12-phase flow (12)

1. 1FRAME
   Apply Rome IV POSITIVE diagnosis — recurrent abdominal pain ≥1 day/week in the last 3 months, onset ≥6 months ago, with ≥2 of: related to defecation / change in stool frequency / change in stool form. Assign subtype by predominant Bristol Stool Form (IBS-D >25% type 6-7 & <25% type 1-2; IBS-C >25% type 1-2 & <25% type 6-7; IBS-M both >25%; IBS-U insufficient abnormal stools). NOT a diagnosis of exclusion (ACG 2021; Rome IV)
   inputs: recurrent_abdominal_pain, altered_bowel_habit, symptom_duration
   actions: workup.ibs_rome_iv
   advance: Rome IV criteria met and subtype assigned
2. 2ENTRY
   Recognise the presenting trigger — recurrent defecation-related abdominal pain, chronic altered bowel habit ± bloating, known-IBS subtype-review visit, or post-infectious onset after enteritis (Klem 2017 PMID 28069350)
   inputs: altered_bowel_habit
   advance: one entry trigger present
3. 3CONTEXT
   Capture age/sex (alarm + pre-test probability), family history of CRC/IBD/coeliac, post-infectious onset, psychological comorbidity (PHQ-9/GAD-7 — bidirectional gut-brain axis), diet/FODMAP triggers, pregnancy status, prior IBS therapy and response (ACG 2021; BSG 2021)
   inputs: age, sex, family_history_crc_ibd_coeliac, post_infectious_onset, psych_comorbidity, pregnancy_status
   actions: calc.phq9, calc.gad7
   advance: context captured
4. 4RED_FLAGS
   ALARM FEATURES override a Rome IV positive diagnosis and reroute to organic-disease workup: age ≥50 with new-onset symptoms, rectal bleeding/melaena, unintentional weight loss, iron-deficiency anaemia, nocturnal/progressive symptoms, palpable abdominal/rectal mass, family history of CRC/IBD/coeliac. §5.5.2 BAYESIAN FRAME — (a) PRE-TEST PRIORS: in a patient <45-50 yr meeting Rome IV WITHOUT alarm features the prior probability of IBS is very high and the prior probability of organic disease is low (PI-IBS cohort prevalence 10-14%, Klem 2017 PMID 28069350; biopsy-proven coeliac OR 4.48, Irvine 2017 PMID 27753436; CRC PPV of isolated rectal bleeding only ~2.2-8.1% even ≥50 yr, Astin 2011) — minimal testing suffices and routine colonoscopy is low-yield. (b) LR+ ≥20 ORGANIC RULE-IN that OVERRIDES a positive IBS diagnosis: faecal calprotectin above the high IBD threshold — van Rheenen BMJ 2010 (PMID 20634346) ADULT pooled sens 0.93 (95% CI 0.85-0.97) / spec 0.96 (95% CI 0.79-0.99) against an ENDOSCOPY+HISTOLOGY reference standard ⇒ LR+ ≈ 0.93/(1-0.96) ≈ 23.3 and LR- ≈ 0.073; a high-positive calprotectin therefore rules IN mucosal inflammation and mandates ileocolonoscopy regardless of Rome-IV positivity (lower binned cut-off ≤50 µg/g LR+ 10.3 / LR- 0.15, Bhattacharya 2023 PMID 37823411 — rule-OUT strength). (c) CONDITIONAL DEPENDENCIES (independence NOT assumed; LRs are not chain-multiplied when present): calprotectin LR+ is conditionally LOWER (more false-positives) with concurrent NSAID use, recent enteric infection, age >65, or PPI use; alarm-feature PPV for CRC is conditional on age (rectal-bleeding PPV rises sharply ≥50 yr; near-baseline <45 yr — Astin 2011); coeliac-serology interpretation is conditional on total-IgA status (anti-tTG IgA falsely negative in selective IgA deficiency → reflex IgG-DGP/total IgA) and on continued gluten intake (serology + biopsy false-negative on a gluten-free diet); symptom-criteria (Rome IV) performance is conditional on subtype (pain-criterion discrimination differs IBS-C vs IBS-D vs IBS-M). (d) THRESHOLDS: TEST-threshold — young, Rome-IV-positive, no alarm: CBC+CRP+anti-tTG IgA(+total IgA) ± calprotectin (IBS-D/M) only; WORKUP-threshold — any alarm OR calprotectin above high cut-off OR positive coeliac serology → ileocolonoscopy/duodenal biopsy/CRC pathway (ACG 2021; BSG 2021; van Rheenen 2010)
   inputs: alarm_features, age, family_history_crc_ibd_coeliac
   actions: workup.colorectal_screening, workup.chronic_diarrhea, workup.microscopic_colitis, workup.dyspepsia
   advance: no alarm feature and calprotectin/serology below organic-disease thresholds, or alarm/positive test rerouted to organic-disease pathway
5. 5INITIAL_WORKUP
   Minimal testing in the absence of alarm features (positive-diagnosis model): CBC, CRP, coeliac serology (anti-tTG IgA + total IgA — biopsy-proven coeliac OR 4.48, 95% CI 2.33-8.60 in IBS vs controls, Irvine 2017 PMID 27753436), and — for IBS-D/IBS-M — faecal calprotectin to partition IBD. Calprotectin operates as a two-threshold Bayesian instrument: rule-OUT at the low binned cut-off ≤50 µg/g (sens 85.8% [95% CI 78.3-91], spec 91.7% [95% CI 84.5-95.7], LR- 0.15 — high NPV in low IBD prevalence, Bhattacharya 2023 PMID 37823411) and rule-IN at the high IBD threshold (van Rheenen BMJ 2010 PMID 20634346 adult sens 0.93 [95% CI 0.85-0.97], spec 0.96 [95% CI 0.79-0.99], LR+ ≈23.3 vs an endoscopy+histology reference standard — a high-positive value OVERRIDES a Rome IV positive diagnosis and mandates ileocolonoscopy). Calprotectin interpretation is conditional on NSAID/PPI use, recent infection, and age (more false-positives). Age-appropriate colorectal cancer screening per USPSTF; consider Giardia/stool studies if travel/exposure. Routine colonoscopy WITHOUT alarm features has low diagnostic yield (organic disease found at rates similar to age-matched controls) and is NOT recommended (ACG 2021; BSG 2021; van Rheenen 2010)
   inputs: cbc, crp, coeliac_serology_ttg_iga, faecal_calprotectin, tsh
   actions: panel.cbc, panel.inflammation, cascade.labs_command
   advance: minimal labs returned and within normal limits (supports IBS) or abnormal — calprotectin above high cut-off / positive coeliac serology → reroute to organic-disease workup
6. 6BRANCHING_WORKUP
   Subtype-directed second tier when warranted: IBS-D not responding — consider bile-acid diarrhoea (SeHCAT retention <10-15% or elevated serum 7αC4 / low FGF19; empiric bile-acid sequestrant trial acceptable where SeHCAT unavailable); positive coeliac serology → duodenal biopsy; elevated calprotectin → ileocolonoscopy for IBD; chronic non-bloody watery diarrhoea in an older woman with macroscopically normal colonoscopy → random biopsies for microscopic colitis; persistent dyspeptic overlap → dyspepsia pathway. Colonoscopy reserved for alarm features, age-appropriate CRC screening, or IBS-D with diagnostic uncertainty (ACG 2021; BSG 2021)
   inputs: faecal_calprotectin, coeliac_serology_ttg_iga
   actions: workup.chronic_diarrhea, workup.microscopic_colitis, workup.colorectal_screening, workup.dyspepsia
   advance: organic disease excluded or rerouted
7. 7DIFFERENTIAL
   Distinguish IBS subtype from IBD (Crohn/UC), coeliac disease, microscopic colitis, bile-acid diarrhoea, colorectal cancer, lactose/carbohydrate malabsorption, SIBO, functional diarrhoea/constipation (no pain criterion), functional dyspepsia overlap, centrally-mediated abdominal pain syndrome, endocrine causes (thyroid, diabetic enteropathy). Confirm IBS subtype (IBS-D / IBS-C / IBS-M / IBS-U) and post-infectious phenotype (ACG 2021; Rome IV)
   inputs: altered_bowel_habit
   advance: IBS subtype confirmed and organic disease excluded
8. 8RISK_STRATIFICATION
   Stratify symptom severity (mild/moderate/severe by IBS-SSS-equivalent, impact on quality of life, healthcare utilisation), psychological comorbidity burden (PHQ-9 / GAD-7 — drives gut-brain neuromodulator and psychological-therapy selection; screen Q9 for suicidality), refractoriness (failure of ≥2 therapy classes → GI/neurogastroenterology referral) (ACG 2021; BSG 2021)
   inputs: psych_comorbidity
   actions: calc.phq9, calc.gad7
   advance: severity tier + psychological burden + refractoriness documented
9. 9TREATMENT
   All subtypes: therapeutic relationship + education, soluble fibre (psyllium), dietitian-led low-FODMAP with structured reintroduction (Black 2021 PMID 33585949), physical activity, sleep. IBS-C: PEG (bloating-limited), secretagogues linaclotide/plecanatide (GC-C agonists), lubiprostone (ClC-2), tenapanor (NHE3). IBS-D: loperamide (stool form only), bile-acid sequestrant if BAD, rifaximin (TARGET — Pimentel NEJM 2011 PMID 21208106; retreatable — Lembo PMID 27528177), eluxadoline (mu-OR agonist/delta antagonist — CONTRAINDICATED if no gallbladder / sphincter-of-Oddi / prior pancreatitis / >3 drinks/day), alosetron (5-HT3 antagonist — REMS, women with severe refractory IBS-D, ischaemic-colitis/severe-constipation risk). Pain/global: gut-brain neuromodulators — low-dose TCA (amitriptyline preferred IBS-D — ATLANTIS Lancet 2023 PMID 37858323), SSRI if IBS-C/comorbid anxiety-depression; antispasmodics + peppermint oil; psychological therapy (CBT, gut-directed hypnotherapy — durable). Deprescribe unindicated PPI contributing to bowel symptoms (ACG 2021; BSG 2021; AGA IBS-C/IBS-D 2022)
   inputs: altered_bowel_habit, creatinine, cholecystectomy_alcohol_pancreatitis, pregnancy_status
   actions: protocol.deprescribing_ppi
   advance: subtype-directed regimen + gut-brain plan agreed with patient
10. 10DISPOSITION
    Outpatient primary-care management for the majority; refer to GI/neurogastroenterology for diagnostic uncertainty, alarm features, refractory symptoms after ≥2 therapy classes, severe psychological comorbidity, or consideration of restricted agents (alosetron REMS); psychiatry/psychology referral for severe affective comorbidity or positive suicidality screen (ACG 2021; BSG 2021)
    inputs: alarm_features
    advance: care setting and referrals set
11. 11MONITORING
    Reassess symptom response at 4-12 weeks per agent; track Bristol stool form and pain; monitor for eluxadoline pancreatitis red flags (severe epigastric/RUQ pain), alosetron ischaemic colitis (new rectal bleeding / worsening abdominal pain) and severe constipation; renal function for secretagogue/rifaximin dosing; PHQ-9/GAD-7 trend on neuromodulator therapy; re-screen for emergent alarm features (any new alarm → re-enter RED_FLAGS organic workup) (ACG 2021; AGA 2022)
    inputs: altered_bowel_habit, creatinine, psych_comorbidity
    actions: calc.phq9, calc.gad7, calc.ckd_epi_2021
    advance: response assessed and safety monitoring documented
12. 12FOLLOWUP
    Mild disease: review at 4-8 weeks then as needed. Moderate-severe / refractory: structured follow-up q4-12 weeks during therapy escalation; reinforce diet reintroduction and self-management; post-infectious IBS — counsel on gradual improvement over months-years (Klem 2017 PMID 28069350). Reassess diagnosis if alarm features emerge or response is atypical; coordinate multidisciplinary care (dietitian, psychology). SPECIAL-POPULATION MATRIX (≥6): (1) PREGNANCY/LACTATION — diet/fibre/PEG first-line; loperamide short-term only (avoid 1st trimester); AVOID eluxadoline and alosetron (no safety data + SOD/ischaemic risk), AVOID rifaximin (animal teratogenicity), defer secretagogues (linaclotide/plecanatide pregnancy data limited; lubiprostone animal loss), TCA/SSRI only if benefit outweighs risk (TCAs assoc. worse fetal outcomes — not for IBS indication in pregnancy) (Medical Letter PMID 32324174; ACG 2021). (2) ELDERLY — TCAs (amitriptyline) and antimuscarinic antispasmodics (dicyclomine/hyoscyamine) on STOPP/Beers (anticholinergic burden, falls, urinary retention, delirium, constipation) — prefer secondary-amine nortriptyline/desipramine at low dose; constipation risk amplifies in IBS-C; tegaserod CONTRAINDICATED ≥65 yr (CV ischaemic risk) (STOPP v3 O'Mahony 2023; ACG 2021). (3) RENAL IMPAIRMENT — secretagogues minimally renally cleared but caution in severe CKD; rifaximin minimal systemic absorption (safe); recheck eGFR via calc.ckd_epi_2021 before TCA/SSRI dose escalation (KDIGO 2024). (4) HEPATIC IMPAIRMENT — eluxadoline CONTRAINDICATED in severe hepatic impairment (Child-Pugh C) and dose-reduce 75 mg in mild-moderate; rifaximin caution Child-Pugh C (↑systemic exposure); TCA/SSRI hepatic metabolism — start low (Lembo NEJM 2016 PMID 26789872; ACG 2021). (5) POST-INFECTIOUS SUBGROUP — distinct natural history (OR 4.2 [3.1-5.7] within 12 mo of enteritis, gradual resolution over months-years; usually IBS-D, female/antibiotic/anxiety risk factors) — counsel on prognosis, avoid over-investigation (Klem 2017 PMID 28069350). (6) PAEDIATRIC — distinct Rome IV PAEDIATRIC functional GI criteria; do NOT apply adult IBS pathway/pharmacology → route OUT to paediatric GI. (7) COMORBID PSYCHIATRIC — bidirectional gut-brain axis (anxiety/depression both predict and worsen IBS and PI-IBS); PHQ-9/GAD-7 at baseline + follow-up, gut-brain neuromodulator + psychological-therapy selection, safety-plan on positive PHQ-9 Q9 (ACG 2021; BSG 2021; Klem 2017) (ACG 2021; BSG 2021)
    inputs: post_infectious_onset
    advance: follow-up interval, self-management plan, special-population adjustments, and multidisciplinary referrals scheduled