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Autoinflammatory disease, X-linked(SAIDX)

MedGen UID:
1811268
•Concept ID:
C5676885
•
Disease or Syndrome
Synonym: AUTOINFLAMMATORY DISEASE, SYSTEMIC, X-LINKED
 
Gene (location): IKBKG (Xq28)
 
Monarch Initiative: MONDO:0800129
OMIM®: 301081

Definition

X-linked systemic autoinflammatory disease (SAIDX) is characterized by the onset of systemic autoinflammation in the first months of life. Features include lymphadenopathy, hepatosplenomegaly, fever, panniculitis, and nodular skin rash. Additional manifestations may include inflammation of the optic nerve, intracranial hemorrhage, and lipodystrophy. Laboratory studies show hypogammaglobulinemia, increased or decreased white blood cell count, autoimmune cytopenias, elevated serum inflammatory markers, and a type I interferon signature (de Jesus et al., 2020 and Lee et al., 2022). [from OMIM]

Clinical features

From HPO
Cerebral hemorrhage
MedGen UID:
423648
•Concept ID:
C2937358
•
Pathologic Function
Hemorrhage into the parenchyma of the brain.
See: Feature record | Search on this feature
Hepatosplenomegaly
MedGen UID:
9225
•Concept ID:
C0019214
•
Sign or Symptom
Simultaneous enlargement of the liver and spleen.
See: Feature record | Search on this feature
Optic neuritis
MedGen UID:
18181
•Concept ID:
C0029134
•
Disease or Syndrome
Inflammation of the optic nerve.
See: Feature record | Search on this feature
Osteomyelitis
MedGen UID:
10497
•Concept ID:
C0029443
•
Disease or Syndrome
Osteomyelitis is an inflammatory process accompanied by bone destruction and caused by an infecting microorganism.
See: Feature record | Search on this feature
Panniculitis
MedGen UID:
45301
•Concept ID:
C0030326
•
Disease or Syndrome
Inflammation of subcutaneous adipose tissue.
See: Feature record | Search on this feature
Panuveitis
MedGen UID:
45303
•Concept ID:
C0030343
•
Disease or Syndrome
Inflammation of the uveal tract in which inflammation affects the anterior chamber, vitreous, retina or choroid.
See: Feature record | Search on this feature
Anterior uveitis
MedGen UID:
22595
•Concept ID:
C0042165
•
Disease or Syndrome
Inflammation of the uveal tract in which the primary site of inflammation is the anterior chamber.
See: Feature record | Search on this feature
Decreased circulating total IgM
MedGen UID:
116095
•Concept ID:
C0239989
•
Finding
An abnormally decreased level of immunoglobulin M (IgM) in blood.
See: Feature record | Search on this feature
Neutropenia
MedGen UID:
163121
•Concept ID:
C0853697
•
Finding
An abnormally low number of neutrophils in the peripheral blood.
See: Feature record | Search on this feature
B lymphocytopenia
MedGen UID:
340780
•Concept ID:
C1855067
•
Finding
An abnormal decrease from the normal count of B cells.
See: Feature record | Search on this feature
Decreased circulating antibody level
MedGen UID:
892481
•Concept ID:
C4048270
•
Finding
An abnormally decreased level of immunoglobulin in blood.
See: Feature record | Search on this feature
Complete or near-complete absence of specific antibody response to unconjugated pneumococcus vaccine
MedGen UID:
1704477
•Concept ID:
C5139463
•
Finding
The inability to synthesize postvaccination antibodies against a pneumococcus antigen, as measured by antibody titer determination following vaccination.
See: Feature record | Search on this feature
Decreased circulating IgG level
MedGen UID:
1720114
•Concept ID:
C5234937
•
Finding
An abnormally decreased level of immunoglobulin G (IgG) in blood.
See: Feature record | Search on this feature
Conical tooth
MedGen UID:
82730
•Concept ID:
C0266037
•
Congenital Abnormality
An abnormal conical form of the teeth, that is, a tooth whose sides converge or taper together incisally.
See: Feature record | Search on this feature
Chorioretinitis
MedGen UID:
942
•Concept ID:
C0008513
•
Disease or Syndrome
An inflammation of the choroid and retina.
See: Feature record | Search on this feature
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Professional guidelines

PubMed

VEXAS syndrome: Clinical, hematologic features and a practical approach to diagnosis and management.
Koster MJ, Lasho TL, Olteanu H, Reichard KK, Mangaonkar A, Warrington KJ, Patnaik MM
Am J Hematol 2024 Feb;99(2):284-299. Epub 2023 Nov 11 doi: 10.1002/ajh.27156. PMID: 37950858
Relapsing polychondritis: Best Practice & Clinical Rheumatology.
Mertz P, Sparks J, Kobrin D, Ogbonnaya SA, Sevim E, Michet C, Arnaud L, Ferrada M
Best Pract Res Clin Rheumatol 2023 Mar;37(1):101867. Epub 2023 Oct 14 doi: 10.1016/j.berh.2023.101867. PMID: 37839908
French practical guidelines for the diagnosis and management of relapsing polychondritis.
Arnaud L, Costedoat-Chalumeau N, Mathian A, Sailler L, Belot A, Dion J, Morel N, Moulis G; Collaborators
Rev Med Interne 2023 Jun;44(6):282-294. Epub 2023 May 24 doi: 10.1016/j.revmed.2023.05.005. PMID: 37236870

Recent clinical studies

Etiology

Spectrum of clonal hematopoiesis in VEXAS syndrome.
Gutierrez-Rodrigues F, Kusne Y, Fernandez J, Lasho T, Shalhoub R, Ma X, Alessi H, Finke C, Koster MJ, Mangaonkar A, Warrington KJ, Begna K, Xie Z, Ombrello AK, Viswanatha D, Ferrada M, Wilson L, Go R, Kourelis T, Reichard K, Olteanu H, Darden I, Hironaka D, Alemu L, Kajigaya S, Rosenzweig S, Calado RT, Groarke EM, Kastner DL, Calvo KR, Wu CO, Grayson PC, Young NS, Beck DB, Patel BA, Patnaik MM
Blood 2023 Jul 20;142(3):244-259. doi: 10.1182/blood.2022018774. PMID: 37084382Free PMC Article
Estimated Prevalence and Clinical Manifestations of UBA1 Variants Associated With VEXAS Syndrome in a Clinical Population.
Beck DB, Bodian DL, Shah V, Mirshahi UL, Kim J, Ding Y, Magaziner SJ, Strande NT, Cantor A, Haley JS, Cook A, Hill W, Schwartz AL, Grayson PC, Ferrada MA, Kastner DL, Carey DJ, Stewart DR
JAMA 2023 Jan 24;329(4):318-324. doi: 10.1001/jama.2022.24836. PMID: 36692560Free PMC Article
Further characterization of clinical and laboratory features in VEXAS syndrome: large-scale analysis of a multicentre case series of 116 French patients.
Georgin-Lavialle S, Terrier B, Guedon AF, Heiblig M, Comont T, Lazaro E, Lacombe V, Terriou L, Ardois S, Bouaziz JD, Mathian A, Le Guenno G, Aouba A, Outh R, Meyer A, Roux-Sauvat M, Ebbo M, Zhao LP, Bigot A, Jamilloux Y, Guillotin V, Flamarion E, Henneton P, Vial G, Jachiet V, Rossignol J, Vinzio S, Weitten T, Vinit J, Deligny C, Humbert S, Samson M, Magy-Bertrand N, Moulinet T, Bourguiba R, Hanslik T, Bachmeyer C, Sebert M, Kostine M, Bienvenu B, Biscay P, Liozon E, Sailler L, Chasset F, Audemard-Verger A, Duroyon E, Sarrabay G, Borlot F, Dieval C, Cluzeau T, Marianetti P, Lobbes H, Boursier G, Gerfaud-Valentin M, Jeannel J, Servettaz A, Audia S, Larue M, Henriot B, Faucher B, Graveleau J, de Sainte Marie B, Galland J, Bouillet L, Arnaud C, Ades L, Carrat F, Hirsch P, Fenaux P, Fain O, Sujobert P, Kosmider O, Mekinian A; French VEXAS group; GFEV, GFM, CEREMAIA, MINHEMON
Br J Dermatol 2022 Mar;186(3):564-574. Epub 2021 Nov 28 doi: 10.1111/bjd.20805. PMID: 34632574
UBA1 Variations in Neutrophilic Dermatosis Skin Lesions of Patients With VEXAS Syndrome.
Zakine E, Schell B, Battistella M, Vignon-Pennamen MD, Chasset F, Mahévas T, Cordoliani F, Adès L, Sébert M, Delaleu J, Jachiet M, Lepelletier C, Lemaire P, Chauvel C, Dhouaieb B, Kim R, Cassius C, Georgin-Lavialle S, Mekinian A, Bagot M, Braun T, Rousset L, Begon E, de Masson A, Fenaux P, Clappier E, Bouaziz JD
JAMA Dermatol 2021 Nov 1;157(11):1349-1354. doi: 10.1001/jamadermatol.2021.3344. PMID: 34495287Free PMC Article
Benign and malignant hematologic manifestations in patients with VEXAS syndrome due to somatic mutations in UBA1.
Obiorah IE, Patel BA, Groarke EM, Wang W, Trick M, Ombrello AK, Ferrada MA, Wu Z, Gutierrez-Rodrigues F, Lotter J, Wilson L, Hoffmann P, Cardona DO, Patel N, Dulau-Florea A, Kastner DL, Grayson PC, Beck DB, Young NS, Calvo KR
Blood Adv 2021 Aug 24;5(16):3203-3215. doi: 10.1182/bloodadvances.2021004976. PMID: 34427584Free PMC Article

Diagnosis

French practical guidelines for the diagnosis and management of relapsing polychondritis.
Arnaud L, Costedoat-Chalumeau N, Mathian A, Sailler L, Belot A, Dion J, Morel N, Moulis G; Collaborators
Rev Med Interne 2023 Jun;44(6):282-294. Epub 2023 May 24 doi: 10.1016/j.revmed.2023.05.005. PMID: 37236870
Estimated Prevalence and Clinical Manifestations of UBA1 Variants Associated With VEXAS Syndrome in a Clinical Population.
Beck DB, Bodian DL, Shah V, Mirshahi UL, Kim J, Ding Y, Magaziner SJ, Strande NT, Cantor A, Haley JS, Cook A, Hill W, Schwartz AL, Grayson PC, Ferrada MA, Kastner DL, Carey DJ, Stewart DR
JAMA 2023 Jan 24;329(4):318-324. doi: 10.1001/jama.2022.24836. PMID: 36692560Free PMC Article
An update on VEXAS syndrome.
Al-Hakim A, Savic S
Expert Rev Clin Immunol 2023 Feb;19(2):203-215. Epub 2022 Dec 26 doi: 10.1080/1744666X.2023.2157262. PMID: 36537591
VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) for the dermatologist.
Sterling D, Duncan ME, Philippidou M, Salisbury JR, Kulasekararaj AG, Basu TN
J Am Acad Dermatol 2023 Dec;89(6):1209-1214. Epub 2022 Feb 2 doi: 10.1016/j.jaad.2022.01.042. PMID: 35121074
Pediatric hemophagocytic lymphohistiocytosis.
Canna SW, Marsh RA
Blood 2020 Apr 16;135(16):1332-1343. doi: 10.1182/blood.2019000936. PMID: 32107531Free PMC Article

Therapy

JAK inhibitors for the treatment of VEXAS syndrome.
Bindoli S, Baggio C, Doria A, Bertoldo E, Sfriso P
Exp Biol Med (Maywood) 2023 May;248(5):394-398. Epub 2023 May 26 doi: 10.1177/15353702231165030. PMID: 37243340Free PMC Article
French practical guidelines for the diagnosis and management of relapsing polychondritis.
Arnaud L, Costedoat-Chalumeau N, Mathian A, Sailler L, Belot A, Dion J, Morel N, Moulis G; Collaborators
Rev Med Interne 2023 Jun;44(6):282-294. Epub 2023 May 24 doi: 10.1016/j.revmed.2023.05.005. PMID: 37236870
Successful azacitidine therapy for myelodysplastic syndrome associated with VEXAS syndrome.
Kataoka A, Mizumoto C, Kanda J, Iwasaki M, Sakurada M, Oka T, Fujimoto M, Yamamoto Y, Yamashita K, Nannya Y, Ogawa S, Takaori-Kondo A
Int J Hematol 2023 Jun;117(6):919-924. Epub 2023 Jan 14 doi: 10.1007/s12185-023-03532-y. PMID: 36641501
VEXAS Syndrome-A Review of Pathophysiology, Presentation, and Prognosis.
Koster MJ, Samec MJ, Warrington KJ
J Clin Rheumatol 2023 Sep 1;29(6):298-306. Epub 2022 Oct 17 doi: 10.1097/RHU.0000000000001905. PMID: 36251488
Somatic Mutations in UBA1 Define a Distinct Subset of Relapsing Polychondritis Patients With VEXAS.
Ferrada MA, Sikora KA, Luo Y, Wells KV, Patel B, Groarke EM, Ospina Cardona D, Rominger E, Hoffmann P, Le MT, Deng Z, Quinn KA, Rose E, Tsai WL, Wigerblad G, Goodspeed W, Jones A, Wilson L, Schnappauf O, Laird RS, Kim J, Allen C, Sirajuddin A, Chen M, Gadina M, Calvo KR, Kaplan MJ, Colbert RA, Aksentijevich I, Young NS, Savic S, Kastner DL, Ombrello AK, Beck DB, Grayson PC
Arthritis Rheumatol 2021 Oct;73(10):1886-1895. Epub 2021 Aug 31 doi: 10.1002/art.41743. PMID: 33779074

Prognosis

French practical guidelines for the diagnosis and management of relapsing polychondritis.
Arnaud L, Costedoat-Chalumeau N, Mathian A, Sailler L, Belot A, Dion J, Morel N, Moulis G; Collaborators
Rev Med Interne 2023 Jun;44(6):282-294. Epub 2023 May 24 doi: 10.1016/j.revmed.2023.05.005. PMID: 37236870
Spectrum of clonal hematopoiesis in VEXAS syndrome.
Gutierrez-Rodrigues F, Kusne Y, Fernandez J, Lasho T, Shalhoub R, Ma X, Alessi H, Finke C, Koster MJ, Mangaonkar A, Warrington KJ, Begna K, Xie Z, Ombrello AK, Viswanatha D, Ferrada M, Wilson L, Go R, Kourelis T, Reichard K, Olteanu H, Darden I, Hironaka D, Alemu L, Kajigaya S, Rosenzweig S, Calado RT, Groarke EM, Kastner DL, Calvo KR, Wu CO, Grayson PC, Young NS, Beck DB, Patel BA, Patnaik MM
Blood 2023 Jul 20;142(3):244-259. doi: 10.1182/blood.2022018774. PMID: 37084382Free PMC Article
VEXAS syndrome: a new paradigm for adult-onset monogenic autoinflammatory diseases.
Vitale A, Caggiano V, Bimonte A, Caroni F, Tosi GM, Fabbiani A, Renieri A, Bocchia M, Frediani B, Fabiani C, Cantarini L
Intern Emerg Med 2023 Apr;18(3):711-722. Epub 2023 Jan 20 doi: 10.1007/s11739-023-03193-z. PMID: 36662445Free PMC Article
An update on VEXAS syndrome.
Al-Hakim A, Savic S
Expert Rev Clin Immunol 2023 Feb;19(2):203-215. Epub 2022 Dec 26 doi: 10.1080/1744666X.2023.2157262. PMID: 36537591
VEXAS Syndrome-A Review of Pathophysiology, Presentation, and Prognosis.
Koster MJ, Samec MJ, Warrington KJ
J Clin Rheumatol 2023 Sep 1;29(6):298-306. Epub 2022 Oct 17 doi: 10.1097/RHU.0000000000001905. PMID: 36251488

Clinical prediction guides

Vacuoles in bone marrow progenitors: VEXAS syndrome and beyond.
Lacombe V, Hadjadj J, Georgin-Lavialle S, Lavigne C, Geneviève F, Kosmider O
Lancet Haematol 2024 Feb;11(2):e160-e167. doi: 10.1016/S2352-3026(23)00375-7. PMID: 38302223
Clinical and genetic features of Japanese cases of MDS associated with VEXAS syndrome.
Kunimoto H, Miura A, Maeda A, Tsuchida N, Uchiyama Y, Kunishita Y, Nakajima Y, Takase-Minegishi K, Yoshimi R, Miyazaki T, Hagihara M, Yamazaki E, Kirino Y, Matsumoto N, Nakajima H
Int J Hematol 2023 Oct;118(4):494-502. Epub 2023 Apr 17 doi: 10.1007/s12185-023-03598-8. PMID: 37062784
Estimated Prevalence and Clinical Manifestations of UBA1 Variants Associated With VEXAS Syndrome in a Clinical Population.
Beck DB, Bodian DL, Shah V, Mirshahi UL, Kim J, Ding Y, Magaziner SJ, Strande NT, Cantor A, Haley JS, Cook A, Hill W, Schwartz AL, Grayson PC, Ferrada MA, Kastner DL, Carey DJ, Stewart DR
JAMA 2023 Jan 24;329(4):318-324. doi: 10.1001/jama.2022.24836. PMID: 36692560Free PMC Article
Translation of cytoplasmic UBA1 contributes to VEXAS syndrome pathogenesis.
Ferrada MA, Savic S, Cardona DO, Collins JC, Alessi H, Gutierrez-Rodrigues F, Kumar DBU, Wilson L, Goodspeed W, Topilow JS, Paik JJ, Poulter JA, Kermani TA, Koster MJ, Warrington KJ, Cargo C, Tattersall RS, Duncan CJA, Cantor A, Hoffmann P, Payne EM, Bonnekoh H, Krause K, Cowen EW, Calvo KR, Patel BA, Ombrello AK, Kastner DL, Young NS, Werner A, Grayson PC, Beck DB
Blood 2022 Sep 29;140(13):1496-1506. doi: 10.1182/blood.2022016985. PMID: 35793467Free PMC Article
Somatic Mutations in UBA1 Define a Distinct Subset of Relapsing Polychondritis Patients With VEXAS.
Ferrada MA, Sikora KA, Luo Y, Wells KV, Patel B, Groarke EM, Ospina Cardona D, Rominger E, Hoffmann P, Le MT, Deng Z, Quinn KA, Rose E, Tsai WL, Wigerblad G, Goodspeed W, Jones A, Wilson L, Schnappauf O, Laird RS, Kim J, Allen C, Sirajuddin A, Chen M, Gadina M, Calvo KR, Kaplan MJ, Colbert RA, Aksentijevich I, Young NS, Savic S, Kastner DL, Ombrello AK, Beck DB, Grayson PC
Arthritis Rheumatol 2021 Oct;73(10):1886-1895. Epub 2021 Aug 31 doi: 10.1002/art.41743. PMID: 33779074

Recent systematic reviews

How to treat VEXAS syndrome: a systematic review on effectiveness and safety of current treatment strategies.
Boyadzhieva Z, Ruffer N, Kötter I, Krusche M
Rheumatology (Oxford) 2023 Nov 2;62(11):3518-3525. doi: 10.1093/rheumatology/kead240. PMID: 37233149
Pulmonary manifestations in VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome: a systematic review.
Kouranloo K, Ashley A, Zhao SS, Dey M
Rheumatol Int 2023 Jun;43(6):1023-1032. Epub 2023 Jan 8 doi: 10.1007/s00296-022-05266-2. PMID: 36617363Free PMC Article

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    Related information

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      Related information in NCBI Gene
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      Related information in GTR
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      Clinical tests in GTR
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      Related records in OMIM
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