Deep Fungal Infections, Blastomycosis-Like Pyoderma, and Granulomatous Sexually Transmitted Infections

Granulomatous diseases are caused by multiple infectious and noninfectious causes. Deep fungal infections can present in the skin or extracutaneously, most commonly with lung manifestations. An Azole or amphotericin B is the universal treatment. Blastomycosis-like pyoderma is a clinically similar condition, which is caused by a combination of hypersensitivity and immunosuppression. Successful treatment has been reported with antibiotics and, more recently, the vitamin A analog, acitretin. Granuloma inguinale and lymphogranuloma venereum cause ulcerative genital lesions with a granulomatous appearance on histology. The Centers for Disease Control and Prevention recommens treatment of these genital infections with doxycycline.

Key points

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Deep fungal infections have similar skin findings and are therefore differentiated by laboratory testing.
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The mainstay of treatment of these diseases is azoles for mild to moderate disease and amphotericin B for severe disease.
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Blastomycosis-like pyoderma (BLP) is clinically indistinguishable from deep fungal infections and responds best to treatment with the vitamin A analog, acitretin.
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Granuloma inguinale and lymphogranuloma venereum (LGV) are 2 sexually transmitted granulomatous diseases that create ulcerative lesions. Both are treated with doxycycline.

A granuloma is a nonspecific histologic finding that can indicate a wide range of diseases from vasculitis or other autoimmune processes to leukocyte oxidase deficiency, hypersensitivity, chemical exposure, malignancy, or infection. Histologically, granulomas have a nodular appearance with a central area of breakdown that is surrounded by a circular or horseshoe-shaped ring of hallmark multinucleated giant cells. Giant cells, also called epithelioid cells, begin as normal macrophages that fuse and transform in the presence of inflammatory and immune cytokines.

The pathogenesis of granuloma formation is mediated by the immune system. Initially, immune cells are drawn to the area because of injury to the tissue through either infection or foreign body reaction. The presence of a nondegradable product continuously stimulates the immune system via T _H1 cells, B-cell activity, and circulating immune complexes. Infections can act as stimuli for both arms of granuloma development because the infectious organism is recognized as an antigen and a foreign body simultaneously.

Three specific types of granuloma-forming infections are reviewed in this article, including deep fungal infections, BLP, and granulomatous sexually transmitted infections (STI).

Etiopathogenesis

Deep Fungal Infections

Blastomycosis, coccidioidomycosis, cryptococcus, histoplasmosis, and sporotrichosis are granulomatous deep fungal infections with cutaneous manifestations. The pathogens are dimorphic fungi that infect both immunocompetent and immunocompromized hosts; however, a patient’s immune status (in addition to the volume or intensity of the exposure) often affects the severity of the infection.

All these diseases present as localized or systemic infections. Aside from sporotrichosis, the granulomatous deep fungal infections are most commonly acquired via inhalation into the respiratory tract, although direct inoculation into the skin is also possible. Generally, these fungal infections have no notable preponderance for one age group or gender. Table 1 compares the infectious organism and common clinical presentations of granulomatous deep fungal infections.

Table 1

Causes and presentation of granulomatous deep fungal infections

Clinical Condition	Fungal Species	Presentation and Systemic Symptoms
Blastomycosis	Blastomyces dermatitidis	Primary pulmonary • Most common • Asymptomatic to acute or chronic pneumonia • Skin findings in 70%–80% of patients • Always treat Primary cutaneous: see Clinical Presentation section Disseminated • 25% osteomyelitis • 10%–20% genitourinary (prostatitis or epididymo-orchitis) • 5%–10% CNS (meningitis or cranial abscess)
Coccidioidomycosis	Coccidioides immitis Coccidioides posadasii	Primary pulmonary • Most common, also called valley fever • Majority asymptomatic or with mild symptoms • Significant pulmonary illness rare but can disseminate • Skin findings in 15% of patients Primary cutaneous: see Clinical Presentation section Disseminated • Bony involvement most common after lungs and skin • CNS involvement rare, but high fatality
Cryptococcus	Cryptococcus neoformans	Primary pulmonary • Typically caused by separate species, Cryptococcus gattii Primary cutaneous: see Clinical Presentation section Disseminated • CNS most common, as meningitis or meningoencephalitis • Skin most common extraneural site (10%–20%) • Osteomyelitis and genital ulcerations, but rarely
Histoplasmosis	Histoplasma capsulatum	Primary pulmonary • Brief malaise to severe respiratory illness • Most cases resolve spontaneously Primary cutaneous: see Clinical Presentation section Disseminated • Chronic, indolent course in immunocompetent • Acute, rapidly fatal in infants and immunosuppressed • Hepatosplenomegaly, pancytopenia from bone marrow involvement, polyarthritis, or CNS
Sporotrichosis	Sporothrix schenckii	Lymphocutaneous: see Clinical Presentation section Fixed cutaneous: see Clinical Presentation section Disseminated • Rare, associated with immunosuppression • Due to hematogenous spread from primary skin lesions • Bone and lung involvement most common • High mortality in pulmonary and CNS disease Extracutaneous • Most rare, associated with immunosuppression • Usually due to inhalation and hematogenous spread • Osteoarticular involvement in 80% of cases