Malabsorption and Small Bowel Disease — Viva Defence

Long case viva — coeliac disease with dermatitis herpetiformis

Candidate's opening statement (SASPOP)

"Doctor, my patient is a 42-year-old woman presenting with coeliac disease. Her problems are: iron deficiency anaemia from proximal small bowel malabsorption (haemoglobin 88, MCV 71, ferritin 4); a 6-kilogram weight loss over 8 months with chronic loose stools; dermatitis herpetiformis on her extensor surfaces; and probable osteoporosis from chronic calcium and vitamin D malabsorption, to be confirmed on DEXA. The diagnosis is confirmed by positive anti-tTG IgA at 14 times the upper limit of normal, positive anti-endomysial antibody, normal total IgA (excluding selective IgA deficiency), and Marsh 3c total villous atrophy on duodenal biopsy. The treatment is a lifelong strict gluten-free diet with nutritional and bone assessment, and dapsone for the dermatitis herpetiformis while the diet takes effect." [1]

Problem list

1. Coeliac disease (Marsh 3c) — confirmed by serology and histology.
2. Iron deficiency anaemia (proximal small bowel malabsorption).
3. Dermatitis herpetiformis (cutaneous manifestation of coeliac disease).
4. Probable osteoporosis (chronic calcium and vitamin D malabsorption) — DEXA pending.
5. Nutritional deficiency — weight loss, possible folate and fat-soluble vitamin deficiency. [1]

Integrated management plan

The gluten-free diet. A lifelong strict gluten-free diet excluding wheat, barley, and rye is the only treatment. Oats may be introduced cautiously. Dietitian referral for education on label reading, hidden gluten, and cross-contamination. Monitor anti-tTG IgA response (should normalise over 6 to 12 months) [1].

Nutritional correction. Iron replacement (oral or intravenous if intolerant), folate, calcium, vitamin D, and fat-soluble vitamins as guided by levels. [1]

Bone health. DEXA scan at diagnosis. Calcium and vitamin D supplementation, with a bisphosphonate if osteoporotic. [1]

Dermatitis herpetiformis. Dapsone provides rapid control of the rash and pruritus within days by inhibiting neutrophil recruitment, used as a bridge while the gluten-free diet takes effect over months. G6PD must be checked before starting dapsone because of the risk of haemolysis [1].

Vaccination. Pneumococcal and influenza vaccination for hyposplenism-associated infection risk. [1]

Family screening. First-degree relatives carry a 10 per cent risk and should be tested by serology. [1]

Surveillance. Annual review with antibody monitoring, DEXA as indicated, and education on alarm symptoms (new weight loss, worsening diarrhoea, abdominal pain) that would prompt investigation for refractory disease or lymphoma. [1]

Examiner probing questions

Examiner: "Why did this patient present with microcytic rather than macrocytic anaemia?" Because iron is absorbed predominantly in the duodenum and proximal jejunum, which are the sites most affected by coeliac enteropathy. Microcytic iron deficiency is therefore the expected haematological pattern and is in fact the single most common adult presentation. Macrocytic anaemia from B12 or folate deficiency would suggest terminal ileum disease (B12) or more diffuse mucosal involvement (folate). The type of anaemia is the single most powerful bedside localiser in the malabsorption workup. [1]

Examiner: "What is the significance of checking total serum IgA alongside the anti-tTG IgA?" Selective IgA deficiency is 10 to 40 times more common in coeliac disease than in the general population. Because anti-tTG IgA and anti-endomysial IgA are IgA-class antibodies, an IgA-deficient patient produces a false-negative serological result. The total IgA must always be checked; if low, IgG-based alternatives (anti-tTG IgG or anti-DGP IgG) should be used. This patient's total IgA was normal at 1.2 grams per litre, so the anti-tTG IgA result is reliable [1].

Examiner: "What would make you concerned about refractory coeliac disease, and how do you classify it?" Persistent or recurrent malabsorptive symptoms with villous atrophy despite a strict gluten-free diet for over 12 months would raise concern — but first I would always exclude inadvertent gluten ingestion (the most common cause of non-response) by dietitian review and anti-tTG monitoring. Other causes of villous atrophy (tropical sprue, common variable immunodeficiency, olmesartan enteropathy, SIBO) must also be excluded. Refractory disease is then classified by intraepithelial lymphocyte phenotyping and T-cell clonality into type 1 (normal phenotype, low lymphoma risk, responds to budesonide) and type 2 (aberrant clonal IELs, 30 to 50 per cent risk of EATL over 5 years, requires specialist centre management) [3].

Branching scenario — tropical sprue

Examiner: "Now consider a 38-year-old man returning from 5 years in rural India with weight loss, chronic diarrhoea, and a macrocytic anaemia with low folate and B12. His coeliac serology is negative. Duodenal biopsy shows partial villous atrophy. What is the diagnosis and how does it differ from coeliac disease?" [1]

This is tropical sprue. The key distinctions from coeliac disease are:

• Negative coeliac serology — anti-tTG and anti-EMA are negative (in contrast to coeliac disease).
• Tropical exposure — the 5-year residence in rural India is essential to the diagnosis.
• Macrocytic anaemia — from folate and B12 deficiency (the terminal ileum is involved), rather than the microcytic iron deficiency of coeliac proximal disease.
• No HLA-DQ2 or DQ8 association — the genetic predisposition is absent.
• Response to folate and tetracycline — tropical sprue responds dramatically to folate supplementation and a 3 to 6 month course of oral tetracycline. This is both diagnostic (a response confirms the diagnosis) and therapeutic [2].

A gluten-free diet would not help. The treatment is fundamentally different from coeliac disease. [1]

Branching scenario — Whipple disease

Examiner: "What if the patient were a 56-year-old man with 5 years of recurrent migratory arthralgia, now with weight loss, chronic diarrhoea, low-grade fever, generalized lymphadenopathy, and hyperpigmentation? Duodenal biopsy shows PAS-positive foamy macrophages in the lamina propria." [1]

This is Whipple disease, caused by Tropheryma whipplei. The tetrad of migratory arthralgia (preceding the GI symptoms by years), malabsorption, systemic features (fever, lymphadenopathy, hyperpigmentation), and potential neurological and cardiac involvement is classic. The PAS-positive foamy macrophages in the lamina propria are diagnostic, and Tropheryma whipplei PCR on the biopsy should confirm the organism. [1]

Treatment requires antibiotics that penetrate the central nervous system, because subclinical CNS infection is common and CNS relapse is devastating. The standard regimen is intravenous ceftriaxone 2 g daily for 2 to 4 weeks as induction, followed by oral trimethoprim-sulfamethoxazole for at least 12 months as maintenance. Tropheryma whipplei is intrinsically resistant to trimethoprim alone, which is why the combination with sulfamethoxazole is required. Treatment that is too short risks relapse, particularly in the CNS [5].

The migratory arthralgia that precedes the malabsorption by years is the cardinal early clue. Oculomasticatory myorhythmia is pathognomonic of CNS Whipple disease. [1]

Branching scenario — short bowel syndrome and teduglutide

Examiner: "A 45-year-old man has 80 cm of jejunum ending in an end-jejunostomy after mesenteric artery thrombosis. He is dependent on parenteral nutrition. What factors determine his prognosis, and what pharmacological therapy can promote intestinal adaptation?" [1]

The four factors determining outcome in short bowel syndrome are: remaining bowel length (80 cm is very short — below 100 cm, parenteral nutrition is almost always required), site of resection (ileal resection is worse tolerated because the ileum is the only site of bile acid and B12 absorption and has slower transit), colon preservation (absent in this patient — the colon salvages fluid, electrolytes, and short-chain fatty acids), and ileocaecal valve preservation (absent — its loss accelerates transit and predisposes to SIBO). [1]

Intestinal adaptation occurs over the first 1 to 2 years, driven by enteral feeding. The pharmacological agent for intestinal rehabilitation is teduglutide, a recombinant analogue of glucagon-like peptide-2 (GLP-2) that stimulates intestinal mucosal growth, increases villous height and crypt depth, and enhances fluid and nutrient absorption. The Jeppesen randomised trial (Gut 2011) showed that teduglutide reduced parenteral nutrition and intravenous fluid requirements by at least 20 per cent in a significant proportion of patients with short bowel syndrome and intestinal failure [8].

I would also maximise enteral feeding (the most powerful stimulus for adaptation), use oral rehydration solution (hypotonic fluids worsen high-output stomas), add loperamide and a PPI (for transient gastric hypersecretion), and refer to an intestinal failure centre with a view to surgical rehabilitation (STEP procedure) if he does not achieve adequate adaptation. Intestinal transplantation is reserved for life-threatening complications of parenteral nutrition. [1]

Branching scenario — bile salt malabsorption after Crohn resection

Examiner: "A 41-year-old woman has chronic watery diarrhoea 2 years after an ileocaecal resection for Crohn disease that removed 40 cm of terminal ileum. She has no steatorrhoea. Her SeHCAT retention is 8 per cent. What is the diagnosis and treatment?" [1]

This is bile salt malabsorption. The SeHCAT retention of 8 per cent is in the moderate range (5 to 10 per cent), predicting a good response to a bile acid sequestrant. The key concept is the distinction between mild and extensive ileal resection. With a modest resection (40 cm, less than 100 cm), the liver compensates for the increased bile acid loss by upregulating synthesis from cholesterol, maintaining an adequate bile salt pool for fat digestion. The excess bile acids reaching the colon irritate the mucosa, stimulating water and electrolyte secretion and producing cholerrhoeic watery diarrhoea — but not steatorrhoea, because fat digestion is preserved. This is why she has watery diarrhoea but no steatorrhoea [7].

The treatment is cholestyramine before meals, a bile acid sequestrant that binds bile acids in the gut lumen and prevents their irritant effect on the colon. It should be started at a low dose and titrated up. If the resection had been extensive (more than 100 cm), the bile salt pool would be too depleted for a sequestrant to work, and a low-fat diet with medium-chain triglycerides would be the correct approach instead. [1]

Short-case discussion — nutritional assessment on examination

Examiner: "Examine this malabsorption patient's abdomen and look for systemic signs." [1]

My routine: general inspection for cachexia, pallor, and the cutaneous manifestations of malabsorption (easy bruising from vitamin K deficiency, dermatitis herpetiformis on extensor surfaces); hands for koilonychia from iron deficiency and clubbing from IBD or lymphoma; mouth for aphthous ulcers (coeliac disease, IBD) and angular cheilitis; eyes for conjunctival pallor; abdomen — inspect for distension from gas and fluid, scars from previous resection or stoma, palpate for a palpable mass (Crohn disease, lymphoma) and hepatosplenomegaly, and auscultate bowel sounds. [1]

Presentation: "On general inspection the patient is cachectic and pale with koilonychia consistent with chronic iron deficiency. There are aphthous mouth ulcers and an intensely pruritic vesicular rash on the elbows and knees consistent with dermatitis herpetiformis. The abdomen is soft with no masses or organomegaly. These findings are consistent with coeliac disease with dermatitis herpetiformis and iron deficiency. I would check coeliac serology with total IgA and arrange a DEXA scan for osteoporosis." [1]

Examiner: "What extraintestinal signs of malabsorption would you look for?" Peripheral neuropathy from B12 deficiency, bone tenderness from osteomalacia, easy bruising from vitamin K deficiency, night blindness from vitamin A deficiency, and dermatitis herpetiformis on extensor surfaces. The specific micronutrient deficiency localises the site of disease. [1]