Anal mycobacterial infections†† Institution: Serviço de Coloproctologia do Hospital São Lucas da PUC-RS.

Lúcio Sarubbi Fillmann Henrique Sarubbi Fillmann Laura Pinho Fillmann Lana Becker Micheletto Michel Hoefel Josenel Maria Barcelos Marçal Rafael Nazario Bringhenti About the authors

Abstract

Background

Mycobacterial infections are a serious public health problem worldwide. Involvement of the anal canal and perineum is very rare, but constitute an important differential diagnosis with other equally serious pathologies that may affect the region, such as malignant neoplasms and Crohn’s disease.

Objectives

To conduct a literature review on mycobacterial infections of the perianal region considering the most recent information for diagnostic and therapeutic guidance of this disease.

Methods

Research was performed on the PUBMED and LILACS databases with the expressions Mycobacterium, Anal, Infection and Tuberculosis. We reviewed articles referring to series of treated cases, clinical reports and literature review published since 2005.

Results

Information was compiled on the epidemiology of mycobacterial infections; the clinical behavior of affected individuals; diagnostic options and their validity in clinical practice; and, finally, therapeutic options.

Conclusions

Mycobacterial infections of the anus and perineum are rare. The most common clinical presentations are the presence of ulceration and fistulization. The diagnosis involves more than one procedure for identifying the bacilli and should consider the presence of manifestations in more than one organ. The treatment is based on pharmacological intervention. Surgery is recommended for acute complications or chronic sequelae of the disease.

Keywords:
Mycobacterial infections; Tuberculosis; Anal canal; Fistula in ano

Resumo

Introdução

Infecções micobacterianas constituem um grave problema de saúde pública a nível mundial. As manifestações anoperineais são raras, mas constituem um importante diagnóstico diferencial com outras patologias igualmente graves que podem acometer a região, como as neoplasias malignas e a doença de Crohn.

Objetivos

Realizar um levantamento da literatura sobre infecções micobacterianas da região anoperineal, considerando as informações mais atuais para orientação diagnóstica e terapêutica dessa enfermidade.

Métodos

Foi realizada pesquisa nos bancos de dados PUBMED e LILACS com as expressões Mycobacterium, Anal, Infection e Tuberculosis. Foram revisados artigos referentes a séries de casos tratados, relatos clínicos e revisão da literatura publicada a partir de 2005.

Resultados

Foram compiladas informações sobre a epidemiologia das infecções micobacterianas; o comportamento clínico dos indivíduos afetados; opções diagnósticas e sua validade na prática clínica; e, por fim, opções terapêuticas.

Conclusões

Infecções micobacterianas da região anoperineal são raras. As apresentações clínicas mais comuns são a formação de ulceras e a fistulização. O diagnóstico envolve mais de um procedimento para identificação dos bacilos, e deve considerar a presença de manifestações em mais de um órgão. O tratamento é principalmente medicamentoso, sendo a cirurgia recomendada nas complicações agudas ou sequelas crônicas da doença.

Palavras-chave:
Infecções por micobactéria; Tuberculose; Canal anal; Fístula anal

Introduction

Mycobacterial infections are a serious health problem worldwide, particularly in developing countries.11 Takakura Y, Fujimori M, Okugawa K, Hiroyuki E, Ohdan H, Kaneko S, et al. Rare case of sacrococcygeal tuberculosis mimicking as an anal fistula. Int J Surg Case Rep. 2018;49:74-7.55 Tago S, Hirai Y, Ainoda Y, Fujita T, Takamori M, Kikuchi K. Perianal tuberculosis: a case report and review of the literature. World J Clin Cases. 2015;3:848-52. The increased life expectancy of the world population, as well as the increased number of individuals with clinical immunosuppression, especially HIV infection, are responsible for the growing number of people with mycobacteriosis, mainly tuberculosis.11 Takakura Y, Fujimori M, Okugawa K, Hiroyuki E, Ohdan H, Kaneko S, et al. Rare case of sacrococcygeal tuberculosis mimicking as an anal fistula. Int J Surg Case Rep. 2018;49:74-7.,22 Mathew S. Anal tuberculosis: report of a case and review of literature. Int J Surg. 2008;6:e36-9. The extrapulmonary clinical presentation, however, is the least common form of the disease.22 Mathew S. Anal tuberculosis: report of a case and review of literature. Int J Surg. 2008;6:e36-9.44 Akgun E, Tekin F, Ersin S, Osmanoglu H. Isolated perianal tuberculosis. Neth J Med. 2005;63:115-7. When it reaches the anal region, this infectious process has several clinical forms, the most common being anal fistula as well as perineal ulcerations.66 Gupta PJ. Ano-perineal tuberculosis: solving a clinical dilemma. Afr Health Sci. 2005;5:345-7. Thus, mycobacteriosis of the anus is a differential diagnosis, with other granulomatous diseases in this region, being important especially regarding Crohn’s disease.55 Tago S, Hirai Y, Ainoda Y, Fujita T, Takamori M, Kikuchi K. Perianal tuberculosis: a case report and review of the literature. World J Clin Cases. 2015;3:848-52.

Objectives

The aim of the present study is to obtain an updated review of the clinical behavior of individuals with anoperineal mycobacterium infection, as well as to investigate diagnostic and therapeutic options for this disease.

Methods

A literature review of the PUBMED and LILACS databases was performed using the terms Mycobacteria, Anorectal, Infection, and Tuberculosis. Articles related to literature review, case series, and clinical reports were included. We reviewed publications identified on these search platforms from 2005 onwards.

Discussion

Based on the review and clinical experience of the authors in dealing with cases of perianal mycobacterium infection, data regarding the disease epidemiological behavior, most frequent clinical presentations, available diagnostic instruments and their sensitivity and specificity, and recommended therapeutic options for disease control were analyzed.

Epidemiology

Mycobacterial infection, especially tuberculosis, is a worldwide epidemic.77 WHO. Global tuberculosis report; 2018 Data from the World Health Organization indicate that tuberculosis is one of the top 10 clinical entities related to human mortality, being the leader among infectious diseases.77 WHO. Global tuberculosis report; 2018 In 2017, it was estimated that 1.3 million people perished as a result of this condition, an increase of at least 300,000 more deaths in HIV-positive individuals.77 WHO. Global tuberculosis report; 2018 The number of cases is especially higher in developing countries, but there are reports in all nationalities and all age groups.11 Takakura Y, Fujimori M, Okugawa K, Hiroyuki E, Ohdan H, Kaneko S, et al. Rare case of sacrococcygeal tuberculosis mimicking as an anal fistula. Int J Surg Case Rep. 2018;49:74-7.55 Tago S, Hirai Y, Ainoda Y, Fujita T, Takamori M, Kikuchi K. Perianal tuberculosis: a case report and review of the literature. World J Clin Cases. 2015;3:848-52.,77 WHO. Global tuberculosis report; 2018 Adults represent approximately 90% of those infected, with 9% of individuals carrying the HIV virus, of which 72% live in the African continent. Two-thirds of all reported cases are found in eight countries: India, China, Indonesia, Philippines, Pakistan, Nigeria, Bangladesh, and South Africa. These eight nations, together with 22 others with high disease rates, account for 87% of all tuberculosis cases.77 WHO. Global tuberculosis report; 2018 Brazil is included in this group of 30 countries.77 WHO. Global tuberculosis report; 2018 Most infections affect the respiratory tract. Extrapulmonary manifestations represent between 5% and 15% of the total cases of the disease.44 Akgun E, Tekin F, Ersin S, Osmanoglu H. Isolated perianal tuberculosis. Neth J Med. 2005;63:115-7.,66 Gupta PJ. Ano-perineal tuberculosis: solving a clinical dilemma. Afr Health Sci. 2005;5:345-7. In tuberculosis, non-pulmonary manifestations include pleura (26%), lymph nodes (17%), genitourinary tract (15%), joints and bones (14%), meninges (6%), peritoneum (4%), and the miliary form (8%).44 Akgun E, Tekin F, Ersin S, Osmanoglu H. Isolated perianal tuberculosis. Neth J Med. 2005;63:115-7. The gastrointestinal tract accounts for only 1% of non-respiratory infections,33 Azadi A, Fard PJ, Farahani MS, Khodadadi B, Almasian M. Anal tuberculosis: a non-healing anal lesion. IDCases. 2018;12:25-8.,44 Akgun E, Tekin F, Ersin S, Osmanoglu H. Isolated perianal tuberculosis. Neth J Med. 2005;63:115-7. a number credited to sanitary measures adopted for a long time such as milk pasteurization.44 Akgun E, Tekin F, Ersin S, Osmanoglu H. Isolated perianal tuberculosis. Neth J Med. 2005;63:115-7. When this region is affected, the disease is mainly located in the ileum and cecum.33 Azadi A, Fard PJ, Farahani MS, Khodadadi B, Almasian M. Anal tuberculosis: a non-healing anal lesion. IDCases. 2018;12:25-8. The anus represents only 1% of the mycobacterial infection sites, especially tuberculosis, which reach the digestive tract.33 Azadi A, Fard PJ, Farahani MS, Khodadadi B, Almasian M. Anal tuberculosis: a non-healing anal lesion. IDCases. 2018;12:25-8. In the United Kingdom, one review identified only 2 cases of perineal tuberculosis in 22 years.22 Mathew S. Anal tuberculosis: report of a case and review of literature. Int J Surg. 2008;6:e36-9. Comprehensive reviews of the international literature performed between 1970 and 2014 and addressing reports of perianal tuberculosis, particularly presenting with abscess, fistula or ulceration type, found only 58 cases and 70.7% of the reports were from the Asiatic continent.55 Tago S, Hirai Y, Ainoda Y, Fujita T, Takamori M, Kikuchi K. Perianal tuberculosis: a case report and review of the literature. World J Clin Cases. 2015;3:848-52. In our service, two cases were diagnosed within 25 years.

Clinical presentation

The development of anal fistula seems to be the most common presentation of mycobacterial infection of the anorectoperineal region.33 Azadi A, Fard PJ, Farahani MS, Khodadadi B, Almasian M. Anal tuberculosis: a non-healing anal lesion. IDCases. 2018;12:25-8.,66 Gupta PJ. Ano-perineal tuberculosis: solving a clinical dilemma. Afr Health Sci. 2005;5:345-7.,77 WHO. Global tuberculosis report; 2018,99 Sahu M, Mishra JK, Sharma A, Fatmi U. A prospective study on tubercular fistula in ano and its management. J Coloproctol (RIO J). 2017;37:211-5. However, there is a low specificity of symptoms reported by patients to characterize the infection as associated with mycobacteria, contrary to the much more frequent complication of a crypto-glandular infectious process.99 Sahu M, Mishra JK, Sharma A, Fatmi U. A prospective study on tubercular fistula in ano and its management. J Coloproctol (RIO J). 2017;37:211-5. Constitutional symptoms, such as anorexia, weight loss and night fever, should reinforce the hypothesis of mycobacterial infection.99 Sahu M, Mishra JK, Sharma A, Fatmi U. A prospective study on tubercular fistula in ano and its management. J Coloproctol (RIO J). 2017;37:211-5. Simultaneous occurrence of respiratory symptoms, such as chronic cough accompanied by poor discharge or sputum, may indicate concomitant pulmonary disease.77 WHO. Global tuberculosis report; 2018 Such condition was reported in approximately 75% of patients in a historical series of anal tuberculosis, where individuals also had active or previously treated lung disease.77 WHO. Global tuberculosis report; 2018 Suspicion should also be reinforced in cases with clinical conditions resulting in immunosuppression.22 Mathew S. Anal tuberculosis: report of a case and review of literature. Int J Surg. 2008;6:e36-9. Clinical investigation of anti-HIV antibodies is especially important, as the reduction of lymphocyte activity by viral infection allows reactivation of dormant foci of mycobacteria in pulmonary and gastrointestinal sites.22 Mathew S. Anal tuberculosis: report of a case and review of literature. Int J Surg. 2008;6:e36-9. It should be noted, however, that most authors reported the occurrence of anoperineal disease in immunocompetent patients.55 Tago S, Hirai Y, Ainoda Y, Fujita T, Takamori M, Kikuchi K. Perianal tuberculosis: a case report and review of the literature. World J Clin Cases. 2015;3:848-52. Moreover, several studies report that the number of men affected is significantly higher than women, and may reach a ratio of 4:1.22 Mathew S. Anal tuberculosis: report of a case and review of literature. Int J Surg. 2008;6:e36-9.,77 WHO. Global tuberculosis report; 2018,97 WHO. Global tuberculosis report; 2018 In our small sample, both patients were male and under 40 years old. Physical examination may contribute significantly to the hypothesis of anal mycobacterial infection. Fistulas often acquire complex features with multiple external orifices and long perineum tracts77 WHO. Global tuberculosis report; 2018. Commonly, ulcer formation is observed in the perianal region, with regular borders, necrotic or fibrin-covered bottom, and discharge of purulent secretion (Fig. 1).33 Azadi A, Fard PJ, Farahani MS, Khodadadi B, Almasian M. Anal tuberculosis: a non-healing anal lesion. IDCases. 2018;12:25-8.,44 Akgun E, Tekin F, Ersin S, Osmanoglu H. Isolated perianal tuberculosis. Neth J Med. 2005;63:115-7. Warty and miliary formations have also been described.33 Azadi A, Fard PJ, Farahani MS, Khodadadi B, Almasian M. Anal tuberculosis: a non-healing anal lesion. IDCases. 2018;12:25-8. These findings resemble other more common pathologies that are part of differential diagnosis, such as Crohn’s disease, herpes, syphilis, skin neoplasms, and traumatic foreign body injuries.22 Mathew S. Anal tuberculosis: report of a case and review of literature. Int J Surg. 2008;6:e36-9. It should also be noted that chronicity is a significant hallmark of the disease.

Fig. 1
Fistulous orifice with perianal ulcer in a patient with mycobacterial infection.

Diagnosis

The perianal mycobacterial infection diagnosis requires a high degree of suspicion by the attending physician. Initially, it is essential that the atypical clinical presentation of perianal disease, whether in its warty, ulcerated form or the formation of complex fistulous tracts, serves to draw the attention of the health professional regarding the possible mycobacterial infection. Indirect diagnostic tests, such as Mantoux, can be performed and will be positive in approximately 75% of non-immunosuppressed patients affected by the disease.66 Gupta PJ. Ano-perineal tuberculosis: solving a clinical dilemma. Afr Health Sci. 2005;5:345-7. Therefore, a negative test in an immunocompetent individual with a normal chest radiograph provides a solid basis for ruling out the possibility of perianal tuberculosis.66 Gupta PJ. Ano-perineal tuberculosis: solving a clinical dilemma. Afr Health Sci. 2005;5:345-7. Another alternative, following the analogy of investigating sputum mycobacteria in suspected lung disease, would be to look for acid-resistant bacilli in the secretion eliminated by the anal fistula. A positive test confirms the diagnosis. However, this finding is seen in less than 25% of cases.66 Gupta PJ. Ano-perineal tuberculosis: solving a clinical dilemma. Afr Health Sci. 2005;5:345-7. If mycobacterial infection is suspected, a biopsy of the perianal lesion should be performed.22 Mathew S. Anal tuberculosis: report of a case and review of literature. Int J Surg. 2008;6:e36-9.,44 Akgun E, Tekin F, Ersin S, Osmanoglu H. Isolated perianal tuberculosis. Neth J Med. 2005;63:115-7.,66 Gupta PJ. Ano-perineal tuberculosis: solving a clinical dilemma. Afr Health Sci. 2005;5:345-7. The characteristic histological aspect is that of an epithelioid granuloma with multinucleated giant cells having an area of caseous necrosis (Fig. 2). 22 Mathew S. Anal tuberculosis: report of a case and review of literature. Int J Surg. 2008;6:e36-9.,44 Akgun E, Tekin F, Ersin S, Osmanoglu H. Isolated perianal tuberculosis. Neth J Med. 2005;63:115-7.,66 Gupta PJ. Ano-perineal tuberculosis: solving a clinical dilemma. Afr Health Sci. 2005;5:345-7. When these findings are identified under microscopy, the bacillus should be screened using Ziehl–Neelsen staining (Fig. 3).22 Mathew S. Anal tuberculosis: report of a case and review of literature. Int J Surg. 2008;6:e36-9.,66 Gupta PJ. Ano-perineal tuberculosis: solving a clinical dilemma. Afr Health Sci. 2005;5:345-7. The secretion culture in order to identify the type of mycobacteria, as well as its susceptibility to antimicrobial agents, should complete the investigation.66 Gupta PJ. Ano-perineal tuberculosis: solving a clinical dilemma. Afr Health Sci. 2005;5:345-7. Polymerase Chain Reaction (PCR) screening for bacterial DNA identification has high sensitivity and specificity and is a faster alternative to culture, with an execution time that can reach up to four weeks (Fig. 4).11 Takakura Y, Fujimori M, Okugawa K, Hiroyuki E, Ohdan H, Kaneko S, et al. Rare case of sacrococcygeal tuberculosis mimicking as an anal fistula. Int J Surg Case Rep. 2018;49:74-7.,44 Akgun E, Tekin F, Ersin S, Osmanoglu H. Isolated perianal tuberculosis. Neth J Med. 2005;63:115-7.,66 Gupta PJ. Ano-perineal tuberculosis: solving a clinical dilemma. Afr Health Sci. 2005;5:345-7.

Fig. 2
Photomicrograph (200×), HE stain, showing dermis with acute inflammatory infiltrate and multinucleated giant cell in the center.
Fig. 3
Photomicrograph (400×) showing positive Ziehl–Neelsen staining and low bacillus density.
Fig. 4
Late postoperative period of patient with anal fistula related to mycobacterial infection. Patient was treated for 6 months with tuberculostatics.

Treatment

The mainstay of treatment for perianal mycobacterial infection is prolonged antibiotic therapy with multiple combined drugs, following the same principle of infections caused by these agents in other organs and systems.22 Mathew S. Anal tuberculosis: report of a case and review of literature. Int J Surg. 2008;6:e36-9.,66 Gupta PJ. Ano-perineal tuberculosis: solving a clinical dilemma. Afr Health Sci. 2005;5:345-7.,99 Sahu M, Mishra JK, Sharma A, Fatmi U. A prospective study on tubercular fistula in ano and its management. J Coloproctol (RIO J). 2017;37:211-5.,1010 Neto IJ, Siá ON, Lopes EA, Macacari RL, Watté HH, Souza RF, et al. Perianal tuberculosis: a rare disease of late diagnosis. J Coloproctol (RIO J). 2014;34:124-7. The recommended treatment regimen involves 6 months of treatment, the first two with rifampicin, isoniazid, pyrazinamide, and ethambutol and the remaining four with only rifampicin and pyrazinamide.99 Sahu M, Mishra JK, Sharma A, Fatmi U. A prospective study on tubercular fistula in ano and its management. J Coloproctol (RIO J). 2017;37:211-5.,1010 Neto IJ, Siá ON, Lopes EA, Macacari RL, Watté HH, Souza RF, et al. Perianal tuberculosis: a rare disease of late diagnosis. J Coloproctol (RIO J). 2014;34:124-7. Some authors, however, have reported a possible need for prolongation of this treatment based on the slow response and tendency to recurrence.99 Sahu M, Mishra JK, Sharma A, Fatmi U. A prospective study on tubercular fistula in ano and its management. J Coloproctol (RIO J). 2017;37:211-5. The decision on the continuity of the treatment regimen should be based on clinical evaluation and follow-up, but these same publications state that it should rarely be discontinued before 18 months.99 Sahu M, Mishra JK, Sharma A, Fatmi U. A prospective study on tubercular fistula in ano and its management. J Coloproctol (RIO J). 2017;37:211-5. Surgical treatment is restricted to a small set of clinical conditions. The presence of abscess in the region is an indication for immediate surgical drainage.22 Mathew S. Anal tuberculosis: report of a case and review of literature. Int J Surg. 2008;6:e36-9.,99 Sahu M, Mishra JK, Sharma A, Fatmi U. A prospective study on tubercular fistula in ano and its management. J Coloproctol (RIO J). 2017;37:211-5. The occurrence of symptomatic stenosis may cause difficulties in long-term management of patients during antimicrobial treatment, and should be corrected early if necessary.22 Mathew S. Anal tuberculosis: report of a case and review of literature. Int J Surg. 2008;6:e36-9.,99 Sahu M, Mishra JK, Sharma A, Fatmi U. A prospective study on tubercular fistula in ano and its management. J Coloproctol (RIO J). 2017;37:211-5. The anal fistula approach should not be attempted before the end of drug treatment, as active infection may lead to therapeutic failure.22 Mathew S. Anal tuberculosis: report of a case and review of literature. Int J Surg. 2008;6:e36-9.,99 Sahu M, Mishra JK, Sharma A, Fatmi U. A prospective study on tubercular fistula in ano and its management. J Coloproctol (RIO J). 2017;37:211-5. In addition, tract healing and closure is possible with the use of tuberculostatics.22 Mathew S. Anal tuberculosis: report of a case and review of literature. Int J Surg. 2008;6:e36-9.,99 Sahu M, Mishra JK, Sharma A, Fatmi U. A prospective study on tubercular fistula in ano and its management. J Coloproctol (RIO J). 2017;37:211-5.

Conclusion

Perianal mycobacterial infection is a major clinical challenge. Although infrequent, it should be present in the differential diagnosis of other clinical entities, such as Crohn’s disease and anus neoplasms. In immunosuppressed patients, tuberculosis becomes more common, and clinical variation combined with changes in host physiological responses represent a new challenge for diagnostic elucidation. In the presence of suspected mycobacterial infection, a biopsy is mandatory, combined with clinical tests to identify other disease outbreaks, in addition to screaming for alcohol-resistant bacilli through bacteriological analysis of secretions, culture or bacterial DNA PCR. Drug treatment is the main therapeutic option, and surgery is indicated in the presence of abscesses, anal stenosis, and healing failure of the perianal fistulous form after the end of drug treatment.

  • Institution: Serviço de Coloproctologia do Hospital São Lucas da PUC-RS.

References

  • 1
    Takakura Y, Fujimori M, Okugawa K, Hiroyuki E, Ohdan H, Kaneko S, et al. Rare case of sacrococcygeal tuberculosis mimicking as an anal fistula. Int J Surg Case Rep. 2018;49:74-7.
  • 2
    Mathew S. Anal tuberculosis: report of a case and review of literature. Int J Surg. 2008;6:e36-9.
  • 3
    Azadi A, Fard PJ, Farahani MS, Khodadadi B, Almasian M. Anal tuberculosis: a non-healing anal lesion. IDCases. 2018;12:25-8.
  • 4
    Akgun E, Tekin F, Ersin S, Osmanoglu H. Isolated perianal tuberculosis. Neth J Med. 2005;63:115-7.
  • 5
    Tago S, Hirai Y, Ainoda Y, Fujita T, Takamori M, Kikuchi K. Perianal tuberculosis: a case report and review of the literature. World J Clin Cases. 2015;3:848-52.
  • 6
    Gupta PJ. Ano-perineal tuberculosis: solving a clinical dilemma. Afr Health Sci. 2005;5:345-7.
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    WHO. Global tuberculosis report; 2018
  • 8
    Tai WC, Hu TH, Lee CH, Chen CH, Huang CC, Chuah SK. Ano-perineal tuberculosis: 15 years of clinical experiences in southern Taiwan. Colorectal Dis. 2009;12:e114-20.
  • 9
    Sahu M, Mishra JK, Sharma A, Fatmi U. A prospective study on tubercular fistula in ano and its management. J Coloproctol (RIO J). 2017;37:211-5.
  • 10
    Neto IJ, Siá ON, Lopes EA, Macacari RL, Watté HH, Souza RF, et al. Perianal tuberculosis: a rare disease of late diagnosis. J Coloproctol (RIO J). 2014;34:124-7.

Publication Dates

  • Publication in this collection
    23 Mar 2020
  • Date of issue
    Jan-Mar 2020

History

  • Received
    5 Aug 2019
  • Accepted
    15 Sept 2019
  • Published
    30 Oct 2019
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