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"Medical Journeys" is a set of clinical resources reviewed by physicians, meant for the medical team 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.

In spite of treatment advances, chronic urticaria continues to impair patients' health-related quality of life (HRQoL) and drive up direct and indirect healthcare costs. As early as 1997, into the impact of chronic urticaria showed that many patients reported health status scores comparable to those patients with coronary artery disease. In 2016, an of U.S. data from a commercially insured population with chronic urticaria found that the mean total healthcare cost per patient was more than $9,000 per year.

"This disease has a very negative impact on quality of life, and the only way to diminish this is to control the disease, especially the itching," John E. Wolf, Jr., MD, of Baylor College of Medicine in Houston, told 番茄社区. "That may be very difficult."

Among the reasons is the unpredictable nature of this predominantly mast cell-driven disease, along with its many comorbidities. Also, international studies show there's room for improvement in physician compliance with evidence-based treatment guidelines and that delays in diagnosis and the implementation of effective therapy are common. In addition, failure to escalate to recommended third-line treatment in patients with antihistamine-refractory disease contributes to the unmet needs of this patient population overall.

"The impact of chronic urticaria on quality of life is enormous," said Alison Ehrlich, MD, of Foxhall Dermatology and Research Center in Washington, D.C. "If you're covered in hives, you're pretty miserable. You can't sleep, you're exhausted. I think the impact of chronic urticaria on quality of life needs to be taken very seriously," she told 番茄社区.

Chris G. Adigun, MD, of the Dermatology & Laser Center of Chapel Hill in North Carolina, agreed: "Chronic urticaria is uncomfortable, disrupts sleep, is physically disfiguring when it involves areas not covered by clothing, and is often totally unpredictable."

The condition is characterized by the development of highly pruritic wheals, with or without angioedema, and typically lasts for at least 6 weeks. It presents as either chronic spontaneous urticaria (CSU) or chronic idiopathic urticaria (CIndU), or both, and is seen in patients of all ages. In adults, CSU and CIndU affect twice as many women as men, with a peak incidence from ages 20 through 40.

"Severe pruritus and the unpredictable occurrence of wheals and angioedema are responsible for sleep disorders, sexual dysfunction, limitations on daily life, work and sports activities," said authors of a 2021 of the global burden of chronic urticaria. The team noted that chronic urticaria lasts for years in up to 75% of patients and that many struggle with symptoms for a year or longer before receiving effective treatment.

The authors also noted that more than 25% of cases are resistant to with non-sedating, second-generation H1-antihistamines, even when the standard dose is increased up to four-fold as recommended for second-line treatment. Notably, two-thirds of the antihistamine-refractory patients also had disease refractory to recommended third- and fourth-line therapies with omalizumab (Xolair) and cyclosporine A, respectively.

The co-morbidities associated with chronic urticaria have a significant impact on HRQoL. "Chronic urticaria patients constitute a multi-morbid group of patients, which must be recognized among treating physicians," said the authors of a 2020 of 1994-2015 data from 12,185 patients with chronic urticaria in the Danish National Patient Registry. There was a higher prevalence and risk of autoimmune disease, especially rheumatoid arthritis, as well as an increased prevalence and future risk of depression, a risk that tended to increase over time, particularly in female patients.

"There are many different things that can impact quality of life and what many would argue would be co-morbidities," said Jonathan Silverberg, MD, PhD, MPH, of George Washington University School of Medicine and Health Sciences in Washington, D.C.

"On the one hand, there can be underlying medical conditions such as thyroid disease that drive urticaria or in some way contribute towards it. On the other hand, urticaria itself can drive other poor outcomes. We think about symptoms of anxiety and depression, sleep disturbance, social stigma and social isolation, mental health burden, and functional impact," he said.

A recent study of the impact of chronic urticaria on sleep showed that patients with CSU had significantly worse sleep quality and higher levels of anxiety and depression compared with 25 healthy controls. Anxiety levels significantly correlated with poor sleep quality, while anxiety and depression scores correlated with itching severity.

"It can be postulated that poor sleep could act as both an effect of anxiety and a risk factor for the development of anxiety," the investigators said.

Almost one out of three patients with chronic urticaria has at least one underlying psychiatric disorder, according to a of 25 studies. The question of which comes first -- the urticaria or the psychiatric comorbidity -- remains unanswered, however.

"This highlights the need for a multidisciplinary therapeutic approach involving prompt recognition and management of any potential psychiatric disorder in addition to urticaria treatment," the authors wrote. "Further studies are needed to assess whether psychiatric disorders coexist with chronic urticaria independently or follow urticaria onset and whether any psychological or psychiatric intervention may help in control."

Timely and appropriate referral of patients with chronic urticaria to specialists to reduce delays in diagnosis and implementation of effective treatment is needed, concluded the authors of a 2015 report on the findings. This is particularly true for the estimated 50% of patients who remain symptomatic despite ongoing treatment with the current standard of care, said Karsten Weller, MD, of Charité-Universitätsmedizin Berlin in Germany, and colleagues.

In an earlier , Weller and other team members found that many patients saw an average of more than two physicians before being referred to a specialist. "Reducing the burden associated with CSU therefore requires a broader understanding of the impact of these unmet needs of patients," the authors wrote.

In 2017, data from the ongoing ASSURE-CRU study showed some improvement in the treatment of chronic urticaria. Nevertheless, the , uncontrolled disease, co-morbid CIndU, significantly impaired QoL, and reliance on healthcare resources was still high. The researchers concluded that the socioeconomic burden of CSU has been underestimated, the unmet patient needs are substantial, and patients with increased disease activity and angioedema have greater HRQoL impairments.

Results from a 2018 analysis of data from the global, observational in 4,224 patients with antihistamine-resistant CSU also highlighted the impact of angioedema on HRQoL. Patients with CSU who also had angioedema had significantly greater impairment in work and non-work activities and reported more use of healthcare resources compared with patients without angioedema.

In 2022, a of the AWARE study among patients in Spain with antihistamine-refractory CSU showed that almost 50% still presented with uncontrolled disease after 12 months. Most were receiving first- and second-line treatment with H1-antihistamines, and in two-thirds, therapy had not been escalated to recommended third-line treatment.

This finding underscores "the need to review the response to treatment every 2 to 4 weeks using the weekly urticaria activity score or the urticaria control test," the researchers said.

Meanwhile, a of 25 patients with CSU and 12 physicians found frustration in both groups. Some patients said they waited 2 years to get medical advice, and then resented "the time it took to reach a diagnosis, with repeated physician visits and different treatments, often without success."

For their part, the physicians seemed to have limited understanding of the psychosocial burden of the disease, the researchers said, with some physicians reporting that patients required "above average" time for care. The physicians also commented on the "sizeable emotional burden and high expectations" of patients with CSU, and said it was difficult to satisfy patients' needs.

"Greater support and further education are needed for patients and physicians," the researchers concluded. "Maintaining open channels of communication and engaging in shared decision-making may benefit the patient–physician relationship, ease frustration, and encourage a more collaborative approach to long-term disease management."

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

Part 4: Case Study: Terrible Recurrent Itchy Wheals All Over This Woman's Body

Part 5: Managing Comorbidities in Chronic Urticaria

Part 6: What's New in the Treatment of Chronic Urticaria?

Part 7: Special Considerations in Treating Urticaria in Pregnant or Lactating Patients

Part 8: Case Study: Sudden Urticaria After a Stroke

Part 9: Managing Urticaria in Children and Elderly Patients