The Diagnosis: Primary Cutaneous Nocardiosis
Comprehensive metabolic panel and complete blood cell count were unremarkable; human immunodeficiency virus screening was nonreactive. Punch biopsies were obtained for histopathology, as well as bacterial, fungal, and mycobacterial cultures. Histopathologic examination of a 4-mm punch biopsy of the forearm nodule showed a dermal abscess with neutrophilic infiltration in the dermis (Figure 1). No organisms were seen on Gram, methenamine-silver, periodic acid–Schiff, or acid-fast bacteria stains. Given the clinical suspicion for lymphocutaneous sporotrichosis, the patient was started on itraconazole. She reported modest improvement but subsequently developed a morbilliform eruption necessitating medication discontinuation.
Figure 1. A, A dermal abscess with neutrophilic infiltration of the dermis (H&E, original magnification ×100). B, No organisms were visible on higher magnification (H&E, original magnification ×400).
Eighteen days after obtaining the tissue culture, acid-fast organisms grew in culture. These organisms were subcultured on Middlebrook 7H11 agar (Sigma-Aldrich) with growth noted at 30°C and 37°C. Gram stain revealed filamentous gram-variable bacteria (Figure 2) that were identified as Nocardia brasiliensis by 16S ribosomal DNA analysis. Given the patient’s sulfonamide allergy, she started oral minocycline 100 mg twice daily. She responded to the therapy and subsequent testing confirmed susceptibility.
Figure 2. Filamentous gram-variable bacteria, later identified as
Nocardia brasiliensis, isolated from subculture on Gram stain (original
magnification ×1000).
The genus Nocardia consists of more than 50 species of gram-positive, weakly acid-fast, aerobic actinomycetes that can cause primary cutaneous infection via percutaneous inoculation. Nocardia brasiliensis is the leading cause (approximately 80% of cases) of primary cutaneous or subcutaneous nocardiosis and is found ubiquitously in soil and decaying vegetation.1 The clinical presentation varies, rendering definitive diagnosis a challenge without histopathologic and microbiologic testing.2 Patients presenting with nocardial cellulitis often are suspected to have Streptococcus pyogenes or Staphylococcus aureus infections. The differential diagnosis for patients presenting with nocardial nodular lymphangitis, also known as lymphocutaneous syndrome, includes atypical mycobacterial infections, leishmaniasis, and lymphocutaneous sporotrichosis.2
Histologic examination of nocardial nodules typically shows granulomatous or neutrophilic inflammation, and organisms may appear in small collections resembling sulfur granules.2 The organism itself is weakly positive on acid-fast stain, and useful stains include acid-fast bacteria, methenamine silver, and periodic acid–Schiff.2 Tissue culture often provides the definitive diagnosis, as the histology is nonspecific and organisms may not be visualized.
Oral trimethoprim-sulfamethoxazole 2.5 to 10 mg/kg and 12.5 to 50 mg/kg, respectively, twice daily is the treatment of choice for primary cutaneous nocardiosis. Minocycline 100 to 200 mg twice daily is an accepted alternative in case of sulfonamide allergy, as in our patient. Antibiotics should be tailored according to the susceptibility profile of the isolated organism.3
This case highlights the importance of forming a broad differential diagnosis for patients presenting with lymphocutaneous syndrome. The incidence and prevalence of N brasiliensis infection is difficult to determine due to its nonspecific clinical presentation and a lack of recent epidemiologic studies. Although primary cutaneous nocardiosis in the United States often is diagnosed in the South or Southwest, cases have been reported in other regions.4-6 Traumatic inoculation of contaminated soil, plants, and other organic matter, a well-known method of Sporothrix schenckii transmission, also is a method of N brasiliensis transmission. Because this organism may not be detected on histologic examination, empiric treatment should be considered if the diagnosis is suspected.