Bacterial | 
Routine culture and Gram stain | 
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Bacillus anthracis (anthrax) | 
Gram (+) rod, biopsy for immunohistochemistry and PCR | 
Wool handler; Western Asia, West Africa, Eastern Europe; injection drug users (heroin); potential bioweapon | 
Lesions on face and arms; painless papule develops into vesicle that dries, forming black eschar that then separates from the base to form an ulcer with marked surrounding gelatinous edema; LN common; injectional anthrax – higher mortality and shock, significant edema | 
Corynebacterium diphtheriae (diphtheria) | 
Gram (+) rod | 
Tropical climates; rare in the United States | 
Ulcer with sharp margins and clean base; pre-existing skin lesions may become infected | 
Francisella tularensis (tularemia) | 
Gram (–) coccobacillus, serology | 
Rabbits, muskrats, beavers; North America, Japan, Europe, former Soviet Union; potential bioweapon | 
Systemic febrile illness; tender ulcer with painful LN | 
Nocardia spp. | 
Branching, beaded gram (+) rod, modified AFB (+) | 
Immunocompromised patients, soil exposure | 
Ulcer with purulent drainage, nodular lymphangitis | 
Pseudomonas aeruginosa (ecthyma gangrenosum) | 
Gram (–) rod, may have associated bacteremia | 
Neutropenic or immunocompromised patients | 
Rapidly progressive eruption from papules to hemorrhagic vesicles or bullae that undergo central necrosis and ulceration | 
Polymicrobial | 
Mixed gram (+), gram (–), and anaerobes | 
Debilitated, immunocompromised, diabetic patients | 
Pressure sores, decubitus ulcers, foot ulcers | 
Yersinia pestis (plague) | 
Gram (–) coccobacillus, bipolar-staining “safety pin” morphology, serology | 
Rodent zoonosis transmitted to humans via fleas; Far East, India, Africa, Central and South America, potential bioweapon | 
Bubonic plague with classic inguinal painful LN; may have skin lesions on lower extremities; pustule, papule, vesicle, or eschar may occur at inoculation site | 
Spirochetes | 
Treponema pallidum (syphilis) | 
Serology | 
Sexually transmitted disease | 
Tertiary syphilis; nodular, ulceronodular, gummas; punched-out ulcer with gummy discharge | 
Fungal | 
Fungal smear, culture | 
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Aspergillus spp. | 
Septate hyphae; serum galactomannan assay in high risk patients | 
Immunocompromised, HIV positive | 
Ulcers, plaques, nodules, pustules; may be associated with trauma, intravenous catheter sites, secondary colonization of existing wounds, or direct extension from lung to chest wall | 
Blastomyces dermatitidis | 
Broad-based budding yeast, dimorphic fungus | 
Sugar cane worker, HIV positive, immunocompromised; North America, Africa | 
Subcutaneous nodule that enlarges and ulcerates, forming a crusted, verrucous plaque; may resemble squamous cell carcinoma | 
Coccidioides immitis | 
Dimorphic fungus, serology | 
Soil exposure, HIV positive; Southwestern United States, Northern Mexico, Central and South America | 
Usually single nodule or plaque; may form pustules, subcutaneous nodules, or abscesses | 
Cryptococcus neoformans | 
India ink, encapsulated yeast, mucicarmine (+) capsule, cryptococcal antigen (serum and CSF) | 
Exposure to pigeons, soil exposure, HIV positive, immunocompromised | 
Papule with crust resembling molluscum contagiosum; also forms ulcers on skin, mouth, and genitalia; may have lung or CNS involvement | 
Histoplasma capsulatum | 
Dimorphic fungus, histoplasma antigen (urine and serum) | 
Bats, birds, and soil exposure; HIV positive, immunocompromised; Eastern and Central United States in Ohio/Mississippi river valleys, Central and South America, West Indies, Africa, Madagascar | 
Papule with crust resembling molluscum contagiosum; ulcerative plaques and oral ulcerations | 
Sporothrix schenckii | 
Dimorphic fungus | 
Rose gardening, soil exposure | 
Papule or pustule at inoculation site develops into subcutaneous nodules or ragged-edged ulcer with proximal nodular lymphangitis; usually on upper extremities | 
Mycobacterial | 
AFB smear, culture | 
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Mycobacterium marinum | 
AFB (+), growth at 30–32°C | 
Water, aquarium enthusiasts | 
Ulcer with thin seropurulent drainage, nodular lymphangitis | 
Mycobacterium ulcerans (Buruli ulcer) | 
AFB (+), PCR for the insertion sequence IS2404 and IS2606 in swabs or tissue samples | 
Africa, Australia, South East Asia, South America, North America (Mexico); 2- to 3-month incubation period, usually associated with trauma | 
Subcutaneous nodule that ulcerates with extensive scarring and contracture formation; edematous lesion rapidly progresses to extensive ulceration, may have osteomyelitis contiguous to ulcer | 
Mycobacterium avium complex | 
AFB (+) | 
HIV positive, immunocompromised; soil, water | 
Multiple subcutaneous nodules or ulcers; may be associated with cervical lymphadenitis drainage to skin, or direct inoculation | 
Mycobacterium haemophilum | 
AFB (+), requires iron-supplemented culture medium and incubation at 30–32°C | 
Australia, United States, Canada, France, Germany, Singapore; HIV positive, transplantation | 
Papules develop into pustules which form deep ulcers, usually on extremities overlying joints; may have septic arthritis +/– osteomyelitis, may have LN | 
Mycobacterium tuberculosis | 
AFB (+), PPD or interferon-γ release assay helpful if positive | 
Worldwide | 
Nodules or ulcers especially in HIV-positive patients, scrofuloderma, plaques | 
Viral | 
Herpes simplex | 
DFA, viral culture | 
Sexually transmitted disease | 
Oral, perineal, genital ulcers; whitlow on hands; lesions with thin-walled vesicles; shallow painful ulcers | 
Parasitic | 
Leishmaniasis | 
Punch biopsy, aspirates, or scrapings of skin for culture, histopathology and touch prep using Wright’s and Giemsa stains looking for amastigotes at base of lesion; serology; PCR of tissue aspirates or peripheral blood | 
Sandfly bites, travel to endemic area (military or civilian); incubation period weeks to months | 
Papule at the site of insect bite enlarges to form a nodule, which then develops into a punched-out ulcer; may have associated LN; rarely nodules form without ulceration; may involve nasal or oral mucosa | 
Old World L. major
 L. tropica
 L. (L.) aethiopica
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Mediterranean, Middle East, Africa, Southern Asia, India | 
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New World L. mexicana complex
 Viannia subgenus:
 L. (V.) braziliensis
 L. (V.) panamensis
 L. (V.) guanensis
 L. (V.) peruviana
 | 
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Latin America, Central and South America | 
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