Diarrhoea for the Acute Physician STEPHEN INNS GASTROENTEROLOGIST AND PHYSICIAN HUTT VALLEY DHB August 2013 Outline Case History 1 Initial assessment of acute diarrhoea Management of fulminant UC Management of acute Crohns disease Diarrhoea in the elderly: C. difficile Patient with diarrhoea Seven times per day, twice at night Diffuse abdominal pain and tenderness What is the differential diagnosis?
Initial Assessment Rigid Sigmoidoscopy Demographics Duration Vomiting Nature of diarrhoea Watery vs inflammatory vs fatty Stool microscopy Prolonged, severe or bloody diarrhoea Stool C. diff, OCP, culture Routine bloods Rigid sigmoidoscopy and biopsy AXR http://emedicine.medscape.com/article/81001- media Investigation of Inflammatory Diarrhoea Investigation of Secretory Diarrhoea Most first presentations will be infection Followed by IBD and ischaemia AXR in all Decision to proceed depends on clinical state Red blood in diarrhoea Proctoscopy and/or flexible sigmoidoscopy R sided/small bowel pain or tenderness; malabsorption Small bowel CT and ileo-colonoscopy Most first presentations will be infection Followed by IBD and ischaemia Coeliac antibodies, careful drug history Decision to proceed depends on chronicity and severity Ileocolonoscopy and biopsy (microscopic colitis) CT enteroclysis Antibiotics in Acute Diarrhoea Case History 1 Empiric use in traveller s diarrhoea Fluoroquinolone, ultrashort course If dysentery (infectious bloody diarrhoea) suspected and amoebae, EHEC, STEC ruled out Fluoroquinolone 3-5 days awaiting culture 35 year old male patient with diarrhoea 2 weeks, gradual onset Seven times per day, twice at night Diffuse abdominal pain and tenderness Red blood and mucus in stool Febrile 37.8C, HR 95/min, ESR 35, Hb 100
ASSESSING SEVERITY OF UC (Truelove & Witts BMJ 1954) stools mild <5/d, trace blood severe >5/d, bloody What is the severity of this colitis? temperature pulse Hb ESR No fever >37.8 <90 >90 Normal <10.5 <30 >30 Daily CRP to monitor response Fulminant colitis mortality reduced from 50% - 1.5% Case History Meticulous clinical care Multidisciplinary approach IV hydrocortisone 100mg qds (60%) Prophylaxis against DVT/PE Cyclosporin 2mg/kg (levels 150-250) 60% initial response, 30% long term Continue steroids, Azathioprine on discharge, PCP prophylaxis Monitor Mg, Cholesterol Biologicals: infliximab 5 mg/kg IV 3 month colectomy rate (7/24) vs. placebo (14/21) Symptomatic remission after IV hydrocortisone BO x 3/day semiformed no blood Corticosteroids in IBD Problems With Steroids Restrict to active IBD Co-prescribe bone protection No prophylactic role Minimise long-term use 65% remission/improvement in 4/12 Given inappropriately Recurrence after stopping Side-effects Failure to heal mucosa
60% remission OR 2.0 cf placebo in meta-analysis Dose dependant Renal toxicity Dose dependant nephritis Class effect 5 ASA for acute UC Case history 2 16 yo male patient with bloody diarrhoea Seven times per day, twice at night Diffuse abdominal pain and tenderness, concentrated in RIF Examination T 38, pale, thin, short, BMI = 16, prepubertal, tender mass RIF Colonoscopy - extensive patchy colitis and terminal ileal involvement US no collection but mass of thickened loops of bowel in RIF Ba follow through - 30 cm of affected ileum CD Activity Scores Harvey-Bradshaw index: General well-being (0 = very well, 1 = slightly below par, 2 = poor, 3 = very poor, 4 = terrible). Abdominal pain (0 = none, 1 = mild, 2 = moderate, 3 = severe). Number of liquid stools per day. Abdominal mass (0 = none, 1 = dubious, 2 = definite, 3 = definite and tender). Complications: arthralgia, uveitis, erythema nodosum, aphthous ulcers, pyoderma gangrenosum, anal fissure, new fistula, abscess (score 1 per item). Case History - what options? 5-ASA Steroids Elemental / polymeric diet Prolonged oral antibiotics Immunosuppression Azathioprine, Methotrexate Stop smoking Infliximab Colectomy + ileostomy +/- IRA Experimental immunological Rx / thalidomide Case History - what options? 5-ASA Steroids Elemental / polymeric diet Prolonged oral antibiotics Immunosuppression Azathioprine, Methotrexate Stop smoking Infliximab/Adalimumab Colectomy + ileostomy +/- IRA Experimental immunological Rx / thalidomide
Steroids in Crohn s disease Azathioprine for remission induction in Crohn s disease Gut, 1994; 35: 360 >17 weeks to have full effect Benefit at 2.5mg/kg but not much beyond Methotrexate in Crohn s disease 141 patients 2:1 25mg im weekly MTX for 16 weeks 20 mg steroid at day 1 and taper N Engl J Med. 1995 Feb 2;332(5):292-7 Methotrexate in Crohn s disease - maintenance Case history Started on azathioprine 2mg/kg after TPMT (normal), tolerates OK Can t tolerate steroids with neuropsychiatric side effects Still not well after 3 weeks despite dietary therapy - pain, diarrhoea Develops perianal soreness and leaking fistula BMI 18, Hb 8.9, Alb 21, CRP 35 What next?
Healing With Anti-TNFalpha Antibodies Results Chronic active 30% remission 30% improvement Fistulation 40% closure Pretreatment 4 Weeks Post treatment Van Dullemen Gastroenterology 1995 Early recurrence on stopping Maintenance treatment essential General Contra-indications AntiTNF: Side-effects Intestinal sepsis pregnancy, lactation (experience reassuring) infection, esp TB heart failure malignancy infusion reactions acute 20% delayed hypersensitivity 2% ANA - 50% dsdna Abs lymphoma? heart failure demyelination, aseptic meningitis infections Paradoxical inflammation!!cost - $10000-30000 per year!! Case History Induction of clinical remission of luminal and perianal disease at 3 months Acute Diarrhoea in the Elderly
Case History 1 Clostridium difficile is a Disease of the Elderly 80 year old female patient with diarrhoea for one week Seven times per day, twice at night Diffuse abdominal pain and tenderness Omeprazole for longstanding non-ulcer dyspepsia 7 days Augmentin 3 weeks ago, infected leg ulcers Past TIA and NSTEMI with PVD What is the differential diagnosis? Testing HVDHB Glutamate dehydrogenase If positive toxin PCR (NAAT) CCDHB GDH If positive Elisa for toxin A&B No serial testing Don t test for cure Odds ratio of C. difficile with PPI 2.5 Vancomycin treatment of choice in severe infection Severe Clostridium difficile Pseudomembranous colitis on endoscopy admission to an intensive care unit or any two of the following factors: an age of more than 60 years temperature above 38.3 C serum albumin less than 25 g/l white-cell count of more than 15x10 9 /L (acute renal failure)
Summary Clinical features dictate the investigative approach Multidisciplinary approach and attention to detail saves lives in fulminant colitis Useful tools to assess severity and guide therapy Steroids temporary option in IBD, always accompanied by bony prophylaxis Biologics available but not a panacea Vancomycin as first line with early surgical assessment for severe CD Questions