Perianal Granuloma

Updated: Oct 09, 2013
  • Author: Burt Cagir, MD, FACS; Chief Editor: John Geibel, MD, DSc, MSc, AGAF  more...
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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 is the most common cause of perianal granulomatous disease in Western nations. Elsewhere, the incidence of non-Crohn perianal granuloma varies, but it may be more common than in the United States. (See the images below.)

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

The incidence of perianal granuloma of non-Crohn disease 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.

Patient education

For patient education information, see the Digestive Disorders Center, as well as Crohn’s Disease, Inflammatory Bowel Disease, and Anal Abscess.



The following causes of perianal granuloma are reported in the medical literature. Crohn disease 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 Crohn disease is not yet known. An infectious etiology is thought to be responsible, as are alterations in the immune response. Granulomas in Crohn disease 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 Crohn disease may be sarcoid-type or nonspecific. [1, 2]


The postulated mechanisms by which the tubercle bacilli reach the perianal region are as follows: (1) hematogenous spread from the primary lung focus in childhood, with later reactivation; (2) ingestion of the bacilli in sputum from active pulmonary focus; (3) direct spread from adjacent organs; and (4) 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 that needs to be recognized, because it can be cured with very specific treatment.

A israelii 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 chronic suppurative perianal disease in patients who are immunocompromised or who have human immunodeficiency virus (HIV) infection. Risk factors also include male gender and diabetes. [3] The diagnosis requires sulfur granules in the infected tissue and a positive anaerobic culture result. [4]

Lymphogranuloma venereum

Lymphogranuloma venereum (LGV) is a sexually transmitted disease caused by Chlamydia trachomatis; specifically, serovars L1, L2, and L3. "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 Crohn disease.

If left untreated, lymphogranuloma venereum 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. [5]


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. There are 15 human cases 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: (1) mixed suppurative and granulomatous inflammation, (2) tissue eosinophilia, (3) thin-walled broad hyphae, and (4) zygospores resembling free-living amoebae. [6, 7, 8]


Amebiasis is a very rare protozoan opportunistic infection caused by Entamoeba histolytica; the condition is seen in immunocompromised patients (ie, 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 Crohn disease. [9] The occurrence of ileal involvement and perianal fistulization suggests that HPS and Crohn disease are truly associated. [10]

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 Crohn disease is 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 rare in most Asian populations. [11]

The remaining causes of perianal granulomatous disease are extremely rare. For example, tubercular perianal disease accounts for less than 10% of all perianal disease and 0.7% of all tuberculosis cases. Ano-perianal tuberculosis may be associated with abdominal tuberculosis, either as an extension of the original lesion or because of spread via the lymphatics. [12] The incidence will vary with the incidence of tuberculosis in the overall population.


History and Physical Examination

Clinical presentation may vary widely from asymptomatic with minimal physical signs to recurrent or persistent problems that are very distressing. Disease presentation 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. [13]

Crohn disease

In about 9% of patients with Crohn disease, 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 compared with the more typical chronic fistula-in-ano. [14]

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


Anorectal tuberculosis often manifests as complex fistulous disease that has failed 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 radiographic chest films. [15] 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, although 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. [12]

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 Crohn disease with perianal localization. [16]


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


Lab Studies

Laboratory tests 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.

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. [17] 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 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, Procedures, and Histology

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 evaluating the possibility of perianal tuberculosis; 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 Crohn disease.
  • Upper GI/small bowel series - Used to evaluate the upper GI tract and terminal ileum for Crohn disease.

[#WorkupDiagnosticProcedures] Procedures

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 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, although this is more rare in Crohn disease than commonly believed. Other infectious agents may be identified with histopathology (eg, fungi, parasites).


Pharmacologic Therapy

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.

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, but long-term fistula healing rates are low. [18]

Antitubercular therapy is instituted for tubercular causes, usually with 3-4 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 penicillin G (20MU/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. [4]

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. [19]

Tetracyclines remain the treatment of choice for lymphogranuloma venereum. Doxycycline or a macrolide antibiotic is required for 3 weeks. [5] The 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. [20]

Failure of corticosteroids and azathioprine in treating perianal lesions in Hermansky-Pudlak syndrome has led to the use of infliximab with clinical improvement. [9]


Preoperative, Intraoperative, and Postoperative Details

Preoperative details

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.

Intraoperative 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. [21] 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, or both.

Lymphogranuloma venereum can cause extensive tissue destruction, sometimes destroying the rectovaginal septum and leaving the patient with a cloacal-like abnormality. Reconstruction in this setting can be exceedingly difficult, considering 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 details

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. Crohn disease 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. Betadine should not be used for dressings, because it retards healing.


Surgical Complications

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.



Prognosis depends on the degree of anatomic changes, whether postsurgical or directly due to the underlying disease, and the ability to treat the causative problem. Intrinsic medication toxicities, which are often significant, are another important prognostic consideration.

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