What is the differential diagnosis for a pregnant woman presenting with fever, maculopapular (maculopapular rash) rash, and polyarthritis (inflammation of multiple joints)?

Differential Diagnosis for Pregnant Woman with Fever, Maculopapular Rash, and Polyarthritis

The most critical immediate consideration is Adult-Onset Still's Disease (AOSD), which classically presents with this exact triad of high-spiking fever, salmon-pink maculopapular rash, and polyarthritis, though life-threatening infectious causes including tickborne rickettsial diseases, disseminated gonococcal infection, secondary syphilis, and parvovirus B19 must be urgently excluded first. 1, 2

Immediate Life-Threatening Exclusions Required

Tickborne Rickettsial Diseases

• Rocky Mountain Spotted Fever (RMSF) carries a 5-10% case-fatality rate and requires immediate empiric doxycycline without waiting for laboratory confirmation if fever + rash + any tick exposure history exists 2
• RMSF initially presents as small blanching pink macules on ankles/wrists 2-4 days after fever, progressing to maculopapular with central petechiae spreading to palms, soles, and trunk 1, 2
• Up to 20% of RMSF cases never develop rash, and less than 50% have rash in first 3 days, making absence of rash unreliable for exclusion 1, 2
• Human Monocytic Ehrlichiosis (HME) presents with maculopapular rash in only 30% of adults, appearing later (median 5 days) with 3% case-fatality rate 1, 2

Other Critical Infectious Causes

• Disseminated gonococcal infection presents with fever, migratory polyarthritis (knees, wrists, ankles), and maculopapular rash progressing to pustular lesions 1
• Secondary syphilis causes maculopapular rash involving palms and soles with polyarthritis and fever 1
• Parvovirus B19 is particularly dangerous in pregnancy, causing miscarriage, stillbirth, premature birth, and intrauterine growth restriction 1

Primary Diagnostic Consideration: Adult-Onset Still's Disease

Classic Triad Presentation

• AOSD presents with high-spiking quotidian or double-quotidian fever exceeding 39°C, lasting under 4 hours, peaking in late afternoon/early evening 1
• The characteristic salmon-pink, evanescent maculopapular rash appears predominantly on proximal limbs and trunk, often accompanying fever spikes, and may be mildly pruritic 1
• Polyarthritis affects knees, wrists, and ankles most frequently (64-100% of patients), presenting as symmetric involvement with joint pain associated with fever spikes 1

Supporting Clinical Features

• Sore throat occurs in 38-92% of cases 1
• Lymphadenopathy in 32-74% of cases 1
• Hepatosplenomegaly and serositis may be present 1
• Myalgias are common (56-84% of cases) 1

Laboratory Hallmarks

• Marked leukocytosis with striking neutrophilia (50% have WBC >15×10⁹/L, 37% have WBC >20×10⁹/L) 1
• Elevated ESR and CRP in virtually all patients 1
• Anemia of chronic disease and reactive thrombocytosis are common 1
• Ferritin levels are typically markedly elevated 1

Additional Differential Considerations

Autoimmune/Rheumatologic Causes

• Systemic lupus erythematosus can present with fever, maculopapular rash, and polyarthritis, but typically has positive ANA and anti-dsDNA antibodies 3
• Dermatomyositis triggered by pregnancy presents with rash, fever, and weakness; various myositis-specific autoantibodies (anti-ARS, anti-MDA-5, anti-Mi-2, anti-TIF-1γ) may be positive 4
• Acute rheumatic fever causes migratory polyarthritis with erythematous macular rash, but requires preceding streptococcal pharyngitis 1, 3

Infectious Causes with Polyarthritis

• Acute Q fever presents with fever, headache, myalgia, and maculopapular or purpuric rash in 5-21% of cases, though polyarthritis is less prominent 1
• Leptospirosis causes fever and maculopapular rash but typically presents with conjunctival suffusion and less prominent polyarthritis 1
• Toxoplasmosis has been associated with AOSD-like presentation with fever, maculopapular rash, and seronegative polyarthritis 5

Drug Hypersensitivity

• Drug reactions can cause maculopapular rash with fever and arthralgias, but true polyarthritis is uncommon 1
• Consider recent medication exposures including antibiotics, particularly if rash appeared after drug initiation 1

Diagnostic Algorithm

Immediate Laboratory Workup

• Complete blood count with differential looking for leukocytosis (AOSD), leukopenia (ehrlichiosis), or thrombocytopenia (RMSF/ehrlichiosis) 1, 2
• Comprehensive metabolic panel assessing for hyponatremia and elevated hepatic transaminases (RMSF/ehrlichiosis) 1, 2
• Inflammatory markers (ESR, CRP) which are markedly elevated in AOSD 1
• Ferritin level which is typically very high in AOSD 1
• Acute serology for Rickettsia rickettsii, Ehrlichia chaffeensis, and Anaplasma phagocytophilum 2
• RPR/VDRL and treponemal testing to exclude secondary syphilis 1
• Parvovirus B19 IgM and IgG given pregnancy implications 1
• Blood cultures for disseminated gonococcal infection 1
• ANA, anti-dsDNA, complement levels if lupus suspected 3

Critical Clinical Assessment Points

• Document fever pattern (quotidian pattern suggests AOSD) 1
• Examine for rash characteristics: evanescent and salmon-pink favors AOSD; progression to petechiae suggests RMSF 1, 2
• Assess for palm and sole involvement (RMSF, secondary syphilis) 1
• Evaluate joint pattern: symmetric polyarthritis of knees, wrists, ankles suggests AOSD 1
• Obtain detailed tick exposure and travel history 2
• Review all medications for potential drug reaction 1

Management Priorities

Empiric Treatment Considerations

• If RMSF cannot be excluded: initiate doxycycline 100 mg twice daily immediately without waiting for laboratory confirmation, as mortality increases with delayed treatment 2
• Doxycycline is safe in pregnancy for short courses when treating life-threatening rickettsial disease 2
• Clinical improvement should occur within 24-48 hours if RMSF/ehrlichiosis is the cause 2

Common Pitfalls to Avoid

• Never dismiss the possibility of RMSF based on absence of tick bite history, as up to 40% report no bite 6
• Do not wait for rash to involve palms and soles before considering RMSF, as this occurs late and in only 50% of cases 1, 2
• Avoid attributing symptoms to benign viral exanthem without excluding life-threatening bacterial causes first 6
• Remember that early RMSF serology is typically negative, so negative testing does not exclude diagnosis 6
• Consider that AOSD diagnosis requires exclusion of infectious and malignant causes first 1

Pregnancy-Specific Considerations

• Parvovirus B19 infection requires urgent fetal monitoring for hydrops fetalis and intrauterine growth restriction 1
• Dermatomyositis in pregnancy requires aggressive treatment to prevent fetal loss; delay in treatment and poor corticosteroid response correlate with poor fetal outcomes 4
• AOSD in pregnancy may require careful immunosuppressive management balancing maternal disease control with fetal safety 1