A coeliac conundrum

A middle-aged woman presented with loose stool and weight loss.  Initially, she refused an endoscopy and a diagnosis of coeliac disease was based a high tissue transglutaminase (tTG) antibody titre.  She was started on a gluten-free diet (GFD) but her symptoms remained despite adherence to the GFD.  After several months she agrees to undergo an endoscopy. The images show the endoscopic view of the duodenal mucosa and the corresponding histology slide stained with haemotoxylin and eosin (H&E).
 
WHAT WOULD YOU DO NEXT?

■ Refer the patient for a dietary review

You are assuming that the pt has Coeliac disease...

■ Request a clonal analysis of the intraepithelial lymphocytes

But is the diagnosis of Coeliac correct? Look at the histology again!

■ Refer for HLA DQ2/DQ8 testing

But the diagnosis has been made on the biopsy...

■ Refer the patient for capsule endoscopy

Tissue was the issue and you've got that already!

■ Add prednisolone to the dietary restrictions

Congratulations you spotted the collagen band?

explanation

Initially, the patient appeared to have classic coeliac disease, with diarrhoea and weight loss together with a positive serology.  The endoscopy was crucial as the duodenal biopsies identified the presence of a thick band-like deposit of collagen just below the duodenal epithelium. On the basis of this finding, collagenous sprue was diagnosed.
 
Collagenous sprue was first described in 1947,1 but it was not until 1970 that Weinstein et al. introduced it as a diagnostic term to the medical nomenclature.2 Collagenous sprue is more frequent in females and in individuals who have other autoimmune diseases.3 It is now recognised that collagenous sprue shares similar clinical features with coeliac disease, such as chronic diarrhoea, anaemia and weight loss. In addition, the endoscopic and histological features of both diseases are similar, with an atrophic and scalloped duodenal mucosa. However, the histological hallmark of collagenous sprue is the presence of a thick subepithelial collagen band.  Such collagen bands may also be found in collagenous gastritis and collagenous colitis.4
 
It has been proposed that collagenous sprue may be a heterogenous condition of collagenous gastroenteritides, including conditions such as collagenous colitis and coeliac disease.5,6 Unlike coeliac disease, in collagenous sprue, the typical histological changes may also be found in the stomach and colon.7 Furthermore, greater numbers of IgG4 plasma cells have been reported in the duodenal mucosa of patients with collagenous sprue when compared with the numbers in patients with coeliac disease, duodenitis or normal duodenal mucosa.8
 
As in our case, patients with collagenous colitis usually also have positive coeliac serology.  For this reason, some believe that the collagen band is simply a marker of particularly severe coeliac disease, which may also be associated with ulceration, perforation and T-cell or B-cell lymphoma.9
 
An interesting report of paraneoplastic collagenous colitis was reported by Freeman et.al.10 In this case a patient with collagen deposits in both the small and large intestine was also found to have a coincidental colon cancer. After surgery, both the malabsorption and the histopathological changes completely resolved!  For this reason, a search for underlying malignant disease should be considered.
 
The response to a GFD is usually disappointing and for this reason, the outlook used to be grave for patients with collagenous sprue.  However, remission of the condition has been reported with courses of corticosteroids11 or immunosuppressive agents such as infliximab.12
 
References

1. Schein J. Syndrome on non tropical sprue with hitherto undescribed lesions of the intestine. Gastroenterology 1947; 8: 438–460.
2. Weinstein WM, Saunders DR, Tytgat GN, et al. Collagenous sprue—an unrecognized type of malabsorption. N Engl J Med 1970; 283: 1297–1301. 
3. Rubio-Tapia A, Talley NJ, Gurudu SR, et al. Gluten-free diet and steroid treatment are effective therapy for most patients with collagenous sprue. Clin Gastroenterol Hepatol 2010; 8: 344–349.e3. 
4. Zhao X and Johnson RL. Collagenous sprue: a rare, severe small-bowel malabsorptive disorder. Arch Pathol Lab Med 2011; 135: 803–809. 
5. Maguire AA, Greenson JK, Lauwers GY, et al. Collagenous sprue. A clinicopathologic study of 12 cases. Am J Surg Pathol 2009; 33: 1440–1449. 
6. Nielsen OH, Riis LB, Danese S, et al. Proximal collagenous gastroenteritides: Clinical management. A systematic review. Ann Med 2014; 46: 311–317. 
7. Robert ME, Ament ME and Weinstein WM. The histologic spectrum and clinical outcome of refractory and unclassified sprue. Am J Surg Pathol 2000; 24: 676–687. 
8. Schoolmeester JK, Jenkins SM, Murray JA, et al. Increased immunoglobulin G4-positive plasma cells in collagenous sprue. Hum Pathol 2013; 44: 1624–1629. 
9. Freeman HJ. Collagenous sprue associated with an extensive T-cell lymphoma. J Clin Gastroenterol 2003; 36(2): 144–6.