麻豆传媒

"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 12-part 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 "special patient populations," age-specific differences in the demographics, clinical features, and treatment of chronic urticaria can present unique management challenges. Given the absence of high-quality data for the efficacy and safety of treatment for pediatric and geriatric urticaria, physicians are advised to proceed with caution, especially in the elderly, even when using recommended therapies.

"The physiological characteristics of these patients, the possible comorbidities, and the intake of other medications often require a very attentive drug selection for chronic urticaria compared with other age groups," noted Cataldo Patruno, MD, PhD, of the Magna Graecia University of Catanzaro in Italy, and colleagues in a 2023 .

With an of 1.4% globally, chronic urticaria affects twice as many women as men overall, with a peak incidence between the ages of 20 and 40 years. In the pediatric population, however, chronic urticaria is most commonly seen in boys ages 5-9 years. After age 60, the disease affects almost as many men as women.

In both children and adults, 80% of chronic urticaria is classified as chronic spontaneous urticaria (CSU) because no definite trigger can be identified; 20% is classified as chronic inducible urticaria (CIndU) because of a link to a specific trigger such as cold or heat; and about 10% of patients present with both subtypes.

Gaps in knowledge about the impact of chronic urticaria therapies in elderly patients are reflected in the current , noted Patruno and co-authors. The recommendations are aimed at the general population and provide no advice specific to older patients. The lower frequency of chronic urticaria in older patients can make differential diagnosis difficult, the team added, particularly in light of "the limited number of blood chemistry investigations for spontaneous chronic urticaria and specific tests for inducible urticaria."

The clinical and laboratory characteristics of chronic urticaria also appear to be age-specific. A of the medical records of 1,319 adults with CIndU revealed significantly fewer women with CIndU in a subgroup of 124 elderly patients compared with younger adults (46.7% vs 82.5%, respectively). Older patients also had comparatively fewer wheals and lower rates of concomitant symptomatic dermographism and angioedema.

When an older patient presents with chronic urticaria, the first order of business is to rule out potential underlying causes -- infectious, autoimmune, and paraneoplastic -- and conduct a comprehensive review of medications, said Chris G. Adigun, MD, of the Dermatology and Laser Center of Chapel Hill in North Carolina.

"Often, the elderly are already on multiple medications, which can potentially interact with medications used to manage chronic spontaneous urticaria," she told 麻豆传媒. "Antihistamine dosage also needs to be carefully reviewed in elderly patients with CSU as their metabolism of these medications can vary widely."

Physicians should keep the possibility of comorbid atopic dermatitis in older patients top-of-mind: Following an of the medical records of 837 patients with chronic urticaria ranging in age from 9 to 84 years, those authors found that of the 37 patients older than 60, 38% had atopic dermatitis compared with 22% of younger patients.

The prevalence of serum-specific immunoglobulin E antibodies to both staphylococcal enterotoxin A and staphylococcal enterotoxin B was significantly higher in elderly patients with chronic urticaria who also had atopic dermatitis compared with those who didn't (37.5% vs 0%, respectively). These findings underscore the importance of identifying the specific clinical features of urticaria in the elderly and recognizing atopic dermatitis in these patients, the investigators said.

Despite the lack of any substantial recommendations specific to the elderly, the guideline strongly recommends against the use of first-generation H1-antihistamines in this patient population, as well as in children. "In adults with urticaria, especially those who are elderly, my main concern is the careful prescription of antihistamines, the mainstay of urticaria control and itching, said John E. Wolf, Jr., MD, MA, of Baylor College of Medicine in Houston.

"One must stick to the less-sedating medications when possible and constantly warn patients to avoid falls," he told 麻豆传媒.

Fall risk is a significant treatment-related concern in elderly individuals with chronic urticaria. The use of first-generation H1-antihistamines, even at the lowest recommended dose, can lead to central nervous system (CNS) effects such as drowsiness, confusion, loss of coordination, and next-day sedation.

"There are questions about whether higher doses of [the first-generation H1-antihistamine] hydroxyzine [Vistaril] could aggravate dementia, increase fall risk, or just make it more difficult to communicate," Jenny Murase, MD, of the University of California, San Francisco (UCSF), told 麻豆传媒.

Standard-dose non-sedating second-generation H1-antihistamines (sgAHs) are recommended as first-line therapy in all types of urticaria. These include loratadine (Claritin), desloratadine (Clarinex), cetirizine (Zyrtec), and levocetirizine (Xyzal), which are safe and effective in patients age 65 and older. However, even at the standard dose, some sgAHs such as cetirizine can increase the risk of falls in elderly patients.

"Certainly, there are fewer concerns with the second-generation H1-antihistamines," said Jonathan Silverberg, MD, PhD, MPH, of George Washington University School of Medicine and Health Sciences in Washington, D.C. "But in the older patient, CNS effects such as orthostatic hypotension, REM sleep disturbance, urinary retention, and dry mouth can be real issues in the medication labeled 'non-sedating,'" he told 麻豆传媒.

Increasing the dose of sgAHs up to four times the standard dose is recommended in adults, but should not be considered in elderly patients, according to a . Not only does this significantly increase the chance of a fall, but it can pose risks in elderly patients with renal, hepatic, and/or cardiac disorders.

In the general population, the guideline recommends omazilumab (Xolair), the injectable monoclonal anti-immunoglobulin E antibody, as second-line therapy when maximum sgAH updosing does not achieve adequate symptom control. There is also evidence for the safety and efficacy of omazilumab in elderly patients who don't respond to sgAHs, the review authors noted.

A 2017 of 322 patients with non-sedating H1-antihistamine-refractory CSU showed that omazilumab was equally effective and well tolerated in 32 patients age 65 and older compared with 290 younger patients. The researchers found no significant differences between the two age groups in weekly itch severity score or hive score, and study drug-related adverse events were less common in the elderly patients compared with younger patients (6.3% vs 10%, respectively).

The use of second-generation H1-antihistamines is also recommended as first-line therapy in children with urticaria. The sgAHs with proven efficacy and safety in pediatric patients include bilastine (Blexten), cetirizine, desloratadine, fexofenadine (Allegra-D), levocetirizine, loratadine, and rupatadine (Rupafin).

However, according to the guideline, many clinicians treating children with urticaria continue to rely on first-generation H1-antihistamines. These physicians wrongly assume that the longer track record of these older medications means they have a better safety profile than sgAHs. The guideline sets the record straight by stating that first-generation H1-antihistamines "have an inferior safety profile compared with second-generation H1-antihistamines, and are not recommended as first-line treatment in children with urticaria."

When a child's urticaria symptoms remain refractory to standard-dose sgAHs, the guideline advises any standard dose increase be carefully considered. "Many of the recommended medications have not yet been adequately studied in children," Adigun confirmed.

Nevertheless, children with urticaria tend to respond better to first-line sgAHs than do adults. In a recent of 751 patients with CSU, only 7% of 162 patients age 12 or younger required second-line treatment with omalizumab compared with 20.8% of 589 adults. "More than half of adult patients are reported to be refractory to even four-fold doses of sgAHs, while pediatric urticaria seems to show a higher response to antihistamine treatment, even controlled by lower doses, and does not require updosing as much as adults," the researchers said.

The analysis also revealed that the characteristics of pediatric urticaria were distinct from adult urticaria. Children had a lower incidence of angioedema compared with adults (19.1% vs 59.8%), and shorter disease duration (5 months vs 12 months). In addition, the characteristics of CSU in adolescents (≥12 years) bore a greater similarity to adult CSU than to pediatric CSU. This suggests that CSU becomes more severe and refractory in adolescents and adults, the investigators said.

Finally, emerging suggest a potential link between atopic dermatitis in childhood and the development of attention deficit/hyperactivity disorder comorbidity. Now, a single points to the aggressive use of antihistamines in children as a potential contributing factor.

"This hasn't been confirmed but it's certainly quite provocative," said Silverberg. "Even stuff that we use frequently and consider to be safe is not without a potential for side effects."

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