A Case of Abdominal Pain Susan Poe, MD 9/22/04 11/7/2018

Introduction Learning Objective to better recognize and manage a surprisingly common disease. No financial support has been provided. 11/7/2018

Case 53 yo Caucasian woman C/o moderately severe RLQ pain Duration 3 wks gradually worsening, now slightly lessened Constant, nausea, sensation of fullness, worsened with movement, poor appetite Missed work 1st time ever Chills but no fever Chronic constipation, sl looser stools lately 6 lb weight loss 11/7/2018

Case …. Pelvic u/s 2.4 cm R ovarian cystic fluid collection Referred to UW gyn clinic Repeat U/S no cyst “no gynecologic cause” Similar but less severe pain in the past 11/7/2018

Case …. PMH: anxiety, benign breast lump, PSH: BTL MEDS: xanax, colace ALLG: sulfa, PCN, erythromycin SH: Heavy smoker, factory worker, spouse with Alzheimer’s, grown son, minimal ETOH GYN: postmenopausal, G3P1Ab2 11/7/2018

PE Alert, oriented,trim, tanned, older appearance than stated age 132/64, 66, wt 152 Chest: clear to A & P CV: RRR no mgr Abd: nl BS’s, soft, RLQ tender to deep palpation, sl guarding. No masses, HSM GYN: nl uterus, no ovarian masses Bimanual confirms, rectal heme neg 11/7/2018

stop 11/7/2018

Labs: WBC: 5.4 Hct: 40 LFTs, lytes, Cr: nl Amylase, lipase nl U/A nl 11/7/2018

stop 11/7/2018

Imaging CT abd: “mass like appearance” to 2nd portion of duodenum, borderline enlarged mesenteric nodes, no retroperitoneal adenopathy, otherwise nl CT pelvis: nl 11/7/2018

Procedure Upper endoscopy: negative gross appearance Colonoscopy: metaplastic polyp 11/7/2018

Biopsy of duodenum: flat mucosa increased intraepithelial lymphocytes C/w celiac sprue 11/7/2018

Celiac Disease DEFINITION: lifelong inflammatory disease of small intestine caused by dietary gluten in genetically predisposed person PATHOLOGY: Villous Atrophy: reduced villous height/ crypt ratio (nl 3-5 to 1), increased intraepithelial lymphocytes, extensive cell surface damage 11/7/2018

11/7/2018

History 250 AD Aretaeus of Cappadocia: 1888 Samuel Gee : assoc with diet 1953 Wilheim Dicke: disease caused by wheat proteins 11/7/2018

Etiology GLUTEN: alcohol soluble fraction of wheat, rye,barley, oats Wheat: gliadin Rye: Secalins Barley: Hordeins Oats (less toxic): avenins 11/7/2018

Pathology Abnormal immune response of small intestine to gluten Gluten absorbed into lamina propria Sensitized T cells recognize gluten antigen in conjunction HLA DQ2 or DQ8 antigens Activates other T cells, CD4 Release cytokines, other inflammatory products 11/7/2018

11/7/2018

11/7/2018

Epidemiology Previously thought to be disease of childhood Adults increasingly recognized Whites of Northern European descent Age 10-40 1 per 250-300 (previously thought 1 in 6000) HLA association: DQA1.0501, DQB1.0201 11/7/2018

Prevalence 13,145 patients US Tested endomysial Ab, positives biopsy confirmed 4508 1st deg relative: 1 in 22 3236 symptoms: 1 in 56 4126 no symptoms: 1 in 135 Arch Int Medicine 2003 Similar ratios in Sweden, Finland, Belfast 11/7/2018

Clinical Classic (children): FTT, malabsorption, short stature, osteomalacia, rickets Adults- usually more atypical Often long standing before dx Diarrhea usually Wt loss Abd pain: typically not severe, borborygmi, visible peristalsis, increased flatulence, bloating, large bulky pale stools Lassitude Symptoms of anemia 11/7/2018

Clinical… Short stature Osteoporosis, vitamin D deficiency Deficiency of iron, ferritin, folic acid, B12, Ca, Mg, albumin Amenorrhea, infertility Spontaneous abortions Lactose, sucrose intolerant Bacterial overgrowth 11/7/2018

Disease Associations: Increased mortality 4-fold Increased risk GI malignancies 5-fold increased risk T cell lymphoma: 10% associated with celiac dz , 10% survival Metabolic bone disease IgA deficiency 10% Hyposplenism common 11/7/2018

Associations … Dermatitis Herpetiformis Aphthous ulcers DM 6-8% 24% of celiac patients 86% have celiac disease by bx Itchy, burning vesicular rash, elbows, knees, buttocks,sacrum, face, neck, trunk or generalized Dx: granular IgA deposits in nl skin Aphthous ulcers DM 6-8% Hypothyroid, other autoimmune disease 11/7/2018

11/7/2018

Diagnosis Serology IgA Antiendomysial Ab, IgA Transglutaminase ELISA Sens 97-100%, spec 98-99% IgA Transglutaminase ELISA Sens 95%, spec 94% IgA Antigliadin Ab less sens, spec IgG Antigliadin Ab 11/7/2018

Diagnosis… Biopsy: Mandatory: 3 samples from duodenum Marsh 1:intraepithelial lymphocytes Marsh 2: mild villous atrophy Marsh 3: completely flattened villi Marsh 4: Severe villous atrophy, loss of crypts 11/7/2018

11/7/2018

Diagnostic Criteria Abnormal Biopsy on gluten diet Normalized on gluten free diet Repeat Biopsy 3-4 months Severity of lesion doesn’t correlate with severity of symptoms 11/7/2018

Treatment… Assess for associated conditions CBC, Lytes, glucose, LFTs, Fe, Ferritin, B12, Vitamin D, TSH DEXA scan Pneumovax (debatable) 11/7/2018

Treatment… Gluten free diet lifelong Support group Internet sites No wheat, barley, rye Limit oats or not at all Dietary counselling Support group Internet sites Prevent bone loss Correct nutritional deficiencies 11/7/2018

Treatment … Treat constipation (common) Monitor for response Rice bran, ispaghula Monitor for response 70% dramatic response within 2 wks 11/7/2018

Failure to respond 30% Continued gluten intake Beer, malted breakfast cereals, snacks, sauces Refractory disease (steroids) Ulcerative jejunitis 33% mortality Lymphoma Chronic pancreatitis, pancreatic lesion 11/7/2018

Irritable Bowel 15% of general population Mayo Clinic Proc, April 2004 152 pts ,32 dyspepsia, 50 IBS, 15 both, 78 no sxms Tested antibody levels, all negative No association Lancet, 2001 300 pts Rome II Criteria IBS 300 controls 4.7% (14) biopsy proven CE in IBS vs 0.7% (2) in controls 11/7/2018

Conclusion Common: 1 in 250-300 Association with irritable bowel Autoimmune response to gluten Wide range of symptoms Serology high sens and spec Biopsy ,mandatory Increased mortality 4-fold Associated with lymphoma, nutritional deficiencies, osteoporosis, autoimmune disease,multiple other conditions Easily treatable ? 11/7/2018

end 11/7/2018