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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): Gene(s) directly associated with this condition or phenotype.	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.

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Hepatosplenomegaly

MedGen UID:: 9225
•Concept ID:: C0019214
•: Sign or Symptom

Simultaneous enlargement of the liver and spleen.

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Optic neuritis

MedGen UID:: 18181
•Concept ID:: C0029134
•: Disease or Syndrome

Inflammation of the optic nerve.

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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.

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Panniculitis

MedGen UID:: 45301
•Concept ID:: C0030326
•: Disease or Syndrome

Inflammation of subcutaneous adipose tissue.

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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.

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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.

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Decreased circulating total IgM

MedGen UID:: 116095
•Concept ID:: C0239989
•: Finding

An abnormally decreased level of immunoglobulin M (IgM) in blood.

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Neutropenia

MedGen UID:: 163121
•Concept ID:: C0853697
•: Finding

An abnormally low number of neutrophils in the peripheral blood.

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B lymphocytopenia

MedGen UID:: 340780
•Concept ID:: C1855067
•: Finding

An abnormal decrease from the normal count of B cells.

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Decreased circulating antibody concentration

MedGen UID:: 892481
•Concept ID:: C4048270
•: Finding

An abnormally decreased level of immunoglobulin in blood.

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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.

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Decreased circulating IgG concentration

MedGen UID:: 1720114
•Concept ID:: C5234937
•: Finding

An abnormally decreased level of immunoglobulin G (IgG) in blood.

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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.

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Chorioretinitis

MedGen UID:: 942
•Concept ID:: C0008513
•: Disease or Syndrome

An inflammation of the choroid and retina.

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Abnormality of head or neck
- Conical tooth
Abnormality of the cardiovascular system
- Cerebral hemorrhage
Abnormality of the digestive system
- Hepatosplenomegaly
Abnormality of the eye
- Chorioretinitis
Abnormality of the immune system

Professional guidelines

PubMed

Relapsing polychondritis: clinical updates and new differential diagnoses.

Mertz P, Costedoat-Chalumeau N, Ferrada MA, Moulis G, Mekinian A, Grayson PC, Arnaud L
Nat Rev Rheumatol 2024 Jun;20(6):347-360. Epub 2024 May 2 doi: 10.1038/s41584-024-01113-9. PMID: 38698240

VEXAS syndrome: Clinical manifestations, diagnosis, and treatment.

Loeza-Uribe MP, Hinojosa-Azaola A, Sánchez-Hernández BE, Crispín JC, Apodaca-Chávez E, Ferrada MA, Martín-Nares E
Reumatol Clin (Engl Ed) 2024 Jan;20(1):47-56. Epub 2023 Dec 29 doi: 10.1016/j.reumae.2023.12.004. PMID: 38160120

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

See all (7)

Recent clinical studies

Etiology

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

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: 37084382 Free 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: 36692560 Free 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

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: 34427584 Free PMC Article

See all (48)

Diagnosis

VEXAS syndrome: An update.

Khitri MY, Hadjadj J, Mekinian A, Jachiet V
Joint Bone Spine 2024 Jul;91(4):105700. Epub 2024 Feb 1 doi: 10.1016/j.jbspin.2024.105700. PMID: 38307404

VEXAS syndrome: Clinical manifestations, diagnosis, and treatment.

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

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

Pediatric hemophagocytic lymphohistiocytosis.

Canna SW, Marsh RA
Blood 2020 Apr 16;135(16):1332-1343. doi: 10.1182/blood.2019000936. PMID: 32107531 Free PMC Article

See all (95)

Therapy

Efficacy and safety of targeted therapies in VEXAS syndrome: retrospective study from the FRENVEX.

Hadjadj J, Nguyen Y, Mouloudj D, Bourguiba R, Heiblig M, Aloui H, McAvoy C, Lacombe V, Ardois S, Campochiaro C, Maria A, Coustal C, Comont T, Lazaro E, Lifermann F, Le Guenno G, Lobbes H, Grobost V, Outh R, Campagne J, Dor-Etienne A, Garnier A, Jamilloux Y, Dossier A, Samson M, Audia S, Nicolas B, Mathian A, de Maleprade B, De Sainte-Marie B, Faucher B, Bouaziz JD, Broner J, Dumain C, Antoine C, Carpentier B, Castel B, Lartigau-Roussin C, Crickx E, Volle G, Fayard D, Decker P, Moulinet T, Dumont A, Nguyen A, Aouba A, Martellosio JP, Levavasseur M, Puigrenier S, Antoine P, Giraud JT, Hermine O, Lacout C, Martis N, Karam JD, Chasset F, Arnaud L, Marianetti P, Deligny C, Chazal T, Woaye-Hune P, Roux-Sauvat M, Meyer A, Sujobert P, Hirsch P, Abisror N, Fenaux P, Kosmider O, Jachiet V, Fain O, Terrier B, Mekinian A, Georgin-Lavialle S; FRENVEX
Ann Rheum Dis 2024 Sep 30;83(10):1358-1367. doi: 10.1136/ard-2024-225640. PMID: 38777378

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: 37243340 Free 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

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

See all (22)

Prognosis

Relapsing polychondritis: clinical updates and new differential diagnoses.

Mertz P, Costedoat-Chalumeau N, Ferrada MA, Moulis G, Mekinian A, Grayson PC, Arnaud L
Nat Rev Rheumatol 2024 Jun;20(6):347-360. Epub 2024 May 2 doi: 10.1038/s41584-024-01113-9. PMID: 38698240

VEXAS syndrome: Clinical manifestations, diagnosis, and treatment.

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

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

See all (28)

Clinical prediction guides

Skin Manifestations of VEXAS Syndrome and Associated Genotypes.

Tan IJ, Ferrada MA, Ahmad S, Fike A, Quinn KA, Groarke EM, Beck DB, Allbritton J, Castelo-Soccio L, Young NS, Patel BA, Grayson PC, Cowen EW
JAMA Dermatol 2024 Aug 1;160(8):822-829. doi: 10.1001/jamadermatol.2024.1657. PMID: 38865133 Free PMC Article

Efficient detection of somatic UBA1 variants and clinical scoring system predicting patients with variants in VEXAS syndrome.

Maeda A, Tsuchida N, Uchiyama Y, Horita N, Kobayashi S, Kishimoto M, Kobayashi D, Matsumoto H, Asano T, Migita K, Kato A, Mori I, Morita H, Matsubara A, Marumo Y, Ito Y, Machiyama T, Shirai T, Ishii T, Kishibe M, Yoshida Y, Hirata S, Akao S, Higuchi A, Rokutanda R, Nagahata K, Takahashi H, Katsuo K, Ohtani T, Fujiwara H, Nagano H, Hosokawa T, Ito T, Haji Y, Yamaguchi H, Hagino N, Shimizu T, Koga T, Kawakami A, Kageyama G, Kobayashi H, Aoki A, Mizokami A, Takeuchi Y, Motohashi R, Hagiyama H, Itagane M, Teruya H, Kato T, Miyoshi Y, Kise T, Yokogawa N, Ishida T, Umeda N, Isogai S, Naniwa T, Yamabe T, Uchino K, Kanasugi J, Takami A, Kondo Y, Furuhashi K, Saito K, Ohno S, Kishimoto D, Yamamoto M, Fujita Y, Fujieda Y, Araki S, Tsushima H, Misawa K, Katagiri A, Kobayashi T, Hashimoto K, Sone T, Hidaka Y, Ida H, Nishikomori R, Doi H, Fujimaki K, Akasaka K, Amano M, Matsushima H, Kashino K, Ohnishi H, Miwa Y, Takahashi N, Takase-Minegishi K, Yoshimi R, Kirino Y, Nakajima H, Matsumoto N
Rheumatology (Oxford) 2024 Aug 1;63(8):2056-2064. doi: 10.1093/rheumatology/kead425. PMID: 37606963

Estimated Prevalence and Clinical Manifestations of UBA1 Variants Associated With VEXAS Syndrome in a Clinical Population.

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: 35793467 Free PMC Article

Somatic Mutations in UBA1 Define a Distinct Subset of Relapsing Polychondritis Patients With VEXAS.

See all (17)

Recent systematic reviews

Clinical characteristics, disease trajectories and management of vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome: a systematic review.

Kouranloo K, Dey M, Almutawa J, Myall N, Nune A
Rheumatol Int 2024 Jul;44(7):1219-1232. Epub 2023 Dec 21 doi: 10.1007/s00296-023-05513-0. PMID: 38129348

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: 36617363 Free PMC Article

See all (3)

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Autoinflammatory disease, X-linked(SAIDX)

Definition

Clinical features

Professional guidelines

PubMed

Recent clinical studies

Etiology

Diagnosis

Therapy

Prognosis

Clinical prediction guides

Recent systematic reviews

Supplemental Content

Table of contents

Genetic Testing Registry

Clinical resources

Practice guidelines

Molecular resources

Consumer resources

Reviews

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