Hormonal Shifts And Surgical Stress Linked To Refractory Urticaria: A Case Study

A 44-year-old woman with a history of chronic idiopathic urticaria (CIU) developed a relapse of symptoms after undergoing a hysterectomy. Although she had previously achieved remission with omalizumab (Xolair), the patient’s condition worsened following surgery, requiring escalating doses of antihistamines and corticosteroids. This case underscores the possible role of hormonal changes and surgical stress in triggering CIU flares and complicating treatment responses. However, without objective hormonal or immunological data, the exact cause remains uncertain, highlighting the need for ongoing monitoring and further research into alternative therapeutic approaches.

Introduction

Chronic idiopathic urticaria (CIU) is a condition characterized by recurring hives lasting more than six weeks, with no identifiable external trigger. It severely impacts the patient’s quality of life, often resulting in distress and long-term medication dependence. While antihistamines are typically used for first-line treatment, more severe cases may require biologics like omalizumab (Xolair). Despite its effectiveness, biologic therapy doesn’t guarantee consistent results, and some patients experience secondary treatment failures. Surgical procedures, especially those altering hormonal balance and immune function, have been linked to flare-ups of CIU. Hormonal fluctuations following gynecological surgeries like hysterectomy might trigger or worsen urticaria, but these relationships need further exploration.

Case Presentation

The patient, a 44-year-old woman, had a long-standing history of CIU, with additional delayed pressure urticaria (DPU) affecting her palms and soles. She initially developed CIU in 2019, and after unsuccessful treatment with antihistamines and steroids, omalizumab brought her symptoms under control. By 2022, she had tapered off the medication without recurrence.

In March 2024, after a hysterectomy for abnormal uterine bleeding, she experienced a relapse of CIU, with symptoms similar to her initial presentation. She required daily prednisone to manage her hives and continued antihistamines, but the severity of her symptoms remained high. Clinical examination confirmed the presence of delayed pressure-induced urticaria, and her treatment regimen was adjusted to include higher doses of antihistamines.

Clinical Course

During her first follow-up visit, the patient’s symptoms remained largely uncontrolled, despite increasing antihistamine doses. As a result, her Xolair treatment was reinitiated at 300 mg every four weeks. Despite receiving two doses of Xolair, she continued to experience significant symptoms, leading to an increase in her prednisone dose and the addition of another antihistamine. A suspected cholinergic component was noted, as her symptoms worsened with physical exertion. However, further testing to confirm this theory was not conducted.

Throughout her treatment, the patient struggled with significant morbidity due to persistent symptoms and reliance on corticosteroids. The recurrence of her symptoms following surgery raised concerns about the influence of hormonal changes on her condition. However, the absence of objective hormonal or immune data limited the ability to confirm this link.

Discussion

This case highlights the challenges of managing CIU, especially when it is complicated by surgical interventions. The patient’s symptoms, which resurfaced after her hysterectomy, point to the possible role of hormonal fluctuations and immune dysregulation in exacerbating CIU. Estrogen and progesterone have been shown to influence mast cell activity and histamine release, potentially explaining why women undergoing gynecological surgeries may experience flare-ups of urticaria. However, the lack of lab data, such as hormone levels, prevents us from definitively linking hormonal changes to her disease relapse.

Despite omalizumab’s effectiveness in many patients with refractory CIU, response to biologic therapies can vary. Secondary treatment failure, as seen in this case, can occur for a number of reasons, including immune system changes or the development of anti-drug antibodies. Monitoring the patient’s response to Xolair and considering additional treatments, such as leukotriene receptor antagonists, may be necessary in cases where biologics fail.

Conclusion

This case illustrates the complexity of treating CIU, particularly when hormonal shifts and surgical interventions contribute to disease flare-ups. Although the hormonal and immune triggers remain speculative without objective data, this case calls attention to the need for further research into the role of surgical stress and hormonal changes in CIU exacerbations. Clinicians should adopt a personalized approach when managing refractory CIU, balancing symptom control with minimizing adverse effects. Future studies should explore potential biomarkers for better treatment stratification and improved patient outcomes.