Evaluating the child with recurrent infections - includes patient information sheet

Author: J. Gary Wheeler
Date: Nov 15, 1996

In evaluating recurrent childhood infections, the physician must keep in mind the rarity of true immunodeficiency and the frequency of atopy, day care, exposure to cigarette smoke and anatomic variations as predisposing factors in recurrent childhood illnesses. Determining true immunodeficiency involves exclusion of risk factors for human immunodeficiency virus infection, identification of a family history of immunodeficiency and recognition of specific physical and laboratory findings. In most cases, screening immunoglobulin studies will distinguish the normal child from the child with an abnormal immune system. Management of the patient with true immunodeficiency is carried out in collaboration with specialists in these uncommon disorders.

Over the past 15 years, the complaint of recurrent childhood infections has become increasingly frequent and worrisome to primary care physicians. The diverse forces behind this phenomenon reflect a rapidly changing society. Widespread information about human immunodeficiency virus (HIV) disease has led to a greater public awareness of the immune system than in the past. As a result, parents have become more concerned about immunity in children with recurrent infections. The shift in family dynamics to two working parents has increased the number of children in day care, where they are vulnerable to frequent infections. In this age of anxiety and mobility, the physician often must fill the grandmother's role in reassuring parents about minor childhood illnesses.

From the physician's perspective, the definition of immunodeficiency has become more complex in the past two decades, and new methods to potentiate the immune system have been explored. Countering this pressure are the realities of capitation and managed care, in which minimal diagnostic studies are desirable. Finally, the threat of litigation from overlooking a serious disorder such as immunodeficiency continues to hover over the practice of medicine.

In an effort to balance these issues, a simplified, practical approach to the evaluation of recurrent infections has been developed. It is based on grouping patients with recurrent infections into three categories: normal children, those with some abnormality for which only symptomatic therapy is indicated and, finally, those rare children with a serious deficiency that requires a specific management plan.

Causes of Recurrent Infections

The first cause of recurrent infections in children is childhood itself. Infants do not have a fully mature immune system at birth. In fact, humoral and phagocytic immunity may not reach full potential until children reach school age.[1,2] As with the developmental milestones of pulling up and walking, some children reach their immunologic milestones later than others and yet fall within the normal bell curve. These children appear to have immune "tardiness," but have no intrinsic problem with their immunity.

Another consideration is immunologic naivete. Children are exposed to a substantial number of new pathogens in their contacts with the environment. Certain situations, such as day care, accelerate this process. As a result, children have more frequent infections than adults do. The number of viral infections in day care children averages from 10 to 20 during the first two years of life. A recent study[3] showed that about two-thirds of day care patients have more than 60 days of respiratory illness per year.[3] The pattern of these illnesses is distinctive. While the parents may complain that their child is "always sick," a careful history reveals a number of distinct illnesses (occurring primarily in the winter), punctuated by periods of well-being.

Other frequent causes of recurrent infections are listed in Table 1. One common association is exposure to tobacco smoke. Recent studies[4,5] have established the important independent role of tobacco smoke in recurrent respiratory disease among children, particularly those under age five, who are most vulnerable to recurrent infections.

TABLE 1Most Common Causesof Recurrent Infections in Children(*)Increased exposure to infections (e.g., day care)Passive smokingAnatomic abnormalitiesAsthma, allergic rhinitisCystic fibrosisGastroesophageal refluxMalnutritionHIV infectionHIV = human immunodeficiency virus.(*)--Primary immunodeficiencies not included (seeTable 5).


The final set of questions emerges in the review of systems (Table 3). Failure to thrive--a feature of T-cell immunodeficiencies, some B-cell deficiencies and HIV disease--is a good example of information routinely obtained in a history. Openended questions to the family and a review of the medical records are likely to uncover significant information such as the presence of congenital heart disease (occurring in DiGeorge syndrome), advanced gum and dental disease (phagocytic syndromes) or eczema (Wiskott-Aldrich syndrome or Omenn's syndrome, a variant of severe combined immunodeficiency).


Physical Examination

A complete physical examination is required. Special attention to the growth percentiles, the skin inspection and the lymph node examination is important. Hypertrophied lymph nodes are found in chronic granulomatous disease, common variable immunodeficiency and HIV disease, whereas absent nodes are characteristic of agammaglobulinemia. Unusual findings such as partial albinism may be markers of specific diseases such as Chediak-Higashi syndrome. Other findings (for example, poor hypopharyngeal tone in a patient who had neonatal brain injury) may explain a recurrent chest syndrome that is actually a result of recurrent aspiration.

Diagnostic Studies and Assessment

A review of previous findings is the next step. Past chest roentgenograms can help clarify a confusing history of pneumonia versus atelectasis associated with asthma. Pneumonia as a result of immunodeficiency is typically interstitial associated with hypoxia or identified as a lobar pneumonia associated with bacterial infection. The presence of a pneumatocele suggests a more destructive process, such as hyperimmunoglobulinemia E syndrome or chronic granulomatous disease. A recent chest film can confirm the presence of a thymus and thus exclude the rare DiGeorge syndrome. A complete blood count with normal results can help rule out congenital neutropenias, and normal-appearing platelets can exclude Wiskott-Aldrich syndrome. Review of the smear can also exclude rare disorders like Chediak-Higashi syndrome, which has characteristic large phagocyte granules.

At this point the physician should decide whether the patient falls into one of the following three groups:

1. The probably normal child, whose rate and severity of infections fall within the normal range or in whom a specific risk factor is identified (i.e., passive smoking, day care). This child requires no further diagnostic testing; reassurance and observation are adequate.

2. The clearly abnormal child, specifically any patient with two unexplained infections requiring hospitalization. Referral or preliminary diagnostic studies are indicated in this child.

3. The probably normal child, typically less than three years of age, in whom some diagnostic studies are warranted to relieve the anxiety of either the physician or the parents.

In the last group, an HIV test (if indicated by the history) and serum IgG and IgA determinations are usually all that need be ordered. One consideration is that 19 percent of women with HIV disease have no known risk factors.[7] Thus, in an area with high seroprevalence, an HIV screen may be indicated even if no specific risks are identified. Immunoglobulin levels are abnormal in 90 percent of primary immunodeficiencies and are an excellent screen for serious disorders. In the remaining 10 percent (phagocytic and complement disorders), the history is highly suggestive and points to special diagnostic tests.

The additional studies that are most often considered include determinations of IgG subclasses and antibody responses to vaccines. Much has been written about the use of subclass studies in children, but little consensus exists concerning their value.[9-11] Abnormal results may be found in normal as well as abnormal patients, and no therapy has been proved effective in managing the recurrent infections associated with deficiencies of subclasses. While subclass deficiencies may be epiphenomena indicative in some cases of disregulation of the immune response, antibody responses more directly measure the function of the immune system in responding to antigenic challenge. Antibody responses to tetanus vaccine (protein antigen) or to pneumococcal vaccine (polysaccharide antigen) are compared with prevaccination values to determine whether the immune response is normal and to help identify the individual in whom early or preventive antibiotic therapy is indicated. Additional studies are probably not needed before referral if immunodeficiency is suspected at this point. The expertise of the specialist in pediatric infectious diseases or immunology is usually helpful, since testing can be very expensive (Table 4) and requires experienced interpretive skills.


The findings in children referred to immunology clinics for recurrent infections suggest that moderate to severe immunodeficiency is uncommon in comparison with other disease processes. As a referral practice, we see only patients who have exceeded the threshold of concern for the referring physician. However, in an informal survey of our immunology clinic patients, only 3 percent were found to have a serious immunodeficiency. IgA deficiency was identified in 6 percent, and mild laboratory abnormalities that resolved with time were found in 9 percent. Recurrent otitis media with an anatomic basis was suspected in 12 percent, and 33 percent had asthma. A recurrent pyoderma syndrome for which no immune defect was found was the complaint in 6 percent. In these patients, chronic respiratory staphylococcal carriage was the presumed vehicle for recurrent skin boils and pyoderma.

The initial evaluation of a child with recurrent infections is outlined in Figure 1.


For patients with no appreciable variance in infection rate or severity above normal, assurance and observation are adequate. For patients in whom the frequency of respiratory infections is increased and in whom some finding is mildly abnormal, such as low but not absent immunoglobulins or poor antibody responses, management should be limited to antiatopic therapies (nasal steroids, antihistamines), prophylactic antibiotic therapy (seasonal amoxicillin, 20 mg per kg at bedtime) and surgery (pressure equalization tubes, endoscopic sinus surgery).

While the use of preventive antibiotics (e.g., amoxicillin, sulfa drugs) is becoming less popular with the increasing prevalence of drug-resistant bacteria, the small number of these patients justifies continuing their preventive therapy. Such therapy can be focused on the winter seasons, with antibiotic vacations during the summers.

Patients with more serious problems suggestive of the diseases in Table 5 should be referred for management to a pediatric allergist/immunologist or an infectious disease specialist. As mentioned earlier, considerable experience is required for cost-effective diagnostic testing and interpretation of the laboratory studies, which are age-dependent in most cases[2] and not routinely available in the primary care setting. Decisions about the use of immunotherapy, such as intravenous immune globulin or postexposure varicella-zoster immune globulin, are complex and disease-specific.


Intravenous immune globulin is used as replacement therapy in patients who have no antibody (Bruton's X-linked agammaglobulinemia), where therapy is clearly indicated, and in patients who cannot form antibody (antibody deficiency syndromes), where therapy is only sometimes indicated. The long-term use of intravenous immune globulin is complicated by variability in dose requirements, side effects and outcome measures.

A final important point is that a patient suspected of having a severe congenital immunodeficiency should not receive live vaccines (varicella, mumps, measles, rubella, oral polio virus, bacille CalmetteGuerin)[8] or blood transfusions with nonirradiated blood (which may lead to graft-versus-host disease). Varicella-zoster immune globulin and immune globulin are available for therapy following exposure to varicella and measles, respectively.

FIGURE 1. Initial evaluation of a child with recurrent infections. (HIV = human immunodeficiency virus)

Does the child have a common underlying cause of recurrent infection other than a primary immune system disorder?

See Table 1

Does the child have a family history of an immune system disorder?

Consider an inherited defect

Is the infectious syndrome in the child suggestive of a specific immune system disorder?

See Table 2

What physical findings in the child might point to a specific immune system disorder?

See Table 3

Which of the following categories does the child's clinical picture fit?

* A clinical course that is within normal limits.

Reassure the parent(s).

* A clinical picture that is clearly abnormal.

Refer the child for special testing and treatment.

* A clinical picture that is probably normal, but preliminary

screening for an underlying immune system disorder is deemed


Order an HIV test and determine serum levels of IgG and IgA.

* An uncertain clinical picture.

Follow the clinical course if the suspected cause of

infections is benign and refer the child

for further evaluation if a more serious cause is suspected.


[1.] Yang KD, Hill HR. Neutrophil function disorders: pathophysiology, prevention, and therapy. J Pediatr 1991;119:343-54. [2.] Wheeler JG, Steiner D. Evaluation of humoral responsiveness in children. Pediatr Infect Dis J 1992;11:304-10. [3.] Wald ER, Guerra N, Byers C. Frequency and severity of infections in day care: three-year follow-up. J Pediatr 1991;118(4 Pt 1):509-14. [4.] Fielding JE, Phenow KJ. Health effects of involuntary smoking. N Engl J Med 1988;319:1452-60. [5.] Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen M, Morgan WJ. Asthma and wheezing in the first six years of life. The Group Health Medical Associates. N Engl J Med 1995;332:133-8. [6.] Boyce WT, Chesterman EA, Martin N, Folkman S, Cohen F, Wara D. Immunologic changes occurring at kindergarten entry predict respiratory illnesses after the Loma Prieta earthquake. J Dev Behav Pediatr 1993;14:296-303. [7.] Update: AIDS among women--United States, 1994 MMWR Morb Mortal Wkly Rep 1995:44:81-4 [Published erratum appears in MMWR Morb Mortal Wkly Rep 1995;44:1351]. [8.] Conley ME, Stiehm ER. Immunodeficiency disorders: general considerations. In: Stiehm ER, ed. Immunologic disorders in infants and children. 4th ed. Philadelphia: Saunders, 1996:201-52. [9.] Moss RB, Carmack MA, Esrig S. Deficiency of IgG4 in children: association of isolated IgG4 deficiency with recurrent respiratory tract infection. J Pediatr 1992;120:16-21. [10.] Shackleford PG, Granoff DM, Polmar SH, Scott MG, Goskowicz MC, Madassery JV, et al. Subnormal serum concentrations of IgG2 in children with frequent infections associated with varied patterns of immunologic dysfunction. J Pediatr 1990;116:529-38. [11.] Herrod HG. Management of the patient with IgG subclass deficiency and/or selective antibody deficiency. Ann Allerg 1993;70:3-8.

The Author

J. GARY WHEELER, M.D. is an associate professor of pediatrics in the divisions of infectious diseases and allergy and clinical immunology at the University of Arkansas for Medical Sciences, Little Rock. He also serves on the staff at the Arkansas Children's Hospital in Little Rock. Dr. Wheeler graduated from Baylor College of Medicine, Houston, and received postgraduate and fellowship training at Emory University School of Medicine, Atlanta, and Bowman Gray School of Medicine, Winston-Salem, N.C.

Address correspondence to J. Gary Wheeler, M.D., Department of Pediatrics, Arkansas Children's Hospital, 300 Marshall St., Slot 512-13, Little Rock, AR 72202.

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