Cutaneous Actinomycosis

Are You Confident of the Diagnosis?

Actinomycosis is often called the “great masquerader” of the head and neck. Prompt diagnosis is difficult because of the lack of clinical symptoms. Patients may present with an insidious onset of constitutional symptoms, such as fever, anorexia, malaise, weight loss, and night sweats. A slowly enlarging, tender mass will also be noted in cases of abscess formation. Sinus tracts with copious granular drainage may be noted as well.

  • What you should be alert for in the history

Patients with cutaneous actinomycosis may have an antecedent history of trauma or surgery. For orofacial infections, this may include recent dental work or radiation therapy. Poor oral hygiene and periodontal disease are also risk factors for the development of the disease. Other common sites of infection are the lungs, abdomen, and pelvis. Surgical procedures, such as recent appendectomy or IUD implantations, can also predispose to the development of abdominal or pelvic actinomycosis. However, sporadic cases of cutaneous actinomycosis have also been reported in patients lacking a history of trauma, emphasizing the importance of a high degree of suspicion in clinically suggestive cases despite history.

  • Characteristic findings on physical examination

Clinical findings include soft tissue swelling with painless subcutaneous nodules. Tenderness of the affected area and a fluctuant or indurated mass may or may not be present. The extent of the mass, if present, may or may not be well defined. Severe cases are associated with skin erosions and sinus tracts, which may drain copious amounts of pus and “sulfur granules.” There may be significant amounts of granulation tissue surrounding the sinuses.

Abscesses are certainly not limited to the face, however, increasing numbers of thoracic, abdominal, and pelvic abscesses are being attributed to Actinomyces species. Because of the polymicrobial nature of the disease, the skin, subcutaneous tissue, muscle, bone may be involved, alone or in combination. Lymphatic involvement is rare, developing late in the course of disease if it does develop.

  • Expected results of diagnostic studies

The principal method of diagnosis is by detection of “sulfur granules,” Gram’s stain, and histopathologic examination. Serologic tests and direct fluorescent antibody staining techniques have been used at times, but they lack sensitivity, specificity, and widespread availability. Imaging studies can be obtained to delineate the abscess limits and extension for surgical planning.

  • Diagnostic confirmation

The principal diagnostic methods are not suitably specific; diagnostic confirmation comes via microbiological culture. Unfortunately, the failure rate is high for a number of reasons: prior antibiotic therapy, overgrowth of other bacteria, or inadequate sample collection. Molecular biological methods are in development to confirm the diagnosis, although most tests are used only in research labs. In these institutions, partial sequencing of the 16s ribosomal RNA (rRNA) gene has become the reference method for bacterial identification. Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry is a promising method that can accurately identify Actinomyces at the genus level; however, 16s rRNA sequencing remains the preferred technique for precise species identification.

Who is at Risk for Developing Actinomycosis?

Actinomycosis affects men more than women (M:F 3:1). The disease most commonly presents in the fourth or fifth decade of life, but has been described between the second and seventh decades. As Actinomyces species are natural colonizers of the oral cavity, a patient with a history of trauma to the oral mucosa, by dental procedures, radiotherapy, poor hygiene, or periodontal disease is at risk for developing the disease. Additionally, other species colonize the respiratory, gastrointestinal, and genitourinary tracts; trauma, surgical procedures, or placement of implants, particularly intrauterine devices (IUDs), are risk factors.

What is the Cause of Actinomycosis?

  • Etiology

  • Pathophysiology

Actinomycosis is a sporadically occurring granulomatous, suppurative infection caused by bacteria of the genera Actinomyces most commonly, as well as Propionibacterium and Bifidobacterium less commonly (collectively known as “Actinomycetes”). The responsible bacteria are filamentous, beaded, Gram-positive, rod-shaped, anaerobic bacteria that normally colonize the mucosal surfaces of humans and animals.

Actinomyces israelii has been linked to intraoral infections and abscesses for many years. However, the number of clinically relevant species has increased dramatically over the past decade as a result of improvements in classification, identification, and detection of the bacteria. Actinomycosis has been described in virtually every part of the body, and different species are associated with infections in specific body sites.

Actinomycetes are normal colonizers of the human body, including the oral cavity. In order to cause infection, there must be an antecedent history of trauma to create an anoxic environment in which the bacteria can multiply freely. The infection does not occur in the absence of other bacteria; rather, polymicrobial environments are needed to aid in tissue invasion.

Systemic Implications and Complications

Most infections occur in immunocompetent hosts. Actinomycosis has been recognized as an indicator of poor prognosis in cases of infected osteoradionecrosis and bisphosphonate-associated osteonecrosis of the jaw. Death from Actinomycosis is exceedingly rare.

Treatment Options

Treatment options are summarized in Table I.

Table I.

Treatment options for cutaneous actinomycosis
Medical Systemic Penicillin +/- B-lactamase
Medical Topical No Benefit
Surgical Excision
Physical Hyperbaric Oxygen

Optimal Therapeutic Approach for Actinomycosis

Optimally, pus with granular material should be collected for culture to detect antibiotic sensitivity prior to the administration of antibiotics. Selective resistance to penicillin has been described, although rarely. Obtaining culture and sensitivities will also reveal synchronous infectious species and enable appropriate therapy.

If abscess formation is suspected, imaging studies should be obtained to delineate the lesion and to provide a baseline to evaluate treatment options. While many actinomycotic abscesses respond to appropriate antibiotic therapy, some may require surgical excision. Imaging studies will also enable the provider to monitor response to treatment.

Systemic medications are critical to treatment success. Therapy with penicillin or its derivatives (ampicillin IV followed by amoxicillin PO) remains the mainstay of treatment. In patients with penicillin allergy, doxycycline, cephalosporins, clindamycin, sulfonamides, imipenem, and lincomycin have been used alternatively with great success. Although the appropriate antibiotics are well known, the proper duration of therapy remains greatly contested.

Uncomplicated infections can be treated with antibiotic therapy alone. The route of administration depends on the clinical impression. Similar results have been described using combination of parenteral followed by oral antibiotics compared to oral antibiotics alone. The optimal duration of therapy remains unclear and should be guided by clinical response to therapy. Because antibiotics have poor penetration into the fibrotic tissues of an abscess, the effectiveness of medical therapy is diminished, necessitating prolonged therapy. In some series, therapy has extended for over a year.

Two sample treatment regimens are as follows, for patients who can or cannot tolerate penicillin. A patient with no history of penicillin allergy should be started on ampicillin-sulbactam 1.5 g IV three times per day for 2 weeks before being switched to amoxicillin 500 mg-clavulanate 125 mg PO two times per day for 10 weeks. Patients who are allergic to or develop side effects to penicillin can be prescribed doxycycline 100 mg IV twice per day for 3 weeks before being switched to doxycycline 100 mg PO twice per day for 9 weeks.

Three months of therapy appears to be the minimum required for long-term success, although treatment failures with long latent periods (up to 16 years) have been reported with longer courses. Imaging studies and physical examination are of critical importance in determining response to therapy; incomplete resolution of infection necessitates prolonged treatment.

Surgical debridement or excision of the abscess is not always needed, but can be performed in cases of antibiotic failure, rapid progression of disease, or for cosmetic reasons. Following excision, traditional courses of antibiotics are prescribed to prevent relapse.

The use of hyperbaric oxygen in refractory cases of actinomycosis is supported by several trials; however, it should only be used as an adjunct to concurrent medical therapy.

Patient Management

Close follow-up of a patient with actinomycosis is critical to the successful treatment of the disease. Clinical signs of improvement after antibiotic therapy has been initiated include steady regression of the abscess or area of induration and erythema. Drainage from sinus tracts will be reduced or cease. Imaging studies may show regression of the abscess.

Important counseling to give to the patient and family revolve around strict compliance with therapy. Because of the proclivity for the disease to recur, even after decades, the prescribed course of antibiotic must be finished. This may include extending the course of therapy for more than a year beyond the initially prescribed course.

Unusual Clinical Scenarios to Consider in Patient Management

Treatment of cutaneous actinomycosis is relatively straightforward, especially when microbiologic susceptibility studies have been performed prior to antibiotic therapy. If the disease does not respond to treatment, consider co-infection or an alternative diagnosis.

What is the Evidence?

Choi, M, Beak, JH, Lee, JN, Park, S, Lee, W.. "Clinical features of abdominopelvic actinomycosis: report of twenty cases and literature review". Yonsei Med J.. vol. 50. 2009 August 31. pp. 555-9.

(An interesting article about the ability of actinomycosis to masquerade as inflammatory pseudotumor.)

Akhtar, M, Zade, MP, Shahane, PL, Bangde, AP, Soitkar, SM.. "Scalp actinomycosis presenting as soft tissue tumour: A case report with literature review". Int J Surg Case Rep.. vol. 16. 2015. pp. 99-101.

(An interesting article which describes a case of tumoriform actinomycosis of the scalp presenting as a pseudocarcinomatous mass.)

Bose, M, Ghosh, R, Mukherjee, K, Ghoshal, L.. "Primary Cutaneous Actinomycosis:A Case Report". Journal of Clinical and Diagnostic Research: JCDR. vol. 8. 2014. pp. YD03-YD05.

(An interesting case report of primary cutaneous actinomycosis in a patient without a history of trauma highlighting the importance of having a high degree of suspicion for actinomycosis in clinically suggestive cases.)

Hall, V.. "Actinomyces. Gathering evidence of human colonization and infection". Anaerobe. vol. 14. 2008. pp. 1-7.

(This article describes the evolution of the diagnostic methods for actinomycosis and the roles of less common Actinomyces species in infectious pathology.)

Lynch, T, Gregson, D, Church, DL.. "Species-Level Identification of Actinomyces Isolates Causing Invasive Infections: Multiyear Comparison of Vitek MS (Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry) to Partial Sequencing of the 16S rRNA Gene". J Clin Microbiol.. vol. 54. 2016 Mar. pp. 712-7.

(This article compares two molecular identification methods: partial sequencing of the 16S ribosomal RNA gene and the matrix-assisted laser desorption ionization-time of flight mass spectrometry [MALDI-TOF MS] in identifying Actinomyces spp.)

Kolm, I, Aceto, L, Hombach, M, Kamarshev, J, Hafner, J, Urosevic-Maiwald, M.. "Cervicofacial actinomycosis: a long forgotten infectious complication of immunosuppression - report of a case and review of the literature". Dermatol Online J.. vol. 20. 2014 May 16. pp. 22640.

(This article describes the diagnosis of culture-negative actinomycosis based on a combination of histopathological findings and isolation of companion bacteria by sequencing the 16S rRNA gene.)

Kolditz, M, Bickhardt, J, Matthiessen, W, Holotnik, O, Hoffken, G, Koschel, D.. "Medical management of pulmonary actinomycosis: data from 49 consecutive cases". J Antimicrobial Chemotherapy. vol. 63. 2009. pp. 839-41.

(An article detailing the antimicrobial options and treatment duration for actinomycosis with and without abscess formation.)

Lall, T, Shehab, TM, Valenstein, P.. "Isolated hepatic actinomycosis: a case report". J Medical Case Reports. vol. 4. 2010. pp. 45.

(An interesting case report that shows the range of organs that can be affected by Actinomyces species.)

Könönen, E, Wade, WG.. "Actinomyces and related organisms in human infections". Clin Microbiol Rev.. vol. 28. 2015 Apr. pp. 419-42.

(A review article describing the identification of new Actinomyces species due to new advanced molecular methods and their propensity for infection in specific body sites.)

Makhija, LK, Jha, MK, Bhattacharya, S, Bhardwaj, M, Rai, A, Mishra, S.. "Dormant primary cutaneous actinomycosis: acute exacerbation after 16 years". J Plast Reconstr Aesthet Surg.

(This article brings the possibility of extremely late treatment failures to light.)

Ngow, HA, Wan Khairina, WMN.. "Cutaneous actinomycosis: the great mimicker". J Clin Pathol. vol. 62. 2009. pp. 766.

(The authors examine the various presentations of actinomycosis infection and some of the treatment options.)

Patil, D, Siddaramappa, B, Manjunathswamy, BS, Pandit, AM, Dastikop, S, Fernandes, C. "Primary cutaneous actinomycosis". Int J Dermatol. vol. 47. 2008. pp. 1271-73.

(A case report of a typical presentation of actinomycosis as well as some of the treatment options.)

Pulverer, G, Shutt-Gerowitt, H, Schaal, KP.. "Human cervicofacial actinomycoses: microbiological data for 1997 cases". Clin Infect Dis. vol. 37. 2003 Aug 15. pp. 490-97.

(A large German case series detailing the epidemiology of actinomycosis, the species responsible for infection, and the microbes that co-infect patients, making actinomycosis possible.)

Smith, AJ, Hall, V, Thakker, B, Gemmell, CG.. "Antimicrobial susceptibility testing of Actinomyces species with 12 antimicrobial agents". J Antimicrobial Chemotherapy. vol. 56. 2005. pp. 407-9.

(This report details the susceptibility of 87 samples of Actinomyces species collected in the United Kingdom.)
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