Clinical features of 18 patients tested for the pathogenic UBA1 variants
| Feature . | Beck et al2,* (N = 25) . | P1-8 . | P9 . | P10 . | P11-18 . |
|---|---|---|---|---|---|
| Mutations, n/N | p.Met41Thr (c.122T>C) (15/25) | p.Met41Thr (c.122 T>C) (5/8) p.Met41Val (c.121A>G) (3/8) | p.Ser56Phe (c.167C>T) | p.(splice) (c.118-1G>C) | UBA1 negative |
| p.Met41Val (c.121A>G) (5/25) | |||||
| p.Met41Leu (c121A>C) (5/25) | |||||
| Demographics | |||||
| Males, n/N (%) | 25/25 (100) | 8/8 | Male | Male | 8/8 |
| Age of onset, mean (range) | 64 (45-80) | 67 (60-74) | 76 | 67 | 60 (40-71) |
| Deceased, n/N (%) | 10/25 (40) | 4/8 (50) | No (current age 81 y) | Yes (age of death 72 y) | 1/8 |
| Laboratory findings | |||||
| CRP, median (IQR), mg/L | 73 (18-128) | 100 (19-268) | 48 (7-204) | 48 (13-84) | 98 (25-263) |
| Paraprotein, n/N | No (8/8) | No | IgGκ | Yes 2/8 | |
| IgAκ ×1 | |||||
| IgAλ ×1 | |||||
| Key Features | |||||
| Fever, n (%) | 23 (92) | 8/8 (100) | Yes | Yes | 8/8 |
| Skin involvement, n (%) | 22 (88) | 7/8 (88) | Painful nodular rash | Painful nodular rash | 5/8 |
| Painful nodular rash (4/8) | Eczematous rash | Painful nodular rash (2/8) | |||
| Panniculitis (1/8) | Erythema nodosum (1/1) | ||||
| Urticarial vasculitis (1/8) | PG (1/1) | ||||
| Bullous vasculitis (1/8) | Sweets (1/1) | ||||
| Eczematous rash (1/8) | Nonspecific (1/1) | ||||
| Periorbital angioedema/cellulitis (1/8) | Cellulitis like (1/1) | ||||
| Pulmonary infiltrate, n (%) | 18 (72) | 2/8 (25) | No | No | No |
| Ear/nose chondritis, n (%) | 16 (64) | 4/8 (50) | No | No | 3/8 |
| Venous thromboembolism, n (%) | 11 (44) | 1/8 (12.5) | No | No | No |
| Macrocytic anemia, n (%) | 24 (96) | 8/8 (100) | Yes | Yes | 4/4, 4/4 Normocytic anemia |
| Other, n/N | N/A | Weight loss (8/8) | Myalgia, generalized stiffness, weight loss, fleeting arthralgia | Orchitis, generalized arthritis | Arthritis (2/8) |
| Arthritis (1/8) | Myalgia (3/8) | ||||
| Liver microabscesses (1/8) | Myofasciitis (1/1) | ||||
| Interstitial nephritis (1/8) | |||||
| Ischemic colitis (1/8) | Splenomegaly (1/1) | ||||
| Principal diagnosis | For details, see Beck et al | AOSD (1/8) | PMR/MDS | Unclassified | AOSD (1/8) |
| Unclassified (6/8) | MDS (3/8) | ||||
| RP (1/8) | GCA/PMR (3/8) | ||||
| PG/sweets (1/) | |||||
| Bone marrow features† | |||||
| Cellularity, n/N | ↑ (4/4) | ↑ (2/2) | ↑ | ↑ | ↑ (2/6) |
| Erythropoiesis, n/N | ↓ (4/4) | ↓ (2/2) | ↑ with dysplastic change, nuclear inclusions | ↓ with dysplastic change | ↓ (2/6) |
| Granulopoiesis, n/N | Expanded with dysplasia (4/4) | Expanded with dysplasia (2/2) | ↓ | ↑ with minor dysplasia (<10%), vacuoles in promyelocytes | Expanded with dysplasia (3/6) |
| Megakaryocytes, n/N | ↑ with dysplastic change (4/4) | ↑ with dysplastic change (1/2) | ↑ with dysplastic change | Normal number with dysplastic change | ↑ with dysplastic change (3/6) |
| Normal number with atypical forms (1/2) | |||||
| Bone marrow vacuoles, n/N | (2/4) | (2/2) | Undetermined | Yes | Undetermined (not commented) |
| Bone marrow diagnosis, n/N | Nondiagnostic (3/4) | Nondiagnostic (1/2) | MDS with multilineage dysplasia | MDS with multilineage dysplasia | MDS (2/6) |
| MDS (1/4) | MDS with excess blasts | MDS-AML (1/6) | |||
| MGUS (2/6) | |||||
| Normal (1/6) | |||||
| Treatment history | |||||
| Glucocorticoids, n,N (%) | 25/25 (100) | 8/8 (100) | Yes PR‡ | Yes PR | 8/8 |
| Synthetic DMARDs, n/N | For details, see Beck et al | CyS (1/8) NR | None | None | CyS (1/8) NR |
| AZA (2/8) NR | AZA (2/8) NR | ||||
| MTX (2/8) NR | MTX (2/8) PR (1/1) | ||||
| CyC (2/8) NR | MMF (2/8) NR | ||||
| MMF (2/8) NR | Dapsone (1/8) NR | ||||
| Dapsone (1/8) NR | Leflunomide (1/8) NR | ||||
| Biological DMARDs, n/N | For details, see Beck et al | Tocilizumab (3/4) 2 NR, 1 PR | None | None | Infliximab (1/1) R |
| Anakinra (1/4) NR | Anakinra (1/1) R | ||||
| Rituximab (1/4) NR | Tocilizumab (1/1) R |
| Feature . | Beck et al2,* (N = 25) . | P1-8 . | P9 . | P10 . | P11-18 . |
|---|---|---|---|---|---|
| Mutations, n/N | p.Met41Thr (c.122T>C) (15/25) | p.Met41Thr (c.122 T>C) (5/8) p.Met41Val (c.121A>G) (3/8) | p.Ser56Phe (c.167C>T) | p.(splice) (c.118-1G>C) | UBA1 negative |
| p.Met41Val (c.121A>G) (5/25) | |||||
| p.Met41Leu (c121A>C) (5/25) | |||||
| Demographics | |||||
| Males, n/N (%) | 25/25 (100) | 8/8 | Male | Male | 8/8 |
| Age of onset, mean (range) | 64 (45-80) | 67 (60-74) | 76 | 67 | 60 (40-71) |
| Deceased, n/N (%) | 10/25 (40) | 4/8 (50) | No (current age 81 y) | Yes (age of death 72 y) | 1/8 |
| Laboratory findings | |||||
| CRP, median (IQR), mg/L | 73 (18-128) | 100 (19-268) | 48 (7-204) | 48 (13-84) | 98 (25-263) |
| Paraprotein, n/N | No (8/8) | No | IgGκ | Yes 2/8 | |
| IgAκ ×1 | |||||
| IgAλ ×1 | |||||
| Key Features | |||||
| Fever, n (%) | 23 (92) | 8/8 (100) | Yes | Yes | 8/8 |
| Skin involvement, n (%) | 22 (88) | 7/8 (88) | Painful nodular rash | Painful nodular rash | 5/8 |
| Painful nodular rash (4/8) | Eczematous rash | Painful nodular rash (2/8) | |||
| Panniculitis (1/8) | Erythema nodosum (1/1) | ||||
| Urticarial vasculitis (1/8) | PG (1/1) | ||||
| Bullous vasculitis (1/8) | Sweets (1/1) | ||||
| Eczematous rash (1/8) | Nonspecific (1/1) | ||||
| Periorbital angioedema/cellulitis (1/8) | Cellulitis like (1/1) | ||||
| Pulmonary infiltrate, n (%) | 18 (72) | 2/8 (25) | No | No | No |
| Ear/nose chondritis, n (%) | 16 (64) | 4/8 (50) | No | No | 3/8 |
| Venous thromboembolism, n (%) | 11 (44) | 1/8 (12.5) | No | No | No |
| Macrocytic anemia, n (%) | 24 (96) | 8/8 (100) | Yes | Yes | 4/4, 4/4 Normocytic anemia |
| Other, n/N | N/A | Weight loss (8/8) | Myalgia, generalized stiffness, weight loss, fleeting arthralgia | Orchitis, generalized arthritis | Arthritis (2/8) |
| Arthritis (1/8) | Myalgia (3/8) | ||||
| Liver microabscesses (1/8) | Myofasciitis (1/1) | ||||
| Interstitial nephritis (1/8) | |||||
| Ischemic colitis (1/8) | Splenomegaly (1/1) | ||||
| Principal diagnosis | For details, see Beck et al | AOSD (1/8) | PMR/MDS | Unclassified | AOSD (1/8) |
| Unclassified (6/8) | MDS (3/8) | ||||
| RP (1/8) | GCA/PMR (3/8) | ||||
| PG/sweets (1/) | |||||
| Bone marrow features† | |||||
| Cellularity, n/N | ↑ (4/4) | ↑ (2/2) | ↑ | ↑ | ↑ (2/6) |
| Erythropoiesis, n/N | ↓ (4/4) | ↓ (2/2) | ↑ with dysplastic change, nuclear inclusions | ↓ with dysplastic change | ↓ (2/6) |
| Granulopoiesis, n/N | Expanded with dysplasia (4/4) | Expanded with dysplasia (2/2) | ↓ | ↑ with minor dysplasia (<10%), vacuoles in promyelocytes | Expanded with dysplasia (3/6) |
| Megakaryocytes, n/N | ↑ with dysplastic change (4/4) | ↑ with dysplastic change (1/2) | ↑ with dysplastic change | Normal number with dysplastic change | ↑ with dysplastic change (3/6) |
| Normal number with atypical forms (1/2) | |||||
| Bone marrow vacuoles, n/N | (2/4) | (2/2) | Undetermined | Yes | Undetermined (not commented) |
| Bone marrow diagnosis, n/N | Nondiagnostic (3/4) | Nondiagnostic (1/2) | MDS with multilineage dysplasia | MDS with multilineage dysplasia | MDS (2/6) |
| MDS (1/4) | MDS with excess blasts | MDS-AML (1/6) | |||
| MGUS (2/6) | |||||
| Normal (1/6) | |||||
| Treatment history | |||||
| Glucocorticoids, n,N (%) | 25/25 (100) | 8/8 (100) | Yes PR‡ | Yes PR | 8/8 |
| Synthetic DMARDs, n/N | For details, see Beck et al | CyS (1/8) NR | None | None | CyS (1/8) NR |
| AZA (2/8) NR | AZA (2/8) NR | ||||
| MTX (2/8) NR | MTX (2/8) PR (1/1) | ||||
| CyC (2/8) NR | MMF (2/8) NR | ||||
| MMF (2/8) NR | Dapsone (1/8) NR | ||||
| Dapsone (1/8) NR | Leflunomide (1/8) NR | ||||
| Biological DMARDs, n/N | For details, see Beck et al | Tocilizumab (3/4) 2 NR, 1 PR | None | None | Infliximab (1/1) R |
| Anakinra (1/4) NR | Anakinra (1/1) R | ||||
| Rituximab (1/4) NR | Tocilizumab (1/1) R |
↑, above normal range; ↓, below normal range; AML, acute myeloid leukaemia; AOSD, adult onset stills disease; AZA, azathioprine; CRP, C reactive protein; CyS, cyclosporin; CyC, cyclophosphamide; DMARDs, disease-modifying antirheumatic drugs; GCA, giant cell arteritis; MDS, myelodysplastic syndrome; MGUS, monoclonal gammopathy of undetermined significance; MMF, mycophenolate; MTX, methotrexate; N/A, not applicable; NR, nonresponder; PG, pyoderma gangrenous; PMR, polymyalgia rheumatica; PR, partial response; R, response; RP, relapsing polychondritis.
Shown as median and interquartile range (IQR).
Summary of bone marrow features of 4 confirmed VEXAS cases which were included in Beck et al.2
Good response to steroids, but now steroid dependent for control of inflammatory symptoms.