Perianal Granuloma

Perianal Granuloma

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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.

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.

For patient education information, see the Digestive Disorders Center, as well as Crohn’s DiseaseInflammatory 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.

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:

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. [3]

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 HIV infection. Risk factors also include male gender and diabetes. [4] The diagnosis requires sulfur granules in the infected tissue and a positive anaerobic culture result. [5]

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 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. [6]

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 [7, 8, 9] :

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 (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. [10] The occurrence of ileal involvement and perianal fistulization suggests that HPS and Crohn disease are truly associated. [11]

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 low in most Asian populations. [12]

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. Anoperianal tuberculosis may be associated with abdominal tuberculosis, either as an extension of the original lesion or because of spread via the lymphatics. [13] The incidence will vary with the incidence of tuberculosis in the overall population.

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.

El-Gazzaz G, Hull T, Church JM. Biological immunomodulators improve the healing rate in surgically treated perianal Crohn’s fistulas. Colorectal Dis. 2012 Oct. 14(10):1217-23. [Medline].

Le Q, Melmed G, Dubinsky M, McGovern D, Vasiliauskas EA, Murrell Z, et al. Surgical outcome of ileal pouch-anal anastomosis when used intentionally for well-defined Crohn’s disease. Inflamm Bowel Dis. 2013 Jan. 19(1):30-6. [Medline].

Ferreira Cardoso M, Carneiro C, Carvalho Lourenço L, Graça Rodrigues C, Folgado Alberto S, Alagoa João A, et al. Actinomycosis Causing Recurrent Perianal Fistulae. ACG Case Rep J. 2017. 4:e82. [Medline].

Coremans G, Margaritis V, Van Poppel HP, et al. Actinomycosis, a rare and unsuspected cause of anal fistulous abscess: report of three cases and review of the literature. Dis Colon Rectum. 2005 Mar. 48(3):575-81. [Medline].

Bauer P, Sultan S, Atienza P. Perianal actinomycosis: diagnostic and management considerations: a review of six cases. Gastroenterol Clin Biol. 2006 Jan. 30(1):29-32. [Medline].

Stark D, van Hal S, Hillman R, et al. Lymphogranuloma venereum in Australia: anorectal Chlamydia trachomatis serovar L2b in men who have sex with men. J Clin Microbiol. 2007 Mar. 45(3):1029-31. [Medline].

Hussein MR, Musalam AO, Assiry MH, et al. Histological and ultrastructural features of gastrointestinal basidiobolomycosis. Mycol Res. 2007 Aug. 111:926-30. [Medline].

Hassan HA, Majid RA, Rashid NG, Nuradeen BE, Abdulkarim QH, Hawramy TA, et al. Eosinophilic granulomatous gastrointestinal and hepatic abscesses attributable to basidiobolomycosis and fasciolias: a simultaneous emergence in Iraqi Kurdistan. BMC Infect Dis. 2013 Feb 20. 13:91. [Medline]. [Full Text].

Vikram HR, Smilack JD, Leighton JA, Crowell MD, De Petris G. Emergence of gastrointestinal basidiobolomycosis in the United States, with a review of worldwide cases. Clin Infect Dis. 2012 Jun. 54(12):1685-91. [Medline].

Kouklakis G, Efremidou EI, Papageorgiou MS, Pavlidou E, Manolas KJ, Liratzopoulos N. Complicated Crohn’s-like colitis, associated with Hermansky-Pudlak syndrome, treated with Infliximab: a case report and brief review of the literature. J Med Case Rep. 2007 Dec 8. 1:176. [Medline]. [Full Text].

Grucela AL, Patel P, Goldstein E, et al. Granulomatous enterocolitis associated with Hermansky-Pudlak syndrome. Am J Gastroenterol. 2006 Sep. 101(9):2090-5. [Medline].

De Matos V, Russo PA, Cohen AB, et al. Frequency and clinical correlations of granulomas in children with Crohn disease. J Pediatr Gastroenterol Nutr. 2008 Apr. 46(4):392-8. [Medline].

Gupta PJ. Ano-perianal tuberculosis–solving a clinical dilemma. Afr Health Sci. 2005 Dec. 5 (4):345-7. [Medline]. [Full Text].

Liu CK, Liu CP, Leung CH, Sun FJ. Clinical and microbiological analysis of adult perianal abscess. J Microbiol Immunol Infect. 2011 Jun. 44(3):204-8. [Medline].

Afsarlar CE, Karaman A, Tanir G, Karaman I, Yilmaz E, Erdogan D, et al. Perianal abscess and fistula-in-ano in children: clinical characteristic, management and outcome. Pediatr Surg Int. 2011 Oct. 27(10):1063-8. [Medline].

Sun X, Yuan L, Li Y, Shen B, Xie H, Liu X. Association of granulomas in mesenteric lymph nodes in Crohn’s disease with younger age and transmural inflammation. J Gastroenterol Hepatol. 2017 Aug. 32 (8):1463-1468. [Medline].

Ammoury RF, Pfefferkorn MD. Significance of esophageal Crohn disease in children. J Pediatr Gastroenterol Nutr. 2011 Mar. 52(3):291-4. [Medline].

Jayanthi V, Robinson RJ, Malathi S, et al. Does Crohn’s disease need differentiation from tuberculosis?. J Gastroenterol Hepatol. 1996 Feb. 11(2):183-6. [Medline].

Van der Bij AK, Spaargaren J, Morre SA, et al. Diagnostic and clinical implications of anorectal lymphogranuloma venereum in men who have sex with men: a retrospective case-control study. Clin Infect Dis. 2006 Jan 15. 42(2):186-94. [Medline].

Hyder SA, Travis SP, Jewell DP, et al. Fistulating anal Crohn’s disease: results of combined surgical and infliximab treatment. Dis Colon Rectum. 2006 Dec. 49(12):1837-41. [Medline].

Park EJ, Song KH, Baik SH, Park JJ, Kang J, Lee KY, et al. The efficacy of infliximab combined with surgical treatment of fistulizing perianal Crohn’s disease: Comparative analysis according to fistula subtypes. Asian J Surg. 2017 Aug 26. [Medline].

Ghahramani L, Minaie MR, Arasteh P, Hosseini SV, Izadpanah A, Bananzadeh AM, et al. Antibiotic therapy for prevention of fistula in-ano after incision and drainage of simple perianal abscess: A randomized single blind clinical trial. Surgery. 2017 Aug 16. [Medline].

Mathew R, Kumaravel S, Kuruvilla S, et al. Successful treatment of extensive basidiobolomycosis with oral itraconazole in a child. Int J Dermatol. 2005 Jul. 44(7):572-5. [Medline].

Bumb RA, Mehta RD. Amoebiasis cutis in HIV positive patient. Indian J Dermatol Venereol Leprol. 2006 May-Jun. 72(3):224-6. [Medline].

Malik A, Hall D, Devaney R, Sylvester H, Yalamarthi S. The impact of specialist experience in the surgical management of perianal abscesses. Int J Surg. 2011. 9(6):475-7. [Medline].

Burt Cagir, MD, FACS Clinical Professor of Surgery, The Commonwealth Medical College; Director, General Surgery Residency Program, Robert Packer Hospital; Attending Surgeon, Robert Packer Hospital and Corning Hospital

Burt Cagir, MD, FACS is a member of the following medical societies: American College of Surgeons, American Medical Association, Society for Surgery of the Alimentary Tract

Disclosure: Nothing to disclose.

Andres Fleury, MD Clinical Assistant Instructor, Department of Surgery, State University of New York Upstate Medical University; Resident, Department of Surgery, Robert Packer Hospital

Andres Fleury, MD is a member of the following medical societies: American College of Surgeons, American Medical Association, National Hispanic Medical Association

Disclosure: Nothing to disclose.

John Geibel, MD, DSc, MSc, AGAF Vice Chair and Professor, Department of Surgery, Section of Gastrointestinal Medicine, Professor, Department of Cellular and Molecular Physiology, Yale University School of Medicine; Director of Surgical Research, Department of Surgery, Yale-New Haven Hospital; American Gastroenterological Association Fellow

John Geibel, MD, DSc, MSc, AGAF is a member of the following medical societies: American Gastroenterological Association, American Physiological Society, American Society of Nephrology, Association for Academic Surgery, International Society of Nephrology, New York Academy of Sciences, Society for Surgery of the Alimentary Tract

Disclosure: Nothing to disclose.

Michael A Grosso, MD Consulting Staff, Department of Cardiothoracic Surgery, St Francis Hospital

Michael A Grosso, MD is a member of the following medical societies: American College of Surgeons, Society of Thoracic Surgeons, and Society of University Surgeons

Disclosure: Nothing to disclose.

Juan B Ochoa, MD Assistant Professor, Department of Surgery, University of Pittsburgh School of Medicine; Medical and Scientific Director, HCN, Nestle Healthcare Nutrition

Disclosure: Nothing to disclose.

Jan Rakinic, MD Chief, Section of Colorectal Surgery, Program Director, SIU Residency in Colorectal Surgery, Southern Illinois University School of Medicine

Jan Rakinic, MD is a member of the following medical societies: American College of Surgeons, American Medical Association, American Medical Women’s Association, American Society of Colon and Rectal Surgeons, and Illinois State Medical Society

Disclosure: Nothing to disclose.

Carol E H Scott-Conner, MD, PhD Professor, Department of Surgery, University of Iowa College of Medicine

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Perianal Granuloma

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