Type of enteropathy | Clinical and laboratory features | Histological/molecular features on duodenal biopsy | Diagnostic tests | Treatment |
Immuno-mediated | ||||
Autoimmune enteropathy | Severe malabsorption with intractable diarrhoea, weight loss and electrolyte imbalance unresponsive to dietary restrictions | IELs can be reduced, decreased globet cells, lymphoplasmacytic infiltrate in lamina propria, neutrophilic cryptitis | Positive anti-enterocyte antibodies | Immunosuppressants (steroids, azathioprine, infliximab) and parenteral nutritional support |
Common variable immunodeficiency | Malabsorption of different severity, arising after age 2 years, poor response to vaccines, recurrent infections of upper airways | Absence of plasma cells, polymorphonuclear infiltrate of the lamina propria, GVHD-like lesions, Crohn’s like lesions | IgG <5 g/L+ low IgA or IgM | Steroids, budesonide, immunoglobulin replacement therapy |
Lymphoproliferative | ||||
EATL (type 1 and type 2) | Severe malabsorption, abdominal pain, fever, bleeding, obstruction and/or perforation; type 1 usually associated to CD, unlike type 2 | Monoclonal population of T cells on IHC or flow cytometry | Inflammatory markers, abdomen CT/PET scan, capsule endoscopy | Consult haematologist+chemotherapy |
CD4+indolent lymphomas | Severe malabsorption, abdominal pain, fever, bleeding, obstruction and/or perforation |
| Inflammatory markers, abdomen CT/PET scan, capsule endoscopy | Consult haematologist+chemotherapy |
IPSID | Malabsorption syndrome of different severity | TCR gamma/beta clonality on duodenal biopsy Full thickness intestinal biopsy | Heavy chains of immunoglobulin | Consult haematologist+chemotherapy+antibiotics |
Iatrogenic | Severe malabsorption and suggestive pharmacological history | VA undistinguishable form CD | Duodenal biopsy and drug withdrawal | Drug withdrawal |
Angiotensin type 2 receptor blockers | Severe malabsorption and suggestive pharmacological history | VA undistinguishable form CD | Duodenal biopsy and drug withdrawal | Drug withdrawal |
Chemotherapy | Severe malabsorption and suggestive pharmacological history | VA undistinguishable from CD, lamina propria fibrosis | Duodenal biopsy | Steroids, consult oncologist to evaluate alternative regimens |
Radiotherapy | Severe malabsorption and history of radiotherapy | Lamina propria fibrosis | Duodenal biopsy | Steroids |
GVHD | Severe malabsorption and history of bone marrow transplantation | Crypt cell necrosis, loss of epithelium | Duodenal biopsy | Steroids or budesonide |
Infectious | ||||
Giardiasis | Malabsorption syndrome of different severity. Consider immune-deficiencies as predisposing conditions | Identification trophozoites on duodenal biopsy | PCR from duodenal aspirate, positive stool specific immunoassay | Metronidazole |
HIV enteropathy | Known history of AIDS, presence of opportunistic infections | Decrease CD4+ T lymphocytes, increase in CD8+ T lymphocytes | HIV test | Antiretroviral therapy, treatment of opportunistic infections |
Tuberculosis | Cough, ascites, night sweats, fever | Granulomatous disease | Interferon-gamma release assay, CT, ascetic fluid/sputum analysis | Specific anti-TB regimens |
Whipple’s disease | History of seronegative migratory arthritis preceding onset of severe malabsorption and fever, enlarged lymphnodes, neurological symptoms | PAS+ macrophagic infiltration of the lamina propria |
| Ceftriaxone/meropenem followed by TMP-SMX/hydroxychloroquine and doxycycline |
Tropical sprue | History of travel to/residency in endemic areas, anaemia with vitamin B12 and folate deficiency | Increased plasma cells and eosinophils in lamina propria, changes in duodenum, jejunum and ileum | Duodenal biopsy, VCE, exclusion of other causes of VA | Tetracycline or doxycycline+folic acid |
Inflammatory | ||||
Eosinophilic gastro-enteritis | History of atopy and allergies | Massive eosinophilic infiltration on duodenal biopsy | Duodenal biopsy and peripheral hyper eosinophilia | Steroids and dietary therapy |
Collagenous sprue | Severe malabsorption | Villous atrophy and subepithelial collagen deposition | Duodenal biopsy | GFD and immunosuppression (budesonide, prednisone, azathioprine) |
Crohn’s disease | Chronic diarrhoea with blood, abdominal pain, fever, weight loss | Villous atrophy, granulomas | Duodenal biopsy, colonoscopy + biopsies, abdomen CT, entero-MRI | Steroids, antibiotics, azathioprine, biological therapy |
Idiopathic | ||||
IVA 1—transient VA likely post-infective | Diarrhoea, weight loss, dyspepsia | Histology usually undistinguishable from CD | Abdominal CT, VCE | Spontaneous resolution within 6 months |
IVA 2—persistent non-lymphoproliferative VA | Severe malabsorption | Histology usually undistinguishable from CD | Abdominal CT, VCE | Immunosuppressants |
IVA 3—persistent VA with lymphoproliferative features | Severe malabsorption, history of lymphoproliferative disorders | Histology usually undistinguishable from CD, monoclonal rearrangement for gamma-TCR | Abdominal CT, VCE | Immunosuppressants, consider haematological consultation |
CD, coeliac disease; CT, computed tomography; EATL, enteropathy associated T-cell lymphoma; GFD, gluten-free diet; GVHD, graft versus host disease; IELs, intraepithelial lymphocytes; IHC, immunohistochemistry; IPSID, immune-proliferative small intestinal disease; IVA, idiopathic villous atrophy; MEITL, monomorphic epitheliotropic T-cell lymphoma; MRI, magnetic resonance imaging; PAS, periodic acid Shiff staining; PET, positron emission tomography; PET, positron emission tomography; TMP-SMX, trimethoprim sulfamethoxazole; VA, villous atrophy; VCE, video-capsule endoscopy.