Pediatric Blastomycosis 

Blastomycosis, which originally was described by Gilchrist and Stokes in 1894 and 1896, is an infection with a highly variable spectrum of clinical presentations. Disease can range from an asymptomatic, self-healing pulmonary infection to widely disseminated fatal disease.

Blastomyces dermatitidis is a dimorphic fungus. The mycelial form grows as a white mold. The conidia (spores) that convert to yeast are infectious to humans. The epidemiology is incompletely understood because of the lack of a sensitive and specific skin test and difficulties in establishing the ecologic niche of the organism in nature. In the United States, most infections are clustered in states adjacent to the Mississippi and Ohio rivers and the Great Lakes region. Although initial epidemiologic studies reported a higher incidence of infection in men, more recent series have shown no predilection for any specific sex, age, race, or occupation or any seasonal variation. The disease is uncommon in children but is now recognized increasingly in immunocompromised hosts, particularly in patients with acquired immune deficiency syndrome (AIDS).^[1]

Infection is acquired via inhalation of the conidia. Once in the lungs, the conidia need to mature into invasive yeast for infection to occur. Immunocompetent hosts have a natural resistance to infection with Blastomyces because alveolar macrophages inhibit the transformation of conidia into yeast. Such natural resistance is supported by studies of blastomycosis epidemics, in which asymptomatic infection occurs in at least 50% of persons in whom Blastomyces has colonized. The factors that determine whether disease develops in infected persons are unclear. Cellular immune host resistance has been difficult to evaluate for its role in protection against infection but is probably an important factor for asymptomatic versus overt infection.

The term B dermatitidis refers to the imperfect (asexual) stage of Ajellomyces dermatitidis, which grows as a yeast at 37°C and mycelial form at room temperature. Two serotypes of B dermatitidis have been detected by exoantigen analysis. The perfect (ie, sexual form), A dermatitidis, is heterothallic and requires 2 compatible mating types for spore formation. The mycelial form, which bears conidiophores, produce single terminal conidia, which measure 2-10 µm in diameter and are round or oval.

Primary infection, which may be subclinical, occurs in the lung following inhalation of fungal conidia. Transition from the mold form to the yeast form occurs after deposition in the distal airways. The phase shift occurs as a result of heat-related stress, followed by uncoupling of oxidative phosphorylation. In the absence of nonspecific host defense mechanisms, cells increase in number in the lung parenchyma. Hilar lymph nodes may become involved, and, subsequently, lymphohematogenous spread to the other organs may occur. Incubation time averages 4-6 weeks and widely varies.

Subclinical cases of blastomycosis occur in at least 50% of infected individuals, thus supporting the hypothesis that some patients have natural resistance. Cellular immune response mediated by antigen-specific T lymphocytes and lymphokine-derived macrophage's cell-mediated immunity plays a critical role in aborting fungal growth.

Frequency

United States

The disease is endemic in midwestern, north central, and southeastern regions. Most clinical cases are reported in states surrounding the Mississippi and Ohio rivers and the Great Lakes region. Incidence of infection in individuals residing in endemic areas is unknown. Point-source epidemics of infection in endemic areas have been associated with recreational and occupational activities in wooded areas along waterways and have implicated activities that include aerosolizing organically enriched soil.

International

Blastomycosis has also been reported in parts of Canada, India, Africa, and Central and South America. Because of the erroneous belief that the disease is limited only to the United States, blastomycosis is often referred to by the term North American blastomycosis, which is an obsolete term. The term European blastomycosis is a confusing synonym of cryptococcosis, a systemic infection caused by the yeastlike fungus Cryptococcus neoformans. Likewise, South American blastomycosis (ie, Brazilian blastomycosis) is an older name for paracoccidioidomycosis, a chronic, often fatal, mycosis caused by a large dimorphic fungus, Paracoccidioides brasiliensis.

Mortality/Morbidity

Before the advent of antifungal therapy, the mortality rate associated with blastomycosis exceeded 60%. The mortality rate in appropriately treated cases is 10% or less. In contrast, one third of immunocompromised patients do not respond to all therapy, and 30-40% die of the disease. Most deaths occur within the first few weeks of therapy.

The clinical course of blastomycosis is more severe in the immunocompromised host, including patients with late stages of AIDS, transplant recipients, and those receiving immunosuppressive or cytotoxic therapy. Severe pulmonary disease complicated by adult respiratory distress syndrome occurs in approximately 20% of compromised hosts.^[2] CNS disease appears to be 3-5 times more common in immunocompromised patients than in normal hosts.

Sex

Although initial epidemiologic studies reported a higher incidence of infection in men, more recent series have shown no predilection for any specific sex, age, race, or occupation or any seasonal variation. In children, as in adults, both sexes are equally susceptible.

Age

Men aged 30-50 years are affected most commonly. The disease is rare in children and adolescents. In 1983-1995, a retrospective study at a children's hospital identified only 10 patients with the disease.^[3] However, in past reviews, about 2-10% of patients reported were younger than 15 years.