Arthritis in primary immunodeficiencies

O.R. Boyarchuk, L.A. Volyanska, T.A. Kovalchuk, M.I. Kinash


The article deals with joint diseases in patients with primary immunodeficiencies. The analysis of the li­terature data based on Scopus, Science Index, Google Scholar, PubMed databases accentuated primary immunodeficiencies associated with the joint damage. Arthritis in patients with primary immunodeficiencies can be septic or aseptic. Chronic autoimmune arthritis with the development of destructive changes in the joint in these patients is always a challenge for the physicians and causes difficulties in the diagnosis and treatment, requires a careful approach to treatment.


primary immunodeficiency; arthritis


Bousfiha AA, Jeddane L, Ailal F, et al. Primary Immunodeficiency Diseases Worldwide: More Common than Generally Thought. J Clin Immunol. 2013;33:1-7. doi: 10.1007/s10875-012-9751-7.

Joshi AY, Iyer VN, Hagan JB, et al. Incidence and temporal trends of primary immunodeficiency: a population-based cohort study. Mayo Clin Proc. 2009;84(1): 6-22. doi: 10.1016/S0025-6196(11)60802-1.

Al-Herz W, Bousfiha A, Casanova JL, et al. Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency. Front Immunol. 2014;5:162. doi: 10.3389/fimmu.2014.00162.

Chernyshova LI. The main achievements and problems of pediatric immunology in Ukraine. Materіali XІІІ Vseukraїns'koї naukovopraktichnoї konferencії z mіzhnarodnoju uchastju “Pitannja іmunologії v pedіatrії”. Sovremennaja pediatrija. 2013;5:209-11. (in Ukrainian).

Wulffraat NM, Sanders LAM, Kuis W. Immunodeficiencies and the Rheumatic Diseases. In Textbook of Pediatric Rheumatology, 7th edition. Cassidy JT, Petty RE, editors. Philadelphia: WB Saunders, 2001:706-23.

Meyer Bahlburg A, Dressler F, Baumann U. Chronic arthritis in a boy with Cernunnos immunodeficiency. Clinical immunology. 2014;154(1):47-8. doi: 10.1016/j.clim.2014.06.003.

Goyal R, Bulua AC, Nikolov NP, Schwartzberg PL, Siegel RM. Rheumatologic and autoimmune manifestations of primary immunodeficiency disorders. Current opinion in rheumatology. 2009;21(1):78-84. doi: 10.1097/BOR.0b013e32831cb939.

Sordet C, Cantagrel A, Schaeverbeke T, Sibilia J. Bone and joint disease associated with primary immunodeficiencies. Joint Bone Spine. 2005;72(6):503-14. doi:10.1016/j.jbspin.2004.07.012.

Bloom KA, Chung D, Cunningham Rundles C. Osteoarticular infectious complications in patients with primary immunodeficiencies. Current opinion in rheumatology. 2008;20(4):480-5. doi: 10.15226/2372-0948/4/1/00145.

Dupuis Girod S, Medioni J, Haddad E, et al. Autoimmunity in Wiskott-Aldrich syndrome: risk factors, clinical features, and outcome in a single-center cohort of 55 patients. Pediatrics. 2003;111(5 Pt1):e622-627. PMID: 12728121.

Akman IO, Ostrov BE, Neudorf S. Autoimmune manifestations of the Wiskott-Aldrich syndrome. Seminars in arthritis and rheumatism. 1998;27(4):218-25. PMID: 9514127.

Sullivan KE, Mullen CA, Blaese RM, et al. A multiinstitutional survey of the Wiskott-Aldrich syndrome. J Pediatr 1994,125:876-85. PMID: 7996359.

Moin M, Aghamohammadi A, Kouhi A, Tavassoli S, Rezaei N, et al. Ataxia-telangiectasia in Iran: clinical and laboratory features of 104 patients. Pediatric neurology. 2007;37(1):21-8. doi:10.1016/j.pediatrneurol.2007.03.002.

Pasini AM, Gagro A, Roić G, Vrdoljak O, Lujić L, Žutelija-Fattorini M. Ataxia Telangiectasia and Juvenile Idiopathic Arthritis. Pediatrics. 2017;139(2). doi: 10.1542/peds.2016-1279.

Pasic S, Cupic M, Jovanovic T, Djukic S, Kavaric M, Lazarevic I. Nijmegen breakage syndrome and chronic polyarthritis. The Italian Journal of Pediatrics. 2013;39:59. doi: 10.1186/1824-7288-39-59.

Kaya N, Al Muhsen S, Al Saud B, et al. ICF syndrome in Saudi Arabia: immunological, cytogenetic and molecular analysis. Journal of clinical immunology. 2011;31(2):245-52. doi: 10.1007/s10875-010-9488-0.

Verloes A, Curry C, Jamar M, et al. Juvenile rheumatoid arthritis and del(22q11) syndrome: a non-random association. Journal of medical genetics. 1998;35(11):943-7. PMID: 9832043.

Kwan A, Manning MA, Zollars LK, Hoyme HE. Marked variability in the radiographic features of cartilage-hair hypoplasia: Case report and review of the literature. Am J Med Genet A. 2012;158A:2911-6. doi: 10.1002/ajmg.a.35604.

Tylki Szymańska A, Pyrkosz A, Krajewska Walasek M, Michałkiewicz J, Kowalska A, Rokicki D. Schimke immuno-osseous dysplasia: two cases. Pediatric radiology. 2003;33(3):216-8. doi: 10.1007/s00247-002-0852-y.

Macías Fernández I. Septic arthritis in a case of hyper-IgE syndrome. Reumatologiá clinica. 2010;6(1):53-5. (in Spanish). doi: 10.1016/S2173-5743(10)70010-1.

Jouhadi Z, Khadir K, Ailal F, et al. Ten-year follow-up of a DOCK8-deficient child with features of systemic lupus erythematosus. Pediatrics. 2014 Nov;134(5):e1458-63. doi: 10.1542/peds.2013-1383.

Nadeau K, Hwa V, Rosenfeld RG. STAT5b deficiency: an unsuspected cause of growth failure, immunodeficiency, and severe pulmonary disease. The Journal of Pediatrics. 2011 May;158(5):701-8. doi: 10.1016/j.clim.2013.04.014.

Plebani A, Soresina A, Rondelli R, et al. Clinical, immunological, and molecular analysis in a large cohort of patients with X-linked agammaglobulinemia: an Italian multicenter study. Clinical immunology. 2002;104(3):221-30. PMID: 12217331.

Winkelstein JA, Marino MC, Lederman HM, et al. X-linked agammaglobulinemia: report on a United States registry of 201 patients. Medicine. 2006;85(4):193-202. doi:10.1097/

Zhu Z, Kang Y, Lin Z, et al. X-linked agammaglobulinemia combined with juvenile idiopathic arthritis and invasive Klebsiella pneumoniae polyarticular septic arthritis. Clinical rheumatology. 2015;34(2):397-401. doi:10.1007/s10067-014-2537-y.

Fu JL, Shyur SD, Lin HY, Lai YC. X-linked agammaglobulinemia presenting as juvenile chronic arthritis: report of one case. Acta Paediatr Taiwan. 1999;40(4):280-3. PMID: 10910631.

Ludwig J, Rossler L. Pediatric mono-arthritis as initial manifestation of X-linked agammaglobulinemia (M. Bruton). Z Othop Ihre Grenzgeb. 1999; 137(5):419-22. (in German). doi: 10.1055/s-2008-1037384.

Wasowska-Krolikowska K, Krogulska A. Agammaglobulinemia and arthritis-diagnostic problems. Mon Sci Monit, 1997;3(4):589-93.

Verbruggen G, De Backer S, Deforce D, et al. X-linked agammaglobulinemia and rheumatoid arthritis. Ann Rheum Dis.2005;64(7):1075-1078. doi: 10.1136/ard.2004.030049.

Yel L, Minegishi Y, Coustan-Smith E, Buckley RH, Trübel H, Pachman LM, Kitchingman GR, et al. Mutations in the mu heavy-chain gene in patients with agammaglobulinemia. The New England journal of medicine. 1996;335(20):1486-93. doi: 10.1056/NEJM199611143352003.

Minegishi Y, Coustan-Smith E, Wang YH, Cooper MD, Campana D, Conley ME, et al. Mutations in the human lambda5/14.1 gene result in B cell deficiency and agammaglobulinemia. The Journal of experimental medicine. 1998;187(1):71-7. PMID: 9419212.

Kelleher P, Misbah S A. What is Good’s syndrome-immunological abnormalities with thymomas. Journal of Clinical Pathology. 2003;56(1):12-6. doi: 10.1136/jcp.56.1.12.

Swirkot J, Lewandowicz-Uszynska A, Chlebicki A, Szmyrka-Kaczmarek M, et al. Rheumatoid arthritis in a patient with common variable immunodeficiency: difficulty in diagnosis and therapy. Clinical rheumatology. 2006;25(1):92-4. doi: 10.1007/s10067-005-1141-6.

Cunningham-Rundles C, Bodian C. Common variable immunodeficiency: clinical and immunological features of 248 patients. Clinical immunology. 1999;92(1):34-48. PMID: 10413651. doi: 10.1006/clim.1999.4725.

Moradinejad MH, Rafati AH, Ardalan M, et al. Prevalence of IgA deficiency in children with juvenile rheumatoid arthritis. Iranian journal of allergy, asthma, and immunology. 2011;10(1):35-40. PMID: 21358013. doi: 010.01/ijaai.3540.

Terzioğlu E, Kokuludağ A, Sin A, et al. Selective IgA deficiency and ankylosing spondylitis. Journal of investigational allergology & clinical immunology. 1997;7(6):619-20. PMID: 9491204.

Castrignano SB, Carlsson B, Carneiro Sampaio MS, Söderström T, Hanson LA. IgA and IgG subclass deficiency in a poor population in a developing country. Scandinavian journal of immunology. 1993 Apr;37(4):509-14. PMID: 8385798.

Beard LJ, Ferris L, Ferrante A. Immunoglobulin G subclasses and lymphocyte subpopulations and function in osteomyelitis and septic arthritis. Acta pædiatrica Scandinavica. 1990;79(6-7):599-604. PMID: 2386051.

Quartier P, Bustamante J, Sanal O, et al. Clinical, immunologic and genetic analysis of 29 patients with autosomal recessive hyper-IgM syndrome due to Activation-Induced Cytidine Deaminase deficiency. Clin Immunol. 2004 Jan;110(1):22-9.doi: 10.1016/j.clim.2003.10.007.

Hazen MM, Woodward AL, Hofmann I, et al. Mutations of the hemophagocytic lymphohistiocytosis-associated gene UNC13D in a patient with systemic juvenile idiopathic arthritis. Arthritis and rheumatism. 2008;58(2):567-70. doi: 10.1002/art.23199.

Wildin RS, Smyk Pearson S, Filipovich AH. Clinical and molecular features of the immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome. Journal of medical genetics. 2002;39(8):537-45. doi: 10.1136%2Fjmg.39.8.537.

Pun T, Chandurkar V. Growth hormone deficiency, short stature, and juvenile rheumatoid arthritis in a patient with autoimmune polyglandular syndrome type 1: case report and brief review of the literature. ISRN Endocrinology. 2011;2011:462759-462759. doi: 10.5402/2011/462759.

Neven B, Magerus-Chatinet A, Florkin B, et al. A survey of 90 patients with autoimmune lymphoproliferative syndrome related to TNFRSF6 mutation. Blood. 2011;118(18):4798- 807.doi: 10.1182/blood-2011-04-347641.

Kotlarz D, Beier R, Murugan D, et al. Loss of interleukin-10 signaling and infantile inflammatory bowel disease: implications for diagnosis and therapy. Gastroenterology. 2012;143(2):347-55. doi: 10.1053/j.gastro.2012.04.045.

Dale RC, Gornall H, Singh-Grewal D, et al. Familial Aicardi-Goutières syndrome due to SAMHD1 mutations is associated with chronic arthropathy and contractures. American journal of medical genetics. Part A. 2010;152A(4):938-42. doi: 10.1002/ajmg.a.33359.

Raptaki M, Varela I, Spanou K, et al. Chronic granulomatous disease: a 25-year patient registry based on a multistep diagnostic procedure, fromthe referral center for primary immunodeficiencies in Greece. Journal of clinical immunology. 2013 Nov;33(8):1302-9. doi: 10.1007/s10875-013-9940-z.

De Ravin SS, Naumann N, Cowen EW, et al. Chronic granulomatous disease as a risk factor for autoimmune disease. Journal of allergy and clinical immunology. 2008;122(6):1097-103. doi: 10.1016/j.jaci.2008.07.050.

Dorman SE, Picard C, Lammas D, et al. Clinical features of dominant and recessive interferon gamma receptor 1 deficiencies. Lancet. 2004 Dec 11-17;364(9451):2113-21. doi: 10.1016/S0140-6736(04)17552-1.

Dickinson RE, Milne P, Jardine L, et al. The evolution of cellular deficiency in GATA2 mutation. Blood. 2014;123(6):863-74. PMID: 24345756. doi: 10.1182/blood-2013-07-517151.

Niehues T, Reichenbach J, Neubert J, et al. Nuclear factor kappaB essential modulator-deficient child with immunodeficiency yet without anhidrotic ectodermal dysplasia. Journal of allergy and clinical immunology. 2004 Dec;114(6):1456-62. doi: 10.1016/j.jaci.2004.08.047.

Szabó J, Dobay O, Erdos M, et al. Recurrent infection with genetically identical pneumococcal isolates in a patient with interleukin-1 receptor-associated kinase-4 deficiency. Journal of medical microbiology. 2007;56(6):863-5. doi: 10.1099/jmm.0.47046-0.

von Bernuth H, Picard C, Jin Z, et al. Pyogenic bacterial infections in humans with MyD88 deficiency. Science. 2008 Aug;321(5889):691-6. doi: 10.1126/science.1158298.

Usluer H, Bircan Z. Protracted familial mediterranean fever arthritis presenting as septic arthritis. Rheumatology international. 2007 Sep;27(11):1083-5. doi:10.1007/s00296-007-0329-2.

Matsuoka N, Iwanaga J, Ichinose Y, et al. Two elderly cases of familial Mediterranean fever with rheumatoid arthritis. International journal of rheumatic diseases. 2014. doi: 10.1111/1756-185X.12354.

Rozenbaum M, Rosner I. Severe outcome of juvenile idiopathic arthritis (JIA) associated with familial Mediterranean fever (FMF). Clinical and Experimental Rheumatology. 2004 Jul-Aug;22(4 Suppl 34):S75-8.

van der Hilst JC, Bodar EJ, Barron KS, et al. Long-term follow-up, clinical features, and quality of life in a series of 103 patients with hyperimmunoglobulinemia D syndrome. Medicine. 2008;87(6):301-310. doi: 10.1097/MD.0b013e318190cfb7.

Hawkins PN, Lachmann HJ, Aganna E, McDermott MF. Spectrum of clinical features in Muckle-Wells syndrome and response to anakinra. Arthritis & rheumatism. 2004;50(2):607-612.doi: 10.1002/art.20033.

Hoffman HM, Rosengren S, Boyle DL, et al. Prevention of cold-associated acute inflammation in familial cold autoinflammatory syndrome by interleukin-1 receptor antagonist. Lancet. 2004;364(9447):1779-1785.doi:10.1016/S0140-6736(04)17401-1.

Boyko YaYe. Cryopyrin-associated syndromes: presentation of clinical cases. Acta medica Leopoliensia. 2013;4:86-93. (in Ukrainian).

Hull KM, Drewe E, Aksentijevich I, et al. The TNF receptor-associated periodic syndrome (TRAPS): emerging concepts of an autoinflammatory disorder. Medicine. 2002;81(5):349-368.

Demidowich AP, Freeman AF, Kuhns DB, Aksentijevich I, Gallin JI, Turner ML, et al. Brief report: genotype, phenotype, and clinical course in five patients with PAPA syndrome (pyogenic sterile arthritis, pyoderma gangrenosum, and acne). Arthritis & rheumatism. 2012;64(6):2022-7. doi: 10.1002/art.34332.

Manouvrier-Hanu S, Puech B, Piette F, Boute-Benejean O, Desbonnet A, Duquesnoy B, et al. Blau syndrome of granulomatous arthritis, iritis, and skin rash: a new family and review of the literature. American journal of medical genetics. 1998;76(3):217-21. PMID: 9508240.

Ombrello MJ, Remmers EF, Sun G, et al. Cold urticaria, immunodeficiency, and autoimmunity related to PLCG2 deletions. The New England Journal of Medicine. 2012;366(4):330-8. doi: 10.1056/NEJMoa1102140.

Pettigrew HD, Teuber S, Gershwin M E. Clinical significance of complement deficiencies. Annals of the New York Academy of Sciences. 2009 Sep;1173:108-123. doi: 10.1111/j.1749-6632.2009.04633.x.

Jönsson G, Sjöholm AG, Truedsson L, Bengtsson AA, Braconier JH, Sturfelt G. Rheumatological manifestations, organ damage and autoimmunity in hereditary C2 deficiency. Rheumatology. 2007;46(7):1133-9. doi: 10.1093/rheumatology/kem023.

Davido B, Dinh A, Lagrange A, et al. Chronic gonococcal arthritis with C5 deficiency presenting with brief flare-ups: case study and literature review. Clinical rheumatology. 2014;33(9):1351-1353. PMID: 24777471. doi: 10.1007/s10067-014-2643-x.

Alcalay M, Bontoux D, Peltier A, Vial MC, Vilde JM, Wautier JL. C7 deficiency, abnormal platelet aggregation, and rheumatoid arthritis. Arthritis & rheumatism. 1981;24(1):102-103. PMID: 7470162.

Jiménez Balderas FJ, Rico Rosillo G, Bravo Gatica C, Mintz Spiro G. Functional abnormalities of complement in familial and sporadic ankylosing spondylitis. Archivos de investigación médica. 1989 Jan-Mar;20(1):79-86. PMID: 2764671.

Brickman CM, Tsokos GC, Balow JE, et al. Immunoregulatory disorders associated with hereditary angioedema. I. Clinical manifestations of autoimmune disease. Journal of allergy and clinical immunology. 1986 May;77(5):749-57. PMID: 3084606.

Rottem M, Miron D, Shiloah E, Horovitz Y and Schlezinger M. Properdin deficiency: rare presentation with meningococcal bone and joint infections. The Pediatric infectious disease journal. 1998;17(4):356- 358. PMID: 9576400.

Nita IM, Genel F, Nilsson SC, et al. Molecular characterization of two novel cases of complete complement inhibitor Factor I deficiency. Molecular immunology. 2011;48(8):1068-1072. doi: 10.1016/j.molimm.2011.01.012.

Rieux Laucat F, Magerus Chatinet A. Autoimmune lymphoproliferative syndrome: a multifactorial disorder. Haematologica. 2010;95(11):1805-1807. doi: 10.3324/haematol.2010.030395.

Gharib A, Gupta S. Skeletal and Joint Manifestations of Primary Immunodeficiency Diseases. SOJ Immunol. 2016;4(1):1-13. doi: 10.15226/2372-0948/4/1/00145.

Boyarchuk O, Volyanska L, Dmytrash L, Denefil O. Bruton agammaglobulinemia: well-known, but still difficult to diagnose (case report). Journal of Clinical Immunology. 2016;36(3):235-334 (abst 4421). doi: 10.1007/s10875-016-0237-x.


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