Introduction
Methods
Study design
Diagnosis of Sjögren’s syndrome
Disease activity scoring and assessment of neurological involvement
Neurological symptoms | Points |
---|---|
Peripheral sensory neuropathy (on NCS or biopsy-proven Small-Fiber Neuropathy) | 5 |
Peripheral motor neuropathy (on NCS with reduced motor performance) | 10 |
Myositis evident on biopsy or image morphology combined with CK elevation | 10 |
Myelitis and/or encephalitis and/or abacterial meningitis | 10 |
Cerebral vasculitis/vascular lesions of presumed autoimmune background | 10 |
Cranial nerve impairment or phrenic nerve affection | 5 |
Myasthenic syndrome | 5 |
Proven cognitive impairment on confrontational testing | 5 |
Statistical and graphical analysis
Results
pSSN | pSS | p value | |
---|---|---|---|
N total | 512 | n/a | |
N (%) | 238 (46%) | 274 (54%) | n/a |
Female, N (%) | 154 (65%) | 233 (85%) | 0.001 |
Age at onset, median (IQR) [y] | 55 (43.5–64.5) | 45 (33–56) | < 0.0001 |
Age at diagnosis, median (IQR) [y] | 59.5 (50–68.5) | 51 (39.5–60) | < 0.0001 |
Initial presentation mode at the site via hospital admission, N (%) | 127 (58%) | 71 (31%) | < 0.001 |
ACR/EULAR classification criteria 2017 | Reported assessment | Pathological, N (%) | Reported assessment | Pathological, N (%) | |
---|---|---|---|---|---|
Evident xerophthalmia [by Schirmer’s test] | 235 | 193 (82%) | 273 | 214 (78%) | 0.01 |
Evident xerostomia [by Saxon test] | 229 | 114 (50%) | 259 | 130 (50%) | 0.9 |
SSA(Ro) antibody positivity | 235 | 125 (53%) | 267 | 167 (63%) | 0.03 |
Sialadenitis grade ≥ 3 (Chisholm and Mason) | 173 | 144 (83%) | 149 | 134 (90%) | 0.08 |
2016 Focus score, mean ± sd | 4.7 ± 1.1 | 4.6 ± 1 | 0.2 | ||
Disease activity | |||||
ESSDAI, mean ± sd | 18.2 ± 21 | 7.7 ± 7.3 | < 0.0001 | ||
ESSPRI total, mean ± sd | 5 ± 2.4 | 4.8 ± 2.3 | 0.5 | ||
ESSPRI subscore: dryness, median (IQR) | 5 (2–7) | 5 (2–7) | 0.5 | ||
ESSPRI subscore: fatigue, median (IQR) | 6 (3–8) | 6 (3–8) | 0.6 | ||
ESSPRI subscore: pain, median (IQR) | 5 (3–8) | 4 (1–7) | 0.1 | ||
NISSDAI, mean ± sd | 10.4 ± 4.9 | n/a | n/a |
Neurological features in Sjögren’s syndrome
Comorbidities, immunological parameters, and baseline laboratory findings
pSSN | pSS | p value | |||
---|---|---|---|---|---|
Information available | Pathological, N (%) | Information available | Pathological, N (%) | ||
Cardiovascular risk factors | |||||
History of TIA | 211 | 2 (1%) | 261 | 8 (3%) | 0.1 |
History of stroke | 224 | 13 (6%) | 271 | 10 (4%) | 0.3 |
KHK | 223 | 11 (5%) | 270 | 11 (4%) | 0.6 |
History of smoking | 149 | 78 (52%) | 239 | 107 (45%) | 0.1 |
Diabetes mellitus | 221 | 21 (10%) | 272 | 14 (5%) | 0.07 |
Reported allergies | |||||
Allergy affected patients | 221 | 84 (38%) | 271 | 128 (47%) | 0.04 |
Drug-related | 221 | 43 (19%) | 271 | 74 (27%) | 0.04 |
Other (nutritional, contact dermatitis, insects, bugs) | 221 | 62 (28%) | 271 | 96 (35%) | 0.1 |
Seasonal | 221 | 31 (14%) | 271 | 57 (21%) | 0.04 |
pSSN | pSS | p value | |||
---|---|---|---|---|---|
Available | Pathological, N (%) | Available | Pathological, N (%) | ||
Immunological parameters | |||||
ANA | 218 | 116 (53%) | 252 | 152 (60%) | 0.1 |
Rheumatoid factor | 232 | 40 (17%) | 263 | 78 (30%) | 0.001 |
Alphafodrin antibody (IgA) | 204 | 69 (34%) | 250 | 88 (35%) | 0.8 |
SSB(La) antibody | 234 | 26 (11%) | 260 | 69 (27%) | < 0.001 |
Sm antibody | 214 | 3 (1%) | 224 | 6 (3%) | 0.4 |
U1SnRNP antibody | 225 | 4 (2%) | 225 | 9 (4%) | 0.3 |
Scl 70 antibody | 214 | 0 (0%) | 224 | 1 (0.5%) | 1.0 |
CENPB antibody | 215 | 4 (2%) | 223 | 9 (4%) | 0.3 |
Jo1 antibody | 217 | 0 (0%) | 231 | 2 (1%) | 0.2 |
CCP antibody | 63 | 4 (6%) | 146 | 3 (2%) | 0.2 |
Baseline parameters before therapy initiation | |||||
IgG, mean ± sd [g/l] | 108 | 11.8 ± 4.1 | 137 | 13.3 ± 5.4 | 0.02 |
IgA, median (IQR) [g/l] | 102 | 1.9 (1.3–3) | 133 | 2.3 (1.6–3) | 0.07 |
IgM, median (IQR) [g/l] | 99 | 1.1 (0.7–1.5) | 134 | 1.2 (0.8–1.6) | 0.3 |
WBC, median (IQR) [thousand/µl] | 142 | 6.3 (5.3–7.5) | 160 | 5.7 (4.6–7.2) | 0.004 |
RBC, mean ± sd [million cells/µl] | 142 | 4.6 ± 0.5 | 159 | 4.6 ± 0.4 | 0.9 |
Hemoglobin, mean ± sd [g/dl] | 142 | 13.7 ± 1.4 | 160 | 13.5 ± 1.2 | 0.1 |
Hematocrit, median (IQR) [%] | 141 | 40.6 (38.1–43.1) | 160 | 40.1 (37.6–41.6) | 0.09 |
Platelets, mean ± sd [thousand/µl] | 141 | 251 ± 70 | 159 | 257 ± 65 | 0.5 |
Neutrophils abs, median (IQR) [thousand cells/µl] | 131 | 3.7 (3–4.6) | 152 | 3.3 (2.7–4.3) | 0.03 |
Neutrophils, mean ± sd [%] | 131 | 59.5 ± 10.8 | 152 | 59.3 ± 11.1 | 0.9 |
Eosinophils abs, median (IQR) [cells/µl] | 130 | 0.2 (0.1–0.2) | 152 | 0.1 (0.04–0.2) | < 0.0001 |
Eosinophils, median (IQR) [%] | 133 | 2.2 (1.5–3.8) | 154 | 1.7 (0.8–2.7) | < 0.0001 |
Basophils abs, median (IQR) [cells/µl] | 131 | 0.01 (0–0.05) | 154 | 0.03 (0–0.06) | 0.07 |
Basophils, median (IQR) [%] | 131 | 0.6 (0.4–0.7) | 155 | 0.5 (0.4–0.9) | 0.7 |
Monocytes abs, mean ± sd [cells/µl] | 132 | 0.6 ± 0.62 | 154 | 0.51 ± 0.6 | 0.2 |
Monocytes, mean ± sd [%] | 130 | 8.5 ± 2.5 | 154 | 8.1 ± 2.6 | 0.2 |
Lymphocytes abs, mean ± sd [cells/µl] | 132 | 2.3 ± 4.7 | 154 | 1.7 ± 0.6 | 0.09 |
Lymphocytes, mean ± sd [%] | 130 | 28.4 ± 9.9 | 154 | 29.4 ± 9.4 | 0.4 |
CRP, median (IQR) [mg/l] | 136 | 1.4 (0.8–4.1) | 156 | 1.3 (0.7–3.1) | 0.4 |
eGFR, median (IQR) [90 ml/min/1.73m2] | 128 | 92 (74.5–100) | 149 | 89 (76–100) | 0.7 |
CK, mean ± sd [U/l] | 136 | 147 ± 156 | 149 | 105 ± 115 | 0.01 |
AST, median (IQR) [U/l] | 132 | 25 (21–34) | 140 | 24 (20–29) | 0.1 |
ALT, mean ± sd [U/l] | 120 | 32 ± 44 | 158 | 28 ± 32 | 0.4 |
YGT, mean ± sd [U/l] | 125 | 33 ± 58 | 155 | 28 ± 26 | 0.4 |
Logistic regression analysis
Variable | Univariate OR [95% CI] | Univariate p value | Multivariate OR [95% CI] | Multivariate p value |
---|---|---|---|---|
Female sex | 0.32 [0.21–0.49] | < 0.001 | 0.33 [0.16–0.65] | 0.001 |
Age at onset | 1.04 [1.02–1.05] | < 0.001 | 1.004 [1.002–1.006] | < 0.0001 |
Age at diagnosis | 1.04 [1.03–1.05] | < 0.001 | n/i | n/i |
Initial presentation mode at site: hospital admission | 3.1 [2.13–4.61] | < 0.001 | 3.2 [1.71–5.99] | < 0.001 |
SSA(Ro) antibodies | 0.68 [0.48–0.97] | 0.03 | n/i | n/i |
SSB(La) antibodies | 0.34 [0.21–0.57] | < 0.001 | n/i | n/i |
Rheumatoid factor | 0.49 [0.32–0.76] | 0.001 | n/i | n/i |
Allergy affected patients | 0.68 [0.48–0.98] | 0.04 | n/i | n/i |
Drug-related allergy | 0.64 [0.42–0.99] | 0.04 | n/i | n/i |
Seasonal allergy | 0.61 [0.38–0.99] | 0.05 | n/i | n/i |
IgG | 0.93 [0.88–0.99] | 0.02 | 0.92 [0.86–0.998] | 0.04 |
WBC | 1.15 [1.02–1.29] | 0.02 | n/i | n/i |
Neutrophils, absolute | 1.11 [0.97–1.28] | 0.1 | n/i | n/i |
Eosinophils, absolute | 1.5 [1.23–1.94] | 0.001 | 1.33 [1.05–1.68] | 0.02 |
Eosinophils, relative | 1.002 [1.001–1.004] | 0.01 | n/i | n/i |
CK | 1.003 [1.0005–1.005] | 0.02 | n/i | n/i |