Fitzpatrick's Color Atlas and Synopsis of Clinical Dermatology, Seventh Edition


Invasive and Disseminated Fungal Infections

Subcutaneous Mycoses ICD-9:117.9 image ICD-10: B48.8

image A heterogeneous group of fungal infections that develop at the sites of transcutaneous trauma.

image Sporotrichosis

image Phaeohyphomycoses:

image Eumycetoma

image Chromoblastomycosis

image Etiology. Fungi resident on plants or in soil

image Melanin-producing (dematiaceous or pigmented): brown to black

image Nonpigmented (hyaline)

image Clinical Manifestations. Slowly enlarging plaques with verrucous lesions, fistulae, sinuses, and scarring, most commonly on lower extremity; can occur at any site of inoculation.

image Host Defense Defect. Infections more extensive. Can disseminate.

image Diagnosis. Clinical findings, demonstration of grains or Medlar bodies, dermatopathology, culture of organism.

Sporotrichosis ICD-9: 117.1 image ICD-10: B42 image

image Etiology. Sporothrix schenckii. Infection follows accidental inoculation of skin.

image Clinical Manifestations

image Nodule or plaque at inoculation site infection.

image Lymphangitis. Chronic nodular lymphangitis (sporotrichoid lymphocutaneous syndrome.

image Subcutaneous swelling occurs proximal to inoculation site.

image Disseminated infection can occur from skin or pulmonary infection with host defense defects.

Etiology and Epidemiology

Etiology. S. schenckii, a thermally dimorphic fungus. Tissue form is an oval, cigar-shaped yeast. Lives as a saprophyte on plants. Worldwide distribution. More common in temperate, tropical zones.

Demography. Occupational exposure important: Agricultural and forest workers, gardeners, farmers, lawn laborers, florists, paper manufacturers, and gold miners. In Uruguay, 80% of cases occur after a scratch by an armadillo.

Transmission. Cutaneous puncture or small abrasion. Zoonosis: Rarely transmitted from cats with sporotrichosis to humans; armadillos.

Pathogenesis. After subcutaneous inoculation, S. schenckii grows locally forming plaque sporotrichosis and can extend proximally to nodular lymphangitis.

Clinical Manifestation

Incubation period 3 weeks (range, 3 days to 12 weeks) after trauma or injury to site of lesion. Lesions are relatively asymptomatic, painless. Afebrile.

Fixed Cutaneous (Plaque) Sporotrichosis. Dermal papule, pustule, or nodule appears at inoculation site several weeks after injury. May enlarge to verrucous plaque or ulcer with induration. Draining lymph nodes become inflamed and enlarged (chancriform syndrome). Distribution: Primary lesion most common on dorsum of hand or finger. Fixed plaque: face in children; upper extremities in adults.

Nodular Lymphangitis. Follows proximal lymphatic extension from inoculation site. Red nodules form in intervening lymphatics; may become indurated, nodular, thickened. Distribution: Inoculation nodule on hand/finger with nodular lymphangiitis extending proximally on arm (Figs. C-1 and C-2).


Figure C-1. Sporotrichosis: nodular lymphangitic type A 78-year-old gardener with tender nodules on hand and arm for 4 weeks. Erythematous nodules in a linear array in lymphatic channels on the dorsum of the hand and forearm. S. schenckii was isolated on culture of a lesional biopsy specimen.


Figure C-2. Sporotrichosis: chronic lymphangitic type An erythematous papule at the site of inoculation on the index finger with a linear arrangement of erythematous dermal and subcutaneous nodules extending proximally in lymphatic vessels of the dorsum of the hand and arm.

Disseminated Sporotrichosis. From pulmonary sporotrichosis, disseminates hematogenously to skin, as well as joints, eyes, and meninges.

Differential Diagnosis

Nodular Lymphangitis. Mycobacterium marinum, Nocardia brasiliensis, Leishmania brasiliensis.

Chancriform Syndrome. Ulcerative lesion at site of primary infection associated with regional lymph node enlargement. Syphilis, nocardiosis, cutaneous tularemia, cutaneous anthrax.


Clinical suspicion and isolation of organism on culture.


Shows little tendency to resolve spontaneously. Responds well to therapy; may relapse.


Itraconazole is the preferred treatment for cutaneous and lymphocutaneous sporotrichosis.

Phaeohyphomycoses ICD-9: 117 image ICD-10 B47 image

Chronic skin and soft tissue infections caused by pigmented and hyaline nonpigmented molds: eumycetoma and chromoblastomycosis. Follows traumatic inoculation, most on the foot.

Etiology and Epidemiology

Etiologic Agents. Opportunistic pathogens. Residents in soil or on plants in subtropical and tropical regions. Infection follows direct inoculation into the skin.

Nocardiosis (actinomycotic mycetomas). Caused by bacteria of the genus Nocardia. Phaeohyphomycoses. Caused by fungi.

• Eumycetomas: Madurella (pigmented or dematiaceous) species most common. Organisms produce melanin; hyphae and conidia (spores) are brown or black. Scedosporium species (nonpigmented or hyaline) molds.

• Chromoblastomycosis: Fonsecaea and Cladophialophora species most common.

Transmission. Cutaneous inoculation of organism: Thorn prick, wood splinter, stone cut, contaminated with soil or plant debris.

Demography. Occur in tropical and subtropical areas of Central and South America, Africa, and India. Most common in male rural laborers who are frequently exposed to the organisms. Most occur on lower legs also hands, arms. Risk factor: poverty.

Clinical Manifestations

Eumycetomas and chromoblastomycosis are chronic infections, occurring on lower extremities, at sites of inoculation, slowing enlarging. Lesions may continue to expand for decades. Relatively asymptomatic, with little pain, tenderness, or fever.

Eumycetoma. Characterized by swelling, development of sinus tracts and fistulae, draining pus with grains (colonies of fungi discharged from the sinus tract). Tissue becomes greatly distorted (Fig. C-3). Central clearing gives older lesions an annular shape. Distribution: Unilateral on the leg, foot, and hand. Untreated infection may extend to adjacent fascia and bony structures resulting in loss of function and disfigurement. Complications: Regional lymphadenopathy; bacterial secondary infections; extension into fascia, muscle, bone; loss of function and disfigurement.


Figure C-3. Eumycetoma The foot, ankle, and leg are grossly distorted with edema and confluent subcutaneous nodules, cauliflower-like tumors, and ulcerations.

Chromoblastomycosis. Smaller lesions coalesce to form nodular, verrucous, or plaque-like lesions (Fig. C-4). Gradually enlarge into contiguous skin and soft tissue; may envelope calf or foot. Infection can also spread along lymphatics and by autoinoculation. May have areas of healing with atrophy and scar formation; margins are raised. Complications: bacterial superinfection; chronic edema, elephantiasis; squamous cell carcinoma (Marjolin ulcer); hematogenous dissemination.


Figure C-4. Chromoblastomycosis Hyperkeratotic and crusted plaque with old scars on the leg had been present for several decades.

Chromoblastomycosis, tumoral form. Chronic disease led to elephantiasis and involvement of the entire lower limb.


Definitive diagnosis of phaeohyphomycosis made by isolation of mold in culture in the setting of inflammatory plaques on lower extremities. CT scan and echosonography define the extent of involvement. X-ray of bone shows multiple osteolytic lesions (cavities), periosteal new bone formation.

Eumycetoma. Lesion with swelling, sinus tracts, grains. Rule out nocardiosis.

Chromoblastomycosis. Medlar bodies (sclerotic cells or ‘copper pennies’): thick-walled pigmented septated fungal hyphal forms, resembling large yeasts seen in lesional scraping (KOH), and/or biopsy specimen; isolation of organism on culture.

Differential Diagnosis

Sporotrichosis, blastomycosis, nontuberculous cutaneous mycobacterial infection, foreign body granuloma, pyoderma gangrenosum, squamous cell carcinoma.


Treatment of eumycetoma and chromoblastomycosis involves both surgical extirpation of lesions and administration of systemic antifungal agents such as itraconazole. Most effective earlier in course.

Systemic Fungal Infections with Dissemination to Skin

Systemic fungal infections with cutaneous dissemination occur most often with host defense defects.

Primary or reactivated fungal lung infection can disseminate hematogenously to multiple organ systems, including the skin.

• Cryptococcosis

• Histoplasmosis

• North American blastomycosis

• Coccidioidomycosis

• Penicilliosis

GI tract or intravascular catheter can be to source of candidemia and disseminated candidiasis. See disseminated candidiasis (see Section 26).

Cryptococcosis ICD-9: 117.5 image ICD-10: B45.0 image

image Cryptococcosis. Primary pulmonary infection. With host defense defects, hematogenous dissemination to meninges and skin.

Etiology and Epidemiology

Cryptococcus neoformans. Yeast serotypes A, B, C, D causing infection in humans. Found in soil and dried bird droppings. Worldwide, ubiquitous. Polysaccharide capsule is major virulence factor; basis for antigen testing.

Incidence. Globally, cryptococcosis (usually meningitis) is the most common invasive mycosis in HIV disease, occurring in up to 9% of persons with advanced untreated HIV disease in the United States and up to 30% in Africa.

Pathogenesis. Primary pulmonary focus of infection may remain localized or disseminate. Reactivation of latent infection in the immunocompromised host may result in hematogenous dissemination to meninges, kidneys, and skin; 10–15% of patients have skin lesions.

Clinical Manifestations

Cutaneous Lesions. Usually asymptomatic. CNS: headache (80%), mental confusion.

Papule(s) or Nodule(s). With surrounding erythema. Lesion may break down and exude mucinous fluid. In HIV disease, lesions occur most commonly on face/scalp. Molluscum contagiosum-like lesionsoccur in HIV disease (see Fig. C-5). Acneiform. Cryptococcal cellulitis mimics bacterial cellulitis, i.e., red, hot, tender, edematous plaque on extremity; possibly multiple noncontiguous sites.


Figure C-5. Cryptococcosis: disseminated Multiple, skin-colored papules and nodules on the face in a person with advanced HIV disease. Cryptococcus disseminated hematogenously from pulmonary infection to skin and meninges. The lesions resemble molluscum contagiosum, which is common in HIV disease. (Courtesy of Loïc Vallant, MD.)

Oral Mucosa. Nodules/ulcers.

Differential Diagnosis

Molluscum contagiosum, disseminated histoplasmosis, acne, sarcoidosis.


Confirmed by skin biopsy and fungal cultures.


In HIV disease in the absence of immune reconstitution, cryptococcal meningitis relapses in 30% of cases after amphotericin B therapy; lifelong secondary prophylaxis with fluconazole reduces relapse rate to 4–8%.


Primary Prophylaxis. In some centers, fluconazole is given to HIV/AIDS-infected individuals with low CD4+ cell counts; the incidence of disseminated infection is reduced, but there is no effect on the mortality rate.

Therapy of Meningitis. Amphotericin B for 2 to 6 weeks depending on severity. In uncomplicated cases and for 6 weeks in complicated cases.

Infection Limited to Skin. Fluconazole, 400–600 mg daily. Itraconazole, 400 mg daily.

Secondary Prophylaxis. In HIV disease (without immune reconstitution), lifelong secondary prophylaxis is given with fluconazole, 200–400 mg daily or itraconazole 200–400 mg/daily.

Histoplasmosis ICD-9: 115.90 image ICD-10: B39 image

Etiology and Epidemiology

Etiology. Histoplasma capsulatum var. capsulatum, an unencapsulated dimorphic fungus. In Africa, H. capsulatum var. duboisii. Skin/bone lesions common. Grows well in soil enriched with bird or bat guano.

Demography. Endemic areas: Ohio/Mississippi River valleys. Equatorial Africa. Caribbean Islands.

Transmission. Inhalation of microconidia in soil contaminated with bird or bat droppings. Acute pulmonary outbreaks may occur from occupational or recreational exposure.

Pathogenesis. In HIV disease, can present as either primary histoplasmosis or reactivation of latent infection.

Clinical Manifestation

Primary Pulmonary Infection. Accompanied or followed by hypersensitivity reactions: erythema nodosum, erythema multiforme. See Sections 7 and 14.

Cutaneous Infection. Hematogenous dissemination occurs with host defense defects. Papules or nodules; erythematous, necrotic, or hyperkeratotic. Guttate psoriasis-like papulosquamous lesions (Fig. C-6). Other morphologies: pustules, acneiform papules; chronic ulcers; vegetative plaques; panniculitis. Diffuse infiltration of skin (Fig. C-7). Erythroderma. Diffuse hyperpigmentation with Addison disease secondary to adrenal infection.


Figure C-6. Histoplasmosis, disseminated to skin A 40-year-old American male with HIV disease had multiple guttate psoriasis-like red scaling papules on the trunk and arms. Lesions occurred during a 2-week period. Multiple yeast forms within macrophages were seen of lesional biopsy specimen. Skin lesions recurred after discontinuation of itraconazole secondary prophylaxis. (Courtesy of JD Fallon, MD.)


Figure C-7. Histoplasmosis, disseminated to skin A 35-year-old African male presented with subacute febrile illness. Diffuse infiltration of the face with crusted erosions is seen. HIV disease with histoplasmosis was diagnosed. The patient died shortly after presentation. (Courtesy of Adam Lipworth, MD.)

Oropharyngeal Lesions. Nodules, vegetations, painful ulcerations of soft palate, oropharynx, epiglottis. Nasal vestibule.

Disseminated Disease. Hepatosplenomegaly, lymphadenopathy, meningitis.

Differential Diagnosis

Miliary tuberculosis, disseminated coccidioidomycosis, or cryptococcosis, leishmaniasis, lymphoma.


Clinical suspicion, confirmed by culture.


Prognosis linked to underlying condition, e.g., HIV disease.


Prevention. Protective clothing when working in areas contaminated with bird/bat droppings.

Systemic Antimycotic Therapy. Life-threatening and Meningeal Infection: IV amphotericin B. Non-Life-Threating Infection: Oral fluconazole 800 mg daily for 12 weeks. Oral itraconazole, 400 mg twice daily for 12 weeks

Secondary Prophylaxis. In HIV disease without immune restoration itraconazole, 200 mg daily or fluconazole, 400 mg daily.

Blastomycosis ICD-9: 116.0 image ICD-10: B40.0 image

image Etiologic Agent. Blastomyces dermatitidis.

image Endemic in southeastern and Great Lakes area of United States.

image Primary pulmonary infection, which in some cases is followed by hematogenous dissemination to skin and other organs.

Etiology and Epidemiology

Etiologic Agent. Blastomyces dermatitidis, a dimorphic fungus. Natural habitat: Wood debris. Lakes, river, wetlands subject to flooding.

Demography. United States: Most cases occur in the southeastern, central, and Great Lakes areas. Canada: Toronto area.

Pathogenesis. Asymptomatic primary pulmonary infection usually resolves spontaneously. Hematogenous dissemination may occur to skin, skeletal system, prostate, epididymis, or mucosa of nose, mouth, or larynx. Risk factors for dissemination: host defense defects.

Clinical Manifestations

Primary Pulmonary Infection. Accompanied or followed by hypersensitivity reactions: erythema nodosum, erythema multiforme. See Sections 7 and 14.

Cutaneous infection following hematogenous dissemination. Initial lesion, inflammatory nodule that enlarges and ulcerates (Fig. C-8); subcutaneous nodule, many small pustules on surface. Subsequently, verrucous and/or crusted plaque with sharply demarcated serpiginous borders. Peripheral border extends on one side, resembling a one-half to three-quarter moon. Pus exudes when crust is lifted. Central healing with thin geographic atrophic scar. Widespread lesions in HIV disease. Distribution: Usually symmetrically on trunk; also face, hands, arms, legs; multiple lesions in one-half of patients


Figure C-8. North American blastomycosis: disseminated Ulcerated, inflammatory plaque with surrounding erythema, edema, and fibrosis on the leg results from dissemination from pulmonary blastomycosis via blood to skin. The lesion must be differentiated from pyoderma gangrenosum. (Courtesy of Elizabeth M. Spiers, MD.)

Mucous Membranes. 25% of patients have oral or nasal lesions; one-half of those have contiguous skin lesions. Laryngeal infection.

Differential Diagnosis

Squamous cell carcinoma, pyoderma gangrenosum, tumor stage of mycosis fungoides, tuberculosis verrucosa cutis.


Clinical suspicion, confirmed by culture.

Course and Treatment

Cutaneous infection usually occurs months or years after primary pulmonary infection. Skin most common site of extrapulmonary infection. Cure rate with itraconazole, 95%. Treat life-threatening infections with IV amphotericin B 120–150 mg per week to a total dose of 2 g.

Coccidioidomycosis ICD-9: 114.9 image ICD-10: B38.0 image

image Etiologic Agent. Coccidioides.

image Endemic to desert areas of southwestern United States, northern Mexico, Central and South America.

image Primary pulmonary infection usually resolves spontaneously.

image Can disseminate hematogenously resulting in chronic, progressive, granulomatous infection in skin, lungs, bone, meninges.

image Cutaneous lesions in coccidioidomycosis.

image Acute coccidioidomycosis.

image Toxic erythema (diffuse erythema, morbilliform, urticaria).

image Erythema nodosum.

image Erythema multiforme (see Sections 7 and 14 for EN and EM).

image Disseminated histoplasmosis.

image Papules, nodules, verrucous plaques.

image Synonyms: San Joaquin Valley fever, valley fever, desert fever.

Etiology and Epidemiology

Etiologic Agents. Coccidioides, a dimorphic fungus. Two species: C. immitis and C. posadasii. On agar media and in soil: filamentous mold; form arthroconidia, which become airborne. In susceptible host, arthroconidia enlarge to become spherules, which contain endospores. Rarely, percutaneous.

Demography. More common in blacks, Filipinos. Risk of dissemination greater in males, pregnant females. Endemic in Arizona and southern California in San Joaquin Valley. Primary pulmonary coccidioidomycosis occurs in individuals living in these regions (endemic) or in visitors to the regions (nonendemic).

Classification. Acute self-limited pulmonary coccidioidomycosis. Disseminated coccidioidomycosis (cutaneous, osteoarticular, meningeal).

Pathogenesis. Spores (microconidia) inhaled, resulting in primary pulmonary infection that is asymptomatic or accompanied by symptoms of coryza. Dissemination outside thoracic cavity occurs in<="" p="">

Clinical Manifestation

Primary Pulmonary Infection. Accompanied or followed by hypersensitivity reactions: “toxic erythema,” erythema nodosum, erythema multiforme.

Primary Cutaneous Inoculation Site (Rare). Nodule eroding to ulcer. May have nodular lymphangitis, regional lymphadenitis.

Hematogenous Dissemination to Skin. Initially, papule (Fig. C-9) evolving with formation of pustules, plaques, nodules. Abscess formation, multiple draining sinus tracts, ulcers; subcutaneous cellulitis; verrucous plaques; granulomatous nodules. Scars. Distribution: face, especially nasolabial fold—preferential site; extremities.


Figure C-9. Coccidioidomycosis: disseminated Ulcerated and crusted nodules on the cheek and nose of an individual with pulmonary coccidioidomycosis with dissemination to the skin. (Courtesy of Francis Renna, MD.)

Differential Diagnosis

Cryptococcosis, molluscum contagiosum.


Detection of Coccidioides spherules in sputum, pus, skin/tissue biopsy specimen. Isolation of Coccidioides on culture.


In untreated HIV disease, mortality rate is high; relapse rate very high.


Fluconazole, itraconazole, amphotericin B.

Penicilliosis ICD-9: 117.3 image ICD-10: B44.9 image

image Etiology. Penicillium marneffei, dimorphic fungus.

image Demography. Occurs in the setting of HIV disease in those living in or traveling to Southeast Asia. With HIV disease, incidence similar to infections with Cryptococcus neoformans and Mycobacterium tuberculosis.

image Pathogenesis. Primary portal of entry is the lung. Hematologic dissemination with host defense defects.

Clinical Manifestations

Primary Pulmonary Infection. Fever, chills, weight loss, anemia, generalized lymphadenopathy, and hepatomegaly.

Disseminated Penicilliosis to Skin. Diffuse disseminated papular lesion (Fig. C-10).


Figure C-10. Penicilliosis in HIV disease: disseminated skin lesions A 27-year-old Vietnamese male with advanced untreated HIV disease presented with fever, weight loss, and disseminated umbilicated skin-colored papules. Hundreds of skin-colored papules of varying sizes, many umbilicated or with central erosion and crust. (Courtesy of Hoang Van Minh, M.D.)


Small yeast cells may be seen on histopathologic examination of tissue. Definitive diagnosis depends on culture of clinical specimens.


Amphotericin B.