Cutaneous Blastomycosis Masquerading as Pyoderma Gangrenosum

Abstract

Cutaneous blastomycosis (CB) is associated with a variety of skin manifestations. Among other entities, CB may be mistaken for pyoderma gangrenosum due to overlap of findings on histopathologic examination. We report a case of CB, initially diagnosed as pyoderma gangrenosum and treated with steroids, leading to disseminated blastomycosis and acute respiratory distress syndrome (ARDS).

CASE REPORT

A 30-year-old male with a history of presumed pyoderma gangrenosum (PG) of the left foot treated with high-dose prednisone was transferred from an outside hospital to our intensive care unit with respiratory distress. Exposure history included working outdoors and landscaping. He was initially treated with noninvasive mechanical ventilation but developed worsening hypoxemia requiring endotracheal intubation for mechanical ventilation. Chest X-ray results demonstrated diffuse bilateral mixed alveolar and interstitial opacities with increased confluence in the left lung consistent with acute respiratory distress syndrome (ARDS). An urgent bronchoscopy was performed. Cytopathologic examination of the bronchoalveolar lavage (BAL) fluid demonstrated abundant broad-based budding yeast, consistent with Blastomyces dermatitidis (Fig. 1A and B). Blastomyces urine antigen was measured at >14.7 ng/ml. Intravenous amphotericin B deoxycholate (1 mg/kg of body weight/day) was started in addition to methylprednisolone (125 mg administered intravenously [i.v.] every 6 h) for severe disseminated blastomycosis and ARDS (1, 2). The patient was placed on RotoProne bed therapy for refractory hypoxic respiratory failure. The hypoxemia improved gradually. He was ultimately extubated, transitioned to oral itraconazole (400 mg twice daily), and discharged home 53 days after admission. Culture of BAL fluid eventually grew B. dermatitidis, which was confirmed by DNA probe (Gen-Probe, Inc., San Diego, CA).

FIG 1.

(A) Diff-Quik stain of the BAL fluid specimen demonstrating the broad-based budding yeast of Blastomyces dermatitidis. (B) The same specimen stained by the Gomori methenamine silver stain method. The double walls of the yeast form of this dimorphic pathogen are clearly visible in both stains. (C) Low-power (original magnification, ×100) examination of a hematoxylin-and-eosin-stained skin biopsy specimen demonstrates pseudoepitheliomatous hyperplasia and a predominately neutrophilic inflammatory infiltrate. (D) High-power magnification (original magnification, ×400) of the skin biopsy specimen reveals a broad-based budding yeast cell and adjacent yeast with thick, refractile double walls within a multinucleate giant cell.

Four months prior to this admission, the patient had noted a painful blister on the medial aspect of his left midfoot which progressed to an ulcer. A punch biopsy specimen of the lesion revealed acute and chronic inflammation with necrosis, possibly representing PG. This biopsy specimen was not submitted for culture. The patient was treated with 100 mg prednisone orally, with some improvement of the lesion.

Later, the slides from this biopsy specimen were retrieved and reviewed by our pathologists, who identified yeast consistent with Blastomyces dermatitidis (Fig. 1).

Cutaneous blastomycosis usually occurs after hematogenous dissemination from a primary pulmonary infection, even in the absence of overt pneumonia (3). Much less commonly, Blastomyces dermatitidis can be directly inoculated into the skin, resulting in cutaneous inoculation blastomycosis (4). These skin lesions are most often described as verrucous or ulcerative; however, a broad variety of presenting lesions, including nodules, pustules, papules, and abscesses, has been described (4, 5). The variety of skin manifestations combined with the presence of suppurating granulomas on histopathological examination has led to multiple reports of initially misdiagnosed cutaneous blastomycosis (3, 4, 6). Most often implicated are granulomatous skin processes, such as scrofuloderma, lupus vulgaris, and granuloma inguinale. Other misdiagnoses include nocardiosis, syphilis, tuberculosis, and endemic mycoses, as well as squamous cell carcinoma and arthropod bite reactions (3, 4, 7). Our patient was initially diagnosed with PG.

Pyoderma gangrenosum is a noninfectious neutrophilic dermatosis that presents as an inflammatory skin lesion progressing to a hemorrhagic pustular ulcer. It is most often associated with underlying systemic disorders, including inflammatory bowel disease, malignancies, arthritides, and hematologic dyscrasias (8). Though there are no pathognomonic clinical or histopathologic features of PG, pathology specimens often exhibit a sterile dermal neutrophilia, with accompanying chronic inflammation and, at times, intradermal abscess and granuloma formation. The clinical and histopathologic overlap with cutaneous blastomycosis may lead to misdiagnosis, particularly in cases where the characteristic yeast forms are not identified. Of note, a condition called blastomycosis-like pyoderma can present as vegetating skin lesions similar to blastomycosis and pseudoepitheliomatous hyperplasia with abscesses on tissue biopsy specimens. It occurs most commonly in the immunocompromised host and is related to infection with common bacterial skin pathogens other than fungi (9). We found two other reported cases of cutaneous blastomycosis misdiagnosed as PG (Table 1). In both cases, a workup for systemic diseases associated with PG yielded negative results and corticosteroids were initiated by subcutaneous injection into the ulcer and/or systemic delivery. In all three cases, inadvertent iatrogenic immunosuppression likely led to clinical worsening, with an especially devastating effect in our patient. Though our patient first presented with a skin lesion, it is much more likely that this was due to secondary dissemination from an asymptomatic lung infection rather than a primary cutaneous inoculation event, since the latter is a much rarer occurrence. We cannot ascertain this because no chest imaging was performed at the time of evaluation for the skin lesion.

TABLE 1.

Reported cases of cutaneous blastomycosis initially diagnosed as PG

Variable(s)	Result(s)a
	Mason et al. (3)	Ross and Keeling (6)	Current study
Age (yr), sex, site	26, F, right palm	63, M, right thigh	30, M, left midfoot
Exposure history	Lesion appeared after a splinter implantation	Forestry worker and recreational boatsman	Working outdoors, landscaping, effluent from a broken sewage pipe in the home
Location of blastomycosis endemicity	Yes (rural South Carolina)	Yes (New Brunswick, Canada)	Yes (Indiana)
Immunocompromising condition	None	None	None
Gross description of skin lesion	Multiple vegetative plaques with a friable verrucous surface	Purplish, multifocal, boggy dermal plaque with overlying crusted scale	Deep ulcer with pale irregular borders; some granulation tissue at margins
Feature(s) on histopathologic examination	Pseudoepitheliomatous hyperplasia without evidence of vasculitis	Necrotizing granulomas	Necrotizing granulomas with acute and chronic inflammation
Fungus noted on initial histopathological examination	No (special stains for fungi and acid-fast bacilli were reported to be negative)	No (special stains did not reveal fungi)	No (no special stains were performed)
Fungus noted on subsequent histopathological examination	Yes (review of initial skin biopsy specimen revealed multiple budding organisms suggestive of blastomycosis)	Unclear (repeat skin biopsy was done, but it was not reported if fungus was directly visualized)	Yes (review of initial skin biopsy specimen revealed multiple budding organisms suggestive of Blastomyces dermatitidis)
Positive culture	Yes (on repeat culture)	Yes (on repeat culture)	Yes
Initial treatment with steroids	Systemic prednisone and intralesional triamcinolone	Intralesional steroid	Systemic prednisone (up to 100 mg daily)
Worsening of skin lesions after steroids	Yes	Yes	No
Pulmonary illness (dissemination after steroid treatment)	Likely (CXR showed evidence of asymptomatic pulmonary disease)	No	Yes (ARDS)
Antifungal treatment	Itraconazole 200 mg daily	Itraconazole 200 mg daily	Amphotericin B for disseminated blastomycosis followed by itraconazole 400 mg twice daily
Outcome	Resolution	Resolution	Ongoing improvement

^aCXR, chest X ray; F, female; M, male.

In areas where Blastomyces dermatitidis is endemic, the differential diagnosis of PG should include cutaneous blastomycosis and should prompt a thorough investigation, including specific fungal stains such as the Gomori methenamine silver and the periodic acid-Schiff stains and cultures of the skin biopsy specimen, in addition to workup of concomitant pulmonary infection. Detection of Blastomyces antigen in urine or serum can also be useful in such a scenario (10–12). The inquiry should be completed prior to initiation of steroids in order to prevent iatrogenic worsening of cutaneous fungal infection and/or systemic dissemination.