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.
Etiology
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]
Tuberculosis
The postulated mechanisms by which the tubercle bacilli reach the perianal region are as follows:
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Hematogenous spread from the primary lung focus in childhood, with later reactivation
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Ingestion of the bacilli in sputum from active pulmonary focus
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Direct spread from adjacent organs
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Transmission through lymph channels from infected nodes
Actinomycosis
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
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] :
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Mixed suppurative and granulomatous inflammation
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Tissue eosinophilia
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Thin-walled broad hyphae
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Zygospores resembling free-living amebae
Amebiasis
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.
Epidemiology
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
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.
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Perianal granuloma and multiple fistulous tracts in patient with severe perianal Crohn disease. Note noncutting seton in place.
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Perianal granuloma in patient with severe perianal Crohn disease.
