Malabsorption and Small Bowel Disease — DCE Clinical Case

Long case

Patient scenario

Mrs LC is a 42-year-old primary school teacher referred to the gastroenterology outpatient clinic with an 8-month history of progressive fatigue, a 6-kilogram weight loss (BMI now 19), and chronic loose stools (two to three times daily, non-bloody, no steatorrhoea). She has also noticed recurrent mouth ulcers and, over the last 6 months, an intensely pruritic blistering rash on her elbows, knees, and buttocks that her general practitioner treated with topical corticosteroids without improvement. [1]

Her general practitioner checked blood tests: haemoglobin 88 grams per litre, MCV 71 femtolitres, ferritin 4 micrograms per litre (iron deficiency), normal vitamin B12 and folate, and normal renal and liver function apart from a slightly low albumin of 33 grams per litre. Coeliac serology was requested: anti-tissue transglutaminase IgA was 14 times the upper limit of normal, total IgA was 1.2 grams per litre (normal), and anti-endomysial IgA was positive. [1]

She was referred for OGD with duodenal biopsies. The duodenal mucosa appeared scalloped and reduced in fold pattern. Histology showed total villous atrophy with crypt hyperplasia and 45 intraepithelial lymphocytes per 100 enterocytes (modified Marsh 3c). [1]

She has a past medical history of hypothyroidism (on levothyroxine 100 micrograms daily) and had two first-trimester miscarriages 3 and 5 years ago. Her mother has type 1 diabetes. She does not smoke and drinks alcohol rarely. She has no prior endoscopies or abdominal surgery. [1]

Examination findings

The patient is thin and pale, alert and oriented, in no acute distress. She is afebrile, heart rate 88, blood pressure 110 over 68 (no postural drop), respiratory rate 14, oxygen saturation 99 per cent on room air. She has bilateral koilonychia. There are two aphthous ulcers on the buccal mucosa and angular cheilitis. There is an intensely pruritic symmetric vesicular and papular rash with excoriations and crusting on the extensor surfaces of the elbows, knees, and buttocks, consistent with dermatitis herpetiformis. The abdomen is soft, non-tender, with no masses, organomegaly, or shifting dullness. Bowel sounds are normal. There is no peripheral oedema, peripheral neuropathy, or lymphadenopathy. [1]

Candidate's opening statement (SASPOP)

"Doctor, my patient is Mrs LC, a 42-year-old teacher 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; probable osteoporosis from chronic calcium and vitamin D malabsorption, to be confirmed on DEXA; a history of two miscarriages and hypothyroidism — an associated autoimmune condition; and a family history of autoimmune disease (mother with type 1 diabetes). The diagnosis is confirmed by positive anti-tTG IgA at 14 times the upper limit of normal, positive anti-endomysial antibody, normal total IgA, and Marsh 3c total villous atrophy on duodenal biopsy. My priorities are a lifelong strict gluten-free diet with dietitian support, correction of nutritional deficiencies, bone density assessment, dapsone for the dermatitis herpetiformis, family screening, and education on alarm symptoms for refractory disease and lymphoma." [1]

Problem list

1. Coeliac disease (Marsh 3c total villous atrophy) — confirmed by serology and histology.
2. Iron deficiency anaemia (proximal small bowel malabsorption).
3. Dermatitis herpetiformis (cutaneous manifestation of coeliac disease).
4. Weight loss and probable malnutrition (low albumin 33).
5. Probable osteoporosis (chronic calcium and vitamin D malabsorption) — DEXA pending.
6. Associated autoimmune disease — hypothyroidism (stable on levothyroxine).
7. Reproductive history — two first-trimester miscarriages (may relate to untreated coeliac disease).
8. Family history — mother with type 1 diabetes (first-degree relatives warrant screening). [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 and sourced gluten-free. Dietitian referral for education on label reading, hidden gluten, cross-contamination, and nutritional adequacy. Monitor anti-tTG IgA response — it should fall to normal over 6 to 12 months on a strict diet [1].

Nutritional correction. Iron replacement (oral ferrous sulfate, or intravenous iron if intolerant), folate, calcium, vitamin D, and the fat-soluble vitamins A, E, and K as guided by levels. Her B12 and folate are currently normal but should be monitored. [1]

Bone health. DEXA scan at diagnosis. Calcium and vitamin D supplementation, with a bisphosphonate if osteoporotic. Vitamin D level to be checked. [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 status must be checked before starting because of the risk of haemolysis and methaemoglobinaemia [1]. A skin biopsy of perilesional skin showing granular IgA at the dermoepidermal junction would confirm the diagnosis, though the clinical picture and positive coeliac serology are highly suggestive.

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

Associated conditions. Continue levothyroxine for hypothyroidism (monitor TSH, as absorption may improve on the gluten-free diet and the dose may need reduction). Screen for other autoimmune conditions (type 1 diabetes antibodies, autoimmune hepatitis). [1]

Family screening. First-degree relatives (her mother, siblings, and children) carry a 10 per cent risk and should be tested by coeliac serology. [1]

Surveillance. Annual review with anti-tTG IgA monitoring, nutritional assessment, and education on alarm symptoms (new weight loss, worsening diarrhoea, abdominal pain, fever, night sweats) that would prompt investigation for refractory disease or enteropathy-associated T-cell lymphoma. [1]

Discussion questions

Examiner: "How does the immunopathogenesis explain why anti-tTG is both the diagnostic test and the autoantigen?" Tissue transglutaminase deamidates gliadin peptides in the lamina propria, creating residues that bind to the HLA-DQ2 or DQ8 groove and activate CD4 T cells. The inflammatory cascade drives villous atrophy. B cells produce autoantibodies against tTG itself — the same enzyme — which are the serological markers. So tTG is simultaneously the autoantigen driving the disease and the target of the diagnostic antibodies [2].

Examiner: "Why is she iron deficient but not B12 or folate deficient?" Iron is absorbed in the duodenum and proximal jejunum, the sites most affected by coeliac enteropathy, so iron deficiency is the expected and earliest haematological abnormality. B12 is absorbed in the terminal ileum (spared in coeliac disease), and folate, though absorbed in the proximal small bowel, has not yet become sufficiently deficient to produce a macrocytosis. This pattern — microcytic iron deficiency with normal B12 and folate — is the classic haematological presentation of adult coeliac disease. [1]

Examiner: "What would make you suspect refractory coeliac disease, and how would you classify it?" Persistent or recurrent symptoms with villous atrophy despite a strict gluten-free diet for over 12 months. The first step is always to exclude inadvertent gluten ingestion (dietitian review, persistent anti-tTG elevation). Refractory disease is classified by intraepithelial lymphocyte phenotyping and T-cell clonality: type 1 has a normal phenotype and low lymphoma risk, responding to enteric-coated budesonide; type 2 has aberrant clonal IELs (surface CD3 and CD8 negative, cytoplasmic CD3 positive) with a monoclonal T-cell receptor, carrying a 30 to 50 per cent risk of enteropathy-associated T-cell lymphoma over 5 years, requiring specialist centre management [3] [4].

Examiner: "What is her lymphoma risk, and does the gluten-free diet modify it?" Coeliac disease carries a modestly increased risk of enteropathy-associated T-cell lymphoma, small bowel adenocarcinoma, and oesophageal and pharyngeal cancer. The risk is highest in undiagnosed or non-adherent disease, refractory type 2 coeliac, and men presenting late in life. A strict gluten-free diet reduces the risk to near-normal. New or worsening symptoms on a strict diet warrant urgent investigation to exclude EATL [4].

Short case — focused abdominal and nutritional examination

Instruction

"Examine this patient's abdomen and nutritional status. She has coeliac disease." [1]

Systematic examination routine

1. End of bed inspection. Assess for cachexia, pallor, the cutaneous manifestations of malabsorption (easy bruising from vitamin K deficiency, dermatitis herpetiformis on extensor surfaces), and signs of associated autoimmune disease (goitre for thyroid disease, vitiligo).
2. Hands. Koilonychia (iron deficiency), clubbing (IBD or lymphoma), and palmar erythema.
3. Face and mouth. Conjunctival pallor, angular cheilitis, aphthous ulcers (coeliac disease, IBD), and dental enamel defects (coeliac disease).
4. Skin. Dermatitis herpetiformis — intensely pruritic symmetric vesicles on extensor surfaces (elbows, knees, buttocks, scalp). Easy bruising (vitamin K deficiency).
5. Abdomen. Inspect for distension (gas, fluid), scars, and stoma. Palpate for tenderness, a palpable mass (Crohn disease, lymphoma), and organomegaly. Auscultate bowel sounds.
6. Legs. Peripheral oedema (hypoalbuminaemia) and peripheral neuropathy (B12 deficiency). [1]

Key signs this patient demonstrates

• Cachexia and pallor from iron deficiency anaemia and malabsorption.
• Koilonychia from chronic iron deficiency.
• Aphthous mouth ulcers and angular cheilitis.
• Dermatitis herpetiformis on extensor surfaces (elbows, knees, buttocks) — intensely pruritic symmetric vesicles with excoriation.
• No abdominal organomegaly or mass. [1]

Presentation template

"Doctor, I examined Mrs LC's abdominal system and nutritional status. She is cachectic and pale with bilateral koilonychia consistent with chronic iron deficiency. There are aphthous mouth ulcers and an intensely pruritic symmetric vesicular rash on the extensor surfaces of the elbows and knees consistent with dermatitis herpetiformis. The abdomen is soft and non-tender with no masses, organomegaly, or shifting dullness. These findings are consistent with coeliac disease with iron deficiency and dermatitis herpetiformis. I would confirm the diagnosis with coeliac serology and duodenal biopsy, assess bone density with a DEXA scan, and initiate a gluten-free diet with nutritional supplementation." [1]

Discussion — investigation pathway and differentials

Examiner: "Outline your investigation pathway for a patient presenting with malabsorption." I use a structured approach. First, establish malabsorption and its pattern: FBC (anaemia type localises the site — microcytic iron from the proximal small bowel, macrocytic B12 or folate from the terminal ileum), albumin (protein-losing enteropathy — alpha-1-antitrypsin clearance if low), and vitamin levels. Second, localise with targeted tests: coeliac serology (anti-tTG IgA with total IgA), faecal calprotectin (IBD), faecal elastase (pancreatic), stool culture and microscopy (infection), SeHCAT (bile salt malabsorption), and hydrogen breath test (SIBO). Third, confirm with endoscopy and biopsy (OGD with duodenal biopsies for coeliac and Whipple disease), capsule endoscopy (small bowel tumours and Crohn disease), and CT or MR enterography (structural disease) [1].

Examiner: "How would the pathway differ if she were returning from rural India with seronegative partial villous atrophy and a macrocytic anaemia?" That would be tropical sprue: negative coeliac serology, tropical exposure, macrocytic anaemia from folate and B12 deficiency, and response to folate and tetracycline for 3 to 6 months. The treatment is fundamentally different from coeliac disease — a gluten-free diet would not help [2].

Examiner: "And if it were a 56-year-old man with migratory arthralgia for years before the malabsorption, with PAS-positive macrophages on biopsy?" That would be Whipple disease (Tropheryma whipplei). The migratory arthralgia preceding the GI symptoms by years is the cardinal early clue. PAS-positive foamy macrophages in the lamina propria and Tropheryma whipplei PCR confirm the diagnosis. Treatment is intravenous ceftriaxone for 2 to 4 weeks followed by oral trimethoprim-sulfamethoxazole for at least 12 months, because subclinical CNS infection is common and CNS relapse is devastating. Tropheryma whipplei is intrinsically resistant to trimethoprim alone [5].

Examiner: "What about a patient with chronic watery diarrhoea after a 40 cm ileal resection for Crohn disease, with a SeHCAT retention of 8 per cent?" That is bile salt malabsorption. The modest resection (less than 100 cm) means the liver compensates for the bile acid loss, maintaining an adequate pool for fat digestion (hence watery diarrhoea but no steatorrhoea). The excess bile acids in the colon cause cholerrhoeic diarrhoea. Treatment is cholestyramine before meals, titrated to response. For resections over 100 cm, the pool is too depleted, and a low-fat diet with medium-chain triglycerides is used instead [7].