IBD, in full.

Outpatient positioning is unchanged from the ACG 2025 UC guideline and the AGA living guideline for moderate-to-severe UC. Confirm UC with endoscopy showing continuous colonic inflammation from the rectum plus histology, after excluding infection with two-step C. difficile testing. Treat mild-moderate disease with 5-ASA chosen by route and extent: suppository for proctitis, enema for left-sided disease, oral plus rectal for extensive disease. If 5-ASA fails, treat as moderate-to-severe rather than stepping up gradually. Position advanced therapy by efficacy tier, not by an anti-TNF-first rule. Advanced-therapy-naive, higher efficacy: infliximab, vedolizumab, ozanimod, etrasimod, upadacitinib, risankizumab, guselkumab. Intermediate: golimumab, ustekinumab, tofacitinib, filgotinib, mirikizumab. Lower: adalimumab. Previously TNF-exposed, higher efficacy: tofacitinib, upadacitinib, ustekinumab. Lower: adalimumab, vedolizumab, ozanimod, etrasimod. After anti-TNF primary non-response, switch mechanism rather than cycling within the class. Treat to target (STRIDE-II): endoscopic improvement, Mayo endoscopic subscore 0-1. Begin CRC surveillance 8-10 years after diagnosis for extensive or left-sided disease; isolated proctitis follows average-risk screening. Inpatient care now follows the 2026 AGA Clinical Practice Update (13 best-practice statements). Admit for severe symptoms refractory to outpatient therapy, suspected complications (obstruction, abscess, toxic megacolon) or significant malnutrition, and identify acute severe UC by Truelove-Witts. Give every patient admitted with diarrhea two-step C. difficile testing. Test for CMV, with early endoscopy, if symptoms worsen, the patient is systemically toxic or disease is steroid-refractory. Give routine VTE prophylaxis with LMWH or fondaparinux unless contraindicated, and individualize post-discharge extension. Give IV methylprednisolone 60 mg/day or equivalent; the AGA living guideline says 40-60 mg/day, and higher doses add no benefit. Do not give adjunctive antibiotics without infection. Involve surgery early. Assess response by day 3 (72 h) using stool frequency and CRP (Oxford criteria); do not continue IV steroids beyond about 7 days without response. Rescue steroid non-responders with infliximab (accelerated or intensified dosing in selected patients with high inflammatory burden or protein-losing colopathy), cyclosporine, or a JAK inhibitor at standard or intensified dosing, or with colectomy. Before discharge, the response should be stable and a transition plan should be in place.

Two current US guidelines govern Crohn's disease and should be read together. ACG 2025 (Lichtenstein et al.) remains the reference for diagnosis, mild-to-moderate disease, perianal, postoperative and abscess management. DIAGNOSIS: fecal calprotectin (>50-100 μg/g) separates inflammatory from noninflammatory disease of the colon. Workup is ileocolonoscopy with biopsies, including uninvolved mucosa, plus small-bowel imaging. CTE and MRE are comparable; prefer MRE in patients <35 y and when serial exams are likely. Intestinal ultrasound is an ungraded adjunct. Do routine CRC surveillance in Crohn's colitis. MILD-TO-MODERATE: recommend against oral mesalamine; sulfasalazine only for symptomatic mild colonic CD; ileal-release budesonide 9 mg for induction in ileocecal disease but not for maintenance. MODERATE-TO-SEVERE (AGA Living Guideline, Scott et al., Gastroenterology 2025;169(7):1397-1448, 16 recommendations: 1 strong, 9 conditional, 6 knowledge gaps; updated quarterly, adult outpatients only): RECOMMEND infliximab, adalimumab, ustekinumab, risankizumab, mirikizumab, guselkumab or upadacitinib over no treatment; SUGGEST certolizumab pegol or vedolizumab over no treatment. Advanced-therapy-naive: suggest higher-efficacy agents (infliximab, adalimumab, vedolizumab, ustekinumab, risankizumab, mirikizumab, guselkumab) over lower-efficacy ones (certolizumab pegol, upadacitinib). Prior advanced-therapy (especially anti-TNF) exposure: suggest higher- or intermediate-efficacy agents (adalimumab, risankizumab, guselkumab, upadacitinib; ustekinumab, mirikizumab) over lower-efficacy ones (vedolizumab, certolizumab pegol). Suggest against thiopurine monotherapy for induction; suggest it for maintenance of remission. Suggest SC/IM methotrexate monotherapy; suggest against oral methotrexate. In thiopurine-naive patients starting infliximab, suggest infliximab + thiopurine over infliximab alone. No recommendation on IFX + MTX, adalimumab + immunomodulator, or non-TNF biologic + immunomodulator. After ≥6 months of steroid-free remission on anti-TNF + immunomodulator, suggest withdrawing the immunomodulator and suggest against withdrawing the anti-TNF. SUGGEST upfront advanced therapy over step-up therapy (corticosteroids and/or immunomodulator first). No recommendation on treating to endoscopic vs symptomatic remission. The ACG 2025 moderate-to-severe recommendations (anti-TNF, IFX + thiopurine combination and IL-12/23/IL-23 agents, each strong/moderate; upadacitinib after anti-TNF exposure; steroids for short-term induction only; TPMT/NUDT15 testing before thiopurines) still stand alongside AGA. ACG perianal (infliximab first; drain abscesses and place setons before escalating), postoperative (endoscopy at 6-12 months; anti-TNF strong, vedolizumab conditional in high-risk patients) and intra-abdominal abscess (>2 cm: antibiotics plus drainage, hold immunosuppression) positions are unchanged. THERAPEUTIC ENDOSCOPY (AGA Clinical Practice Update, CGH 2026; details below come from AGA news coverage, not the full text, and are ungraded advice): get cross-sectional imaging before the procedure. Endoscopic balloon dilation is first-line for short strictures (about ≤4-5 cm) with few risk factors (fistula, prestenotic dilation >5 cm, high CRP, prior anti-TNF). Longer or multiple strictures, or ≥3 risk factors, favor surgery.

Two current US guidelines govern Crohn's disease and should be read together. ACG 2025 (Lichtenstein et al.) remains the reference for diagnosis, mild-to-moderate disease, perianal, postoperative and abscess management. DIAGNOSIS: fecal calprotectin (>50-100 μg/g) separates inflammatory from noninflammatory disease of the colon. Workup is ileocolonoscopy with biopsies, including uninvolved mucosa, plus small-bowel imaging. CTE and MRE are comparable; prefer MRE in patients <35 y and when serial exams are likely. Intestinal ultrasound is an ungraded adjunct. Do routine CRC surveillance in Crohn's colitis. MILD-TO-MODERATE: recommend against oral mesalamine; sulfasalazine only for symptomatic mild colonic CD; ileal-release budesonide 9 mg for induction in ileocecal disease but not for maintenance. MODERATE-TO-SEVERE (AGA Living Guideline, Scott et al., Gastroenterology 2025;169(7):1397-1448, 16 recommendations: 1 strong, 9 conditional, 6 knowledge gaps; updated quarterly, adult outpatients only): RECOMMEND infliximab, adalimumab, ustekinumab, risankizumab, mirikizumab, guselkumab or upadacitinib over no treatment; SUGGEST certolizumab pegol or vedolizumab over no treatment. Advanced-therapy-naive: suggest higher-efficacy agents (infliximab, adalimumab, vedolizumab, ustekinumab, risankizumab, mirikizumab, guselkumab) over lower-efficacy ones (certolizumab pegol, upadacitinib). Prior advanced-therapy (especially anti-TNF) exposure: suggest higher- or intermediate-efficacy agents (adalimumab, risankizumab, guselkumab, upadacitinib; ustekinumab, mirikizumab) over lower-efficacy ones (vedolizumab, certolizumab pegol). Suggest against thiopurine monotherapy for induction; suggest it for maintenance of remission. Suggest SC/IM methotrexate monotherapy; suggest against oral methotrexate. In thiopurine-naive patients starting infliximab, suggest infliximab + thiopurine over infliximab alone. No recommendation on IFX + MTX, adalimumab + immunomodulator, or non-TNF biologic + immunomodulator. After ≥6 months of steroid-free remission on anti-TNF + immunomodulator, suggest withdrawing the immunomodulator and suggest against withdrawing the anti-TNF. SUGGEST upfront advanced therapy over step-up therapy (corticosteroids and/or immunomodulator first). No recommendation on treating to endoscopic vs symptomatic remission. The ACG 2025 moderate-to-severe recommendations (anti-TNF, IFX + thiopurine combination and IL-12/23/IL-23 agents, each strong/moderate; upadacitinib after anti-TNF exposure; steroids for short-term induction only; TPMT/NUDT15 testing before thiopurines) still stand alongside AGA. ACG perianal (infliximab first; drain abscesses and place setons before escalating), postoperative (endoscopy at 6-12 months; anti-TNF strong, vedolizumab conditional in high-risk patients) and intra-abdominal abscess (>2 cm: antibiotics plus drainage, hold immunosuppression) positions are unchanged. THERAPEUTIC ENDOSCOPY (AGA Clinical Practice Update, CGH 2026; details below come from AGA news coverage, not the full text, and are ungraded advice): get cross-sectional imaging before the procedure. Endoscopic balloon dilation is first-line for short strictures (about ≤4-5 cm) with few risk factors (fistula, prestenotic dilation >5 cm, high CRP, prior anti-TNF). Longer or multiple strictures, or ≥3 risk factors, favor surgery.

Two current US guidelines govern Crohn's disease and should be read together. ACG 2025 (Lichtenstein et al.) remains the reference for diagnosis, mild-to-moderate disease, perianal, postoperative and abscess management. DIAGNOSIS: fecal calprotectin (>50-100 μg/g) separates inflammatory from noninflammatory disease of the colon. Workup is ileocolonoscopy with biopsies, including uninvolved mucosa, plus small-bowel imaging. CTE and MRE are comparable; prefer MRE in patients <35 y and when serial exams are likely. Intestinal ultrasound is an ungraded adjunct. Do routine CRC surveillance in Crohn's colitis. MILD-TO-MODERATE: recommend against oral mesalamine; sulfasalazine only for symptomatic mild colonic CD; ileal-release budesonide 9 mg for induction in ileocecal disease but not for maintenance. MODERATE-TO-SEVERE (AGA Living Guideline, Scott et al., Gastroenterology 2025;169(7):1397-1448, 16 recommendations: 1 strong, 9 conditional, 6 knowledge gaps; updated quarterly, adult outpatients only): RECOMMEND infliximab, adalimumab, ustekinumab, risankizumab, mirikizumab, guselkumab or upadacitinib over no treatment; SUGGEST certolizumab pegol or vedolizumab over no treatment. Advanced-therapy-naive: suggest higher-efficacy agents (infliximab, adalimumab, vedolizumab, ustekinumab, risankizumab, mirikizumab, guselkumab) over lower-efficacy ones (certolizumab pegol, upadacitinib). Prior advanced-therapy (especially anti-TNF) exposure: suggest higher- or intermediate-efficacy agents (adalimumab, risankizumab, guselkumab, upadacitinib; ustekinumab, mirikizumab) over lower-efficacy ones (vedolizumab, certolizumab pegol). Suggest against thiopurine monotherapy for induction; suggest it for maintenance of remission. Suggest SC/IM methotrexate monotherapy; suggest against oral methotrexate. In thiopurine-naive patients starting infliximab, suggest infliximab + thiopurine over infliximab alone. No recommendation on IFX + MTX, adalimumab + immunomodulator, or non-TNF biologic + immunomodulator. After ≥6 months of steroid-free remission on anti-TNF + immunomodulator, suggest withdrawing the immunomodulator and suggest against withdrawing the anti-TNF. SUGGEST upfront advanced therapy over step-up therapy (corticosteroids and/or immunomodulator first). No recommendation on treating to endoscopic vs symptomatic remission. The ACG 2025 moderate-to-severe recommendations (anti-TNF, IFX + thiopurine combination and IL-12/23/IL-23 agents, each strong/moderate; upadacitinib after anti-TNF exposure; steroids for short-term induction only; TPMT/NUDT15 testing before thiopurines) still stand alongside AGA. ACG perianal (infliximab first; drain abscesses and place setons before escalating), postoperative (endoscopy at 6-12 months; anti-TNF strong, vedolizumab conditional in high-risk patients) and intra-abdominal abscess (>2 cm: antibiotics plus drainage, hold immunosuppression) positions are unchanged. THERAPEUTIC ENDOSCOPY (AGA Clinical Practice Update, CGH 2026; details below come from AGA news coverage, not the full text, and are ungraded advice): get cross-sectional imaging before the procedure. Endoscopic balloon dilation is first-line for short strictures (about ≤4-5 cm) with few risk factors (fistula, prestenotic dilation >5 cm, high CRP, prior anti-TNF). Longer or multiple strictures, or ≥3 risk factors, favor surgery.

Outpatient positioning is unchanged from the ACG 2025 UC guideline and the AGA living guideline for moderate-to-severe UC. Confirm UC with endoscopy showing continuous colonic inflammation from the rectum plus histology, after excluding infection with two-step C. difficile testing. Treat mild-moderate disease with 5-ASA chosen by route and extent: suppository for proctitis, enema for left-sided disease, oral plus rectal for extensive disease. If 5-ASA fails, treat as moderate-to-severe rather than stepping up gradually. Position advanced therapy by efficacy tier, not by an anti-TNF-first rule. Advanced-therapy-naive, higher efficacy: infliximab, vedolizumab, ozanimod, etrasimod, upadacitinib, risankizumab, guselkumab. Intermediate: golimumab, ustekinumab, tofacitinib, filgotinib, mirikizumab. Lower: adalimumab. Previously TNF-exposed, higher efficacy: tofacitinib, upadacitinib, ustekinumab. Lower: adalimumab, vedolizumab, ozanimod, etrasimod. After anti-TNF primary non-response, switch mechanism rather than cycling within the class. Treat to target (STRIDE-II): endoscopic improvement, Mayo endoscopic subscore 0-1. Begin CRC surveillance 8-10 years after diagnosis for extensive or left-sided disease; isolated proctitis follows average-risk screening. Inpatient care now follows the 2026 AGA Clinical Practice Update (13 best-practice statements). Admit for severe symptoms refractory to outpatient therapy, suspected complications (obstruction, abscess, toxic megacolon) or significant malnutrition, and identify acute severe UC by Truelove-Witts. Give every patient admitted with diarrhea two-step C. difficile testing. Test for CMV, with early endoscopy, if symptoms worsen, the patient is systemically toxic or disease is steroid-refractory. Give routine VTE prophylaxis with LMWH or fondaparinux unless contraindicated, and individualize post-discharge extension. Give IV methylprednisolone 60 mg/day or equivalent; the AGA living guideline says 40-60 mg/day, and higher doses add no benefit. Do not give adjunctive antibiotics without infection. Involve surgery early. Assess response by day 3 (72 h) using stool frequency and CRP (Oxford criteria); do not continue IV steroids beyond about 7 days without response. Rescue steroid non-responders with infliximab (accelerated or intensified dosing in selected patients with high inflammatory burden or protein-losing colopathy), cyclosporine, or a JAK inhibitor at standard or intensified dosing, or with colectomy. Before discharge, the response should be stable and a transition plan should be in place.

Outpatient positioning is unchanged from the ACG 2025 UC guideline and the AGA living guideline for moderate-to-severe UC. Confirm UC with endoscopy showing continuous colonic inflammation from the rectum plus histology, after excluding infection with two-step C. difficile testing. Treat mild-moderate disease with 5-ASA chosen by route and extent: suppository for proctitis, enema for left-sided disease, oral plus rectal for extensive disease. If 5-ASA fails, treat as moderate-to-severe rather than stepping up gradually. Position advanced therapy by efficacy tier, not by an anti-TNF-first rule. Advanced-therapy-naive, higher efficacy: infliximab, vedolizumab, ozanimod, etrasimod, upadacitinib, risankizumab, guselkumab. Intermediate: golimumab, ustekinumab, tofacitinib, filgotinib, mirikizumab. Lower: adalimumab. Previously TNF-exposed, higher efficacy: tofacitinib, upadacitinib, ustekinumab. Lower: adalimumab, vedolizumab, ozanimod, etrasimod. After anti-TNF primary non-response, switch mechanism rather than cycling within the class. Treat to target (STRIDE-II): endoscopic improvement, Mayo endoscopic subscore 0-1. Begin CRC surveillance 8-10 years after diagnosis for extensive or left-sided disease; isolated proctitis follows average-risk screening. Inpatient care now follows the 2026 AGA Clinical Practice Update (13 best-practice statements). Admit for severe symptoms refractory to outpatient therapy, suspected complications (obstruction, abscess, toxic megacolon) or significant malnutrition, and identify acute severe UC by Truelove-Witts. Give every patient admitted with diarrhea two-step C. difficile testing. Test for CMV, with early endoscopy, if symptoms worsen, the patient is systemically toxic or disease is steroid-refractory. Give routine VTE prophylaxis with LMWH or fondaparinux unless contraindicated, and individualize post-discharge extension. Give IV methylprednisolone 60 mg/day or equivalent; the AGA living guideline says 40-60 mg/day, and higher doses add no benefit. Do not give adjunctive antibiotics without infection. Involve surgery early. Assess response by day 3 (72 h) using stool frequency and CRP (Oxford criteria); do not continue IV steroids beyond about 7 days without response. Rescue steroid non-responders with infliximab (accelerated or intensified dosing in selected patients with high inflammatory burden or protein-losing colopathy), cyclosporine, or a JAK inhibitor at standard or intensified dosing, or with colectomy. Before discharge, the response should be stable and a transition plan should be in place.

Outpatient positioning is unchanged from the ACG 2025 UC guideline and the AGA living guideline for moderate-to-severe UC. Confirm UC with endoscopy showing continuous colonic inflammation from the rectum plus histology, after excluding infection with two-step C. difficile testing. Treat mild-moderate disease with 5-ASA chosen by route and extent: suppository for proctitis, enema for left-sided disease, oral plus rectal for extensive disease. If 5-ASA fails, treat as moderate-to-severe rather than stepping up gradually. Position advanced therapy by efficacy tier, not by an anti-TNF-first rule. Advanced-therapy-naive, higher efficacy: infliximab, vedolizumab, ozanimod, etrasimod, upadacitinib, risankizumab, guselkumab. Intermediate: golimumab, ustekinumab, tofacitinib, filgotinib, mirikizumab. Lower: adalimumab. Previously TNF-exposed, higher efficacy: tofacitinib, upadacitinib, ustekinumab. Lower: adalimumab, vedolizumab, ozanimod, etrasimod. After anti-TNF primary non-response, switch mechanism rather than cycling within the class. Treat to target (STRIDE-II): endoscopic improvement, Mayo endoscopic subscore 0-1. Begin CRC surveillance 8-10 years after diagnosis for extensive or left-sided disease; isolated proctitis follows average-risk screening. Inpatient care now follows the 2026 AGA Clinical Practice Update (13 best-practice statements). Admit for severe symptoms refractory to outpatient therapy, suspected complications (obstruction, abscess, toxic megacolon) or significant malnutrition, and identify acute severe UC by Truelove-Witts. Give every patient admitted with diarrhea two-step C. difficile testing. Test for CMV, with early endoscopy, if symptoms worsen, the patient is systemically toxic or disease is steroid-refractory. Give routine VTE prophylaxis with LMWH or fondaparinux unless contraindicated, and individualize post-discharge extension. Give IV methylprednisolone 60 mg/day or equivalent; the AGA living guideline says 40-60 mg/day, and higher doses add no benefit. Do not give adjunctive antibiotics without infection. Involve surgery early. Assess response by day 3 (72 h) using stool frequency and CRP (Oxford criteria); do not continue IV steroids beyond about 7 days without response. Rescue steroid non-responders with infliximab (accelerated or intensified dosing in selected patients with high inflammatory burden or protein-losing colopathy), cyclosporine, or a JAK inhibitor at standard or intensified dosing, or with colectomy. Before discharge, the response should be stable and a transition plan should be in place.

Outpatient positioning is unchanged from the ACG 2025 UC guideline and the AGA living guideline for moderate-to-severe UC. Confirm UC with endoscopy showing continuous colonic inflammation from the rectum plus histology, after excluding infection with two-step C. difficile testing. Treat mild-moderate disease with 5-ASA chosen by route and extent: suppository for proctitis, enema for left-sided disease, oral plus rectal for extensive disease. If 5-ASA fails, treat as moderate-to-severe rather than stepping up gradually. Position advanced therapy by efficacy tier, not by an anti-TNF-first rule. Advanced-therapy-naive, higher efficacy: infliximab, vedolizumab, ozanimod, etrasimod, upadacitinib, risankizumab, guselkumab. Intermediate: golimumab, ustekinumab, tofacitinib, filgotinib, mirikizumab. Lower: adalimumab. Previously TNF-exposed, higher efficacy: tofacitinib, upadacitinib, ustekinumab. Lower: adalimumab, vedolizumab, ozanimod, etrasimod. After anti-TNF primary non-response, switch mechanism rather than cycling within the class. Treat to target (STRIDE-II): endoscopic improvement, Mayo endoscopic subscore 0-1. Begin CRC surveillance 8-10 years after diagnosis for extensive or left-sided disease; isolated proctitis follows average-risk screening. Inpatient care now follows the 2026 AGA Clinical Practice Update (13 best-practice statements). Admit for severe symptoms refractory to outpatient therapy, suspected complications (obstruction, abscess, toxic megacolon) or significant malnutrition, and identify acute severe UC by Truelove-Witts. Give every patient admitted with diarrhea two-step C. difficile testing. Test for CMV, with early endoscopy, if symptoms worsen, the patient is systemically toxic or disease is steroid-refractory. Give routine VTE prophylaxis with LMWH or fondaparinux unless contraindicated, and individualize post-discharge extension. Give IV methylprednisolone 60 mg/day or equivalent; the AGA living guideline says 40-60 mg/day, and higher doses add no benefit. Do not give adjunctive antibiotics without infection. Involve surgery early. Assess response by day 3 (72 h) using stool frequency and CRP (Oxford criteria); do not continue IV steroids beyond about 7 days without response. Rescue steroid non-responders with infliximab (accelerated or intensified dosing in selected patients with high inflammatory burden or protein-losing colopathy), cyclosporine, or a JAK inhibitor at standard or intensified dosing, or with colectomy. Before discharge, the response should be stable and a transition plan should be in place.

Diagnose anorectal abscess and fistula-in-ano clinically: a disease-specific history and physical examination assessing symptoms, relevant history, abscess and fistula location, and secondary cellulitis (1C), with digital rectal exam and anoscopy/proctoscopy as needed. Routine diagnostic imaging is NOT typically necessary (1B); reserve imaging for selected patients with occult abscess, recurrent or complex fistula, immunosuppression, or anorectal Crohn's disease (MRI sensitivity 97% vs 74% for endoanal ultrasound in complex fistula; combined accuracy approaches 100%). Treat acute anorectal abscess promptly with incision and drainage (1C), placing the incision close to the anal verge to limit subsequent tract length and preserve the sphincter complex; packing is not required and unpacked wounds gave better resolution, less pain and faster healing in randomized trials. Reserve antibiotics for abscess complicated by cellulitis, systemic signs of infection, or underlying immunosuppression (2B); routine antibiotics after uncomplicated drainage in healthy patients do not improve healing or reduce recurrence, and conversely immunosuppressed patients with low neutrophil counts and no fluctuance may initially be treated with antibiotics alone rather than drainage. Concomitant fistulotomy at the time of drainage may be performed in selected patients with a simple anal fistula (2B), balancing lower recurrence (RR 0.13 in a 479-patient meta-analysis) against a non-significant increase in continence disturbance. For simple fistula-in-ano with normal sphincter function, lay-open fistulotomy heals over 90% (1B); for low fistulas involving less than one third of the external sphincter the clinically significant incontinence risk is minimal, and marsupialization improves healing and reduces bleeding. Sphincter-preserving options: endorectal advancement flap (1B; 66% to 87% initial healing, but up to 35% mild-to-moderate incontinence) and, for transsphincteric tracts, ligation of the intersphincteric fistula tract (LIFT) (1B; 76% pooled success, 1.4% incontinence). A cutting seton may be used selectively for complex cryptoglandular fistula (2C, downgraded from 2B; reported incontinence ranges 0% to 67%). The anal fistula plug and fibrin glue are relatively ineffective (1B, upgraded from 2B; contemporary healing 50% or less). Endoscopic or laser closure techniques (VAAFT, FiLaC, OTSC) have reasonable short-term healing but unknown long-term healing and recurrence rates (2C). In Crohn's disease, where abscess and fistula arise from penetrating inflammation rather than cryptoglandular infection, management is multidisciplinary and a draining seton is typically useful and may be used for long-term disease control (1B, upgraded from 1C); Crohn's disease is a named risk factor for failure or recurrence of fistulotomy, advancement flap, LIFT, and plug.

DIAGNOSIS (patient must be on a gluten-containing diet). Serologic testing consists of TTG-IgA plus, if IgA deficiency has not previously been excluded, concurrent total IgA; if IgA deficiency is present, measure an IgG-based serology (DGP-IgG and/or TTG-IgG). This algorithm, previously restricted to those >=2 years, now applies to adults and children at ANY age. An elevated TTG-IgA should proceed to EGD with duodenal biopsy. A negative TTG-IgA in a non-IgA-deficient patient adequately rules out CD only when pretest probability is low or moderate; in symptomatic patients whose pretest suspicion is high (>5%), EGD with duodenal biopsy should be performed irrespective of serologic result. ACG recommends EGD with multiple duodenal biopsies to confirm the diagnosis in both children and adults with suspicion of CD (STRONG recommendation, moderate quality; 1 dissent); sampling should be 1 or 2 biopsies from the bulb (9-o'clock or 12-o'clock position) and at least 4 from the distal duodenum. Lymphocytic duodenosis (>=25 IELs/100 epithelial cells) without villous atrophy is NOT specific for CD. NONBIOPSY PATHWAY (CONDITIONAL recommendation, moderate quality): a combination of high-level TTG-IgA (>10x ULN) with a positive EMA in a SECOND blood sample is suggested as reliable for diagnosis in CHILDREN, and only if the family agrees with the no-biopsy strategy; in SYMPTOMATIC ADULTS unwilling or unable to undergo upper GI endoscopy the same criteria may be considered AFTER THE FACT, as a diagnosis of 'likely CD', ACG does not endorse a prospective no-biopsy pathway in adults, noting a >=10-fold TTG-IgA elevation carries a PPV of only ~95% in adults, which may be unacceptably low given lifelong treatment implications. HLA-DQ2/DQ8 is not required for diagnosis but is useful for serology-histology discrepancy or in patients already on a GFD; if negative, CD is ruled out. TREATMENT AND MONITORING. Strict lifelong GFD. A visit with a dietitian after diagnosis is MANDATORY, with subsequent visits as needed to reinforce education and adherence encouraged; interview with a dietitian experienced in the GFD is the standard of care for assessing adherence. ACG RECOMMENDS consumption of gluten-free oats (STRONG recommendation, moderate quality), with the qualifier that gluten contamination of oats, variable toxicity across oat varieties, and a small risk of immune reaction to avenin require monitoring for oat tolerance (monitoring intervals are not known). ACG suggests AGAINST routine use of gluten detection devices in food or biospecimens (conditional, low quality; 1 dissent), and finds INSUFFICIENT EVIDENCE to recommend for or against probiotics (evidence gap). ACG suggests setting a goal of intestinal healing as an end point of GFD therapy, advocating individualized discussion of goals beyond clinical and serological remission (CONDITIONAL recommendation, low quality). Follow-up may require multiple visits in the first year (e.g. 3, 6, and 12 months) and regular visits (e.g. twice a year or yearly) thereafter, tracking symptoms and TTG or DGP serology; other tests may include CBC, ALT, AST, vitamins A/D/E/B12, copper, zinc, folic acid, ferritin, and iron, with follow-up bloodwork individualized to verify correction of values abnormal at baseline. Preventive care includes vaccines and DXA. Symptoms improve within days of strict adherence (diarrhea improved in 80% within 60 days), but mucosal healing lags: median time from GFD onset to mucosal healing in adults is 3 years, so it is reasonable to consider a follow-up biopsy in adults after 2 years of starting a GFD, in the ABSENCE of symptoms, after shared decision-making; children heal faster (95% within 2 years), altering the risk-benefit calculus. Repeat biopsy is the only reliable method to document mucosal healing, seroconversion correlates poorly. Upper endoscopy with biopsies is also indicated for lack of clinical response or relapse of symptoms despite a GFD. VACCINATION: ACG suggests vaccination to prevent pneumococcal disease in patients with CD (CONDITIONAL recommendation, low quality), because increased pneumococcal risk is attributed to hyposplenism (frequently subclinical) present in roughly one-third of patients. The regimen follows CDC recommendations by age, immunization record, and comorbidity: for an adult with CD and functional asplenia not previously vaccinated or with unknown history, 1 dose of PCV15 (followed by PPSV23 at least 1 year later) or 1 dose of PCV20 (no PPSV23 indicated); for an adult with CD and no other condition carrying a specific CDC recommendation, ACG suggests 1 dose of PCV20 alone, or 1 dose of PCV15 first and then consider PPSV23 at least 1 year later. NONRESPONSIVE CD (NRCD): defined as persistent symptoms, signs, or laboratory abnormalities typical of CD despite 6-12 MONTHS of dietary gluten avoidance. Evaluation should review and confirm the initial diagnosis of CD, assess for inadvertent gluten exposure (via expert dietitian assessment and serology, positive serologies despite 12 months of GFD suggest ongoing gluten ingestion), assess for a coexisting functional disorder, and selectively test based on clinical suspicion for food intolerances (e.g. lactose, fructose), pancreatic insufficiency, microscopic colitis, and small intestinal bacterial overgrowth, among others. REFRACTORY CD (RCD) is a separate, rarer entity (<1% of patients outside referral centers): ongoing malabsorptive symptoms and signs with villous atrophy despite strict adherence to a GFD for MORE THAN 12 months and absence of other disorders including overt lymphoma; initial assessment centers on distinguishing RCD type 1 from type 2 by CD3/CD8 immunostains, T-cell receptor clonality by PCR, and/or flow cytometry of duodenal biopsies.