What is the best course of action for a patient with a history of autoimmune disorders, presenting with a feverish feeling and persistent runny nose, despite having normal white blood cell (WBC) counts?

Management of Feverish Feeling with Persistent Runny Nose and Normal WBC in Autoimmune Patients

In a patient with autoimmune disease presenting with subjective fever, persistent rhinorrhea, and normal white blood cell counts, you should immediately obtain at least two sets of blood cultures from different anatomic sites before any antibiotic administration, followed by a CBC with differential to assess for elevated band counts (>1,500/mm³) or neutrophil percentage >90%, which strongly suggest bacterial infection despite normal total WBC. 1

Initial Diagnostic Priorities

Blood Work and Cultures

• Obtain blood cultures first (at least two sets from different anatomic sites) as this is the highest-yield initial test for identifying occult bacteremia, even when total WBC appears normal 1
• Order CBC with differential immediately—the total WBC count can be misleading; an elevated band count >1,500/mm³ has a likelihood ratio of 14.5 for bacterial infection, and neutrophil percentage >90% has a likelihood ratio of 7.5 for bacterial infection 1
• The normal total WBC does not exclude serious bacterial infection in immunosuppressed patients 2

Critical History Elements

• Document all medications started within the past 3 weeks, as drug-induced fever has a mean lag time of 21 days after drug initiation and is common in patients on immunosuppressive therapy 1
• Obtain detailed travel history within the past 3 weeks, as enteric fever and rickettsial infections commonly cause prolonged fever in returned travelers 1
• Ask specifically about tick exposure or outdoor activities in wooded areas, as tickborne rickettsial diseases present with nonspecific fever and normal or low WBC counts 1, 3

Distinguishing Infection from Disease Flare

Features Suggesting Infection Over Autoimmune Flare

• Prolonged fever >10 days with normal leukocyte count, thrombocytopenia, and increased liver enzymes is suggestive of acute Q fever infection 2
• Persistent rhinorrhea with subjective fever may indicate upper respiratory viral infection or early bacterial sinusitis, which can progress to serious infection in immunosuppressed patients 4
• Maintain high index of suspicion for opportunistic infections, including cytomegalovirus reactivation, which presents with fever and normal WBC counts in immunosuppressed patients 1

Features Suggesting Autoimmune Disease Activity

• Fever in systemic lupus erythematosus and other autoimmune diseases typically presents with other systemic manifestations including rash, arthritis, or serositis 2, 5
• Patients with Adult-Onset Still's Disease characteristically have sore throat (68-92% of cases), myalgia (56-84%), and evanescent rash (51-94%) accompanying fever 2
• Autoinflammatory syndromes present with recurrent febrile attacks, often with characteristic patterns and associated symptoms 2, 6

Specific Testing Based on Clinical Context

For Suspected Bacterial Sinusitis

• Azithromycin is indicated for acute bacterial sinusitis due to Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae 4
• Culture and susceptibility tests should be performed before treatment when possible, though therapy may be initiated before results are available 4

For Suspected Tickborne Illness (if outdoor exposure)

• Order CBC immediately—thrombocytopenia and leukopenia are characteristic findings that guide early diagnosis 3
• Obtain comprehensive metabolic panel to assess liver function, as hepatic abnormalities occur in 50-75% of ehrlichiosis and anaplasmosis cases 3
• PCR testing on EDTA-anticoagulated whole blood for Anaplasma phagocytophilum, Ehrlichia chaffeensis, and spotted fever group rickettsiae should be collected before initiating doxycycline 3
• Serologic testing (acute serum) for Borrelia burgdorferi, E. chaffeensis, and A. phagocytophilum 3

For Immunosuppressed Patients

• Viral studies including CMV, HHV6, EBV, parvovirus, and HIV to identify underlying infections 7
• For Grade 3 lymphopenia (250-499 lymphocytes/μL), initiate weekly CBC monitoring and CMV screening 7
• For Grade 4 lymphopenia (<250 lymphocytes/μL), initiate Pneumocystis jirovecii prophylaxis and consider Mycobacterium avium complex prophylaxis 7

When to Start Empiric Antibiotics

Start empiric antibiotics immediately if any of the following are present: 1

• Signs of hemodynamic instability
• Septic shock
• Altered mental status
• Respiratory distress
• Suspected cholangitis

Do not delay treatment while awaiting laboratory results when clinical suspicion is high, particularly for Rocky Mountain spotted fever which has high mortality 3

Common Pitfalls to Avoid

• Do not rely on normal total WBC to exclude bacterial infection—check the differential for elevated bands and neutrophil percentage 1
• Negative acute-phase serology does not exclude tick-borne disease, as antibodies are typically absent during the first 7 days of illness 3
• Distinguishing between disease flare, medication effect, and new-onset infection is challenging in autoimmune patients—when in doubt, treat for infection first 7, 5
• Lymphopenia increases risk for opportunistic infections; prophylaxis should be considered for severe cases 7
• Patients with sinonasal symptoms and autoimmune disorders have more severe subjective and objective presentations than typical chronic rhinosinusitis patients 8