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Primary mammary actinomycosis challenged with penicillin allergy
  1. Josephine B de Leoz,
  2. Devi Suravajjala,
  3. Hashmi Rafeek and
  4. Vani Selvan
  1. Family and Community Medicine, Texas Tech University Health Sciences Center School of Medicine Permian Basin, Odessa, Texas, USA
  1. Correspondence to Dr Vani Selvan; vani.selvan{at}ttuhsc.edu

Abstract

Actinomycosis is a subacute-to-chronic bacterial infection caused by gram-positive, filamentous, non-acid-fast, facultative anaerobic bacteria. It is a normal commensal bacterium found in the oral cavity and the lower reproductive tract of women. We present a case of primary actinomycosis of the breast. A postmenopausal woman, complicated by penicillin allergy, presented with a left breast lump clinically simulating malignancy. The first line of treatment for actinomycosis is penicillin. Due to a penicillin allergy, the patient was initially treated with doxycycline. However, doxycycline was discontinued due to tremors, and was replaced by clindamycin. The patient had a good clinical response with resolution of the abscess.

  • general practice / family medicine
  • drugs: infectious diseases
  • ultrasonography
  • breast cancer
  • general surgery

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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.

Discussion

Actinomycosis is a subacute-to-chronic suppurative granulomatous disease that tends to produce draining sinus tracts. It is often a misdiagnosed disease and it has been stated that no disease is so often missed by even well-experienced clinicians.6 Infection may result from inoculation of the organism through the nipple due to trauma, lactation or kissing.1 In our patient, the primary source may be a break to her skin after trauma from a fall. Microbiological identification of the Actinomyces strains occurs only in a minority of cases.5 The most common strain is Actinomyces israelii, present in 78% of patients; other strains like Actinomyces viscosus, Actinomyces turicensis and Actinomyces radingae have been isolated causing primary actinomycosis.

The literature reports that primary actinomycosis of the breast mostly involves premenopausal women.5 10 Our case is a postmenopausal woman, which is rare, with few cases reported in the literature.de Barros et al reported the first case of primary actinomycosis in a postmenopausal woman in a 66-year-old diabetic woman treated with a prolonged course of penicillin.4

Two-thirds of the cases presented as persistent/recurrent breast abscess with or without sinuses. In the remaining one-third, the clinical presentation was a breast lump that was very difficult to distinguish from inflammatory carcinoma.6 10 Thambi et al and Jain et al reported primary breast actinomycosis clinically simulating malignancy.5 11 It is important to exclude chronic suppurative mastitis, tuberculosis, syphilis and chronic osteomyelitis.

Capobianco et al reported a case of primary actinomycosis of the breast diagnosed by fine-needle aspiration cytology under ultrasound guidance for culturing potential bacterial culture and to rule out malignancies form such as inflammatory carcinoma of the breast.10 The most appropriate clinical specimens are tissue from a surgical biopsy; swabs must be avoided.9

Demonstration of the gram-positive filamentous organism and sulfur granules on histological examination is strongly supportive of the diagnosis of actinomycosis.2 The diagnosis is made by histopathological examination of biopsy or mastectomy specimen, in which we can see the characteristic sulfur granules representing the bacterial colonies. We did an ultrasound-guided FNAC to obtain samples for diagnosis. H&E and PAS revealed the characteristic branching sulfur granules. This was followed by surgical drainage of the lesion due to its persistence and slow response to medical treatment. Histopathological report of the biopsy was negative for malignant cells and S. anginosus group was isolated from the culture. The role of these coisolates in the pathogenesis of actinomycosis is unclear, many of the organisms are copathogens, so the initial phase of treatment should cover other bacteria found on the site of infection.9 The bacteriological identification of Actinomyces from a sterile site confirms the diagnosis of actinomycosis.

However, isolation and identification of these causative bacteria occur in only a minority of cases; the failure is high because of previous antibiotic therapy, inhibition of Actinomyces growth by concomitant and/or contaminant micro-organism, inadequate culture conditions or inadequate short-term incubation. Both aerobic and anaerobic cultures should be performed, but the culture yields positive results in only fifty percent of patients.5 A gram stain of the specimen is usually more sensitive than culture, especially if the patient has received antibiotics.4 9

The presence of granules in histological sections composed of actinomycotic colonies showing a characteristic appearance establishes the diagnosis when culture is not successful or suitable specimen for culture is not available.4

Actinomycosis, regardless of species, should be treated with high doses of penicillin for a prolonged period although therapy needs to be individualised. Current guidelines recommend a high dose of penicillin intravenously for 2–6 weeks, followed by oral therapy with penicillin or penicillin derivatives for three3–6 months or even to 12 months if recurrence occurs. Alternative non-penicillin antibacterial treatment includes doxycycline, erythromycin or clindamycin.2 7 If actinomycosis presents with a well-defined abscess, then surgical debridement followed by long-term antibacterial therapy is indicated.

Patient’s perspective

The thought of being hospitalised was initially so dreaded. Initially, my breast lump was thought to be infectious, but I was worried about my allergies. My history of multiple drug allergies to common medications such as penicillin, sulfa drug, Levaquin, Zofran, and more, made me worrisome.

My initial experience was anxious; due to excruciating pain from the lump on my breast, multiple investigations, inconclusive diagnosis, and repeated admissions, and have not always been encouraging. I was in fear when the doctor told me about the possibility of breast cancer, and they had to do a further test. I felt everything stopped. I was lying helpless; all I can hear was my heart pounding; everything was blurry. The hospital days were agonising, and I had to count each day that passed by. What if it turned out to be breast cancer? The thought of my children and family flashed in my mind. I made a firm resolution to fight this with great perseverance.

My doctors had been so helpful, empathetic, and went through each step of the process with me. It was a great relief when I heard that my breast lump was not cancer and was a rare infection that can be cured with prolonged antibiotic treatment. It was a not simple infection of the breast after all. Finishing up the course of antibiotics for 3 months was not easy, coming to the infusion centre initially and then remembering to take them daily. My doctors and medical staff reassured and comforted me at each step of my treatment. I felt blessed to have been treated with an excellent team of doctors. I am happy to share my experience with other people. I have consented to publish my journey with this disease as a case report.

Learning points

  • Actinomycosis of the breast often mimics other infections and malignancy, clinically and radiologically. A high level of suspicion is essential for the diagnosis and cure.

  • In general, actinomyces is common in men, but actinomycosis of the breast is mostly reported in premenopausal women. Few cases have been reported in postmenopausal women.

  • Actinomyces spp are usually extremely susceptible to B-lactams especially penicillin G and amoxicillin, which is the drug of choice.

  • Doxycycline, clindamycin, erythromycin and minocycline are suitable for patients who are allergic to penicillin.

Ethics statements

Acknowledgments

Ashley, Editor, Texas Tech University Health Centers. Medical Center Hospital, Odessa, Texas 79763.

References

Footnotes

  • Contributors JBdL, DS, HR, VS, literature search, analysis/interpretation of the data,drafting of the manuscript, revising the manuscript for important intellectual content, approval of the last version of the manuscript, submission of the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.