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Journal of Health Sciences and Medicine

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Original Article
Is rheumatoid arthritis a neglected comorbidity in neurofibromatosis type 1?
Abstract
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.

Keywords : Neurofibromatosis type 1, arthritis, rheumatoid arthritis, autoimmune disease, joint

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1. Gutmann DH, Ferner RE, Listernick RH, Korf BR, Wolters PL,Johnson KJ. Neurofibromatosis type 1. Nat Rev Dis Primers.2017;3(1):17004. doi:10.1038/nrdp.2017.4
2. Messiaen LM, Callens T, Mortier G, et al. Exhaustive mutationanalysis of the NF1 gene allows identification of 95% ofmutations and reveals a high frequency of unusual splicingdefects. Hum Mutat. 2000;15(6):541-555. doi:10.1002/1098-1004(200006)15:6<541::AID-HUMU6>3.0.CO;2-N
3. Çarman KB. Neurofibromatosis type-1: Evaluation of 49 cases.Haydarpasa Numune Med J. 2017. doi:10.14744/hnhj.2017.86580.
4. Williams VC, Lucas J, Babcock MA, Gutmann DH, Korf B,Maria BL. Neurofibromatosis type 1 revisited. Pediatrics.2009;123(1):124-133. doi:10.1542/peds.2007-3204
5. Brems H, Beert E, de Ravel T, Legius E. Mechanisms in the pathogenesisof malignant tumours in neurofibromatosis type 1. Lancet Oncol.2009;10(5):508-515. doi:10.1016/S1470-2045(09)70033-6
6. Le LQ, Parada LF. Tumor microenvironment and neurofibromatosistype I: connecting the GAPs. Oncogene. 2007;26(32):4609-4616.doi:10.1038/sj.onc.121026
7. Esra S, Ceren G, Erdal S, Hatice B, Fatma E, Banu A. Is there atendency for autoimmunity in neurofibromatosis type 1? —casereports. Indian J Pediatr. 2022;89(5):510-512. doi:10.1007/s12098-021-04010-1
8. Till SH, Amos RS. Neurofibromatosis masquerading asmonoarticular juvenile arthritis. Br J Rheumatol 1997;36(2):286-288. doi:10.1093/rheumatology/36.2.286
9. Gundogdu B, Yolbas S, Yildirim A, Gonen M, Koca SS. Coexistenceof ankylosing spondylitis and neurofibromatosis type 1. Case RepRheumatol. 2016;2016:1-3. doi:10.1155/2016/4039801
10. Mbekeani JN, Galvez-Ruis A, Nezzar H, Conca W, AhmedM. Antiphospholipid syndrome and neurofibromatosis typeI: A coincidence or new association? Arq Bras Oftalmol.2019;82(2):155-157. doi:10.5935/0004-2749.20190032
11. Akyüz SG, Çaltik A, Bülbül M, Erdoğan Ö, Renda R, Demircin G.An unusual pediatric case with neurofibromatosis and systemiclupus erythematosus. Rheumatol Int. 2012;32(8):2345-2347.doi:10.1007/s00296-011-1966-z
12. Rischin A, De Silva T, Le Marshall K. Reversible eruptionof neurofibromatosis associated with tofacitinib therapy forrheumatoid arthritis. Rheumatology. 2019;58(6):1111-1113.doi:10.1093/rheumatology/kez012
13. Drago F, Pastorino C, Cecchi F, Parodi A. Segmental eruptiveneurofibromatosis infliximab-induced. J Eur Acad DermatolVenereol. 2016;30(2):356-357. doi:10.1111/jdv.12770
14. Aletaha D, Neogi T, Silman AJ, et al.. 2010 Rheumatoid arthritisclassification criteria: an American College of Rheumatology/European League Against Rheumatism collaborativeinitiative. Ann Rheum Dis. 2010;69(9):1580-1588. doi:10.1136/ard.2010.138461
15. Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American Collegeof Rheumatology Guideline for the treatment of rheumatoidarthritis. Arthritis Rheumatol. 2016;68(1):1-26. doi:10.1002/art.39480
16. Oliver JA, Lapinski PE, Lubeck BA, et al. The Ras GTPase-activating protein neurofibromin 1 promotes the positiveselection of thymocytes. Mol Immunol. 2013;55(3-4):292-302.doi:10.1016/j.molimm.2013.03.005
17. Hiatt K, Ingram DA, Huddleston H, Spandau DF, Kapur R, ClappDW. loss of the Nf1 tumor suppressor gene decreases fas antigenexpression in myeloid cells. Am J Pathol. 2004;164(4):1471-1479. doi:10.1016/S0002-9440(10)63233-6
18. Nanda A. Autoimmune diseases associated with neurofibromatosistype 1. Pediatr Dermatol. 2008;25(3):392-393. doi:10.1111/j.1525-1470.2008.00692.x
19. Kallionpää RA, Ahramo K, Aaltonen M, Pennanen P, Peltonen J,Peltonen S. Circulating free DNA in the plasma of individuals withneurofibromatosis type 1. Am J Med Genet A. 2021;185(4):1098-1104. doi:10.1002/ajmg.a.62081
20. Galeazzi M, Morozzi G, Piccini M, et al. Dosage andcharacterization of circulating DNA: present usage and possibleapplications in systemic autoimmune disorders. Autoimmun Rev.2003;2(1):50-55. doi:10.1016/s1568-9972(02)00101-5
21. Lee DM, Weinblatt ME. Rheumatoid arthritis. The Lancet.2001;358(9285):903-911. doi:10.1016/S0140-6736(01)06075-5
22. Bousoik E, Montazeri Aliabadi H. “Do We Know Jack” AboutJAK? A Closer Look at JAK/STAT Signaling Pathway. Front Oncol.2018;8. doi:10.3389/fonc.2018.00287
23. Akar S, Birlik M, Gurler O, et al. The prevalence of rheumatoidarthritis in an urban population of Izmir-Turkey. Clin ExpRheumatol. 2004;22(4):416-420
24. Çapkin E, Cakirbay H, Karkucak M, et al. Prevalence of rheumatoidarthritis in the eastern Black Sea region of Turkey. Int J RheumDis. 2010;13(4):380-384. doi:10.1111/j.1756-185X.2010.01562.x
25. Tuncer T. Prevalence of Rheumatoid arthritis and spondyloarthritisin Turkey: a nationwide study. Arch Rheumatol. 2018;33(2):128-136. doi:10.5606/ArchRheumatol.2018.6480
26. Kyburz D, Gabay C, Michel BA, Finckh A. The long-term impactof early treatment of rheumatoid arthritis on radiographicprogression: a population-based cohort study. Rheumatology.2011;50(6):1106-1110. doi:10.1093/rheumatology/keq424
27. Stewart DR, Korf BR, Nathanson KL, Stevenson DA, Yohay K.Care of adults with neurofibromatosis type 1: a clinical practiceresource of the American College of Medical Genetics andGenomics (ACMG). Genetics in Medicine. 2018;20(7):671-682.doi:10.1038/gim.2018.28
28. Gunal EK, Sarvan FO, Kamali S, et al. Low frequency of HLA-B27in ankylosing spondylitis patients from Turkey. Joint Bone Spine.2008;75(3):299-302. doi:10.1016/j.jbspin.2007.06.021
29. Saidane O, Cherif I, Tekaya R, Mahmoud I, Abdelmoula L. Sacroiliacjoint involvement in von recklinghausen neurofibromatosis. ArchRheumatol. 2017;32(1):76-79. doi:10.5606/ArchRheumatol.2017.6016
30. Moskop A, Dalrymple A, Dolatshahi L. Systemic LupusErythematosus, Evans Syndrome, and Neurofibromatosis: AnUnusual Combination in Pediatric Patient. J Pediatr Hematol Oncol.2020;42(4):e244-e247. doi:10.1097/MPH.0000000000001490
31. Richards S, Aziz N, Bale S, et al. Standards and guidelinesfor the interpretation of sequence variants: a joint consensusrecommendation of the American College of Medical Genetics andGenomics and the Association for Molecular Pathology. Geneticsin Medicine.. 2015;17(5):405-424. doi:10.1038/gim.2015.30
Article available in :
Volume 6, Issue 5, 2023
Page : 910-918
https://doi.org/10.32322/jhsm.1310764
Article Information
Received : 07 Haz 2023
Accepted : 13 Ağu 2023
Published : 28 Eyl 2023
Corresponding Author :

Adem Ertürk: Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Afyonkarahisar Health Sciences University, Afyonkarahisar, Turkey

[email protected]
Citation : Ertürk A, Sarı A, Akçin Aİ, Uysal AS, Elmas M, Turan Ç. Is rheumatoid arthritis a neglected comorbidity in neurofibromatosis type 1?. J Health Sci Med. 2023;6(5):910-918.

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