E028 Seronegative arthritis in the context of CHIP: is this a new entity that needs further investigation?
Authors: Mohamed Sarah , McKerrell Thomas , Makkuni Damodaran 
Published: April 2023

Abstract

Background/Aims
We describe a seronegative, non-erosive arthritis in the context of clonal haematopoiesis of indeterminant potential (CHIP), the premalignant stage of most myeloid malignancies and myelodysplastic syndromes (MDS). The use of targeted next-generation sequencing (NGS) has helped the clinician to identify the high risk individuals who are at an increased risk of haematological malignancies. Patients presenting with persistent neutropenia and inflammatory arthritis in addition to bone marrow examination, these genomic sequencing should be considered to identify clonal cytopenia and the risk for progression to myeloid malignancies.

Methods
A 70-year-old man referred to rheumatology clinic with pain and swelling in the small joints of the hands along with shoulder, hip and knee pains. There were few psoriatic patches but no typical features of psoriatic arthropathy. Clinically he had evidence of synovitis in the MCP joints, high inflammatory markers (CRP 157) and a low neutrophil count. Bone marrow examination at time of initial review was reported as completely normal as there was no evidence of MDS and the neutropenia was attributed to his underlying autoimmune condition. His X-rays showed no evidence of erosions and USS scan confirmed synovitis in the MCP joints. He was RF and anti-CCP negative and the diagnosis of suspected seronegative RA was considered. He was initially treated with steroids and hydroxychloroquine but the symptoms relapsed while tapering dose of steroids. A year later, adalimumab was introduced to manage the inflammatory arthritis. He did not show much response to it and golimumab was started, to which he responded very well. He was maintaining excellent clinical remission for 3 years however the neutropenia worsened. He was referred back to haematology for further investigations.

Results
The neutrophil counts had been fluctuating between 0.3 and 0.9 while receiving golimumab. Slight improvement in the count was noted after taking a 6-month break from biologics. However, this improvement was very transient. A repeat BM biopsy including myeloid next-generation genomic sequencing which diagnosed a high-risk CHIP/clinical cytopenia of unknown significance (CCUS) (mutation profile: IDH 1 R132 (12%VAF), IDH2 R140 (36% VAF), SRSF2 P95 (47% VAF) with no morphological evidence of MDS. Since this is a premalignant condition and there is a significant risk of developing AML, a decision was taken to stop golimumab and start rituximab. The neutrophil count has increased from 0.36 to 1.89 after starting the rituximab and the inflammatory arthritis remains in remission.

Conclusion
This case highlights low threshold of suspicion of CHIP in patients presenting with features of inflammatory arthritis and neutropenia and/or other cytopenias. Thus, detailed bone marrow sampling including targeted myeloid NGS panels should be undertaken to exclude CHIP or CCUS. This will potentially help us to guide treatment.
Disclosure
S. Mohamed: None. T. McKerrell: None. D. Makkuni: None.