Introduction
Inflammatory bowel disease (IBD) is a chronic inflammatory condition that comprises two different clinical diseases of the gastrointestinal tract: Crohn’s disease (CD) and ulcerative colitis (UC). The Centers for Disease Control and Prevention approximates that IBD affects over 3 million US adults, approximately 1.3% of the population, with the prevalence increasing yearly. It is more common than previously believed. IBD has a bimodal distribution, with peaks at 15–30 years of age and another at 50–80 years of age. Americans of Jewish descent are among those found to have an increased prevalence. It is also important to note that the incidence of IBD is rising in children, with about 25% of all diagnosed cases occurring in patients under the age of 18. The two entities of IBD, CD and UC, have many shared characteristics; however, they are distinguished by certain pathologic and clinical findings.
Etiology and Pathogenesis
There are many factors that are known to contribute to the pathogenesis of IBD. These include environmental, genetic, immune, and bacterial. The combined effects of these factors result in dysregulated immune responses that cause the gastrointestinal inflammation that characterizes IBD. Crohn’s disease is classically described as transmural inflammation characterized by skip lesions that can involve the entire GI tract, from mouth to anus. The transmural inflammation may lead to fibrosis and strictures, as well as obstruction of the colon. Ulcerative colitis on the other hand solely involves the mucosa of the colon, invariably affecting the rectum and extends proximally to other regions of the colon. Both CD and UC tend to have a relapsing and remitting course. With improving technology and research, the pathogenesis of IBD has been found to include other components of the inflammatory process, including immunopathogenic components of epithelial cells, endothelial cells, cellular components, and inflammatory mediators. Interestingly, smoking has been found to be one of the most important modifiable risk factors for Crohn’s disease, whereas it may confer a protective benefit for ulcerative colitis.
Clinical Features
Although there are shared signs and symptoms in UC and CD, there are features of IBD that are uniquely specific to each. Over 50% of IBD patients have a chief complaint of abdominal/pelvic pain on presentation. Chronic pelvic pain has been reported in about 14% of IBD. Pain can be from acute inflammation during relapses, partial or full bowel obstructions due to strictures or adhesions, fistulas, abscesses, or chronic pain from visceral hypersensitivity. Fever, weakness, and diarrhea are also common complaints. About 90% of patients affected with Crohn’s disease report bloody diarrhea, whereas patients with UC have a main complaint of cramping that subsides with defecation. Both forms of IBD can lead to reduced appetite and, in turn, unintended weight loss.
Given that IBD causes a chronic systemic inflammatory state, a new emphasis has been put on symptoms that occur outside of the GI tract, called extraintestinal manifestations (EIM). It has been estimated that 6%–47% of adult patients and approximately 25% of pediatric patients are affected by EIMs. The most common form of EIMs occurs in the musculoskeletal system in the form of peripheral and axial joint disease. Some examples of these commonly include metacarpophalangeal joint arthropathies that are usually self-limiting, to the more severe form of ankylosing spondylitis and sacroiliitis. Cutaneous manifestations of IBD occur in the form of erythema nodosum and pyoderma gangrenosum; however, most dermatological manifestations are usually associated as a complication of IBD therapies. Ocular manifestations of IBD are well known, however, rare with only 2%–5% of IBD patients developing them. These manifestations include uveitis and scleritis. Hepatobiliary conditions are also associated with IBD, with up to 50% of IBD patients developing a hepatobiliary manifestation at some point in their disease process. Primary sclerosing cholangitis is the most common. It is seen mostly in patients with CD, affecting up to 7.5% of these patients with a predisposition toward middle-aged men.
Diagnosis
IBD is diagnosed via endoscopic evidence of inflammatory changes to the digestive tract as well as chronic changes seen on histology from tissue biopsy. Upper endoscopy and colonoscopy are the two modalities most commonly used, while flexible sigmoidoscopy or capsule endoscopies are alternative options. It is important to rule out other causes of GI discomfort and/or bleeding with an extensive medical history, lab tests for infectious causes, and other imaging modalities for anatomical causes of obstruction including cancer and other masses.
Physical Exam Findings
Physical exam findings are typically nonspecific in IBD. Visceral abdominal pain is a common finding, with or without abdominal palpation. Cachexia may be seen in severe cases in which anorexia is related to unrelenting abdominal pain and related GI symptoms. Cutaneous findings of erythema nodosum and pyoderma gangrenosum may be seen. Given the common involvement of joints, signs of arthropathy such as metacarpal and phalangeal warmth and swelling may be observed. Further, stiffness and loss of range of motion along the spinal column due to ankylosing spondylitis is another possible EIM finding. Due to the recurring and often debilitating nature of the disease, many patients often suffer from a psychiatric standpoint. It is prudent to evaluate for anxiety, depression, and any maladaptive behavior or thought patterns (e.g., catastrophizing) as these mental health conditions are often comorbid with the disease.
Treatment
Pain management in IBD is complicated and often requires an interdisciplinary approach with coordination of care among primary care, gastroenterologists and other medical specialists, pain management, and mental health providers. Chronic abdominal pain with visceral hypersensitivity complicated by significant mental health disease and/or maladaptive coping skills and thought patterns may require patient-centered care plans to educate both the patient and their network of support for successful treatment outcomes. It is always important to make the distinction between pain of an acute exacerbation (i.e., relapse) of IBD versus chronic visceral pain when determining the treatment plan. Evaluations for active clinical disease and relapses should be managed by the gastroenterologist. Patients with IBD are always at risk for surgical interventions should an obstruction, fistula, perforation, abscess, or other severe complications develop.
Lifestyle Modification and Conservative Therapies
Regular aerobic exercise, mindfulness-based stress reduction, meditation, and yoga are all self-management interventions that can be learned and implemented to help patients reduce stress and promote a healthy lifestyle and resiliency. These should be discussed as part of the interdisciplinary treatment plan
Pharmacologic
Most of the disease-specific medical treatments will be managed by a gastroenterologist. These may include antiinflammatory medications such as corticosteroids or aminosalicylates, immunosuppressive agents (e.g., azathioprine), or newer biologic drugs that block tumor necrosis factor, integrins, cytokines, or transcription factors.
NSAIDs
These are typically effective when used for pain related to arthropathies from EIMs; however, in general, they should be avoided as a specific treatment for IBD-related visceral pain. The inhibition of cyclooxygenase and subsequent reduction of prostaglandin can adversely affect the intestinal mucosa, which is already pathologically altered in IBD.
Adjuvant analgesics—SNRIs, TCAs, SSRIs, AEDs
There are no randomized controlled trials demonstrating the effectiveness of these classes of medications on IBD-related symptoms or disease progression. The SNRIs and SSRIs would be indicated for the treatment of comorbid anxiety and depression when appropriate. The SNRIs, TCAs, and AEDs may also be beneficial for the treatment of central sensitization and visceral hypersensitivity.
Opioids
Use with caution and close monitoring for chronic visceral pain. Well-defined short opioid courses for acute pain related to IBD relapses or surgery may be appropriate until remission and surgical healing occur, respectively. A bowel regimen must be implemented as toxic megacolon is a risk with opioid use in IBD. Narcotic bowel syndrome is another concern with chronic opioid use because frequently recurring abdominal pain makes it difficult to distinguish active IBD pain from this opioid-related adverse effect.
Novel therapies
New molecular targets are being studied, but translational research is still being developed. One such marker that is gaining interest is the bioactive peptide nociceptin. It has been shown that this peptide is involved in pain signaling and reversal of stress-induced analgesia. Further, it has also been implicated in the pathophysiology of IBD suggesting that targeting this peptide may not only alleviate pain but also help affect the chronic course of the disease. , Other molecular pathways of interest involve transient receptor potential (TRP) channels (e.g., TRPV1/TRPA1 mixed antagonists and TRPV4 antagonists) and cytokine signaling utilizing Janus kinase inhibitors.
Psychological Interventions
There has been an increased interest in determining the efficacy and role of psychotherapy (including psychodynamic therapy, cognitive behavioral therapy, systemic therapy, brief therapy, supportive therapy, patient education, and coping skills) and other psychological interventions in IBD treatment. In 1989, Drossman commented on the impairment that IBD can have on many aspects of the patient’s life but emphasized that emotional behavior might be the most negatively affected of all. As this approach has gained traction, multiple authors have reported that IBD activity may be closely related to corresponding increases and decreases in anxiety/depression and the degree of psychological disturbance appears to correlate with disease severity. , This has led to the hypothesis that the improvement of psychosocial factors may have consequences on both the patient’s psychosocial well-being, as well as the course of IBD itself. This has been controversial in the literature with conflicting results.
A large Cochrane systematic review in 2011 aimed to address this question. Twenty-one studies were selected, including both randomized controlled trials as well as observational studies. Their objective was to assess the effects of psychological interventions in IBD and resulting disease activity. The review concluded that there was no evidence for the efficacy of psychological therapy in adult patients with IBD. However, it was suggested that in adolescents psychologic interventions may be beneficial and more research is needed in this specific population.
Dietary Restrictions
Patients with IBD often have a strong interest in implementing dietary modifications into their treatment plan for controlling and managing their IBD. There is evidence that dietary factors may influence the risk of developing and/or further worsening intestinal mucosal inflammation. There is a known link between the environment, especially diet, and the composition of the gut microbiome. However, there is currently a paucity of rigorous data from controlled trials and translational research to allow for patient guidelines. Reported diets with success include carbohydrate-free, gluten-free, specific carbohydrate diet, the fermentable oligosaccharides, disaccharides, and monosaccharides diet and the Paleolithic diet. Each of these diets manipulates the types of substances the gut is exposed to in a way that is supposed to reduce inflammation. However, essentially all food groups have been self-reported by patients to exacerbate their symptoms with a high degree of individual variability. Therefore, patients are often instructed to be aware of their diet, make note of which foods exacerbate their symptoms, and tailor their eating habits to their specific requirements.
Interventional Pain Management
There have not been any interventional pain modalities that have been reported to aid in the treatment of pain specifically from IBD. However, in patients with visceral sensitization, there may be a role for neuromodulation of the dorsal columns or dorsal horns in the regions of the spinal cord that correspond to innervation of the gut. Kapural and colleagues (2010) published a case series on 35 consecutive spinal cord stimulation (SCS) trials for chronic visceral abdominal pain. Epidural access can be obtained from the lumbar region ( Fig. 18.1 ). They placed the electrode in the midline with the tips at T5–T6 ( Fig. 18.2 ) for epigastric/periumbilical pain or T11–L1 for lower abdominal/pelvic pain. Most of the patients had a primary diagnosis of pancreatitis or adhesive disease. There was no diagnosis of IBD. Moreover, 86% had a successful trial (>50% reduction in pain). Nineteen patients were followed for a year and their average visual analog scale pain scores were 50% of baseline at 1 year. Further, a national survey published the same year analyzed 70 cases of SCS utilized for chronic visceral pain of which only 4 failed the SCS trial. Sixty-six patients were implanted with midline electrode tips at T5–6 and significant sustained pain relief (>50% reduction in pain) and a significant reduction in opioid consumption was found at an average follow-up of 84 weeks.
