Rheumatologic Disorders in the Intensive Care Unit

Donough G. Howard

I. OVERVIEW. This chapter reviews the important rheumatic diseases most likely to be encountered in the intensive care unit (ICU). Brief descriptions and treatment options are discussed with a constant emphasis on the ongoing risk of infectious complications that may lead to critical illness.

II. RHEUMATOID ARTHRITIS

A. General principles. A chronic inflammatory disorder affecting the synovial lining of joints, tendons, and bursae in addition to a large variety of extra-articular structures. The etiology of rheumatoid arthritis (RA) is unknown. Patients may require ICU admission because of disease complications or complications of therapy, typically infections.

B. Treatment. Table 139-1 details current treatment with disease-modifying antirheumatic drugs (DMARDs). As a general rule, immunosuppressive DMARDs should be withheld in critically ill patients.

1. RA therapy and infection risk.

a. Biologic therapy is considered to be associated with an increased risk of infection and with an increase in morbidity and mortality from infection.

b. The risk of reactivation of latent TB is increased with biologic therapy.

c. Reactivation of hepatitis B in chronic carriers has also been reported with some biologic therapies.

d. Rare cases of progressive multifocal leukoencephalopathy (PML) due to reactivation of JC virus has been reported with the use of rituximab.

e. Biologic and steroid therapy may attenuate the normal presentation of sepsis.

C. System-specific considerations in RA.

1. Pulmonary.

a. Pleural disease.

i. Pleural inflammation/effusions occur frequently.

ii. May be asymptomatic or lead to large symptomatic effusions.

iii. Effusions require aspiration to rule out infection or other causes.

iv. Effusions are exudative with low glucose levels.

b. Parenchymal lung involvement.

i. Interstitial lung disease (ILD).

ii. Bronchiolitis obliterans with organizing pneumonia (BOOP) or cryptogenic organizing pneumonia (COP).

iii. Lung toxicity from medications, principally methotrexateinduced pneumonitis.

iv. Infection due to immunocompromised state, including tuberculosis.

v. Pulmonary rheumatoid nodules.

c. Diagnosis.

i. Presence of ground glass and reticular changes on high-resolution computed tomography (CT) scanning.

ii. Bronchoscopy and bronchoalveolar lavage (BAL) are useful to rule out opportunistic infection.

iii. Open lung biopsy or video-assisted thoracic surgery (VATS) is reserved for cases where there is diagnostic confusion or in patients who have failed to respond to initial treatment.

d. Treatment.

i. BOOP and acute methotrexate toxicity tend to be steroid responsive and usually do not require other immunosuppressive agents.

ii. ILD treatment in RA is controversial. Corticosteroids, mycophenolate, and cyclophosphamide have been used in rapidly advancing disease.

TABLE 139-1 Treatment of RA with DMARDs

	Dose/administration	Class	Adverse reactions	Special considerations
Oral DMARDs
Methotrexate	7.5-25 mg q wk PO, SC/IM	Dihydrofolate reductase inhibitor	Hepatotoxicity, bone marrow suppression, ILD, decreased resistance to infection	Concomitant use of folic acid recommended, monitor complete blood count (CBC), liver function tests (LFTs)
Leflunomide (Arava)	10-20 mg daily PO	Pyrimidine synthesis inhibitor	Diarrhea, alopecia, rash, hepatotoxicity, decreased resistance to infection, increases hepatotoxicity of other drugs	Metabolized through enterohepatic circulation with half-life of > 90° Urgent elimination requires treatment with cholestyramine
TNF inhibitors
Etanercept (Enbrel)	50 mg q wk SC in single or divided doses	TNF receptor blocker	Sepsis, reactivation of TB	Caution in CHF (NYHA class III/IV); avoid live vaccines; contraindicated in serious infections
Adalimumab (Humira)	40 mg q 2 wk SC	Monoclonal anti-TNF antibody	Sepsis, reactivation of TB	Caution in CHF; avoid live vaccines; contraindicated in serious infections
Certolizumab (Cimzia)	200 mg q 2 wk SC	Pegylated monoclonal anti-TNF antibody	Sepsis, reactivation of TB	Caution in CHF; avoid live vaccines; contraindicated in serious infections
Golimumab (Simponi)	50 mg q 4 wk SC	Monoclonal antibody	Sepsis, reactivation of TB	Caution in CHF; avoid live vaccines; contraindicated in serious infections
Infliximab (Remicade)	3-5 mg/kg q 4-8 wk IV infusion	Monoclonal anti-TNF antibody	Sepsis, reactivation of TB, infusion reactions	Caution in CHF; avoid live vaccines; contraindicated in serious infections
Other biologic medications
Anakinra (Kineret)	100 mg qd SC	IL-1 receptor antagonist	Diarrhea, increased risk of infection	Avoid live vaccines; not used in combination with other biologic DMARDs
Rituximab (Rituxan)	1,000 mg IV on day 1 and 15 repeated q 6 mo	Monoclonal anti-CD20 antibody	Sepsis, infusion reactions	Patients remain B-cell depleted and immunocompromised for months after treatment; rare cases of PML due to reactivation of JC virus have been reported; not used in combination with other biologic DMARDs
Abatacept (Orencia)	500-1,000 mg IV q 4 wk	Inhibits T-cell activation	Sepsis, may exacerbate COPD	Reactivation of TB, reactivation of hepatitis B reported; avoid live vaccines; not used in combination with other biologic DMARDs
Tocilizumab	8 mg/kg IV q 4 wk	IL-6 inhibition	Sepsis, infusion reactions, increased liver transaminases, hypercholesterolemia	Reactivation of TB, monitor aspartate aminotransferase or alanine aminotransferase (AST/ALT) every 4-8 wk for first 6 mo, avoid live vaccines; not used in combination with other biologic DMARDs
Tofacitinib	5 mg b.i.d PO	Janus kinase inhibitor	Infections including opportunistic. hyperlipidemia, cytopenias	New class of DMARD recently licensed
PO, per oral; mg, milligram; SC, subcutaneous; IM, intramuscular; TNF, tumor necrosis factor; TB, tuberculosis; CHF, congestive heart failure; IV, intravenous; COPD, chronic obstructive pulmonary disease; DMARDs, disease-modifying antirheumatic drugs; IL-1, interleukin 1.