2017 European Ulcerative Colitis Guidelines – Diagnosis – Part One of Two Parts

Section 6: Opportunistic Infections

ECCO statement 6A [statement 2B in Rahier et al.11]

Ulcerative colitis patients at risk of opportunistic infections are those treated with immunomodulators [EL1], especially in combination [EL3], and those with malnutrition [EL5]. In addition, comorbidities and a history of serious infections should be considered. Age is an independent risk factor for opportunistic infections [EL3]

UC patients per se are not immunocompromised, but may have altered immune responsiveness as a consequence of their medical treatment [see statement 2A in Rahier et al.11]. Older age is an independent risk factor for OI and OI-related adverse events in UC.364,365 Corticosteroids increase the risk of OI when administered in a dosage greater than 20 mg of prednisolone daily for more than 2 weeks.366,367 All IMs used for IBD increase the hazard of OI, and the use of more than one IM at a time may carry an increased risk of more than 14-fold.368

ECCO statement 6B [statement 3B in Rahier et al.11]

All ulcerative colitis patients should be tested for HBV [HBsAg, anti-HBAbs, anti-HBcAb] at diagnosis. In patients with positive HBsAg, viraemia [HBV-DNA] should also be quantified [EL2]

ECCO statement 6C [statement 3C in Rahier et al.11]

HBV vaccination is recommended in all HBV anti-HBcAb seronegative patients with ulcerative colitis [EL5]. Efficacy of hepatitis B vaccination is impaired in inflammatory bowel disease, probably by the disease itself and by the anti-TNF drugs. Anti-HBs response should be measured after vaccination. Higher doses of the immunising antigen may be required to provide protection [EL 4]. Maintenance of HBs antibody should be monitored in patients at risk [EL 5]

ECCO statement 6D [statement 3D in Rahier et al.11]

Before, during, and for at least 12 months after immunomodulator treatment has ceased, patients who are HBsAg positive should receive potent anti-viral agents [nucleoside/nucleotide analogues with high barrier to resistance] regardless of the degree of viraemia, in order to avoid hepatitis B flare [EL2]

ECCO statement 6E [adapted from statement 3E in Rahier et al.11]

Reactivation of occult HBV rarely occurs with immunosuppressive therapy used in ulcerative colitis [EL2]. Viraemia [HBV DNA] should be assessed every 2–3 months but antiviral therapy is not recommended unless HBV-DNA is detected [EL5]

Given the increased risk of OI while receiving IMs, UC patients should be encouraged to receive HIV testing.11 Seropositivity is not a definite contraindication for IMs [see statement 3F in Rahier et al.11].375–377 UC patients should also be tested for HCV-Ab and, if positive, the result should be confirmed by HCV-RNA detection. IMs per se do not worsen HCV infection, unless a concomitant infection associated with HBV or HIV is present,378 but they can worsen the liver toxicity of medications in HCV-Ab positive subjects.

Information on CMV, HSV, VZV, EBV, HPV, or influenza virus can be found in Supplementary material, available as Supplementary data at ECCO-JCC online.

6.3. Parasites and fungal agents

Additional information on parasites and fungal agents can be found in Supplementary material, available as Supplementary data at ECCO-JCConline.11,185,357,379–400  

[See References Download for the above references on parasites and fungal disease]

ECCO statement 6F [statement 6A in Rahier et al.11]

Reactivation of latent tuberculosis in patients treated with anti-TNF is increased and is more severe than in the background population [EL2]. Latent tuberculosis should be diagnosed by a combination of patient history, chest X-ray, tuberculin skin test, and interferon-gamma release assays according to local prevalence and national recommendations. Screening should be considered at diagnosis and always performed before anti-TNF therapy [EL5]. Interferon-gamma release assays are likely to complement the tuberculin skin test and are preferred in BCG-immunised individuals [EL1]

6.3.2. Bacterial agents

Pneumococcal vaccination should be offered to UC patients before starting IM, and should ideally be administered 2 weeks before treatment initiation. IM can impair immunity to Streptococcus pneumoniae after polysaccharide vaccination [see statement 7A & 7B in Rahier et al.11].403,406 UC patients taking IM who develop pneumonia should be tested for pneumococcal infections and Legionella pneumophila.407,408 UC patients receiving IM therapy experience more severe infections with Salmonella spp. [see statement 7E in Rahier et al.11]. Withholding IM until active infections are resolved is recommended [see statements 7C to 7E in Rahier et al.11]. IMs, especially anti-TNF, increase the risk of systemic and central nervous infections with Listeria monocytogenes [see statement 7F in Rahier et al.11].403 The same applies to Nocardia spp.-related systemic or skin infections [see statement 7G in Rahier et al.11].373,409–411 Anti-TNF therapy should be withdrawn during infection, and infectious disease experts should be consulted before reintroducing IM.

ECCO statement 6G [adapted from statement 7H in Rahier et al.11]

Ulcerative colitis is an independent risk factor for infection with C. difficile [EL3]

ECCO statement 6H [statement 7K in Rahier et al.11]

Metronidazole and oral vancomycin are equally effective in treating mild to moderate C. difficile-associated disease [EL1]. It remains to be established if this applies to patients with ulcerative colitis. Other antibiotics should be stopped if possible. For severe disease, vancomycin has been shown to be superior in patients without ulcerative colitis [EL1] and is therefore preferable. In C. difficile-associated disease, use of immunomodulators should be guided by careful risk benefit evaluation and clinical judgement [EL4]

IMs are independent predictors of severe C. difficile-associated disease.11,413,413

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