Chronic Hives: Symptoms, Diagnoses & New Treatments

Chronic hives (chronic urticaria) is a common and often debilitating skin condition that affects millions of people worldwide. Recurring hives or itchy welts and swelling that last for six weeks or more can keep you up at night and leave you feeling tired and anxious. Even though chronic hives are initially thought of as a skin problem, the real culprit is your immune cells — and they can itch severely. After months of sleepless nights, many people with chronic hives try over-the-counter hives treatments before finally receiving a proper diagnosis and effective treatment plan.

The management of chronic urticaria is rapidly evolving with the introduction of more effective treatments, better ways to measure disease activity, and stepwise management algorithms. Consequently, healthcare systems and payers are updating their coverage policies, documentation requirements and escalation criteria for the effective management of chronic urticaria.

Why It Matters

Chronic hives (chronic urticaria) not only leave itchy patches of skin, but they also have the ability to affect your daily routine, your work, and your relationships. Activities of daily living, such as dressing or showering, can become embarrassingly painful. Chronic hives may cause you to be on edge or irritable, and, conversely, make you more sensitive to pain. Although you may be sleeping adequately, you may wake up feeling miserable. You may be tired during the day and miss work or school due to your hives. Chronic urticaria is one of the most common and distressing skin conditions affecting adults and children. Its unpredictable nature means that some days can be worse than others. The flare-up can occur daily or even worse at night, interfering with sleep. Health care workers can tell patients with chronic hives that their goal is not only to reduce the number of welts, but also to help them get to sleep, go to school or work, or do the things that they want to do with confidence. Chronic urticaria is a significant health problem due to its potential for delayed diagnosis and inadequate treatment, resulting in unnecessary testing and evaluation, and the prescription of ineffective or even toxic therapy. Patients and clinicians commonly resort to over the counter treatments for itching and skin inflammation, sometimes switching to other products and resorting to sedating oral antihistamines that affect activities during the waking state. Short courses of oral steroids can provide effective symptom relief in the short term but can in the long run worsen problems and lead to serious side effects and flares. However, by following a stepwise diagnostic approach and an escalated treatment plan, clinicians can rapidly stabilize the patient and relieve pressure off of crowded clinical, ambulatory, and emergency department settings.

Chronic hives viewed from a systems perspective is an “invisible” disease that affects not only the quality of life of the person who is suffering from it but also increases the use of healthcare services and lost productivity. Individuals with chronic hives look well but are badly ill, waking up barely sleeping due to itching, fatigue or swelling of the face or lips. Parents are waked up at night by their children who have hives. Students have difficulty in school due to inadequate sleep and are sedated during the day from their antihistamines. Employers and occupational health professionals see the indirect effects of hives on their workers through absenteeism and presenteeism and the many doctor visits needed to manage the condition.

Chronic urticaria is primarily distressing due to its associated symptoms. However, there is a safety issue. Symptoms of chronic urticaria can be confused with those of other conditions, and the choices for managing chronic urticaria have several potential limitations. Most severe swelling episodes are not life-threatening but are frightening to both patient and physician. There are, however, some episodes of swelling that require immediate emergency care. Moreover, many patients and their physicians incorrectly attribute every episode of swelling to an allergic reaction to something in their environment when, in reality, the patient has chronic spontaneous urticaria (CSU) without external cause. The safe management of chronic urticaria therefore requires an awareness of conditions that may mimic urticaria and vigilance to detect potential serious complications, all while finding effective treatment with minimal side effects.

What Chronic Hives Look Like in Real Life

What look like bugs biting you all over are actually hives. Hives are areas of skin that have swelling, and usually they are circular in shape with a pale center and a ring of red. They can be anywhere, and may change shape or location over the course of hours or days. Usually, individual welts fade away within 24 hours, but new welts can appear elsewhere. Some people describe their hives as feeling burning or stinging, rather than itchy. Flare-ups can be caused by factors like heat and humidity, pressure, clothing, being ill, drinking alcohol, or being stressed, though for most people there is no single, consistent trigger for hives. Angioedema is the condition of having hives plus swelling that is deeper than a surface wheal. The swelling can be localized (to areas like the eyelids, lips, hands, feet, or genitals) or generalized. Swelling caused by chronic hives tends to be tender, hard and persistent. However, swelling can result from other causes and in some cases, swelling can occur without surface hives (such as angioedema).

Why Patients Often Feel Dismissed

Chronic hives (uricaria) are often misunderstood and given short shrift. Because they wax and wane and multiple tests yield a normal result, chronic urticaria is frequently viewed by patients and physicians alike as no more than another set of allergies. Despite the sometimes subtle and variable symptoms, patients are suffering greatly, and effective treatment is available. The key to treating a patient with chronic urticaria is to acknowledge and describe the full extent of the patient’s suffering; to explain how chronic urticaria typically behaves; and to reassure the patient that effective treatment exists, even if an single cause cannot be identified. This approach educates the patient as to what is happening to her body, helps her to face her symptoms rather than fear them, and starts her on the road to effective management.

Although chronic urticaria can occur in any age group, it most commonly begins in adults, with a predominance of women affected. The condition is often persistent, lasting for months or even years with periods of remission and relapse. The frequency of symptoms can vary, with daily, weekly, or less frequent episodes all constituting chronic urticaria. As such, a comprehensive management plan needs to address both the control of ongoing symptoms and the specific management of flares.

The diagnosis and treatment of chronic hives must always be approached with the differential diagnosis of additional immune or allergic disease in mind. Many individuals with chronic hives will have other atopic conditions, such as thyroid autoimmunity (e.g. Hashimoto’s thyroiditis or Graves’ disease) or atopic conditions like allergic rhinitis, asthma or eczema. Anxiety and depression also are frequently seen in individuals with chronic hives either as a result of their chronic itchy insomnia provoking anxiety and depression or due to worry about when the hives will next appear. The clinician must have a full understanding of the patient’s current and past medical history, current and past medications, stressors, and other present day inflammatory medical conditions.

The primary care clinician is most likely to be the first healthcare professional seen by patients with chronic urticaria. They need to make an early diagnosis, decide on appropriate investigation and initiate safe and effective management. Many patients can be managed in primary care if managed appropriately using a logical step-wise approach. They need to be able to differentiate chronic urticaria from acute urticaria caused by an allergy and give patients and their families realistic advice for when to contact the doctor again. They need to avoid putting patients on unnecessary food avoidance diets, tests, urgent care or emergency department visits. They also need to be aware of underlying conditions which may co-exist with chronic urticaria such as anemia, thyroid disease, sleep disorders and/or mental health disorders.

Dermatologists, allergists or immunologists are the stakeholders for these patients. They can help confirm unusual patterns of symptoms, consider alternative diagnoses, counsel the patient regarding the use of biologic therapy and other novel approaches for treatment, and help determine whether the patient’s symptoms result from a different pathophysmechanism than typical histamine-induced urticaria.

The stakeholders involved in the care and treatment of patients with Allergic Rhinoconjunctivitis (AR) include payers, pharmacy benefit managers, and health system leaders and administrators. Many of the newer therapies for AR are now prescribed for patients with severe disease, after failure of step therapy to less effective medications, or after failure of maximal doses of antihistamine medications. In addition, documentation of the impact of the patient’s symptoms on their activity level and quality of life is becoming more important. Utilization of standardized, patient-reported measures of these disease-specific factors can facilitate consistent access to effective AR medications and treatments, reducing frustration for patients and providers.

Patients with chronic urticaria are active participants in their care by tracking their symptoms, their triggers, and how their body is responding to treatment. Chronic urticaria is unpredictable and highly variable, making patient reported outcomes a key component in making optimal decisions. Patients and their healthcare providers need to make informed and timely decisions about effective therapies, as well as safely increasing or decreasing the dose of a medication to maintain optimal control of symptoms. Tracking itch intensity, amount of hives, swelling, insomnia, and their experience of how a medication is working helps to ensure that patients receive the most appropriate therapy.

The Role of Patient-Reported Measures

Validated symptom scores provide valid translated patient symptoms that can be used in timely treatment decisions including whether to escalate, continue or taper a particular treatment. A brief daily or weekly patient symptom assessment (e.g. Itching, Number of Hives, Sleep Disturbance, Interference with usual activities) can enhance clinical dialogue and document evidence of medical necessity for expensive biologic and other emerging treatments to contain costs. What Else

Treatment of chronic urticaria is becoming more standardized with a stepwise management approach. In the past, chronic urticaria was often treated with steroids with little follow-up treatment, as if chronic urticaria were treated in a vacuum of effective long-term therapy. A step-thereapy policy helps to facilitate uniform and predictable third party reimbursement decisions when there is a step-wise approach to managing chronic urticaria, appropriate therapy prescribed, and documentation of the patient’s symptoms.

Symptoms and Diagnosis, What Clinicians Should Document

Chronic urticaria is a clinical diagnosis characterised by recurrent itchy wheals with or without swelling (angioedema) lasting more than six weeks. Record the duration of symptoms, the frequency of wheals, the characteristics of individual lesions and their duration. ‘Less than 24 hours per lesion’ supports the diagnosis of chronic urticaria. Lesions that last longer, become bruised or leave marks should be evaluated by a specialist.

A focused medical history is essential for diagnosing angioedema and for avoiding unnecessary testing in urgent situations looking for “red flag” symptoms of a more serious condition. A complete history includes past illnesses (especially recent infections), current or past medications, and explores the patient’s occupation, activities of daily living, and life style (e.g., stress, alcohol, exercise, NSAID use) as potential precipitants of angioedema. Consideration should also be given to symptoms of swelling of lips, eyelids, tongue, or throat and associated symptoms such as wheezing, faintness, or severe shortness of breath that may indicate an alternative diagnosis requiring urgent intervention.

Although the basic laboratory tests have the potential for full utilization in the biodefense laboratory, the chain of events from sample to result in the clinical laboratory is typically governed by the clinical history and findings on physical examination rather than by a test-and-learn approach whereby all samples might be screened. Therefore, we initiate a complete blood count and an acute phase reactant. We then add thyroid studies if indicated by clinical symptoms or history that suggests thyroid disease or autoimmunity. Testing for conditions that suggest the diagnosis of vasculitis, infection, or systemic inflammatory disease then follows. This strategy is a reasonable compromise between safe, cost-effective laboratory testing and testing that will actually alter the course of management.

First-Line Treatment, Getting Antihistamines Right

For most skin allergy patients, second-generation H1 antihistimes remain the first-line treatment, as they are generally effective for a variety of symptoms and do not produce sedation. The most common reason that antihistimes fail is that the patient is not taking an adequate dose on a consistent basis – either because of forgetfulness (noncompliance) or because they are symptom-directed and take a tablet or take their ointment on an as needed basis during flares, and feel that they are not relieving their symptoms adequately. A few minutes of education can help the patient understand how to and when to take the antihistime, and also appreciate the value of taking a daily medication in order to prevent symptoms.

For patients not getting adequate relief of symptoms, the evidence supports the use of an increased dose of a non-sedating antihistamine up to 4-5 times the approved labeling. This should be done cautiously and with the patient on medical supervision for signs and symptoms of increased central nervous system depression. The clinician and patient should be aware of the sedating first generation antihistamines potential to cause significant daytime impairment and risk of falls and these agents should not be prescribed as first line treatment for symptoms of allergic rhinitis unless absolutely necessary.

Oral steroids can on occasion be used for a short period for severe atopic dermatitis “flares”. Their use should however be avoided as far as possible because of the risk of “rebound” symptoms as well as symptoms such as mood changes and insomnia. Oral steroids also increase the risk of developing diabetes and in general should not be used as part of the standard management of atopic dermatitis. The role of antihistamines has evolved with the introduction of new high quality agents. In general targeted therapies should only be used for patients whose atopic dermatitis is not well controlled on optimal antihistamine therapy.

Targeted therapies, including hormone therapy, monoclonal antibodies, small molecule inhibitors, proteasome inhibitors and immune therapies, have all become crucial for the management of a wide array of cancers. It is therefore fundamental that oncologists are not

For the patient who remains symptomatic despite maximum doses of antihistamines new options have emerged for the treatment of antihistamine refractory chronic spontaneous urticaria. Several anti-IgE biologic therapies have been shown to target the immune activation of the mast cell that leads to symptoms of chronic spontaneous urticaria. They provide relief of symptoms of itching and whealing and can improve quality of life for these patients. In addition, many of these treatments have been shown to reduce the need for oral steroids and to prevent emergency office visits for hives. Due to the nature of these medications (injectable), strong documentation of the severity of the patient’s symptoms, and appropriate trials of other treatments must be included in the patient’s record prior to ordering medication and prior authorization.

New oral targeted agents to the mast cell activated pathway are rapidly emerging. Therefore, providers and patients and families are having discussions regarding the benefits and burdens of oral versus intramuscular (IM) administration as well as the monitoring of side effects and interactions with other medications. Patients do not want to take injections and prefer to take oral medication because it is easier to take and does not require going to the clinic for administration. Therefore, providers must take a shared decision-making approach with patients and families regarding these topics. Once providers and patients and families learn about a particular treatment, the patients’ and families’ opinions regarding the advantages and disadvantages of that treatment as compared to other options will highly influence adherence to the plan of treatment.

As more targeted therapies have become available for clinical use, the approach to safety monitoring and counseling has gradually moved from a general immunosuppression approach to a more therapy specific, individualized approach. While targeted therapies have a better toxicity profile than many of the traditional immunosuppressive medications, each has unique toxicities, potential infections, comorbidities and practical considerations that impact monitoring and safety. Organized health system pathways for follow-up, refills and management of potential toxicity are important for effective monitoring and safety of patients on these medications.

Practical Clinical Perspective, A Simple Stepwise Plan

A practical care pathway for patients with chronic urticaria would start by confirming the chronic nature of symptoms; commencing daily non-sedating antihistamine therapy; and informing patients and their carers about their condition, its triggers and the expected outcome. Patients and their families need to understand the cause of chronic urticaria (often a complex interplay of factors) and that avoidance of foods is not a general strategy for management unless evidence exists of an immediate type allergic reaction. Importantly, individuals and their families need to understand how best to manage their symptoms in flare and know when urgent help for symptoms is required.

Once initial treatment has been started, if symptoms are not well controlled, then dose can be optimised and adherence ensured (are medications taken on time? Is there unwanted daytime sedation? Are there other medications or substances that might be interacting with medications to impair sleep?). Advice on sleep hygiene for patients who are wakeful at night could also be helpful. The poor sleep in itself is likely to increase the perceived severity of symptoms and decrease coping ability.

For persistent/uncontrolled disease, it is generally better to start targeted therapy earlier rather than later. The frequency of symptoms, the degree to which symptoms keep a patient awake at night, and the impact of the disease on a patient’s function can be measured using patient-reported scales to help decide whether to refer a patient as well as to fulfill some payers’ requirements. The goal of therapy should be to achieve stable disease control and full restoration of function, as opposed to a series of incomplete remissions.

Multidisciplinary Care and Mental Health Support

Where possible complex cases are managed jointly with primary care, dermatology/allergy, pharmacy and mental health. Complex skin conditions and treatments can cause persistent itching that prevents sleep which in turn can worsen anxiety and depression which in turn can worsen the symptoms of the skin condition and decrease the individual’s ability to cope with their symptoms. However simple measures to enhance sleep, reduce stress and screen for anxiety/depression can be effective in symptom control and outcomes, particularly with access to mental health care to reduce the burden of illness and improve treatment adherence.

We partner with the pharmacies to quickly complete prior authorizations for medications for which patients need approval. We also work closely with our nurses to ensure our patients receive the follow-up care they need. Many patients take themselves off of beneficial medications because they do not feel well quickly, or because they worry about side effects. Working together as a team to educate patients and families regarding medications, and to provide realistic expectations regarding clinical improvement and potential side effects is an important part of our role. This is particularly important when our patients are beginning a new biologic or oral targeted therapy.

Looking Ahead, What Health Systems Should Prepare For

Recent advances in oral therapies and next-generation biologics continue to evolve the PsA therapeutic armamentarium and will inform formulary decisions, prior authorization criteria and management strategies. Health systems must also become more discerning in the selection of therapy based on measures of disease activity and function. By implementing the practice of obtaining patient-reported scores at initiation and follow-up of treatment, health systems can facilitate effective treatment decisions for patients with PsA in a cost-effective manner and improve the real-world clinical and cost-effectiveness of available PsA treatments.

For physicians, the initial goal will be to diagnose, evaluate, and quickly work up the algorithm to deliver appropriate treatment. Early stabilization of patients will be key to reducing unnecessary testing and office visits. As payers and policymakers struggle to contain health care costs, the decision to fund expensive disability-inducing medications for the treatment resistant hives patient will become more problematic. The condition will become more targeted and amenable to treatment and will become much more manageable for many patients than is current.

References:

https://pmc.ncbi.nlm.nih.gov/articles/PMC6526977/