Rash micro differential

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Excellent - Goldman-Cecil has a table of causes by rash morphology, and Harrison's has dedicated sections. Let me pull these key sources in parallel:
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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 / DiseaseKey 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 HIVAcute 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
CMVMononucleosis-like; rash uncommon unless given ampicillin
Dengue virus"Breakbone fever"; flushing, then maculopapular/petechial rash; thrombocytopenia
Zika virusMild fever, rash, conjunctivitis, arthralgia; teratogenic
Parvovirus B19Fifth disease; "slapped cheek" in children; reticular lacy rash on limbs
West Nile virusRash with neurologic involvement; mosquito-borne
Rocky Mountain spotted fever (R. rickettsii)Initially central then spreads peripherally to palms/soles - watch for evolution
EhrlichiosisRare 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. pneumoniaeRash 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 / DiseaseKey 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 endocarditisJaneway 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 measlesPeripheral 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 / DiseaseKey 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 diseasePolymorphous 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 / DiseaseKey Features
Varicella-zoster (VZV) - chickenpoxPruritic vesicles in different stages ("dewdrops on rose petal"); centripetal distribution
VZV - Herpes zosterDermatomal 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 / MonkeypoxAll lesions in same stage (cf. varicella); centrifugal; rash on palms/soles
Vibrio vulnificusHemorrhagic bullae; liver disease/immunocompromised; raw oyster exposure
Necrotizing fasciitisBullae 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 / DiseaseKey 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 feverThrombocytopenia, 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 canimorsusDog bite; asplenic/alcoholic patients; severe purpura/DIC
EnterovirusesPetechial rash may mimic meningococcal disease
Noninfectious: ITP, HSP (IgA vasculitis), TTP, leukemia, adverse drug reaction

6. Nodular Eruptions

Organism / DiseaseKey Features
Disseminated candidiasisPink nodules in neutropenic/immunocompromised patients
Disseminated cryptococcosisUmbilicated papules resembling molluscum; HIV patients
Disseminated gonococcemia (N. gonorrhoeae)Septic embolic pustular/petechial lesions; migratory arthritis; sexually active young adults
Mycobacterium avium complexNodular 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 / CoccidioidomycosisDisseminated in immunocompromised
Sporothrix schenckiiSporotrichoid spread along lymphatics; rose-thorn injury

7. Urticaria-like Eruptions

Organism / DiseaseKey Features
Acute HBVSerum sickness-like; urticaria + arthritis + elevated LFTs
HCVUrticaria, cryoglobulinemia
EBV / CMVRare urticarial presentation
StrongyloidesLarva currens - serpiginous urticarial track (perianal/buttocks); very rapid movement
Early Lyme diseaseAnnular urticarial expanding plaque
Drug reactions most common cause overall

8. Eschar-Associated Eruptions

(Black necrotic lesion at inoculation site)
Organism / DiseaseArthropod/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 leishmaniasisSandfly; endemic regions

Quick High-Yield Summary by Pattern

Rash + SignThink First
Petechiae + fever + meningismN. meningitidis
Petechiae starting wrists/anklesRMSF
Rose spots + relative bradycardiaTyphoid
Palms + soles copper lesionsSecondary syphilis
Koplik's spotsMeasles
Erythema migrans (bull's eye)Lyme disease
Eschar + travel AsiaScrub typhus
Sandpaper rash + pharyngitisScarlet fever
Rash after amoxicillinEBV (mono)
Slapped cheek + lacy rashParvovirus B19
Vesicles in different stagesVaricella (VZV)
Dog bite + purpura + asplenicCapnocytophaga
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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