In a pilot study, autologous IgG injections show early, lasting symptom and quality-of-life gains in antihistamine-resistant chronic spontaneous urticaria (CSU).
A prospective open-label pilot study suggests that intramuscular injections of autologous total IgG may improve disease activity, symptom control, and quality of life (QOL) in patients with chronic spontaneous urticaria (CSU) who remain symptomatic despite antihistamine therapy.1
Although second-generation H1 antihistamines remain standard first-line CSU treatment, many patients continue to experience persistent symptoms despite dose escalation. In prior research, autologous immunoglobulin therapy (AIGT) has demonstrated clinical efficacy, safety, and immunomodulatory effects in patients with moderate to severe atopic dermatitis.2
The present study evaluated AIGT in 15 adults aged 19 to 75 years with antihistamine-refractory CSU lasting at least 6 months and persistent symptoms despite antihistamine therapy. The median baseline Urticaria Activity Score 7 (UAS7) score was 25, and the median Urticaria Control Test (UCT) score was 7.
Overall, investigators hoped to answer the following questions:
Participants continued their baseline antihistamine regimens during the study. Several patients had previously received additional therapies without adequate disease control, including omalizumab, cyclosporine, methotrexate, or oral corticosteroids.
To prepare the intervention, investigators collected 400 mL of autologous blood from each participant. Total IgG was purified from plasma using Protein A affinity chromatography. Patients then received weekly intramuscular injections of 100 mg autologous IgG from week 0 through week 8, for a total of 9 injections and a cumulative dose of 900 mg.
The primary end point was the change in UAS7 from baseline to week 12. Secondary end points included changes in UCT, chronic urticaria–specific QOL, and patient-reported disease burden measured using a visual analog scale.
At week 12, investigators observed significant improvements across all primary and secondary outcome measures. The median change in UAS7 from baseline was −13.0 points. Disease control also improved, with UCT scores increasing by a median of 4 points. QOL measures improved substantially, while patient-reported disease burden decreased markedly.
Longitudinal analyses demonstrated that improvements in symptom burden and QOL became apparent by week 4 and persisted throughout follow-up. Significant improvements in disease control, defined as UCT scores of 12 or higher, emerged by week 8 and were maintained through week 24.
Although categorical remission outcomes were less robust, some patients achieved low disease activity or complete remission over time. By the end of week 24, 27.3% of patients who completed follow-up achieved complete remission, defined as UAS7 of 0. Investigators also noted that clinical benefit was not limited to treatment-naive patients. Several participants with prior inadequate responses to omalizumab or cyclosporine experienced reductions in disease activity and improvements in QOL following AIGT.
Exploratory immunologic analyses showed no significant changes in total IgE levels after treatment. However, total serum IgG concentrations increased significantly by week 12, with modest increases observed in IgG1 and IgG2 subclasses. No significant changes occurred in IgG3, IgG4, IgA, or IgM levels. The proportion of patients with positive autologous serum skin tests decreased during the study, although this change did not reach statistical significance.
AIGT was generally well tolerated. No serious adverse events were reported during the study period. Mild transient adverse events included upper respiratory infections, fatigue, headache, and cystitis. No patients discontinued treatment due to adverse events, and laboratory monitoring did not reveal any clinically significant safety concerns.
The authors concluded that AIGT may represent a potentially beneficial therapeutic option for patients with antihistamine-refractory CSU. They emphasized that the persistence of clinical improvement beyond the active treatment period suggests possible immunomodulatory effects rather than temporary symptomatic relief alone.
However, they also noted important limitations, including a small sample size, an open-label design, and the absence of a control group. Larger randomized controlled studies with mechanistic end points can better define the efficacy, durability, and mechanism of action of AIGT in CSU.
References
1. Ye YM, Kim ME, Kwon B, Nahm DH. Clinical efficacy and safety of intramuscular injections of autologous total IgG in patients with chronic spontaneous urticaria: an open-label prospective pilot trial. Exp Dermatol. 2026;35(4):e70249. doi:10.1111/exd.70249
2. Nahm DH, Ye YM, Shin YS, et al. Efficacy, safety, and immunomodulatory effect of the intramuscular administration of autologous total immunoglobulin G for atopic dermatitis: a randomized clinical trial. Allergy Asthma Immunol Res. 2020;12(6):949-963. doi:10.4168/aair.2020.12.6.949
