Verrucous Lesion on Upper Arm

Blastomycosis is a systemic infection caused by the dimorphic fungus Blastomyces dermatitidis, which is endemic to North America, specifically the Mississippi and Ohio River Valley regions (although it is not restricted solely to North America).1 It previously was known as...

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Blastomycosis is a systemic infection caused by the dimorphic fungus Blastomyces dermatitidis, which is endemic to North America, specifically the Mississippi and Ohio River Valley regions (although it is not restricted solely to North America).¹ It previously was known as Gilchrist’s disease, after Thomas Casper Gilchrist, who first described the disease in 1894 but who originally attributed the cause to a protozoan.² Gilchrist, along with a collaborator, later identified the responsible organism as the fungus B. dermatitidis.³ 

Soil is an important reservoir for the fungus, and infection usually is acquired through airborne inhalation of the conidia. As such, those who work outside, such as construction workers, are at high risk for acquiring the illness. All ages and genders are at risk; however, some series have reported a higher incidence in men.⁴ This is thought to be because men are more likely to participate in activities or occupations that put them at higher risk for exposure to B. dermatitidis, such as hunting, fishing, construction, or forestry work, and not because they are inherently more susceptible to the organism.⁴

Following inhalation of the conidia, the lungs are the first site of infection; the resulting pulmonary disease may range from being asymptomatic to severe and frank pneumonia, with cough, fever, sputum production, chest pain, and pulmonary infiltrates/consolidations seen on imaging.^4,5 Pulmonary disease may clear spontaneously or progress and secondarily disseminate, leading to extrapulmonary disease in the skin and bones, most commonly, or the genitourinary tract and central nervous system, uncommonly.⁵

The skin is the most common site of extrapulmonary spread, which is reported in up to 40% to 80% of cases.⁴ A cutaneous lesion often leads to the diagnosis, especially in cases in which pulmonary symptoms are relatively mild. Primary cutaneous blastomycosis from direct inoculation of the skin is uncommon; therefore, a thorough search for systemic disease should be undertaken in all patients with cutaneous lesions.⁴

A well-demarcated verrucous plaque with central ulceration, scale-crust, and pustules is a common cutaneous presentation of blastomycosis.^5,6 Advanced cases with large central ulceration may mimic pyoderma gangrenosum. Lesions may begin as well-circumscribed non-painful papules, nodules, or plaques that become verrucous and/or ulcerate, at which time they may become painful. Patients may have one to several lesions, which tend to be on sun-exposed sites.⁴

Biopsy with identification of the fungus and corroborating culture results is the preferred method to diagnose skin disease.⁵ A punch biopsy should be performed from a pustule or from the thick, verrucous edge of the lesion (avoiding the ulcerated areas). On histopathology, there typically is pseudoepitheliomatous hyperplasia (thickening of the epidermis and adnexal structures), neutrophilic inflammation (forming microabscesses), as well as granulomatous inflammation (composed of histiocytes and giant cells).⁶

In tissue, B. dermatitidis exists as round yeast forms that are approximately 8 to 15 microns in diameter and have thick, double-contoured walls.⁴ They may be found in the neutrophilic microabscesses or within giant cells and characteristically bud from 1 to another with a broad base.

The size, thick wall, and budding pattern are helpful features in differentiating blastomycosis from other fungal infections. The fungal forms can be highlighted with periodic acid-Schiff or Grocott methenamine silver staining on formalin-fixed, paraffin-embedded tissue section.⁴ Additionally, broad-based budding yeast can be identified quickly in the office by collecting a sample from the purulent discharge, placing it directly onto a microscope slide, and covering it with 10% or 20% potassium hydroxide.⁴ Skin or pus can be cultured for species identification, but these results may take a few weeks to finalize. If available, polymerase chain reaction–based assays are useful and may yield results more quickly.⁴

Conditions that should be considered in the differential diagnosis of blastomycosis include cutaneous infections, inflammatory dermatoses, and neoplasms. Cutaneous infections from other dimorphic fungi (such as chromomycosis or histoplasmosis), nocardia, mycobacteria (including atypical mycobacteria and tuberculosis), and bacteria may present like blastomycosis. One study used the terminology “blastomycosis-like pyoderma,” for the clinical appearance of a large verrucous plaque studded with multiple pustules appearing like cutaneous blastomycosis.⁴ Typically, this is in reference to a chronic, vegetating bacterial infection, most commonly Staphylococcus aureus. Pyoderma gangrenosum is an inflammatory dermatosis that may mimic advanced cases of blastomycosis.⁶ Halogenoderma may be considered with corroborating historical information.

Squamous cell carcinoma and basal cell carcinoma should be considered in the clinical differential diagnosis as well. Although there may be clinical and histopathologic overlap, a biopsy that identifies the typical yeast forms will help differentiate cutaneous blastomycosis from these entities. Culture results will solidify the diagnosis.⁴

Blastomycosis almost always requires systemic antifungal therapy, and the Infectious Diseases Society of America has published clinical guidelines for treatment.⁷ Mild to moderate disease is treated with a prolonged course of itraconazole for 6 to 12 months. When the infection is severe, progressive, or disseminated, or if the patient is immunocompromised, amphotericin B is given first, for 1 to 2 weeks, to gain control, then itraconazole is given for 6 to 12 months. Fluconazole, ketoconazole, and voriconazole can be used as alternatives to itraconazole, but they are less effective and have greater potential to cause adverse outcomes.⁷

In the case presented, a punch biopsy of the lesion showed hyperplasia of the epidermis, with dermal inflammation containing numerous neutrophils (forming microabscesses) as well as histiocytes and giant cells. Scattered, round-thick walled forms approximately 8 to 15 microns in diameter were seen in the microabscesses and in some giant cells. Some of these forms were broadly connected to one another. The patient also had evidence of pulmonary disease on imaging. Given the progressive course, he was started on amphotericin B in the hospital and transitioned to itraconazole with complete clearance of the lesions over the next several months.

Andrew Fischer, MD is a board-certified dermatologist at Elite Dermatology in Houston, Texas.

References

1. Centers for Disease Control and Prevention. Fungal diseases. Blastomycosis. CDC website.. Accessed September 29, 2020. https://www.cdc.gov/fungal/diseases/blastomycosis/index.html
2. Gilchrist TC. Protozoan dermatitis. J Cutan Gen Dis. 1894;12:496-499.
3. Gilchrist TC, Stokes WR. A case of pseudo-lupus vulgaris caused by blastomyces .J Exp Med. 1898;3(1):53-78.
4. Saccente M, Woods GL. Clinical and laboratory update on blastomycosis. Clin Microbiol Rev. 2010;23(2):367-381.
5. Kauffman C. Infectious diseases. Blastomyces dermatitidis. Infectious Disease Advisor website. Accessed October 4, 2020. https://www.infectiousdiseaseadvisor.com/home/decision-support-in-medicine/infectious-diseases/blastomyces-dermatitidis/
6. Scuderi S, O’Brien B, Robertson I, Weedon D. Heterogeneity of blastomycosis-like pyoderma: a selection of cases from the last 35 years. Australas J Dermatol. 2017;58(2):139-141.
7. Chapman SW, Dismukes WE, Proia LA, et al. Clinical practice guidelines for the management of blastomycosis: 2008 update by the Infectious Diseases Society of America. Clin Infect Dis. 2008;46(12):1801-1812.