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Internal Medicine Clinical Practice Guidelines: 2018 Midyear

John Anello; Brian Feinberg; John Heinegg; Yonah Korngold; Richard Lindsey; Cristina Wojdylo; Olivia Wong, DO

July 10, 2018

Acute Pancreatitis
American Gastroenterological Association

The diagnosis of acute pancreatitis (AP) requires at least 2 of the following features: characteristic abdominal pain;
biochemical evidence of pancreatitis (ie, amylase or lipase elevated >3 times the upper limit of normal); and/or
radiographic evidence of pancreatitis on cross-sectional imaging.

Presentations of AP occur along a clinical spectrum and can be categorized as mild, moderately severe, or severe,
based on the recent revised Atlanta classification.

Most cases of AP (around 80%) are mild, with only interstitial changes of the pancreas without local or systemic

Moderately severe pancreatitis is characterized by transient local or systemic complications or transient organ
failure (<48 hours), and severe AP is associated with persistent organ failure.

Necrotizing pancreatitis is characterized by the presence of pancreatic and/or peripancreatic necrosis, and is
typically seen in patients with moderately severe or severe AP.

There are 2 overlapping phases of AP, early and late. The early phase of AP takes place in the first 2 weeks after
disease onset, and the late phase can last weeks to months thereafter.

In patients with AP, the AGA suggests against the use of hydroxymethyl starch (HES) fluids.

In patients with predicted severe AP and necrotizing AP, the AGA suggests against the use of prophylactic

In patients with acute biliary pancreatitis and no cholangitis, the AGA suggests against the routine use of urgent

In patients with AP, the AGA recommends early (within 24 hr) oral feeding as tolerated, rather than keeping the
patient nil per os.

In patients with AP and inability to feed orally, the AGA recommends enteral rather than parenteral nutrition.

In patients with predicted severe or necrotizing pancreatitis requiring enteral tube feeding, the AGA suggests either
nasogastric or nasojejunal route.

In patients with acute biliary pancreatitis, the AGA recommends cholecystectomy during the initial admission rather
than after discharge.

In patients with acute alcoholic pancreatitis, the AGA recommends brief alcohol intervention during admission.


Crockett SD, Wani S, Gardner TB, et al. American Gastroenterological Association Institute Guideline on
Initial Management of Acute Pancreatitis. Gastroenterology. 2018 Mar;154(4):1090-1101.
European Society for Clinical Microbiology and Infectious Diseases, the European Confederation of Medical
Mycology and the European Respiratory Society Joint Clinical Guidelines

Chest computed tomography as well as bronchoscopy with bronchoalveolar lavage (BAL) in patients with suspicion
of pulmonary invasive aspergillosis (IA) are strongly recommended.

For diagnosis, direct microscopy, preferably using optical brighteners, histopathology, and culture are strongly

Serum and BAL galactomannan measures are recommended as markers for the diagnosis of IA.

PCR should be considered in conjunction with other diagnostic tests.

Pathogen identification to species complex level is strongly recommended for all clinically relevant Aspergillus
isolates; antifungal susceptibility testing should be performed in patients with invasive disease in regions with
resistance found in contemporary surveillance programs.

Isavuconazole and voriconazole are the preferred agents for first-line treatment of pulmonary IA, whereas
liposomal amphotericin B is moderately supported.

Combinations of antifungals as primary treatment options are not recommended.

Therapeutic drug monitoring is strongly recommended for patients receiving posaconazole suspension or any form
of voriconazole for IA treatment, and in refractory disease, where a personalized approach considering reversal of
predisposing factors, switching drug class and surgical intervention are also strongly recommended.

Primary prophylaxis with posaconazole is strongly recommended in patients with acute myelogenous leukemia or
myelodysplastic syndrome receiving induction chemotherapy.

Secondary prophylaxis is strongly recommended in high-risk patients.


Ullmann AJ, Aguado JM, Arikan-Akdagli S, et al. Diagnosis and management of Aspergillus diseases:
executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clin Microbiol Infect. 2018 Mar 12.

Benign Prostatic Hyperplasia Management

American Urological Association

Men with lower urinary tract symptoms (LUTS) that have been attributed to BPH should be offered transurethral
resection of the prostate (TURP) as a treatment option.

Either the monopolar or bipolar approach to TURP can be used, depending on the expertise of the clinician.

For patients with large prostates, clinicians should consider open, laparoscopic, or robotic-assisted prostatectomy,
depending on expertise.

Photoselective vaporization of the prostate (PVP) with 120W or 180W platforms should be considered as an

Consider PUL if prostate volume is less than 80g and there is verified absence of an obstructive middle lobe, but
patients should be told that symptom reduction and flow rate improvement are not as significant as with TURP.

Water vapor thermal therapy may be offered if prostate volume is less than 80g, but patients should be told that
evidence of efficacy is limited.
Consider holmium laser enucleation of the prostate (HoLEP) or thulium laser enucleation of the prostate (ThuLEP),
depending on expertise.

HoLEP, PVP, and ThuLEP should be considered in patients at higher risk of bleeding (eg, those on anticoagulation


Foster HE, Barry MJ, Dahm P, et al. Surgical Management of Lower Urinary Tract Symptoms Attributed to
Benign Prostatic Hyperplasia: AUA Guideline. J Urol. May 15, 2018.

AUA Releases New Clinical Guideline for Surgical Management of Lower Urinary Tract Symptoms
Attributed to Benign Prostatic Hyperplasia. American Urological Society. May 17, 2018. PR Newswire.
Cision. Chicago.

Biliary Cholangitis
UK-PBC and the British Society of Gastroenterology

Recommend that any patient with persistently elevated cholestatic liver biochemistry (raised ALP or GGT) without
an alternative cause should have autoantibodies checked for anti-mitochondrial (AMA) and anti-nuclear (ANA)

The presence of antimitochondrial antibodies (>1 in 40) or highly PBC-specific antinuclear antibodies, in the
appropriate context of cholestatic liver biochemistry, without alternative explanation, is usually sufficient for
confidently reaching the diagnosis of PBC.

All patients with PBC should be offered structured life-long follow-up, recognizing that different patients have
different disease courses and may require different intensity of follow-up.

Risk assessment should evaluate disease severity and activity at baseline and on treatment. We recommend a
combination of serum liver tests (to identify those with an elevated bilirubin, a platelet count <150 or biochemical
disease activity on treatment), imaging (liver ultrasound to identify overt cirrhosis and splenomegaly; transient
elastography to identify increased liver stiffness) and recognition of young age at disease onset (<45 years) and
male sex.

To identify those at greatest risk of disease progression, we recommend that all patients have individualized risk
stratification using biochemical response indices following 1 year of ursodeoxycholic acid (UDCA) therapy. We
suggest that UDCA treated patients with an alkaline phosphatase (ALP) >1.67 x upper limit of normal (ULN) and/or
elevated bilirubin <2 x ULN represent a group of high-risk patients in whom there is randomized controlled trial
evidence for the addition of second-line therapy.

Recommend oral UDCA at 13–15 mg/kg/day be used as the first-line pharmacotherapy in all patients with PBC. If
tolerated, treatment should usually be life-long.

In patients with inadequate response to UDCA (or UDCA intolerance) as defined by ALP >1.67 x ULN and/or
elevated bilirubin <2 x ULN, the addition of obeticholic acid (OCA) has been associated with improvements in
biochemical surrogates of disease activity reasonably likely to predict improved outcomes. We therefore
recommend, in keeping with the National Institute for Health and Care Excellence (NICE) evaluation of OCA, that
the addition of OCA for patients with an inadequate response to UDCA, or intolerant of UDCA, is considered. We
recommend dose adjustment in patients with advanced liver disease as per the drug label.

Recommend that all patients be evaluated for the presence of symptoms, particularly fatigue and itch. Clinicians
should recognize that severity of symptoms does not correlate with stage of disease.

True overlap with autoimmune hepatitis is probably rare, and we suggest that, when suspected, liver biopsy with
expert clinicopathologic review is needed to make the diagnosis and guide treatment.
Recommend that patients with PBC be offered the chance to seek support from patient support groups.


Hirschfield GM, Dyson JK, Alexander GJM, et al. The British Society of Gastroenterology/UK-PBC primary
biliary cholangitis treatment and management guidelines. Gut. 2018 Mar 28.

Cervical Cancer Screening in HIV Patients

New York State Department of Health (NYSDOH) AIDS Institute Medical Care Criteria Committee

Offer all individuals with HIV, aged 9 to 26 years, the 9-valent human papillomavirus (HPV) vaccine 3-dose regimen
regardless of previous Pap test results or CD4 cell count.

A history of HPV-related cervical cytologic changes should not exclude individuals from being vaccinated.

Available data do not support HPV vaccination in all adults older than 26 years, including those with HIV.

Eligible for screening include all people with HIV who have a cervix and/or vagina, including cisgender women
(individuals assigned female at birth who identify as female), transgender men (individuals assigned female at birth
but who identify as male), and nonbinary individuals who were assigned female at birth but who identify as neither
male nor female.

Vaginal screening is reserved for those who have had a total hysterectomy and have a history of abnormal cervical

The guideline strongly encourages care providers to ask patients about any previous history of cervical
abnormalities and about gender-reassignment and gynecologic surgeries to determine whether a patient needs
cervical or vaginal screening.

Because the source of most cervical dysplasia is genital HPV, a sexually transmitted infection, the Committee does
not recommend Pap tests before sexual debut.

The Pap test is useful for identifying patients who need further evaluation, which may include HPV testing, more
frequent Pap tests, referral for colposcopy with directed biopsy, and treatment of biopsy-proven histologic

HPV co-testing (a cervical cytologic test with a concurrent HPV test) is routinely performed in persons aged 30
years or older. HPV testing in response to an abnormal cervical Pap test result (HPV reflex testing) is performed in
persons younger than age 30 years with a Pap test that shows atypical squamous cells (ASCs) of undetermined
significance (ASC-US) or above, or a persistent ASC-US Pap, and in persons aged 30 years or older who did not
receive an HPV co-test at the time of their cervical Pap test.

A diagnosis of high-risk HPV infection requires follow-up with colposcopy. In addition, colposcopy should be
performed in response to the following Pap test results: persistent ASCs, high-grade squamous intraepithelial
lesion (HSIL) cannot be excluded; low-grade squamous intraepithelial lesion; HSIL; and any result of atypical
glandular cells.

HPV testing as a primary screening test without cytologic screening is not recommended for persons with HIV.

The diagnostic standard for cervical dysplasia is a histologic specimen, which is obtained through colposcopy-
directed biopsy. Colposcopy should not be used as a primary screening method. Persons who require colposcopy
are identified through the screening Pap test. Random biopsies are not useful for cervical dysplasia diagnosis.
Colposcopy should be performed by an experienced clinician.


Norwood CD. Cervical Cancer Screening in Patients With HIV: Updated Guidelines. Medscape HIV/AIDS.
WebMD Inc. March 19, 2018.
Chronic Kidney Disease-Mineral and Bone Disorder
The Kidney Disease: Improving Global Outcomes Work Group

Use of dual-energy X-ray absorptiometry testing is reasonable, provided that findings of a low or diminishing bone
mineral density (BMD) lead to the initiation of new interventions to either prevent falls or treat osteoporosis.

Because dual-energy X-ray absorptiometry is unable to differentiate between different types of renal
osteodystrophy, it is reasonable to carry out a bone biopsy, provided that results will prompt a change in treatment.

It is no longer recommended that physicians obtain a bone biopsy before introducing antiresorptive therapy in
patients with CKD stage G4 to G5D; evidence now supports the effectiveness of antiresorptive therapies in patients
with CKD stage 3a to G4.

In patients with CKD G3a to G5D, treatments of CKD-MBD should be based on serial assessments of phosphate,
calcium, and PTH levels considered together, not as single values.

Only patients with hyperphosphatemia should be treated, and hypercalcemia should be avoided in patients with
CKD G3a to G5D.

Prevention, as opposed to treatment of hyperphosphatemia, may be beneficial in patients with CKD stage G3a to

In patients with CKD G5D, use a dialysate calcium concentration of between 1.25 and 1.50 mmol/L (2.5 and 3.0

The decision to initiate treatment with a phosphate-lowering agent in patients with CKD with stage G3a to G5D
should be based on either progressively or persistently elevated serum phosphate levels.

When treatment is initiated, restrict the dose of calcium-based phosphate binders.

Patients with CKD stage G3a to G5D should limit their dietary intake of phosphate as part of their treatment
regimen to reduce phosphate levels.

Secondary hyperparathyroidism

Treat only those patients not receiving dialysis with CKD stage G3a to G5 whose PTH values are either
progressively increasing or persistently above the upper limit of normal, and do not to treat on the basis of a single
elevated value. Factors that can contribute to high PTH levels, including high serum phosphate levels, low serum
calcium levels, too much dietary phosphate, and vitamin D deficiency, should be modified where possible.

Caution against routine use of both calcitriol and vitamin D analogues in patients with CKD stage G3a to G5 not
receiving dialysis; reserve their use for patients with CKD stage G4 to G5 with severe and progressive

If dialysis patients need to have PT levels lowered, suggest calcimimetics, calcitriol, or vitamin D analogues, or a
combination of calcimimetics with calcitriol or vitamin D analogues.


Ketteler M, Block GA, Evenepoel P, et al. Evaluation, Prevention, and Treatment of Chronic Kidney
Disease–Mineral and Bone Disorder: Synopsis of the Kidney Disease: Improving Global Outcomes 2017
Clinical Practice Guideline Update. Ann Intern Med. 2018 Feb 20.

Harrison P. KDIGO Releases CKD-MBD Guidelines, Targets PCPs, Nephrologists. Medscape Medical
News. WebMD Inc. February 22, 2018.

European Association for the Study of the Liver

In patients with decompensated cirrhosis, the etiologic factor, should be removed, particularly alcohol consumption
and hepatitis B or C virus infection, as this strategy is associated with decreased risk of decompensation and
increased survival.

Strategies based on targeting abnormalities in gut-liver axis by antibiotic administration (ie, rifaximin), improving the
disturbed systemic circulatory function (ie, long-term albumin administration), decreasing the inflammatory state (ie,
statins), and reducing portal hypertension (ie, beta blockers) have shown potential benefit to decrease cirrhosis
progression in patients with decompensated cirrhosis.

A diagnostic paracentesis is recommended in all patients with new onset grade 2 or 3 ascites, or in those
hospitalized for worsening of ascites or any complication of cirrhosis.

Neutrophil count and culture of ascitic fluid culture (bedside inoculation blood culture bottles with 10 ml fluid each)
should be performed to exclude bacterial peritonitis. A neutrophil count above 250 cells/µl is required to diagnose
spontaneous bacterial peritonitis (SBP).

Ascitic total protein concentration should be performed to identify patients at higher risk of developing SBP.

The serum ascites albumin gradient (SAAG) should be calculated when the cause of ascites is not immediately
evident, and/or when conditions other than cirrhosis are suspected.

Cytology should be performed to differentiate malignancy-related from non-malignant ascites.

Since the development of grade 2 or 3 ascites in patients with cirrhosis is associated with reduced survival, liver
transplantation (LT) should be considered as a potential treatment option.

A moderate restriction of sodium intake (80–120 mmol/day, corresponding to 4.6–6.9 g of salt) is recommended in

patients with moderate, uncomplicated ascites. This is generally equivalent to a no-added-salt diet with avoidance
of pre-prepared meals. Adequate nutritional education of patients on how to manage dietary sodium is also

Diets with a very low sodium content (<40 mmol/day) should be avoided, as they favor diuretic-induced
complications and can endanger a patient's nutritional status.

Patients with the first episode of grade 2 (moderate) ascites should receive an anti-mineralocorticoid drug alone,
starting at 100 mg/day with stepwise increases every 72 hr (in 100 mg steps) to a maximum of 400 mg/day if there
is no response to lower doses.

In patients who do not respond to anti-mineralocorticoids, as defined by a body weight reduction of less than
2 kg/wk, or in patients who develop hyperkalemia, furosemide should be added at an increasing stepwise dose
from 40 mg/day to a maximum of 160 mg/day (in 40 mg steps).

Patients with long-standing or recurrent ascites should be treated with a combination of an anti-mineralocorticoid
drug and furosemide, the dose of which should be increased sequentially according to the response.

Torasemide can be given in patients exhibiting a weak response to furosemide.

During diuretic therapy, a maximum weight loss of 0.5 kg/day in patients without edema and 1 kg/day in patients
with edema is recommended.

Once ascites has largely resolved, the dose of diuretics should be reduced to the lowest effective dose.

In patients presenting with GI hemorrhage, renal impairment, hepatic encephalopathy, hyponatremia, or alterations
in serum potassium concentration, these abnormalities should be corrected before starting diuretic therapy. In
these patients, cautious initiation of diuretic therapy and frequent clinical and biochemical assessments should be
performed. Diuretic therapy is generally not recommended in patients with persistent overt hepatic encephalopathy.

Diuretics should be discontinued if severe hyponatremia (serum sodium concentration <125 mmol/L), acute kidney
injury (AKI), worsening hepatic encephalopathy, or incapacitating muscle cramps develop.
Furosemide should be stopped if severe hypokalemia occurs (<3 mmol/L). Anti-mineralocorticoids should be
stopped if severe hyperkalemia occurs (>6 mmol/L).

Albumin infusion or baclofen administration (10 mg/day, with a weekly increase of 10 mg/day up to 30 mg/day) is
recommended in patients with muscle cramps.

Large volume paracentesis (LVP) is the first-line therapy in patients with large ascites (grade 3 ascites), which
should be completely removed in a single session. LVP should be followed with plasma volume expansion to
prevent post-paracentesis circulatory dysfunction (PPCD).

In patients undergoing LVP greater than 5 L of ascites, plasma volume expansion should be performed by infusing
albumin (8 g/L of ascites removed), as it is more effective than other plasma expanders, which are not
recommended for this setting.

In patients undergoing LVP less than 5 L of ascites, the risk of developing PPCD is low. However, it is generally
agreed that these patients should still be treated with albumin because of concerns about use of alternative plasma

Non-steroidal anti-inflammatory drugs should not be used in patients with ascites because of the high risk of
developing further sodium retention, hyponatremia, and AKI.

Repeated LVP plus albumin (8 g/L of ascites removed) is recommended as first-line treatment for refractory

Diuretics should be discontinued in patients with refractory ascites who do not excrete >30 mmol/day of sodium
under diuretic treatment.

Antibiotic prophylaxis is recommended in cirrhotic patients with acute GI bleeding because it reduces the incidence
of infections and improves control of bleeding and survival. Treatment should be initiated on presentation of
bleeding and continued for up to 7 days. Ceftriaxone (1 g/24 hr) is the first choice in patients with decompensated
cirrhosis, those already on quinolone prophylaxis, and in hospital settings with high prevalence of quinolone-
resistant bacterial infections. Oral quinolones (norfloxacin 400 mg bid) should be used in the remaining patients.


European Association for the Study of the Liver. EASL Clinical Practice Guidelines for the management of
patients with decompensated cirrhosis. J Hepatol. 2018 Apr 10. https://www.journal-of-

Clostridium difficile Infection

Infectious Diseases Society of America and Society for Healthcare Epidemiology of America

Diagnosis (adults)

Patients with unexplained and new-onset ≥3 unformed stools in 24 hours are the preferred target population for
testing for CDI.

Use a stool toxin test as part of a multistep algorithm (ie, glutamate dehydrogenase [GDH] plus toxin; GDH plus
toxin, arbitrated by nucleic acid amplification test [NAAT]; or NAAT plus toxin) rather than NAAT alone for all
specimens when there are no preagreed institutional criteria for patient stool submission.

Use NAAT alone or a multistep algorithm for testing (ie, GDH plus toxin; GDH plus toxin, arbitrated by NAAT; or
NAAT plus toxin) rather than a toxin test alone when there are preagreed institutional criteria for patient stool

Do not perform repeat testing (within 7 days) during the same episode of diarrhea and do not test stool from
asymptomatic patients, except for epidemiologic studies.

Diagnosis (pediatric)
Because of the high prevalence of asymptomatic carriage of toxigenic C. difficile in infants, testing for CDI should
never be routinely recommended for neonates or infants ≤12 months of age with diarrhea.

C. difficile testing should not be routinely performed in children with diarrhea who are 1-2 years of age unless other
infectious or noninfectious causes have been excluded.

In children ≥2 years of age, C. difficile testing is recommended for patients with prolonged or worsening diarrhea
and risk factors (eg, underlying inflammatory bowel disease or immunocompromising conditions) or relevant
exposures (eg, contact with the healthcare system or recent antibiotics).

Treatment (adults)

Discontinue therapy with the inciting antibiotic agent(s) as soon as possible, as this may influence the risk of CDI

Antibiotic therapy for CDI should be started empirically for situations where a substantial delay in laboratory
confirmation is expected, or for fulminant CDI.

Either vancomycin or fidaxomicin is recommended over metronidazole for an initial episode of CDI. The dosage is
vancomycin 125 mg orally 4 times per day or fidaxomicin 200 mg twice daily for 10 days.

In settings where access to vancomycin or fidaxomicin is limited, metronidazole is suggested for an initial episode
of nonsevere CDI only. The suggested dosage is metronidazole 500 mg orally 3 times per day for 10 days. Avoid
repeated or prolonged courses due to risk of cumulative and potentially irreversible neurotoxicity.

For fulminant CDI, vancomycin administered orally is the regimen of choice. If ileus is present, vancomycin can
also be administered per rectum. The vancomycin dosage is 500 mg orally 4 times per day and 500 mg in
approximately 100 mL normal saline per rectum every 6 hours as a retention enema. Intravenously administered
metronidazole should be administered together with oral or rectal vancomycin, particularly if ileus is present. The
metronidazole dosage is 500 mg intravenously every 8 hours.

If surgical management is necessary for severely ill patients, perform subtotal colectomy with preservation of the
rectum. Diverting loop ileostomy with colonic lavage followed by antegrade vancomycin flushes is an alternative
approach that may lead to improved outcomes.

Treat a first recurrence of CDI with oral vancomycin as a tapered and pulsed regimen rather than a second
standard 10-day course of vancomycin; OR treat a first recurrence of CDI with a 10-day course of fidaxomicin
rather than a standard 10-day course of vancomycin; OR treat a first recurrence of CDI with a standard 10-day
course of vancomycin rather than a second course of metronidazole if metronidazole was used for the primary

Fecal microbiota transplantation is recommended for patients with multiple recurrences of CDI who have failed
appropriate antibiotic treatments.

Treatment (pediatric)

Either metronidazole or vancomycin is recommended for the treatment of children with an initial episode or first
recurrence of nonsevere CDI.

For children with an initial episode of severe CDI or with a second or greater episode of recurrent CDI, oral
vancomycin is recommended over metronidazole.


McDonald LC, Gerding DN, Johnson S, et al. Clinical Practice Guidelines for Clostridium difficile Infection in
Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for
Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018 Feb 15.

Lewis R. New C difficile Guidelines Refine Diagnosis, Add FMT. Medscape Medical News. WebMD Inc.
February 16, 2018.
Crohn Disease
American College of Gastroenterology

Fecal calprotectin is a helpful test that should be considered to help differentiate the presence of inflammatory
bowel disease (IBD) from irritable bowel syndrome (IBS).

In patients at particularly high risk for colorectal neoplasia (eg, personal history of dysplasia, primary sclerosing
cholangitis), chromoendoscopy should be used during colonoscopy, as it may increase the diagnostic yield for
detection of colorectal dysplasia, especially compared with standard-definition white light endoscopy.

For patients undergoing surveillance colonoscopy, there is insufficient evidence to recommend universal
chromoendoscopy for IBD colorectal neoplasia surveillance if the endoscopist has access to high-definition white
light endoscopy.

Narrow-band imaging should not be used during colorectal neoplasia surveillance examinations for Crohn's

Nonsteroidal anti-inflammatory drugs (NSAIDs) may exacerbate disease activity and should be avoided when
possible in patients with Crohn's disease.

Cigarette smoking exacerbates disease activity and accelerates disease recurrence and should be avoided.

Usage of antibiotics should not be restricted in Crohn's disease patients in order to prevent disease flares.

Perceived stress, depression, and anxiety, which are common in IBD, are factors that lead to decreased health-
related quality of life in patients with Crohn's disease, and lead to lower adherence to provider recommendations.
Assessment and management of stress, depression, and anxiety should be included as part of the comprehensive
care of the Crohn's disease patient.

Sulfasalazine is effective for treating symptoms of colonic Crohn's disease that is mild to moderately active and can
be used as treatment for this patient population.

Controlled ileal release budesonide at a dose of 9 mg once daily is effective and should be used for induction of
symptomatic remission for patients with mild-to-moderate ileocecal Crohn's disease.

Metronidazole is not more effective than placebo as therapy for luminal inflammatory Crohn's disease and should
not be used as primary therapy.

For patients with low risk of progression, treatment of active symptoms with antidiarrheals, other non-specific
medications, and dietary manipulation, along with careful observation for inadequate symptom relief, worsening
inflammation, or disease progression, is acceptable.

Oral corticosteroids are effective and can be used for short-term use in alleviating signs and symptoms of
moderate to severely active Crohn's disease. Thiopurines (azathioprine, 6-mercaptopurine) are effective and
should be considered for use for steroid sparing in Crohn's disease.

Azathioprine and 6-mercaptourine are effective therapies and should be considered for treatment of patients with
Crohn's disease for maintenance of remission.

Thiopurine methyltransferase (TPMT) testing should be considered before initial use of azathioprine or 6-
mercaptopurine to treat patients with Crohn's disease.

Methotrexate (up to 25 mg once weekly IM or SC) is effective and should be considered for use in alleviating signs
and symptoms in patients with steroid-dependent Crohn's disease and for maintaining remission.

Anti-TNF agents (infliximab, adalimumab, certolizumab pegol) should be used to treat Crohn's disease that is
resistant to treatment with corticosteroids.

Anti-TNF agents should be given for Crohn's disease refractory to thiopurines or methotrexate.
Combination therapy of infliximab with immunomodulators (thiopurines) is more effective than treatment with either
immunomodulators alone or infliximab alone in patients who are naive to those agents.

For patients with moderately to severely active Crohn's disease and objective evidence of active disease, anti-
integrin therapy (with vedolizumab) with or without an immunomodulator is more effective than placebo and should
be considered to be used for induction of symptomatic remission in patients with Crohn's disease.

Natalizumab is more effective than placebo and should be considered to be used for induction of symptomatic
response and remission in patients with active Crohn's disease.

Natalizumab should be used for maintenance of natalizumab-induced remission of Crohn's disease only if serum
antibody to John Cunningham (JC) virus is negative. Testing for anti-JC virus antibody should be repeated every 6
months and treatment stopped if the result is positive.

Ustekinumab should be given for moderate-to-severe Crohn's disease patients who failed previous treatment with
corticosteroids, thiopurines, methotrexate, or anti-TNF inhibitors or who have had no prior exposure to anti-TNF

Intravenous corticosteroids should be used to treat severe or fulminant Crohn's disease.

Anti-TNF agents (infliximab, adalimumab, certolizumab pegol) can be considered to treat severely active Crohn's

Infliximab may be administered to treat fulminant Crohn's disease. Infliximab is effective and should be considered
in treating perianal fistulas in Crohn's disease. Infliximab may be effective and should be considered in treating
enterocutaneous and rectovaginal fistulas in Crohn's disease.

Adalimumab and certolizumab pegol may be effective and should be considered in treating perianal fistulas in
Crohn's disease.

Thiopurines (azathioprine, 6-mercaptopurine) may be effective and should be considered in treating fistulizing
Crohn's disease.

The addition of antibiotics to infliximab is more effective than infliximab alone and should be considered in treating
perianal fistulas.

Drainage of abscesses (surgically or percutaneously) should be undertaken before treatment of fistulizing Crohn's
disease with anti-TNF agents.

Once remission is induced with corticosteroids, a thiopurine or methotrexate should be considered.

Anti-TNF therapy, specifically infliximab, adalimumab, and certolizumab pegol, should be used to maintain
remission of anti-TNF-induced remission.

Anti-TNF monotherapy is effective at maintaining anti-TNF induced remission, but because of the potential for
immunogenicity and loss of response, combination with azathioprine/6-mercaptopurine or methotrexate should be

Imidazole antibiotics (metronidazole and ornidazole) at doses between 1 and 2 g/day can be used after small
intestinal resection in Crohn's disease patients to prevent recurrence.

In high-risk patients, anti-TNF agents should be started within 4 weeks of surgery in order to prevent postoperative
Crohn's disease recurrence.

An intra-abdominal abscess should be treated with antibiotics and a drainage procedure, either radiographically or


Lichtenstein GR, Loftus EV, Isaacs KL, et al. ACG Clinical Guideline: Management of Crohn's Disease in
Adults. Am J Gastroenterol. 2018 Apr;113(4):481-517.

Crohn Disease Management

Expert Panel, including the Society of Abdominal Radiology Crohn's Disease-Focused Panel, the Society of
Pediatric Radiology, and the American Gastroenterological Association

The number of involved bowel segments and their location, as well as the length and degree of upstream dilation of
Crohn strictures, should be reported by radiologists to help gastroenterologists and surgeons determine the best
therapeutic plan.

Radiologists should state if mural inflammation is present when describing areas with stricture or penetrating

Cross-sectional enterography should be performed at CD diagnosis.

Consider cross-sectional enterography for disease monitoring in patients with small-bowel disease or penetrating

While a dedicated pelvic MR is needed in patients with perianal disease, all CT enterographies and MR
enterographies should also include imaging of the anus.

Radiologists should comment on and describe intramural T2 hyperintensity, restricted diffusion, peri-enteric
stranding, wall thickness, and mural ulcerations seen on imaging because they typically correlate with disease

MRE is preferred over CTE to estimate response to medical treatment in patients with asymptomatic disease.

Non-contrast MRE with T2-weighted and diffusion-weighted imaging is an “acceptable alternative” when
intravenous contrast agents cannot be used.

Radiologists should evaluate CTE and MRE examinations for signs of mesenteric venous thrombosis, occlusions,
or small-bowel varices.


Experts Offer Guidance on Cross-sectional Enterography in Crohn's Disease. Reuters News. January 23,

Bruining DH, Zimmermann EM, Loftus EV Jr, et al. Consensus Recommendations for Evaluation,
Interpretation, and Utilization of Computed Tomography and Magnetic Resonance Enterography in Patients
With Small Bowel Crohn's Disease. Gastroenterology. 2017 Dec 30.

Flu Vaccine and Egg Allergy

Influenza Vaccine and Egg Allergy Practice Parameter Workgroup

Influenza vaccines should be administered to individuals with egg allergy of any severity, just as they would be to
individuals without egg allergy.

No special precautions beyond those recommended for the administration of any vaccine to any patient are
necessary for administration of influenza vaccine to egg-allergic individuals.

Live attenuated influenza vaccine (LAIV) may be administered to patients with egg allergy of any severity in the
age group for which it is approved (ages 2-49 years)—in particular, countries and seasons when LAIV is
recommended as an agent (based on effectiveness in prior seasons).

A large number of studies have reported inactivated influenza vaccine (IIV) to be safe for egg-allergic recipients,
including those with a history of anaphylaxis to egg, with low rates of minor reactions among egg-allergic recipients
that are no greater than those incurred by non–egg-allergic recipients.
Furthermore, these studies have demonstrated that special precautions, such as prevaccine skin testing or
stepwise challenge, are unnecessary for risk stratification.

Moreover, the ovalbumin content in all IIV available in the United States is less than 1 µg per dose, an amount
considered highly unlikely to cause reactions even in the most severely egg-allergic recipients.

Two non–egg-based influenza vaccines have been introduced. One (ccIIV4) is grown in cell culture and in theory
could contain 50 fg of ovalbumin (1 fg equals 1e-9µg). It is approved for recipients 4 years and older. The other
(RIV, available both as trivalent RIV3 and quadrivalent RIV4) uses recombinant hemagglutinin protein produced in
an insect cell line and does not contain egg protein. It is approved for patients 18 years and older. Use of non–egg-
based influenza vaccines (ccIIV3, RIV3, or RIV4) in egg-allergic individuals in the age groups for which they are
approved is acceptable but not medically necessary or preferred.


Kelly JC. New Guideline: Flu Vaccine Safe for Persons With Egg Allergy. Medscape News. WebMD Inc.
December 19, 2017.

Greenhawt M, Turner PJ, Kelso JM. Administration of influenza vaccines to egg allergic recipients: A
practice parameter update 2017. Ann Allergy Asthma Immunol. 2018 Jan;120(1):49-52.

Hepatitis E
European Association for the Study of the Liver

EASL suggests testing for hepatitis E in patients with unexplained flares of chronic liver disease.

EASL recommends HEV testing in all immunosuppressed patients with unexplained abnormal liver function tests

Travelers with hepatitis returning from areas endemic for HEV gt (genotype) 1 or 2 should be tested for HEV.

Pregnant women with HEV gt 1 or 2 should be cared for in a high-dependency setting and transferred to a liver
transplant unit if liver failure occurs.

EASL recommends HEV testing, irrespective of LFT results, in patients presenting with neuralgic amyotrophy (NA)
and GBS (Guillain-Bare syndrome) and suggests HEV testing for patients with encephalitis/myelitis.

EASL suggests testing patients with HEV infection for proteinuria.

Patients with acute or chronic HEV infection who develop new-onset proteinuria may be considered for a renal

EASL suggests antiviral treatment for patients with chronic HEV infection and associated glomerular disease.

EASL recommends using a combination of serology and nucleic acid amplification technique (NAT) testing to
diagnose HEV infection.

EASL recommends NAT testing to diagnose chronic HEV infection.

All patients with hepatitis should be tested for HEV, as part of the first-line virological investigation, irrespective of
travel history.

Patients presenting with suspected drug-induced liver injury (DILI) should be tested for HEV.

Patients with abnormal LFTs after receiving blood products should be tested for HEV.

EASL recommends that blood donor services screen blood donors for HEV by NAT, informed by local risk-
assessment and cost-effectiveness studies, both of which may vary considerably by geographic location.
Ribavirin treatment may be considered in cases of severe acute hepatitis E or acute-on-chronic liver failure.

EASL recommends decreasing immunosuppression at diagnosis of chronic HEV infection in solid organ transplant
recipients, if possible.

In patients with persisting HEV replication three months after detection of HEV RNA, EASL recommends ribavirin
monotherapy for a duration of 12 weeks.

At the end of the scheduled period of therapy, HEV RNA should be assessed in the serum and in the stool. If HEV
RNA is undetectable in both, EASL suggests stopping ribavirin.

In patients in whom HEV RNA is still detectable in the serum and/or in the stool after 12 weeks, ribavirin
monotherapy may be continued for an additional three months (six months therapy overall).

Liver transplant recipients who show no response to ribavirin can be considered for treatment with PEGylated-

Immunocompromised individuals and those with chronic liver diseases should avoid consumption of undercooked
meat (pork, wild boar, and venison) and shellfish.

EASL suggests that immunocompromised patients consume meat only if it has been thoroughly cooked to
temperatures of at least 70 °C.


EASL Clinical Practice Guidelines on hepatitis E virus infection. European Association for the Study of the
Liver. J Hepatol. 2018 Jun;68(6):1256-1271.

Infectious Diseases Society of America and American Society of Tropical Medicine and Hygiene

Although there is a wide range of clinical manifestations of NCC, the 2 most common clinical presentations are with
seizures and increased intracranial pressure.

Initial evaluation should include careful history, physical examination, and neuroimaging studies.

Recommend serologic testing with enzyme-linked immunotransfer blot (EITB) as a confirmatory test in patients
with suspected NCC. Enzyme-linked immunosorbent assay (ELISA) tests using crude antigens should be avoided
because of poor sensitivity and specificity.

Recommend both a brain magnetic resonance imaging (MRI) and a non-contrast computed tomography (CT) scan
for classifying patients with newly diagnosed NCC.

Suggest screening for latent tuberculosis infection in patients likely to require prolonged corticosteroids.

Suggest screening or empiric therapy for Strongyloides stercoralis in patients likely to require prolonged

Recommend that all patients with NCC undergo a funduscopic examination before initiation of anthelminthic

Suggest that patients with NCC who have probably acquired NCC in a non-endemic area have their household
members be screened for tapeworm carriage. Remark: This is a public health issue and can often be addressed by
the local health department.

Recommend that patients treated with albendazole for more than 14 days be monitored for hepatotoxicity and
No additional monitoring is needed for patients receiving combination therapy with albendazole and praziquantel
beyond that recommended for albendazole monotherapy.

In patients with untreated hydrocephalus or diffuse cerebral edema, we recommend management of elevated
intracranial pressure alone and not antiparasitic treatment. Remarks: The management of patients with diffuse
cerebral edema should be anti-inflammatory therapy such as corticosteroids, whereas hydrocephalus usually
requires a surgical approach.

In the absence of elevated intracranial pressure, we recommend the use of antiparasitic drugs in all patients with

For patients with one to two viable parenchymal cysticerci, we recommend albendazole monotherapy for 10–14
days compared with either no antiparasitic therapy or combination antiparasitic therapy. Remarks: The usual dose
of albendazole is 15 mg/kg/day divided into two daily doses for 10–14 days with food. We recommend a maximum
dose of 1,200 mg/day.

We recommend albendazole (15 mg/kg/day) combined with praziquantel (50 mg/kg/day) for 10–14 days rather
than albendazole monotherapy for patients with more than two viable parenchymal cysticerci.

We suggest re-treatment with antiparasitic therapy for parenchymal cystic lesions persisting for 6 months after the
end of the initial course of therapy.

We suggest that MRI be repeated at least every 6 months until resolution of the cystic component.

We recommend antiepileptic drugs for all patients with single enhancing lesions (SEL) and seizures.

In patients who have been seizure free for 6 months, we suggest tapering off and stopping antiepileptic drugs after
resolution of the lesion in patients with SEL without risk factors for recurrent seizures.

We suggest albendazole therapy rather than no antiparasitic therapy for all patients with SEL.

We recommend MRI with three-dimensional (3D) volumetric sequencing to identify intraventricular and
subarachnoid cysticerci in patients with hydrocephalus and suspected neurocysticercosis (NCC).

We recommend that patients with hydrocephalus from SAN be treated with shunt surgery in addition to medical

We recommend corticosteroid treatment of patients with SN with evidence of spinal cord dysfunction (eg,
paraparesis or incontinence) or as adjunctive therapy along with antiparasitic therapy.


White AC, Coyle CM, Rajshekhar V, et al. Diagnosis and Treatment of Neurocysticercosis: 2017 Clinical
Practice Guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of
Tropical Medicine and Hygiene (ASTMH). Am J Trop Med Hyg. 2018 Apr;98(4):945-966.

Neuropathic Pain Pharmacotherapy

Japanese Society of Pain Clinicians

First-line drugs

Pregabalin inhibits the release of excitatory neurotransmitters by combining with alpha-2-delta subunits of voltage-
dependent calcium channels in the central nervous system. Similarly, gabapentin and gabapentin enacarbil work
by combining with alpha-2-delta subunits.

The analgesic effect of serotonin-noradrenaline reuptake inhibitors (SNRIs) is considered to be mediated by

activation of the descending pain inhibitory system. Duloxetine improves not only pain, but also quality of life in
patients with peripheral neuropathy. In addition to duloxetine, two other SNRIs, venlafaxine and milnacipran, are
Second-line drugs

The extract from inflamed cutaneous tissue of rabbits inoculated with vaccinia virus (ERV) has been found to be
effective, particularly for post-herpetic neuralgia.

Tramadol acts as both a mu-opioid receptor agonist and SNRI. It is categorized as an opioid analgesic [weak],
which is not designated as a restricted opioid for medical use. The analgesic effects of tramadol have been
demonstrated for painful diabetic polyneuropathy, postherpetic neuralgia, and cancer-related neuropathic pain.

Third-line drugs

Opioid analgesics are effective for a variety of diseases associated with peripheral and central neuropathic pain,
including painful diabetic polyneuropathy and post-herpetic neuralgia.

There is abundant evidence for the analgesic efficacy of morphine and oxycodone. Transdermal fentanyl (both 1-
and 3-day patches) has been approved for moderate-severe cancer pain when switching from other opioid
analgesics. Buprenorphine hydrochloride is a partial agonist for mu-opioid receptors, showing equivalent efficacy.


Sumitani M, Sakai T, Matsuda Y, et al. Executive summary of the Clinical Guidelines of Pharmacotherapy for
Neuropathic Pain: second edition by the Japanese Society of Pain Clinicians. J Anesth. 2018 Jun;32(3):463-

Postbariatric Care
European Association for the Study of Obesity

The ingestion of solid foods in the first days after surgery is impossible, and a gradual change of food consistency
in the first postoperative weeks is preferred in order to avoid or minimize regurgitation and vomiting, which can
threaten the integrity and safety of the recent surgical procedure and result in severe vitamin B1 (thiamine)

A low-sugar, clear-liquid meal program is usually initiated within 24 hours after surgery, and patients are then
instructed to gradually and progressively change the food consistency, moving from clear liquids to soft or creamy
foods and then to solid, chewable items over a period of 2-4 weeks.

After the end of the postoperative diet and thereafter, patients should receive periodic counseling by a registered
dietitian about long-term dietary modifications in order to maximize the results of the bariatric procedure and
reduce the risk of late weight regain.

Patients with gastric restriction should be counseled to eat 3 small meals during the day and chew small bites of
food thoroughly before swallowing, without drinking beverages at the same time (more than 30 minutes apart).

Dietary counseling should address the problem of protein intake, particularly in the first months after surgery.
Current guidelines suggest a minimal protein intake of 60 g/day and up to 1.5 g/kg ideal body weight per day, but
higher amounts of protein intake (up to 2.1 g/kg ideal body weight per day) may be required in individual cases.
The use of liquid protein supplements (30 g/day) can facilitate adequate protein intake in the first period after

In case of persistent (>6 months) and/or frequent vomiting, a physical cause should be suspected and a surgical
diagnostic work-up considered. Persistent vomiting heavily disturbing normal eating and greatly reducing energy
intake can precipitate the onset of an acute state of thiamine deficiency that needs to be considered and

Dumping refers to the postprandial occurrence of a constellation of symptoms elicited by the rapid transit of calorie-
dense food to the small bowel. Nutritional manipulation is usually sufficient to control dumping. Nutritional tips
comprise eating small but frequent meals, avoiding ingestion of liquids within 30 minutes of a solid-food meal,
avoiding simple sugars, increasing intake of fiber and complex carbohydrates, and increasing protein intake.
The occurrence of vitamin and mineral deficiencies is one of the most common and compelling problems after
bariatric surgery. Prevention, detection, and treatment of these deficiencies represent cornerstones of long-term
follow-up in postbariatric patients.

Prophylactic empiric iron supplementation is recommended after gastric bypass, biliopancreatic diversion,
duodenal switch, and sleeve gastrectomy.

Even in the absence of conclusive evidence concerning the long-term risk of fractures after bariatric surgery,
calcium and vitamin D routine supplementation is strongly recommended after gastric bypass and malabsorptive

Routine fat-soluble vitamin supplementation is recommended in all patients having undergone biliopancreatic
diversion or biliopancreatic diversion with duodenal switch.

Suggested daily supplementation for patients with gastric bypass and sleeve gastrectomy includes 2 adult
multivitamin plus mineral supplements (containing iron, folic acid, and thiamine); 1,200-1,500 mg of elemental
calcium (in diet and as citrated supplement in divided doses); at least 3,000 IU of vitamin D (titrated to therapeutic
25-hydroxyvitamin D levels >30 ng/ml); and vitamin B12 titrated to maintain normal levels. Routine supplementation
with adequate amounts of fat-soluble vitamins should be added to this regimen after biliopancreatic diversion or
duodenal switch. In the case of gastric banding, the suggested daily supplementation may be reduced to adult
multivitamin plus mineral supplement and at least 3,000 IU of vitamin D (titrated to vitamin D levels) with or without
1,200-1,500 mg of elemental calcium (in diet and as citrated supplement in divided doses).

Ideally, metabolic control should be optimized in patients with obesity and type 2 diabetes in preparation for a
bariatric procedure. HbA1c levels of 6.5-7%, fasting glucose levels <110 mg/dl, and 2-hour postload glucose <140
mg/dl should be targeted.

Nutritional deficiencies are more common in the first 12-18 months after surgery, when maximal weight loss occurs.
A higher incidence of stillbirths has been reported when pregnancy occurs in the first year after surgery.
Furthermore, obstetric complications after bariatric surgery are more frequent at higher BMI. Pregnancy is hence
not recommended during 12-18 months following surgery.


Parry NM. Guidelines for Medical Care of Postbariatric Patients. Medscape News. WebMD Inc. December
22, 2017.

Busetto L, Dicker D, Azran C, et al. Practical Recommendations of the Obesity Management Task Force of
the European Association for the Study of Obesity for the Post-Bariatric Surgery Medical Management.
Obes Facts. 2017 Dec 6;10(6):597-632.

Testosterone Deficiency
British Society for Sexual Medicine

Screen all men presenting with ED, loss of spontaneous erections, or low sexual desire.

Screen for TD in all men with type 2 diabetes mellitus, BMI >30 kg/m2, or waist circumference >102 cm.

Screen for TD in all men on long-term opiate, antipsychotic, or anticonvulsant medication.

Restrict diagnosis of TD to men with persistent symptoms suggesting TD and confirmed low T.

Measure fasting T levels in the morning before 11 AM, acknowledging that, in normal life, nonfasting levels could
be up to 30% lower.

Repeat total testosterone (TT) assessment on ≥2 occasions by a reliable method; in addition, measure free
testosterone (FT) in men with levels close to the lower normal range (8-12 nmol/L) or those with suspected or
known abnormal sex hormone binding globulin (SHBG) levels.
Measure luteinizing hormone (LH) serum levels to differentiate primary from secondary TD.

Perform cardiovascular, prostate, breast, and hematologic assessments before start of treatment.

Offer T therapy to symptomatic men with TD syndrome for treated localized low-risk prostate cancer (Gleason
score <8, stages 1-2, preoperative PSA level <10 ng/mL, and not starting before 1 year of follow-up) and without
evidence of active disease (based on measurable PSA level, DRE result, and evidence of metastatic disease).

Assess response to therapy at 3, 6, and 12 months and every 12 months thereafter.

Aim for a target TT level of 15-30 nmol/L to achieve optimal response.

Assess prostate health by PSA and DRE before commencing testosterone replacement therapy followed by PSA
at 3-6 months, 12 months, and every 12 months thereafter.


Hackett G, Kirby M, Edwards D, et al. British Society for Sexual Medicine Guidelines on Adult Testosterone
Deficiency, With Statements for UK Practice. J Sex Med. 2017 Dec;14(12):1504-23.

Medscape © 2018 WebMD, LLC

Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.

Cite this: John Anello, Brian Feinberg, John Heinegg, et. al. Internal Medicine Clinical Practice Guidelines: 2018
Midyear Review - Medscape - Jul 10, 2018.