Enthesitis-related Arthritis

Enthesitis-related arthritis (ERA) is a disease predominantly affecting the joints and entheses of the lower extremities and has the potential to eventually affect the sacroiliac joints and spine evolving to juvenile ankylosing spondylitis. ERA is also characterized by rheumatoid factor seronegativity, paucity of antinuclear antibody, and a strong association with the human leukocyte antigen-B27. ERA accounts for a higher proportion of juvenile idiopathic arthritis (JIA) cases in the Asian population compared to other populations. Advances in the understanding of ERA pathogenesis continue to progress and have led to the development of new treatments targeting pro-inflammatory cytokines. In particular, tumor necrosis factor-α inhibitors have become a mainstay of therapy for patients in whom therapy with anti-inflammatory drugs and/or disease-modifying anti-rheumatic drugs are inadequate or contraindicated. Compared to other JIA subtypes, ERA is associated with a poorer quality of life, worse function, and a higher likelihood of ongoing active disease after the initial treatment. Because the current guidelines for the management of ERA is not considered separately from other categories of JIA, there is a need for treatment guidelines specific to ERA to improve the overall disease outcomes.

Accuracy of maximal expiratory flow-volume curve curvilinearity and fractional exhaled nitric oxide for detection of children with atopic asthma / 소아과

PURPOSE: Airway pathology in children with atopic asthma can be reflected by the concave shape of the maximal expiratory flow-volume (MEFV) curve and high fractional exhaled nitric oxide (FeNO) values. We evaluated the capacity of the curvilinearity of the MEFV curve, FeNO, and their combination to distinguish subjects with atopic asthma from healthy individuals. METHODS: FeNO and angle β, which characterizes the general configuration of the MEFV curve, were determined in 119 steroid-naïve individuals with atopic asthma aged 8 to 16 years, and in 92 age-matched healthy controls. Receiver operating characteristic (ROC) curve analyses were performed to determine the cutoff points of FeNO and angle β that provided the best combination of sensitivity and specificity for asthma detection. RESULTS: Asthmatic patients had a significantly smaller angle β and higher FeNO compared with healthy controls (both, P<0.001). For asthma detection, the best cutoff values of angle β and FeNO were observed at 189.3° and 22 parts per billion, respectively. The area under the ROC curve for the combination of angle β and FeNO improved to 0.91 (95% confidence interval [CI], 0.87–0.95) from 0.80 (95% CI, 0.75–0.86; P<0.001) for angle β alone and 0.86 (95% CI, 0.82–0.91; P=0.002) for FeNO alone. In addition, the combination enhanced sensitivity with no significant decrease in specificity. CONCLUSION: These data suggest that the combined use of the curvilinearity of the MEFV curve and FeNO is a useful tool to differentiate between children with and without atopic asthma.

Relationships of bronchodilator response with asthma control and fractional exhaled nitric oxide in children with atopic asthma

PURPOSE: Because bronchodilator response (BDR) is variable among asthmatic patients, there are practical limitations in using BDR to assess asthma control. We investigated the relationships of BDR with asthma control status and fractional exhaled nitric oxide (FeNO) in children with atopic asthma. METHODS: One hundred ninety-one patients aged 8 to 16 years with atopic asthma were enrolled. Pulmonary function tests including BDR and FeNO were serially measured 10 times or more over 2 years when subjects were not receiving controller medications. During the last year of follow-up, the loss of asthma control was assessed in all participants. RESULTS: We identified 114 children (60%) with at least 1 positive BDR (> or =12%) over the 2-year observation period. Higher levels of BDRs and higher rates of positive BDRs were associated with lower lung function and lower methacholine PC20 (provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second). The loss of asthma control occurred in 106 of individuals (93%) who had positive BDRs, as compared to 52 of 77 (68%) with negative BDRs (P21 parts per billion than those who maintained asthma control (all P<0.001). CONCLUSION: Positive BDRs are linked to a higher probability of asthma control loss in children with atopic asthma. In addition, high FeNO is associated with asthma control loss in asthmatic children with negative BDRs.

House dust mite-specific immunoglobulin E and longitudinal exhaled nitric oxide measurements in children with atopic asthma / 소아과

PURPOSE: House dust mite (HDM) has been suggested to be the most important aeroallergen responsible for atopic asthma in Korea. We aimed to investigate that specific IgE antibodies to HDM and other common indoor aeroallergens contribute differently to total serum IgE and show different relationships with longitudinal fractional exhaled nitric oxide (FeNO) measurements in Korean atopic asthmatic patients. METHODS: A total of 193 children aged 8 to 16 years with intermittent or mild persistent atopic asthma were recruited. Sera were assayed for total IgE and specific IgE antibodies to HDM and other common indoor allergens. FeNO was serially measured 10 times or more over 2 years when subjects were not receiving controller medications. RESULTS: In 152 children who completed the study, IgE antibodies to specific HDM were more prevalent than those to other common indoor aeroallergens. In addition, IgE antibody titers to HDM were the strongest contributor to total IgE increases. Furthermore, only HDM-specific IgE antibody titer significantly correlated with maximum FeNO (r=0.21, P=0.029) and the rate of FeNO higher than 21 parts per billion (ppb) (r=0.30, P=0.002). Eight patients (5%) were found to have maximum FeNO of 21 ppb or less, suggesting the presence of a low FeNO phenotype among atopic asthmatic patients. CONCLUSION: The quantity of HDM-specific IgE antibody provides a possible explanation for increases of total IgE and significantly correlates with the amount and frequency of FeNO increases in Korean atopic asthmatic patients.

A Study of a Patient with Hypereosinophilic Syndrome Presenting with Generalized Cutaneous Blisters / 대한피부과학회지

Hypereosinophilic syndrome is a multisystem disorder with unexplained persistent eosinophilia and marked preference for systemic organ involvement. More than half of all patients have cutaneous involvement, usually presenting as angioedema, urticarial lesions, and eczematous, pruriginous papules. Hypereosinophilic syndrome presenting with generalized cutaneous blisters is rare, and we report the findings of a patient who was successfully treated with interferon-alpha.

Relationship between methacholine PC20 level and asthma control status among pediatric patients with atopic asthma

PURPOSE: Although methacholine PC20 helps clinicians to identify asthma, there are practical limitations in using methacholine PC20 to assess asthma control. We assessed the relationship between methacholine PC20 levels and asthma control status in child patients with atopic asthma. METHODS: We enrolled 153 children of 8 to 15 years of age with atopic asthma and measured methacholine PC20 of these children when their asthma was controlled. We followed up these patients for more than 2 years with measurements of asthma control score, lung function, bronchodilator response (BDR), and fractional exhaled nitric oxide (FeNO). RESULTS: The geometric mean of methacholine PC20 in the study population was 2.81 mg/mL. Lower methacholine PC20 was found to be associated with lower lung function, higher rate of BDR greater than 12%, higher level of BDR, higher rate of FeNO levels greater than 23 ppb, higher FeNO, higher numbers of asthma aggravation per year, and higher rate of asthma control test scores of 19 or less. CONCLUSION: These data provide evidences that the degree of methacholine PC20 is linked to disease severity in children with atopic asthma. Thus, regular and close monitoring of asthma control should be required for patients with lower levels of methacholine PC20.

Measurements of fractional exhaled nitric oxide in pediatric asthma / 소아과

Exhaled nitric oxide (NO) has been extensively investigated as a noninvasive marker of airway inflammation in asthma. The increased NO expression induced by inflammatory mediators in airways can be monitored easily in exhaled air from asthmatic children. Based on the relationship between the increased NO expression and eosinophilic airway inflammation, fractional exhaled nitric oxide (FeNO) measurements become an important adjunct for the evaluation of asthma. In addition, the availability of portable devices makes it possible to measure FeNO more easily and frequently in the routine pediatric practice. Despite various confounding factors affecting its levels, FeNO can be applicable in diagnosing asthma, monitoring treatment response, evaluating asthma control, and predicting asthma exacerbations. Thus, although pulmonary function tests are the standard tools for objective measurements of asthmatic control, FeNO can broaden the way of asthma monitoring and supplement standard clinical asthma care guidelines.

Tuberculous Pericarditis Presenting as Multiple Free Floating Masses in Pericardial Effusion

Pericarditis is a rare manifestation of tuberculosis (Tb) in children. A 14-yr-old Korean boy presented with cardiac tamponade during treatment of pulmonary tuberculosis. He developed worsening anemia and persistent fever in spite of anti-tuberculosis medications. Echocardiography found free floating multiple discoid masses in the pericardial effusion. The masses and exudates were removed by pericardiostomy. The masses were composed of pink, amorphous meshwork of threads admixed with degenerated red blood cells and leukocytes with numerous acid-fast bacilli, which were confirmed as Mycobacterium species by polymerase chain reaction. The persistent fever and anemia were controlled after pericardiostomy. This is the report of a unique manifestation of Tb pericarditis as free floating masses in the effusion with impending tamponade.

Prevalence of Primary Immunodeficiency in Korea

This study represents the first epidemiological study based on the national registry of primary immunodeficiencies (PID) in Korea. Patient data were collected from 23 major hospitals. A total of 152 patients with PID (under 19 yr of age), who were observed from 2001 to 2005, have been entered in this registry. The period prevalence of PID in Korea in 2005 is 11.25 per million children. The following frequencies were found: antibody deficiencies, 53.3% (n = 81), phagocytic disorders, 28.9% (n = 44); combined immunodeficiencies, 13.2% (n = 20); and T cell deficiencies, 4.6% (n = 7). Congenital agammaglobulinemia (n = 21) and selective IgA deficiency (n = 21) were the most frequently reported antibody deficiency. Other reported deficiencies were common variable immunodeficiencies (n = 16), X-linked agammaglobulinemia (n = 15), IgG subclass deficiency (n = 4). Phagocytic disorder was mostly chronic granulomatous disease. A small number of patients with Wiskott-Aldrich syndrome, hyper-IgE syndrome, and severe combined immunodeficiency were also registered. Overall, the most common first manifestation was pneumonia. This study provides data that permit a more accurate estimation PID patients in Korea.

Fractional exhaled nitric oxide and forced expiratory flow between 25% and 75% of vital capacity in children with controlled asthma / 소아과

PURPOSE: Fractional exhaled nitric oxide (FeNO) and forced expiratory flow between 25% and 75% of vital capacity (FEF25-75) are not included in routine monitoring of asthma control. We observed changes in FeNO level and FEF25-75 after FeNO-based treatment with inhaled corticosteroid (ICS) in children with controlled asthma (CA). METHODS: We recruited 148 children with asthma (age, 8 to 16 years) who had maintained asthma control and normal forced expiratory volume in the first second (FEV1) without control medication for > or =3 months. Patients with FeNO levels >25 ppb were allocated to the ICS-treated (FeNO-based management) or untreated group (guideline-based management). Changes in spirometric values and FeNO levels from baseline were evaluated after 6 weeks. RESULTS: Ninety-three patients had FeNO levels >25 ppb. These patients had lower FEF25-75% predicted values than those with FeNO levels 25 ppb.

Relevance of Exhaled Nitric Oxide Levels to Asthma Control Test Scores and Spirometry Values in Children with Atopic Asthma / 소아알레르기및호흡기학회지

PURPOSE: Fractional exhaled nitric oxide (FeNO) has been proposed as a tool for assessing airway inflammation in patients with atopic asthma. We evaluated the relationship between FeNO with asthma control test (ACT) scores and spirometry values in children with atopic asthma. METHODS: One hundred twenty-six children with atopic asthma, 8-16 years of age, were included in the study. None of the participants received regular controller therapy for at least 4 weeks before the study. The ACT (for children >12 years of age) or the Childhood Asthma Control Test (C-ACT; for children between the ages of 8 and 11 years of age), FeNO measurements and pulmonary function tests were performed. RESULTS: The geometric mean of the FeNO in children with atopic asthma (16.1 parts per billion [ppb]; 95% CI, 14.5-17.8 ppb) was significantly higher than that healthy controls (7.5 ppb; 95% CI, 7.0-8.1 ppb; P 20 in 82% of enrolled patients and correlated with the %FEV1, FEV1/FVC, and %FEF25-75. However, FeNO was not related to %FEV1, FEV1/FVC, %FEF25-75, and scores for asthma controls. FeNO levels in asthmatic children were not significantly different with respect to age, gender, BMI, and tobacco exposure. CONCLUSION: FeNO was not related to the spirometry values and scores for asthma control. Measurement of FeNO may be a complementary tool in the assessment of asthma control.

Pathogenesis and clinical manifestations of juvenile rheumatoid arthritis / 소아과

Juvenile rheumatoid arthritis (JRA) is the most common rheumatic childhood disease; its onset is before 16 years of age and it persists for at least 6 weeks. JRA encompasses a heterogeneous group of diseases that is classified according to 3 major presentations: oligoarthritis, polyarthritis, and systemic onset diseases. These presentations may originate from the same or different causes that involve interaction with specific immunogenetic predispositions, and result in heterogeneous clinical manifestations. An arthritic joint exhibits cardinal signs of joint inflammation, such as swelling, pain, heat, and loss of function; any joint can be arthritic, but large joints are more frequently affected. Extra-articular manifestations include high fever, skin rash, serositis, and uveitis. The first 2 types of JRA are regarded as T helper 1 (Th1) cell-mediated inflammatory disorders, mainly based on the abundance of activated Th1 cells in the inflamed synovium and the pathogenetic role of proinflammatory cytokines that are mainly produced by Th1 cell-stimulated monocytes. In contrast, the pathogenesis of systemic onset disease differs from that of other types of JRA in several respects, including the lack of association with human leukocyte antigen type and the absence of autoantibodies or autoreactive T cells. Although the precise mechanism that leads to JRA remains unclear, proinflammatory cytokines are thought to be responsible for at least part of the clinical symptoms in all JRA types. The effectiveness of biologic therapy in blocking the action of these cytokines in JRA patients provides strong evidence that they play a fundamental role in JRA inflammation.

Clinical characteristics of acute lower respiratory tract infections due to 13 respiratory viruses detected by multiplex PCR in children / 소아과

PURPOSE: This study was performed to investigate the epidemiologic and clinical features of 13 respiratory viruses in children with acute lower respiratory tract infections (ALRIs). METHODS: Nasopharyngeal aspirates were prospectively obtained from 325 children aged 15 years or less from May 2008 to April 2009 and were tested for the presence of 13 respiratory viruses by multiplex real-time-polymerase chain reaction (RT-PCR). RESULTS: Viruses were identified in 270 children (83.1%). Co-infections with > or =2 viruses were observed in 71 patients (26.3%). Respiratory syncytial virus (RSV) was the most common virus detected (33.2%), followed by human rhinovirus (hRV) (19.1%), influenza virus (Flu A) (16.9%), human metapneumovirus (hMPV) (15.4%), parainfluenza viruses (PIVs) (8.3%), human bocavirus (hBoV) (8.0%), adenovirus (ADV) (5.8%), and human coronavirus (hCoV) (2.2%). Clinical diagnoses of viral ALRIs were bronchiolitis (37.5%), pneumonia (34.5%), asthma exacerbation (20.9%), and croup (7.1%). Clinical diagnoses of viral bronchiolitis and pneumonia were frequently demonstrated in patients who tested positive for RSV, hRV, hMPV, or Flu A. Flu A and hRV were most commonly identified in children older than 3 years and were the 2 leading causes of asthma exacerbation. hRV C was detected in 14 (4.3%) children, who were significantly older than those infected with hRV A (mean+/-SD, 4.1+/-3.5 years vs. 1.7+/-2.3 years; P=0.009). hBoV was usually detected in young children (2.3+/-3.4 years) with bronchiolitis and pneumonia. CONCLUSION: This study described the features of ALRI associated with 13 respiratory viruses in Korean children. Additional investigations are required to define the roles of newly identified viruses in children with ALRIs.

Relationship of Indoor Aeroallergen Specific IgE with Total IgE and Airway Hyperresponsiveness in Children with Atopic Asthma / 소아알레르기및호흡기학회지

PURPOSE:We assessed the relationship of indoor aeroallergen specific IgE levels with total IgE level, airway hyperresponsiveness (AHR) and lung function in children with atopic asthma. METHODS:Two hundred twenty-eight children with atopic asthma in Cheongju area were studied. Sera were assayed for total IgE and specific IgE antibodies to important indoor allergens including Dermatophagoides pteronyssinus (Der p), Dermatophagoides farinae (Der f), Alternaria, cats, dogs, and cockroaches. One hundred eighty children sensitized to house dust mites (HDMs) were evaluated for %FEV1 and methacholine PC20. RESULTS:Serum specific IgE to HDMs presented the highest prevalence (90.0% for Der p and 92.7% for Der f), followed by specific IgE to Alternaria (21.6%). A contribution of > 10% of the total was only common for IgE antibody to Der p or Der f. The level of specific IgE to Der p (r=0.677, P<00.001) or Der f (r=0.657, P<00.001) was significantly correlated with total IgE level. Higher level of Der f-specific IgE was associated with higher incidence of AHR and FEV1 decline. CONCLUSION:Concentration of specific IgE antibody produced to HDMs provides an explanation for the higher total IgE levels found in a major portion of children with atopic asthma and has a close relationship with AHR and lung function.

Correlation of Serum Chemokine Levels with SCORAD Index in Children with Atopic Dermatitis / 소아알레르기및호흡기학회지

PURPOSE:CCL17, CCL27 and CCL18 have attracted significant interest with regard to understanding the mechanisms of T cell trafficking. We tested whether levels of serum CCL17, CCL27 and CCL18 would be useful markers for atopic dermatitis (AD) in children. METHODS:Serum concentrations of CCL17, CCL27, CCL18, total IgE and eosinophil cationic protein (ECP) in AD (n=40) and healthy control (n=40) children were compared. The correlation between the studied parameters and activity of AD was investigated. The severity of AD was assessed according to the SCORAD (scoring atopic dermatitis) index. The serum concentrations of CCL17, CCL27 and CCL18 were measured by means of ELISA. RESULTS:The levels of all studied parameters were significantly higher in children with AD than those of control subjects. A positive correlation was found between the levels of CCL17, CCL18 and CCL27 and the SCORAD index in AD children (P<0.05, P<0.001 and P<0.001) The correlation of CCL17 and CCL27 concentrations with severity appears to be age-dependent because a stronger correlation was found in AD children over the age of 2 years than those with younger than 2 years of age. A weaker correlation in AD children younger than 2 years may be attributed to higher concentrations of these chemokines because higher concentrations of these chemokines were detected in control subjects younger than 2 years (CCL17=205+/-281 pg/mL, CCL27=999+/-783 pg/mL) than those of older than 2 years.(CCL17=49+/-54 pg/mL; P= 0.012, CCL27=630+/-820 pg/mL; P=0.041, respectively) CONCLUSION:Our findings suggest that levels of serum CCL17, CCL27 and CCL18 can be used as useful markers for the severity of AD.

The Correlation between Increased Sensitization Rate to Weeds in Children and the Annual Increase in Weed Pollen in Korea / 소아알레르기및호흡기학회지

PURPOSE: Recently allergic diseases have gradually increased in schools and among preschool aged childhood. Pollen amount of weeds also, especially ragweed, were increased. We evaluated the increased pollen count of weed was associated with the sensitization rate to weed in childhood. METHODS: Airborne particles carrying allergens were collected daily from eight stations nationwide(Seoul, Guri, Cheongju, Daegu, Kwangju, Busan, Kangneung, and Jeju) by using 7 days-Burkard sampler(Burkard Manufacturing Co Ltd, Hertfordshire, UK), for 7 years in South Korea(July 1, 1997-June 30, 2004). They were counted and recorded along with the weather. Data was collected through pediatric patients with allergic symptoms, who visit the pediatrics allergy clinics and capable of allerfy skin test among hospitals that have pollen collecting centers. RESULTS: Airborne pollen has two peak seasons:May and September in Korea. There were the tree pollen seasons from the middle of February to late July, then followed the grasses and weed season from the middle of July to the end of October. Ragweed was one of the most common pollens of autumn in Korea. In skin prick tests, Mugwort was the highest sensitization rate(7.6 percent), followed by ragweed(7.1 percent), birch(6.1 percent), alder, grasses mix among the pollen extracts in Korean school aged children. Ragweed pollen counts have gradually increased since 2000. In the same period, sensitization rates for airborne pollen, especially weeds, in Korean children have increased annually(1999:4.4 percent, 2000:7.1 percent, 2001:7.4 percent, 2002:8.5 percent, 2003:7.7 percent). CONCLUSION: Sensitization rates for outdoor airborne pollens have increased in Korean children. These findings might result from the changes of life styles and living environments in Korea.

Association of IL-10 Gene Polymorphism with Development of Atopy / 소아알레르기및호흡기학회지

PURPOSE: There has been accumulating evidence that interleukin-10 (IL-10) influences on the production of proinflammatory cytokines, regulating the development of atopic diseases. In this study, we tested the genetic association between IL-10 haplotype polymorphism and the development of atopy. METHODS: The frequency of three single nucleotide polymorphisms (SNPs) at positions- 1082 (A/G), -819 (C/T), -592 (A/C) and corresponding haplotypes in the promotor region of the IL-10 gene were analysed in 174 atopic and 130 non-atopic children using Taqman method. The data were assessed for correlations with the eosinophil count and total serum IgE concentration. RESULTS: Three haplotypes (ATA, ACC, GCC) were identified without any ambiguous phasing due to linkage disequilibrium among SNPs. The frequency of IL-10 haplotype ACC was higher in non-atopic children compared to atopic children. (P=0.04) The frequency of IL-10 haplotype ATA was higher in atopic children compared to non-atopic children, but a statistical significance was not found. (P=0.099) ATA/ATA and ATA/ACC accounted for 80 percent of six different genotypes. Although the frequency of ATA/ATA genotype was higher in atopic children, there was no statistical significance. Although medians of serum IgE level and total eosinophil count were higher among atopic children with ATA/ATA genotype than in atopic children with ATA/ACC, no statistical significance was found. CONCLUSION: These results suggest that IL-10 promotor polymorphism may be associated with a genetic risk factor for the development of atopy in Korean children.

Expression and Purification of the Capsid Protein of the Japanese Encephalitis Virus and Production of its Polyclonal Antibody

Japanese encephalitis virus (JEV) is a member of Flaviviruses, transmitted by mosquitoes. The core of JEV is composed of the capsid (C) proteins. In order to produce the recombinant viral C protein and the antiserum specifically recognizing the JEV C protein, we have expressed and purified the JEV C protein as a Glutathion-S-Transferase (GST) fusion protein in E. coli. The JEV C protein-coding region was PCR-amplified using the infectious cDNA of a JEV Korean isolate, and the amplicons were cloned into the pGEX4T-1 E. coli expression vector. GST-C fusion proteins were purified using a glutathione sepharose column. Subsequently, the GST-C fusion proteins were used for immunization of rabbits, and the antisera were obtained from those immunized animals. Western blot analysis using the JEV-infected BHK21 cell lysates showed that these antisera specifically reacted with the JEV C proteins. This study will provide a useful reagent for the diagnosis and understanding of the viral morphogenesis in the JEV-infected cells.

Correlation of Appearance of Nasal Eosinophils with Levels of Total Eosinophil Counts, Total IgE, and House Dust Mite Specific IgE in Children with Symptoms of Rhinitis / 소아알레르기및호흡기학회지

PURPOSE: Nasal cytology for eosinophils has been reported to be very useful for the diagnosis of allergic rhinitis. The purpose of this study is to describe the relationship of the appearance of nasal eosinophils with the levels of total eosinophil counts, total IgE, and house dust mite specific IgE in child patients with symptoms of rhinitis. METHODS: Two hundred seventy eight children with symptoms of rhinitis less than 16 years of age were recruited and evaluated for the following variables: total eosinophil counts, total IgE concentrations, house dust mite specific IgE concentrations, and nasal cytology for eosinophils. RESULTS: The rate of appearance of nasal eosinophils graded as positive rose as the children's age increased. The levels of total eosinophil counts, total IgE concentrations and house dust mite-specific IgE concentrations were significantly higher in children with nasal eosinophils graded as positive than those with less than 5 percent of nasal eosinophils. The rates of appearance of nasal eosinophils graded as positive below and above 250/microL of total eosinophil counts, 250 kUa/L of total IgE concentrations, and 2 kUa/L of house dust mite (D. pteronyssinus or D. farinae) specific IgE concentrations were 16 and 41 percent, 27 and 56 percent, and 13 and 68 percent, respectively CONCLUSION: The levels of total eosinophil counts, total IgE concentrations, and house dust mite specific IgE concentrations correlate significantly with the recovery of nasal eosinophils in children with symptoms of rhinitis.

Detection and Diagnosis of Primary Immunodeficiency Diseases / 소아과

Primary immunodeficiency diseases result from innate defects of immune system. As a consequence, recurrent viral, bactrial, fungal, and protozoal infections of varying severity ensue. Although primary immunodeficiency diseases are relatively rare, intensive study of these disorder has expanded our understanding of immunity. Recent progress in immunobiology and genetics has identified the causes of many of the primary immunodeficiency diseases. Diagnosis and therapy can as a result be more specific and effective. Appreciation of the genetic nature of a host immunologic defect makes possible family counseling, carrier detection and prenatal diagnosis. A high index of suspicion and prompt diagnosis of patients with primary immunodeficiency diseases can led to lifesaving treatment or significant improvement in quality of life. Therefore, it is critical for the primary care provider to maintain an index of suspicion for immunodeficiency.