Supplementary Table 1: Budapest Research Criteria

Supplementary Table 1: Budapest Research criteria

(1) Continuing pain, which is disproportionate to any inciting event
(2) Must report at least one symptom in each of the four following categories:
– Sensory: reports of hyperesthesia and/or allodynia
– Vasomotor: reports of temperature asymmetry and/or skin color changes and/or skin color asymmetry
– Sudomotor/edema: reports of edema and/or sweating changes and/or sweating
asymmetry
– Motor/trophic: reports of decreased range of motion and/or motor dysfunction
(weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin)
(3) Must display at least one sign at time of evaluation in two or more of the following categories:
– Sensory: evidence of hyperalgesia (to pinprick) and/or allodynia (to light touch and/or deep somatic pressure and/or joint movement)
– Vasomotor: evidence of temperature asymmetry and/or skin color changes and/or asymmetry
– Sudomotor/edema: evidence of edema and/or sweating changes and/or sweating asymmetry
– Motor/trophic: evidence of decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin)
(4) There is no other diagnosis that better explains the signs and symptoms

Supplementary Table 2: Secondary analysis- Odds ratios and P-values estimated for HLA-A alleles typed among CRPS cases and control subjects.

HLA-A alleles / Serotype / % Cases / % Controls / OR / 95% CI / P / Pc
A*01 / A1 / 34 / 34 / 1.04 / [0.72 – 1.49] / 0.852 / 1.000
A*02 / A2 / 44 / 49 / 0.80 / [0.57 – 1.14] / 0.250 / 0.997
A*03 / A3 / 34 / 29 / 1.23 / [0.85 – 1.77] / 0.287 / 0.999
A*11 / A11 / 11 / 12 / 0.94 / [0.54 – 1.63] / 0.890 / 1.000
A*23 / A23 / 1 / 2 / 0.47 / [0.09 – 2.36] / 0.375 / 1.000
A*24 / A24 / 16 / 16 / 0.99 / [0.62 – 1.58] / 1.000 / 1.000
A*25 / A25 / 4 / 2 / 1.95 / [0.81 – 4.66] / 0.216 / 0.992
A*26 / A26 / 5 / 4 / 1.12 / [0.50 – 2.48] / 0.830 / 1.000
A*29 / A29 / 8 / 5 / 1.69 / [0.91 – 3.13] / 0.120 / 0.922
A*30 / A30 / 6 / 5 / 1.33 / [0.66 – 2.69] / 0.537 / 1.000
A*31 / A31 / 5 / 6 / 1.01 / [0.48 – 2.14] / 1.000 / 1.000
A*32 / A32 / 4 / 6 / 0.64 / [0.28 – 1.52] / 0.358 / 1.000
A*33 / A33 / 3 / 2 / 1.71 / [0.65 – 4.45] / 0.343 / 1.000
A*34 / A34 / 0 / 0 / NA / NA / NA / NA
A*36 / A36 / 0 / 0 / NA / NA / NA / NA
A*66 / A66 / 1 / 1 / 1.91 / [0.37 – 9.90] / 0.545 / 1.000
A*68 / A68 / 10 / 9 / 1.12 / [0.63 – 1.98] / 0.760 / 1.000
A*69 / A69 / 0 / 0 / NA / NA / NA / NA
A*74 / A74 / 0 / 0 / NA / NA / NA / NA
A*80 / A80 / 0 / 0 / NA / NA / NA / NA

CRPS = Complex Regional Pain Syndrome; OR = Woolf – Haldane odds ratio; 95% CI= 95% confidenceinterval; NA = not applicable because of low numbers; Pc= P values corrected for multiple testing using the method of Edwards for 20 alleles.

SupplementaryTable 3: Primary andsecondary analysis -Odds ratios and P-values estimated for HLA-B alleles typed among CRPS cases and control subjects.

HLA-B alleles / Serotype / % Cases / % Controls / OR / 95% CI / P / Pc
Primary analysis
B*15:01 / B62 / 18 / 15 / 1.22 / [0.78 – 1.92] / 0.458
Secondary analysis
B*07 / B7 / 24 / 25 / 0.95 / [0.63 – 1.42] / 0.838 / 1.000
B*08 / B8 / 27 / 26 / 1.07 / [0.72 – 1.58] / 0.762 / 1.000
B*13 / B13 / 8 / 4 / 2.24 / [1.20 – 4.15] / 0.024 / 0.612
B*14 / B14 / 6 / 4 / 1.71 / [0.84 – 3.46] / 0.174 / 1.000
B*15:17 / B63 / 0 / 1 / 0.47 / [0.03 – 7.71] / 0.627 / 1.000
B*15:18 / B71 / 0 / 0 / NA / NA / NA / NA
B*15:03 / B72 / 1 / 0 / 2.41 / [0.46 – 12.57] / 0.467 / 1.000
B*15:02 / B75 / 0 / 0 / NA / NA / NA / NA
B*15:12 / B76 / 0 / 0 / NA / NA / NA / NA
B*15:13 / B77 / 0 / 0 / NA / NA / NA / NA
B*18 / B18 / 11 / 7 / 1.55 / [0.89 – 2.69] / 0.175 / 1.000
B*27 / B27 / 6 / 7 / 0.88 / [0.44 – 1.78] / 0.734 / 1.000
B*35 / B35 / 16 / 19 / 0.81 / [0.51 – 1.28] / 0.372 / 1.000
B*37 / B37 / 7 / 3 / 2.32 / [1.18 – 4.56] / 0.041 / 0.805
B*38 / B38 / 5 / 3 / 1.75 / [0.83 – 3.71] / 0.212 / 1.000
B*39 / B39 / 2 / 4 / 0.64 / [0.22 – 1.86] / 0.496 / 1.000
B*40:01 / B60 / 12 / 12 / 1.02 / [0.61 – 1.72] / 1.000 / 1.000
B*40:02 / B61 / 2 / 4 / 0.73 / [0.25 – 2.13] / 0.631 / 1.000
B*41 / B41 / 1 / 2 / 0.73 / [0.14 – 3.72] / 0.724 / 1.000
B*42 / B42 / 0 / 0 / NA / NA / NA / NA
B*44 / B44 / 19 / 22 / 0.83 / [0.53 – 1.28] / 0.398 / 1.000
B*45 / B45 / 2 / 1 / 1.77 / [0.49 – 6.34] / 0.653 / 1.000
B*46 / B46 / 0 / 0 / NA / NA / NA / NA
B*47 / B47 / 0 / 1 / 0.72 / [0.044 – 11.82] / 1.000 / 1.000
B*48 / B48 / 0 / 0 / NA / NA / NA / NA
B*49 / B49 / 1 / 1 / 0.75 / [0.15 – 3.81] / 1.000 / 1.000
B*50 / B50 / 1 / 1 / 0.75 / [0.15 – 3.81] / 1.000 / 1.000
B*51 / B51 / 8 / 11 / 0.81 / [0.44 – 1.49] / 0.563 / 1.000
B*52 / B52 / 0 / 1 / 0.42 / [0.03 – 6.82] / 0.631 / 1.000
B*53 / B53 / 0 / 1 / 0.52 / [0.03 – 8.54] / 1.000 / 1.000
B*54 / B54 / 0 / 0 / NA / NA / NA / NA
B*55 / B55 / 4 / 4 / 0.97 / [0.41 – 2.31] / 1.000 / 1.000
B*56 / B56 / 2 / 1 / 1.94 / [0.66 – 5.75] / 0.431 / 1.000
B*57 / B57 / 6 / 7 / 0.98 / [0.48 – 1.98] / 1.000 / 1.000
B*58 / B58 / 2 / 2 / 1.14 / [0.32 – 4.04] / 1.000 / 1.000
B*67 / B67 / 0 / 0 / NA / NA / NA / NA
B*73 / B73 / 0 / 0 / NA / NA / NA / NA
B*78 / B78 / 0 / 0 / NA / NA / NA / NA
B*81 / B81 / 0 / 0 / NA / NA / NA / NA

SupplementaryTable 4: Secondary analysis- Odds ratios and P-values estimated for HLA-C alleles typed among CRPS cases and control subjects.

HLA-C alleles / Serotype / % Cases / % Controls / OR / 95% CI / P / Pc
C*01 / Cw1 / 7 / 6 / 1.27 / [0.65 – 2.47 ] / 0.568 / 1.000
C*02 / Cw2 / 8 / 10 / 0.83 / [0.45 – 1.54] / 0.561 / 1.000
C*03 / Cw3 / 31 / 30 / 1.08 / [0.75 – 1.57] / 0.699 / 1.000
C*04 / Cw4 / 15 / 23 / 0.58 / [0.36 – 0.94] / 0.020 / 0.251
C*05 / Cw5 / 9 / 14 / 0.66 / [0.37 – 1.19] / 0.156 / 0.906
C*06 / Cw6 / 24 / 16 / 1.64 / [1.09 – 2.47] / 0.023 / 0.274
C*07 / Cw7 / 56 / 56 / 1.02 / [0.72 – 1.44] / 0.929 / 1.000
C*08 / Cw8 / 6 / 4 / 1.58 / [0.78 – 3.21] / 0.266 / 0.987
C*12 / Cw12 / 11 / 8 / 1.36 / [0.78 – 2.36] / 0.336 / 0.997
C*14 / Cw14 / 2 / 2 / 0.90 / [0.25 – 3.19] / 1.000 / 1.000
C*15 / Cw15 / 5 / 5 / 1.11 / [0.53 – 2.35] / 0.841 / 1.000
C*16 / Cw16 / 8 / 6 / 1.32 / [0.70 – 2.51] / 0.460 / 0.100
C*17 / Cw17 / 1 / 2 / 0.65 / [0.13 – 3.29] / 0.728 / 1.000
C*18 / Cw18 / 0 / 0 / NA / NA / NA / NA

SupplementaryTable 5: Secondary analysis- Odds ratios and P-values estimated for HLA-DR alleles typed among CRPS cases and control subjects.

HLA-DR alleles / Serotype / % Cases / % Controls / OR / 95% CI / P / Pc
DRB1*01 / DR1 / 18 / 22 / 0.77 / [0.49 – 1.20] / 0.241 / 0.979
DRB1*03:01 / DR17 / 26 / 28 / 0.93 / [0.63 – 1.37] / 0.767 / 1.000
DRB1*03:02 / DR18 / 0 / 0 / NA / NA / NA / NA
DRB1*04 / DR4 / 37 / 28 / 1.51 / [1.05 – 2.16] / 0.030 / 0.348
DRB1*07 / DR7 / 18 / 20 / 0.89 / [0.57 – 1.39] / 0.656 / 1.000
DRB1*08 / DR8 / 5 / 6 / 0.75 / [0.34 – 1.66] / 0.473 / 1.000
DRB1*09 / DR9 / 2 / 3 / 0.65 / [0.19 – 2.31] / 0.589 / 1.000
DRB1*10 / DR10 / 3 / 2 / 1.46 / [0.56 – 3.79] / 0.554 / 1.000
DRB1*11 / DR11 / 24 / 17 / 1.57 / [1.05 – 2.36] / 0.043 / 0.461
DRB1*12 / DR12 / 3 / 4 / 0.90 / [0.35 – 2.34] / 1.000 / 1.000
DRB1*13 / DR13 / 26 / 25 / 1.07 / [0.72 – 1.58] / 0.760 / 1.000
DRB1*14 / DR14 / 8 / 7 / 1.21 / [0.64 – 2.29] / 0.596 / 1.000
DRB1*15 / DR15 / 21 / 24 / 0.86 / [0.57 – 1.31] / 0.535 / 1.000
DRB1*16 / DR16 / 2 / 3 / 0.63 / [0.18 – 2.24] / 0.593 / 1.000

SupplementaryTable 6:Primary andsecondary analysis - Odds ratios and P-values estimated for HLA-DQ alleles typed among CRPS cases and control subjects.

HLA-DQ alleles / Serotype / % Cases / % Controls / OR / 95% CI / P / Pc
Primary analysis
DQB1*03:02 / DQ8 / 28 / 19 / 1.65 / [1.12 – 2.42] / 0.014
Secondary analysis
DQB1*02 / DQ2 / 37 / 39 / 0.93 / [0.65 – 1.32] / 0.718 / 1.000
DQB1*03:01 / DQ7 / 37 / 30 / 1.38 / [0.96 – 1.97] / 0.100 / 0.468
DQB1*03:03 / DQ9 / 6 / 9 / 0.69 / [0.34 – 1.38] / 0.282 / 0.863
DQB1*04 / DQ4 / 5 / 6 / 0.80 / [0.36 – 1.78] / 0.581 / 0.995
DQB1*05 / DQ5 / 28 / 33 / 0.81 / [0.55 – 1.19] / 0.301 / 0.883
DQB1*06 / DQ6 / 44 / 44 / 0.98 / [0.69 – 1.39] / 0.929 / 1.000

Supplementary Table 7: Multivariate logistic regression model examining the associationbetween HLA-DQ8 and CRPS without dystonia

B (SE) / OR (95%CI) / P-value
HLA-DQ8 / 0.65 (0.22) / 1.91 (1.23-2.95) / 0.00379
Age / 0.23 (0.02) / 1.26 (1.22-1.29) / <0.00001
Sex / 1.18 (0.24) / 3.24 (2.04-5.14) / <0.00001