Perianal Granuloma

Updated: Dec 01, 2022
Author: Burt Cagir, MD, FACS; Chief Editor: John Geibel, MD, MSc, DSc, AGAF 


Practice Essentials

A spectrum of diseases, mostly infectious or inflammatory conditions, can produce granulomas in the perianal region and perineum. Perianal granulomas present some degree of diagnostic difficulty, with standard histologic diagnosis often doing little to clarify their etiology. The treatment of these lesions varies from entity to entity.

A granuloma is a nodule consisting of mainly epithelioid macrophages. The nodule may also consist of other cells (eg, inflammatory, immune) and extracellular matrix. A granuloma is often surrounded by a lymphocyte cuff and fibrosis.

Granulomas can form when the immune system attempts to fend off and isolate an antigen, such as an infectious pathogen or a foreign body. In many cases, however, granulomas form without apparent cause in autoimmune disorders. Crohn disease (CD) is the most common cause of perianal granulomatous disease in Western nations.[1, 2]  Elsewhere, the incidence of non-CD perianal granuloma varies, but it may be more common than in the United States.

The incidence of perianal granuloma of non-CD etiology seems to be increasing worldwide, albeit more slowly in the Western world than in the developing world. Many of the infectious agents responsible are resistant to conventional therapy. Early diagnosis is nearly unknown. This group of diseases should be considered in the differential diagnosis whenever an unusual lesion is found in the perianal region or when no response occurs to conventional surgical treatment.

Knowledge of the anatomy of the male and female perineal floor, as well as of perianal anatomy, is required of the surgical specialist treating complications of perianal granulomatous disease. If the inflammatory process extends anteriorly, consultation with urologic or gynecologic specialists can be invaluable.

Medical therapy directed at the causative factor is usually initiated following disease recurrence after several trials of surgical treatment. Specific medical therapy depends on the etiology defined.


The following causes of perianal granuloma are reported in the medical literature. CD is by far the most common cause, followed by tuberculosis and actinomycosis, both of which must be considered in the evaluation of the perianal fistula or fissure that does not heal or that recurs after appropriate treatment.

Crohn disease

The cause of CD is not yet known. An infectious etiology is thought to be responsible, as are alterations in the immune response. Granulomas in CD have been postulated to represent an adaptive mechanism for removal or localization of the causative agent because patients with a long clinical history show fewer granulomas than do those with a shorter clinical history. The granulomas of CD may be sarcoid-type or nonspecific.[3, 4, 5]


The postulated mechanisms by which the tubercle bacilli reach the perianal region are as follows:

  • Hematogenous spread from the primary lung focus in childhood, with later reactivation
  • Ingestion of the bacilli in sputum from active pulmonary focus
  • Direct spread from adjacent organs
  • Transmission through lymph channels from infected nodes


Primary anal actinomycosis of cryptoglandular origin is due to Actinomyces israelii. Actinomycosis represents a very rare cause of anal suppurative disease; recognition is important because this condition can be cured with very specific treatment.[6]

A israelii organisms are gram-positive, non-spore-forming, non-acid-fast, facultative anaerobic rods. The pathogenesis is not clearly understood, but the source of infection comes from the gastrointestinal (GI) tract. What occasionally converts this saprophyte into a pathogen is not clear. It should be considered in patients with chronic suppurative perianal disease who are immunocompromised or who have HIV infection. Risk factors also include male gender and diabetes.[7] The diagnosis requires sulfur granules in the infected tissue and a positive anaerobic culture result.[8]

Lymphogranuloma venereum

Lymphogranuloma venereum (LGV) is a sexually transmitted disease caused by Chlamydia trachomatis—specifically, serovars L1, L2, and L3. The L serovars are invasive and cause severe inflammation with granuloma formation. LGV can present as an inguinal syndrome with painful inguinal lymphadenopathy or as an anorectal syndrome with acute proctitis and excessive proliferation of perirectal lymphatic tissue that may mimic CD.

If left untreated, LGV may cause fistulae, strictures, and genital elephantiasis. The diagnosis is based on deoxyribonucleic acid (DNA) detection via polymerase chain reaction (PCR) assay in infected tissue. Correct treatment consists of doxycycline or a macrolide for 3 weeks.[9]


Basidiobolomycosis is a very rare infection caused by Basidiobolus ranarum in immunocompromised hosts. It is a fungus found in the dung of amphibians, reptiles, and bats. Only a very few human cases have been described in the literature. The disease is usually reported around river banks in Africa and South America and typically involves children.

The diagnosis is based on the following[10, 11, 12] :

  • Mixed suppurative and granulomatous inflammation
  • Tissue eosinophilia
  • Thin-walled broad hyphae
  • Zygospores resembling free-living amebae


Amebiasis is a very rare protozoan opportunistic infection caused by Entamoeba histolytica; the condition is seen in immunocompromised patients (eg, persons with HIV infection). The etiologic theories include sexual transmission or spread from the large intestine. Perianal amebiasis occurs when the invasive amoebae escape from the colon, penetrating the perianal area and causing lysis of the skin and subcutaneous necrosis.

Amebiasis can present as multiple tender ulcers with irregular margins covered with necrotic slough. Treatment is based on oral metronidazole. This pathology should be kept in mind for every patient with HIV with nonhealing perianal granuloma.

Hermansky-Pudlak syndrome

Hermansky-Pudlak syndrome (HPS) is a rare, inherited, autosomal recessive disorder consisting of a triad of albinism, increased bleeding tendency secondary to platelet dysfunction, and systemic complications associated with ceroid depositions within the reticuloendothelial system.

HPS has been associated with GI complications related to granulomatous colitis, with pathologic features suggestive of CD.[13] The occurrence of ileal involvement and perianal fistulization suggests that HPS and CD are truly associated.[14]

Other causes

Other causes of perianal granuloma include foreign body reaction, schistosomiasis, and granuloma pyogenicum. Schistosomiasis can produce genital and perigenital granulomas during the oviposition stage.


The prevalence of CD has been estimated at 3-5 cases per 100,000 persons in most areas of the world. Prevalence is less in African Americans than in whites and is quite low in most Asian populations.[15]  Although CD and ulcerative colitis (UC) can occur at any age, people are more frequently diagnosed between the ages of 15 and 35. As many as one third of patients with CD are diagnosed before the age of 21 years.

In the United States, as many as 70,000 new cases of inflammatory bowel disease (IBD) are diagnosed each year.[16] Extrapolation from Olmsted County study data to the current United States population has suggested that approximately 780,000 Americans currently have CD and 907,000 currently have UC. In the United Kingdom, it has been estimated that at least 115,000 people currently have CD, given an estimated CD prevalence of 157 per 100,000.[17]

The remaining causes of perianal granulomatous disease are extremely rare. For example, tubercular perianal disease accounts for fewer than 10% of all cases of perianal disease and fewer than 0.7% of all tuberculosis cases. Anoperianal tuberculosis may be associated with abdominal tuberculosis, either as an extension of the original lesion or because of spread via the lymphatics.[18] The incidence will vary with the incidence of tuberculosis in the overall population.


Prognosis depends on the degree of anatomic changes, whether postoperative or directly due to the underlying disease, and on the ability to treat the causative problem. In patients with CD, the presence of granulomas may reflect a more aggressive disease phenotype.[19]

Intrinsic medication toxicities, which are often significant, are another important prognostic consideration.

The noncompliant patient presents another facet of prognosis. Therapy for many of these unusual diseases can be lengthy and may cause unpleasant adverse effects. A great deal of family or community support may be needed for patients to accept and complete therapy.



History and Physical Examination

The clinical presentation of perianal granuloma may vary widely, ranging from asymptomatic with minimal physical signs to recurrent or persistent problems that are highly distressing. Manifestations of disease may range from an asymptomatic nodule to a simple fistula or a draining sinus to the complex presentations of multiple, draining fistulas or sinuses and wide involvement, with undermining of previously normal tissues.[20]

Crohn disease

In about 9% of patients with Crohn disease (CD), anorectal manifestations are the first indication of the disease (see the images below). The lesions are usually abscesses or fistulas and may be solitary or multiple, simple or complex. Crohn fistulae may look relatively indolent in comparison with the more typical chronic fistula-in-ano.[21, 22]

Perianal granuloma and multiple fistulous tracts i Perianal granuloma and multiple fistulous tracts in patient with severe perianal Crohn disease. Note noncutting seton in place.
Perianal granuloma in patient with severe perianal Perianal granuloma in patient with severe perianal Crohn disease.


Anorectal tuberculosis often manifests as complex fistulous disease that has not been sufficiently well managed by initial surgical therapy. Approximately 10% of patients with anorectal tuberculosis have active pulmonary tuberculosis as well, and nearly all of the remaining patients have evidence of old pulmonary tuberculosis on chest radiographs.[23]  The diagnosis of tubercular anorectal disease should be considered whenever anorectal fistulas or abscesses heal poorly or recur after initial therapy.

Most cases of anorectal tuberculosis are primary presentations, though secondary infection of the pilonidal sinus has been reported. The most frequent presentations are suppurations and fistulae, but the disease can also present as anal pain, fever, weight loss, or perianal nonhealing ulcers.[18]

The typical histologic lesion is the epithelioid and giant cell tubercle around a zone of caseous necrosis, but the pathognomonic presence of caseation is not constant and presents a diagnostic challenge, especially in cases of coexisting CD with perianal localization.[24]


The remaining causes are clarified with the help of tissue biopsies for histopathologic, serologic, and other special testing.



Laboratory Studies

Laboratory tests in patients with perianal granuloma are of help only after it has become obvious that the disease process is due to some unusual causative organism. In general, laboratory tests are not diagnostic in Crohn disease (CD).

The choice of laboratory tests is dictated by the clinical presentation, and results are more indicative of the degree of illness than of the etiology.[25]  When an unusual etiology for the disease process becomes apparent, directed investigative tests become useful.

Superficial wound cultures are usually of no diagnostic use and yield only colonizing bacteria (usually of skin or gastrointestinal [GI] tract origin) rather than true pathogens. However, biopsy of a nonhealing or recurrent wound with stains and culture of the tissue may yield identification.

Other tests that may be useful include the following:

  • Potassium hydroxide (KOH) preparation - Can help to identify yeast organisms
  • Acid-fast bacillus (AFB) staining - Although commonly performed in this setting, this usually yields negative results (tissue cultures produce a higher yield but take 7-21 days)
  • A Tzanck preparation - May be helpful in excluding herpes

Imaging Studies

Imaging tests that aid in the diagnosis and evaluation of causative diseases in perianal granuloma include the following:

  • Radiography - Should be obtained when the possibility of perianal tuberculosis is being evaluated; nearly all patients with perianal or anorectal tuberculosis have chest radiographic findings suggestive of old or active pulmonary tuberculosis
  • Barium enemas - May be used to evaluate the colorectal mucosa in the differential diagnosis of CD
  • Upper GI/small-bowel series - Used to evaluate the upper GI tract and terminal ileum for CD


Endoscopic evaluation may aid in obtaining material for pathology and culture. Proctoscopy is probably most useful. Sigmoidoscopy and colonoscopy can be helpful in the evaluation of inflammatory bowel disease (IBD) or in more proximal involvement of the colon with infectious agents.

Examination under anesthesia, with biopsy or scraping of wounds or ulcerations, can also yield material for diagnostic evaluation.

Histologic Findings

Regular histopathology should always be requested on tissue specimens. The presence of so-called sulfur granules is characteristic of Actinomyces. Granulomas, caseating or noncaseating, may be observed, though this is more rare in CD than is commonly believed. Other infectious agents (eg, fungi and parasites) may be identified with histopathology.



Medical Care

Medical therapy directed at the causative factor is usually initiated when the disease recurs after several trials of surgical treatment. Specific medical therapy depends on the etiology defined.

Some studies show that infliximab therapy in combination with examination under anesthesia/seton drainage is a safe and effective short-term treatment for fistulating anal Crohn disease (CD), but long-term fistula healing rates are low.[26, 27]  A study by Lawrence et al found that in CD patients with granulomas, anti–tumor necrosis factor (TNF) therapy greatly reduced the risk of perianal fistula.[28]

Antitubercular therapy is instituted for tubercular causes, usually with three or four drugs for a prolonged course of therapy, and also for pulmonary disease, if present. The causative organisms often display resistance to multiple drugs.

First-line medical treatment of actinomycosis is penicillin or a penicillin-related antibiotic. Classically, intravenous (IV) penicillin G (20 MU/day) is recommended for 4-6 weeks, followed by oral amoxicillin for up to 1 year. The exact duration of therapy depends on the severity of the disease and the immune status of the patient.[8, 29]

Antifungals are used when a fungus is believed to be the etiology. The specific drug depends on the fungus identified. The treatment of choice for basidiobolomycosis is ketoconazole or itraconazole.[30]

Tetracyclines remain the treatment of choice for lymphogranuloma venereum (LGV). Doxycycline or a macrolide antibiotic is required for 3 weeks.[9]  Surgical treatment of this condition is particularly difficult because of the degree of tissue destruction often observed in long-standing cases.

Perianal amebiasis in patients with HIV is treated with HIV medications, in order to improve the individual’s immune status, plus oral metronidazole.[31]

Failure of corticosteroids and azathioprine in treating perianal lesions in Hermansky-Pudlak syndrome has led to the use of infliximab with clinical improvement.[13]

Surgical Care

Preparation for surgery

Knowledge of the correct diagnosis greatly increases the likelihood that surgical therapy will be successful in perianal granulomatous disease. Since the diagnosis is often not considered until the disease is advanced or has recurred, surgeons must endeavor to maintain a high index of clinical awareness whenever a presentation seems unusual.

Operative details

Surgical intervention is predicated on presentation. If symptoms are related to fistulous disease, procedures for fistulas may be considered. If the fistula is associated with a perirectal abscess, drainage should be performed to control the sepsis source.

Surgical therapy is very straightforward, and the various procedures used in the surgical treatment of perianal granulomatous disease are largely those also used in the treatment of perianal abscess and fistula. Esoteric causes are not sought until after the disease has recurred, sometimes after several surgical procedures.[32]  For symptomatic granulomas, excision may be chosen to relieve symptoms. Simple granulomas may be excised, with the skin left open to close by secondary intention.

Unusual lesions should be generously biopsied, not necessarily excised, because this may not be necessary when the etiology is known. Pus must be drained, taking care to preserve sphincter function and continence. If unforeseen extensive fistulous tracts are found, simple drainage is the correct action, with postoperative investigation of the anatomy using magnetic resonance imaging (MRI), endorectal or endoanal ultrasonography (US), or both.

LGV can cause extensive tissue destruction, sometimes destroying the rectovaginal septum and leaving the patient with a cloacalike abnormality. Reconstruction in this setting can be exceedingly difficult, given that the rectum and, often, the sigmoid are also abnormal, thus making diversion with an end colostomy the only option. HIV testing should be considered.

Postoperative Care

Nonhealing or recurrence after an otherwise simple perianal operative procedure must prompt evaluation of causes other than cryptoglandular disease of the anorectum, sebaceous cysts, or pilonidal disease. CD is always prominent in the differential diagnosis, and tuberculosis is becoming so.

Wounds are cared for as after any anorectal surgical procedure, with damp-to-dry dressings of isotonic sodium chloride solution, avoidance of constipation and diarrhea, and careful cleansing of the region. Granulation may be slow in the patient who is immunocompromised. On occasion, sharp debridement may be needed. If the wound is granulating poorly, switching from isotonic sodium chloride solution to a quarter-strength Dakin solution for 5-10 days can be helpful. Povidone-iodine should not be used for dressings, because it retards healing.


Aside from recurrence, which may occur until identification of the true etiology of the granulomas, the complications are chiefly those of any anorectal surgical procedure.

However, patients may undergo multiple procedures before the cause is identified, and the underlying etiology may cause anatomic changes in the perianal region as well. Because of this, these patients are at higher risk for complications, such as sphincter dysfunction with impaired continence, stenosis, mucosal ectropion, and rectovaginal fistula. These patients also bear the morbidity associated with the underlying etiology. Some of them may also be immunocompromised.