Dermatology Online Journal

Disseminated cutaneous nocardiosis mimicking cellulitis and erythema nodosum
Saira J George MD, Allison M Rivera MD, Sylvia Hsu MD
Dermatology Online Journal 12 (7): 13

Department of Dermatology, Baylor College of Medicine, Houston, Texas

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Abstract

Infection with Nocardia asteroides is a rare, life-threatening infection, which is most commonly encountered in immunocompromised patients. Cutaneous involvement is usually seen with disseminated infection but may also occur as primary cutaneous nocardiosis. We present a case of an immunocompromised patient who presented with cellulitis of the right hand and disseminated subcutaneous nodules of the lower extremities resembling erythema nodosum. Cultures from both a skin biopsy of a subcutaneous nodule on the leg as well as a surgical specimen from the debridement of her hand grew Nocardia asteroides. The patient was treated successfully with trimethoprim-sulfamethoxazole. This case likely represents primary cutaneous nocardiosis with secondary dissemination, which has been rarely reported. It also emphasizes that nocardial infection should be considered in the differential diagnosis of lesions suggestive of cellulitis or erythema nodosum in the severely immunocompromised patient.

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Clinical synopsis

Figure 1
Several tender subcutaneous nodules on shins (and thighs)

A 53-year-old female renal-transplant patient was seen in consultation for evaluation of tender red nodules on her shins. In addition to the renal transplant, her past medical history was significant for hypertension, diabetes mellitus, and sarcoidosis associated with three prior episodes of erythema nodosum. She had been discharged from the hospital following an uncomplicated left total hip replacement less than 2 weeks prior to presentation but was promptly readmitted with cellulitis of the right hand presumed to be secondary to trauma from intravenous catheterization and venipuncture attempts at the site. Despite 5 days of broad spectrum antibiotic therapy with vancomycin and piperacillin-tazobactam, her cellulitis progressed. She also noted several new, tender subcutaneous nodules on her anterior shins and later developed a constellation of additional symptoms including high fevers, severe headache, and nausea. She denied any respiratory complaints including cough, shortness of breath, or pleuritic chest pain.

Physical examination revealed massive edema, erythema, warmth, and tenderness of her dorsal right hand extending to the distal forearm. There were also few scattered erythematous, tender, 1-2 cm subcutaneous nodules on each anterior shin and distal upper thigh (Fig. 1).

Histologic evaluation of a punch biopsy of one the nodules revealed a suppurative infiltrate in the subcutaneous fat with a structure recognizable as a grain around which were abundant neutrophils. Cultures of the skin biopsy specimen as well as those from a subsequent debridement of the right hand grew Nocardia asteroides. An MRI of the brain revealed a 2-cm frontal-lobe abscess with numerous additional foci throughout the cerebral hemispheres consistent with nocardial brain abscesses. Chest radiographs at presentation showed no evidence of pulmonary involvement.

She is currently being treated with trimethoprim-sulfamethoxazole with improvement in her cellulitis, lower extremity lesions, and brain abscesses occurring within 2 weeks of initiating therapy.

Comment

The members of the genus Nocardia are filamentous gram positive bacteria that are ubiquitous soil saprophytes. They cause an estimated 1000 infections annually in the United States, with Nocardia asteroides being the most common cause of human disease [1]. The majority of nocardial infections occur in severely immunocompromised patients who are particularly susceptible to pulmonary disease and dissemination [2, 3]. Risk factors include a history of long-term glucocorticoid therapy, advanced AIDS (CD4 <50), transplant immunosuppression, lymphoreticular malignancy, chronic bronchopulmonary disease, cirrhosis, renal failure, and sarcoidosis.

The infection is usually acquired via inhalation of the microorganisms, which allows for the establishment of a focal pneumonitis that often progresses to necrosis and abscess formation. Patients with pulmonary nocardiosis typically present with dyspnea, cough, or pleuritic chest pain in addition to fever, malaise, and anorexia. Although the specific radiographic findings of pulmonary nocardiosis are variable and range from interstitial or nodular pulmonary infiltrates to mass lesions and effusions, virtually all patients appear to demonstrate some abnormality on routine chest radiographs [4]. Disseminated disease develops in at least one third of patients with pulmonary nocardiosis. Central nervous system involvement is detected in 20-40 percent and generally manifests with fever, headache, stiff neck, or altered mental status. Cutaneous dissemination, which occurs in 10 percent, most commonly presents as tender, firm, and usually non-ulcerating subcutaneous nodules that favor the lower extremities. Disseminated disease has also been reported to lead to abscess formation in the psoas muscle, liver, adrenal gland, and abdominal cavity as well as retinitis, septic joint, myositis, pericarditis and osteomyelitis [3, 5, 6, 7].

The lack of pulmonary symptoms and of findings on chest radiography suggest that the portal of entry for this patient may have been her skin, leading to a primary nocardial cellulitis of her right hand. Primary cutaneous nocardiosis (PCN) comprises only 5 percent of nocardial infections and can present as an acute superficial skin infection with pustules, abscesses, pyoderma, and cellulitis or as a lymphocutaneous infection bearing striking similarity to Sporothrix schenckii infection [8]. It is most commonly acquired by traumatic inoculation. Predisposing conditions include exposure to soil or sand, gardening, farming, and traumatic injury from shrubs. Less commonly, inoculation at the time of surgery, intraarticular steroid injection, contaminated immunotherapy injections or with trauma such as insect bites and cat scratches have been reported in PCN [9, 10, 11, 12, 13]. Hematologic dissemination from PCN is exceedingly rare; we are aware of only a handful of reports of patients developing disseminated disease from primary cutaneous infection [14, 15].

Sulfonamides have been the mainstay of treatment for more than 50 years. The synergy of trimethoprim and sulfamethoxazole against Nocardia coupled with its ability to effectively penetrate the blood-brain barrier make it especially ideal for treating disseminated disease [5, 16, 17]. Others agents effective against Nocardia include minocycline, augmentin, amikacin, cefuroxime, ceftriaxone, quinolones, imipenem, and most recently linezolid [18, 19, 20, 21]. Treatment failure occurs in up to 20 percent of patients with disseminated disease and mortality in nocardemic patients is 44-85 percent, emphasizing the need for the prompt recognition of this serious infection that may mimic a variety of other more benign infectious and inflammatory skin conditions.

References

1. Beaman BL, Burnside J, Edwards B, et al. Nocardial infections in the United States, 1972-1974. J Infect Dis 1976; 134:286-9.

2. Saubolle MA, Sussland D. Nocardiosis: review of clinical and laboratory experience. J Clin Microbiol 2003; 41:4497-501.

3. Lederman ER, Crum NF. A case series and focused review of nocardiosis: clinical and microbiologic aspects. Medicine (Baltimore) 2004; 83:300-13.

4. Hui CH, Au VW, Rowland K, et al. Pulmonary nocardiosis re-visited: experience of 35 patients at diagnosis. Respir Med. 2003;97:709-17.

5. Boudoulas O, Camisa C. Nocardia asteroides infection with dissemination to skin and joints. Arch Dermatol 1985; 121:898-900.

6. Santamaria Saber LT, Figueiredo JF, Santos SB,et al. Nocardia infection in renal transplant recipient: diagnostic and therapeutic considerations. Rev Inst Med Trop Sao Paulo 1993; 35:417-21

7. Tokumoto JI, Jacobs RA. Case report: Nocardia osteomyelitis. Am J Med Sci 1994; 307:428-33

8. Palmer DL, Harvey RL, Wheeler JK. Diagnostic and therapeutic considerations in Nocardia asteroides infection. Medicine (Baltimore) 1974; 53:391-401.

9. Astudillo L, Dahan S, Escourrou G, et al. Cat scratch responsible for primary cutaneous Nocardia asteroides in an immunocompetent patient. Br J Dermatol 2001; 145:684-5.

10. Aydingoz IE, Candan I, Dervent B,et al. Primary cutaneous nocardiosis associated with intra-articular corticosteroid injection. Int J Dermatol 2001; 40:196-8.

11. Laurent F, Mick V, Boiron P. [Nocardia infections: clinical and biological aspects]. Ann Biol Clin (Paris) 1999; 57:545-54.

12. Paredes BE, Hunger RE, Braathen LR, et al. Cutaneous nocardiosis caused by Nocardia brasiliensis after an insect bite. Dermatology 1999; 198:159-61.

13. Taylor GD, Turner AR. Cutaneous abscess due to Nocardia after "alternative" therapy for lymphoma. Cmaj 1985; 133:767.

14. Kahn FW, Gornick CC, Tofte RW. Primary cutaneous Nocardia asteroides infection with dissemination. Am J Med 1981; 70:859-63.

15. Lakshmi V, Sundaram C, Meena AK, et al. Primary cutaneous nocardiosis with epidural abscess caused by Nocardia brasiliensis: a case report. Neurol India 2002; 50:90-2.

16. Huang CC, Lee CC, Chu NS. A case of cerebral nocardiosis successfully treated with trimethoprim-sulfamethoxazole. J Formos Med Assoc 1991; 90:407-10.

17. Lo W, Rolston KV. Use of imipenem in the treatment of pulmonary nocardiosis. Chest 1993; 103:951-2.

18. Brown-Elliott BA, Ward SC, Crist CJ,et al. In vitro activities of linezolid against multiple Nocardia species. Antimicrob Agents Chemother 2001; 45:1295-7.

19. Gomez-Flores A, Welsh O, Said-Fernandez S, et al. In vitro and in vivo activities of antimicrobials against Nocardia brasiliensis. Antimicrob Agents Chemother 2004; 48:832-7.

20. Moylett EH, Pacheco SE, Brown-Elliott BA, et al. Clinical experience with linezolid for the treatment of nocardia infection. Clin Infect Dis 2003; 36:313-8.

21. Lewis KE, Ebden P, Wooster SL, et al. Multi-system Infection with Nocardia farcinica-therapy with linezolid and minocycline. J Infect 2003; 46:199-202.

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