Disseminated blastomycosis presenting as a retro-orbital mass

Abstract

A 43-year-old man with history of non-Hodgkins’ lymphoma presented with unilateral eye swelling, pain and vision deficits which had been progressive over 2 months. Symptoms followed a presumed bacterial pneumonia 4 months prior. Imaging demonstrated retro-orbital soft tissue swelling with bony erosion concerning for a mass; surgical decompression was performed with histology confirming disseminated Blastomyces dermatitidis. Symptoms responded rapidly to antifungal therapy with amphotericin followed by itraconazole. Orbital dissemination of blastomycosis is extremely rare; accurate diagnosis requires tissue biopsy to facilitate timely targeted therapy and minimise morbidity.

Background

Blastomyces dermatitidis, a dimorphic fungus endemic to areas of central and eastern North America, most often results in an acute pulmonary illness. Haematogenous dissemination can lead to skin, bone, genitourinary, and less frequently, central nervous system involvement.¹ Diagnosis is often delayed due to the wide spectrum of disease, non-specific symptoms, relative rarity and lack of serological diagnostic testing. Diagnosis relies on tissue sampling for culture and histology, and is essential so that appropriate antifungal therapy may be initiated.

Case presentation

A 43-year-old Caucasian man with history of non-Hodgkins’ lymphoma, in remission following chemotherapy the year prior, presented with unilateral eye pain and vision changes. Left upper eyelid swelling and erythema began 2 months earlier, progressing to pain with horizontal eye movements and diplopia with extreme lateral gaze deviation. There were no constitutional symptoms. Four months prior to symptom onset, he had been treated for pneumonia as an outpatient with gradual resolution. The patient resided near a river bank in the Mohawk Valley region of Upstate New York, reported no other travel or environmental exposures. On exam, he was afebrile, with left-sided proptosis, lateral gaze restriction and decreased visual acuity (20/80). No pupillary defect, chemosis or discharge was observed. Fundoscopic exam showed mild disc oedema. Skin exam revealed a single 1×1.5 cm non-tender papular lesion with irregular borders located on the posterior left thigh (figure 1).

Figure 1.

Verrucous and non-tender posterior left thigh lesion with irregular borders measuring 1×1.5 cm.

Investigations

Contrast-enhanced CT of the orbits showed homogenous retro-orbital soft tissue swelling resulting in proptosis of the globe with bone erosion and optic nerve compression (figure 2). He underwent endoscopic decompression and debridement of the left orbital apex and optic nerve. Pathology revealed necrotising granulomatous inflammation (figure 3). Grocott’s methenamine silver stain of both the left orbital bone and subsequent biopsy of the thigh lesion showed broad-based budding yeast consistent with B. dermatitidis (figure 4). Chest radiography from the time of his diagnosis with pneumonia, obtained from an outside facility, demonstrated a right upper lobe opacity, likely representing an initial pulmonary blastomycosis (figure 5).

Figure 2.

(A) Homogenously enhancing soft tissue along the left sphenoid bone extruding into the left superior and lateral rectus muscles, with resulting proptosis of the left globe. (B) Effacement of the left superior orbital fissure and encasement of the left optic canal.

Figure 3.

Biopsy of the left orbital lesion showed non-caseating granulomatous inflammation with central necrosis (H&E, 100× magnification).

Figure 4.

Multiple budding yeast forms characteristic of Blastomyces dermatides (GMS, 300× magnification).

Figure 5.

Initial chest radiograph from 4 months prior to presentation, showing a right upper lobe infiltrate.

Differential diagnosis

Based on his unilateral eyelid erythema and swelling, the differential diagnosis on initial presentation included preseptal cellulitis. His subacute presentation was less consistent with typical bacterial cellulitis, and other infectious etiologies (including fungal and non-tuberculosis mycobacteria) were discussed. Given his indolent course, recent history of malignancy and mass-like CT findings, there was a high level of concern for recurrent lymphoma. Non-infectious causes of granulomatous inflammation, such as sarcoidosis, were also a consideration.

Treatment

He was treated with daily liposomal amphotericin B for 4 weeks, after which he was switched to oral itraconazole 200 mg two times per day for a planned 12-month course.

Outcome and follow-up

The patient experienced rapid symptomatic improvement on amphotericin-based therapy. Within the first 4–6 weeks of therapy he had complete resolution of all signs and symptoms, with no residual deficits on visual acuity testing. He was then maintained on oral itraconazole, which was well tolerated.

Discussion

Disseminated blastomycosis presenting as a retro-orbital mass is a very rare manifestation of an uncommon disease.¹ Blastomycosis most frequently presents with an acute pulmonary infection; dissemination may result in varied indolent presentations that can mimic more familiar conditions, such as malignancy, resulting in delays in treatment. The lungs are the usual site of entry for blasto, and while up to 50% may be asymptomatic, a thorough history may reveal chronic (more commonly) or acute pneumonia, as was seen in this case.² Haematogenous dissemination can lead to skin, bone, genitourinary, and less frequently, CNS involvement. A careful skin exam may reveal characteristic skin lesions, the most common extrapulmonary site of infection, which further suggests the diagnosis. Skin findings can begin as subcutaneous nodules, and classically present as verrucous lesions with irregular, raised borders.² CNS blastomycosis is uncommon, seen in <5% of cases and may manifest as meningitis, epidural abscess or intracranial abscesses.³

While blastomycosis is common in several regions of central and eastern North America, it has been identified with increasing frequency outside of traditionally endemic areas, including the Mohawk Valley region and Capital District of upstate New York.⁴ Serology is not useful in the diagnosis of blastomycosis, reinforcing the need for microbiological and histological evaluation. Visualisation of the yeast form on biopsy may allow for a presumptive diagnosis, though culture remains the gold standard.³ Treatment for blastomycosis with CNS involvement comprises induction liposomal amphotericin followed by prolonged step-down azole therapy—voriconazole is typically chosen, if tolerated, due to good CSF penetration compared with itraconazole and excellent activity against B. dermatitidis.⁵ This case illustrates the importance of a broad differential diagnosis, thorough history and physical exam, and timely tissue biopsy.

Learning points.

• While blastomycosis typically presents with pulmonary disease, haematogenous dissemination can lead to almost any organ involvement, most commonly skin and bone.

• The presentation of blastomycosis is non-specific, overlapping with more familiar conditions, so a high index of suspicion is essential.

• As there is no reliable serology for identifying Blastomyces dermatitidis, culture and/or tissue biopsy is vital for diagnosis.