When Should I Be Worried About Immune Deficiency In The Setting Of Recurrent Upper Re

[dr.Ira]

When Should I Be Worried About Immune Deficiency In The Setting Of Recurrent Upper Respiratory Tract Infections?Adam L. Hersh, MD, PhD

It is not unusual for immunocompetent children to have 6 to 8 self-limited upper respi- ratory tract infections (URIs) or “colds” per year; children in day care or those with older siblings may experience even more frequent infections. Likewise recurrent otitis media is common in healthy children. Predisposing factors to recurrent URIs and otitis media include allergies, passive exposure to cigarette smoke, anatomical defects of the upper or lower airway, and even gastroesophageal reflux. Sometimes, however, recurrent URIs can sometimes be the presenting sign of a more serious underlying immune defect, which limits the capacity of the patient to mount effective immune responses.

Host defense against microbes (eg, viruses, bacteria, and fungi) are the result of a complex network of cells capable of recognizing a broad array of pathogens. The immune system can be broadly divided into 2 categories: innate and adaptive immunity. Innate immune cells are found in relative abundance throughout the body and include neutro- phils, basophils, mast cells, eosinophils, monocytes, macrophages, and dendritic cells. The adaptive immune system includes T and B lymphocytes. These cells express a cell-surface receptor (the T-cell or B-cell receptor). Through a complex developmental process, these receptors allow relatively rare cells to recognize a specific infection and respond accordingly. The amplification of T- and B-cell populations is the basis of the generation of protective immunity from vaccination. Typically, patients who have immune deficiency in the setting of recurrent URIs have deficiencies in adaptive immunity. In particular, dysfunction in either B or T cells leads to poor antibody production (or quality) and subsequent susceptibility to sinopulmonary infections. Most commonly, these humoral immune deficiencies lead to recurrent infection with encapsulated organisms, including Streptococcus pneumonia and Haemophilus influenzae. Antibody production disorders can have varied levels of T-cell dysfunction that may place the patient at increased risk for severe viral or opportunistic infections as well. Humoral immune deficiencies that might present with recurrent URIs include X-linked agammaglobulinemia, common variable immunodeficiency (CVID), selective immunoglobulin (Ig)A deficiency, polysaccharide antibody deficiency with or without IgG subclass deficiency, and hyper IgM syndrome (with the X-linked being the most severe because of T-cell dysfunction). Of these, CVID and selective IgA deficiency would be the highest consideration in a patient with recur- rent URIs as these 2 disorders are most prevalent. Transient hypogammaglobulinemia of infancy be also be considered in young children. Other immune deficiencies that have been associated with recurrent URIs, including otitis media, include human immunode- ficiency virus infection, DiGeorge syndrome, and Wiskott-Aldrich syndrome.

When a patient presents with recurrent URIs, the clinical history is the starting point. Increased frequency of infection, increased severity of infections, or infections with unusual organisms should raise suspicion of immune deficiency, as should episodes of otitis media or sinusitis that fail to respond to oral antibiotics. Frequent URIs seen in the context of other frequent infections such a pneumonia or meningitis are another “red flag.” If a patient has 4 or more distinct episodes of severe (does not respond with typical therapy or requires repeated parenteral therapy) otitis media or 2 or more episodes of pneumonia/sinusitis in 1 year, immunodeficiency should at least be considered. A family history of severe infections requiring courses of antibiotics and/or hospitalization also raises concern.

Screening tests for suspected humoral immune deficiency include a complete blood count, quantitative serum immunoglobulins (IgG, IgA, IgM, quantitative IgG subclasses), IgG levels to specific protein vaccine antigens such as diphtheria or tetanus, and HIV anti- body. When indicated by clinical examination or abnormalities in screening laboratories, lymphocyte subset analysis to document appropriate numbers and proportions of B and T cells might also be performed.

If consideration of allergic rhinitis as a cause of frequent or recurrent sinopulmonary infections is being given, then referral to an allergist may be helpful. However, if there is significant concern that the child in fact has recurrent infections that are out of the norm for his or her age group, then referral to an immunologist or an infectious diseases specialist may be warranted for further diagnostic testing and treatment strategies.