joints) with restriction of movement should be regarded as having septic arthritis until proven otherwise”.

Septic arthritis is defined as joint space infection which can occur in either a native or prosthetic joint. The most commonly implicated organism is Staphylococcus aureus. Other causes of bacterial septic arthritis include Streptococcus pneumonia, Salmonella species (associated with sickle cell disease), Pseudomonas aeruginosa (associated with IV drug use and puncture wounds) and Neisseria gonorrhoea (in those with concomitant gonococcal genitourinary infection).

Risk factors for development of septic arthritis include:

• Prosthetic joints
• Prior joint damage, such as from RA/gout
• Diabetes mellitus
• Immunodeficiency 
• Intravenous drug use
• Recent steroid injections or joint surgery
• Bacterial infections at another site (haematogenous spread)
• Previous joint infection
• Older age

Diagnosis

It is vital that a suspected septic joint is investigated and managed as early as possible, as untreated infection quickly leads to joint destruction and can be fatal. 

Signs and symptoms

The typical case is of an acute red, hot, swollen joint in a systemically unwell patient with a fever – however, it is important to note that in many cases, the patient may not appear systemically unwell. 

Symptoms include pain and swelling, usually in one joint – most commonly the knee (can be polyarticular in a minority of patients). The patient will typically have an inability to weight bear and limited range of motion in the affected joint. Infections in other joints can lead to a variety of symptoms, e.g. sacroiliac joint infections may present as buttock or hip pain, and sternoclavicular joint infections may present with chest pain.

Investigations

A joint aspiration should be prioritised as it ideally needs to be performed prior to antibiotic administration to obtain the highest yield results. The synovial fluid would typically be cloudy in appearance in the presence of infection and should be examined for:

• Culture & Sensitivity
• Gram stain
• White Cell Count (typically >50,000/mm3)
• Polarising crystal microscopy

Other important investigations include: FBC, CRP and blood cultures. U&E and LFTs should be checked, as this may impact on choice of antibiotics. If Neisseria gonorrhoea is suspected, then cultures of extended sites (i.e. rectal, cervical, urethral or pharyngeal) for gonococcal infection will be required as this organism is poorly cultured in synovial fluid. 

Plain radiographs are usually of no diagnostic benefit in septic arthritis but should be obtained if there is suspicion of injury or fracture. They may show chondrocalcinosis in pseudogout or osteomyelitis if the infection has progressed further into the bone, necessitating a longer treatment course.

Differential diagnoses

• Crystal arthropathy – this includes gout and pseudogout, which are common causes of an acute hot joint. Their clinical features are extremely difficult to differentiate from septic arthritis as the patient may even have a fever/raised inflammatory markers. Joint aspiration is vital in these cases, showing uric acid crystals (negatively birefringent) in gout; and calcium pyrophosphate crystals (positively birefringent) in pseudogout.
• Reactive arthritis – this is often confused with gonococcal septic arthritis but is a different condition entirely. Reactive arthritis is an inflammatory process usually triggered by a systemic genitourinary or gastrointestinal infection. In reactive arthritis, the joint aspirate is sterile. It may present in a mono- or poly-articular manner.
• Injury – this is important to consider prior to a joint aspiration, particularly if the patient is unable to give an accurate history, e.g. due to young age or confusion. If in doubt, perform a radiograph prior to aspiration.
• Lyme arthritis caused by infection with Borrelia burgdorferi – this is not a true septic arthritis as it is a systemic infection which results in joint inflammation. It usually causes polyarthralgia and joint inflammation many months after the original infection.

Management

Septic arthritis may be managed by the rheumatology or orthopaedic teams according to local trust policies. However, in the case of prosthetic joint infections, the orthopaedics team ought to be involved.

The mainstay of treatment is a prolonged course of antibiotics, initially intravenous for at least two weeks, followed by 2-4 weeks of oral antibiotics. The most common organisms are covered by Flucloxacillin, and therefore, this is usually used as empirical treatment (Clindamycin if penicillin allergic). In some cases, a surgical joint washout will be needed. 

References

• Coakley G, on behalf of the British Society for Rheumatology Standards G and AWG, Mathews C, on behalf of the British Society for Rheumatology Standards G and AWG, Field M, on behalf of the British Society for Rheumatology Standards G and AWG, et al. BSR & BHPR, BOA, RCGP and BSAC guidelines for management of the hot swollen joint in adults. Rheumatology [Internet]. 2006 Aug 1;45(8):1039–41. Available from: https://academic.oup.com/rheumatology/article/45/8/1039/1784962 
• Momodu II, Savaliya V. Septic Arthritis [Internet]. PubMed. Treasure Island (FL): StatPearls Publishing; 2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK538176/

Emergencies in Systemic Sclerosis

Background

Systemic sclerosis – also known as Scleroderma – is an autoimmune multi-system connective tissue disease characterised by increased fibroblast activity causing abnormal growth and deposition of collagen, vascular damage and fibrosis of connective tissues. This usually occurs in the skin (hence the name scleroderma) along with internal organs such as the GI tract, lungs and heart. It can also occur in the vasculature, resulting in manifestations such as Raynaud’s, pulmonary arterial hypertension and renal disease. Typical cutaneous features of systemic sclerosis include microstomia and ‘salt-and-pepper’ appearance of skin due to areas of hypo- and hyper-pigmentation. 

Classification of systemic sclerosis

Systemic sclerosis has two main subtypes:

1. Limited cutaneous systemic sclerosis (more common type)
   • The areas of skin involved include the face, arms (distal to the elbows) and legs (distal to the knees)
   • Additional features can be summarised as CREST (CREST syndrome is the old name for this sub-type): Calcinosis, Raynaud’s, oEsophageal dysmotility, Sclerodactyly, Telangiectasia
   • Slow onset and progression
2. Diffuse cutaneous systemic sclerosis (less common type)
   • The areas of skin involved include the trunk, proximal arms to the elbow and proximal legs to the knee
   • Higher mortality due to higher incidence of multi-organ involvement
   • Rapid onset with early skin thickening and Raynaud’s

Antibodies

There are a number of antibodies associated with systemic sclerosis, and each has associations with particular complications which can help with screening and prognostication.

• Anti-topoisomerase-1 antibody (also known as anti-Scl-70): strong association with lung fibrosis, renal disease, and poor prognosis.
• Anti-centromere antibody (ACA): seen in patients with limited cutaneous systemic sclerosis; associated with pulmonary hypertension.
• Anti-RNA-polymerase-III antibody: seen in patients with diffuse cutaneous systemic sclerosis and strongly associated with renal disease, and in particular, ‘scleroderma renal crisis’.

Scleroderma Renal Crisis

Scleroderma renal crisis is a life-threatening complication, presenting with sudden-onset malignant hypertension and severe progressive renal failure. Other manifestations include hypertensive encephalopathy, congestive cardiac failure and microangiopathic haemolytic anaemia.

It most commonly presents in patients with the diffuse cutaneous sub-type; it is very rare in those with limited cutaneous disease. It usually occurs early in the disease course and can occasionally be the presenting feature.

Pathophysiology

Blood vessels undergo structural changes (thickening and proliferation of the intima with fibrin deposition), which causes reduced blood flow, further exacerbated by vasospasm. When this occurs in the kidneys, renal ischaemia develops, causing activation of the renin-angiotensin-aldosterone system (RAAS) and subsequent rise in blood pressure. The hypertension causes even further damage to renal blood vessels, and this cycle of events eventually results in malignant hypertension and fulminant renal failure. 

Management

Since activation of the RAAS is the basis of the pathogenesis of the scleroderma renal crisis, management is based on inhibition of this pathway using Angiotensin-Converting Enzyme (ACE) inhibitors. Patients should be admitted for blood pressure control and careful monitoring of renal function. Despite the potential to further worsen the renal function, ACE inhibitors are an essential part of the treatment of scleroderma renal crises. In some cases, dialysis may be needed, but renal recovery can occur up to 24 months after the crisis and decisions about transplantation should be delayed until this point.

Scleroderma Pulmonary Hypertensive Crisis

Pulmonary arterial hypertension (PAH) in systemic sclerosis is a rare but potentially fatal complication. It may occur either as a primary process or secondary to pulmonary fibrosis. Early clinical symptoms of PAH are non-specific, including breathlessness, light-headedness, syncope, fatigue and weakness. Patients should be screened at the time of diagnosis and annually thereafter. However, some patients may go unscreened, particularly if they develop a compensatory sedentary lifestyle which limits symptoms. In these patients, PAH may progress for some time and become quite severe before it is detected.

The gold standard diagnostic tool is right heart catheterisation. Patients can sometimes present acutely, and, in this case, it will be diagnosed on an echo doppler of the heart.

Clinical signs associated with PAH

• Split heart sounds with a loud P₂
• Tricuspid regurgitation (systolic murmur)
• Parasternal heave
• Raised JVP
• Ascites
• Hepatomegaly with a pulsatile liver
• Peripheral oedema

Pathophysiology

In primary pulmonary arterial hypertension, vasospasm and intimal proliferation with fibrin deposition in the lungs lead to vascular resistance and remodelling, which ultimately results in right ventricular dysfunction.

Management 

Management revolves around targeting these pathways to restore the balance between vasoconstriction and vasodilation. Thus, vasodilators (nitric oxide and prostacyclin) and proliferative mediators (endothelin-1) are targeted using the following medications:

• Prostacyclin analogues, e.g. Epoprostenol, Iloprost
• Endothelin-receptor antagonists, e.g. Bosentan
• Phosphodiesterase Type-5 Inhibitors (which increase nitric oxide production), e.g. Sildenafil 

In the acute setting, patients can present significantly hypoxic and, require IV prostacyclin, and may require advanced respiratory support for oxygenation. Respiratory involvement in systemic sclerosis, either pulmonary fibrosis or PAH, is the most common cause of death for patients living with this condition.

References

• Tidy C. Systemic sclerosis (scleroderma) [Internet]. Patient.info. 2022 [cited 2023 Feb14]. Available from: https://patient.info/doctor/systemic-sclerosis-scleroderma 
• Vaidya PN, Basyal B, Finnigan NA. Scleroderma And Renal Crisis [Internet]. PubMed. Treasure Island (FL): StatPearls Publishing; 2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482424/
• Kolton Schneider L, Ali Y, Agnew JD. Scleroderma-Associated Pulmonary Arterial Hypertension: Early Detection For Better Outcomes [Internet]. PubMed. Treasure Island (FL): StatPearls Publishing; 2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK576387/