Abstract
Objective
The objective of the study was to review the diagnosis and treatment of primary immunodeficiency disease (PID) and the role of otolaryngologists in the management of PID.
Methods
A search was conducted of PubMed and the Web sites of organizations for PID patients for literature pertaining to the diagnosis and treatment of PID, with an emphasis on the role of otolaryngologists. The reference lists of selected articles were reviewed for additional articles.
Results
Patients with PID commonly present with respiratory tract infections (eg, recurrent ear, nose, or throat infections) and chest disease. Diagnostic delays or inadequate treatment of PID may lead to significant morbidity and premature mortality. Immunoglobulin (Ig) replacement is the cornerstone of therapy for most patients with PID. Although intravenous Ig is the most popular route of administration in the United States, subcutaneous Ig administration may be appropriate for patients with poor venous access, those who are unable to tolerate intravenous Ig, or those who prefer the independence and flexibility of self-administration.
Conclusions
Recognition and diagnosis of PID by otolaryngologists are critical to optimizing patient outcomes. Several therapeutic regimens for Ig replacement are now available that offer patients increased flexibility and independence.
1
Introduction
Primary immunodeficiency disease (PID) refers to a class of genetically heterogeneous disorders in which components of the host defense system (eg, antibody production, cell-mediated immunity, phagocytic cells, or complement) are intrinsically impaired . The approximately 120 genes that have been implicated in PID account for more than 150 PID phenotypes .
The incidence and prevalence of PID have been estimated in a patient survey and population-based analysis. A national telephone survey of about 10,000 randomly selected households conducted in 2005 and sponsored by the Immune Deficiency Foundation (IDF) provided the first population-based estimate of the prevalence of PID in the United States . About 1 in 1200 individuals in the United States (or 250 000 people) has been diagnosed with PID . This figure is likely to underestimate the incidence because many cases of PID are undiagnosed. The first population-based analysis of the incidence of PID was conducted in Olmsted County, Minnesota (2000 US census population of 124 277) . The historical cohort study conducted from January 1, 1976, to December 31, 2006, showed that the overall incidence of PID for the 31-year period was 4.6 per 100 000 person-years. The rate of PID, as measured in incidence per 100 000 person-years, increased from 2.4 from 1976 to 1980, to 5.5 from 1996 to 2000, and to 10.3 from 2001 to 2006. The authors attributed the increase to better diagnostic techniques and greater physician awareness of PID .
Recognition of PID is particularly relevant for otolaryngologists because chronic or recurrent sinopulmonary infections (eg, pneumonia, sinusitis, bronchiectasis, chronic obstructive pulmonary disease) and chronic otitis media are common presentations . Recurrent sinopulmonary infections are the most prevalent infection among PID patients . Patients with PID also experience an increased frequency of chest infections, meningitis and/or sepsis, and gastrointestinal (GI) and cutaneous infections . Untreated or inadequately treated PID may have substantial adverse consequences. Delays in the recognition and treatment of PID may result in unnecessary or unsuccessful surgical procedures and exposure of patients to potentially harmful treatments (eg, excessive use of antibiotics) .
Guidelines from the IDF and the American Academy of Allergy, Asthma, and Immunology/American College of Allergy, Asthma, and Immunology recommend basing a diagnosis on the results of diagnostic testing, particularly of the patient’s ability to produce specific antibodies, as well as patient history and physical examination . Treatment of PID must be individualized to the diagnosis and patient and generally comprises one or more of the following: careful upper and lower airway hygiene, antimicrobial prophylaxis, immunization, antibody supplementation with intravenous (IV) or subcutaneous (SC) immunoglobulin (Ig) therapy, stem cell transplantation, gene therapy, and cytokine therapy .
Ig replacement is the cornerstone of therapy for most patients . An SC formulation of IgG (SCIg) recently became available that may offer advantages over intravenous Ig (IVIg) administration for some patients, most notably those who prefer to self-administer at home. This article reviews the identification and diagnosis of PID in clinical practice by otolaryngologists and the role of Ig therapy in the management of PID.
2
Methods
An electronic literature search was conducted of the PubMed database for articles about the diagnosis and treatment of PID. Search terms included primary immune deficiency or primary immunodeficiency disease alone and coupled with diagnosis and treatment ; immunoglobulin therapy alone and paired with intravenous , intramuscular , and subcutaneous ; otolaryngologists coupled with PID ; and the more common subtypes of PID: common variable immunodeficiency (CVID), IgA deficiency, Bruton’s X-linked agammaglobulinemia (XLA), IgG subclass deficiency, chronic granulomatous disease (CGD), and severe combined immunodeficiency (SCID) . The search did not have a prescribed period, although more recent data were given priority in the selection of references. Both primary research and literature review articles were consulted.
The reference lists of identified articles were reviewed for additional articles not identified in the electronic searches. Finally, the Web sites of professional and patient-oriented organizations were consulted for information about the incidence and management of PID, as well as for additional references.
2.1
Primary immunodeficiency: characterization and diagnosis
Pathologic hallmarks of PID are common infections (otitis, sinusitis) that are frequently recurrent, unusually persistent, or severe. By far, the most common infection in patients with CVID is sinusitis . Infections caused by microorganisms that rarely cause disease in healthy people (eg, Pneumocystis , Serratia , nontuberculous mycobacteria) suggest the need for an immunodeficiency evaluation . PID should be suspected when a usually mild childhood infection leads to a severe, possibly life-threatening complication such as mastoiditis following otitis, brain abscess associated with sinusitis, or pneumonia with empyema. Low or persistently high neutrophil or lymphocyte counts should also be investigated . The Primary Immunodeficiency Resource Center (Jeffrey Modell Foundation) lists 10 warning signs to help identify patients with PID ( Table 1 ) . The presence of 2 or more warning signs or a history of prolonged antibiotic treatment should prompt assessment for PID .
| 1. ≥8 New ear infections within 1 y |
| 2. ≥2 Serious sinus infections within 1 y |
| 3. ≥2 mo on antibiotics with little effect |
| 4. ≥2 Episodes of pneumonia within 1 y |
| 5. Failure of an infant to gain weight or grow normally |
| 6. Recurrent deep skin or organ abscesses |
| 7. Persistent thrush in mouth or on skin after age 1 y |
| 8. Need IV antibiotics to clear infections |
| 9. ≥2 Deep-seated infections |
| 10. Family history of PID |
Comorbid conditions, particularly autoimmune and GI disorders, may help identify patients with PID. Autoimmune disorders (eg, autoimmune endocrine disorders, rheumatic conditions, autoimmune hemolytic anemia, or thrombocytopenia) may be associated with antibody deficiency, especially IgA deficiency or CVID . A complement deficiency may correlate with an autoimmune disease such as lupus or lupus-like syndromes . Between 20% and 47% of patients with primary antibody deficiencies report GI disorders . Infections and diseases of the GI tract (eg, Crohn disease, ulcerative colitis, celiac disease) are common in patients with IgA deficiency and CVID , and GI obstruction may occur in some patients with CGD .
2.1.1
Presentations of common immunodeficiencies in adult and pediatric patients
Many of the approximately 150 phenotypes of PID are uncommon. Only 6 diagnoses were listed in the 2005 IDF survey: CVID, reported by 35% of respondents; IgA deficiency, reported by 26%; Bruton XLA, 13%; and IgG subclass deficiency, CGD, and SCID, all approximately 9% . These findings are generally in agreement with those of an analysis of 237 adult and pediatric patients referred to a medical center by internists, pediatricians, or allergists for suspicion of immunodeficiency . Immune defects were identified in 48% of patients, with the most common being CVID (in 34%), IgG subclass deficiency (12%), and selective IgA deficiency (11%) .
Table 2 describes the clinical presentations and immunological findings associated with the most common PIDs. Bruton XLA and hyper-IgM syndrome are usually diagnosed during the first years of life; but the other antibody deficiencies (CVID, selective IgA deficiency, and IgG subclass deficiency) can present at any age and are associated with the upper respiratory tract infections, most notably sinusitis and otitis media, that are seen by an otolaryngologist . For example, respiratory tract and ear infections were the most frequently identified infections at the time of diagnosis in a study of 224 patients with CVID. The 5 most frequently identified infections were acute bronchitis, 62.9% of patients; pneumonia, 49%; acute otitis, 38.4%; chronic bronchitis, 33.9%; and chronic sinusitis, 36.6% . An analysis of data from the DEFI Study Group, a French data collection network of people with PID, found that 240 (91%) of 252 patients with CVID exhibited respiratory symptoms, usually an infection, at diagnosis. The most common infections were recurrent bronchitis (69%), recurrent sinusitis (63%), and pneumonia (58%). Bronchiectasis developed in 37% of patients . Similarly, of 45 patients with CVID or agammaglobulinemia, computed tomography (CT) of the lungs and paranasal sinuses identified chronic sinusitis in 41 patients, pulmonary changes in 26, and bronchiectasis in 16. The type or severity of infection did not correlate with the particular PID diagnosis . A retrospective analysis of 32 children with CVID found clinical presentations of recurrent or chronic respiratory tract infections in 88% and both sinusitis and recurrent otitis media in 78%. Eighty percent had a history of otolaryngologic surgeries .
| PID | Type of deficiency or defect | Characteristic presentation | Laboratory results |
|---|---|---|---|
| CVID | Antibody deficiency | Recurrent sinopulmonary infections with encapsulated or unusual bacteria | Variable reduction in ≥1 Ig class, and/or impaired specific antibody formation; occasionally low or absent peripheral blood B-cell counts |
| Selective IgA deficiency | Antibody deficiency | Estimated that up to 90% of patients are asymptomatic; recurrent respiratory tract infections (otitis media, sinusitis, bronchitis); GI tract infections; atopy, autoimmune disease, and malignancy may be associated clinical manifestations | Serum IgA level <7 mg/dL with normal IgG and IgM levels in patients >4 y of age in whom other causes of hypogammaglobulinemia have been ruled out; normal functional antibody production determined by antibody titers to vaccine antigens; assays for cellular immunity, phagocyte function, and complement typically normal; autoimmune antibodies commonly present; allergy tests often positive |
| XLA | Antibody deficiency | Recurrent sinopulmonary infections (particularly otitis media, sinusitis, and pneumonia) with encapsulated bacteria in first 2 y of life | Hypogammaglobulinemia or agammaglobulinemia associated with absent peripheral blood B cells |
| CGD | Phagocyte defect | Superficial and deep-seated infection, abscess with granuloma formation | Normal or elevated leukocyte count; abnormal phagocyte oxidase production |
| SCID | Combined deficiency | Failure to thrive, diarrhea, opportunistic infection, rash | Complete absence of specific immunity; laboratory phenotype depends on molecular defect but may include panhypogammaglobulinemia or lymphopenia; absence of cellular immune function assessed with in vitro stimulation tests |
Antibody deficiencies are a major susceptibility factor for refractory sinusitis or chronic rhinosinusitis . For example, a retrospective analysis of patients (n = 87) who had endoscopic sinus surgery for chronic rhinosinusitis sought to identify which comorbidity (eg, asthma, allergic rhinitis, deviated septum, gastroesophageal reflux disease, or immunodeficiency) was associated with a greater likelihood for squamous metaplasia, which is considered a marker for chronic inflammation. Immunodeficiency was the only comorbidity found to be more prevalent in patients with squamous metaplasia. Histologic grading of surgical specimens identified significantly more severe inflammation with squamous metaplasia . The high prevalence of immune dysfunction among patients with refractory sinusitis or chronic rhinosinusitis suggests that immune testing should be part of their evaluations . Children with recurrent rhinosinusitis that does not improve after the age of 3 years should be evaluated for PID. Rhinosinusitis secondary to an IgA or IgG subclass deficiency is usually managed medically, with sinus surgery reserved for adjunctive use as needed to remove loculations from persistent disease .
Antibody deficiencies may be an underdiagnosed cause of chronic sinusitis. Examinations of 79 patients with refractory sinusitis who had undergone at least 1 sinus surgery and/or had at least 3 sinus infections diagnosed by endoscopy or CT in the previous year identified low levels of IgG, IgA, and IgM in 18%, 17%, and 5%, respectively . CVID was diagnosed in 10% and selective IgA deficiency in 6% . A study in 61 children with chronic, refractory sinusitis referred for an allergy evaluation found that 18% had low Ig levels, 10% had both low Ig levels and hyporesponsiveness to vaccine (indicative of an antibody deficiency), and 28% demonstrated poor vaccine responsiveness only .
Some forms of PID do not present with symptoms associated with otolaryngology. For example, the primary clinical manifestations of CGD are deep-seated granulomatous infections with bacteria and fungi and abscesses with granuloma formation; disease onset is typically in infancy . Patients with SCID usually present within the first few months of life with failure to thrive; diarrhea; rashes; and recurrent, persistent, or severe infections . SCID is considered a medical emergency, warranting prompt referral to an immunologist .
2.1.2
Delay in diagnosing PID
Many patients with PID experience a prolonged delay between the initial onset of symptoms and their diagnosis. Among 1500 patients with PID, 40% were not diagnosed until they were 30 years or older , although most PIDs are diagnosed in infancy . The delay between onset of symptoms and diagnosis of PID is usually between 4 and 5 years , although one study found an almost 9-year delay . Joshi et al identified a median interval between symptom onset and diagnosis of 4.7 years. An analysis of an Internet-based patient database in Europe revealed a mean diagnostic delay of 4.08 years (median, 2 years) for PID overall and 4.75 years (median, 2 years) for antibody deficiencies . Similarly, a retrospective chart review conducted in the United Kingdom reported a mean delay of 4.4 years (median, 2 years) for diagnosis of primary antibody deficiency . A longer delay in diagnosis has been associated with recurrent sinusitis and pneumonia . Key reasons for underdiagnosis and delays in diagnosis include lack of awareness, absence of family history, the variable and complex presentation of PID, and masking of symptoms with frequent antibiotic use .
However, data published since 2008 indicate that the diagnostic delay may be decreasing. The analysis of the DEFI data from France found that, among PID patients (n = 138) diagnosed before 1990, the median delay between symptom onset and diagnosis was 15.6 years. For patients (n = 114) with initial symptoms after 1990, the delay was only 2.9 years . In the historical cohort study in Minnesota, the median interval declined from 17.5 years for patients with a symptom onset before 1986 to a median of 2.7 years for patients with onset after 1996 .
2.1.3
Assessment of patients with suspected PID
Antibody deficiency is the most likely PID to present with recurrent otolaryngologic infections . Fig. 1 summarizes the process of diagnosing antibody deficiencies . A detailed family history may, when positive, provide useful information because some antibody deficiencies (eg, Bruton XLA, CVID) are genetic or familial . Although most PID patients present with a normal physical examination, findings suggestive of antibody-production defects include the following :
- •
Absent or small tonsils and lymph nodes
- •
Swollen lymph nodes and splenomegaly
- •
Scarred tympanic membranes
- •
Abnormal breath sounds (rales, rhonchi)
- •
Clubbed fingers
Diagnostic tests include complete blood count/differential; quantitative serum concentrations of IgG, IgA, IgM, and IgE; and measurement of specific antibody responses to vaccines . A culture of infected material and HIV testing may also aid in differential diagnosis . Measurement of specific, functional antibody plays a particularly important role in the diagnosis of antibody deficiencies. It is crucial to note that merely measuring Ig isotypes (IgA, IgG, and IgM) is insufficient for a diagnosis of PID. Patients whose initial antibody testing indicates an antibody deficiency or low age-adjusted lymphocyte, neutrophil, or platelet counts should be referred to an immunologist .
The American Academy of Allergy, Asthma, and Immunology/American College of Allergy, Asthma, and Immunology guidelines define selective IgA deficiency as serum IgA levels of less than 7 mg/dL in a patient older than 4 years with normal serum IgG and IgM concentrations and in whom other causes of hypogammaglobulinemia have been ruled out . Immunoglobulin A deficiency affects about 1 in 300 to 700 individuals, the majority of whom are asymptomatic .
Immunoglobulin G subclass deficiency is defined as 1 or more IgG subclass levels that are at least 2 standard deviations less than the age-adjusted mean and normal levels of total IgG and IgM . However, the sensitivity and specificity of IgG subclass determinations as a test for PID are generally considered to be too low to represent a useful diagnosis. Therefore, there are unresolved questions about the clinical significance of IgG subclass deficiency and whether it is actually a PID. Consequently, an IgG subclass deficiency is generally not considered sufficient for a diagnosis of PID without an impaired antibody response to vaccination . Many immunologists no longer include measurement of IgG subclasses in their evaluation of patients with recurrent infection.
Although much less common than antibody deficiencies, a combined immunodeficiency with abnormal serum Ig concentrations and/or vaccine responses has been seen in some patients . The younger the patient, the more likely that the antibody deficiency will be associated with a defect in cell-mediated immunity. Although patients at any age with defined antibody abnormalities may benefit from consultation with an immunologist , children younger than 4 years with an antibody abnormality should be referred to a physician experienced in the diagnosis and management of PID.
Patients with disorders of phagocytic cell numbers or function (eg, chronic or cyclic neutropenia, CGD, leukocyte adhesion defect syndrome) commonly present during the first years of life with abscesses of the superficial or deep tissues . Staphylococcus aureus is the most common infecting organism , but infections with low-virulence organisms that seldom infect normal hosts are also seen in these patients. Otolaryngology surgeons have the opportunity to identify these PID patients. Culturing an unusual pathogen such as Serratia , Pseudomonas , or Aspergillus from a cervical adenitis, facial cellulitis, or sinus irrigation should prompt an evaluation of phagocytic cell function .
Although the rarest of defined PIDs, complement deficiencies should be considered in patients with recurrent ear infections . Other associated infections are pneumonia, meningitis, and disseminated neisserial disease . Complement screening assays (CH50/AH50) are recommended laboratory tests for patients with suspected complement defects. If the CH50 or AH50 result is abnormal, specific complement component assays are indicated . If results of these tests are abnormal, patients should be referred to an immunologist .
2.2
Immunoglobulin replacement therapy
Ig replacement therapy is the cornerstone of effective management of PID patients with significant disorders of antibody production. Most immunologists make decisions on Ig therapy based on an assessment of the infection history and laboratory evaluation. No data define exactly how many infections are too many or what laboratory results mandate treatment. There is a considerable difference of opinion about both subjects among experienced immunologists. According to guidelines presented at the 2006 European Society for Immune Deficiency meeting, Ig replacement therapy is indicated for all patients with IgG levels of less than 200 mg/dL . Individuals with IgG levels between 200 and 500 mg/dL should receive Ig replacement therapy only in the presence of frequent infections and a specific antibody deficiency. For patients with IgG levels exceeding 500 mg/dL, Ig replacement therapy is recommended only if severe recurrent infections have occurred and a specific antibody deficiency has been identified. These recommendations are among the most conservative regarding the use of Ig replacement; and given that each patient has a unique IgG level, the decision on when to initiate Ig replacement therapy should be individualized to each patient .
Just as a lapse has been identified between the onset of PID symptoms and diagnosis, a lag between diagnosis and initiation of Ig therapy has been observed. A study of patients with CVID found an interval of 5.8 years (range, 0.2-14.3 years) between symptom onset and Ig replacement therapy .
2.2.1
History of Ig replacement therapy
The first reported case of an antibody deficiency successfully treated with Ig replacement therapy was in 1952, when Ogden C. Bruton described an 8-year-old boy with a 4-year history of recurrent infections and poor responses to a variety of medications . After determining that the boy’s serum did not contain gammaglobulin, Bruton successfully treated him with a human Ig preparation administered subcutaneously . Subsequently, intramuscular injections became the preferred route of administration. Intramuscular administration, however, causes marked discomfort and carries a risk of nerve injury. Furthermore, adequate dosing is often not possible because of the large volumes required .
IVIg products became widely available in the 1980s, and IV has since become the most popular form of administration in the United States . Despite the benefits of IVIg, some patients experience severe adverse reactions or find IVIg inconvenient because of the time required for infusion, the difficulty of at-home infusion, and the need to receive their infusions at a physician’s office or hospital .
Prospective, open-label, multicenter studies have demonstrated that SCIg replacement therapy is safe and effective in children and adults with PID . Rapid SCIg administration appears safe, provokes few systemic adverse events, produces high and consistent serum IgG levels, and facilitates self-infusion of therapy at home . A gammaglobulin preparation designed for SC administration has been licensed in the United States since 2006 .
2.2.2
Advantages and disadvantages of IVIg and SCIg
The availability of different Ig preparations with similar efficacy permits individualization of treatment for patients with PID . Table 3 lists the advantages and disadvantages of IVIg and SCIg .
| SC | IV | |
|---|---|---|
| Advantages | 1. Lack of requirement for venous access 2. Gradual adsorption obviates rapid, large changes in serum IgG and reduces severe headaches and other adverse effects 3. Maintenance of more consistent IgG levels eliminates low troughs 4. Facilitates self-infusion, increasing patient’s autonomy; may improve patient’s self-image and sense of control | 1. Convenient and well tolerated by most patients 2. Ability to give large volume per infusion permits intermittent dosing (every 2-4 wk) |
| Disadvantages | 1. Requires dosing every 1-2 wk 2. Successful self-infusion requires reliable patient or caregiver | 1. Requires venous access and trained personnel in most situations 2. Rapid increase in serum IgG may cause adverse events at or just after infusion and increased infections during the low-trough period preceding the next infusion |
A medical professional is generally needed to administer IVIg. According to the 2003 IDF patient survey, almost 90% of patients indicated that a nurse or physician usually administers the IVIg infusion; and only 5% of patients claimed that they usually self-administer . Some centers, however, have taught patients or caregivers to provide their own IVIg . In addition, IVIg may be problematic for some patients, especially infants and small children, with poor venous access . Indwelling central venous devices facilitate administration of IVIg, but these devices are associated with risks of infection and thromboembolic complications .
Only 2% to 6% of patients receiving IVIg replacement therapy experience systemic reactions . Mild infusion-related reactions with IVIg such as headache, flushing, or nausea are most common, whereas more severe reactions, including thromboembolic events or anaphylaxis, rarely occur . IVIg therapy can lead to hematologic complications (hemolysis, transient neutropenia), neurologic effects (rare cases of acute aseptic meningitis), renal toxicity, and dermatologic reactions (erythema multiforme) . However, the incidence of these events is rare; and they occur primarily in elderly patients with cerebrovascular risk factors or a history of renal disease or diabetes mellitus . Studies indicate that the percentage of patients experiencing systemic adverse events with SCIg therapy ranges from zero to 3.3% .
IVIg should be used with caution in patients with selective IgA deficiency because of the very small risk of developing IgE anti-IgA antibodies that could cause an anaphylactic reaction . Observations from 2 small patient populations (15 patients in one study and 8 of 88 patients in a second study) suggest that SCIg treatment may be safe in patients with CVID and anti-IgA antibodies who have had anaphylactic reactions to IVIg .
Dosing regimens vary for IVIg and SCIg and with the type and severity of PID. For patients with antibody defects, IVIg is usually administered every 2 to 4 weeks, whereas SCIg is given every 1 to 2 weeks . Typical monthly doses of Ig range from 400 to 800 mg/kg . Dose adjustments are necessary during childhood but, after a dose has been established, are not routinely required during adulthood unless infections are not well controlled . Subcutaneous Ig is typically administered with an infusion pump, but it can also be successfully administered via “push” therapy as often as every day .
The costs associated with IgG replacement therapy comprise the cost of the drug (including shipping, storage, reconstitution for dry powder products, and pooling into an IV bag) and the cost of administration. Both the drug costs themselves and administration costs are quite variable. Clearly, however, home administration by the patient or a caregiver eliminates most of the nondrug costs .
2.2.3
Long-term effects of untreated or undertreated PID
Diagnostic delays and inappropriate or inadequate treatment of PID may lead to premature mortality, severe life-threatening infections, and chronic organ damage, such as permanent hearing loss, bronchiectasis, pulmonary hypertension, left ventricular impairment, and right heart dilation . Patients with significant hypogammaglobulinemia and recurrent sinopulmonary infections who are not treated adequately do not grow normally . Individuals with inadequately or inappropriately treated PID experience more missed work or school days and more days in the hospital than those receiving Ig therapy . Permanent loss of function (eg, hearing, mobility) before diagnosis contributes to activity impairment that cannot be reversed with Ig therapy .
2.2.4
Defining adequate therapy for PID
2.2.4.1
Beyond the primary goal of decreasing infections
Compared with healthy individuals, adults with untreated PID have a significantly reduced quality of life . In contrast, the diagnosis of PID and initiation of Ig therapy are associated with improvement in health-related quality of life (HRQoL) and, to a lesser extent, reduction of limitations on activity . In the 1997 IDF Treatment Survey, the majority of patients described their self-reported health status as poor in the year before diagnosis; and less than 20% said their health status was good, very good, or excellent . Patients reported an improvement in their overall health following diagnosis and during their last year of Ig therapy, with nearly half reporting their health as good, very good, or excellent.
A study conducted in Sweden found that 18 months of weekly SCIg therapy significantly improved self-rated health and health-related functioning in previously untreated patients with hypogammaglobulinemia . Two other Swedish studies examined the impact of switching from hospital-based IVIg to home-based SCIg on HRQoL and treatment satisfaction . In children, changing to SCIg therapy was associated with significantly improved health and school/social functioning, fewer social limitations, and reduced school absences . Adults with PID reported improvements in vitality, mental health, and social functioning following a switch to SCIg .
A North American study investigated the impact of switching to weekly SCIg treatment on HRQoL, treatment satisfaction, and patient preference in adults previously treated with IVIg at the hospital/physician’s office (n = 28) or at home (n = 16) . HRQoL was noticeably better at baseline for patients receiving IVIg at home than at the hospital/physician’s office. Among patients who had received IVIg at the hospital/physician’s office, switching to SCIg resulted in significant improvement in HRQoL at 12 months. No significant changes were observed for patients who had previously received at-home IVIg treatment, except for significant improvement on the general health scale of the Short-Form 36 HRQoL questionnaire.
2.3
Long-term monitoring
Practitioners use many different laboratory testing and imaging schedules to monitor PID patients. A hemogram and comprehensive metabolic panel should be obtained at least once a year. Some immunologists monitor IgG levels several times a year. In our experience, frequent IgG testing is not helpful once the patient is doing well on a stable dose . We recommend measuring an IgG annually and whenever there is a major infection (communication from author, RL Wasserman, November 2009). Patients with a history of pneumonia should have a spirometry and a high-resolution CT of the chest at the time of diagnosis. The frequency of repeat chest CTs is determined by physical findings and the frequency and severity of chest infections.
It is important to note that young patients with subtle antibody production defects whose infection frequency and severity justify IgG replacement therapy may experience an improvement in endogenous antibody production. It is, therefore, appropriate to reassess periodically the need for IgG therapy in growing children. There are no studies that provide guidance on this issue; however, in our experience, when a child has done well, with few to no bacterial infections for 2 or 3 winters, reevaluation is reasonable. Because IgG therapy must be discontinued before laboratory evaluation, we usually stop treatment in April, after the major viral respiratory tract infection season, and begin the laboratory evaluation 2 months later. This timing allows for a washout of exogenous IgG and the completion of the testing during the summer so that IgG therapy can be restarted if necessary. Reevaluation should include measurement of Ig classes, IgA, IgG, and IgM, as well as assaying the response to revaccination with pneumococcal polysaccharide and diphtheria/tetanus toxoid vaccines (communication from author, RL Wasserman, November 2009).
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