Delayed breast cellulitis: An evolving complication of breast conservation

Delayed breast cellulitis: An evolving complication of breast conservation.

December 1, 2006

Indelicato DJ,
Grobmyer SR,
Newlin H,
Morris CG,
Haigh LS,
Copeland EM 3rd,
Mendenhall NP.

Department of Radiation Oncology, University of Florida College of Medicine, Jacksonville, FL.

Purpose: Delayed breast cellulitis (DBC) is characterized by the late onset of breast erythema, edema, tenderness, and warmth. This retrospective study analyzes the risk factors and clinical course of DBC. Methods and Materials: From 1985 through 2004, 580 sequential women with 601 stage T0-2N0-1 breast cancers underwent breast conserving therapy. Cases of DBC were identified according to accepted clinical criteria: diffuse breast erythema, edema, tenderness, and warmth occurring >3 months after definitive surgery and >3 weeks after radiotherapy. Potential risk factors analyzed included patient comorbidity, operative technique, acute complications, and details of adjunctive therapy. Response to treatment and long-term outcome were analyzed to characterize the natural course of this syndrome.

Results: Of the 601 cases, 16%, 52%, and 32% were Stage 0, I, and II, respectively. The overall incidence of DBC was 8% (50/601). Obesity, ecchymoses, T stage, the presence and aspiration of a breast hematoma/seroma, removal of >5 axillary lymph nodes, and arm lymphedema were significantly associated with DBC. The median time to onset of DBC from the date of definitive surgery was 226 days. Ninety-two percent of DBC patients were empirically treated with antibiotics. Fourteen percent required more invasive intervention. Twenty-two percent had recurrent episodes of DBC. Ultimately, 2 patients (4%) underwent mastectomy for intractable breast pain related to DBC. Conclusion: Although multifactorial, we believe DBC is primarily related to a bacterial infection in the setting of impaired lymphatic drainage and may appear months after completion of radiotherapy. Invasive testing before a trial of antibiotics is generally not recommended.

Abstract

Antibiotic-resistant cellulitis acquired in Turkey.

Antibiotic-resistant cellulitis acquired in Turkey.
Y W Wong MB MRCP D Waghorn FRCPath 1 R C Ratnavel DM FRCP
Department of Dermatology, Amersham Hospital, Amersham HP7 0JD, UK1 Department of Microbiology, Wycombe General Hospital, High Wycombe HP11 2TT, UK

Correspondence to: Dr Y W Wong E-mail: yatfink@yahoo.co.uk


When cellulitis proves unresponsive to the usual antibiotics, a history of travel may be relevant.

CASE HISTORY

A woman of 70 sought advice from her general practitioner when her right lower leg had been painful and swollen for two weeks. A few days before the onset of symptoms, when she was on holiday in Turkey, she had sustained insect bites on that leg. Flucloxacillin and amoxycillin were prescribed, but the condition worsened and new lesions appeared on her left ankle. On referral to the dermatology department the patient had low-grade pyrexia and bilateral inguinal lymphadenopathy. Her right lower leg was hot and swollen with well-demarcated erythema and multiple pus-filled bullae (Figure 1). Similar lesions were present on the posterior aspect of the left ankle. White cell count was 14.4 x 109/L with 73% neutrophils; C reactive protein was 213 mg/L. Multiple skin swabs and pus aspirates were sent for microbiological examination. The bullous abscesses were incised and drained with partial relief of pain. Highdose intravenous benzylpenicillin and flucloxacillin were administered, with negligible benefit. X-rays of the chest and legs were normal.

The aspirates contained moderate numbers of pus cells but no evident organisms. After three days, however, Nocardia asteroides, with typical dry white colonies and an earthy odour, grew on blood agar from both skin swabs and pus aspirates. Blood cultures remained negative. Skin biopsies showed a dense mixed dermal inflammatory infiltrate with granulomata extending to subcutaneous fat (Figure 2). Gram and methanamine silver staining did not reveal any organisms; acid-fast staining was not done. The granulomatous histology and positive cultures from pus supported a diagnosis of primary cutaneous nocardiosis. She had not been in direct contact with soil and the infection was presumed to have been transmitted by the insect bites. Her immune function was normal. She was treated with co-trimoxazole 960 mg twice daily for three months and the lesions healed without recurrence.

COMMENT

Nocardia spp. are soil saprophytes belonging to the order of Actinomycetales. The main species pathogenic in man are N. asteroides complex (N. asteroides, N. nova, N. farcinica) and N. brasiliensis. Nocardiosis is most commonly seen in Central and South America, North Africa and India. In France, a retrospective study suggested 150 to 250 new cases a year from 1987 to 19901. The organism is a fine branching Gram-positive bacillus with an irregular beaded appearance. It is weakly acid fast but not alcohol fast and stains with modified Ziehl—Neelsen. It can take up to two weeks to grow under aerobic conditions on blood agar, Sabouraud's glucose agar or Löwenstein—Jensen medium. Nocardia spp. are readily overgrown by other organisms and may therefore be missed on culture.

Primary cutaneous nocardiosis has three distinct clinical presentations. First, a superficial infection can occur with cellulitis, abscess formation or multiple ulcers as in the case presented here. This presentation has not been reported often2, possibly because the condition is misdiagnosed as staphylococcal infection and on occasion resolves without specific antimicrobial therapy2. In rare circumstances, superficial cutaneous nocardia infection can disseminate to other organs. A second, lymphocutaneous, form of disease presents with clinical features similar to those of sporotrichosis; a cervicofacial subtype in childhood is recognized with cervical lymphadenopathy and nasolabial lesions, often with no preceding cutaneous injury. The third type of presentation is with an actinomycetoma or Madura foot—a chronic granulomatous mass with sinus formation. This must be differentiated from infection caused by Actinomycetes spp. or fungi.

N. brasiliensis is the most common cause of primary cutaneous nocardiosis but overall only accounts for 10% of nocardia infection. Transmission is usually through a minor skin injury, including a cat scratch or thorn prick. The possibility of insect bites acting as a vector for the transmission of nocardia infection has been noted previously3. Although it is unclear whether our patient had insect bites on both lower legs, the spread from the right to left leg can be explained by the direct skin to skin contamination. The incubation period of Nocardia spp. can vary from a week to several months. N. asteroides tends to be associated with pulmonary disease. From the lungs the infection can disseminate with widespread abscess formation4. Disseminated nocardiosis most commonly occurs in the setting of immunosuppression such as HIV infection, leukaemia or lymphoma and pre-existing chronic pulmonary disease.
The efficacy of antimicrobials in primary cutaneous nocardiosis is difficult to assess. The choice is often determined by their in-vitro activity5. Clinical experience and in-vitro activity favour co-trimoxazole. As an alternative, minocycline or a quinolone antibiotic may be effective but the sensitivity to such agents varies between species. Some of the intravenous agents such as amikacin, co-trimoxazole, cefotaxime and imipenem are reported to have synergistic in-vitro effects and may therefore be useful in combination for disseminated and severe cases.

Acknowledgments

We thank Dr D M Bailey for his contribution on photomicrographs.

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© 2003 The Royal Society of Medicine