| Etiology of fever and rash | Typical rash characteristics | Hints/clues associated with syndrome | General next steps in evaluation |
| Common etiologies |
| Bacterial SSTI | Impetigo, ecthyma, folliculitis, cellulitis, abscess/furuncles, plaques, ulcerations, ecthyma gangrenosum | - Diabetes mellitus
- Presence of psoriasis
- Presence of lymphedema
- Active/recent use of IV catheter
| - Culture of any purulent fluid (if present)
- Blood cultures (if fever is present)
|
| Syphilis | Primary: solitary painless papule/ulcer Secondary: diffuse rash (can present in a variety of ways) is most common; condylomata lata (warts) and mucous patches can present occasionally Tertiary: cutaneous gummas | - Multiple sexual partners
- Recent sexual activity
- History of STIs
- Painless regional lymphadenopathy
- Rash involving the palms and soles
- Presence of condyloma lata
| - Syphilis IgG and/or RPR
- If painless chancre, direct microscopy of scrape
|
| Gonorrhea | Painless pustular/vesiculopustular lesions (2 to 10 in number) located on the trunk, extremities, or palms/soles | - Multiple sexual partners
- Recent sexual activity
- History of STIs
- Accompanying tenosynovitis and arthralgias
| - Neisseria gonorrhea NAAT (urine or vaginal swab)
|
| Acute HIV infection | Diffuse maculopapular rash | - Presence of mononucleosis/flu-like symptoms
- Recent sexual activity
- Multiple sexual partners
| - HIV testing, if not already done
- If known acute HIV infection, diagnosis is usually made based on history and physical exam
|
| Genital HSV | Painful vesicular lesions in the genital area | - Fever is typically only present in the primary episode of HSV infection
- Multiple sexual partners
- Recent sexual activity
- History of STIs
| - Collect lesion swab sample and send for HSV PCR (can also perform viral culture or DFA on swab sample)
|
| VZV | Localized cluster of vesicular lesions on erythematous base in single or several contiguous dermatomes | - Low CD4 count
- Recent (re)initiation of ART
| - Diagnosis is usually made based on history and physical exam
|
| IRIS | Variable depending on underlying infection | - Recent (re)initiation of ART, especially in setting of low CD4 count
| - Evaluate for underlying infection
|
| Drug reactions |
| | Painful, exanthematous rash that evolve into dusky erythema, purpuric spots, flaccid bullae, and then eventually skin sloughing | - Accompanying malaise, fever, myalgia, and conjunctivitis
- Mucosal/buccal involvement
| - Requires treatment as soon as possible
|
| | Variable, often a maculopapular rash | - Recent (re)initiation of ART
| |
| | Variable; morbilliform and urticarial rashes are common | - Variable; most common culprit drugs include trimethoprim-sulfamethoxazole, sulfadiazine, and amino-penicillins
| |
| Less common etiologies |
| Nontuberculous mycobacteria | Variable | - Low CD4 count
- History of water exposure (eg, swimming pools, aquariums), penetrating injury, surgery, or injection
| - Obtain sample of fluid from abscess or refer for drainage or biopsy. Send sample for acid-fast staining and mycobacterial culture.
|
| Tuberculosis | Variable: scrofuloderma, gummatous lesions, lupus vulgaris, and pustules | - Risk factors for tuberculosis
- Having lived or traveled to endemic areas
- Working/living in a homeless shelter or a prison
- Close contact with known or suspected tuberculosis
- Low CD4 count
| - Obtain sample of fluid from abscess or refer for drainage or biopsy. Send sample for acid-fast staining and mycobacterial culture.
|
| Leishmaniasis | Macular, papular, nodular, and plaque-like lesions that later ulcerate | - Risk factors for leishmaniasis
- Having lived or traveled to leishmaniasis endemic areas (eg, Mexico, Central and South America, Middle East and North Africa, East Africa, India)
- Local outbreak (eg, areas of conflict, refugee camps)
| - Obtain sample of lesion and send for Leishmania spp testing
|
| Scabies | Variable; most commonly presents as diffuse, intensely pruritic, erythematous, papulosquamous or papulovesicular rash | - Low CD4 count
- Close contacts with a similar pruritic rash
| - Microscopic examination and visualization of the mite on a scabies preparation of a skin scraping
|
| Mpox | Starts as macules that progress to painful umbilicated papules/vesicles, then pseudo-pustules, and eventually crust over | - Multiple sexual partners
- Recent sexual activity
- History of STIs
- Local outbreak
| - Collect lesion swab sample and send for orthopoxvirus DNA PCR
|
| Skin syndromes associated with hepatitis B | SSLR: variable, pruritic, urticarial rash PAN: palpable purpura or livedo reticularis | - Risk factors for hepatitis B
- Recent diagnosis of acute hepatitis B
- Chronic hepatitis B
| - Diagnosis is usually made based on history and physical exam
- Skin biopsy
|
| Parvovirus B19 | Lacy reticular rash on trunk and extremities | - Low CD4 count
- Severe anemia
- Exposure to daycare centers or young children
| |
| Cryptococcosis | Variable; ulcers, nodules, papules, pustules, umbilicated vesicular lesions | - CD4 count <100 cells/microL
| - Serum cryptococcal antigen
|
| Endemic mycoses |
| | Variable | - Lesions located on face, chest, and extremities
- Lived or traveled to histoplasmosis-endemic areas
| - Urine Histoplasma antigen
|
| | Papules, pustules, ulcers, subcutaneous nodules, cold abscesses, or verrucoid lesions | - Lived or traveled to blastomycosis-endemic areas
| - Urine Blastomyces antigen; occasionally can be diagnosed by visualization of characteristic skin lesions on physical exam
|
| | Hemorrhagic pustules, nodules, ulcers, verrucous plaques, or erythematous papules | - Lived or traveled to coccidioidomycosis-endemic areas
| |
| | Ulcerative lesions that follow a lymphatic drainage pattern | - Trauma to skin involving rose thorns and/or soil
- Engagement in landscaping, tree farming, rose gardening, or working with hay bales
- Motor vehicle accidents that involve inoculation of soil into wounds
| - Diagnosis is usually made based on history and physical exam
|
| | Papules with central umbilication, usually on trunk or the face | - Lived or traveled to talaromycosis-endemic areas (eg, Southeast Asia, Northeastern India, Southern China, Hong Kong, and Taiwan)
- CD4 count <100 cells/microL
| - Send skin biopsy sample for fungal staining and culture
|
| | Papules, plaques, and ulcers | - Lived or traveled to emergomycosis-endemic areas
- CD4 count <100 cells/microL
| - Send skin biopsy sample for fungal staining and culture
|
| Bacillary angiomatosis | Hemangiomatous, small papules that evolve into large, friable nodules | - Recent cat scratches or exposure
- CD4 count <100 cells/microL
| |
| Kaposi sarcoma | Non-blanching, painless violaceous papules/patches that evolve into coalescing and ulcerating plaques or nodules | - CD4 count <50 cells/microL
- Lesions mostly on trunk, face, and extremities
| |
