Do conditions like microscopic colitis, celiac disease, or immune checkpoint inhibitor enterocolitis typically present with lymphocytosis on complete blood count (CBC)?

Lymphocytosis in Microscopic Colitis, Celiac Disease, and Immune Checkpoint Inhibitor Enterocolitis

Microscopic colitis, celiac disease, and immune checkpoint inhibitor enterocolitis typically present with tissue lymphocytosis but do not commonly cause peripheral blood lymphocytosis on CBC. While these conditions are characterized by significant lymphocytic infiltration in affected tissues, this localized immune response rarely translates to elevated lymphocyte counts in peripheral blood.

Microscopic Colitis

Microscopic colitis is characterized by significant lymphocytic infiltration in the intestinal mucosa, but this does not typically manifest as peripheral lymphocytosis:

• Tissue findings: Increased intraepithelial lymphocytes (IELs) in the colonic mucosa, with 10-65 lymphocytes per 100 surface epithelial cells (normal: 4-10) 1
• Subtypes:
  • Lymphocytic colitis (LC): Characterized by intraepithelial lymphocytosis without collagen deposition
  • Collagenous colitis (CC): Features subepithelial collagen deposition along with inflammatory infiltrate 1, 2
• Blood findings: No characteristic peripheral blood lymphocytosis pattern

Celiac Disease

Celiac disease has a strong association with microscopic colitis and features prominent tissue lymphocytosis:

• Association: Approximately one-third of celiac disease patients show features of lymphocytic colitis, while about one-fourth of lymphocytic colitis patients have celiac disease 1, 2
• Tissue findings: Duodenal intraepithelial lymphocytosis, villous atrophy, and production of tissue transglutaminase autoantibodies 2
• Terminal ileum involvement: Increased IELs in terminal ileum biopsies (>5 IELs/100 epithelial cells) is highly specific for LC and CC (specificity 98%) 3
• Blood findings: No characteristic peripheral blood lymphocytosis on CBC

Immune Checkpoint Inhibitor Enterocolitis

Immune checkpoint inhibitor (ICI) therapy can cause immune-related enterocolitis with two distinct histological patterns:

• Histological patterns:
  • Active colitis with neutrophilic crypt micro-abscesses and epithelial cell apoptosis
  • Lymphocytic colitis with increased intraepithelial lymphocytes 1, 2
• Incidence: IR-microscopic colitis causes chronic watery diarrhea in patients treated with anti-PD-1 or anti-CTLA-4 therapy 1
• Laboratory findings: Patients may have elevated white blood cell count and increased inflammatory markers (C-reactive protein, erythrocyte sedimentation rate), but specific peripheral lymphocytosis is not a characteristic feature 1

Clinical Implications

When evaluating patients with these conditions:

• Diagnostic approach: Endoscopy with biopsies remains the gold standard for diagnosis of these lymphocytic processes in the GI tract 2
• Correlation with symptoms: Patient symptoms do not correlate well with endoscopic findings or predict response to treatment in ICI enterocolitis 1
• Screening: Consider celiac disease screening in patients with lymphocytic colitis, as there is significant overlap between these conditions 1, 4
• Treatment considerations:
  • Microscopic colitis: Budesonide is effective, particularly for ICI-associated microscopic colitis 1
  • ICI enterocolitis: Corticosteroids for mild cases, infliximab for severe or refractory cases 1

Important Caveats

• The lymphocytic infiltration in these conditions is primarily tissue-based rather than systemic, explaining why peripheral blood lymphocytosis is not typically observed
• Lymphocytic disorders of the GI tract tend to cluster in patients, with 13.7% of patients with microscopic colitis having another type of lymphocytic disorder 4
• Terminal ileum involvement is common in microscopic colitis, with significantly higher IEL counts compared to inflammatory bowel disease or normal controls 3
• ICI therapy may unmask subclinical celiac disease in genetically susceptible individuals 5

In summary, while these conditions feature prominent tissue lymphocytosis, they do not characteristically present with peripheral blood lymphocytosis on complete blood count.