What are the differential diagnoses for a petechial rash on the lower extremities?

Differential Diagnoses for Lower Extremity Petechial Rash

Life-Threatening Causes Requiring Immediate Action

If fever is present with petechial rash on lower extremities, initiate doxycycline 100 mg twice daily immediately without waiting for laboratory confirmation, as Rocky Mountain Spotted Fever carries a 5-10% mortality rate and delays in treatment significantly increase death risk. 1

Meningococcemia

• Presents with rapidly progressive petechial rash that can evolve to purpura fulminans with full-thickness skin necrosis 2
• Rash progresses more rapidly than RMSF, often within hours rather than days 3
• Look for fever, altered mental status, hypotension, and signs of septic shock 3
• CSF analysis shows gram-negative diplococci, very low glucose (<20-30 mg/dL), and neutrophilic pleocytosis 3
• Requires immediate empiric treatment for both meningococcemia and RMSF if neither can be ruled out 3

Rocky Mountain Spotted Fever (RMSF)

• Initial presentation: small (1-5 mm) blanching pink macules on ankles and wrists appearing 2-4 days after fever onset 1
• Progresses to maculopapular with central petechiae, spreading centripetally to involve entire body including palms and soles 3, 1
• Classic petechial rash typically appears on day 5-6 of illness and signifies severe disease progression 3
• Critical red flags: fever + headache + tick exposure (or endemic area) + thrombocytopenia/hyponatremia 1
• Up to 20% never develop rash, and 40% do not report tick bite history 3, 4
• Expect clinical improvement within 24-48 hours of starting doxycycline 1

Infectious Causes

Viral Infections

• Parvovirus B19: During outbreaks, causes generalized petechial rashes in 76% of affected children, typically dense and widely distributed with accentuation in distal extremities, axillae, or groin 5
• Associated with mild constitutional symptoms, fever (85% of cases), leukopenia, and thrombocytopenia 5
• Parvovirus DNA detectable in serum even when IgM is negative 5
• Enteroviral infections: Most common cause of maculopapular rashes but typically spare palms, soles, face, and scalp 1, 6

Human Monocytic Ehrlichiosis (HME)

• Rash occurs in only 30% of adults (up to 66% in children), appearing later in disease course (median 5 days after onset) 3, 1
• Varies from petechial or maculopapular to diffuse erythema 3
• Rarely involves palms and soles 3, 1
• 3% case-fatality rate 1
• Look for leukopenia (up to 53%), thrombocytopenia (up to 94%), and elevated liver transaminases 3

Hematologic and Vasculitic Causes

Henoch-Schönlein Purpura (HSP)

• IgA-mediated vasculitis presenting with nonthrombocytopenic petechial or purpuric rash on lower extremities 7
• Associated with migratory polyarthralgias, abdominal pain, and renal complications 7
• Skin biopsy shows vascular immune reactivity with IgA deposition 8
• Can be presenting manifestation of acute myeloid leukemia in rare cases 8

Immune Thrombocytopenic Purpura (ITP)

• Petechial rash associated with low platelet count 3
• Distinguish from HSP by presence of thrombocytopenia on CBC 3

Post-Streptococcal Purpura

• Petechial rash can occur after group A streptococcal pharyngitis 3
• Look for recent history of sore throat or positive strep testing 3

Other Infectious Considerations

Secondary Syphilis

• Can present with maculopapular rash involving palms and soles 3
• Obtain RPR/VDRL and sexual history 3

Disseminated Gonococcal Infection

• Maculopapular or petechial rash with associated arthritis 3
• Consider in sexually active patients with joint complaints 3

Infective Endocarditis

• Petechial rash on extremities, particularly in setting of fever and new heart murmur 3
• Obtain blood cultures and echocardiography 3

Non-Infectious Causes

Drug Hypersensitivity Reactions

• Nonspecific drug eruptions present as fine reticular maculopapular rashes or broad erythematous macules 1, 6
• Query about antibiotics (especially ampicillin/amoxicillin), NSAIDs, anticonvulsants, or any new medications within past 2-3 weeks 6

Thrombotic Thrombocytopenic Purpura (TTP)

• Petechial rash with associated thrombocytopenia, hemolytic anemia, renal dysfunction, and neurologic changes 3
• Requires urgent hematology consultation 3

Immediate Diagnostic Workup

Obtain these tests immediately if RMSF/ehrlichiosis suspected:

• Complete blood count with differential (looking for leukopenia, thrombocytopenia, immature bands) 3, 1
• Comprehensive metabolic panel (looking for hyponatremia, elevated hepatic transaminases) 3, 1
• Peripheral blood smear (looking for morulae, schistocytes) 3
• Acute serology for R. rickettsii, E. chaffeensis, and A. phagocytophilum 1
• Blood cultures if sepsis suspected 3
• Coagulation studies (PT, PTT, fibrinogen, D-dimer) 3

Critical Pitfalls to Avoid

• Do not exclude RMSF based on absence of tick bite history, as 40% of patients do not report tick exposure 4
• Do not wait for serologic confirmation before starting doxycycline if RMSF suspected, as IgM/IgG are not detectable before the second week 4
• Do not assume petechial rash is benign—multiple life-threatening infections present this way 4
• Less than 50% of RMSF patients have rash in first 3 days of illness 1
• Distinguishing RMSF from HME in children with rash can be difficult, requiring empiric treatment for both 3