A total of 16 patients entered this study. Their baseline characteristics are described in Table 1 and Additional file 1. There were 8 male patients and 8 female patients with an average age of 11.08 (IQR: 5.32–11.90) years old when starting thalidomide treatment, and the average course of disease was 6.20 ± 3.91 years. The age of disease onset was 1.0 (IQR: 0.33–4.73) years, the age at diagnosis was 7.25 (IQR:4.42–11.08) years, and the time from onset to diagnosis was 3.59 (IQR:1.38–7.0) years.

The patients shared some common characteristics, particularly recurrent fevers (8, 50.0%) and typical rash (12, 75.0%) depending on the subtype of monogenic AIDs. Various degrees of growth or intellectual disability were presented in 6 patients (37.50%). Hematological involvement was observed in 7 patients including 1 patient with thrombocytopenia and 6 patients diagnosed with anemia (Additional file 1). Regarding inflammatory indicators, eleven patients (68.75%) had increased CRP at the time of thalidomide add-on, and nine patients (56.25%) had elevated ESR. Before thalidomide treatment, 12 patients (75.0%) were taking immunosuppressive agents, 11 patients (68.75%) were taking glucocorticoids, and 2 patients (12.50%) were under treatment with biologics.

Four patients discontinued thalidomide gradually after reaching 3 months of treatment due to the inability to reduce lower inflammatory indicators to the normal range, failure to improve clinical symptoms or disease-free activities, or worsening of symptoms after discontinuation of glucocorticoids (Table 2).

After 3 months of treatment, 16 patients remained in this study, and the fever had resolved in all of them. The rash had disappeared in 9 (75.0%) patients (Fig. 2A). Among the 12 patients who took thalidomide for 12 months, seven patients had fever and nine patients had rash at baseline, the fever improved in all patients (100.0%) and rash improved in 7 (77.78%) patients with thalidomide treatment (Fig. 2B).

Efficacy evaluation in thalidomide. A–B Heatmaps showing the number of patients with different outcomes before and after thalidomide treatment. The horizontal axis represents the disease type, with baseline conditions on the left and endpoints on the right. The vertical axis represents clinical, laboratory, and treatment features. The color intensity reflects different numerical values, darker colors indicating higher values. A Baseline and 3 months after thalidomide treatment in 16 patients. B Baseline and 12 months after thalidomide treatment in 12 patients. C Efficacy rate after 3 months of thalidomide treatment. The number above the bar graph is the ratio of the patients with effective treatment out of all patients with different types of AIDs. D Efficacy rate after 12 months of thalidomide treatment. The number above the bar graph is the ratio of the patients with effective treatment out of all patients with different types of AIDs

In terms of disease activity, 13 (81.25%) patients had disease activity comparable to baseline in the 3 months before thalidomide treatment (Table 2). Eleven patients (68.75%) had disease activity improvement (9, 81.82%) or continued disease-free activities (2, 18.18%) after 3 months of thalidomide treatment. Twelve patients were followed up for 1 year, including 10 patients (83.33%) with disease activity that improved from baseline (8, 80.0%) or remained absent (2, 20.0%).

Thalidomide was added to patients with AGS because of an elevated ESR (Case 1), recurrent rashes (Cases 1, 2), and the desire to withdraw glucocorticoid (Cases 1 and 2). In Case 1, the inflammatory markers decreased to normal, and glucocorticoid was successfully discontinued after treatment for 1 year. Case 2 had sustained ESR. Two patients with Blau syndrome (Cases 4 and 6) had persistent inactive arthritis after thalidomide treatment, of whom Case 4 discontinued glucocorticoid and remained on thalidomide alone by the end of follow-up. Furthermore, all four patients with Blau syndrome exhibited no activity of ophthalmia. The AIDAI decreased with the addition of thalidomide in 2 CINCA, 1 FMF and 1 TRAPS patients after the addition of thalidomide. After treatment with thalidomide, symptoms improved in patients with DADA2, HA20, and PLAID (Table 2).

Eleven patients had elevated CRP and nine had elevated ESR at baseline among the 16 patients treated with thalidomide for 3 months. Among them, the CRP levels in 10 patients (62.50%) and ESR levels in 16 patients (100.0%) reached the normal ranges (Fig. 2A). Of the 12 patients followed for 1 year, 8 patients (66.67%) had elevated CRP and 5 patients (41.67%) had elevated ESR at baseline. Eight patients (66.67%) had CRP values within the normal range at the end of follow-up (Fig. 2B), and the CRP of the three patients whose CRP remained abnormal at the end of follow-up decreased to more than 80% of the original values; ESR decreased to the normal range after 1 year of treatment in 11 patients (91.67%) (Figs. 2B and 3B).

Time courses for CRP (A) and ESR (B) for each disease. The data were taken at baseline, 3 months before thalidomide and at months 3, 6, 9, and 12 on thalidomide. The color difference outlines the difference in disease types, and the numbers are P values from the paired test for each patient. P < 0.05 was considered statistically significant. Points on lines represent the mean values of the inflammatory index for each disease

The CRP levels of patients at baseline were significantly higher than those before thalidomide treatment (P = 0.021), and the ESR levels were also higher than those before thalidomide treatment, but this difference did not reach statistical significance (P = 0.163), which means that patients under the original treatment regimen might not have maintained the inflammatory indicators in the normal ranges. After 1 year of treatment with thalidomide, the values of CRP and ESR were decreased from baseline (P = 0.002, 0.014), indicating that thalidomide can effectively dampen the inflammatory status. Furthermore, the level of ESR after 3 months of thalidomide was significantly lower than at baseline (P < 0.001), while there was no significant change in CRP from baseline to 3 months (P = 0.126) (Fig. 3A, B and Table 3).

Twelve patients (75.0%) received immunosuppressive agents at baseline (Table 1) and 1 (8.3%) of whom discontinued MTX after 3 months of treatment. Eleven patients (68.8%) received treatment for glucocorticoids before the screening period and 2 of whom discontinued glucocorticoids after 3 months of treatment with thalidomide (Fig. 2A). Among the 12 patients followed for 1 year, 3 patients (25.0%) discontinued glucocorticoids, 3 (25.0%) discontinued immunosuppressive agents, and 1 (8.3%) patient discontinued the biologic agent. Among them, 1 patient with Blau syndrome discontinued glucocorticoids and immunosuppressive agents simultaneously, and 3 patients (cases 4,12,13) were treated with thalidomide alone (Fig. 2B). Two patients (12.5%, cases 6 and 14) had their glucocorticoids or immunosuppressive agents reduced to low-dose maintenance therapy.

In summary, considering the clinical manifestations or disease activity scores, inflammation markers and background medication adjustments, the efficacy rate in 16 patients after 3 months and 12 month of thalidomide treatment in children with monogenic AIDs was 56.3% (Fig. 2C, D). Efficacy in DADA2, FMF, HA20 and PLAID after 12 months of thalidomide treatment was 100.0%. The efficacy in other groups of AIDs of thalidomide treatment for 3 and 12 months was shown in Fig. 2C and D.

Two patients (12.50%, cases 5 and 12) experienced anorexia and nausea at a dose of 25 mg/d (1.0–1.5 mg/kg), which resolved after dosage reduction, and no obvious discomfort was reported after that. None of the patients had adverse events such as peripheral neuropathy and somnolence.