Rheumatoid Arthritis: Management and Complications in the ED

Authors: Samantha Berman, MD (EM Chief Resident, Rutgers – RWJMS) and Joshua Bucher, MD (Assistant Professor of EM, Rutgers – RWJMS) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW Med Ctr / Parkland Memorial Hospital) and Brit Long, MD (@long_brit, EM Attending Physician at SAUSHEC)

Introduction:

Rheumatoid arthritis is a progressive systemic polyarticular inflammatory arthritis of unclear etiology.  Its prevalence in the U.S. is about 1%, and it affects women roughly twice as often as men. While not fatal itself, complications of the disease make it the most common rheumatic disease requiring ICU admission (2). Understanding of this disease is necessary for the emergency medicine physician to improve patient morbidity and mortality.

Admission to the hospital follows either an infection or a disease flare. Typical disease presentation includes severe joint pain with symmetric synovial joint involvement. If left untreated, patients have a risk of deformity and disability. However, with the advent of disease modifying anti-rheumatic drugs (DMARDs) and newer biologic agents, the disease course has changed dramatically.

So what can we as EM docs do? Being armed with the knowledge of this disease and its complications can lead to earlier recognition and diagnosis as well as optimal outcomes.

Initial Presentation:

A 50 year-old female with no significant PMH presents with 2 month history of pain, swelling, and warmth in both of her feet and ankles and a 2 week history of the same complaints in her hands. She sought medical care when pain and morning stiffness failed to improve with OTC ibuprofen and prohibited her from playing tennis.  Physical exam revealed tender, swollen, and warm ankles bilaterally and swelling of the digits in her hands bilaterally. No nodules or deformity were noted.  Vital signs are within normal limits.

Diagnostics:

-Rheumatoid arthritis is a CLINICAL diagnosis in the emergency department.

-ESR, CRP, and Rheumatoid factor lack sensitivity and specificity and may be elevated in several other disease states. Therefore they are low yield in the ED.

ED Treatment of Acute Flares (3):

-NSAIDs are first line for a trial period following a diagnosis of RA. These do not prevent joint destruction, and no particular agent has superior efficacy. It is permissible to trial one for 4 weeks at high doses and if that one does not alleviate symptoms, you can switch to a different class of NSAIDs for another 4 weeks.

-Steroids can be used should NSAIDs fail. Appropriate regimens include:

• Methylprednisolone: 2-32mg PO daily x 1-4 weeks taper
• Prednisone: 5-10 mg PO daily with a 4 week slow taper

-Disease modifying anti-rheumatic drugs (DMARDs) are the definitive treatment and the mainstay of RA therapy. They can take 2-3 months to take effect so use of NSAIDs or steroids as a bridge is necessary. DMARDs can halt disease progression and are highly recommended.

** The ED doc will encounter adverse effects of DMARDs in patients who have been both recently started on them and who have been on them for decades**

Adverse Effects of Common DMARDs:

MTX: Nausea, vomiting, diarrhea, stomatitis, bone marrow suppression, liver toxicity, pneumonitis, AKI

Sulfasalazine: GI upset, rash, allergic reactions, headache, alopecia, G6PD deficiency hemolytic anemia, liver, renal and pulmonary toxicity, bone marrow suppression, Stevens-Johnson syndrome

Leflunomide: Hepatotoxicity

Hydroxychloroquine: GI upset, photosensitivity, rash, reduced peripheral and night vision, tinnitus, CNS disturbances, ataxia, irritability, and hepatotoxicity

Biologics: When first line treatment and other DMARDs have failed, many patients are started on biologic agents, which are synthetic, genetically engineered proteins designed to target specific areas of the immune system to suppress inflammation.

The most commonly recognized biologics are the TNF-blockers (-umabs, -imabs).

Other specific drug targets include interleukin-6 inhibitors (tocilizumab), B cell antagonists (rituximab), T cell antagonists (abatacept), interleukin-1 blocker (anakinra), and Janus kinase inhibitors (tofacitinib).

Major side effect profiles of all the above biologics include increased risk of severe infection from immunosuppression including tuberculosis, as well as bone marrow suppression, hepatotoxicity, anaphylaxis and GI distress. These patients are considered immunocompromised and must be treated as such (5,7).

**Pregnancy: all the above meds are Class X except certolizumab. Physicians have an obligation to inform all newly pregnant patients or patients trying to become pregnant to stop taking the medications.

Many vaccines are ineffective while a patient is on DMARDs. Tdap is safe, but the MMR and zoster vaccines should not be given to patients taking anti-TNF meds!

Complications by Organ System (1,4):

AIRWAY

Atlanto-axial subluxation results from long-standing disease. Structural changes render joint facets and ligaments unstable which increases risk of injury. Forward dislocation is the most common with a vertical dislocation being most dire (8). Warning signs include new occipital pain, distal finger paresthesias, sensory disturbances, and myelopathy from spinal canal narrowing. Diagnostics include a lateral flexion c-spine x-ray, CT scan, or MRI, which is the preferred modality. CAUTION: It is unwise to passively flex the neck in patients with RA as subluxation can be SILENT. This must be considered in traumas, falls, and MVCs. Even minor trauma can cause permanent neurological injury and even sudden death.

** Difficult Intubation Alert! Neck and TMJ immobility and severely restricted range of motion may make direct laryngoscopy very difficult.

** TIP: utilize airway adjuncts, fiberoptics, PREP FOR CRIC, and avoid neck hyperextension

Cricoarytenoid arthritis affects 30% of RA patients. It is usually asymptomatic; however, symptomatic presentations include hoarseness, foreign body sensation, throat pain, inspiratory stridor, cough, dysphagia, and wheezing. Physical exam reveals tenderness over cartilaginous structures. Diagnosis is made via CT or fiberoptic laryngoscopy, which might show edema, reduced vocal cord motility, upper airway obstruction, or arytenoid cartilage asymmetry. Treatment is high dose steroids (9).

** Difficult Airway Alert! May require emergent surgical airway.

PULMONARY

Interstitial pulmonary fibrosis can occur as a result of chronic inflammatory changes to lung interstitium. Pulmonary hypertension develops secondarily which leads to respiratory failure. Symptoms are usually slowly progressive with cough and exertional dyspnea as presenting symptoms.

CARDIOVASCULAR

Accelerated coronary atherosclerosis (RR 3.0 of developing atherosclerosis in RA) leads to unrecognized myocardial infarction resulting from atypical anginal symptoms and attribution of chest pain to arthritis. Patients are less likely to undergo invasive evaluations and therefore less likely to receive appropriate treatment so missed MI is a common pitfall in this population. Fibrosis of the myocardium also leads to acute heart failure, cardiomyopathy, conduction disturbances, pericarditis, and tamponade.

VASCULAR

**Catastrophic Antiphospholipid Syndrome is a rare, rapidly progressive vaso-occlusive process involving the simultaneous venous and arterial thrombosis leading to multiorgan failure from pulmonary embolus, renal failure (main organ system involved), stroke, MI, ultimately progressing to DIC. It carries a 50% mortality rate despite treatment with heparin, high dose steroids, IVIG, and plasmapheresis.

MUSCULOSKELETAL

Septic arthritis is a CAN’T MISS DIAGNOSIS in rheumatoid arthritis. It is often overlooked in the early stages of infection due to attribution to an RA flare. The average delay in diagnosis is 1-3 weeks, which results in irreversible joint damage. Mortality approaches 30% with delayed diagnosis and treatment (8).

HEMATOLOGICAL

Felty’s syndrome is a tetrad of neutropenia, leukopenia, splenomegaly, and recurrent bacterial infections. Anemia of chronic disease and non-Hodgkin’s lymphoma are other heme-related complications that can often arise from either the disease process itself or disease treatment.

RENAL

** Renal complications are a major source of morbidity and mortality. Complications include acute nephritis syndrome, renal vein thrombosis, rhabdomyolysis, and fulminant renal failure.

OCULAR

Episcleritis, peripheral ulcerative keratitis and keratoconjunctival sicca are rare but possible complications that are treated with artificial tears, topical ophthalmic steroids, and systemic NSAIDs.

GASTROINTESTINAL

The most common GI complication is hemorrhage secondary to drug therapy side effects, bowel ischemia, ulcers, or vasculitis. Other more rare complications are cholecystitis, diverticulitis, bowel edema from recurrent inflammation, abdominal angina, strictures, stenosis, and bowel obstruction.

Summary:

Rheumatoid arthritis, a seemingly benign disease entity itself, carries a host of anxiety-inducing complications that every ED doc should be able to address. While RA is largely a clinical diagnosis in the ED, prompt recognition of its complications can lead to decreases in morbidity and mortality down the road for these patients.

Key take-home points:

-RA patients may present with difficult airways from A-A instability. Prepare for surgical airway when intubating.

-Maintain a high suspicion for septic arthritis when evaluating a hot, swollen joint in an RA patient.

-Diagnosis of RA is made CLINICALLY in the ED. Consider it in a patient with an insidious course of symmetric arthralgias of the smaller joints.

-Cornerstone of treatments of flares in the ED is high dose NSAIDs and steroids.

-Remember that patients taking DMARDs are immunocompromised and are thus prone to severe infection and end organ dysfunction.

References / Further Reading:

1. Arnold I, Andresen J. Medical Emergencies due to Rheumatoid Arthritis (RA) and Ankylosing Spondylitis (AS). Aktuelle Rheumatologie [serial online]. n.d.;35(1):61-75. Available from: Science Citation Index, Ipswich, MA. Accessed August 15, 2016
2. Cabling M, Colburn K, Hawkins R. Rheumatoid Arthritis: An Emergency Physician’s Perspective. Emergency Medicine Reports [serial online]. November 16, 2014;35(24):285-291. Available from: Academic Search Premier, Ipswich, MA. Accessed August 15, 2016.
3. Bingham C. Rheumatoid Arthritis: Treatment. Arthritis Information. http://www.hopkinsarthritis.org/arthritis-info/rheumatoid-arthritis/ra-treatment/#new. Published March 21, 2016. Accessed August 26, 2016.
4. Morabito GC, Tartaglino B. Emergencies in Systemic Rheumatic Diseases. In: Tintinalli J, ed. Emergency Medicine: A Comprehensive Study Guide. 7th ed. New York, NY: McGraw-Hill; 2011:1911-1920.
5. Singh JA, Furst DE, Bharat A, Curtis JR, Kavanaugh AF, Kremer JM, et al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2012 May;64(5):625-39.
6. Harvey S. Rheumatoid Arthritis. http://umm.edu/health/medical/reports/articles/rheumatoid-arthritis. Published March 18, 2013. Accessed September 1, 2016.
7. Baghai M, Osmon DR, Wolk DM. Fatal Sepsis in a Patient With Rheumatoid Arthritis Treated With Etanercept. Elsevier. 2001;76(6):653-656. doi:10.4065/76.6.653.
8. Slobodin G, Hussein A, Rozenbaum M. The emergency room in systemic rheumatic diseases. Emergency Medicine Journal. 2006;23(9):667-671. doi:10.1136/emj.2005.033233.
9. Leicht M, Harrington T. Cricoarytenoid arthritis: A cause of laryngeal obstruction. Annals of Emergency Medicine. 1987;16(8):885-888. doi:http://dx.doi.org/10.1016/S0196-0644(87)80527-9.