Primary mammary actinomycosis challenged with penicillin allergy

Background

Actinomycosis is a subacute-to-chronic bacterial infection caused by filamentous, gram-positive, non-acid-fast, anaerobic-to-microaerophilic bacteria from the genus Actinomyces. Typical clinical presentations include cervicofacial actinomycosis following poor dental hygiene, abdominopelvic actinomycosis in women with an intrauterine device and pulmonary actinomycosis in smokers with poor dental hygiene.1 2 Actinomycosis is seen in all age groups and regions globally but occurs frequently between ages 15 and 35. The disease is common in premenopausal women and three times more common in men. Usually, patients are otherwise in good health, with no associated illness.3 4 A comprehensive clinical review by Wong et al, identified orofacial actinomycosis a most common site and comprises about 50% of cases, while other sites include: thoracic (15%–20%), abdominopelvic (20%) and the rest of the body (5.9%). Rare sites of actinomycosis include the central nervous system, bones, muscle tissue and prosthetic joints.2 3

Primary actinomycosis of the breast is a rare disease, with fewer than 32 cases reported since its first description by Ammentrop in 1893. Breast actinomycosis may present as a sinus tract or with mass-like features mimicking malignancy. The clinical presentation makes it difficult to distinguish primary actinomycosis from mastitis and inflammatory carcinoma.5 6 Actinomycosis, regardless of species, should be treated with high doses of antibacterial agents for a prolonged period, although therapy needs to be individualised. The mainstay treatment for actinomycosis is penicillin and the beta-lactam group of antibiotics. Non-penicillin treatment options include doxycycline, minocycline, clindamycin and erythromycin.2 7

We report a case of primary actinomycosis of the breast in a postmenopausal woman who presented with a breast mass simulating malignancy. The patient’s course of treatment was complicated by the background of a severe allergy to penicillin along with an adverse reaction to doxycycline.

Case presentation

A 51-year-old postmenopausal woman presented to the clinic with worsening pain and swelling on her left breast for approximately 3 weeks duration which started after a fall. Her medical history included treatment-naive hepatitis C, depression, anxiety and chronic obstructive pulmonary disease. She is an active chronic smoker who smokes one pack per day. Her drug allergies include sulfa drugs, quinolones and penicillin. Penicillin caused her throat tightness and generalised body swelling. There was no history of gingivitis, dental problems, fever, chills or discharge from the nipple. On physical examination, there was an approximately 3.0×4.5 cm fluctuant to rubbery tender mass on the medial aspect of the upper quadrant approximately 2 cm from the nipple of the left breast. The overlying skin was erythematous, indurated, warm and tender with an orange peel appearance. The areola and nipple were intact without discharge. No palpable adenopathy was found. The patient was diagnosed with a case of left breast abscess. She underwent incision and drainage and was discharged on oral doxycycline 100 mg two times per day.

The patient was hospitalised within 2 days due to persistent pain and swelling. Since the patient had a history of previous methicillin-resistant Staphylococcus aureus soft-tissue infection, vancomycin at 25 mg/kg was initiated. Initial labs revealed normal white cell count (6.6×10⁹/L), kidney (creatinine of 0.8 mg/dL), and liver functions (Aspartate transaminase (AST) of 14 units/L and Alanine transaminase (ALT) of 19 units/L). Blood culture did not yield growth of any organism. Breast ultrasound revealed a 0.9×0.8 cm mass in left breast tissue suspecting infection or inflammatory or malignancy. Despite a 5-day course of intravenous vancomycin treatment, there was a poor resolution of the swelling and tenderness. Underlying inflammatory breast malignancy was highly suspected. The patient underwent further workup with a repeat ultrasound of the left breast and mammogram. The Ultrasound of the left breast (figure 1) showed a 2.2×2.3 cm irregular hypoechoic mass at 11 o’clock with indistinct margins 2 cm from the left nipple. The mammogram (figure 2) of the left breast showed ill-defined asymmetric radiopaque calcified lesion extending from 10:00 to 2:00 o’clock in the left upper breast suspicious for malignancy (Breast Imaging Reporting and Database System (BI-RADS) category 4) but could not rule out infectious process. The patient was then subjected to fine-needle aspiration and cytology (FNAC) (figure 3). While awaiting results, the patient was discharged on oral doxycycline 100 mg two times per day.

Figure 1

Ultrasound of the left breast. Actinomycosis of the left breast: ultrasound of the left breast, showing a 2.2x2.3 cm irregular hypoechoic areas of the left breast at 11 o’clock with indistinct margins.

Figure 2

Mammogram of the left breast. Actinomycosis of the left breast: mammogram of the left breast, showing an ill-defined asymmetric radiopaque lesion extending from 10:00 to 2:00 o'clock in the left upper breast suspicious for malignancy (BIRADS category 4) but cannot rule out an infectious process.

Figure 3

Ultrasound-guided fine-needle aspiration of the left breast abscess.

The patient was readmitted for persistent and worsening erythema and tenderness of the left breast within 2 days. A new ultrasound of left breast (figure 4) showed a 2.7×1.5 cm irregularly marginated fluid collection with surrounding breast oedema most consistent with an abscess which re-accumulated after aspiration. The results of FNAC of the lesion were negative for malignant cells. There was an unexpected result of mammary actinomycosis confirmed by recovery of sulphur granules with branching filaments in H&E (figure 5) and Periodic acid-Schiff stain (PAS) (figure 5). Because of the worsening and recurrent nature of the mass not responsive to antibiotic therapy, surgical excision and drainage were also performed under general anaesthesia. An aggregate of 5.0×3 cm irregular fragments of yellow-red to soft fibrofatty breast tissue was submitted for culture (aerobic and anaerobic) and cytopathology. Streptococcus anginosus group was isolated as a copathogen from culture. The histopathological report of the biopsy was negative for malignant cells. The patient was treated as a case of mammary actinomycosis based on the cytology report. Timeline of the disease progression is explained schematically (figure 6).

Figure 4

Ultrasound of the left breast—recurrence of the mass. Actinomycosis of the left breast: ultrasound of the left breast, showing a 2.7×1.5 cm irregularly marginated fluid collection with surrounding breast edema most consistent with an abscess. 2D, two dimensional ultrasound; CF, color flow mode; AOC, area of concern; TAC1, tissue abberation correction.

Figure 5

Actinomycosis in H&E stain (left) and PAS (right) on higher magnification. PAS, Periodic acid-Schiff stain.

Figure 6

Timeline of disease progression. BI-RADS, Breast Imaging Reporting and Database System; FNAC, fine-needle aspiration and cytology; USG, ultrasound.

Penicillin is the first-line treatment for actinomycosis. Surgical drainage followed by antibiotics was initiated with close follow-up. Surgical drainage was performed due to persistence and poor response to initial treatment. With the limitation of severe penicillin allergy, the patient was placed on intravenous doxycycline. However, doxycycline was discontinued due to tremors, and was switched to clindamycin. For the first 4 weeks, the patient was treated with intravenous clindamycin and followed by step down to oral clindamycin for a total of 3 months. The patient had a good clinical response with the combination of both medical and surgical approaches.

Investigations

1. Ultrasound (figure 1): revealed a 2.2×2.3 cm irregular hypoechoic areas in the left breast at 11 o’clock with indistinct margins, related to an infectious/inflammatory process (phlegmon/abscess); malignancy cannot be excluded.

2. Mammogram (figure 2): showed calcifications with an ill-defined asymmetric radiopaque lesion extending from 10:00 to 2:00 o’clock in the left upper breast suspicious for malignancy (BI-RADS category 4 but could not rule out infectious process.

3. Ultrasound (figure 3): ultrasound-guided fine-needle aspiration of the left breast mass at 11 o’clock recovered 4 mL of blood-tinged purulent fluid, immune histochemical stains, cell block and cytological examinations were performed.

4. The histopathological report of the biopsy was negative for malignant cells.

5. An additional ultrasound (figure 4): recurrence of the mass 2.7×1.5 cm irregularly marginated fluid collection with surrounding breast oedema most consistent with an abscess. Reaccumulated after aspiration, recurrent abscess of the breast.

6. Cytology (figure 5): mammary actinomycosis, organism identified on H&E (left) and PAS (right), with the background of abundant fibropurulent debris.

7. Wound culture: Streptococcus anginosus group was also isolated from culture as a copathogen.

Differential diagnosis

The 51-year-old postmenopausal woman was evaluated for a left-sided breast mass. The physical examination revealed erythema, swelling and tenderness, with a subacute clinical course. Our initial impression was a breast abscess secondary to a bacterial infection, however, the use of antibiotics such as oral doxycycline and intravenous vancomycin did not yield any improvement. Additionally, a normal leucocyte count and negative blood culture further supported the noninfectious cause of the lesion. Further workup was done in the line of breast malignancy, mammogram and FNAC. Mammogram showed irregular asymmetry with calcifications suggestive of malignant nature of mass, BIRADS category 4. Ultrasound of the breast showed fluid collection compatible with the inflammatory process. At this point, breast malignancy was considered but a breast abscess had not been ruled out. FNAC of the lesion was negative for malignant cells but positive result for Actinomyces spp confirmed by recovery of sulfur granules with branching filaments in H&E and PAS stain. Clinical presentation makes it difficult to distinguish primary actinomycosis from mastitis and inflammatory carcinoma. Imaging techniques such as ultrasonography, mammography and FNAC provided a good diagnostic orientation. Mammary actinomycosis explains the recurrence and persistent nature of the mass lesion with poor response to antimicrobial agents. In summary, the differential diagnosis includes: complicated mastitis, breast abscess, tuberculosis, inflammatory breast cancer and mammary actinomycosis.

Treatment

Penicillin is the first-line treatment of actinomycosis. The patient had multiple drug allergies including penicillin. With this limitation in mind, treatment was initiated with 3 weeks of intravenous doxycycline followed by oral doxycycline, however, the patient developed tremors. Doxycycline was switched to intravenous clindamycin for 3 weeks, followed by oral clindamycin for 3 months. The culture was also positive for S. anginosus as a copathogen, which was sensitive to clindamycin. Incision and drainage of the lesion were performed due to persistence and poor response to initial treatment. The patient had a good clinical response with the combination of both medical and surgical approaches.

The Actinomyces spp are generally sensitive to penicillin, so this is recommended as the first-line therapy. Prolonged antibiotic courses are required (typically 6 months) for the treatment of penetrating abscesses and infected tissue. However, combined surgical-medical treatment such as resection of infected tissue followed by antimicrobial therapy may shorten the required antimicrobial therapy duration. Therapy duration of lesser than 3 months is not recommended due to the high risk of recurrence.8 9

The risk of Actinomyces developing penicillin resistance is low. In vitro studies have reported that Actinomyces are susceptible to a wide range of antimicrobial agents. Clinical isolates of Actinomyces showed that most were susceptible to beta-lactams, doxycycline, clindamycin and erythromycin.2 A drug susceptibility study by Valour et al reported that doxycycline is considered to have a poor activity on Actinomyces spp, but good clinical success has been reported.9

In summary, the first-line treatment for actinomycosis is penicillin. Doxycycline, minocycline, clindamycin and erythromycin are suitable for patients who are allergic to penicillin.2 9

Outcome and follow-up

The patient frequented the hospital for intravenous antibiotic administration, during which, wound care and healing were assessed to monitor her clinical outcome. Additionally, she had a regular follow-up with her the primary care provider while on treatment for 3 months. The patient had a good clinical response with no recurrence of the abscess.