Clinical characteristics of 77 patients with VEXAS stratified based on UBA1 genotype and typical CH mutations
| Characteristic . | Total . | UBA1 genotype . | Typical CH . | Typical CH subgroup . | Typical CH VAF . | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M41T . | M41V . | M41L . | c.118-1 G>C . | P value . | Yes . | No . | P value . | D/T . | D&T . | Others with or without D/T . | No typical CH . | P value . | VAF <10% . | VAF ≥10% . | P value . | ||
| Number (n) | 77 | 49 | 16 | 9 | 3 | 46 | 31 | 19 | 7 | 20 | 31 | 54 | 23 | ||||
| Median UBA1 VAF, % (range) | 74.3 (8.7, 97.3) | 75.3 (24.0, 97.3) | 71.6 (8.7, 93.3) | 80.5 (47.5, 86.4) | 64.7 (59.3, 65.7) | .3 | 7.2 (8.7, 97.3) | 75.1 (24.0, 89.3) | 1 | 81.9 (35.0, 97.3) | 57.3 (28.4, 94.7) | 74.0 (8.7, 93.3) | 75.1 (24.0, 89.3) | .2 | 74.2 (8.7, 93.3) | 76.1 (28.4, 97.3) | .4 |
| Median age, years (range)∗ | 69.3 (48.4, 88.7) | 71.0 (48.4, 88.7) | 62.8 (55.9, 78.0) | 69.0 (62.5, 75.7) | 62.8 (61.0, 71.3) | .06 | 70.0 (55.0, 83.0) | 68.0 (48.0, 89.0) | .2 | 70.8 (57.6, 82.7) | 71.0 (58.0, 80.4) | 69.4 (55.4, 78.7) | 68.0 (48.4, 88.7) | .6 | 69.1 (48.4, 88.7) | 70·8 (55.4, 82.7) | .4 |
| Median follow-up from symptom onset, years (range) | 3.7 (0.1, 20.6) | 3.2 (0.2, 20.6) | 3.3 (0.1, 11.2) | 5.5 (1.8, 6.8) | 3.7 (3.0, 4.6) | .5 | 3.2 (0.1, 20.6) | 4.4 (0.2, 9.0) | .6 | 2.8 (0.5, 15.5) | 3.2 (0.9, 6.4) | 4.4 (0.1, 20.6) | 4.4 (0.2, 9.0) | .5 | 4.0 (0.1, 13.8) | 2.9 (0.5, 20.6) | .6 |
| Median time to follow-up from sequencing, years (range) | 0.8 (0.05, 6.3) | 0.8 (0.05, 2.9) | 0.8 (0.1, 6.3) | 1.2 (0.1, 2.0) | 0.9. (0.5, 0.9) | .5 | 0.9 (0.05, 6.3) | 0.8 (0.07, 2.8) | .7 | 0.8 (0.05, 6.3) | 0.9 (0.2, 2.9) | 0.8 (0.1, 2.3) | 0.8 (0.1, 2.8) | .8 | 0·8 (0.05, 6.3) | 0.8 (0.2, 2.3) | .9 |
| Hematologic manifestations and diagnoses | |||||||||||||||||
| Cytopenias, no (%) | |||||||||||||||||
| Tranfusion-dependent anemia | 18 (23) | 10 (20) | 4 (25) | 4 (44) | 0 (0) | .5 | 9 (20) | 9 (29) | .5 | 4 (21) | 3 (43) | 2 (10) | 9 (29) | .3 | 13 (24) | 5 (22) | 1 |
| Thrombocytopenia (<100 × 103/μL) | 19 (25) | 11 (22) | 5 (31) | 2 (22) | 0 (0) | .9 | 11 (24) | 7 (23) | 1 | 5 (26) | 1 (14) | 5 (25) | 7 (23) | .9 | 12 (22) | 6 (26) | 1 |
| Presumed MDS, n (%)† | 14 (18) | 7 (14) | 3 (19) | 4 (44) | 0 (0) | .2 | 8 (17) | 6 (19) | 1 | 4 (21) | 2 (29) | 2 (10) | 6 (19) | .5 | 9 (17) | 5 (22) | .7 |
| Plasma cell disorder, n (%) | |||||||||||||||||
| MGUS | 15 (19) | 10 (20) | 4 (25) | 0 (0) | 1 (33) | .4 | 11 (24) | 4 (13) | .4 | 3 (16) | 3 (43) | 5 (25) | 4 (13) | .3 | 8 (15) | 7 (30) | .2 |
| Multiple myeloma | 2 (3) | 1 (2) | 0 (0) | 1 (11) | 0 (0) | .3 | 1 (2) | 1 (3) | 1 | 0 (0) | 0 (0) | 1 (5) | 1 (3) | 1 | 2 (4) | 0 (0) | 1 |
| Venous thromboembolism, n (%) | 44 (57) | 28 (57) | 10 (63) | 6 (67) | 0 (0) | .3 | 28 (61) | 16 (52) | .7 | 11 (58) | 4 (57) | 13 (65) | 16 (52) | .9 | 30 (56) | 14 (61) | .9 |
| Inflammatory manifestations and diagnosis | |||||||||||||||||
| Relapsing polychondritis n (%) | 46 (59) | 31 (63) | 6 (38) | 6 (67) | 3 (100) | .1 | 25 (54) | 21 (68) | .3 | 10 (53) | 5 (71) | 10 (50) | 21 (68) | .5 | 34 (63) | 12 (52) | .4 |
| Sweet syndrome, n (%) | 16 (21) | 8 (16) | 3 (19) | 3 (33) | 2 (67) | .1 | 8 (17) | 8 (26) | .5 | 3 (16) | 1 (14) | 4 (20) | 8 (26) | .9 | 12 (22) | 4 (17) | .8 |
| Symptom based | |||||||||||||||||
| Systemic symptoms‡ | 71 (92) | 45 (92) | 15 (94) | 8 (89) | 3 (100) | 1 | 42 (91) | 29 (94) | 1 | 18 (95) | 6 (86) | 18 (90) | 29 (94) | .7 | 51 (94) | 20 (87) | .4 |
| Skin involvement | 62 (81) | 38 (78) | 14 (88) | 7 (78) | 3 (100) | .8 | 37 (80) | 25 (81) | 1 | 16 (84) | 3 (43) | 18 (90) | 25 (81) | .1 | 46 (85) | 16 (73) | .1 |
| Periorbital edema | 25 (32) | 13 (27) | 11 (24) | 0 (0) | 1 (33) | <.01 | 21 (46) | 4 (13) | <.01 | 8 (42) | 3 (43) | 10 (50) | 4 (13) | .02 | 16 (30) | 9 (39) | .4 |
| Inflammatory eye disease | 8 (10) | 1 (2) | 4 (25) | 3 (33) | 0 (0) | .7 | 14 (30) | 10 (32) | 1 | 9 (47) | 1 (14) | 4 (20) | 10 (32) | .3 | 19 (35) | 5 (22) | .3 |
| Inner ear involvement§ | 39 (51) | 23 (47) | 9 (56) | 5 (55) | 2 (67) | .8 | 22 (48) | 17 (55) | .7 | 8 (42) | 5 (71) | 9 (45) | 17 (55) | .6 | 29 (54) | 10 (43) | .5 |
| Chondritis (ear/nose) | 42 (55) | 29 (59) | 5 (31) | 5 (55) | 3 (100) | .1 | 25 (54) | 17 (55) | 1 | 10 (53) | 5 (71) | 10 (50) | 17 (55) | .8 | 29 (54) | 13 (57) | 1 |
| Cardiac manifestations | 9 (12) | 5 (10) | 2 (13) | 2 (22) | 0 (0) | .7 | 4 (9) | 5 (16) | .5 | 2 (10) | 0 (0) | 2 (10) | 5 (16) | .8 | 6 (11) | 3 (13) | 1 |
| Pulmonary/pleural issues | 43 (56) | 29 (59) | 9 (56) | 5 (55) | 0 (0) | .3 | 26 (57) | 17 (55) | 1 | 11 (58) | 6 (86) | 9 (55) | 17 (55) | .3 | 27 (50) | 16 (70) | .1 |
| Musculoskeletal‖ | 56 (73) | 35 (71) | 12 (75) | 7 (78) | 2 (67) | 1 | 35 (76) | 21 (68) | .6 | 15 (79) | 6 (86) | 14 (70) | 21 (68) | .8 | 36 (67) | 20 (87) | .1 |
| Characteristic . | Total . | UBA1 genotype . | Typical CH . | Typical CH subgroup . | Typical CH VAF . | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M41T . | M41V . | M41L . | c.118-1 G>C . | P value . | Yes . | No . | P value . | D/T . | D&T . | Others with or without D/T . | No typical CH . | P value . | VAF <10% . | VAF ≥10% . | P value . | ||
| Number (n) | 77 | 49 | 16 | 9 | 3 | 46 | 31 | 19 | 7 | 20 | 31 | 54 | 23 | ||||
| Median UBA1 VAF, % (range) | 74.3 (8.7, 97.3) | 75.3 (24.0, 97.3) | 71.6 (8.7, 93.3) | 80.5 (47.5, 86.4) | 64.7 (59.3, 65.7) | .3 | 7.2 (8.7, 97.3) | 75.1 (24.0, 89.3) | 1 | 81.9 (35.0, 97.3) | 57.3 (28.4, 94.7) | 74.0 (8.7, 93.3) | 75.1 (24.0, 89.3) | .2 | 74.2 (8.7, 93.3) | 76.1 (28.4, 97.3) | .4 |
| Median age, years (range)∗ | 69.3 (48.4, 88.7) | 71.0 (48.4, 88.7) | 62.8 (55.9, 78.0) | 69.0 (62.5, 75.7) | 62.8 (61.0, 71.3) | .06 | 70.0 (55.0, 83.0) | 68.0 (48.0, 89.0) | .2 | 70.8 (57.6, 82.7) | 71.0 (58.0, 80.4) | 69.4 (55.4, 78.7) | 68.0 (48.4, 88.7) | .6 | 69.1 (48.4, 88.7) | 70·8 (55.4, 82.7) | .4 |
| Median follow-up from symptom onset, years (range) | 3.7 (0.1, 20.6) | 3.2 (0.2, 20.6) | 3.3 (0.1, 11.2) | 5.5 (1.8, 6.8) | 3.7 (3.0, 4.6) | .5 | 3.2 (0.1, 20.6) | 4.4 (0.2, 9.0) | .6 | 2.8 (0.5, 15.5) | 3.2 (0.9, 6.4) | 4.4 (0.1, 20.6) | 4.4 (0.2, 9.0) | .5 | 4.0 (0.1, 13.8) | 2.9 (0.5, 20.6) | .6 |
| Median time to follow-up from sequencing, years (range) | 0.8 (0.05, 6.3) | 0.8 (0.05, 2.9) | 0.8 (0.1, 6.3) | 1.2 (0.1, 2.0) | 0.9. (0.5, 0.9) | .5 | 0.9 (0.05, 6.3) | 0.8 (0.07, 2.8) | .7 | 0.8 (0.05, 6.3) | 0.9 (0.2, 2.9) | 0.8 (0.1, 2.3) | 0.8 (0.1, 2.8) | .8 | 0·8 (0.05, 6.3) | 0.8 (0.2, 2.3) | .9 |
| Hematologic manifestations and diagnoses | |||||||||||||||||
| Cytopenias, no (%) | |||||||||||||||||
| Tranfusion-dependent anemia | 18 (23) | 10 (20) | 4 (25) | 4 (44) | 0 (0) | .5 | 9 (20) | 9 (29) | .5 | 4 (21) | 3 (43) | 2 (10) | 9 (29) | .3 | 13 (24) | 5 (22) | 1 |
| Thrombocytopenia (<100 × 103/μL) | 19 (25) | 11 (22) | 5 (31) | 2 (22) | 0 (0) | .9 | 11 (24) | 7 (23) | 1 | 5 (26) | 1 (14) | 5 (25) | 7 (23) | .9 | 12 (22) | 6 (26) | 1 |
| Presumed MDS, n (%)† | 14 (18) | 7 (14) | 3 (19) | 4 (44) | 0 (0) | .2 | 8 (17) | 6 (19) | 1 | 4 (21) | 2 (29) | 2 (10) | 6 (19) | .5 | 9 (17) | 5 (22) | .7 |
| Plasma cell disorder, n (%) | |||||||||||||||||
| MGUS | 15 (19) | 10 (20) | 4 (25) | 0 (0) | 1 (33) | .4 | 11 (24) | 4 (13) | .4 | 3 (16) | 3 (43) | 5 (25) | 4 (13) | .3 | 8 (15) | 7 (30) | .2 |
| Multiple myeloma | 2 (3) | 1 (2) | 0 (0) | 1 (11) | 0 (0) | .3 | 1 (2) | 1 (3) | 1 | 0 (0) | 0 (0) | 1 (5) | 1 (3) | 1 | 2 (4) | 0 (0) | 1 |
| Venous thromboembolism, n (%) | 44 (57) | 28 (57) | 10 (63) | 6 (67) | 0 (0) | .3 | 28 (61) | 16 (52) | .7 | 11 (58) | 4 (57) | 13 (65) | 16 (52) | .9 | 30 (56) | 14 (61) | .9 |
| Inflammatory manifestations and diagnosis | |||||||||||||||||
| Relapsing polychondritis n (%) | 46 (59) | 31 (63) | 6 (38) | 6 (67) | 3 (100) | .1 | 25 (54) | 21 (68) | .3 | 10 (53) | 5 (71) | 10 (50) | 21 (68) | .5 | 34 (63) | 12 (52) | .4 |
| Sweet syndrome, n (%) | 16 (21) | 8 (16) | 3 (19) | 3 (33) | 2 (67) | .1 | 8 (17) | 8 (26) | .5 | 3 (16) | 1 (14) | 4 (20) | 8 (26) | .9 | 12 (22) | 4 (17) | .8 |
| Symptom based | |||||||||||||||||
| Systemic symptoms‡ | 71 (92) | 45 (92) | 15 (94) | 8 (89) | 3 (100) | 1 | 42 (91) | 29 (94) | 1 | 18 (95) | 6 (86) | 18 (90) | 29 (94) | .7 | 51 (94) | 20 (87) | .4 |
| Skin involvement | 62 (81) | 38 (78) | 14 (88) | 7 (78) | 3 (100) | .8 | 37 (80) | 25 (81) | 1 | 16 (84) | 3 (43) | 18 (90) | 25 (81) | .1 | 46 (85) | 16 (73) | .1 |
| Periorbital edema | 25 (32) | 13 (27) | 11 (24) | 0 (0) | 1 (33) | <.01 | 21 (46) | 4 (13) | <.01 | 8 (42) | 3 (43) | 10 (50) | 4 (13) | .02 | 16 (30) | 9 (39) | .4 |
| Inflammatory eye disease | 8 (10) | 1 (2) | 4 (25) | 3 (33) | 0 (0) | .7 | 14 (30) | 10 (32) | 1 | 9 (47) | 1 (14) | 4 (20) | 10 (32) | .3 | 19 (35) | 5 (22) | .3 |
| Inner ear involvement§ | 39 (51) | 23 (47) | 9 (56) | 5 (55) | 2 (67) | .8 | 22 (48) | 17 (55) | .7 | 8 (42) | 5 (71) | 9 (45) | 17 (55) | .6 | 29 (54) | 10 (43) | .5 |
| Chondritis (ear/nose) | 42 (55) | 29 (59) | 5 (31) | 5 (55) | 3 (100) | .1 | 25 (54) | 17 (55) | 1 | 10 (53) | 5 (71) | 10 (50) | 17 (55) | .8 | 29 (54) | 13 (57) | 1 |
| Cardiac manifestations | 9 (12) | 5 (10) | 2 (13) | 2 (22) | 0 (0) | .7 | 4 (9) | 5 (16) | .5 | 2 (10) | 0 (0) | 2 (10) | 5 (16) | .8 | 6 (11) | 3 (13) | 1 |
| Pulmonary/pleural issues | 43 (56) | 29 (59) | 9 (56) | 5 (55) | 0 (0) | .3 | 26 (57) | 17 (55) | 1 | 11 (58) | 6 (86) | 9 (55) | 17 (55) | .3 | 27 (50) | 16 (70) | .1 |
| Musculoskeletal‖ | 56 (73) | 35 (71) | 12 (75) | 7 (78) | 2 (67) | 1 | 35 (76) | 21 (68) | .6 | 15 (79) | 6 (86) | 14 (70) | 21 (68) | .8 | 36 (67) | 20 (87) | .1 |
P values obtained using Wilcoxon rank sum test or Kruskal-Wallis test for continuous variables, and χ2 test or Fisher exact test for discrete variables. P values <.05 are shown in bold.
D/T, DNMT3A or TET2 mutations; D&T, DNMT3A and TET2 mutations; MPN, myeloproliferative neoplasm; MGUS, monoclonal gammopathy of unknown significance.
A reported age is at the time of sequencing for CH.
Patients without a BM evaluation is clinically justified because preserved blood counts were counted as not having MDS (n = 10).
Systemic symptoms included at least having one of the following: fatigue, fever, or unintentional weight loss.
Inner ear involvement includes at least having one of the following: vestibular symptoms, hearing loss, tinnitus, or vertigo.
Musculoskeletal includes at least having one of the following: joint pain, arthritis, or tenosynovitis.