Is rheumatoid arthritis a neglected comorbidity in neurofibromatosis type 1?

Aims: Neurofibromatosis type 1 (NF-1) is a relatively rare disorder with autosomal dominant inheritance. Despite current reports highlighting the association between NF-1 and some rheumatic diseases (e.g., systemic lupus erythematosus, juvenile idiopathic arthritis, ankylosing spondylitis, and antiphospholipid antibody syndrome), the literature seems to have missed focusing on its relationship with rheumatological disorders. Hence, the present study attempted to explore definite NF-1 molecular genetic mutation in association with accompanying rheumatic diseases, particularly rheumatoid arthritis. Methods: The patients (n=23) aged 18 years who were diagnosed with NF-1 genetic mutation between 2010-2022 in the medical genetics department of our university were recruited for medical examination regarding rheumatic disorders in our rheumatology outpatient clinic. Results: There were a total of 23 patients in this study, 14 (60.9%) males and 9 (39.1%) females, with a mean age of 27.4±9.2 years (18-51 years). As a result, 4 (17.3%) patients were diagnosed with rheumatoid arthritis (RA), 3 with seropositive RA, and one with seronegative RA. Of the diagnoses, two were established RA, and two were early RA. All patients with RA had a positive metacarpophalangeal joint (MCP) squeeze test and experienced pain in bilateral hands and wrists and morning stiffness for more than 45 min. Conclusion: While the community prevalence of RA is about 1%, it is noteworthy that we detected RA in 17.3% of our patients. In the follow-up of patients with NF-1, routine examinations for pain in bilateral hands and wrists, morning stiffness over 45 minutes, and positivity of the MCP squeeze test are thought to allow early diagnosis of RA and, thus, relevant therapies.