Chronic Inflammation May Predispose to the Development of Plasma Cell Dyscrasias.
Authors: Blanchard Elizabeth M. , Lawler Elizabeth , Brophy Mary , Fiore Louis , Munshi Nikhil C. 
Published: October 2019

Abstract
Background: It has been hypothesized that chronic antigenic stimulation in response to chronic inflammation or infection may predispose to the development of plasma cell dyscrasias (PCD) including multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS). Using Department of Veterans Affairs (VA) administrative databases we explored associations between PCD and chronic inflammatory diseases (CID) including rheumatoid arthritis (RA), inflammatory bowel diseases (IBD), psoriasis, asthma, the chronic infections hepatitis C (HEPC) and hepatitis B (HEPB), as well as history of agent orange exposure (AO).
Methods: To identify a source population of veterans who are regular users of the VA system for medical care, we gathered data on patients seen in the inpatient or outpatient setting with a diagnosis of hypertension (HTN), diabetes (DM) or coronary artery disease (CAD) between Oct 1, 1996 and Sept 30, 2003. This source population represents more than 70% of all users of the VA healthcare system. Within this population, we identified from ICD-9 codes all prevalent cases of PCD inclusive of MM and MGUS and also current diagnoses of RA, HEPB, HEPC, IBD, psoriasis and asthma. Agent Orange (AO) exposure was ascertained through administrative records. Crude and age-adjusted prevalence odds ratios for associations with PCD are reported.
Results: The source population consisted of 4,050,741 veterans who visited the VA Healthcare System nationwide during this time period. Of these patients, 12,936 (0.32%) carried a diagnosis of PCD, including either multiple myeloma or MGUS or both. Odds ratios are presented in Table I.
Table I: Associations of Plasma Cell Dyscrasias and Inflammatory Conditions
Chronic Condition # of cases Crude OR (95% CI) Age-adjusted OR (95% CI) RA 92511 2.20 (2.03,2.39) 2.15 (1.98,2.32) Hepatitis B 22958 2.03 (1.72,2.38) 3.07 (2.60,3.61) Hepatitis C 116615 1.40 (1.28,1.53) 2.326 (2.12,2.55) IBD 2675 2.83 (1.89,4.23) 3.26 (2.18,4.87) Asthma 183753 1.19 (1.10,1.29) 1.30 (1.20,1.40) Psoriasis 76697 1.43 (1.29,1.59) 1.42 (1.28,1.58) BPH 989271 1.81 (1.75,1.88) 1.53 (1.47,1.58) Agent Orange 69710 1.62 (1.45,1.80) 2.37 (2.07,2.58)
Conclusions: We have identified strong associations (OR > 2) between plasma cell dyscrasias and inflammatory conditions including rheumatoid arthritis, IBD and the chronic infections hepatitis B and C. Agent Orange exposure (already known to be associated with plasma cell dyscrasias) served as the positive control and had an age adjusted OR of 2.37. We suspect that residual confounding may be responsible for what appears to be a weak association with benign prostatic hypertrophy (BPH). Asthma and psoriasis do not appear to have a strong association with the development of plasma cell dyscrasias. A detailed ethnic and age adjusted analysis that includes other inflammatory and non-inflammatory conditions is underway in an effort to identify other associations. This study provides a basis for future research efforts focused on identifying cytokine pathways that may link these disorders and subsequently serve as targets for novel interventions to prevent the development or progression of plasma cell dyscrasias.