Small Intestinal Bacterial Overgrowth
The microbiota of the small intestine is essential for proper immune regulation and nutrient absorption. Typically, the concentration of bacteria is less in the proximal small intestine compared to the distal small intestine. Bacterial concentration of the proximal to mid- small intestine is approximately 10 4 organisms per milliliter, compared to the terminal ileum, in which the bacterial concentration may be as high as 10 9 organisms per milliliter. The colon has the highest concentration on average, reaching levels of 10 12 organisms per milliliter. The ileocecal valve acts as a barrier to prevent contamination of bacteria from the colon into the small intestine.
Small intestinal bacterial overgrowth (SIBO) is a condition in which there are excessive small intestinal microorganisms causing a negative impact on bowel function. Many conditions can predispose an individual to SIBO. Most of these conditions cause stagnant fecal transit, due to either a mechanical obstructive process or an underlying myopathic or neuropathic functional abnormality that leads to intestinal dysmotility. In addition, mucosal disease causing malabsorption is another factor that can lead to excessive bacterial overgrowth.
Patients may present with a variety of symptoms including diarrhea, abdominal distension, flatulence, malodorous stools, and malabsorption.
Short bowel syndrome is a condition with a clear association to SIBO. Intestinal resection of the bowel can lead to mechanical and functional obstruction from anastomotic strictures, and nerve damage disrupting bowel motility. In addition, patients who have had their ileocecal valve resected are at particular risk for SIBO due to reflux of bacteria from the colon into the small intestine.
Hypochlorhydria secondary to chronic acid suppression has been implicated in causing SIBO. Gastric acid serves an important role in acting as a barrier against excessive bacterial overgrowth. The use of proton pump inhibitors (PPIs) have been associated with an increased risk of Clostridium difficile infection for this reason.
The association between intestinal microbiota and irritable bowel syndrome (IBS) has recently been recognized. A recent study in children diagnosed with IBS found that 66% of 50 children studied were found to have a positive lactulose breath test. The use of rifaximin, an antibiotic found to be effective in the treatment of SIBO, resulted in improvement of symptoms in those children that carried a dual diagnosis of IBS and SIBO.
Other conditions, including immunodeficiency, connective tissue disease, and pseudoobstruction, also predispose individuals to SIBO.
Evaluation
Breath hydrogen and methane testing have been used to diagnosis patients with intolerance to lactose, fructose, and sucrose. In addition, using lactulose as the substrate administered during testing has allowed breath testing to be applied as a diagnostic tool for SIBO. Breath test analysis, before and after the ingestion of lactulose, measures the hydrogen and methane concentration in the exhaled air. If the hydrogen concentration is greater than 20 parts per million (ppm) at any point during the testing, the patient is considered to be positive for SIBO. Glucose can be used instead of lactulose. When glucose is the substrate being used, a rise in the hydrogen level greater than 12 ppm is considered positive. If a patient has rapid small bowel transit, a false-positive breath hydrogen test can occur as the carbohydrate is rapidly delivered into the colon. An early peak should be sought as evidence of SIBO. Methane is also measured, because some organisms are primarily methane producers, which could lead to inaccurate test results if only measuring hydrogen.
Culture of jejunal aspirates can be used to diagnose SIBO. A concentration greater than 10 3 organisms per milliliter is considered positive. There are several limitations to acquiring jejunal aspirates, including the invasiveness of testing (requiring endoscopy) and poor reproducibility of results. In addition, bacterial overgrowth may be found in other parts of the small intestine. Bacterial contamination from the oral cavity should also be considered.
Endoscopic evaluation with tissue biopsy is of limited value because the majority of SIBO cases lack inflammation, thus yielding normal results.
Management
Antimicrobial therapy has been found to be clinically effective in the treatment of SIBO. Rifaximin, which is a nonabsorbable antibiotic with minimal side effects, has been found to be very effective in treating SIBO with less likelihood of developing clinical resistance compared to other antibiotics. In one study, rifaximin at a dose of 800 mg per day for 4 weeks was found to be effective in reducing symptoms of SIBO and normalizing glucose breath testing in 50% of patients. Other antibiotics that may be used include metronidazole, amoxicillin-clavulanate, trimethoprim-sulfamethoxazole, neomycin, gentamicin, doxycycline, ciprofloxacin, and norfloxacin.
There is conflicting data pertaining to the role of probiotic therapy. However, some evidence exists suggesting a supportive role for probiotic and prebiotic therapy in combination with antimicrobial treatment.
Microscopic Colitis
Microscopic colitis, as the name implies, is colitis identified on histopathologic evaluation without macroscopic evidence of inflammation. Patients present with symptoms of diarrhea and fecal urgency without a history of rectal bleeding. By definition, patients typically present with three stools or more per day, with at least one stool of watery consistency. There are two primary subtypes of microscopic colitis: lymphocytic and collagenous. A third, or mixed type of microscopic colitis, is recognized as containing features of both lymphocytic and collagenous colitis.
The etiology of microscopic colitis has not been definitively established. There appears to be a familial pattern and a tendency to affect women more than men. Microscopic colitis typically occurs in adulthood, but may also occur in children.
Some studies have suggested that bacterial toxins may play a role. A drug-induced inflammatory response has also been suggested, especially nonsteroidal antiinflammatory drugs and PPIs. The mechanism is likely idiosyncratic given the disproportionate number of people using these medications compared to the number of patients diagnosed with microscopic colitis.
An association between celiac disease, type 1 diabetes mellitus, and immunodeficiency has been made in children diagnosed with lymphocytic colitis.
Evaluation
The diagnosis of microscopic colitis is based on histopathologic findings. Colonoscopy reveals no visual evidence of inflammatory changes.
Patients with lymphocytic colitis demonstrate an increased number of intraepithelial lymphocytes (more than 20 intraepithelial lymphocytes per 100 epithelial cells) on biopsy. The major distinguishing feature of collagenous colitis is a thickened subepithelial fibrous band measuring greater than10 µm in width ( Figure 49-1 ).
Management
Pharmacologic treatment options vary and are typically used during flares. If an environmental exposure (i.e., medication) is thought to be causing microscopic colitis, then the primary intervention is to discontinue the inciting agent. Patients with celiac disease usually respond to a gluten-free diet.
Budesonide therapy is an effective medical treatment for microscopic colitis. In one study, 86% of patients using 9 mg of budesonide daily were found to be in histologic remission after 6 weeks.
Other therapies implemented for treatment of microscopic colitis have been less successful. These include aminosalicylates, cholestyramine, glucocorticoids, antibiotics, and bismuth subsalicylate.
Celiac Crisis
Celiac disease is found in up to 1% of the general population. It is an autoimmune disease characterized by gluten sensitivity that leads to small intestinal inflammation featuring villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes. The diagnosis is made by serologic and small intestinal histopathologic evaluation. Patients respond well to gluten restriction, which leads to both symptom and histologic remission. Gastrointestinal signs and symptoms in children may include abdominal pain, distension, diarrhea, and failure to thrive. Extraintestinal manifestations are not uncommon and include arthralgia, anemia, transaminasemia, short stature, dental enamel defects, and dermatitis herpetiformis.
Albeit rare, patients with severe celiac disease may be susceptible to celiac crisis, a life-threatening syndrome associated with high mortality if not recognized and treated immediately. These patients typically have extremely high serologic markers and severe small intestinal inflammation. Symptoms of celiac crisis include substantial diarrhea, vomiting and dehydration, as well severe metabolic and electrolyte abnormalities. The cause of celiac crisis is likely a combination of significant intestinal inflammation compounded by an environmental trigger, which may include infection and/or surgery, further stimulating the immune system.
Evaluation
Given that this syndrome is associated with hypokalemia, hyponatremia, hypocalcemia, and hypomagnesemia, electrolytes should be immediately tested if there is clinical suspicion of celiac crisis. A hepatic function panel should be included given the high incidence of hypoproteinemia, likely secondary to poor nutrition.
Management
Treatment involves immediate removal of gluten from the patient’s diet. Most likely, the patient will require bowel rest and initiation of total parenteral nutrition. Due to the severity of this syndrome, many patients will require admission to an intensive care unit for close monitoring and treatment to restore electrolyte balance. Given these electrolyte disturbances, the patient should be placed on continuous cardiac monitoring due to the high risk of cardiac arrhythmia. Corticosteroids are commonly used to reduce the immune response and bowel inflammation.
Diverticular Disease
A colonic diverticulum is an outpouching of mucosa originating from the lumen of the bowel. Diverticulosis is a condition in which the colon has multiple diverticulum. In many cases, this is a benign condition without symptoms. “Diverticulitis” is when the diverticula become inflamed, which leads to significant gastrointestinal symptoms. Diverticulitis is likely caused by stool becoming impacted in the diverticula leading to infection. Poor fiber intake, abnormal colonic motility, and obesity have been linked to diverticular disease.
Diverticular disease is common, especially in industrialized nations. Diverticula tend to occur in the rectosigmoid colon. Diverticulosis is seen in patients older than 40 years of age, with the majority occurring in patients older than age 80.
Collagen cross-linking abnormalities of the colonic wall may predispose patients to develop diverticulosis. This is particularly true in patients with Ehlers-Danlos or Marfan syndrome, who have similar abnormalities and are at high risk of developing diverticulosis at a young age. With increased collagen cross-linking, the bowel wall becomes less compliant and more susceptible to perforation.
Another mechanism in which diverticula form is related to poor fiber intake and abnormal colonic motility. Poor dietary fiber intake and slow colonic transit lead to constipation and subsequent increased intraluminal pressure from chronic straining leading to formation of diverticula.
Evaluation
Patients presenting with diverticulitis typically have signs of left-sided rebound tenderness with guarding. A palpable mass and hypoactive bowel sounds may be appreciated. A complete blood count usually reveals leukocytosis, and serum inflammatory markers will likely be elevated.
An abdominal radiograph is useful for identifying potential pneumoperitoneum; however, a computed tomography (CT) scan of the abdomen and pelvis with water-soluble contrast is the diagnostic study of choice. A recent Swiss study prospectively evaluated the sensitivity of CT scan in 423 patients with confirmed diverticulitis; CT was 97% sensitive in detecting diverticulitis.
A contrast enema may be complementary to CT; Water-soluble contrast should be used and air contrast should be avoided given the high risk of perforation. Similarly, endoscopy is relatively contraindicated because of risk of perforation. There is some data demonstrating that ultrasound has sensitivity equal to that of CT; however, most studies support CT as the more sensitive study and still the primary imaging modality of choice.
Management
Patients with diverticulitis who present early may be candidates for outpatient therapy. Diagnostic criteria include no peritoneal signs, ability to tolerate oral fluids and nutrition, absence of leukocytosis, and no significant comorbid conditions. A 10-day course of amoxicillin-clavulanic acid, sulfamethoxazole-trimethoprim with metronidazole, or a quinolone with metronidazole is appropriate.
Inpatient management consists of correcting any electrolyte imbalance and initiating intravenous antimicrobial therapy. Choices include metronidazole or clindamycin in combination with an aminoglycoside or third-generation cephalosporin. Clinical improvement is seen within 2 to 4 days. Once improved, patients can be transitioned to outpatient therapy with continued oral antibiotics for a total of 10 days. Most patients recover with standard medical therapy alone. However, between 15% and 30% of patients fail medical therapy and require surgical intervention with subsequent bowel resection.
Diverticulosis may also result in colonic bleeding. Fortunately, the majority of patients will not require intervention as the bleeding spontaneously resolves. Up to 20%, however, require some form of intervention. This may include angiography with microcoils, surgery, or endoscopic injection of epinephrine and/or Endoclip placement ( Figure 49-2 ).
Ehlers-Danlos Syndrome
Ehlers-Danlos syndrome (EDS) is a hereditary disease with a pattern consistent with autosomal dominant inheritance. The major clinical diagnostic criteria include joint hypermobility and skin hyperextensibility. Easy bruising and poor wound healing are other features. Patients with EDS have abnormalities related to collagen processing in the musculoskeletal system, multiple organs, integumentary and vascular systems. In classic EDS, gene mutations include COL5A1 and COL5A2 , which are responsible for type V collagen production. A less recognized feature of EDS is the higher rate of functional gastrointestinal disorders, including IBS and dyspepsia.
A recent study by Zeitoun et al., found that in 135 patients studied, IBS, constipation, gastroesophageal reflux disease (GERD), and hiatal hernia were present in 48%, 36%, 79%, and 14%, respectively. EDS patients are also more susceptible to diverticulosis compared to the general population ( Table 49-1 ).
| Upper Gastrointestinal Symptoms | Lower Gastrointestinal Symptoms |
|---|---|
| Heartburn/regurgitation/hiatal hernia | Constipation |
| Dysphagia | Irritable bowel syndrome |
| Epigastric pain | High risk for bowel perforation |
| Nausea | |
| Gastroparesis |
Dysphagia may occur in EDS secondary to defective collagen synthesis leading to megaesophagus. Spontaneous rupture of the esophagus has been reported in patients with EDS.
Evaluation
Clinical diagnosis is based on the major diagnostic criteria which differs dependending on the type of EDS. In addition, there are minor diagnostic criteria which are supportive of this diagnosis. Family history is important, but spontaneous mutations are not uncommon. Genetic testing is available for EDS and a referral for genetic counseling in patients suspected of having this diagnosis should be made.
Management
GERD is a common gastrointestinal problem in patients with EDS. Patients with EDS do not respond well to acid suppressant therapy and have a higher incidence of hiatal hernia. Because of poor wound healing and a higher rate of surgical complications, conservative medical management is preferred.
Patients with EDS typically have problems related to constipation. Given that patients are predisposed to developing diverticulosis, aggressive laxative management should be initiated early on.
Due to the high risk of gastrointestinal perforation, colonoscopy is relatively contraindicated in EDS. Noninvasive diagnostic means utilizing radiologic methods should be performed in place of endoscopy when possible.
Hidradenitis Suppurativa
Hidradenitis suppurativa (HS), also known as acne inversa, is a chronic inflammatory condition of the skin that involves the intertriginous regions including the axillae and perineum ( Figure 49-3 ). Chronic follicular occlusion leads to deep nodule and abscess formation, which is tender to palpation. Infection is typically secondary to the inflammatory condition and not the cause. The affected region becomes fibrotic with sinus tract formation. Crohn’s disease should be included in the differential diagnosis as there is an association between both conditions.
HS affects approximately 1% to 4% percent of the population. It can lead to significant social and emotional distress. Hurley et al. developed a grading system based on the severity of presentation ( Table 49-2 ).
| Grade 1 | Abscess formation, single or multiple without sinus tracts and scarring |
| Grade 2 | Recurrent abscesses with sinus tract formation and scarring |
| Grade 3 | Diffuse involvement, multiple interconnected tracts and abscesses |
Onset is usually after puberty, and is most common around the third decade of life. Potential risk factors include obesity and smoking. Family history is also a risk factor, especially for earlier presentation of HS.
Infection, such as cellulitis, and lymphatic obstruction leading to lymphedema are complications of HS. Squamous cell carcinoma of the buttocks is a serious consequence of HS.
Evaluation
Specific testing is not warranted if clinical suspicion is strong. A thorough physical exam of the axillae, groin, and perineal region, will reveal multiple, painful nodules, abscesses, and sinus tracts.
Endoscopic evaluation may be required to rule out Crohn’s disease, especially if gastrointestinal symptoms are present. Cutaneous biopsy should be performed only in patients in which the diagnosis is not clear or there is a question of carcinoma.
Management
Surgical intervention is often necessary; this may include incision and drainage, extensive unroofing, and excision of the affected skin.
Topical antibiotics, such as clindamycin, may be used for minor cases. In more severe cases, oral antibiotics, including dicloxacillin, erythromycin, tetracycline, and minocycline may be useful. Cephalosporins can be added if secondary cellulitis is suspected. Hormonal therapy and oral retinoids, including isotretinoin, have been used for treatment.
Biologic agents are a promising form of treatment for HS. In a systemic review of 105 cases by Haslund et al., 90 patients had a positive treatment response with infliximab, with only 7 nonresponders. Furthermore, it appears that long-term therapy produced more sustained remission than short-term therapy.
Typhlitis
Typhlitis, also known as neutropenic colitis, is primarily a disease involving cancer patients. Chemotherapy causes neutropenia, which can lead to colitis associated with high rate of mortality. Signs include fever, abdominal pain, diarrhea, and rectal bleeding. In one study at a tertiary pediatric surgical center, the incidence found in oncology patients was 6.7%, and as high as 11.6% in those receiving chemotherapy. It is thought that a combination of cytotoxic drugs and a compromised immune system increases susceptibility to enteric infection, typically localized to the ileocecal region.
Two significant risk factors include stem cell transplantation and a history of chemotherapy within the preceding 2 weeks. Albeit rare, typhlitis has been described in non-immunocompromised patients.
Evaluation
CT is the most accurate means of diagnosing typhlitis and can exclude appendicitis and abscesses. Typically, the abnormal radiologic findings involve the cecum, which may include colonic wall thickening and distension. Ultrasound has been used but may be less sensitive.
Exploratory surgery should be considered in cases in which there are peritoneal signs and clinical decompensation necessitating a more rapid diagnostic and therapeutic approach.
Management
The management of typhlitis is based on severity of presentation. If the patient is stable at the time of diagnosis, conservative management using antibiotic therapy, including piperacillin-tazobactam, is appropriate. If Clostridium difficile infection is suspected, metronidazole or vancomycin can be added. Antifungal therapy may be necessary depending on the degree of neutropenia and clinical severity.
Granulocyte colony-stimulating factor (G-CSF) has been used in cases that are refractory to antimicrobial therapy. Improving neutropenia accelerates the healing process and prevents further deterioration of bowel mucosa.
Surgical intervention is reserved for severe cases where clinical deterioration, such as peritonitis and bleeding, preclude conservative management. Involved bowel is resected, often resulting in a right hemicolectomy and ileostomy.
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