Perianal Ulcerative Tuberculosis: A Case Report

Background: Extra pulmonary tuberculosis (TB), with or without pulmonary lesions, can be found in any organ, including cutaneous involvement, which is a relatively uncommon manifestation and can be acquired either exogenously or endogenously. Among them, rare individuals develop tuberculosis cutis oricialis (TCO) of the mucosa and oricial skin (nose, mouth and anus). Those patients usually suffer from both advanced TB of the gastrointestinal tract, lungs, or genitourinary tract and dramatically impaired cell-mediated immunity. Perianal TB is an extremely rare form which anal mucocutaneous junction becomes infected when mycobacteria are introduced by autoinoculation from gastrointestinal tract draining active TB infection. Due to its rarity, perianal TB could be misclassied as other diseases (e.g. inammatory bowel disease) and leads to delayed managements in the clinical practise. Case presentation: We report a 73-year-old male patient presented with a refractory perianal ulcer. The diagnosis of TB is rendered by histological examination and conrmed by Polymerase chain reaction (PCR). The lesion was responsive to initial short-course treatment of 2HRZE/4HR antitubercular regimen, but shortly relapsed. The patient was nally cured by supplemental intensive treatment of 3HRZE/6HR regimen. Conclusions: Perianal TB is extremely rare but need to be excluded in immunosuppressed patients with refractory perianal ulcer that do not respond to antibacterial treatment. Microbiological tests should be performed for any suspicious persistent nonhealing wound or ulcer. Differential diagnoses, especially inammatory bowel disease, are important. Early and sucient antitubercular treatment should be initiated to minimize morbidity.

diagnosis of TB is rendered by histological examination and con rmed by Polymerase chain reaction (PCR). The lesion was responsive to initial short-course treatment of 2HRZE/4HR antitubercular regimen, but shortly relapsed. The patient was nally cured by supplemental intensive treatment of 3HRZE/6HR regimen.
Conclusions: Perianal TB is extremely rare but need to be excluded in immunosuppressed patients with refractory perianal ulcer that do not respond to antibacterial treatment. Microbiological tests should be performed for any suspicious persistent nonhealing wound or ulcer. Differential diagnoses, especially in ammatory bowel disease, are important. Early and su cient antitubercular treatment should be initiated to minimize morbidity.

Background
Although there has been progress in the delivery of tuberculosis (TB) care and a decline in TB-related deaths globally, TB still remains a major public health concern, especially in developing countries (1). Extrapulmonary TB can be found in any organ of the body, with or without pulmonary lesions, constituted 15% of the seven million incident cases according to World Health Organization data (1). Cutaneous involvement is a relatively uncommon manifestation of extrapulmonary TB and accounts for less than 2% of all extrapulmonary manifestations (2).
Tuberculosis cutis ori cialis (TCO) is rare and usually develops in individuals with both advanced TB of the gastrointestinal tract, lungs, or genitourinary tract and dramatically impaired cell-mediated immunity (3). The distal and lateral tongue is the most frequent sites but perianal lesions were also reported (4), especially in HIV infection or chemoradiotherapy (5,6). Ghiya  Perianal TB comes in different presentations, including ulceration, stula, verrucous, lupoid and military.
The majority English literatures and almost all Chinese literatures focused on anal stula and perianal abscess of anorectal TB. Recently Garg et al. analyzed a set of 410 anal stula patients, which found that 57 patients positive for TB in 410 patients, this is similar to his review of literature (7). Tuberculous stula has no preferred site to differ from a cryptoglandular stula, but TB was associated with more complex and recurrent stulas. However, there are only limited case reports on ulceration form of perianal TB. Our experience of managing the refractory perianal ulcer on an elder male with uneventful medical history could shed some light on diagnosis and treatment for ulcer form perianal TB.

Case Presentation
A 73-year-old heterosexual man presented with painful perianal ulceration for 6 months. He reported a small unpainful lump in perianal area initially and rapidly progressed to a super cial ulcer with thin purulent exudate. He had a prior biopsy performed at outside community hospital, which showed unspeci c atypical hypertrophic squamous epithelium. Treatment with oral antibiotics, topical dexamethasone and antibiotic ointment was ineffective. His past medical history was otherwise unremarkable. In particular, he had no history of TB or known contact with the disease.
Physical examination showed an afebrile, well-nourished male with 5 cm ulcer in the right perianal region with a nearly round shape (Fig. 1). The ulcer was deep to subcutaneous adipose tissue in the center but was super cial along periphery with a clear "punched-out" margin. Purulent exudate was seen. The patient was given a four-drug antitubercular regimen with short course, which included isoniazid 300mg qd, rifampicin 450mg qd, pyrazinamide 1500mg qd and ethambutol 750mg qd, the course of treatment was four drugs for two months followed by two drugs (isoniazid and rifampicin) for four months. Perianal ulcer was shrunken remarkably within six weeks, and healed about fourteen weeks later. Unfortunately, four weeks after drug withdrawal, ulceration relapsed at the central of the primary lesion.
The patient started second round of antitubercular treatment with long-course, which were four drugs for three months followed by two drugs for six months. The recurrent small ulcer was completely healed four weeks from the beginning of the second course of treatment. No recurrence was detected at the last follow-up nineteen months after the end of the second round of treatment. This study is approved by Ethics Committee of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine. Reference number: 20210203-30. Informed consent to publish this case report was obtained from the patient.

Discussion And Conclusions
Perianal TB is an extremely rare form of TCO. The pathogenesis for perianal TB is usually considered as a result of spreading from TB lesion in the lungs. Ingestion of the bacilli from sputum may lead to invasion of the gastrointestinal wall or ori ce mucosa or adjacent skin (8). However, Akgun et al. presented a case of isolated perianal TB without pulmonary or gastrointestinal involvement (9).
Diagnosis of our case is challenging. The patient presented with no history of active TB with negative skin test and absence of TB antibody. Tuberculin skin tests could be negative in patients with TCO due to associated impairment in host immunity. However, our patient was not on any immunosuppressive therapy or have a history of immunosuppression. His HIV screening is also negative. Colonoscopy ruled out TB in colon, including ileocecal region, which is the most frequent predilection site accounting for more than 85% in the gastrointestinal tract TB. The only evidence suggestive of TB is the image nding of streak and nodular opacities in both upper lungs. Up to 5% of patients with upper lobe brocalci c changes thought to be indicative of healed primary TB (10). We speculated that this patient had been infected but the disease was well con ned by host immune system until perianal lesion presented. M. tuberculosis released with sputum, ingested to GI tract and inoculated to perianal mucosa and skin.
De nite diagnosis of perianal TB depends on pathologic and M. tuberculosis identi cation by laboratory studies. The typical histological nding is tuberculoid granuloma, an accumulation of epithelioid histiocytes and Langhans-type giant cells that demonstrates a variable degree of central caseation necrosis and a peripheral rim composed of numerous lymphocytes. However, many clinical cases lack these typical histological characteristics. An acid-fast stain (Ziehl-Neelsen) can help to identify the bacilli, but positive bacteria visualized on a slide may represent M. tuberculosis or nontuberculous mycobacteria, therefore, culture or nucleic acid ampli cation tests is required for species identi cation. Although conventional culture is the most sensitive tool for detection of TB, regular culture usually reveals contamination only, because the M. tuberculosis grows very slowly and perianal tuberculosis was often companied by nonspeci c infection. New diagnostic technique, such as ampli cation by PCR has been successfully performed, which can detect the presence of the bacterial DNA with a higher sensitivity compared to histology (7,11) .
It is essential to distinguish perianal TB from perianal involvement of Crohn's disease because the latter is much more common compare to TCO and initiation of immunosuppressive therapy in a patient with tuberculous enteritis can lead to dissemination (12,13). Zhao et al. found that TB-IGRA was a useful indicator in the differential diagnosis of intestinal tuberculosis and Crohn's disease (14). Other differential diagnosis includes sarcoidosis, neoplasm, other microorganism infections like amebiasis, Yersinia infection and actinomycosis (15).
The treatment of perianal tuberculosis depends on the form of the lesion. Ulcerative lesion do not need surgical procedure except a biopsy (5), whereas TB stula or abscess need local drainage combined with antitubercular treatment. Six months short course antitubercular treatment was reported successfully applied to cure perianal tuberculosis (5,13) and directly observed treatment short course was reported as an effective strategy in cutaneous tuberculosis (16). However, in our case, the perianal ulcer shortly relapsed after the end of 2HRZE/4HR antitubercular treatment. He was nally cured by an additional 3HRZE/6HR regimen. There have been physicians preferred to extend treatment duration to at least nine months (17). We recommend an initial short course treatment, but if disease recurrent, a more powerful antitubercular treatment should be applied with a course of at least nine months.

Consent for publication
Informed consent to publish this case report was obtained from the patient and a statement to this effect is also included in the manuscript.

Availability of data and materials
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Competing interests
The authors declare that they have no competing interests.

Funding
No funding sponsors.