How to manage persistent leukocytosis (elevated white blood cell count) in a patient with Rheumatoid Arthritis (RA)?

Management of Persistent Leukocytosis in Rheumatoid Arthritis

In a patient with RA and persistent leukocytosis of 14,000, first determine if the patient is on corticosteroids, as this is the most common cause of leukocytosis in RA patients; if corticosteroids are being used, the leukocytosis is likely benign and related to medication rather than infection or disease activity. 1

Immediate Assessment Algorithm

Step 1: Medication Review

• Corticosteroid use is the primary driver of leukocytosis in RA patients, with 40% of patients on steroids (mean dose 7 mg prednisone daily) developing leukocytosis, compared to only 7.5% of those not on steroids 1
• Other medications associated with leukocytosis include lithium and beta agonists 2
• The elevation is predominantly neutrophilic in nature 1

Step 2: Evaluate for Infection

• Rule out occult infection as the priority, particularly if leukocytosis is newly detected 1
• However, in the absence of fever, localizing symptoms, or clinical signs of infection, an infectious cause is rarely found 1
• Maintain vigilance for spontaneous bacterial peritonitis if the patient has cirrhosis, as immunosuppressive therapy increases infection risk 3

Step 3: Assess RA Disease Activity

• Patients with leukocytosis tend to have more active arthritis, though this is a weaker association than corticosteroid use 1
• Measure disease activity using validated tools (SDAI ≤11 or CDAI ≤10 for low disease activity target) 4
• The treatment goal should be remission or low disease activity, with assessment every 1-3 months 5

Management Strategy Based on Clinical Context

If Patient is on Corticosteroids:

• The leukocytosis is likely medication-related and benign 1
• Consider tapering corticosteroids if the patient is in remission, as long-term use beyond 1-2 years carries risks including osteoporosis, cataracts, and cardiovascular disease 4
• Very low-dose glucocorticoids (1-3 mg prednisone equivalent) may be acceptable for disease control 4

If Patient is NOT on Corticosteroids:

• Investigate for infection more thoroughly, as the prevalence of leukocytosis without steroids is only 7.5% 1
• Assess for active RA disease activity and optimize DMARD therapy if disease is not controlled 4
• Consider that physical or emotional stress can transiently elevate WBC counts 2

If WBC Count is Extremely Elevated (>100,000):

• This represents a medical emergency requiring immediate evaluation for primary bone marrow disorders, as there is risk of brain infarction and hemorrhage 2
• Suspect primary bone marrow disorders if there are concurrent abnormalities in red blood cells or platelets, weight loss, bleeding, bruising, or organomegaly 2

Optimizing RA Treatment to Address Disease Activity

If disease activity is contributing to leukocytosis:

• Ensure methotrexate is optimized (15-25 mg weekly with folic acid 1 mg daily) as first-line therapy 5
• If inadequate response at 3 months or target not achieved at 6 months, escalate therapy 4
• Add biologic DMARDs (TNF inhibitors, abatacept, tocilizumab, or rituximab) for persistent moderate-to-high disease activity 4

Common Pitfalls to Avoid

• Do not aggressively pursue infectious workup in asymptomatic patients on corticosteroids, as the leukocytosis is most likely medication-related 1
• Do not overlook corticosteroid contribution when evaluating leukocytosis, even at low doses (mean 7 mg daily in the study) 1
• Do not assume leukocytosis always indicates poor disease control, as the association with disease activity is weaker than the medication effect 1
• Avoid unnecessary escalation of immunosuppression based solely on WBC count without assessing validated disease activity measures 4