Rheumatolological Emergencies
URK Rao*, V Shantaram**

Most of the rheumatological disorders are insidious in onset and chronic in nature. However, clinicians do encounter emergencies in rheumatological practice. Common medical disorders may present as emergencies in a patient with rheumatic disease such as hypoglycaemia in a patient with diabetes mellitus (DM) and rheumatoid arthritis (RA) on hypoglycaemic agents and nonsteroidal anti-inflammatory drugs (NSAIDs). Problems involving multiorgans such as lungs, kidneys, heart, brain and joints may present in a catastrophic manner increasing the morbidity and mortality. Some of the rheumatological disorders may present as an emergency e.g. systemic lupus erythematosus (SLE) with cardiac tamponade, antiphospholipid antibody (Hughes) syndrome (APS) as a stroke.

Table 1 depicts a few rheumatological emergencies organ-wise and Table 2. enlists emergencies caused by certain rheumatic disorders.

Table 1: Rheumatological emergencies organ-wise.

Central nervous system • Encephalopathy • Psychosis • Cranial neuritis • Seizures Eye • Optic neuritis • Iridocyclitis • Scleritis Heart • Pericarditis • Myocarditis • Endocarditis Lungs • Adult respiratory distress syndrome (ARDS) • Pneumonitis (lupus, infective or hypersensitive) Gastrointestine • Gastritis • Bleeding of perforated peptic ulcer Kidney • Acute glomerulonephritis • Acute interstitial nephritis • Diffuse arteritis Blood • Thrombocytopenia • Aplastic anaemia • Haemolysis Skin • Exfoliative dermatitis • Steven Johnson syndrome • Toxic epidermal necrolysis Bone and joints • Septic arthritis • Osteoporotic fractures

Table 2: Rheumatological emergencies - disease-wise.

Rheumatoid arthritis • Atlanto-axial dislocation • Scleromalacia perforans • Vasculitis • Acute exacerbation of synovitis • Infections Seronegative sponyloarthropathy • Iridocyclitis Systemic lupus erythematosus • Seizures, psychosis, encephalopathy • Pericarditis, myocarditis, endocarditis • Pneumonitis, ARDS • Acute glomerulonephritis • Vasculitis • Hypertensive crisis • Acute pancreatitis • Polyserositis • Infections Antiphospholipid antibody syndrome • Stroke • Acute myocardial infarction • Retinal vessel thrombosis • Pulmonary embolism and infarction • Thrombocytopenia • Placental ischaemia and foetal loss • Catastrophic APL syndrome Vasculitis • Cerebral vasculitis • Optic neuritis • Uveitis • Mesenteric vasculitis • Acute nephritis • Hypertensive crisis Systemic sclerosis and mixed connective tissue disease • Digital vasculitis and ischaemia • Scleroderma renal crisis Inflammatory myositis (poly / dermatomyositis) • Respiratory failure Crystal-induced arthropathies • Acute gout • Acute interstitial nephritis Arthritis related to infections • Septic arthritis • Reactive arthritis Osteoporosis • Fracture Miscellaneous disorders • Haemophilic arthropathy • Rupture of Baker’s cyst

Drugs commonly used in various rheumatological disorders can also cause certain toxic effects presenting as emergencies (Table 3)

Table 3: Drugs - Emergencies

Nonsteroidal anti-inflammatory drugs • Acute gastritis • Perforated / bleeding peptic ulcer • Acute enteritis • Analgesic nephropathy • Acute interstitial nephritis • Hypersensitivity reactions • Thrombocytopenia • Pancytopenia • Steven Johnson syndrome • Erythema multiforme • Toxic epidermal necrolysis • Acute interstitial nephritis Glucocorticoids • Psychosis • Acute Addisonian crisis due to withdrawal Disease- modifying antirheumatic drugs • Hypersensitivity reactions • Thrombocytopenia • Aplastic anaemia • Exfoliative dermatitis • Steven Johnson syndrome

Direct involvement of vital organs by the disease process can present as an event e.g. rheumatoid lung, neurolupus, scleroderma kidney.

A common basis for most emergencies in rheumatological disorders is necrotising vasculitis with inflammation leading to target organ ischaemia and vital organ failure. Vascular occlusion and target organ damage may also occur due to thrombosis in both arterial and venous system as seen in APS syndrome.

Assessment of a patient presenting with a rheumatological emergency is based upon thorough history and clinical examination. The primary aim of the attending physician is to save life and to prevent irreversible organ damage by instituting suitable and aggressive therapy.

A team approach involving anesthetists, nephrologists, cardiologists and other relevant specialists as required in an individual case is essential for management of any rheumatological emergency.

Institution of aggressive therapy beginning with high dose of glucocorticosteroids (GCS) should be used whenever a patient has life-threatening SLE that is likely to respond to steroids (Table 4).1

Infections must be carefully excluded before instituting or increasing GCS therapy. Consideration must also be given to the presence of co-morbid conditions such as hypertension diabetes mellitus, obesity, osteoporosis and psychiatric disorders.

Table 4: Life threatening manifestations of SLE -responses to glucocorticoids (GCS)

a. Manifestations usually responsive to high doses of GCS • Severe dermatitis of subacute cutaneous lupus • Acute polyarthritis • Polyserositis • Myocarditis • Lupus pneumonitis • Glomerulonephritis • Haemolytic anemia • Thrombocytopenia • Diffuse CNS syndrome • Lupus crisis (high fever and prostration) b. Manifestations not often responsive to GCS • Thrombosis • Scarred end stage renal disease • Membranous glomerulonephritis • Psychosis not related to SLE

Initial therapy should be either high dose daily GCS (1-1.5 mg/kg) given in divided doses or IV methyl prednisolone pulses (500-1000 mg/d for 3 days) followed by oral prednisolone. Combining GCS with cytotoxic drugs such as cyclophosphamide and azathioprine is superior to GCS alone in controlling acute severe SLE, reducing irreversible tissue damage and prolonging survival.2

Cyclophosphamide is typically given with GCS either orally (1-3 mg/kg daily) or intravenously (0.5 to 1.0 gm/m2 of body surface area). The most commonly used intravenous regimen consists of monthly infusions for a course of 6 months followed by infusions every 3-6 months.3

New therapies for aggressive SLE include intravenous gammaglobulins,4 mycophenolate mofetil (blocks de novo guanosine synthesis)5 and immunoablation with autologous stem cell transplantation.6 Despite early reports of efficacy comparative randomized trials have failed to show the superiority of apheresis-cyclophosphamide over IV cyclophosphamide alone in active lupus nephritis.7 Trials with B-lymphocyte depletion by rituximab are showing promising results in SLE.8

Antiphospholipid (Hughes) Syndrome (APS)

APS is a noninflammatory autoimmune disease. The critical pathologic process is thrombosis, which results in most of the clinical features suffered by the patients. Any organ and any size of vessel can be affected leading to some emergencies. Clinical manifestations of APS associated with central nervous system include arterial thrombotic events, psychiatric features and non-thrombotic neurological syndromes. Stroke at a younger age is the most common manifestation of APS associated with antiphospholipid antibodies(apl).9,10,11 The most important cardiac manifestations presenting as emergencies in APS are valve disease and coronary artery disease.12 Pulmonary manifestations of APS include pulmonary hypertension. Some cases of diffuse alveolar haemorrhage have also been described.13 Haematological manifestations such as thrombocytopenia (most frequent), obstetric manifestations with maternal and foetal complications are well described with APS. Renal involvement includes thrombosis of glomerular capillary, thrombotic microangiopathy, cortical necrosis, renal artery thrombosis and renal vein thrombosis.14

Recurrent arterial and venous thrombosis can be prevented with warfarin anti-coagulation to an INR International normalized ratio) of = 3. Lifelong anticoagulation of patients is necessary in most of the situations. Catastrophic vascular occlusion leading to multi-organ failure is usually sudden, diagnostically confusing and immediately life threatening. Most effective treatment combines full dose anticoagulation, high dose GCS, plasmapheresis and intravenous immunoglobulins.15

Vasculitides

The vasculitides are heterogenous group of uncommon diseases characterized by blood vessel inflammation and necrosis. These conditions often have overlapping clinical and pathologic manifestations. Most of the vasculitides are systemic and may involve multiple organs. Primary vasculitis (when no underlying diseases were found) encompass vasculitis affecting predominantly large, medium and small sized blood vessels. Secondary vasculitis include vasculitis secondary to rheumatic diseases such as RA and SLE and vasculitis secondary to non-rheumatic diseases like sarcoidosis, malignancy and severe bacterial infections.16

Apart from some uncommon acute events (Table-5), rare forms of emergencies are encountered in the patients with vasculitides e.g. cerebral infarction in Wegner’s granulomatosis.17

Management has to be individualized depending upon the organ involved and type of vasculitis.

Not uncommonly the initial management of these emergencies could be based on a presumptive diagnosis.

Therapy should not be deferred pending confirmation of diagnosis by laboratory tests. The treatment involves GCS, cyclophosphamide, azathioprine, methotrexate, cyclosporine and immunoglobulins based upon the emergency situation.18

References
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