Rheumatological disorders in Critical Care

Question 1

What are somereasons patients with rheumatological conditions may need ICU care?

Answer 1

• End organ failure due to complications of their rheumatological disease
• Severe/atypical infection due to immune suppression
• Drug reaction from therapy for their rheumatological condition (DMARDs)
• Acute compromise unrelated but exacerbated by their condition or treatment e.g. bowel obstruction/perforation complicated by skin/wound problems or immunosuppression.

Question 2

Why are rheumatological conditions important in critical care?

Answer 2

• immunosuppression
• difficult to differentiate from sepsis
• difficult to diagnose
• require a high degree of suspicion
• can have a high mortality

Question 3

What is Macrophage Activation Syndrome (MAS)?

Answer 3

Macrophage activation syndrome is a form of haemophagocytic histiocytosis (HLH).
Primary (genetic) HLH is mainly a disease of infancy.
Secondary (acquired) HLH/MAS may occur in:
- malignancy
- Inflammatory/Rheumatological conditions (systemic juvenile idiopathic arthritis, adult onset stills disease, SLE, vasculitis)
- Organ transplant patients
- acquired immunodeficiency
- secondary to sepsis

It is characterised by loss of regulation of the immune response leading to macrophage and T cell mediated hyper inflammation with associated cytokine storm.

Clinically it presents with a:
- sepsis/SIRS type picture
- multiorgan involvement/dysfunction
- persisting fevers.
- coagulopathy/DIC
- lymphadenopathy/splenomegaly/hepatomegaly
- neurological features - confusion, seizures, coma

Biochemically it shows a:
- pancytopenia (may be thrombocytopenia predominantly)
- markedly elevated ferritin
- elevated triglycerides

Question 4

What is the management of macrophage activation syndrome?

Answer 4

Manage the patient in an ABCDE approach.
Specific features include:
- early aggressive supportive care and organ support.
- Elimination of suspected trigger(s).
- differentiation and exclusion of infection (often difficult)
- immunosuppression with high-dose corticosteroids +/- cyclosporin
- IVIg may have a role
- vigilance for secondary infection

Question 5

What is scleroderma renal crisis and how is it managed?

Answer 5

Scleroderma renal crisis is the presence of severe hypertension and rapidly declining renal function leading to oliguria/anuria in a patient with systemic sclerosis.
It is thought to be due to arterial renal vessel wall involvement/thickening leading to reduced perfusion and excessive renin release.

Patients may present with neurological features of hypertension or renal failure:
- oedema
- pulmonary oedema
- encephalopathy
- seizures
- headache
- LVF

Patient should be managed in A to E approach correction abnormalities as they are found.
The specific focus of care is:
- controlled reduction in blood pressure
- prevention of permanent renal damage.
- ACEi are central to treatment
- may be supported with beta blockers, CCBs and GTN.
- RRT may be required
- Plasma exchange may be required

Prognosis:
- renal function may never fully recover and may take a long time to liberate from RRT (up to 36 months).
- overall 5 year mortality is about 35%

Question 6

What is vasculitis?

Answer 6

Inflammation of blood vessels. Vasculitis refers specifically to an immune-mediated or autoimmune inflammation.
It can be divided into size of blood vessels it affects:
- large vessel (Takayasu’s, giant cell)
- medium vessel (Buerger’s, Kawasaki’s, polyarteritis nodosa)
- small vessel (EGPA, GPA, Bechet’s, HSP, microscopic polyangiitis (MPA))

Or the presence of associated serological phenomena:
- ANCA positivity (EGPA, GPA, MPA)
- ANCA negative

Question 7

What are the anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides? How can they be differentiated?

Answer 7

• Eosiniophilic granulomatosis with polyangiitis (EGPA - Churg-strauss)
• Granulomatosis with polyangiitis (GPA - Wegener’s)
• Microscopic polyangiitis (MPA)

EGPA - presence of eosinophilia, more likely to have cardiac involvement (pericarditis, myocarditis, dysrhythmias), nasal polyps, myeloperoxidase (MPO) antigen positive, pANCA, biopsy - extravascular eosinophils

GPA - More likely to have pulmonary involvement, pulmonary haemorrhage and subglottilc stenosis, proteinase 3 (PR3) antigen positive, cANCA positive, biopsy - granulomas with multi-nucleated giant cells.

MPA - more likely to have renal involvement as leading abnormality, but others also likely to have renal involvement, myeloperoxidase (MPO) antigen positive, pANCA positive

Question 8

What are the potential complications of ANCA positive vasculitis in critical care patients?

Answer 8

Usually small vessel disease, so any organ can be affected.
Predominantly associated with clinical features of:

• Renal impairment: uraemia, hyperkalaemia, fluid overload
• pulmonary impairment: hypoxia, hypercarbia, diffuse alveolar haemorrhage, ARDS picture, subglottilc stenosis (GPA)

Other complications:
- cardiovascular: hypotension, arrhythmias, pericarditis, myocarditis
- gastrointestinal: perforation, ulceration, pancreatitis, hepatitis
- neurological: cerebritis, encephalopathy, seizures, confusion, coma
- skin: cutaneous involvement, ulceration, rashes
- drug therapy related: immunocompromised infections, adverse drug reactions or side effects.

Question 9

What are the treatments for ANCA vasculitis?

Answer 9

• steroids
• cyclophosphamide
• rituximab
• plasma exchange

Question 10

What pharmacological therapies are you aware of for rheumatological disease?

Answer 10

• steroids for broad immune suppression and control of flare ups
• DMARDs e.g. methotrexate (analogue of folic acid), sulfasalazine
• Biologics e.g. anti-TNF (infliximab, ertanercept), IL-6 inhibitors (tocilizumab), B cell depletors (rituximab)