Why is a haemorrhoid never infected?

Abstract

A breach in the anal and perianal epithelium can occur as a result of daily natural events such as passing a hard stool, prolapsing a haemorrhoid or even excessive wiping with toilet paper. Additionally, it may occur as a result of a fissure or surgical wound such as after haemorrhoidectomy or fistulotomy. If the immune system is healthy then significant infection rarely, if ever, occurs. In wounds outside the anal region, a concentration of 10 bacteria per gram of biopsied tissue is associated with the development of infection, regardless of the aerobic or facultative anaerobic nature of the bacteria [1]. Therefore, given the high bacterial load in the anal canal, one would anticipate that any epithelial injury would lead to fulminant infection and disturbed wound healing but this is not the case. In 1991, De Paula et al. examined the anal wounds of 20 patients who underwent open haemorrhoidectomy and found that half the anal wounds were colonized by greater than 10 bacteria per gram during serial cultures. However, this high bacterial load did not impair wound healing despite the presence of an aerobic dominant polymicrobial pattern including facultative pathogens [2]. A recent meta-analysis encompassing 1326 patients revealed that post-operative wound infection is only 1.7 percent for both open and sutured haemorrhoidectomy [3]. Furthermore, reduction of the bacterial load at the haemorrhoidectomy wound by topical antibiotics does not improve the wound healing or decrease local infection [4]. Because of the minor role of bacterial load in wound healing after haemorrhoidectomy, unique local immune-inflammatory defences must play a role in the higher resistance to the presence of contamination in the anal canal. Even strangulated haemorrhoids seldom associated with infection requiring antibiotics. However, if the immune system is impaired, as it is for patients with HIV/AIDS or patients having chemotherapy for leukaemia, the most minor anal breech, e.g., an acute fissure, can lead to overwhelming sepsis [5]. It is a commonly held belief that it is good blood supply that explains good wound healing in the anus and for that matter throughout the gastrointestinal tract, mouth to anus. However, immune deficiency results in life-threatening infection despite the good blood supply. The obvious exception to ‘infection control’ in the anal region is cryptoglandular infection (anal abscess and fistula). Recent studies revealed the absence of viable bacteria in the perianal fistula tract [6,7]. There is some evidence to suggest that the chronic inflammation in perianal fistulas occurs as a result of a defect in the local immune system of the anal gland ducts [8]. Matzinger believes that it is not the presence of pathogens that induces an immune response, but the danger signals generated from injured or damaged cells and tissues [9]. The response to these signals differs between columnar epithelium and squamous epithelium. The dual-allergen exposure hypothesis suggests that early exposure to antigens through the skin can lead to allergy, while exposure to the columnar epithelium at an early age may actually result in tolerance [10]. Anal gland ducts are located in the crypts of Morgagni, at the junction of columnar and squamous epithelium. In this zone, there is a transition between these two different immunological pathways, and these anogenital transition zones are prone to chronic inflammation in case of tissue damage [11]. The local chronic inflammation could lead to tissue stem cell failure or change in the differentiation pattern of epithelial stem cells, explaining the non-healing character of perianal fistulas [8]. The entire gastrointestinal tract clearly has a specialised mucosal immune system. This extends from the mouth to the anus. It protects the human ‘host’ from the resident microbiome with micro-organisms in the same order as the host’s total cell count. Little is known about the immune subsets that reside within the anal canal. It is difficult to obtain specimens of the different regions of the anal canal from the same healthy subject. Another challenge is that to harvest cells from these tissues, different digestion strategies are necessary [12]. Using healthy human tissue derived from surgery, a recent study was the first to show the unique repertoires of epithelial mononuclear phagocytes that reside in squamous anogenital mucosal tissues (anal canal, vagina and inner foreskin, glans penis and fossa navicularis) which differed considerably from abdominal skin and outer foreskin [13]. It will be of great interest to clarify how these specific cells interact with T-cells and establish or suppress inflammation. A complete understanding of the repertoire of all immune cells in the anal canal and all other anogenital tissues is underway. This project, The Human Cell Atlas, aimed to create a comprehensive reference map of all of the estimated 37 trillion cells that make up a human body [14]. By decoding the genes active in single cells from all the different human tissues, and investigating how these cells interact with other cells, the map will offer insight into how the body works and what goes wrong in disease. The anus is but the distal end of the amazing gastrointestinal tract. Studies to explain clinical