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VEXAS syndrome(VEXAS)

MedGen UID:
1765785
Concept ID:
C5435753
Disease or Syndrome
Synonyms: vacuoles, E1 enzyme, X-linked, autoinflammatory and somatic syndrome; VEXAS
SNOMED CT: VEXAS syndrome (1290093003); Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome (1290093003)
 
Gene (location): UBA1 (Xp11.3)
 
Monarch Initiative: MONDO:0026777
OMIM®: 301054
Orphanet: ORPHA596753

Definition

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome) is an adult-onset inflammatory disease that primarily affects males and is caused by somatic, not germline, mutations. The disorder is characterized by adult onset of rheumatologic symptoms at a mean age of 64 years. Features include recurrent fevers, pulmonary and dermatologic inflammatory manifestations, vasculitis, deep vein thrombosis, arthralgias, and ear and nose chondritis. Laboratory studies indicate hematologic abnormalities, including macrocytic anemia, as well as increased levels of acute-phase reactants; about half of patients have positive autoantibodies. Bone marrow biopsy shows degenerative vacuolization restricted to myeloid and erythroid precursor cells, as well as variable hematopoietic dyspoiesis and dysplasias. The condition does not respond to rheumatologic medications and the features may result in premature death (summary by Beck et al., 2020). [from OMIM]

Clinical features

From HPO
Arthralgia
MedGen UID:
13917
Concept ID:
C0003862
Sign or Symptom
Joint pain.
Fatigue
MedGen UID:
41971
Concept ID:
C0015672
Sign or Symptom
A subjective feeling of tiredness characterized by a lack of energy and motivation.
Night sweats
MedGen UID:
10351
Concept ID:
C0028081
Sign or Symptom
Occurrence of excessive sweating during sleep.
Myelodysplasia
MedGen UID:
10231
Concept ID:
C0026985
Congenital Abnormality
Clonal hematopoietic stem cell disorders characterized by dysplasia (ineffective production) in one or more hematopoietic cell lineages, leading to anemia and cytopenia.
Arteritis
MedGen UID:
13916
Concept ID:
C0003860
Pathologic Function
Arterial inflammation.
Sensorineural hearing loss disorder
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
Macrocytic anemia
MedGen UID:
1920
Concept ID:
C0002886
Disease or Syndrome
A type of anemia characterized by increased size of erythrocytes with increased mean corpuscular volume (MCV) and increased mean corpuscular hemoglobin (MCH).
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Thromboembolism
MedGen UID:
21532
Concept ID:
C0040038
Pathologic Function
The formation of a blood clot inside a blood vessel that subsequently travels through the blood stream from the site where it formed to another location in the body, generally leading to vascular occlusion at the distant site.
Deep venous thrombosis
MedGen UID:
57448
Concept ID:
C0149871
Disease or Syndrome
Formation of a blot clot in a deep vein. The clot often blocks blood flow, causing swelling and pain. The deep veins of the leg are most often affected.
Erythroid dysplasia
MedGen UID:
459714
Concept ID:
C2987488
Finding
Dysplasia in the erythroid lineage, which presents with a variety of morphological changes in the bone marrow, including nuclear budding or irregular nuclear contour in erythroblasts.
Megakaryocyte dysplasia
MedGen UID:
1611304
Concept ID:
C4540467
Finding
The presence of micro-megakaryocytes, hypo-lobed, or non-lobed nuclei in megakaryocytes of all sizes and multiple, widely-separated nuclei.
Arthritis
MedGen UID:
2043
Concept ID:
C0003864
Disease or Syndrome
Inflammation of a joint.
Nasal chondritis
MedGen UID:
1720694
Concept ID:
C0151219
Disease or Syndrome
Inflammation of the cartilage of the nose.
Pulmonary infiltrates
MedGen UID:
116009
Concept ID:
C0235896
Finding
A finding indicating the presence of an inflammatory or neoplastic cellular infiltrate in the lung parenchyma.
Chondritis of pinna
MedGen UID:
488931
Concept ID:
C0741305
Pathologic Function
Inflammation of the cartilage of the external ear.
Inflammatory abnormality of the skin
MedGen UID:
849741
Concept ID:
C3875321
Disease or Syndrome
The presence of inflammation of the skin. That is, an abnormality of the skin resulting from the local accumulation of fluid, plasma proteins, and leukocytes.
Autoimmune antibody positivity
MedGen UID:
868268
Concept ID:
C4022660
Finding
The presence of an antibody in the blood circulation that is directed against the organism's own cells or tissues.
Neutrophilic infiltration of the skin
MedGen UID:
1620481
Concept ID:
C4531258
Anatomical Abnormality
A predominantly neutrophilic infiltrate of the dermis and or epidermis (i.e., a large number of neutrophils inferred to have migrated into the skin).
Elevated erythrocyte sedimentation rate
MedGen UID:
57727
Concept ID:
C0151632
Finding
An increased erythrocyte sedimentation rate (ESR). The ESR is a test that measures the distance that erythrocytes have fallen after one hour in a vertical column of anticoagulated blood under the influence of gravity. The ESR is a nonspecific finding. An elevation may indicate inflammation or may be caused by any condition that elevates fibrinogen.
Recurrent fever
MedGen UID:
811468
Concept ID:
C3714772
Sign or Symptom
Periodic (episodic or recurrent) bouts of fever.
Elevated circulating C-reactive protein concentration
MedGen UID:
892906
Concept ID:
C4023452
Finding
An abnormal elevation of the C-reactive protein level in the blood circulation.
Skin plaque
MedGen UID:
69134
Concept ID:
C0241148
Finding
A plaque is a solid, raised, plateau-like (flat-topped) lesion greater than 1 cm in diameter.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVVEXAS syndrome

Professional guidelines

PubMed

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
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
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

Recent clinical studies

Etiology

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
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
Delaleu J, Lepelletier C, Calugareanu A, De Masson A, Charvet E, Petit A, Giurgea I, Amselem S, Karabina S, Jachiet M, Mahevas T, Ram-Wolff C, Vignon-Pennamen MD, Bagot M, Battistella M, Bouaziz JD
Rev Med Interne 2022 Dec;43(12):727-738. Epub 2022 Jul 20 doi: 10.1016/j.revmed.2022.06.007. PMID: 35870984
Hochman MJ, DeZern AE
Lancet Haematol 2022 Jul;9(7):e523-e534. doi: 10.1016/S2352-3026(22)00138-7. PMID: 35772431
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

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
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
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
Delaleu J, Lepelletier C, Calugareanu A, De Masson A, Charvet E, Petit A, Giurgea I, Amselem S, Karabina S, Jachiet M, Mahevas T, Ram-Wolff C, Vignon-Pennamen MD, Bagot M, Battistella M, Bouaziz JD
Rev Med Interne 2022 Dec;43(12):727-738. Epub 2022 Jul 20 doi: 10.1016/j.revmed.2022.06.007. PMID: 35870984
Hochman MJ, DeZern AE
Lancet Haematol 2022 Jul;9(7):e523-e534. doi: 10.1016/S2352-3026(22)00138-7. PMID: 35772431

Therapy

Guerineau H, Kohn M, Al Hamoud A, Sellier J, Osman J, Cabannes-Hamy A
Ann Hematol 2024 Jun;103(6):2169-2171. Epub 2024 Apr 9 doi: 10.1007/s00277-024-05750-8. PMID: 38589717
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
Sangle SR, Hughes CD, Barry L, Qureshi S, Cheah CK, Poh YJ, D'Cruz DP
Autoimmun Rev 2023 Aug;22(8):103352. Epub 2023 May 4 doi: 10.1016/j.autrev.2023.103352. PMID: 37146927
Casal Moura M, Baqir M, Tandon YK, Samec MJ, Hines AS, Reichard KK, Mangaonkar AA, Go RS, Warrington KJ, Patnaik MM, Koster MJ, Ryu JH
Respir Med 2023 Jul;213:107245. Epub 2023 Apr 14 doi: 10.1016/j.rmed.2023.107245. PMID: 37062498
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

Prognosis

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
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
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
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
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

Clinical prediction guides

Vitale A, Caggiano V, Martin-Nares E, Frassi M, Dagna L, Hissaria P, Sfriso P, Hernández-Rodríguez J, Ruiz-Irastorza G, Monti S, Tufan A, Piga M, Giardini HAM, Lopalco G, Viapiana O, De Paulis A, Triggianese P, Vitetta R, de-la-Torre A, Fonollosa A, Caroni F, Sota J, Conticini E, Sbalchiero J, Renieri A, Casamassima G, Wiesik-Szewczyk E, Yildirim D, Hinojosa-Azaola A, Crisafulli F, Franceschini F, Campochiaro C, Tomelleri A, Callisto A, Beecher M, Bindoli S, Baggio C, Gómez-Caverzaschi V, Pelegrín L, Soto-Peleteiro A, Milanesi A, Vasi I, Cauli A, Antonelli IPB, Iannone F, Bixio R, Casa FD, Mormile I, Gurnari C, Fiorenza A, Mejia-Salgado G, Kawakami-Campos PA, Ragab G, Ciccia F, Ruscitti P, Bocchia M, Balistreri A, Tosi GM, Frediani B, Cantarini L, Fabiani C
Semin Arthritis Rheum 2024 Jun;66:152430. Epub 2024 Mar 18 doi: 10.1016/j.semarthrit.2024.152430. PMID: 38554594
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
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
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
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

Recent systematic reviews

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
Boyadzhieva Z, Ruffer N, Kötter I, Krusche M
Rheumatology (Oxford) 2023 Nov 2;62(11):3518-3525. doi: 10.1093/rheumatology/kead240. PMID: 37233149
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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