Nonfistulizing Perianal Crohn's Disease

Abstract

Perianal Crohn's disease (CD) includes a wide range of nonfistulizing sequela, including fissures and ulcers, skin tags, anal stricture, and anal cancer. Symptoms related to perianal manifestations of CD are often disabling and have a significant impact on patients' quality of life. They include pain, drainage, bleeding, difficulty with hygiene and may cause secondary difficulties with sexual and defecatory dysfunction. The care of patients with perianal CD requires a thoughtful approach, including detailed history taking, physical examination, and often multidisciplinary care teams to maximize quality of life and ameliorate symptoms.

Nonfistulizing perianal Crohn's disease (CD) captures a large spectrum of conditions with varying underlying etiologies: from benign to malignant, intermittently symptomatic to chronic, and with or without associated luminal pathology. Approximately 40% of patients with CD patients report perianal disease and the estimated probability of having a perianal lesion other than fistula is 30% at 10 years. ^{1 2}

Perianal pathology can cause a range of disabling symptoms and is associated with a significant negative impact on quality of life for patients. ^{3 4} Appropriate evaluation and treatment includes detailed history and physical examination, selective use of imaging and diagnostic tests, and perhaps most importantly, fostering a close and candid rapport with patients and setting appropriate expectations. A multidisciplinary approach is often necessary, as management intersects medical and surgical strategies. ^{1 2}

Anal Fissures and Ulcers

Epidemiology, Risk Factors, and Etiology

The inciting event for anal fissures in patients with CD is thought to be trauma to the anal canal. This may be due to hard stools or frequent watery bowel movements. In one large series of 569 Crohn's patients, 8% reported a history of anal fissure and another 6% developed an anal fissure during the period of study observation. ¹ CD patients are more likely to have multiple fissures, nonmidline fissures, or painless fissures than patients with idiopathic fissures. However, a significant proportion of CD patients present with painful, midline fissures. Sweeney et al. reported 44% of CD patients with anal fissures reported associated pain and 87% were located at the midline. ⁵ The CD perianal environment is one of acute and chronic inflammation and anal trauma secondary to frequent stooling, consistent with the theory that fissures are a result of trauma, inflammation, or ischemia of the anal tissue.

Clinical Presentation and Classification

Anal fissures can be classified as idiopathic or atypical. Idiopathic fissures are generally located in the anterior (10%) or posterior (90%) midline. The conventional teaching is that an off-midline fissure should raise suspicion for CD. While this is true, it is important to recognize that even in Crohn's patients, most fissures are in the posterior midline (66%) ( Fig. 1 , posterior fissure) and with classic symptoms (84%). ⁶ Patients often report sharp pain in their anal region and occasional bright red blood with bowel movements as well as pruritus and discharge. They are associated with a hypertonic internal anal sphincter. ⁶ Atypical fissures ( Fig. 1 , anterior fissure) classically have a granulating base, overhanging edges and may extend beyond the verge onto the perianal skin. They are located off midline and multiple fissures may be present. They are frequently asymptomatic. The deep, wide ulcerations may lead to seepage, which can cause perianal dermatitis and associated perianal discomfort. Atypical fissures are not associated with increased sphincter tone but rather are related to inflammation. Biopsies demonstrate non-necrotizing epithelioid cell granulomas in roughly three-quarters of cases. ⁷ Presence of atypical fissures in patients without a history of Crohn's should also raise concern for other anal pathologies, including carcinoma, radiation-related changes, sexually transmitted infections, tuberculosis, or leukemia. ⁸

Fig. 1.

Atypical anterior anal fissure and posterior (classic) anal fissure in patient with perianal Crohn's disease.

Medical Management

The management of anal fissures aims to mitigate the underlying factors that caused and perpetuate their development: anal trauma from irregular bowel function, inflammation, and/or increased sphincter tone. This can range from conservative measures, such as decreasing bowel movements in the context of diarrhea-related fissures via things like fiber and antidiarrheal medications to surgical approaches, such as lateral internal sphincterotomy. In CD patients, lateral internal sphincterotomy is almost never appropriate secondary to high rates of complications. ⁹ In Crohn's patients, idiopathic fissures can be managed with the same approach as non-Crohn's patients, although disease-specific data are limited. Atypical fissures, i.e., those related directly to Crohn's inflammation, are challenging to treat. Frequently, treating the underlying CD through appropriate medical interventions improves the fissures as it will decrease the diarrhea and inflammation that is driving the process.

Nonsurgical management options include optimizing bowel habits and medical therapies. Controlling frequency of bowel movements with antidiarrheal or bulking agents, minimizing toilet time, gentle perianal skin care and topical agents such as nitroglycerine and calcium channel blockers are reasonable options. Prior to the advent of antitumor necrosis factor (anti-TNF) agents, early reports of medically managed anal fissures cite a roughly 50% success rate in CD patients, with greater rates of healing in cases of painless and acute fissures. ⁶ Topical options include metronidazole 10% and tacrolimus 0.1%. In one small prospective study of 14 patients, topical metronidazole was shown to improve pain, drainage, induration, and Perianal Crohn's Disease Activity Index (PCDAI) at 4 weeks. ¹⁰ However, in a similar study of 74 CD patients, the reduction in PCDAI was not significantly different than that of a placebo group. ¹¹ Topical tacrolimus has been shown to improve ulceration compared with placebo and reduce PCDAI score compared with bacterial suppositories and steroidal ointments in two small, randomized controlled trials. ^{12 13} Systemic therapies including steroids, antibiotics, aminosalicylates, and immunomodulators have shown inconsistent results. ^{5 12 14 15 16}

The gold standard for treatment of perianal CD is systemic anti-TNF medications, such as infliximab and adalimumab. Most rigorous randomized controlled trial data specifically investigate outcomes in fistulizing perianal CD. ^{17 18 19 20} One study specifically investigating 94 CD patients with ulcers demonstrated a 42.5% complete response rate to infliximab after induction therapy and a 72.3% complete response rate at long-term follow-up (median: 175 weeks). ²¹

Surgical Management

Caution must be taken when pursuing traditional surgical options for anal fissures or ulcers in Crohn's patients as such strategies can threaten continence in patients who may already have impaired control and diarrhea. Data have also demonstrated a high rate of complications and disease recurrence in these patients. ^{22 23} In one study, six patients who failed conservative management of anal fissure underwent Botox injection of the anal sphincter. An additional two underwent concurrent fissurectomy. In this small series, 50% of patients had complications, including failure to heal the surgical wound/fissure and recurrence of the fissure. ²² In another small series of 56 CD patients (obtained retrospectively from a single institution between 1957 and 1990), seven of the eight who underwent sphincterotomy or fissurectomy had complete healing of their fissure, with three developing long-term complications. Although this study reported much higher failure rates of healing in the medically managed group (49 vs. 60% in the surgical group), it did not include anti-TNF medications and therefore may not be applicable to most patients at this time. ⁶ In general, surgical management of anal fissures in CD patients should be avoided and the goal of treatment should include medical management to induce and maintain disease remission; most fissure and ulcers will then resolve.

Skin Tags

Epidemiology, Risk Factors, and Etiology

Anal skin tags are a relatively frequent manifestation of perianal CD. The cumulative 10-year incidence of skin tags among CD patients is estimated as 19%. ² There is an association with colonic disease distribution (as opposed to ileitis or ileocolitis) and the presence of skin tags. ^{24 25} Patient factors associated with the presence of skin tags include female gender, former smokers, and presence of extraintestinal disease manifestations. ² It has been proposed that the etiology of skin tags in CD may be lymphatic obstruction. ²⁶

Clinical Presentation and Classification

The morphology of anal skin tags can be divided into two general groups: Type I—often described as “elephant ear” skin tags ( Fig. 2A ) versus Type II—those arising as the sequelae of fissures, ulcers, or hemorrhoids ( Fig. 2B ). ²⁴ Elephant ear skin tags are described as flat or round, flesh colored and painless; however, they can occasional have a cyanotic or painful quality. Conversely, skin tags as sequelae of other perianal pathology are often edematous, hard, cyanotic, and more likely to be painful. They sometimes develop at the distal aspect of fissures. ²⁷ When biopsied, anal skin tags associated with CD can have the characteristic noncaseating granulomas that are pathognomonic of Crohn's histology, at a rate similar to rectal biopsies. In one study of known CD patients, 35% of anal tags contained granulomas versus 31% of rectal biopsies. ²⁸ Of the 35% of patients with granulomas seen in anal skins tags, roughly 56% also had granulomas on rectal biopsy.

Fig. 2.

( A ) Type I skin tags (elephant ear) in patient with perianal Crohn's disease. ( B ). Type II anal skin tags in patient with perianal Crohn's disease.

Clinically, skin tags may be asymptomatic. Alternatively, they can cause discomfort, pruritis, or pain. Skin tags may also cause difficulty with hygiene, particularly in the context of softer bowel motions. Like all perianal disease, even in the absence of symptoms, they may be psychologically distressing to patients from a cosmesis perspective. In patients with abdominal symptoms who have not been diagnosed with CD, the presence of abnormal appearing anal skin tags should prompt further workup for the disease. ^{29 30}

Medical Management

First and foremost, treatment should be directed at disease-related inflammation and minimizing anal trauma. This includes sitz baths, moistened wipes for hygiene, and gentle cleansing. Barrier creams may also be useful. Appropriate management of diarrhea or bowel frequency is also imperative. Patients with active disease and skin tags should receive appropriate medical therapy, such as anti-TNF medications or steroids when appropriate. There is not compelling data to support medical therapies specific to skin tags. Counseling patients regarding the rationale for avoiding surgery is an important part of caring for patients who request specific treatment or removal of tags.

Surgical Management

It is rarely necessary or appropriate to manage skin tags surgically. As many skin tags are asymptomatic, the risk of postoperative complications or poor wound healing outweighs the potential benefits. However, in the case that skin tags are narrow based and symptoms, such as hygiene issues, are impacting quality of life, excision may be considered in patients whose CD is in long-term, deep remission. This often represents elephant ear skin tags as opposed to those related to fissures or ulcers. ³¹ In a group of 22 CD patients who underwent skin tag excision, no cases of delayed wound healing were reported, supporting that in the case of appropriately selected patients, excision can be safe. ³²

Hemorrhoids

Epidemiology, Risk Factors, and Etiology

Despite representing an incredibly common anorectal pathology, symptomatic hemorrhoids are relatively rare in CD patients. It is estimated that roughly 4% of the U.S. population has symptomatic hemorrhoids. ³³ In a cohort of 50,000 patients with hemorrhoids, only 20 had CD. ³⁴ In patients with inflammatory bowel disease (IBD), the incidence of symptomatic hemorrhoids has been reported to range between 3 and 20%. ³⁵ However, in the setting of more debilitating anorectal pathology, the reported incidence may be an underestimation due to higher attention paid to other clinical features of CD. ²² Symptomatic hemorrhoids in CD are not felt to represent an extension of the CD inflammatory pathology. Rather, some consider symptomatic hemorrhoids to be an incidental finding, perhaps relating to chronic diarrhea. ³⁵

Clinical Presentation and Classification

Hemorrhoids represent a component of normal anal anatomy. Lying along the anal canal in three columns, hemorrhoids aid in protecting the anal sphincter muscles, augment anal canal closure, and thus contribute to continence. Patients with symptomatic hemorrhoids often complain of anal bleeding, pruritus, hygiene concerns, or mild discomfort. In the case of thrombosed external hemorrhoids, patients often present with sudden, severe pain. In CD patients, symptomatic hemorrhoids must be differentiated from anal skin tags and even fissures, which can have a similar presentation. ³⁶

Medical Management

The initial management of symptomatic hemorrhoids in CD patients is the same as non-CD patients. It includes nonoperative strategies such as optimizing bowel habits, warm sitz baths, and reducing straining. In a small prospective study of 45 CD patients with hemorrhoids, 17 (roughly 38%) failed conservative management—defined as diet modification, sitz baths, and/or oral diosmin. ²² In our experience, most patients respond well to conservative therapy and medical optimization of their CD. Other options to avoid surgery (i.e., excisional hemorrhoidectomy) include less invasive procedures such as banding and sclerotherapy of internal hemorrhoids; these are usually well tolerated in the office, but data specific to CD patients are limited. ^{22 36 37}

Surgical Management

It has generally been felt that hemorrhoid surgeries in patients with CD have poor outcomes; however, data are limited and most of it is historical and cannot be applied to current patients. In one systematic review, of the 99 CD patients who underwent hemorrhoidectomy, 17 had a complication, with 10% ultimately requiring a proctectomy. ³⁵ Reasons for proctectomy included fecal incontinence ( n  = 2), anal stenosis ( n  = 4), and anal fissure ( n  = 1). ³⁵ The majority of these data are, however, outdated, and it is not possible to determine causation between hemorrhoid surgery and progression to proctectomy as opposed to association between severe perianal disease and the ultimate need for proctectomy. More recent data suggest rates of proctectomy after hemorrhoidectomy are much lower (0 of 36 CD patients required proctectomy at a median follow-up of roughly 2.5 years), likely reflecting modern improvements in medical management of perianal disease and improved patient selection. ³⁷ As is true in general for the management of perianal CD, it is likely carefully selected patients with luminal remission can undergo operative management with reasonable outcomes.

Anal Stenosis and Stricture

Epidemiology, Risk Factors, and Etiology

Anal stenosis is estimated to occur in up to 22% of CD patients. ³⁸ Stenosis and stricturing are related to inflammation and subsequent fibrotic changes. However, either can occur in patients with other perianal manifestations or those without skin tags, fissures, ulcers, fistulas, or other forms of perianal CD. Anal stenosis can cause significant impact on quality of life and require permanent stoma, particularly when it is found in combination with other perianal manifestations of CD.

Clinical Presentation and Classification

The Cardiff classification for perianal CD includes a subclass for anal stricture: S0 (not present), S1 (reversible), and S2 (irreversible). S1 strictures are due to inflammation and spasm, whereas S2 strictures are due to fibrotic changes. In reality, both inflammation and fibrosis are often present. ³⁹ CD patients sometimes present with more severe anal stenosis because chronic diarrhea limits the onset of symptoms as stenosis develops. However, after a period of being asymptomatic, patients may present with perianal pain, fecal incontinence, overflow diarrhea, or constipation. ⁴⁰ Patients with more solid bowel motions may experience difficulty with evacuation or incomplete evacuation.

Medical and Endoscopic Management

In the case of reversible stenosis, medical treatment aims to reduce CD-related inflammation. Starting or optimizing the use of anti-TNF-α treatment has been associated with decreased risk disease progression in patients with stenosis. ³⁹ Some patients have a good response to serial dilation. This can be done with digital dilation or using Hegar dilators, either in the office or operating room. Subsequently, patients can be taught to dilate at regular intervals at home. Typically, dilation to 16 or 18 mm is sufficient for adequate bowel fuction. ⁴⁰ Balloon dilation is another option but is more expensive and is frequently done in the context of colonoscopy. Risks of serial dilation include bacteremia, worsening pain, and perforation. Fecal incontinence from injury to the sphincter combined with fibrosis is also a concern. In addition to dilation, endoscopic stricturotomy has been described. In this procedure, a transverse cut can be made at the posterior wall to minimize iatrogenic injury to the sphincter or vagina. ^{40 41} To the authors' knowledge, no data exist on the long-term outcomes of endoscopic dilation or stricturotomy specifically in regard to CD anal strictures. The summative data capturing outcomes on all CD strictures (intestinal, anastomotic, and anal) suggest that the most patients require repeat dilation and progression to surgery is high (reported as anywhere from 21 to 75% of patients). ^{42 43} Endoscopic stricturotomy has even fewer reported outcomes; however, limited data suggest lower rates of requiring surgery (with roughly 85% of patients remaining surgery free at 10 months in one study), but similarly high rates of serial endoscopic interventions (roughly 61% of patients in this same time frame requiring a second stricturotomy and/or endoscopic dilation). ^{42 44}

Surgical Management

Surgical options for anal stenosis include fecal diversion and proctectomy with permanent stoma, which is frequently required in the case of chronic stenosis. ⁴⁰ Fecal diversion is often indicated due to complex perianal disease in addition to stricture. In the case of anal stricturing and stenosis, diversion provides effective relief of symptoms. Diversion is unlikely, however, to result in the resolution of fibrotic anal stricture. After diversion, if there is no plan to restore intestinal continuity after medical optimization and other treatment, proctectomy should be performed due to cancer risk in the retained rectum. The presence of a stricture may make surveillance less feasible. Ultimately, about half of patients with an anal stricture eventually undergo proctectomy, with the combination of anal stricture and perianal fistulizing disease portending a higher risk. ^{45 46}

Anal Carcinoma

Epidemiology, Risk Factors, and Pathogenesis

Chronic inflammation leads to malignancy in many organ systems. Patients with CD are at increased risk of colorectal cancer due to uncontrolled and/or chronic inflammation. This is also true for anal cancer and cancers that occur in fistulae. However, the absolute risk is low, with two cases per 100,000 people reported as the annual incidence of anal squamous cell carcinoma (SCC) in CD patients. ^{47 48} The cancers that occur in the perianal region of CD patients may be adenocarcinoma or SCC. The risk is increased in CD patients with anal or perianal disease and some authors postulate that conjunction of human papillomavirus (HPV) infection and CD-related chronic local inflammation contributes to this increased risk. ^{49 50 51}

The clinical presentation, diagnosis, and management of anal cancer in CD patients does not differ from that of sporadic anal cancer, except when it occurs in a fistula. “Anal cancer” broadly represents (1) cancer of the anal canal, (2) perianal cancer, and (3) fistula-associated cancer. When CD patients are diagnosed with SCC, the treatment is usually the same as sporadic SCC and includes radiation, 5-FU and mitomycin-C for stages I through III (Modified Nigro protocol). Finally, fistula-associated cancer tends to be adenocarcinoma, which is managed as a rectal cancer. ⁵²

Squamous Cell Carcinoma

Differentiating chronic perianal disease from anal dysplasia or malignancy can be challenging. ^{53 54} A high clinical suspicion must exist for chronic perianal disease that becomes suddenly symptomatic, as this can represent malignant degeneration. If there is mucoid or solid tissue that is debrided from a fistula tract, it should be sent for pathological examination. In addition, any atypical tissue noted on exam should be biopsied. It may be pertinent to exercise more vigilance in CD patients with other risk factors for anal cancer, such as those with high-risk HPV infection or men who have sex with men—although data to provide guidance are sparse. ^{54 55} In a recent study looking at roughly 4,000 patients who are men who have sex with men, there was no difference in prevalence of HSILs or anal cancer in those with or without IBD. ⁵⁵

Anal Adenocarcinoma

CD patients are also at increased risk of developing anal adenocarcinoma, typically in fistulae. The incidence is reported as 0.38 per 1,000 patient years in those with past or current perianal lesions. ⁴⁹ In one systematic review, over 50% of patients with fistula-associated adenocarcinoma had a fistula for over 10 years. ⁵⁶ Fistula-associated adenocarcinoma is managed similar to a rectal cancer; thus, patients typically require an abdominoperineal resection, if surgery is indicated, in addition to medical or radiation therapies. The most common presenting symptom is worsening perianal pain or a reemergence of symptoms in a previously quiescent fistula tract. ⁵⁶

Crohn's Disease and Hidradenitis Suppurativa

Hidradenitis suppurativa (HS) is an autoimmune disease of the apocrine glands of the skin. Like perianal CD, it manifests as painful lesions, abscesses, and sinuses. However, perianal fistulae are not part of the HS spectrum. Although HS can occur at many regions of the body, it is common in the perianal region, may occur concurrently with CD, and can thus cause diagnostic challenges. The cumulative risk of an IBD patient developing HS is approximately 1 and 3% at 10 and 30 years, respectively, with the overall risk of developing HS nine times greater in patients with IBD compared with the general population. ⁵⁷ The converse is also true: a recent systematic review found a 2.12-fold increased odds for CD in patients with HS. ⁵⁸ Risk factors for each also overlap including diabetes, female sex, obesity, and smoking. ⁵⁹

Despite their similarities, several features can aid in distinguishing HS from CD. Biopsy of the affected area can be useful, as the presence of granulomas supports a diagnosis of CD. ⁶⁰ Furthermore, isolated perianal CD is rare—so findings consistent with HS in the absence of intestinal symptoms are unlikely to represent CD. Perianal abscesses or sinuses that are superficial are common in HS where fistulas or rectal involvement are more common in CD. ^{60 61} Magnetic resonance imaging can be useful in distinguishing the two, with one study reporting 100% sensitivity in distinguishing HS from CD in cases of HS where there was posterior involvement, bilaterality of disease and absence of rectal wall thickening. ⁶¹

CD and HS overlap in both pathological features and genetic susceptibility. ^{62 63} For example, increased interleukin expression and TNF-immune dysregulation has been implicated in both diseases. ^{64 65} Consequently, both diseases can be effectively treated with anti-TNF-α agents, although higher doses than typical may be needed for disease control. ⁶⁰ Interestingly, there have been case reports and small case series of paradoxical development of HS in CD patients treated with anti-TNF-α medications. ⁶⁶ The underlying mechanism for this observed paradox is yet to be uncovered. Given the association between HS and CD, further endoscopic evaluation is warranted in patients with HS and gastrointestinal symptoms or HS that is otherwise indistinguishable from perianal CD.

Treatment of HS in patients with CD is very complicated. A reasonable approach includes beginning with incision and drainage of any fluctuant abscesses, as a means of alleviating pain and preventing sepsis, with the understanding between provider and patient that recurrence rates approach 100%. The next step should include optimizing medical management with anti-TNF medications and/or immunomodulators with the hopes of addressing both HS and CD symptoms. Higher doses than usual of anti-TNF medications may be required in this patient population. In the case that medical management is ineffective regarding HS, it may be necessary to proceed with resection, which includes removing the involved hair follicles and sebaceous glands. The concern unique to HS in CD patients is the potential for postoperative healing. As with all CD patients undergoing surgery, optimization of CD medical management prior to operative intervention is imperative, but ultimately, surgery is likely reasonable if otherwise indicated. ⁶²