Do patients with inflammatory bowel disease have an increased risk of light‑chain monoclonal gammopathies, and should they be screened for these disorders?

Light Chain Disease and Inflammatory Bowel Disease: Limited Evidence for Direct Correlation

There is insufficient evidence to support routine screening of IBD patients for light-chain monoclonal gammopathies, as the association remains poorly documented with only isolated case reports rather than population-based studies demonstrating increased risk. 1, 2

Current Evidence Base

The relationship between IBD and light-chain disorders is based primarily on case reports rather than systematic epidemiological data:

• Two case reports from 1999 described multiple myeloma occurring in middle-aged women with longstanding ulcerative colitis and Crohn's disease, both during inactive phases of intestinal inflammation, with progression from MGUS to multiple myeloma 2

• A 2024 case series reported two women in their early 60s with light chain deposition disease (LCDD) presenting with IBD-like symptoms and protein-losing gastroenteropathy, where gastrointestinal biopsies showed κ-light chain deposits 1

• No population-based studies have demonstrated an increased incidence of monoclonal gammopathies in IBD cohorts compared to the general population 1, 2

Clinical Recognition Rather Than Screening

Rather than routine screening, clinicians should maintain awareness of specific presentations:

• Unexplained gastrointestinal symptoms in IBD patients that don't respond to standard IBD therapy, particularly protein-losing enteropathy or refractory diarrhea 1

• Extracellular deposits on gastrointestinal biopsies that are Congo red negative should prompt immunohistochemistry for immunoglobulin light chains to exclude LCDD 1

• Middle-aged or older women with longstanding IBD who develop serum monoclonal protein should be evaluated for progression risk using standard MGUS risk stratification 2

Standard MGUS Evaluation When Detected

If monoclonal protein is incidentally discovered in an IBD patient, follow established guidelines:

• Initial workup includes serum protein electrophoresis with immunofixation, serum free light chain assay with kappa:lambda ratio, complete blood count, comprehensive metabolic panel with calcium and creatinine, and quantitative immunoglobulins 3, 4

• Risk stratification using the Mayo Clinic model: assess M-protein concentration (<15 g/L vs ≥15 g/L), immunoglobulin type (IgG vs non-IgG), and free light chain ratio (normal vs abnormal) 4

• Low-risk MGUS (IgG isotype, M-protein <15 g/L, normal FLC ratio) requires follow-up at 6 months, then every 1-2 years if stable, with 5% progression risk at 20 years 4

• Bone marrow biopsy is indicated only for M-protein >15 g/L, concerning symptoms, or abnormal laboratory parameters suggesting progression 3

Inflammatory State Hypothesis

While chronic inflammation theoretically could predispose to plasma cell disorders, this remains speculative:

• Polyclonal free light chain elevation (indicating inflammatory state) has been associated with 2.6-fold increased risk of developing monoclonal gammopathy in the general population 5

• IBD represents chronic inflammation, but no studies have specifically examined whether IBD-associated inflammation increases monoclonal gammopathy risk beyond baseline population rates 5

Critical Pitfalls to Avoid

• Do not perform routine MGUS screening in asymptomatic IBD patients, as population screening is not recommended even in high-risk groups 4

• Do not attribute all gastrointestinal symptoms to IBD without considering alternative diagnoses when symptoms are atypical or refractory to standard therapy 1

• Do not overlook monoclonal protein if detected incidentally during workup for other conditions—proceed with standard risk stratification regardless of IBD diagnosis 3, 4

• Do not assume stability once MGUS is diagnosed—follow guideline-based monitoring intervals based on risk category 6, 4