Perianal Actinomycosis: A Case Study of this Rare Infection Associated with Nicorandil Usage

Introduction

Actinomycosis is a rare bacterial infection that can be difficult to diagnose. The Actinomyces bacteria that are responsible, contribute to the normal flora of the oropharynx, gastro intestinal tract and female genital tract and are rarely pathogenic. Actinomycosis most commonly affects the cervico-facial, thoracic and abdomino-pelvic regions, but neurological and cutaneous infections also occur. Perianal actinomycosis is extremely rare. Nicorandil is a potassium channel agonist used in the treatment of ischaemic heart disease, and is associated with perianal ulceration and delayed wound healing. We report a case of perianal actinomycosis complicating a longstanding perianal ulcer associated with long-term nicorandil usage.

Case presentation

A 79-year-old man was referred to the surgical clinic, by his general practitioner, with a one-month history of a painful perianal swelling associated with weight loss and anorexia. He had undergone incision and drainage of a perianal abscess three years previously but prior to this had no history of perianal disease. The surgical wound had failed to heal and had developed into a small chronic ulcer. His past medical history included ischaemic heart disease for which he had been taking nicorandil for over five years.

On examination there was a large, ulcerated, indurated swelling situated just anterior to the anal margin and extending towards the scrotum. The initial impression was that this could represent an ulcerated anal cancer and an examination under anaesthetic was performed. Biopsies and swabs were taken. Actinomyces bacteria were seen on microscopy, in the form of a ‘sulphur granule’, and this was subsequently confirmed with gram and periodic acid Schiff staining. The diagnosis of perianal actinomycosis was made.

Treatment was with a one-month course of intravenous benzylpenicillin followed by a six-month course of oral amoxicillin. After cardiology consultation, nicorandil was discontinued and treatment changed to isosorbide mono nitrate. Satisfactory resolution was observed at regular outpatient review and the patient was discharged from follow-up after seven months, following complete healing.

Discussion

Nicorandil is a potassium channel agonist used in the treatment of ischaemic heart disease. It is recognized as a cause of perianal ulceration ¹ and is associated with delayed wound healing. ²

Actinomycosis is a rare, chronic infection caused by Actinomyces bacteria. It is seen worldwide but more so in rural and farming communities, and is associated with poor dental hygiene, low socioeconomic status, immunocompromise and male sex.

Actinomyces are saprophytes, found in soil and putrefied vegetables, but also form part of the normal microbial flora of the human oropharynx, gastrointestinal tract and female genital tract. They are fastidious, Gram-positive, catalase-positive, non-motile, non-acidfast, facultative anaerobic bacilli. They were first believed to be fungi as they form delicate filaments, like fungal hyphae, but are non-spore-forming. Like bacteria their cell walls contain muramic acid, they have prokaryotic nuclei and they are susceptible to antibiotics.

Actinomycosis is not infectious but Actinomyces bacteria can be transmitted from person-to-person. They are usually non-virulent and cannot cross mucous membranes. However, in combination with other bacteria, Actinomyces can become pathogenic if there is a break in the normal mucosal or skin barrier and in the presence of devitalized tissue. Actinomyces israelii is the most common cause of actinomycosis in humans and is named after James Israel, who first identified Actinomyces in humans in the late nineteenth century.

A characteristic feature of actinomycosis is the presence of small (1–2 mm diameter), yellow so-called ‘sulphur’ granules within a thin, watery, purulent discharge. These granules are aggregates of organisms consisting of a central core of intertwined, branching filaments surrounded by a peripheral zone of rays terminating in club-shaped structures, which are believed to be antigen complexes. This structure, when viewed under the microscope, has a sun burst appearance and it is from this that the name Actinomyces derives. In Greek ‘aktis’ means ray and ‘myces’ means fungus.

The diagnosis of actinomycosis can be challenging. Identification of sulphur granules, with typical microscopic appearances, is highly suggestive of the diagnosis, but they are not always present. Indeed, in a review of six cases of perianal actinomycosis occurring over 17 years by Bauer et al., sulphur granules were not observed in any of the cases and watery pus was only seen in only one. ³ Ideally pus, granules or tissue should be sent expeditiously to the laboratory in an anaerobic supporting medium. Anaerobic culture at 35–37°C using an enriched medium is required for up to 10 days.

Once established, the infection precipitates an intense inflammatory reaction in the human host characterized by granuloma formation, tissue fibrosis, abscess formation, localized swelling with suppuration and draining sinuses. Spread of the infection is contiguous and invasion of the surrounding tissue and organs is seen. The features of invasive spread across tissue planes, associated tumour and induration can raise the clinical suspicion of malignancy.

Actinomycosis can occur anywhere in the body but is recognized as primarily occurring in the cervicofacial, thoracic and abdominopelvic regions, but neurological and cutaneous manifestations are also recognized. Perianal actinomycosis is extremely rare. It can be mistaken for perianal Crohn's disease or anorectal malignancy. ⁴ It often follows a very indolent course and patients can present with recurrent perianal sepsis over many years. ⁵ It has also been observed as a complication of perianal fistula ⁶ or can present as multiple fistulae of the perineum. ⁷

The treatment involves a prolonged course of penicillin to clear the infection and prevent recurrence. ⁸ There are no established guidelines for the duration of antimicrobial treatment, and advice should be sought from the local microbiology laboratory and therapy tailored to response.

In our case the operation note from the original incision and drainage, three years previously, described an acute, simple, perianal abscess. It, therefore, seemed unlikely that this original abscess was due to actinomycosis. The delayed healing of the surgical wound and the development of a chronic perianal ulcer was thus attributed to long-term nicorandil usage rather than actinomycosis. We believe that this ulcer provided the conditions conducive to Actinomyces colonization and the subsequent development of perianal actinomycosis. This is the first time an association between perianal actinomycosis and nicorandil usage has been made.

Conclusion

Perianal actinomycosis results in chronic infection which spreads across tissue planes and can resemble an ulcerated malignancy. Nicorandil usage can result in perianal ulceration and produces conditions which are conducive to actinomycosis infection. In such cases, nicorandil therapy should be discontinued, if possible. Long-term systemic antibiotics form the mainstay of treatment.

Learning Points

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Nicorandil usage is associated with perianal ulceration and delayed wound healing;

Author contributions: DJA edited case presentation, wrote discussion and conclusion, edited document and formatted for submission; JRW wrote case presentation and assisted in editing process; and MSB oversaw project.