An 80-Year-Old Man With a Nonhealing Glabellar Lesion

An 80-year-old white man presented for evaluation of a nonhealing, ulcerated glabellar lesion with persistent purulent drainage of 1 month's duration. The lesion appeared after the patient fell, lacerated the bridge of his nose with his glasses, and got soil in the wound. Approximately 3 weeks prior to the fall, the patient had been diagnosed with giant cell arteritis and was started on prednisone 60 mg by mouth daily, which had been tapered to 40 mg daily at the time of presentation.Physical examination revealed a 3 × 3 cm ulcer with elevated borders around an erythematous base, and a thick eschar overlying grainy tissue (Figure 1). Green pus was expressed from the lesion with minimal manipulation, and significant sinus tracking was present from the lesion's borders.A shave biopsy was performed for tissue culture and histologic evaluation. Histologic sections demonstrated marked pseudoepitheliomatous hyperplasia with focal surface ulceration, scale crust, and epidermal neutrophilic microabscesses (Figure 2). The dermis demonstrated prominent multifocal neutrophilic microabscesses. The dermal inflammation also consisted of lymphocytes, histiocytes, plasma cells, and rare eosinophils. No definitive organisms were seen with the routine hematoxylin-eosin stain. The Grocott methenamine silver stain, however, demonstrated numerous branching filamentous organisms (Figure 3). The organisms were predominantly within the epidermal and dermal microabscesses; however, they were also present within the interstitium. A modified acid-fast stain (Ziehl-Neelsen) of the purulent exudates demonstrated weak acid-fast staining of branching, beaded, filamentous organisms (Figure 4). Of note, the routine acid-fast stain (Kinyoun) did not demonstrate the organisms. The tissue culture grew round white confluent colonies on an aerobic medium.What is your diagnosis?Cutaneous nocardiosis is caused by aerobic actinomycetes in the Nocardia genus. Primary cutaneous nocardiosis can present with ulcerative lesions, pyoderma, cellulitis, or subcutaneous abscesses. Culture is the gold standard for diagnosis, with positive Grocott methenamine silver staining and weakly positive staining with a modified acid-fast (Ziehl-Neelsen) stain. Histologically, Nocardia can be visualized as loosely dispersed organisms within microabscesses or dermal interstitium. Nocardia is ubiquitous in soil and is capable of direct inoculation. Immunosuppression from systemic steroids is an independent risk factor for infection, and the incidence has been increasing as the number of patients in the population who are immunocompromised has increased. Sulfonamide therapy confers a mortality benefit in the treatment of nocardiosis. Trimethoprim–sulfamethoxazole is the treatment of choice in immunologically intact patients, while combination therapy with sulfonamides and amikacin may be indicated initially for immunocompromised patients.Nocardiosis is caused by aerobic actinomycetes in the Nocardia genus and has been recognized for the past 100 years as a bacterial pathogen capable of systemic and suppurative infections.1 Nocardia organisms are ubiquitous in the soil. The most common means of inoculation is through inhalation, although cutaneous inoculation can occur secondary to trauma.2 There are 4 types of cutaneous Nocardia infection: primary cutaneous, lymphocutaneous, cutaneous involvement from disseminated focus, and mycetoma.3 Primary cutaneous nocardiosis can present with ulcerative lesions, pyoderma, cellulitis, or subcutaneous abscesses.45The differential diagnosis of pathogens capable of direct inoculation from soil and of causing this clinical presentation includes Nocardia, Actinomyces and related bacilli, Sporothrix schenckii and other dimorphic fungi, Paracoccidioides braziliensis, atypical mycobacteria, and, less likely, Mycobacterium tuberculosis.Culture remains the gold standard for diagnosis; however, biopsy and histologic evaluation can be very helpful in narrowing the differential diagnosis. The histologic picture described in our patient is typical for nocardiosis. The bacteria are positive with a Grocott methenamine silver (GMS) stain and are weakly positive with a modified acid-fast stain. The histologic picture in infections caused by Actinomyces and related bacilli is identical to that seen with nocardiosis. These bacteria will also stain positive with a GMS stain; however, they are not weakly acid-fast–positive. Botryomycosis is a chronic suppurative infection of skin caused by pyogenic bacteria. This process demonstrates pseudoepitheliomatous hyperplasia and neutrophilic microabscesses, like nocardiosis; however, the abscesses typically contain grains. These grains are clumps of aggregated nonfilamentous bacteria that typically have a peripheral deposition of eosinophilic material termed the Splendore-Hoeppli reaction. The bacteria will stain with a tissue Gram stain but are not positive for GMS or modified acid-fast stains. Although the Splendore-Hoeppli reaction can rarely be seen in nocardiosis, it is much more common for the organisms to be loosely dispersed within the microabscesses or dermal interstitium. Sporotrichosis and infections with other dimorphic fungi can present with pseudoepitheliomatous hyperplasia; however, the dermal inflammation is typically granulomatous. Necrosis and microabscesses can be seen; however, areas of true granulomatous inflammation should also be present. The GMS stain will demonstrate fungal yeast forms, which are quite distinctive from Nocardia. Mycobacteria, both atypical forms and M. tuberculosis, demonstrate both caseating and noncaseating granulomatous inflammation. Mycobacterial organisms will not stain with the GMS stain but demonstrate strong positivity with a routine acid-fast stain and a modified acid-fast stain.There are 500 to 1000 reported new cases of Nocardia infection each year.1 Although infection can occur in immunocompetent patients, the majority of patients are immunocompromised, and therefore the incidence of Nocardia infection is increasing as the number of patients who are immunocompromised (from organ transplantation, human immunodeficiency virus infection, etc) increases. Steroid use has been shown to be an independent risk factor for Nocardia infection, as patients receiving cyclosporin as steroid-sparing therapy after organ transplantation have a lower incidence of Nocardia infection than do transplant recipients receiving steroids.67