Systemic rheumatic diseases

Antiphospholipid syndrome

• Classic characteristics
  • Multiple venous and arterial thromboses
  • Recurrent miscarriages
  • Haemolysis
  • Livedo reticularis
  • Thrombocytopaenia
  • TIA
  • Catastrophic antiphospholipid syndrome

• Primary vs. Secondary
  • Primary makes up 50% of cases
  • Secondary from SLE (35%), RA, systemic sclerosis and Sjogren’s
  • SLE-related antiphospholipid syndrome
    • More likely to suffer arthritis, livedo reticularis, valve disease, thrombocytopaenia and leukopaenia
• Emergencies
  • ARDS, PE, acute limb/organ ischaemia, severe anaemia, bleeding, vision loss, catastrophic antiphospholipid syndrome

• Risk of thromboses increased for:
  • Positive lupus anticoagulant
  • Moderate to high anticardiolipin
• Stroke is the greatest risk w.r.t. arterial thrombosis
• Catastrophic antiphospholipid syndrome
  • Widespread thromboses with MODS
  • 50% mortality

Ankylosing spondylitis

• Characteristics
  • Axial skeleton chronic inflammation
  • Young adults, back pain (improves with exercise), buttock, hip, sacroiliac, shoulder
  • Fever, malaise, fatigue, weight loss, myalgias
  • Uveitis
  • Restrictive pulmonary failure due to costovertebral rigidity
  • Secondary amyloidosis
• Emergencies
  • Acute spinal cord or nerve compression
  • Atlantoaxial subluxation
  • Aortic regurgitation
  • Fracture of ‘bamboo spine’

Adult Still’s disease

• Characteristics
  • Inflammatory arthritis
  • Systemic fever, fatigue, malaise, weight loss, myalgia
  • Evanescent rash
  • Pharyngitis, lymphadenopathy, splenomegaly, anaemia, thrombocytopaenia
  • Pericarditis, myocarditis, pleurisy
• Emergencies
  • ARDS
  • Arrhythmias, heart failure, pericarditis, myocarditis, pleurisy
  • Fulminant hepatic failure
  • Red cell aplasia
  • DIC
  • Microangiopathic haemolytic anaemia

Behcet’s disease

• Characteristics
  • Chronic, relapsing inflammatory disease
  • Systemic vasculitis of all size (mostly carotid, pulmonary, aortic, lower limb vessels)
  • Systemic fever, malaise, fatigue, weight loss, myalgia
  • Recurrent painful skin and mucosal lesions
  • Asymmetric, non-deforming arthritis of medium-large joints
  • Thrombophlebitis and DVT
  • Ocular complications
  • Neuropsychiatric complications
  • Pericarditis, myocarditis

• Emergencies
  • Hypopyon, retinal vasculitis, optic neuritis
  • Dural sinus thrombosis, aseptic meningitis
  • Arrhythmias
  • Superior and inferior vena cava syndromes
  • PE
  • Abdominal aortic emergencies
  • Bowel perforation

Dermatomyositis/polymyositis

• Characteristics
  • Muscle weakness, myalgia, muscle tenderness, elevated CK
  • Systemic fever, malaise, fatigue, weight loss
  • Raynaud
  • Non-erosive inflammatory polyarthritis
  • Oesophageal dysfunction
  • Interstitial lung disease
• Emergencies
  • ARDS
  • Respiratory failure due to chest wall/diaphragm weakness
  • Alveolar haemorrhage
  • ILD
  • Heart failure, arrhythmias, conduction disturbances

Rheumatoid arthritis

• Characteristics
  • Chronic, systemic inflammatory disorder
  • Symmetric destructive arthritis
  • Systemic features
  • Skin lesions, splenomegaly
  • Cervical spine involvement
  • Pleuritis, ILD
  • Pericarditis, myocarditis, aortitis
  • Cricoarytenoid disease
  • Ocular involvement
  • Peripheral artery disease
  • Sjogren’s syndrome
  • Anaemia, leukopaenia, thrombocytosis, Felty’s syndrome
  • Increased risk of Non-Hodgkin’s lymphoma

• Emergencies
  • Airway obstruction (cricoarytenoid arthritis)
  • Obliterative bronchiolitis
  • ARDS
  • ACS, heart failure, thoracic aortic dissection, arrhythmias and conduction disturbances
  • Atlanto-axial subluxation (25% of patients)
  • Bowel ischaemia and perforation
  • Septic arthritis
  • Scleritis

SLE

• Characteristics
  • Systemic autoimmune disease with relapses and remissions
  • Systemic complaints (FATIGUE), symmetric polyarticular arthalgia (small joints of hands/wrist/knees), malar rash, mucocutaneous manifestations, oral/nasal ulcers (painless)
    • Arthritis is rarely deforming
    • Photosensitivity is common
    • Alopecia
  • Raynaud’s (50%)
  • Neuropsychiatric manifestations
  • Pleurisy, lupus pneumonitis, shrinking or vanishing lung syndrome, interstitial lung disease, pulmonary hypertension
  • Libman-Sacks endocarditis, pericarditis, myocarditis
    • Pericarditis is the most common cardiac sequelae affecting 25% of patients
  • Renal impairment, leukopaenia, mild anaemia of chronic disease, thrombocytopaenia
  • Antiphospholipid syndrome (with inherent risk of VTE and arterial thromboembolism)
  • Ocular complications
    • Keratoconjunctivitis sicca is most common due to secondary Sjogren’s
  • Vasculitis
    • Mostly small vessel cutaneous with palpable purpura, petechiae, livedo reticularis, panniculitis, splinter haemorrhages and superficial ulcerations

• Labs
  • FBC – Mild anaemia of chronic disease, leukopaenia, thrombocytopaenia
  • UEC – Renal impairment
  • Urinalysis – Nephritic syndrome
  • ANA
    • Positive in nearly all patients at some point in course of illness
    • If positive – then test for anti-dsDNA, anti-Smith, Anti-Ro/SSA, anti-La/SSB
    • Anti-dsDNA and anti-Smith are highly specific but not sensitive
  • Antiphospholipid antibodies (anticardiolipin, lupus anticoagulant)
  • C3/C4 both low
  • ESR/CRP raised

• Emergencies
  • Airway obstruction
  • ARDS, respiratory failure, alveolar haemorrhage
  • ACS, cardiac tamponade, heart failure, arrhythmias
  • PE, stroke
  • Acute renal failure
  • GBS, transverse myelitis, seizures
  • Bowel ischaemia, perforation, GI bleeding
  • Acute pancreatitis
  • Haemolytic anaemia
  • Thrombotic microangiopathic haemolytic anaemia

Drug-induced lupus

• Prilocaine and anti-TNFalpha therapies often result in positive ANA but NOT symptoms
• Hydralazine
• Diltiazem
• Isoniazid
• Quinidine
• Methyldopa
• Chlorpromazine

Sjogren’s

• Primary or secondary to RA, SLE, polymyositis
• Xerophthalmia, xerostomia
• Systemic symptoms, arthralgia, Raynaud’s
• ILD, pulmonary hypertension
• Pericarditis
• Neuropsychiatric manifestations
• Peripheral neuropathy
• Hepatic and renal impairment
• Increased risk of Non-Hodgkin’s lymphoma

• Emergencies
  • Hypokalaemic respiratory arrest due to distal RTA
  • Heart block
  • PE
  • Ischaemic stroke, transverse myelitis, optic neuritis
  • Distal RTA
  • Pancreatitis

Systemic sclerosis

• Collagen deposition in all tissues
• Endothelial dysfunction, vascular spasm, narrowing of vascular lumen
• Systemic complaints, finger/face/hand lesions
• Carpal tunnel syndrome
• Raynaud’s
• ILD
• Renal impairment
• GI dysmotility, GORD, aspiration pneumonitis, strictures
• Vascular ectasia in stomach (Watermelon stomach)

• Emergencies
  • Scleroderma renal crisis
  • Respiratory failure, ARDS, aspiration pneumonitis, pulmonary hypertension, alveolar haemorrhage
  • Heart failure, arrhythmias, conduction disturbances

Airway emergencies

• Cricoarytenoid joint arthritis
  • Seen in RA, SLE
  • Can lead to acute upper airway obstruction
  • Throat pain, tenderness over cartilage, foreign body sensation or fullness in throat, voice change, hoarseness, dyspnoea, cough, stridor
  • CT and nasendoscopy can evaluate
  • Dexamethasone 10mg IV
• Subglottic stenosis
  • May be presentation of Wegener’s granulomatosis with inability to clear secretions

• Intubation in patients with systemic rheumatic diseases
  • Anticipate difficulty
  • Awake preferred option always
  • Consider fibreoptic intubation and double set up
  • RA and AS can suffer TMJ dysfunction with reduced mouth opening
  • Cervical ankylosis
    • 25% of patients with RA or AS have atlanto-axial subluxation so avoid neck hyperextension
    • Neck extension may be limited anyway
    • High risk of C-spine fracture with minor trauma
  • Scleroderma can harden skin of neck and face limiting mouth opening and neck mobility

Pulmonary emergencies

• Infection or primary pulmonary disease are both common emergencies
• Systemic sclerosis, RA, SLE, Wegener’s granulomatosis, polymyositis/dermatomyositis
• Primarily interstitial lung disease and vascular disease
• Even mild infection can lead to respiratory failure in these patients due to underlying disease
• Respiratory arrest has been described in:
  • SLE and polymyositis from phrenic nerve involvement
  • RA with cervicomedullary compression from atlantoaxial dislocation
  • Sjogren’s due to hypokalaemic paralysis secondary to distal RTA
• May present with chronic deterioration in pulmonary function or acute deterioration from infection or alveolar haemorrhage

• Alveolar haemorrhage
  • Uncommon but catastrophic
  • Complications of SLE, antiphospholipid syndrome, vasculitis, Wegener’s, polymyositis, microscopic polyangiitis and systemic sclerosis
  • Symptom onset is usually abrupt with rapid deterioration
  • Classic triad of haemoptysis, pulmonary infiltrates on X-ray and rapid fall in Hb support diagnosis
  • New lung infiltrates (83-100%) and anaemia (75-100%) are more sensitive signs
  • Most commonly initially misdiagnosed as atypical pneumonia
  • If high fever present, difficult to distinguish acute infectious pneumonia, acute lupus pneumonia and alveolar haemorrhage
  • Therapeutic options are diametrically opposite so must work this out (immunosuppression vs. antibiotics)
  • Emergency bronchoscopy with BAL can confirm diagnosis

• Interstitial lung disease
  • RA, Systemic sclerosis, polymyositis, HSP
• Pulmonary hypertension
  • Can be a complication of any rheumatic disease with pulmonary fibrosis and ILD
  • Most common in systemic sclerosis and SLE
  • Pulmonary vasculitis and PE can also lead to this e.g. antiphospholipid syndrome

Cardiovascular emergencies

• Acute coronary syndrome
  • RA has 3-fold risk of MI
  • SLE has 6-fold risk of MI
  • Consider as ‘risk factor’ for cardiovascular disease
  • Risk of MI in premenopausal women with SLE is twice that of usual population
  • Coronary arteritis, fibrosis and coronary artery vasospasm are seen in systemic sclerosis and vasculitis

• Acute heart failure
  • Myocardial disease – Ischaemia, cardiomyopathy, myocarditis, fibrosis
  • Pericardial tamponade or constrictive
  • Valvular disease
  • Conduction or rhythm disturbance
  • Systemic sclerosis
    • Diastolic dysfunction, malignant hypertension during sclerodermal renal crisis or decompensated pulmonary HTN are all possible

• Cardiac arrhythmias
  • Especially RA, systemic sclerosis, SLE and polymyositis
  • 40% higher risk of AF in RA
• Malignant hypertension
  • Typically systemic sclerosis during a ‘renal crisis’
  • Also seen in catastrophic antiphospholipid syndrome, PAN
• Valvular heart disease
  • Ankylosing spondylitis – Aortic or mitral insufficiency due to fibrosis
  • Behcet’s often involves abdominal aorta

• Thromboembolism
  • Behcet’s – Superficial thrombophlebitis and DVT both common
  • Also seen in antiphospholipid syndrome and SLE
• Catastrophic antiphospholipid syndrome
  • Uncommon vaso-occlusive crisis with multiorgan failure usually associated with SLE (also RA, systemic sclerosis, polymyositis)
  • Kidney is primary organ involved and 50% have precipitant (e.g. infection, surgery, trauma, cancer)
  • Other organs include lungs (ARDS, embolism), CNS (CVA, seizures) and skin (necrosis)
  • Mortality 50%
  • Livedo reticularis and thrombocytopaenia are important clinical clues

Neurological emergencies

• CVA
  • Libman-sacks vegetation embolism
  • Vasculitis of cerebral vessels
  • Vasculitis of extra-cranial vessels e.g. giant cell arteritis
• Spinal cord compression and spinal fractures
  • Degenerative disease of cervical spine in RA and AS – acute spinal cord compression, vertebral artery compression syndrome, gait abnormalities, paraesthesias and obstructive hydrocephalus
  • AS risks fracture and spinal cord injury due to rigidity of spine
  • AS can have occult fracture with radiculopathy, paraparesis or tetraparesis
    • Most common symptom is severe and progressive pain
    • Cauda equina is rare

• Instability of cervical spine
  • RA – Instability of atlantoaxial joint with spontaneous subluxation can cause acute cervical myelopathy
    • Severe neck pain, radiation to occiput and paraesthesias or motor weakness in upper extremities
    • Instability can cause vertigo or vertebral insufficiency
    • Electric shock with neck flexion, change in bladder function or progressive quadriparesis
    • Can be clinically silent, so avoid flexion or hyperextension of neck
• Transverse myelitis
  • Often insidious onset of pain, weakness, urinary retention, overflow incontinence and autonomic/sensory deficits
  • Increased risk in Sjogren’s, SLE
  • Vasculitis syndromes can cause anterior spinal artery syndrome 

Ocular emergencies

• Ocular pain, vision disturbance, red eye, tearing, photophobia, diplopia or reduced visual acuity all require very careful assessment
• Optic neuritis and keratitis are common complications of systemic rheumatic disorders
• Sudden and permanent blindness
  • Temporal arteritis
  • Giant cell arteritis

Renal emergencies

• Almost always involved in systemic rheumatic disorders and major factor in morbidity and mortality
• Acute renal failure
  • May be primary disease progression, acute nephritic syndrome, renal thrombotic events, renal artery lesions or rhabdomyolysis OR treatment-related
  • Most common cause of death in systemic sclerosis and sudden scleroderma renal crisis can be catastrophic
• Distal renal tubular acidosis
  • 30% of patients with primary Sjogren’s
  • Hyperchloraemic metabolic acidosis (NAGMA) with low bicarb and hypokalaemia

GI emergencies

• Ischaemia (vasculitis) is most common
  • Lupus mesenteric vasculitis is one of the most serious complications of SLE with mortality of 13%
• Infarction
• Perforation
• Infection 
• Haemorrhage

Infectious emergencies

• Disease itself leads to immunosuppression
• Treatment worsens this
• Anatomic changes that predispose to infection or more severe infection (e.g. pulmonary manifestations)
• Isolated organisms often the usual culprits, however, immunosuppressive state does predispose to opportunistic Candida, PCP, Legionella and TB
• Septic arthritis
  • 2x more common in RA patients if on steroids or TNF-alpha blockers
  • Physical findings of severe pain or limited ROM may be absent or may mimic typical exacerbation of systemic rheumatic disease
  • Arthrocentesis is key with low threshold

Last Updated on October 8, 2021 by Andrew Crofton