CLINICAL HISTORY:

Signs and symptoms:  She reported a two-week history of worsening symptoms after stepping on a sharp object while walking barefoot at home. The patient experienced pain at the base of her left first toe, but could not identify an obvious puncture wound or foreign body at the time of injury.

Previous Treatment:  Initially, the patient was seen at an urgent care center and was treated with prednisone for a suspected bite reaction on her toe. The patient was then seen five days later by her primary care physician and received cephalexin for a suspected cellulitis. Her prednisone was also discontinued at that time.

Other information:  Her past medical history was significant for hypertension and hyperlipidemia. Medications included olmesartan, rosuvastatin, and a multivitamin. The patient admitted to having chills a few days prior to her presentation at our office. The patient was sent to the emergency room for cultures and radiographic studies. She was subsequently admitted and placed on empiric antibiotic therapy with clindamycin and vancomycin. The patient was also started on itraconazole to cover a possible fungal infection, pending tissue biopsy and culture results.

PHYSICAL EXAM:

Initial examination revealed erythema, swelling, and increased calor of the dorsal left foot with erythematous, lymphangitic streaking extending from the left lower medial leg up to the groin. Approximately two days later, the patient developed tense, suppurative bullae extending superiorly in a sporotrichoid pattern up her left medial leg and left posterior thigh. The lesions were drained, debrided, and biopsied by dermatology (Figures 1,2).

Left medial leg. Demonstrating the sporotrichoid pattern of the unroofed bullous lesions.

Left posterior thigh. Demonstrating an unroofed bullous lesion.

Granules were not grossly identified while performing these procedures. An x-ray and MRI of the left foot demonstrated no evidence of osteomyelitis, but did reveal extensive subcutaneous edema consistent with cellulitis.

LABORATORY TESTS:

Punch biopsy specimens were sent for tissue culture, which eventually yielded gram-positive, branching filaments, consistent with Nocardia species. Final culture results subsequently isolated Nocardia braziliensis as the causative agent.

DERMATOHISTOPATHOLOGY:

A punch biopsy specimen from one of the debrided areas of the left leg revealed spongiotic changes of the epidermis, superficial perivascular and interstitial inflammation with neutrophils, and deep dermal and subcutaneous neutrophilic abscess formation. No asteroid bodies or any evidence of the Splendore-Hoeppli phenomenon were identified. No microorganisms were identified by hemotoxylin and eosin sections. PAS, GMS, AFB, and Gram stains also revealed no definitive fungal, mycobacterial, or bacterial organisms.

DIFFERENTIAL DIAGNOSIS:

1.   Lymphocutaneous Nocardiosis
2.   Sporotrichosis
3.   Cutaneous tuberculosis
4.   Other mycobacterium
5.  

SCROLL DOWN FOR ANSWER AND DISCUSSION.

CORRECT DIAGNOSIS:

Lymphocutaneous Nocardiosis caused by Nocardia brasiliensis

DISCUSSION:

Nocardia species are gram-positive, aerobic, weakly acid-fast bacilli with fine branching filaments. Colonies will grow on Löwenstein-Jensen culture media, Sabouraud’s glucose agar, and blood agar and are usually rough with a velvety surface. They typically have a white or light orange color and a characteristic moldy or earthy odor. Optimum growth occurs at 37º, but growth is slow. Colonies may not be visible for 48 to 72 hours of incubation, and all culture specimens of possible Nocardia should be observed for a full two weeks. Histopathology shows a mixed acute abscess and granulomatous response with fibrosis. Occasionally, the bacteria are clumped together with surrounding homogeneous eosinophilic material. This is known as the Splendore-Hoeppli phenomenon. More often, the bacteria are loosely dispersed and poorly demonstrated with hematoxylin-eosin stain. They are Gram-positive, Grocott-silver-positive, and weakly acid-fast with modified Ziehl-Neelsen stain.
Nocardia species are native to soil and decaying vegetable matter and only accidentally infect man. Infection occurs after direct inoculation of the skin or by inhalation. The Nocardia species pathogenic in man include N. asteroides, N. brasiliensis, and N. otitidiscaviarum. In North America, most Nocardia infections are caused by N. asteroides, whereas in Latin America, most are caused by N. brasiliensis. N. asteroides usually presents as pleuropulmonary or less commonly skin infection in immunosuppressed hosts, whereas N. brasiliensis more commonly causes primary cutaneous disease. In laboratory animals, the virulence of N. brasiliensis exceeds that of N. asteroides, which supports observations that N. asteroides is predominantly an opportunistic pathogen, whereas N. brasiliensis causes skin infections in normal hosts.
Nocardiosis is divided into systemic and cutaneous types. Systemic nocardiosis almost exclusively begins in the respiratory tract. Cutaneous nocardiosis can have one of four clinical manifestations: (1) mycetoma, (2) lymphocutaneous (sporotrichoid) infection, (3) superficial skin infections such as cellulitis, abscesses, ulcers, or granulomas, and (4) disseminated disease with cutaneous involvement.
As seen in our case, the lymphocutaneous (sporotrichoid) infection of nocardiosis usually begins as an ulcerated papule at the site of inoculation, followed by advancing lymphangitis and subcutaneous erythematous nodules along the lymphatic drainage. Typical lesions are located on the extremities with a history of a puncture wound or farm/garden work. Most patients lack systemic manifestations such as fever, leukocytosis, or weight loss.
Many cases of cutaneous nocardiosis mimic more familiar skin eruptions, such as cellulitis or bacterial abscesses, and are treated with drainage and antibiotics without Gram stain or culture. Other causes for the sporotrichoid pattern of spread besides N. brasiliensis and N. asteroides, includes Sporothrix schenckii, Coccidioides immitis, Blastomyces dermatitidis, Histoplasma capsulatum, tularemia, lymphatic tumors, Mycobacterium marinum, Mycobacterium kansasii, and Mycobacterium chelonei. Potential clues to the diagnosis of Nocardia infection include: history of traumatic inoculation, occupational exposure (gardening, farming), tendency for cutaneous infections to recur, worsening of infection despite “standard” antibiotic treatment, chronic cutaneous infections with “negative cultures” (see culture media and duration requirements above), acid-fast organisms, and sulfur granules.
Nocardiosis often requires months of antibiotic therapy. The drugs of choice are sulfonamides, while other reports suggest efficacy with minocycline and aminoglycosides, especially amikacin. Surgical drainage of suppurative cutaneous infections is also an important part of treatment.

TREATMENT:

The patient’s antibiotic regimen was changed to trimethoprim/sulfamethoxazole for appropriate coverage. Further debridement and abscess drainage was also required in our office (Figures 3,4).

Left medial leg. Demonstrating lesions two weeks after discharge from hospital.

Left medial leg. Two weeks after hospital discharge, demonstrating healthy, granulation tissue following further debridement in our office.

She is currently following with infectious disease and dermatology. Her wounds have been healing successfully, and the patient must remain on oral trimethoprim/sulfamethoxazole for the next few months before complete resolution is expected.

REFERENCES:

1)Kalb RE, Kaplan MH, Grossman ME. Cutaneous nocardiosis: case reports and review. J Am Acad Dermatol 1985; 13: 125-33.
2)Karakayali G, Karaarslan A, Artuz F, Alli N, Tereli A. Primary cutaneous Nocardia asteroides. Br J Dermatol 1998; 139: 919-20.
3)Aly R, Maibach HI. Subcutaneous mycoses: mycetoma, chromoblastomycoses, sporotrichosis. In: Atlas of infections of the skin. New York: Churchill Livingstone, 1999: 67-70.
4)Elder D, Elenitsas R, Jaworsky C, Johnson B, eds. Bacterial disease. In: Lever’s histopathology of the skin. Philadelphia: Lippincott Williams and Wilkins, 1997: 496-7.

Additional Comment:

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