AAFP

Summary of   Dec AAFP


1) Cirrhosis: Diagnosis, Management, and Prevention

Cirrhosis is the 12th leading cause of death in the United States. It accounted for 29,165 deaths in 2007, with a mortality rate of 9.7 per 100,000 persons. Alcohol abuse and viral hepatitis are the most common causes of cirrhosis, although nonalcoholic fatty liver disease is emerging as an increasingly important cause. Primary care physicians share responsibility with specialists in managing the most common complications of the disease, screening for hepatocellular carcinoma, and preparing patients for referral to a transplant center. Patients with cirrhosis should be screened for hepatocellular carcinoma with imaging studies every six to 12 months. Causes of hepatic encephalopathy include constipation, infection, gastrointestinal bleeding, certain medications, electrolyte imbalances, and noncompliance with medical therapy. These should be sought and managed before instituting the use of lactulose or rifaximin, which is aimed at reducing serum ammonia levels. Ascites should be treated initially with salt restriction and diuresis. Patients with acute episodes of gastrointestinal bleeding should be monitored in an intensive care unit, and should have endoscopy performed within 24 hours. Physicians should also be vigilant for spontaneous bacterial peritonitis. Treating alcohol abuse, screening for viral hepatitis, and controlling risk factors for nonalcoholic fatty liver disease are mechanisms by which the primary care physician can reduce the incidence of cirrhosis

Common Etiologies of Cirrhosis

Infammation Viral Hepatitis B (15 percent) Hepatitis C (47 percent) Schistosomiasis Autoimmune (types 1, 2, 3) Sarcoidosis Toxic Alcohol (18 percent) Methotrexate

Genetic/congenital Primary biliary cirrhosis ɑ1-antitrypsin defciency Hemochromatosis Nonalcoholic fatty liver disease Wilson disease Congestive heart failure (chronic passive congestion) Venoocclusive disease (Budd-Chiari syndrome) Unknown (14 percent)

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendation	Evidence rating	References
Screening and prevention
All patients should be screened for alcohol abuse.	B	4
All pregnant women should be screened for hepatitis B virus.	A	4
Patients who have cirrhosis associated with a Model for End-stage Liver Disease score of 15 or greater or with complications of cirrhosis should be referred to a transplant center.	A	[8] , [11]
Patients with cirrhosis should be screened for hepatocellular carcinoma every six to 12 months.	B	[8] , [12]
Ascites
Ascites should be treated with salt restriction and diuretics.	A	[8] , [15]
Patients with new-onset ascites should receive diagnostic paracentesis consisting of cell count, total protein test, albumin level, and bacterial culture and sensitivity.	C	[8] , [11]
If ascitic fuid polymorphonuclear cell count is greater than 250 cells per mm3, the patient should receive antibiotics within six hours if hospitalized and within 24 hours if ambulatory.	A	[8] , [11] ,[16]
Hepatic encephalopathy
Patients with hepatic encephalopathy should have paracentesis performed during the hospitalization in which the encephalopathy is diagnosed.	C	8
Persistent hepatic encephalopathy should be treated with disaccharides or rifaximin (Xifaxan).	B	[8] , [18]
Patients with hepatic encephalopathy should be counseled about not driving.	C	8
Esophageal varices
Screening endoscopy for esophageal varices should be performed within 12 months in patients with compensated cirrhosis, and within three months in patients with complicated cirrhosis.	B	[8] , [21]
Patients with cirrhosis and medium or large varices should receive beta blockers and/or have endoscopic variceal ligation performed.	A	[8] , [16] ,[21]
Patients with acute episodes of gastrointestinal bleeding should be treated with somatostatin or somatostatin analogue within the frst 12 hours.	B	[8] , [16]
Patients with acute episodes of gastrointestinal bleeding should receive prophylactic antibiotics and have endoscopy performed within 24 hours.	A	[8] , [11]

2) Diagnosis and Management of Crohn's Disease

Crohn's disease is a chronic inflammatory condition affecting the gastrointestinal tract at any point from the mouth to the rectum. Patients may experience diarrhea, abdominal pain, fever, weight loss, abdominal masses, and anemia. Extraintestinal manifestations of Crohn's disease include osteoporosis, inflammatory arthropathies, scleritis, nephrolithiasis, cholelithiasis, and erythema nodosum. Acute phase reactants, such as C-reactive protein level and erythrocyte sedimentation rate, are often increased with inflammation and may correlate with disease activity. Levels of vitamin B₁₂, folate, albumin, prealbumin, and vitamin D can help assess nutritional status. Colonoscopy with ileoscopy, capsule endoscopy, computed tomography enterography, and small bowel follow-through are often used to diagnose Crohn's disease. Ultrasonography, computed axial tomography, scintigraphy, and magnetic resonance imaging can assess for extraintestinal manifestations or complications (e.g., abscess, perforation). Mesalamine products are often used for the medical management of mild to moderate colonic Crohn's disease. Antibiotics (e.g., metronidazole, fluoroquinolones) are often used for treatment. Patients with moderate to severe Crohn's disease are treated with corticosteroids, azathioprine, 6-mercaptopurine, or anti–tumor necrosis factor agents (e.g., infliximab, adalimumab). Severe disease may require emergent hospitalization and a multidisciplinary approach with a family physician, gastroenterologist, and surgeon.

Table 1   -- Location of Crohn's Disease and Associated Symptoms

Location	Symptoms	Comment s	Frequency (%)	Common diagnostic testing
Ileum and colon	Diarrhea, cramping, abdominal pain, weight loss	Most common form	35	Colonoscopy with ileoscopy, CT enterography, biopsy
Colon only	Diarrhea, rectal bleeding, perirectal abscess, fstula, perirectal ulcer	Skin lesions and arthralgias more common	32	Colonoscopy with ileoscopy, CT enterography, biopsy
Small bowel only	Diarrhea, cramping, abdominal pain, weight loss	Complications may include fstula or abscess formation	28	Colonoscopy with ileoscopy, CT enterography, capsule endoscopy, small bowel follow-through, enteroscopy, biopsy, magnetic resonance enterography
Gastroduodenal region	Anorexia, weight loss, nausea, vomiting	Rare form	5	Esophagogastroduodenoscopy, small bowel follow-through, enteroscopy
		May cause bowel obstruction

Table 2   -- Features of Crohn's Disease and Ulcerative Colitis

Feature	Crohn's disease	Ulcerative colitis
Location	Any area of gastrointestinal tract	Continuous lesions starting in rectum
		Generally only occurs in the colon
Thickness	Transmura involvement	Mucosa and submucosa only
Colonoscopy fndings	Skip lesions, cobblestoning, ulcerations, strictures	Pseudopolyps, continuous areas of infammation
Anemia	+	+ +
Abdominal pain	+ +	+
Rectal bleeding	+	+ +
Colon cancer risk	+ +	+ + + +

+= more common or prevalent. Table 3   -- Differential Diagnosis of Crohn's Disease Celiac disease Irritable bowel syndrome Chronic pancreatitis Ischemic colitis Colorectal cancer Lymphoma of small bowel Diverticulitis Sarcoidosis Infection (e.g., Yersinia, Mycobacterium) Ulcerative colitis Information from reference 9. Table 4   -- Prevalence of Extraintestinal Manifestations of Crohn's Disease Extraintestinal manifestation Prevalence (%) Anemia 9 to 74 Anterior uveitis 17 Aphthous stomatitis 4 to 20 Cholelithiasis 13 to 34 Episcleritis 29 Erythema nodosum 2 to 20 Infammatory arthropathies 10 to 35 Nephrolithiasis 8 to 19 Osteoporosis 2 to 30 Pyoderma gangrenosum 0.5 to 2 Scleritis 18 Venous thromboembolism 10 to 30 Information from reference 10. able 5   -- Accuracy of Common Radiologie Tests in the Diagnosis of Infammatory Bowel Disease[*]  Test Sensitivity (%) Specifcity (%) Positive likelihood ratio [‡] [‡] Negative likelihood ratio [‡] [‡] Positive predictive value (%) [‡] Negative predictive value (%) [‡] Computed axial tomography 84.3 95.1 3.8 0.03 79.0 96.5 Magnetic resonance imaging 93.0 92.8 2.8 0.02 73.9 98.3 Scintigraphy 87.8 84.5 1.2 0.03 55.4 96.9 Ultrasonography 89.7 95.6 4.4 0.02 81.6 97.5

Table 6   -- Laboratory Tests to Assess Disease Activity and Complications in Patients with Crohn's Disease

Category	Test	Initial testing	Subsequent testing	Comments
General	White blood cell count	✓	•	Elevated with infammation or infection, or secondary to glucocorticoid use
				Decreased with 6-mercaptopurine and azathioprine (Imuran) use
	Hemoglobin and hematocrit level	✓	✓	Anemia
Acute phase reactants	Platelet count	✓	✓	Increased with infammation or decreased with treatment (e.g., azathioprine)
	C-reactive protein level and erythrocyte sedimentation rate	✓	✓	If elevated, may correlate with disease activity
Stool studies	Stool for culture, ova and parasites, and Clostridium diffciletoxin	✓	✓	To rule out major infectious cause of diarrhea
Nutritional status	Iron, ferritin, vitamin B12, and folate levels; total iron-binding capacity		✓	Decreased absorption or increased iron loss leading to anemia
	Albumin and prealbumin levels		✓	Decreased with poor nutritional status and with protein-losing enteropathy
	Vitamin D and calcium levels		✓	Decreased secondary to malabsorption, small bowel resection, or corticosteroid impairment of vitamin D metabolism
				Measure when initiating corticosteroid therapy
Complications	Liver function testing	✓	✓	Performed to rule out sclerosing cholangitis, screen for adverse effects of therapies
	Blood urea nitrogen and creatinine levels	✓	✓	Monitor renal function
Diagnosis	Fecal lactoferrin and calprotectin levels		✓	Surrogate marker for bowel infammation
				May distinguish between fare-up of Crohn's disease and symptoms of irritable bowel syndrome
	Antibodies to Escherichia coli outer membrane porin andSaccharomyces cerevisiae; perinuclear antineutrophil cytoplasmic antibody		✓	Distinguish between Crohn's disease and ulcerative colitis

Information from references [8] , [14] , and 15.

Table 7   -- Accuracy of Common Endoscopic Diagnostic Tests for Active Small Bowel Crohn's Disease^[*] 

Test	Sensitivity (%) [16]	Specifcity (%)1 [6]	Positive likelihood ratio [‡] [‡]	Negative likelihood ratio [‡] [‡]	Positive predictive value (%) [‡]	Negative predictive value (%) [‡]
Individual test
Capsule endoscopy	83	53	0.38	0.07	27.9	93.4
Colonoscopy with ileoscopy	74	100	∞	0.06	100	94.6
CT enterography	82	89	1.6	0.04	62.0	95.7
Small bowel follow-through	65	94	2.4	0.08	70.4	92.4
Pairs of tests
Capsule endoscopy plus colonoscopy with ileoscopy	100	57	0.51	0.00	33.8	100
Capsule endoscopy plus CT enterography	92	53	0.43	0.03	30.0	96.8
Capsule endoscopy plus small bowel follow-through	92	53	0.43	0.03	30.0	96.8
CT enterography plus colonoscopy with ileoscopy	84	94	3.0	0.03	75.4	96.4
CT enterography plus small bowel follow-through	85	94	3.1	0.04	75.6	96.6
Small bowel follow-through plus colonoscopy with ileoscopy	78	100	∞	0.05	100	95.4

Table 8   -- Comparison of Various Diagnostic Tests for Crohn's Disease

Test	Comment
Capsule endoscopy	Better yield for nonstricturing small bowel Crohn's disease than small bowel follow-through and colonoscopy with ileoscopy; capsule retention possible with small bowel stricture
Colonoscopy with ileoscopy	Direct visualization of infammation, fstula, or stricture of terminal ileum and colon; ability to obtain biopsies from the ileum and colon
Computed tomography enterography	Permits visualization of the bowel wall and lumen; exposes patient to ionizing radiation
Computed tomography	Reveals intraintestinal infammation and extraintestinal manifestations; exposes patient to ionizing radiation
Magnetic resonance enterography	Permits visualization of the bowel and lumen; expensive; no ionizing radiation
Magnetic resonance imaging	Reveals intraintestinal infammation and extraintestinal manifestations without radiation
Scintigraphy	Uses radiolabeled leukocytes to diagnose bowel infammation and to estimate disease extent and activity; role in clinical practice is limited
Small bowel follow-through	Radiographic examination of small bowel after ingestion of contrast medium (barium)
Ultrasonography	Detects increase in vascular fow, abscess, sinus tracts, and lymphadenopathy

Table 9   -- Immunomodulator Therapy for Crohn's Disease

Drug	Dosage	Common adverse effects	FDA boxed warning	Monitoring	Cost of generic (brand) [*]
6-mercaptopurine	50 mg by mouth per day (maximum: 1.5 mg per kg per day)	Myelosuppression, hepatic toxicity, immunosuppression, hepatic encephalopathy, pancreatitis, rash, hyperpigmentation, lymphoma, fever	None	Creatinine level at baseline Complete blood count with differential weekly during induction Liver enzyme tests weekly during induction White blood cell count, platelet count, hemoglobin level	$93 ($207)
Azathioprine (Imuran)	50 mg by mouth per day (maximum 2.5 mg per kg per day)	Gastritis, nausea, vomiting, lymphoma, fever May cause pancreatitis, leukopenia, anemia, thrombocytopenia	Chronic immunosuppression increases risk of neoplasia	Creatinine level at baseline Complete blood count weekly for one month, then every two weeks for two months, then monthly and when dose changes Liver enzyme tests White blood cell count, platelet count, hemoglobin level	$28 ($160)
Budesonide (Entocort EC)	9 mg by mouth every morning for up to eight weeks (induction)	Diarrhea, nausea, arthralgias, headache, respiratory tract infection, sinusitis	None	Signs and symptoms of hypercorticism and adrenal suppression with long-term therapy	NA ($1,560)[‡]
Methotrexate	25 mg subcutaneously or intramuscularly per week	Alopecia, photosensitivity, rash, diarrhea, anorexia, nausea, vomiting, stomatitis, leukopenia, pneumonitis May also cause hyperuricemia, gastrointestinal hemorrhage, myelosuppression, hepatotoxicity, lung fibrosis, renal failure	Fetal death and congenital abnormalities (not recommended for use in women of childbearing age), hepatotoxicity	Chest radiography at baseline Complete blood count with differential and platelet count at baseline then monthly	$32 (NA)
Prednisone	20 to 40 mg by mouth per day	Hypertension, fluid retention, hypernatremia, osteoporosis, depression, increased risk of infection	Fibrosis and cirrhosis with prolonged use	Blood urea nitrogen measurement, creatinine level, and liver
Anti-tumor necrosis factor agents			Malignant lymphoma may occur	enzyme tests at baseline then every four to eight weeks
Adalimumab (Humira)	160 mg subcutaneously once at week 0, then 80 mg once at week 2, then 40 mg every two weeks	Injection site reactions (e.g., erythema, itching, hemorrhage, pain, swelling), infection, tuberculosis, malignancies (e.g., lymphoma), autoantibodies/lupus-like syndrome	None	Blood pressure, electrolyte panel, blood glucose level, mental status, ophthalmic examination (with prolonged therapy), dual energy x-ray absorptiometry	$12 (NA)
Certolizumab pegol (Cimzia)	400 mg subcutaneously once at weeks 0, 2, and 4, then 400 mg every four weeks	Injection site reactions, upper respiratory tract infection, headache, hypertension, rash, infections	Active tuberculosis, reactivation of latent tuberculosis, invasive fungal infections[‡]	Purified protein derivative test and chest radiography at baseline Monitor for signs and symptoms of tuberculosis and active hepatitis B (in those who are carriers of hepatitis B virus)	NA (more than $2,000) for 80 mg
Infiximab (Remicade)	5 mg per kg intravenously once at weeks 0, 2, and 6, then 5 mg per kg every eight weeks	Infusion-related reactions (e.g., dyspnea, flushing, headache, rash, chest pain, hypotension, pruritus, urticaria, anaphylaxis), delayed reaction (e.g., serum sickness, myalgia, arthralgia), infections, pneumonia, cellulitis, abscess, skin ulceration, sepsis, bacterial infection, autoantibodies/lupus-like syndrome, lymphoma	Active tuberculosis, reactivation of latent tuberculosis, invasive fungal infections[‡], lymphoma and other malignancies	Purified protein derivative test and chest radiography at baseline Monitor for signs and symptoms of tuberculosis and active hepatitis B (in those who are carriers of hepatitis B virus)	NA ($1,755) for 200 mg[§]
			Active tuberculosis, reactivation of latent tuberculosis, invasive fungal infections[‡], hepatosplenic T-cell lymphoma	Purified protein derivative test and chest radiography at baseline Monitor for signs and symptoms of tuberculosis and active hepatitis B (in those who are carriers of hepatitis B virus) Dermatologic examination in patients with psoriasis	NA ($753) for 100 mg

Table 10   -- Supportive and Preventive Measures in Patients with Crohn's Disease

Treatment modality	Preventive measure
All therapies	Stop smoking
	Avoid nonsteroidal anti-infammatory drugs and oral contraceptives (associated with symptom exacerbation)
	Ensure routine immunizations are current (e.g., infuenza, pneumococcal vaccination)
	Avoid pregnancy in women of childbearing age
Anti–tumor necrosis factor therapy	Obtain purifed protein derivative test and chest radiography before initiating therapy
	Update immunizations, including hepatitis B
Corticosteroids	Baseline dual energy x-ray absorptiometry; calcium and vitamin D supplementation; consider bisphosphonate therapy
Sulfasalazine (Azulfdine) and methotrexate	Folic acid supplementation

Table 11   -- Mesalamine Products Commonly Used for Treating Crohn's Disease

Brand name	Generic name	Location of action	Formulation	Dosage	Cost [*]
Apriso	Mesalamine	Colon	0.375-g extended-release capsule	1.5 g orally every morning	NA ($271)
Asacol Asacol HD	Mesalamine	Colon and terminal ileum	400- and 800-mg delayed-release tablets	800 mg orally three times per day	NA ($390)
Canasa	Mesalamine	Rectum	1,000-mg rectal suppository	1,000 mg rectally at bedtime	NA ($522)t
Lialda (multimatrix system)	Mesalamine	Colon	1.2-g delayed-release tablet	2.4 to 4.8 g orally once per day	NA ($512)
Pentasa (pH controlled)	Mesalamine	Small bowel, ileum, colon	250- and 500-mg extended-release capsules	1,000 mg orally four times per day	NA ($635)
Rowasa	Mesalamine	Descending colon	4 g per 60 mL rectal enema suspension	4 g rectally at bedtime	$36 ($95[‡]) for 60-mL bottle[‡]
Colazal (5-aminosalicylic acid plus inert carrier)	Balsalazide	Colon	750-mg capsule	2.25 g orally three times per day	$103 ($400)
Dipentum (two molecules of 5-aminosalicylic acid)	Olsalazine	Colon	250-mg capsule	500 mg orally twice per day	NA ($347)
Azulfdine	Sulfasalazine	Colon	500-mg tablet	500 mg orally four times per day	$23 ($79)

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendation	Evidence rating	References
Ultrasonography, computed axial tomography, scintigraphy, and magnetic resonance imaging are helpful for excluding extramural complications in persons with Crohn's disease.	C	[8] , [12]
Colonoscopy with ileoscopy and biopsy is a valuable initial test in the diagnosis of ileocolonic Crohn's disease.	C	8
Esophagogastroduodenoscopy is recommended in patients with Crohn's disease who have upper gastrointestinal symptoms.	C	8
There is no difference between elemental and nonelemental diets in inducing remission in patients with Crohn's disease.	A	18
Budesonide (Entocort EC) is effective in inducing, but not maintaining, remission in patients with Crohn's disease.	B	[21] , [37]
Corticosteroids are more effective than placebo and 5-aminosalicylic acid products in inducing remission in patients with Crohn's disease.	A	22
Azathioprine (Imuran) and 6-mercaptopurine are effective in inducing remission in patients with active Crohn's disease.	A	23
Methotrexate is effective in inducing and maintaining remission in patients with Crohn's disease.	B	[25] , [33]

3) Subacute Management of Ischemic Stroke
Ischemic stroke is the third leading cause of death in the United States and a common reason for hospitalization. The subacute period after a stroke refers to the time when the decision to not employ thrombolytics is made up until two weeks after the stroke occurred. Family physicians are often involved in the subacute management of ischemic stroke. All patients with an ischemic stroke should be admitted to the hospital in the subacute period for cardiac and neurologic monitoring. Imaging studies, including magnetic resonance angiography, carotid artery ultrasonography, and/or echocardiography, may be indicated to determine the cause of the stroke. Evaluation for aspiration risk, including a swallowing assessment, should be performed, and nutritional, physical, occupational, and speech therapy should be initiated. Significant causes of morbidity and mortality following ischemic stroke include venous thromboembolism, pressure sores, infection, and delirium, and measures should be taken to prevent these complications. For secondary prevention of future strokes, antiplatelet therapy with aspirin should be initiated within 24 hours of ischemic stroke in all patients without contraindications, and one of several antiplatelet regimens should be continued long-term. Statin therapy should also be given in most situations. Although permissive hypertension is initially warranted, antihypertensive therapy should begin within 24 hours. Diabetes mellitus should be controlled and patients counseled about lifestyle modifications to reduce stroke risk. Rehabilitative therapy following hospitalization improves outcomes and should be considered.

Table 1   -- Risk Factors for Ischemic Stroke (Embolic or Thrombotic)

Embolic Arrhythmia (atrialfbrillation/futter) Artery-to-artery embolization Bacterial endocarditis Bioprosthetic or mechanical heart valve Dilated cardiomyopathy Heart failure with ejection fraction of less than 30 percent Myocardial infarction within the past month Patent foramen ovale Rheumatic mitral or aortic valve disease

Thrombotic Aortic dissection Arteritis/vasculitis Atherosclerosis Fibromuscular dysplasia Hypercoagulable disorders Polycythemia vera Thrombocytosis Vasoconstriction

Table 2   -- Goals of Hospital Care After Ischemic Stroke

Monitoring for neurologic complications Diagnostic evaluation Restorative therapy Nutritional therapy Physical and occupational therapy Speech therapy Prevention of medical complications Venous thromboembolism Pressure sores Infection Delirium

Prevention of future ischemic strokes Antiplatelet therapy Lipid therapy Blood pressure control Management of diabetes mellitus Lifestyle modifcations Depression screening and treatment Discharge planning