Rash micro differential
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I now have comprehensive data from Harrison's 22e, Goldman-Cecil, and Rosen's. Let me compile the full answer.
Rash - Microbiology Differential Diagnosis
Organized by lesion morphology (the most practical approach at the bedside), with infectious causes prioritized.
1. Centrally Distributed Maculopapular Eruptions
(Truncal predominance - most common type)
| Organism / Disease | Key Features |
|---|---|
| Measles (Paramyxovirus) | Starts at hairline, spreads downward, Koplik's spots (pathognomonic), cough/coryza/conjunctivitis |
| Rubella (Togavirus) | Spreads hairline to feet, clears from original sites; postauricular adenopathy; forchheimer spots (palatal petechiae) |
| EBV (mono) | Maculopapular rash; splenomegaly, pharyngitis, atypical lymphocytes; rash intensifies with amoxicillin |
| Primary HIV | Acute retroviral syndrome; diffuse maculopapular rash + pharyngitis + lymphadenopathy |
| HHV-6 (Roseola) | High fever then rash after defervescence; mainly children <2 years |
| Enteroviruses (Echovirus/Coxsackievirus) | Non-specific; may mimic rubella/measles |
| CMV | Mononucleosis-like; rash uncommon unless given ampicillin |
| Dengue virus | "Breakbone fever"; flushing, then maculopapular/petechial rash; thrombocytopenia |
| Zika virus | Mild fever, rash, conjunctivitis, arthralgia; teratogenic |
| Parvovirus B19 | Fifth disease; "slapped cheek" in children; reticular lacy rash on limbs |
| West Nile virus | Rash with neurologic involvement; mosquito-borne |
| Rocky Mountain spotted fever (R. rickettsii) | Initially central then spreads peripherally to palms/soles - watch for evolution |
| Ehrlichiosis | Rare rash (~30%); pancytopenia, elevated LFTs |
| Typhoid fever (S. typhi/paratyphi) | "Rose spots" - faint salmon-pink macules, 2-4mm, on trunk; relative bradycardia |
| Secondary syphilis (T. pallidum) | Diffuse including palms/soles; condylomata lata, mucous patches |
| Lyme disease (B. burgdorferi) | Erythema migrans (expanding annular lesion with central clearing); tick exposure |
| Acute meningococcemia (N. meningitidis) | Early stage can be maculopapular before becoming petechial |
| M. pneumoniae | Rash in ~17%; often maculopapular, occasionally bullous (Stevens-Johnson association) |
| Rat bite fever (Streptobacillus/Spirillum) | Fever, rash, polyarthritis after rat bite |
| Noninfectious: Drug reaction, SLE, Still's disease, Sweet syndrome, DRESS, erythema marginatum |
2. Peripheral Rashes
(Palms + soles involvement - HIGH-YIELD clinically)
| Organism / Disease | Key Features |
|---|---|
| RMSF (R. rickettsii) | Starts wrists/ankles, spreads centrally; petechiae/purpura later; tick bite in endemic area; treat empirically |
| Secondary syphilis (T. pallidum) | Copper-colored papules on palms and soles; painless |
| Bacterial endocarditis | Janeway lesions (painless, palms/soles), Osler nodes (painful, fingertips), splinter hemorrhages |
| Hand-foot-mouth disease (Coxsackievirus A16, EV71) | Vesicles on palms/soles + oral ulcers; children |
| Atypical measles | Peripheral vesicular/petechial distribution |
| Rickettsialpox (R. akari) | Eschar at bite site + maculopapular then vesicular rash; house mouse mite vector |
3. Confluent Desquamative Erythematous Eruptions
(Diffuse erythema + desquamation)
| Organism / Disease | Key Features |
|---|---|
| Scarlet fever (S. pyogenes) | Sandpaper rash, pastia lines, circumoral pallor, strawberry tongue; pharyngitis; Desquamates on fingertips |
| Toxic shock syndrome (TSS) (S. aureus) | Diffuse sunburn-like erythroderma; hypotension; multi-organ failure; desquamation at 1-2 weeks |
| Streptococcal TSS (S. pyogenes) | Similar to staph TSS; often with necrotizing fasciitis |
| Kawasaki disease | Polymorphous rash, bilateral conjunctival injection, cracked lips, strawberry tongue; children; coronary aneurysms |
| Staphylococcal scalded skin syndrome (SSSS) | Exfoliative; children; cleavage at granular layer (cf. TEN - at dermal-epidermal junction) |
4. Vesiculobullous Eruptions
| Organism / Disease | Key Features |
|---|---|
| Varicella-zoster (VZV) - chickenpox | Pruritic vesicles in different stages ("dewdrops on rose petal"); centripetal distribution |
| VZV - Herpes zoster | Dermatomal distribution; reactivation; painful |
| Herpes simplex virus (HSV) | Grouped vesicles; oral or genital; can disseminate in immunocompromised |
| Coxsackievirus (HFMD) | Palms, soles, oral mucosa |
| Rickettsialpox (R. akari) | Vesicular with eschar |
| Smallpox / Monkeypox | All lesions in same stage (cf. varicella); centrifugal; rash on palms/soles |
| Vibrio vulnificus | Hemorrhagic bullae; liver disease/immunocompromised; raw oyster exposure |
| Necrotizing fasciitis | Bullae with severe pain/tenderness, crepitus; S. pyogenes, S. aureus, polymicrobial |
| Anthrax (B. anthracis) | Single black eschar (cutaneous) |
5. Petechial / Purpuric Eruptions
(Most critical to identify - can indicate life-threatening infection)
| Organism / Disease | Key Features |
|---|---|
| N. meningitidis (meningococcemia) | Rapidly spreading petechiae/purpura; fever, meningism; purpura fulminans; medical emergency |
| RMSF (R. rickettsii) | Peripheral petechiae spreading centrally; tick bite; thrombocytopenia |
| Epidemic typhus (R. prowazekii) | Louse-borne; starts on trunk; petechial in severe cases |
| Septicemic plague (Y. pestis) | "Black death" - hemorrhagic/purpuric lesions; DIC |
| Endocarditis (viridans streptococci, S. aureus, HACEK) | Petechiae, Janeway lesions, Osler nodes, Roth spots |
| Dengue hemorrhagic fever | Thrombocytopenia, positive tourniquet test, spontaneous bleeding |
| Viral hemorrhagic fevers (Ebola, Marburg, Lassa) | Hemorrhagic rash + multi-organ failure; travel history critical |
| DIC (from any gram-negative sepsis) | Purpura fulminans; underlying bacteremia (meningococcus, H. influenzae, S. pneumoniae) |
| Capnocytophaga canimorsus | Dog bite; asplenic/alcoholic patients; severe purpura/DIC |
| Enteroviruses | Petechial rash may mimic meningococcal disease |
| Noninfectious: ITP, HSP (IgA vasculitis), TTP, leukemia, adverse drug reaction |
6. Nodular Eruptions
| Organism / Disease | Key Features |
|---|---|
| Disseminated candidiasis | Pink nodules in neutropenic/immunocompromised patients |
| Disseminated cryptococcosis | Umbilicated papules resembling molluscum; HIV patients |
| Disseminated gonococcemia (N. gonorrhoeae) | Septic embolic pustular/petechial lesions; migratory arthritis; sexually active young adults |
| Mycobacterium avium complex | Nodular rash in AIDS patients |
| Cat scratch disease (Bartonella henselae) | Regional lymphadenopathy; cat exposure |
| Erythema nodosum (TB, histoplasmosis, strep, leprosy, sarcoid) | Painful red nodules on anterior shins; not specific |
| Histoplasmosis / Coccidioidomycosis | Disseminated in immunocompromised |
| Sporothrix schenckii | Sporotrichoid spread along lymphatics; rose-thorn injury |
7. Urticaria-like Eruptions
| Organism / Disease | Key Features |
|---|---|
| Acute HBV | Serum sickness-like; urticaria + arthritis + elevated LFTs |
| HCV | Urticaria, cryoglobulinemia |
| EBV / CMV | Rare urticarial presentation |
| Strongyloides | Larva currens - serpiginous urticarial track (perianal/buttocks); very rapid movement |
| Early Lyme disease | Annular urticarial expanding plaque |
| Drug reactions most common cause overall |
8. Eschar-Associated Eruptions
(Black necrotic lesion at inoculation site)
| Organism / Disease | Arthropod/Exposure |
|---|---|
| RMSF (R. rickettsii) | Tick (Dermacentor) |
| Scrub typhus (O. tsutsugamushi) | Trombiculid mite; Asia-Pacific |
| Rickettsialpox (R. akari) | Mouse mite |
| Anthrax (B. anthracis) | Animal/soil/bioterrorism |
| Tularemia (F. tularensis) | Tick/rabbit contact; ulcero-glandular form |
| Cutaneous leishmaniasis | Sandfly; endemic regions |
Quick High-Yield Summary by Pattern
| Rash + Sign | Think First |
|---|---|
| Petechiae + fever + meningism | N. meningitidis |
| Petechiae starting wrists/ankles | RMSF |
| Rose spots + relative bradycardia | Typhoid |
| Palms + soles copper lesions | Secondary syphilis |
| Koplik's spots | Measles |
| Erythema migrans (bull's eye) | Lyme disease |
| Eschar + travel Asia | Scrub typhus |
| Sandpaper rash + pharyngitis | Scarlet fever |
| Rash after amoxicillin | EBV (mono) |
| Slapped cheek + lacy rash | Parvovirus B19 |
| Vesicles in different stages | Varicella (VZV) |
| Dog bite + purpura + asplenic | Capnocytophaga |
| Dewdrops → pustules on palms/soles (same stage) | Smallpox/Monkeypox |
Sources:
- Harrison's Principles of Internal Medicine 22e, Chapter 21 (Fever and Rash, Kaye & Kaye)
- [Goldman-Cecil Medicine, Table 259-2](Causes of Fever and Rash by Rash Morphology)
- Rosen's Emergency Medicine (Fever and Nonblanching Rash / Meningococcemia)
- Sherris & Ryan's Medical Microbiology, 8th ed.
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