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"Medical Journeys" is a set of clinical resources reviewed by doctors, meant for physicians and other healthcare professionals as well as the patients they serve. Each episode of this journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.

This month: A noteworthy case study.

What to do for a 68-year-old woman who has suffered from 6 months of recurrent wheals dispersed over her entire body, and a recent history of facial swelling? That's what Wolfram Hoetzenecker, MD, PhD, of Kepler University Hospital and Johannes Kepler University in Austria, and colleagues had to determine.

As the team reported in , when the patient presented for assessment, clinicians noted the wheals, but at least at that time there were no signs of angioedema.

The patient's medical history included high blood pressure and an intolerance to ibuprofen. Given that the symptoms had persisted beyond 6 weeks and had no identifiable trigger, clinicians made the diagnosis of chronic spontaneous urticaria (CSU).

Laboratory results showed a total immunoglobulin (Ig)E of 111 kU/L, but no evidence of IgG anti-thyroid peroxidase (TPO) autoantibodies, with a test finding of < 28 IU/mL.

The patient noted that previous treatment with a second-generation antihistamine had failed to provide any relief from the itchy rash. The medical team therefore moved to the next guideline-recommended step: systemic therapy with omalizumab (Xolair), given at 300 mg SC every 4 weeks.

On day 3 after receiving her first injection, the patient developed significant urticaria, which caused 50+ wheals, and pruritus -- a Urticaria Control Test (UCT) score of 0 -- despite continuing to take the maximum dose of desloratadine 4 times daily.

In an effort to address the symptoms, clinicians started her on prednisolone 50 mg/day. When 2 days of this dose provided no relief from the itchiness, the team increased the dose to 75 mg/day, after which the symptoms did resolve. Over the following 20 days, the dose was gradually reduced to 5 mg daily, but at that point the symptoms returned.

When the patient was next assessed, she was taking a stable dose of 10 mg/day of prednisolone, which again reduced the symptoms. The regimen of desloratadine 4 times daily was continued, but the severe wheals persisted. As advised in the guideline, the team increased the monthly dose of omalizumab to 450 mg per month.

The symptoms disappeared for a few days, but the hives soon reappeared, along with new episodes of angioedema. The next treatment recommended on the therapeutic algorithm was cyclosporine A, but this was contraindicated due to the patient's chronic kidney failure.

Several months later, the patient attended a follow-up appointment. To rule out other differential diagnoses, the medical team obtained a skin sample for biopsy. Histologic analysis did not detect any evidence of urticaria vasculitis or a specific increased cytokine expression.

Findings included "very mild perivascular superficial lymphocytic inflammatory infiltrate, without neutrophils or nuclear dust," Hoetzenecker and co-authors said. There was also scattered telangiectasia. However, neither myeloperoxidase staining nor direct immunofluorescence detected any pathological findings. The team arrived at a diagnosis of urticaria.

After 6 months of combination treatment with omalizumab, glucocorticosteroids (5 mg/day), and antihistamine therapy, the patient continued to have more than 50 wheals, although there were no more episodes of angioedema.

Her UCT score had now improved to 7, and she underwent repeated unsuccessful attempts to wean her off glucocorticosteroids.

Given the patient's age and her long-standing hypertension and kidney disease, she was started on additional therapy with dupilumab (Dupixent), a monoclonal antibody against IL-4 and IL13 receptor α. An initial injection of 600 mg was followed by 300 mg every 2 weeks.

"After the third injection of dupilumab, the patient was free of symptoms (no new wheals or angioedema; UCT = 16)," the case authors reported. She remained symptom-free and was able to discontinue maintenance therapy with glucocorticosteroids, and reduce her long-time use of antihistamines to twice daily. Furthermore, the dual therapy with omalizumab and dupilumab produced no adverse effects.

Based on the significant improvement and efficacy, omalizumab therapy was reduced to the standard dose of 300 mg every 4 weeks, without any symptom recurrence.

The plan as of the time of the case report in Jan. 2023 was to reassess the patient in 6 months, and if the disease was still controlled, her omalizumab therapy would be further reduced.

Discussion

"In summary, to our knowledge this is the first report of an adjunctive therapy of dupilumab in combination with omalizumab achieving complete control of clinical symptoms in a patient who had no history of manifest atopic dermatitis," the team concluded, noting that "chronic urticaria can be very debilitating, and patients' can be extremely low."

The current international joint from the European Academy of Allergy & Clinical Immunology, Global Allergy and Asthma Network, European Dermatology Forum, and Asia Pacific Association of Allergy, Asthma and Clinical Immunology states that the goal of treatment is complete symptom control. As this patient's case reflects, second-generation antihistamines "even at higher-than-approved doses," are the first-line of treatment, with the addition of omalizumab when symptom control is inadequate.

Nevertheless, even this combined treatment has been reported to fail in CSU, Hoetzenecker and co-authors noted: "More frequently, patients failed to respond to omalizumab therapy if they had a low total IgE and/or elevated IgG anti-TPO antibodies."

Beyond the guideline, some limited points to several medications approved for other indications -- including dupilumab -- that may be effective in CSU patients, the case authors noted.

While IL-4 and IL-13 "play a crucial role in IgE class switching," their involvement in CSU is poorly understood, the team continued, adding that it does appear that blocking these cytokines may help in treatment of urticaria that is or .

The team also cited a in which treatment with dupilumab was associated with long-term remission, "suggesting a possible disease-modifying effect."

This may be clarified when final results of the of dupilumab in the treatment of CSU are published, Hoetzenecker and colleagues noted, adding that "dupilumab could be a future treatment option for CSU as an alternative or additional therapy."

Read previous installments in this series:

Part 1: Urticaria/Hives: The Search Continues for Causes

Part 2: Keys to Diagnosis of Urticaria

Part 3: Chronic Spontaneous Urticaria and Autoimmunity