What is the diagnosis and treatment for a patient presenting with intermittent fever, jaw pain, fatigue, and rash?

Differential Diagnosis and Management of Intermittent Fever, Jaw Pain, Fatigue, and Rash

The combination of intermittent fever, jaw pain, fatigue, and rash requires immediate consideration of Adult-Onset Still's Disease (AOSD), tick-borne rickettsial infections (particularly Rocky Mountain Spotted Fever), and less commonly Q fever or autoinflammatory syndromes, with empiric treatment decisions based on clinical presentation and epidemiologic risk factors.

Critical Initial Assessment

History and Exposure Evaluation

• Document the temporal relationship between fever onset and rash appearance, as this provides crucial diagnostic clues—rash appearing simultaneously with fever suggests AOSD, while rash appearing 2-5 days after fever onset suggests RMSF 1
• Obtain detailed tick exposure history, including outdoor activities in wooded or grassy areas, as RMSF requires only 2-10 hours of tick attachment for transmission 2
• Assess for animal exposures and unpasteurized dairy products, as these increase risk for Q fever which presents with prolonged fever and fatigue 3
• Characterize the fever pattern specifically—quotidian (daily) high-spiking fevers >39°C are highly characteristic of AOSD 2
• Document jaw pain characteristics, as pharyngitis/sore throat is a major criterion for AOSD, while jaw claudication would suggest different pathology 2

Rash Characterization

• Determine if the rash is evanescent (transient) and salmon-colored, which is pathognomonic for AOSD and typically appears on the trunk and extremities during fever spikes 2, 4
• Check for palm and sole involvement, as this occurs in approximately 50% of RMSF cases but is uncommon in AOSD 2
• Note whether the rash is maculopapular progressing to petechial, which strongly suggests RMSF and requires immediate empiric doxycycline 1

Diagnostic Approach Based on Clinical Pattern

If AOSD is Suspected (Intermittent High Fevers + Transient Rash + Arthralgia)

• Obtain complete blood count looking for leukocytosis >10,000 with >80% granulocytes, which is a major Yamaguchi criterion 2
• Check ferritin level immediately—extreme hyperferritinaemia (often >1000 ng/mL) with glycosylated ferritin <20% strongly supports AOSD 2, 4
• Measure ESR and CRP, as markedly elevated inflammatory markers are expected 2, 4
• Obtain liver function tests, as hepatic transaminase elevations are a minor criterion 2
• Check RF and ANA, which should be negative in AOSD 2
• Apply Yamaguchi criteria: diagnosis requires 5 criteria with at least 2 major (fever >39°C for >1 week, arthralgia >2 weeks, typical rash, WBC >10,000 with >80% granulocytes) after excluding infections, malignancies, and other rheumatic diseases 2

If Tick-Borne Disease is Suspected (Recent Outdoor Exposure + Fever + Rash)

• Do not delay empiric doxycycline while awaiting laboratory confirmation if RMSF is suspected, as delay in treatment is the most important factor associated with death 2, 1
• Obtain CBC, comprehensive metabolic panel, and acute serology for R. rickettsii, E. chaffeensis, and A. phagocytophilum, but initiate treatment immediately 2, 1
• Look for thrombocytopenia (present in 40% of R. parkeri cases), mild leukopenia (50%), and elevated hepatic transaminases (78%), though these may be normal early in illness 2
• Start doxycycline 100 mg twice daily immediately if clinical suspicion exists, regardless of laboratory results 2, 1

If Q Fever is Considered (Prolonged Fever + Fatigue + Animal/Dairy Exposure)

• Obtain serologic testing for Coxiella burnetii phase I and II IgG and IgM antibodies, though treatment should not await results 2
• Perform thorough cardiovascular examination and consider echocardiography if valvular disease or vascular abnormalities are present, as these patients are at high risk for chronic Q fever endocarditis 2
• Check phase I IgG titers—levels ≥1:1024 with identifiable nidus of infection (endocarditis, vascular infection) indicate chronic Q fever requiring prolonged combination therapy 2

Treatment Algorithms

For Confirmed or Highly Suspected AOSD

• Initiate NSAIDs (indomethacin or naproxen preferred over aspirin) as first-line therapy, though only 7-15% of patients achieve disease control with NSAID monotherapy 2
• Add corticosteroids (prednisone 0.5-1 mg/kg/day) if inadequate response to NSAIDs within 1-2 weeks, as 88% of patients ultimately require steroids 2
• Consider early biologic therapy with IL-1 inhibitors (canakinumab) or IL-6 inhibitors for patients with severe systemic features or inadequate steroid response 4
• Monitor for chronic articular pattern development, which occurs in patients with polyarthritis and root joint involvement at onset and carries worse prognosis 2

For Suspected or Confirmed RMSF

• Administer doxycycline 100 mg twice daily immediately, as this is the treatment of choice regardless of patient age 2, 1
• Continue treatment for at least 3 days after fever resolves and until evidence of clinical improvement, typically 5-7 days total 2
• Hospitalize patients with evidence of organ dysfunction, severe thrombocytopenia, or altered mental status 1

For Chronic Q Fever (Phase I IgG ≥1:1024 + Identifiable Infection)

• Treat with doxycycline 100 mg twice daily PLUS hydroxychloroquine 200 mg three times daily, as combination therapy is necessary for bactericidal activity 2
• Obtain baseline ophthalmologic examination before starting hydroxychloroquine and repeat every 6 months due to retinal toxicity risk 2
• Continue treatment for at least 18 months for native valve infections and 24 months for prosthetic valve infections 2
• Monitor monthly with serologic testing and clinical evaluations, checking hydroxychloroquine levels (target 0.8-1.2 μg/mL) and doxycycline levels (target ≥5 μg/mL) if inadequate response 2

Critical Pitfalls to Avoid

• Do not wait for rash to appear before treating suspected RMSF—the classic triad of fever, rash, and tick bite is rarely present at initial presentation 2
• Do not assume absence of tick bite excludes RMSF—many patients do not recall tick exposure 2, 1
• Do not treat chronic Q fever based on elevated titers alone—clinical evidence of organ infection must be present 2
• Do not use aspirin as first-line NSAID for AOSD—indomethacin and naproxen are more effective 2
• Do not delay steroids in AOSD patients with severe systemic features—76-95% ultimately require corticosteroids 2
• Recognize that 67% of AOSD patients with chronic articular pattern require joint replacement—early aggressive treatment is critical 2

Long-Term Monitoring Requirements

For AOSD Patients

• Monitor for disease pattern evolution—monocyclic systemic (single episode), intermittent/polycyclic (recurrent flares), or chronic articular (dominant joint destruction) 2
• Patients with polyarthritis and root joint involvement at onset require closer monitoring for chronic articular pattern development 2

For Acute Q Fever Patients

• Perform serologic monitoring and physical examination at 3,6,12,18, and 24 months after acute infection 2
• Advise lifelong vigilance for symptoms in patients with valvular defects or vascular abnormalities, as they remain at high risk for chronic Q fever 2
• If phase I IgG titers rise to ≥1:1024 during monitoring, perform thorough clinical assessment to identify potential organ infection before initiating chronic treatment 2