Collagenous Sprue

Definition

• Enteropathy demonstrating subepithelial collagen deposition combined with villous changes typical of celiac disease

Alternate/Historical Names

• Refractory celiac disease
• Refractory sprue

Diagnostic Criteria

• Irregular, thickened collagen layer below the luminal basement membrane
  • Envelops capillaries and inflammatory cells
  • Ragged interface with lamina propria
  • Normal basement membrane is 1-2 microns, with different inclusion criteria
    • Range 48-260 microns maximum thickness (Maguire)
    • Over 5 microns thickness (Vakiani)
  • Trichrome stain is useful for demonstration of the layer
• Villous atrophy ranging from partial to total
• Increased intraepithelial lymphocytes in small intestine
• 6-92 / 100 enterocytes
• T cell phenotype
• CD3+, CD8 variable
• CD3 stain is useful for identification and counting
• T cell clonality may be present
  • Seen in both intestinal tissues and peripherally
  • Not clearly related to disease outcome
• Chronic inflammatory infiltrate in lamina propria
• Lymphocytes, plasma cells and eosinophils most common
• Surface mucosa may detach
• Anti-endomysial antibody may be present (4 of 12 cases)
• There is some debate regarding whether or not collagenous sprue is a distinct entity
  • It has been suggested that it may simply represent a pattern of refractory celiac disease

Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting/updates: 11/11/09, 12/3/09, 10/25/10

Differential Diagnosis

• Radiation
  • Diffuse fibrosis rather than just below basement membrane
• Scleroderma
  • Fibrosis also around crypts and may be diffuse
• Artifact of sectioning
  

  Tangential Sectioning	Collagenous Sprue
  Present only where adjacent glands cut as cross-sections	Present even when adjacent glands are cut longitudinally
  Indistinct edges but no entrapped elements	Jagged edges with entrapped capillaries and inflammatory cells
  Lacks chronic inflammatory infiltrate	Prominent chronic inflammatory infiltrate in lamina propria

Clinical

• Patients present with diarrhea, malabsorption and weight loss
  • Has been included under the term Refractory Celiac Disease
• Frequently associated with collagenous colitis (33%)
  • Collagenous gastritis in 15%
• Other associations
  • Lymphocytic gastritis (10%)
  • Ulcerative jejunitis (1 of 12 cases)
• Age range 22 to 84 years
• Variable response to steroids or gluten free diet
• Variable reports of prognosis and response to therapy
  • High mortality rate due to malnutrition in one series reporting very thick deposition(Maguire)
  • 17/19 responsive to immunomodulatory therapy or gluten free diet with only 1/19 mortality in another series including only mild thickening(Vakiani)

Bibliography

• Maguire AA, Greenson JK, Lauwers GY, Ginsburg RE, Williams GT, Brown IS, Riddell RH, O donoghue D, Sheahan KD. Collagenous Sprue: A Clinicopathologic Study of 12 Cases. Am J Surg Pathol. 2009 ;33:1440–1449..
• Vakiani E, Arguelles-Grande C, Mansukhani MM, Lewis SK, Rotterdam H, Green PH, Bhagat G. Collagenous sprue is not always associated with dismal outcomes: a clinicopathological study of 19 patients. Mod Pathol. 2010;23:12-26.
• Gopal P, McKenna BJ. The collagenous gastroenteritides: similarities and differences. Arch Pathol Lab Med. 2010 Oct;134(10):1485-9.