What is the diagnosis and management of an ascending macular rash without fever or systemic symptoms?

Ascending Macular Rash Without Fever or Systemic Symptoms

The most likely diagnosis is secondary syphilis, which classically presents as a painless macular rash that ascends from the trunk to involve the palms and soles without fever or systemic symptoms. 1

Primary Diagnostic Consideration: Secondary Syphilis

Secondary syphilis should be at the top of your differential diagnosis for an ascending macular rash without fever. The key distinguishing features include:

• Painless maculopapular rash that characteristically involves palms and soles 1
• Absence of fever or systemic symptoms is typical 1
• Rash typically begins on trunk and ascends to extremities 1
• Diagnosis requires clinical examination coupled with serological testing (rapid plasma reagin) 1

Critical Alternative Diagnoses to Rule Out

Rocky Mountain Spotted Fever (RMSF)

While RMSF can present with macular rash, it has distinct features that help differentiate it:

• Rash begins as small blanching pink macules on wrists/ankles and spreads centrally (opposite pattern from your case) 2
• Rash typically appears on day 3-5 of illness and progresses to maculopapular with central petechiae by day 5-6 2
• Fever, severe headache, and myalgias are usually prominent (absent in your case) 2
• Up to 20% may lack rash entirely, making diagnosis challenging 2
• Palms and soles involvement occurs in only 50% of cases and typically late in disease 2

Drug Reaction

Consider adverse drug reaction, particularly if recent medication changes:

• Lamotrigine and other anti-epileptics can cause progressive macular rash 3
• May initially present indolently without systemic symptoms 3
• Can progress to severe conditions like toxic epidermal necrolysis 3
• Medication history is critical, especially recent dose changes 3

Viral Exanthems (Less Likely Without Fever)

The absence of fever makes viral causes less probable:

• Human herpesvirus 6 (HHV6) is most common viral cause of fever with maculopapular rash in children (24%) 4
• Measles, rubella, and EBV typically present with fever 2, 5
• Enteroviruses can cause petechial rashes but usually with fever 2

Diagnostic Algorithm

Step 1: Obtain Detailed History

• Sexual history and recent exposures 1
• Medication changes in past 2-8 weeks, especially anti-epileptics 3
• Tick exposure history (RMSF can rarely present without fever) 2, 6
• Travel history to endemic areas 2

Step 2: Physical Examination Focus

• Examine palms and soles carefully for macular lesions (pathognomonic for secondary syphilis) 1
• Assess rash distribution pattern: ascending (syphilis) vs. descending from wrists/ankles (RMSF) 2, 1
• Look for mucosal lesions (drug reaction, syphilis) 3
• Check for lymphadenopathy 5

Step 3: Laboratory Evaluation

• Rapid plasma reagin (RPR) or VDRL for syphilis - first-line test 1
• Complete blood count to assess for thrombocytopenia (RMSF, vasculitis) 7
• If RMSF suspected despite absent fever, obtain Rickettsia rickettsii antibody testing 6

Management Approach

For Secondary Syphilis (Most Likely)

Treat immediately with benzathine benzylpenicillin 2.4 million units intramuscularly 1

If Diagnosis Uncertain

• Do not delay treatment for syphilis if clinical suspicion is high 1
• If RMSF cannot be excluded and patient deteriorates, empiric doxycycline should be initiated 2
• Discontinue any recently started or dose-adjusted medications 3

Critical Pitfalls to Avoid

• Do not assume absence of fever rules out RMSF - up to 20% have atypical presentations 2
• Do not wait for palms/soles involvement to diagnose RMSF - this occurs late and in only 50% of cases 2
• Do not overlook medication history - drug reactions can present indolently before becoming life-threatening 3
• Do not forget to treat sexual partners if syphilis is diagnosed 1
• Do not dismiss the diagnosis of syphilis based on previous negative testing - timing of serological testing matters 1