objectives - american college of...

Byron P. Vaughn, MD

Spectrum of Diverticular Disorders:SUDD, SCAD

Byron P. Vaughn, MDAssistant Professor of Medicine

Division of Gastroenterology, Hepatology and Nutrition

University of Minnesota

Objectives

• View diverticular disease as a spectrum of inflammatory diseases

• Focus on pathophysiology and treatment of: I. Symptomatic uncomplicated diverticular disease

(SUDD)II. Segmental colitis associated with diverticula

(SCAD)

2016 ACG Midwest Regional Postgraduate Course Copyright 2016 American College of Gastroenterology

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Byron P. Vaughn, MD

Diverticula

Vasa recta Diverticulum

False (pseudo) diverticula herniation of mucosa and submucosa through lamina propria

Mimura T. Pathophysiology of diverticular disease. Best Pracice & Research Clinical Gastroenterol. 2002;16:563-76

Spectrum of diverticular disease

Diverticulosis

Diverticular disease

Diverticulitis

Acute diverticulitis

Chronic diverticulitis

Chronic recurrent

diverticulitisSCAD

SUDD

Asymptomatic diverticulosis

Strate LL, et al. Am J Gastroenterol. 2012;107:1486-93


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Byron P. Vaughn, MD

Diverticular disease

Low grade inflammation

Alterations in gut microbiota

Visceral hypersensitivity

Abnormal colon motility

Strate LL, et al. Am J Gastroenterol. 2012;107:1486-93

Increased colonic pressure

Constipation

Diverticular obstruction

Low fiber diet

Symptomatic Uncomplicated Diverticular Disease (SUDD)

• Estimated 20% prevalence in subjects with diverticulosis• Sometimes called: smoldering diverticulitis• Definition not consistent in literature

– Abdominal pain AND change in bowel habits2

– Abdominal pain OR change in bowel habits3

• Clinical criteria for SUDD separate from IBS4

– Prolonged less frequent abdominal pain (>24 hours)– No relief with defecation

1Elisei W, et al. Ann Gastroenterol. 2016;29:24-322Kohler L, et al. Surg Endosc. 1999;13:430-63Strate LL, et al. Am J Gastroenterol. 2012;107:1486-934Annibale B, et al. Int J Colorectal Dis. 2012;27:1151-59

Persistent abdominal pain attributed to diverticula in the absence of macroscopic inflammation (colitis or diverticulitis)1


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Byron P. Vaughn, MD

SUDD as spectrum of inflammatory disease

Acute diverticulitis SUDDMacroscopic

inflammation Microscopic inflammation

10-25% of subjects with SUDD may develop acute diverticulitis

Inflammation in SUDD

• Mayo surgical records: sigmoid resection for diverticular disease (1988 – 1997)

• 5% (n=47) done for smoldering DD (aka SUDD)

Acute and chronic mucosal inflammation

Complete resolution of presenting symptom

and pain free

Horgan AF et al. Dis Colon Rectum 2001;44:1315-8

No correlation


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Byron P. Vaughn, MD

TNF elevated in SUDD

AUD SUDD AD SCAD UC HC

AUD: Acute uncomplicated diverticulitisAD: Asymptomatic diverticulosisHC: Healthy controlTursi A, et al. Colorectal Dis. 2012;14:e258-63

Visceral hypersensitivity / IBS overlap

Clemens CHM, et al. Gut 2004;54:717-722

Isobaric distention of the sigmoid and rectum


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Byron P. Vaughn, MD

SUDD and colonic microbiota

• Bacterial overgrowth in setting of fecal stasis• Low fiber diet putative risk factor for SUDD

– Low fiber associated with lower levels of Bifidobacteria and Faecalibacterium prausnitzii

• Toll-like receptor abnormalities in mucosa of subjects with SUDD versus healthy controls– Reverses or improves with rifaximin

Cianci R, et al. J Immunol Res. 2014:696812Hooda S, et al. J Nutr. 2012; 142:1259-65

SUDD Treatment

• Fiber– Conflicting results from small trials– Pressure?– Microbiome?

• Mesalamine – 3 RCTs– Varying dosing of mesalamine– General trend of improving symptoms with

daily therapy (1.6g/day)• Antibiotics

– Rifaximin + fiber: 29% reduction in symptoms versus fiber alone

• Smooth muscle relaxer ? • Probiotics ?

– Lack of comparative studies– Pre/post analysis favors probiotics plus

fiber

Brodribb AJ. Lancet. 1977;26:664-6Gatta L, et al. J Clin Gastroenterol. 2010;44:113-9Bianchi M, et al. Aliment Pharmacol Ther. 2011;33:902-10

Rifaximin: risk reduction

Scaioli E, et al. Dig Dis Sci. 2016;61:673-683


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Byron P. Vaughn, MD

Segmental colitis associated with diverticula (SCAD)

• Early 1980 – reports of endoscopically active inflammation in the sigmoid in areas of diverticula

• Classic presentation: age >60 (M > F), subacute hematochezia, altered bowel function and abdominal pain

• Endoscopy: patchy mucosal hemorrhage granularity and exudate without gross ulceration

• Biopsies: Focal chronic active colitis withoutgranulomas

• Prevalence in pts with diverticulosis: 0.26 – 1.5%Cawthorn SJ, et al. Gut 1983;25:500Peppercorn Ma, J Clin Gastroenterol. 2004;38:S8-10

Mann NS, Hoda KK. Hepatogastroenterology. 2012;59:2119-21Tursi A, et al. Colorectal Dis. 2010:12:464-70

Pathology of SCAD

SCAD• Cryptitis• Crypt abscesses • Mononuclear infiltrate in LP• Basal lymphoid aggregates • Chronicity:

– Basal lymphoplasmacytosis– Crypt distortion – Paneth cell metaplasia

Not in SCAD• Granulomas

– Except in setting of crypt rupture

• Inflammation beyond mucosa (generally)

• Rectal involvement• Overt changes of

diverticulitis

Lamps LW and Knapple WL. Clin gastroenterol Hepatol 2007; 5:27

Ulcerative colitisCrohn’s colitis

Infectious colitisNSAID colitis

Ischemic colitis


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Byron P. Vaughn, MD

SCAD: pathophysiology

Lamps LW and Knapple WL. Clin gastroenterol Hepatol 2007; 5:27Strate LL, et al. Am J Gastroenterol. 2012;107:1486-93

Ludeman L, Shepard NA. Pathology. 2002;34:568Mulhall AM, et al. Dis Colon Rectum. 2009; 52:1072Iedardi E, et al. Dig Dis Sci. 2008;53:1865-8

Mucosal prolapse

Fecal stasis

Local ischemia

Subserolsal peridiverticulosis

Dysbiosis

Immunologic•Tissue TNF elevated

in SCAD

10% will progress to IBD

Endoscopic patterns of SCAD

Crescentic fold

Mild to moderate UC - like

Crohn’s colitis - like Severe UC-

like

Tursi A, et al. Colorectal Dis. 2010:12:464-70

A B

C D


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Byron P. Vaughn, MD

SCAD treatment

• Retrospective case series/cohorts– Observation alone– 5-ASA (UC dosing):

• 80% symptom resolution within 6 months

– Antibiotics: Ciprofloxacin or metronidazole

– Prednisone/steroids – Surgical resection:

refractory symptoms. bleeding/anemia, obstruction

• Prospective– Beclomethasone

Dipropionate + VSL #3• 12 subjects, open label, no

control group

Freeman HJ. Dig Dis Sci. 2008;53:2452-7Makapugay LM and Dean PJ. Am J Surg Pathol. 1996;20:94-102Tursi A, et al. J Clin Gastroenterol. 2005;39:644-5

Generally a mild, self limited course

SCAD treatment – Systematic review

227 subjects71%SCAD

142 medically 28 surgically

~25%recurred

after “treatment”

Mulhall AM, et al. Dis Colon Rectum. 2009;52:1072-9

18 studies(1974-2008)

Remainder IBD and diverticulitis


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Byron P. Vaughn, MD

Take home points:• Paradigm of diverticular disease is changing

– Spectrum of chronic inflammation• SUDD

– Appears distinct from IBS– Inflammatory component– Evidence for mesalamine and antibiotics

• SCAD– Generally mild course– Observation, mesalamine and antibiotics– ~10% progression to overt IBD– Steroids and surgery may be needed

Thank you


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