Cutaneous lesions and early presentation of disseminated blastomycosis: A case report

Abstract

Blastomycosis is a fungal infection caused by Blastomyces dermatitidis, which is hyperendemic to areas of Northwestern Ontario, Canada. Delayed diagnosis is common due to the condition’s nonspecific clinical presentation, often resembling malignancy or other dermatological and infectious diseases. We report the case of a 27-year-old otherwise healthy male with an early presentation of disseminated cutaneous blastomycosis. Early recognition of cutaneous blastomycosis can significantly reduce morbidity, mortality, and the overall treatment burden by facilitating timely antifungal therapy. This case shares valuable early clinical presentation and photographs for clinical reference, aiding in earlier disease recognition.

Introduction

Blastomycosis is a fungal infection caused by Blastomyces dermatitidis, a thermally dimorphic fungus endemic to specific regions in North America, including the Great Lakes regions, the Mississippi River Valleys, and southeastern United States. ¹ Endemic areas typically have an incidence of 0.5–2 cases/100,000/year. In Canada, blastomycosis is most notably hyperendemic in Northwestern Ontario. Between 2019 and 2023, the annual incidence for the Northwestern Health Unit ranged from 17.2 to 50.4 cases/100,000/year, which is up to a 100-fold increase compared to anywhere in North America.^2,3 Blastomycosis became a reportable disease in Ontario in May 2018, reflecting the public health significance of its increasing regional prevalence. ³

The infection occurs following the inhalation of fungal spores and rarely, from direct inoculation into the skin. The spores are found in acidic soil rich in decomposing organic matter. As such, common risk factors include exposure in endemic regions, especially with activities that disrupt the soil such as construction, gardening, or camping. However, cases without evident exposures have also occurred. The incubation period ranges from 21 to 106 days, with a median of 43 days. There is no known method to eradicate B. dermatitidis from the soil, nor to confirm its absence in a given plot. ⁴ Notably, the disease is not transmissible from person to person, nor from animals to humans. ³

Blastomycosis most commonly presents as a pulmonary infection, with extrapulmonary manifestations occurring in 25%–30% of cases due to hematogenous dissemination. Skin involvement is the most frequent extrapulmonary site, followed by lytic bone lesions and, less commonly, genitourinary or central nervous system involvement. Unlike many other fungal infections, blastomycosis can occur in both immunocompetent and immunocompromised hosts. ¹ Misdiagnosis and delays in diagnosis of blastomycosis are common, with up to 40% of patients experiencing delays of a month or more. ² Most case reports in literature reflect this, with patients often being definitively diagnosed months to years after initial presentation. These delays lead to increased mortality rates and unnecessary healthcare costs. ²

In this case report, we describe the early diagnosis of cutaneous blastomycosis in a hyperendemic region. We will highlight the clinical manifestations and diagnostic challenges of this potentially severe infection and discuss the treatment thereof. Written patient consent was obtained.

Case description

An otherwise healthy 27-year-old male living in Northwestern Ontario presented to the local Emergency Department with a 3-day history of tender and purulent nodules localized to the right inner arm, left elbow, and lower lip (Figures 1–3). He denied systemic symptoms such as fever, weight loss, or night sweats, and had no respiratory symptoms. Initial management included topical mupirocin for empiric treatment of methicillin resistant staphylococcus aureus (MRSA)-infected lesions. He returned to the Emergency Department the next day due to progression of the rash, which had erupted in new areas. These pustules were treated with oral cephalexin. He was followed up at a family practice 2 days later, with new eruptions on multiple fingers, plantar feet, and knees. He also developed tenderness in both his hands and knees (see Figures 1–4). Cephalexin was discontinued, and he was treated empirically for disseminated gonorrhea with ceftriaxone and doxycycline. Skin biopsies were obtained for fungal and bacterial cultures, as well as pathology. The following day, the laboratory informed the ordering physician that blastomycosis was visible on direct microscopy.

Figure 1.

Pustule on right hand middle finger within first week of presentation, verrucous transformation 2 weeks in.

Figure 2.

Pustules on right inner arm at first week of presentation and evolution 2 weeks in.

Figure 3.

Lip lesion within first week of presentation.

Figure 4.

Swelling of right thumb within first week of initial presentation.

One week later, additional history was obtained, revealing a 1-month history of cough. The patient also disclosed that he had been gardening in black earth and worked as a caretaker with duties in landscaping and tree cutting. One of his pet dogs was also recently treated for blastomycosis. At this point, his lesions had evolved to have a more verrucous appearance (see Figure 5). His chest radiographs demonstrated a new right pleural effusion with retrosternal density. A subsequent computed tomography (CT) scan chest found trace right pleural effusion, multiple pulmonary nodules, cavitating lesions, and mediastinal lymphadenopathy.

Figure 5.

Verrucous appearing lesions at 2 weeks within initial presentation.

The patient’s investigations eventually returned normal for bacterial cultures (no pathogens isolated, skin flora present), viral cultures (Herpes Simplex Virus, Varicella Zoster Virus), blood cultures, anti-streptolysin O titre, creatinine, liver enzymes, serum electrolytes, complete blood count, syphilis, hepatitis B and C, ANA, anti-ds DNA, complement factors 3 and 4, rheumatoid factor, gonorrhea and chlamydia, and urine culture. His C-reactive protein was elevated at 19.9 mg/dL. CT imaging of the head, legs, and abdomen ruled out further intracranial or bony dissemination but demonstrated hepatomegaly and mild splenomegaly.

Tissue pathology described the presence of intraepidermal neutrophils, hyperkeratosis, acanthosis, and collections of micro-abscesses within the epidermis. Tissues were stained with hematoxylin and eosin, methenamine silver stain, and periodic acid Schiff, which all confirmed the presence of thick-walled, broad-budding yeast within the deep dermis suggestive of blastomycosis. The fungal culture from biopsy tissue eventually isolated B. dermatitidis/Blastomyces gilchristii a few weeks later.

Management

The patient was started on treatment with itraconazole 200 mg orally three times a day for 3 days, then 200 mg orally twice daily, for disseminated blastomycosis and ceftriaxone and doxycycline were discontinued. The patient’s skin lesions completely resolved with oral itraconazole and his cough significantly improved within 1 month of antifungal therapy. Follow-up bloodwork was completed on a monthly basis to monitor for any potential complications of itraconazole. The patient was found to have developed thrombocytopenia which reached a nadir of 86,000/µL from his baseline of 177,000/µL. This was suspected to be related to sequestration from hepatosplenomegaly, presumed to be secondary to the disseminated disease and was monitored closely without further complication. Itraconazole was discontinued at 9 months instead of the initially planned duration of 12 months due to drastic clinical improvement and resolution of chest radiograph findings.

Discussion

There are significant challenges in the early diagnosis of cutaneous blastomycosis, often referred to as “the great pretender” due its mimicry of other conditions. ² Early recognition and treatment are essential, as the mortality rate is 5%–10% with treatment and reported to vary from 40% to 89% without.^2,5 Delay in treatment can lead to severe disseminated infection resulting in bone, central nervous system, and genitourinary tract involvement.

The patient’s presentation with tender, purulent nodules is consistent with the early manifestation of disseminated blastomycosis. These lesions eventually crust and evolve into verrucous plaques, ulcerations, or hyperkeratotic nodules.^1,2 Such advanced presentations are more commonly reported in the literature due to delays in diagnosis. The clinical and histologic findings of cutaneous lesions often resemble other conditions, including squamous cell carcinoma, pyoderma gangrenosum, syphilis, and other fungal infections, further complicating the diagnostic process. Even histological evaluation may be misleading, as findings of pseudoepitheliomatous hyperplasia, hyperkeratosis, acanthosis, hypergranulosis with neutrophilic infiltrate, and noncaseating granulomas can overlap with pyoderma gangrenosum or other granulomatous diseases. ⁶

Blastomycosis lacks pathognomonic clinical or radiographic features, necessitating direct visualization of the organism for definitive diagnosis. This is achieved through fungal microscopy of sputum or tissue samples, with fungal culture serving as the gold standard despite its time-intensive nature.^1,7 Cutaneous involvement is the most common extrapulmonary manifestation and is occasionally the primary site of inoculation. The accessibility of skin lesions makes them a valuable diagnostic tool, offering an opportunity for biopsy and early identification of the disease. Urinary antigen testing is another sensitive, specific, and noninvasive test. It is recommended for this reason, but it is not widely available in Canada. ⁸ Failure to respond to empiric antibiotic therapy, as in this case, should prompt clinicians to expand their differential diagnoses.

A high index of suspicion is particularly important in patients with a history of living, working, or traveling in endemic areas. In this case, the patient’s dog had also been treated for blastomycosis. While the disease is not transmissible from animals to humans, canine infection underscores the likelihood of environmental exposure to fungal spores, as dogs are more prone to infection due to their proximity to the ground. ⁴ This epidemiological clue further supported the diagnosis.

Conventional treatment for blastomycosis involves lipid formulations of intravenous amphotericin B in severe cases, for up to 2 weeks until clinical improvement is demonstrated, or 6 weeks in cases with central nervous system involvement. Patients are then stepped down to oral itraconazole for 6–12 months, with the absolute duration contingent upon clinical response. However, amphotericin B is associated with numerous adverse effects, including renal tubular necrosis. Therefore, mild and moderate cases not requiring inpatient management can often be treated with oral itraconazole only. Hepatotoxicity is chief among the adverse effects of itraconazole (which are less frequent than amphotericin B).^9,10 Itraconazole levels were completed and within therapeutic range. The patient was also advised to take it with sips of Coca-Cola as acidic beverages enhance absorption. ¹¹ Monthly monitoring labs were completed on this patient, including his complete blood count, liver enzymes, and renal function tests. In this case, the patient developed mild thrombocytopenia, which improved after completion of itraconazole therapy. Given intensity and duration of therapy can be adjusted based on clinical response, early diagnosis is beneficial in reducing the eventual burden of medication side effects as well as clinical outcomes related to the disease processes themselves.

Conclusion

This case emphasizes the importance of maintaining a high index of suspicion for blastomycosis in patients with persistent, nonresponsive cutaneous lesions, especially in endemic areas. Unlike most published reports, which describe delayed cases, this report captures the initial clinical workup along with photographs of early-stage lesions, offering a valuable reference for clinicians. It underscores how prompt recognition and diagnosis of early-stage cutaneous manifestations can significantly reduce associated mortality and support timely, effective treatment, even enabling earlier cessation of antifungal therapy.