Allergy/immunology is a specialty that places importance on the transition of care due to the recognition that atopic conditions and immunologic diseases are often lifelong processes. In fact, the specialty of allergy/immunology is not a subspecialty of pediatrics or internal medicine, but rather has a single board, the American Board of Allergy and Immunology, which oversees both pediatric and adult allergists/immunologists. In addition, all allergy/immunology fellowships require that fellows cross-train and learn about the care of both children and adults. Most private practice allergists already take care of both children and adults and are keenly aware of the need to transition their patients to an adult care model as they move from childhood to adulthood. Although this change is often made easier if a patient can stay under the care of the same physician, general issues of increased independence and self-management still apply as these patients transition from childhood to adolescence and emerging adulthood. Those allergists/immunologists who practice in academic centers often belong to either the pediatrics or internal medicine department and therefore see only children or adults, respectively, although this is not uniformly the case. The transition of those patients who obtain their care in an academic center will, therefore, be complicated by having to change physicians and sometimes clinical settings.
Transition of Care for Allergic/Immunologic Conditions
Although the onset of most allergic/immunologic conditions can be quite variable, those that present in childhood often persist into or relapse in adulthood. For these conditions, patients must often use daily medications for many years, cautiously avoid allergic triggers for the duration of their lives, monitor closely for complications, and oftentimes employ daily lifestyle measures such as moisturizing or airway clearance to prevent flares of their underlying disease. The time and energy involved in taking these precautions over most of one's life, day after day and year after year, can have psychological implications and impact quality of life, ultimately leading to fatigue, frustration, and even nonadherence. These issues can be particularly relevant during the adolescent/young adulthood years when patients are transitioning from taking medications and following other precautionary measures with the support of primary caregivers to doing these things independently based on an understanding of why these measures are important and how exactly they will contribute to one's overall health. Without an appropriate understanding of one's underlying disease process and the reasoning behind medication and nonmedication interventions, patients in this transition period are less able to actively manage their chronic conditions and may not receive regular follow-up care, sometimes leading to a flare or loss of control of an underlying disease process. For maximal success, the transition from passive to active participant in one's care should begin as early as possible during preadolescence and adolescence, as a child begins to demonstrate the emotional and cognitive skills necessary to assume increased responsibility. This concept is not unique to the field of allergy/immunology, but rather applies to most chronic conditions that span from childhood into adulthood. Awareness of this need among both pediatric and adult allergists/immunologists is crucial to ensure a smooth transition through adolescence and young adulthood, even in private practices where the physician or clinical setting remains unchanged.
The main disease processes managed by allergists/immunologists include (1) primary and secondary immunodeficiency; (2) allergies to environmental aeroallergens, food, hymenoptera venom, latex, and drugs; (3) allergic and nonallergic rhinitis, conjunctivitis, and chronic sinusitis with or without nasal polyposis; (4) asthma with its many phenotypes and endotypes, including exercise-induced bronchoconstriction; (5) paradoxical vocal fold motion; (6) eosinophilic esophagitis and other eosinophilic disorders; (7) chronic urticaria, angioedema, and anaphylaxis; (8) mast cell disorders; (9) atopic dermatitis; and (10) contact dermatitis. Of these conditions, there are several that present differently among children and adults and others that present quite similarly. In addition, some of these diseases change over time. Understanding the differences and similarities between childhood and adult presentations of the same disease can help specialists in the field to better manage patients as they transition from pediatric to adult practices.
Rhinitis, Conjunctivitis, and Sinus Disease
Allergic rhinitis and allergic conjunctivitis present similarly among allergic children and adults, but certain conditions like vernal keratoconjunctivitis are more common in children and others like giant papillary conjunctivitis, which affects patients who wear contact lens, or atopic keratoconjunctivitis, which affects a small subset of patients with atopic dermatitis, tend to be more prevalent in adults.1 Nonallergic rhinitis is more common in adults, including rhinitis of pregnancy, vasomotor rhinitis, gustatory rhinitis, and atrophic rhinitis.2 Similarly, chronic sinusitis with nasal polyposis is much more common in adults. In particular, aspirin-exacerbated respiratory disease, also known as Sampter's Triad, which includes chronic eosinophilic sinusitis with nasal polyposis, adult-onset asthma, and worsening of respiratory symptoms after nonsteroidal anti-inflammatory drug ingestion, is almost exclusively adult in onset, although adolescents do rarely present with the disease.3 When seen in children, nasal polyps should raise suspicion for cystic fibrosis.
Asthma is a heterogenous disease managed by allergists/immunologists or pulmonologists, and often by both subspecialists in collaboration. Although many children outgrow their asthma, a significant number have asthma that persists, relapses, or even is newly diagnosed in adulthood. The existence of a second wave of asthma diagnosis during young adulthood was most notably demonstrated by the 1958 British birth cohort study of over 18,000 children observed through age 42 years, with a subset having laboratory evaluation 2 to 3 years later.4 Although this study examined wheezing, with or without an actual diagnosis of asthma, which could affect the incidence, it demonstrated that almost one-half of adults with wheezing illness have their onset in adulthood. Atopy and existing cigarette smoking are the two main risk factors for wheeze in an adult age 40 years and older, whether it be newly diagnosed or a recurrence of childhood symptoms after prolonged remission.4 The Tucson study5 of 1,246 children examined this second wave further by observing children through age 22 years and looking at risk factors for predicting persistence of asthma into young adulthood or new-onset asthma in this period. Only 27% of the people with asthma at age 22 years had been newly diagnosed between ages 16 and 22 years, with the rest having had a history of childhood asthma. This study5 demonstrated that young men were more likely to have remission of their asthma by age 22 years, and that 71% of asthma that is newly diagnosed between ages 16 and 22 years affects young women. Many of the factors found to predispose to asthma persistence into young adulthood were evident in early childhood, including onset prior to age 6 years, persistent wheezing in early life, and reduced lung function and bronchial hyperresponsiveness at age 6 years. Interestingly, many of these same factors were predictors for asthma that was newly diagnosed at age 22 years.5 Another study6 of 613 children from New Zealand observed children from age 9 to 26 years with intermittent questionnaires, allergy testing, and pulmonary physiology testing. Although many of the children experienced remission of their asthma before age 26 years, over 25% demonstrated persistence of their wheezing or relapse of wheeze in young adulthood after remission. In this study, sensitization to house dust mites, airway hyper-responsiveness, female sex, smoking, early age at onset, and persistently low lung function predicted asthma persistence or risk of relapse.6 The risk of chronic obstructive pulmonary disease has also been shown to increase in patients with a history of childhood wheezing illnesses, including both asthma (odds ratio [OR] = 6.37) and wheezy bronchitis (OR = 1.8).7
Given the complicated natural history of asthma, this is a disease in which transition planning is particularly important. Patients whose asthma seems to have improved in their adolescent years should be educated about the natural history of asthma and the possibility that their asthma may worsen again in their 20s. This will enable patients to seek care earlier if asthma signs or symptoms begin to develop. Appropriate transfer of care between pediatric and adult physicians can help the adult allergists/immunologist monitor more closely for subtle signs that asthma is possibly re-emerging as a problem and monitor spirometry intermittently to detect signs of airway obstruction even in patients who may not be perceiving symptoms.
Eosinophilic esophagitis (EoE) is another heterogenous condition, which is often co-managed by allergists/immunologists and gastroenterologists, with the help of nutritionists, social workers, and behavioral health specialists. Pediatric and adult EoE are thought to be a continuum in many cases, although there are several important differences between the childhood and adult presentations of EoE. Notably, the main symptoms of EoE change over time from abdominal pain, dysphagia, food refusal, nausea, vomiting, and failure to thrive in children to dysphagia, food sticking, and retrosternal pain in adulthood.8 This is thought due, at least in part, to scarring and fibro-stenotic changes that generally take years to develop and are therefore more common in adulthood. Importantly, a delay in diagnosis was the only risk factor for stricture formation at the time of EoE diagnosis.9 Several studies have demonstrated that the efficacy of six food elimination diets, which remove the six most common allergenic foods, is approximately 75% effective in both children and adults with EoE.10–13 Similarly, both adults and children respond quite well to swallowed steroids. Interestingly, the chance for attaining a partial or complete histologic response seems to be higher in adults, whereas improvement of symptoms seems to be higher in children treated with swallowed steroids as compared with adults.14
EoE is one of the few disease processes in the field of allergy/immunology with literature providing a framework for transition planning and eventual transfer of care as youth become adults.15 The model proposed takes into account elements of health care transition (HCT) that have proven important and successful in other disease processes (eg, introduction in early adolescence with individualization of timing, a dedicated transition coordinator, ongoing transition readiness assessment, and the use of transition clinics), but also aspects of HCT unique to EoE, including the need for multidisciplinary teams, intermittent and sometimes frequent endoscopies, and occasionally enteral feeding tubes, special nutritional formulations, and home care companies.15
Food allergy can present at any time and with any food, although the six most common food allergens are egg, cow's milk, peanut/tree nut/shellfish, wheat, fish, and soy. Of those, egg, cow's milk, wheat, and soy are the more common childhood allergens, which often resolve in adulthood, although they can certainly persist. Peanut and tree nut allergies, which often begin in childhood, tend to persist into adulthood with a prevalence of 0.6% and 0.5%, respectively.16 Fish and shellfish allergies more commonly have their onset in adulthood and have a prevalence of approximately 0.5% and 2.5%, respectively.16 Understanding these differences between children and adults is important in managing patients allergic to certain foods.
Importantly, there are psychosocial implications to worrying about accidental food exposures and associated reactions, cautiously avoiding certain foods, and always being sure to carry an epinephrine auto-injector. These implications are especially relevant during the transition through adolescence and emerging adulthood. One study17 looked at several mental health parameters for 1,303 people ranging from age 14 to 21 years through questionnaire data obtained from both the patients and their mothers. Although self-reports did not indicate a higher rate of mental health conditions in patients with food allergens, maternal reports indicated an increased rate of depression (OR = 4.5), anxiety (OR = 2.68), and attention-deficit/hyperactivity disorder (OR = 3.14) in adolescence, with persistence of the elevated depressive symptoms into young adulthood (OR = 2.05). This study not only emphasizes the importance of assessing psychosocial parameters in patients with food allergens, but also indicates the need to involve parents in this assessment because patients may not be aware of or willing to admit to psychological issues.17 Another study18 looking at 59 adolescents and 190 children also found a discrepancy between parental and patient responses (ie, regarding self-management). Although parental responses regarding the degree of self-management correlated with those of younger children, this correlation was not seen for adolescents, for whom parents tended to believe adolescents were less likely to notice allergic reactions, follow dietary restrictions, and explain the requirements of the allergy than what the adolescents themselves believed. This same study administered an anxiety questionnaire, which demonstrated a high rate of anxiety among these patients. Interestingly, a history of a life-threatening reaction increased degree of self-management for children, but only increased anxiety levels for adolescents, without an impact on self-management.18
Adolescents at risk for anaphylaxis, most commonly due to a food allergy but also due to venom allergy or idiopathic causes, should be prescribed an epinephrine auto-injector and trained on its use and importance, ideally with the opportunity to practice in the clinic.19 Anaphylaxis rates increase each year after age 2 years,20 possibly due to increased autonomy and risk-taking behavior as well as more meals and activities outside the home and greater reluctance to carry an epinephrine auto-injector. In a survey21 of adolescents and emerging adults age 13 to 21 years, only 61% responded that they always carry their auto-injector, and the lowest likelihood was when participating in sports, wearing tight clothes, or sharing various social activities with friends. The highest likelihood of carrying an epinephrine auto-injector was with activities like going to a restaurant or traveling.21 Education of schools, camps, restaurants, and colleges is extremely important as well, and patients should be taught that they will often be the ones to impart this education.19
Mast Cell Disorders
Mast cell disorders generally differ between children and adults, with pediatric disease being much more likely to be limited to the skin. Isolated cutaneous mastocytosis (CM) in its various forms tends to have a better prognosis than systemic mastocytosis (SM), which more commonly presents in adulthood and generally persists over the lifespan.22 Of pediatric patients whose CM does not resolve prior to adulthood, approximately 15% to 30% develop involvement of other organs and are diagnosed with SM.23 Therefore, adolescents with persistent CM should be educated regarding the other symptoms associated with SM, which most commonly include diarrhea, flushing, presyncope and syncope as well as hives, angioedema, and anaphylaxis.
Urticaria and Angioedema
Acute urticaria, generally due to medication, food, or environmental allergies, can affect patients of any age. Chronic urticaria and angioedema, however, is much more common in adults and is generally idiopathic in origin. Of the bradykinin-mediated angioedema syndromes, hereditary angioedema, most commonly a genetic disorder of the C1 esterase gene, generally has its onset in childhood and persists throughout a person's life. Acquired angioedema, on the other hand, generally affects adults and is often associated with hematologic malignancies.
Although atopic dermatitis (AD) is more prevalent in childhood, a National Health Interview Survey demonstrated that 10.2% of the adults (n = 27,157) surveyed had eczema in the past year and that they were approximately 8% and 9% more likely to develop asthma and allergic rhinitis, respectively.24 In one study of AD during childhood and emerging adulthood, the most patients with onset in childhood continued to have AD into emerging adulthood.25 Another study26 with 7,157 children and emerging adults age 2 to 26 years enrolled in the Pediatric Eczema Elective Registry for 2 to 5 years noted that at every age, >80% of participants had symptomatic AD and/or were needing medication to treat their AD. In fact, approximately 50% of patients did not have a 6-month symptom and treatment free period.26 Although addressing food allergies is more relevant in the management of pediatric eczema, the remaining principles that guide management of atopic dermatitis apply to children and adults alike: avoiding aeroallergens, moisturizing well, using topical and rarely oral anti-inflammatory therapies, and breaking the itch-scratch cycle.
Most primary immunodeficiencies have a genetic basis and therefore present in early infancy or childhood. Severe combined immunodeficiency (SCID) is now a part of the newborn screen, which allows for early diagnosis of this condition to proceed immediately to treatment. Hematopoeitic stem cell transplant (HSCT) dramatically increases life expectancy for patients with SCID, which is otherwise uniformly fatal in childhood. The 5-year-survival rate for all patients after HSCT is 70% to 80% and as high as 80% to 95%, regardless of donor or conditioning, in those patients receiving their transplant prior to infection and before age 3.5 months.27 HSCT can also be used for patients with other primary immunodeficiency disorders, including Wiskott-Aldrich syndrome, chronic granulomatous disease, leukocyte adhesion deficiency, familial hemophagocytic syndromes, as well as other rare conditions. Similarly, thymic transplantation has been lifesaving for infants with “complete” DiGeorge syndrome, but long-term survival and complication data are not yet available.28 Similarly, although transplanted SCID patients have started to live into adolescence and adulthood, long-term studies are lacking, and newly recognized long-term complications of SCID may become evident with time. In addition, these patients and their physicians will need to monitor for the long-term complications of the transplants themselves or the conditioning regimens used to prepare for transplant in some patients.27
Common variable immunodeficiency (CVID), which is the most common immunodeficiency, can present at any age. Patients with CVID can develop various clinical conditions in addition to their immunodeficient state, including autoimmune diseases, malignancy, and granulomatous lymphocytic involvement of various organs that can lead to pulmonary, intestinal, or liver disease.29 Similar complications can be associated with various other primary immunodeficiencies. Awareness of these potential associations is extremely important in identifying disease processes early and preventing permanent or progressive organ damage that can result from delayed diagnosis or treatment. Patients with complicated primary immunodeficiencies require careful transition of care when they reach adolescence and emerging adulthood, including education of both the patient and their primary care provider about possible complications other than an increased risk of infection. Also important is ensuring that patients at the time of transition can navigate arranging for their immunoglobulin infusions, particularly with the changes in insurance that often occur in emerging adulthood.
Although all allergists/immunologists cross-train in both internal medicine and pediatrics, some ultimately feel more comfortable treating mainly children or mainly adults based on their primary residency. These allergists/immunologists will often pair with one another in private practice to make this possible. In addition, allergists/immunologists in academic institutions are often affiliated with either the pediatric or internal medicine department and therefore end up caring for primarily children or adults rather than both age groups. In these cases, careful transition planning is paramount as the actual provider often changes in adolescence or emerging adulthood. Even when the allergist/immunologist remains the same, however, transfer to an adult care model is important given the psychosocial changes that occur in adolescence and emerging adulthood and the increased independence that is inherent in this transition. It is important for primary care providers and specialists to understand that many atopic diseases and immunodeficiencies are chronic conditions and illnesses that often change over time. Successful transition for patients with chronic allergic/immunologic conditions involves an understanding of the natural history of these conditions, education of adolescents and emerging adults about the expected trajectory of their disease, an emphasis on independence and self-management in these age groups, and careful communication between pediatric and adult specialists as care is transitioned.
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