Aeroallergen sensitization in school-age children with allergic rhinitis: What has changed during the COVID-19 pandemic?

BACKGROUND: Pandemic period may affect aeroallergen sensitization. OBJECTIVE: The study aimed to investigate changes in allergen sensitivities of skin prick test (SPT) in patients with allergic rhinitis (AR) during pandemic and to evaluate relationship with disease severity. METHODS: In all, 164 AR patients with or without asthma, aged 6-17 years, who have undergone SPTs prior to the pandemic and after October 1, 2021 (18th month of the pandemic), were evaluated retrospectively. The wheal size of allergens in performed SPTs during and prior to the pandemic were compared. Detected changes in allergen sensitivities via SPT results were compared with changes in the disease severity parameters (AR severity, asthma severity, and the number of asthma exacerbations per year), frequency of upper respiratory tract infections and antibiotic use, laboratory parameters, demographic characteristics, and visual analogue scores (VAS). RESULTS: House dust mites (HDMs), cat, pollen, Artemisia, and Cupressus sensitization increased in AR patients during the Coronavirus disease 2019 (COVID-19) pandemic. HDM, mold, and pollen wheal diameters increased in SPTs. Proportion of polysensitization increased during the pandemic, compared to pre-pandemic period (9.1% vs 3%; P < 0.001), and number of non-sensitized patients decreased during the pandemic period compared to the pre-pandemic period (7.9% vs 22.6%; P < 0.001). An increase in HDM sensitivity in SPTs was correlated with VAS for nasal blockage, and an increase in cat sensitivity was correlated with VAS for all nasal symptoms. CONCLUSION: We believe that inhalant allergen sensitization might have been affected by the lifestyle changes of patients during the pandemic. Hence, it is important to evaluate patients for allergen sensitization, especially patients with moderate/severe AR, to revise disease control measurements.

Aeroallergen sensitization in school-age children with allergic rhinitis: What has changed during the COVID-19 pandemic?

Background: Pandemic period may affect aeroallergen sensitization. Objective: The study aimed to investigate changes in allergen sensitivities of skin prick test (SPT) in patients with allergic rhinitis (AR) during pandemic and to evaluate relationship with disease severity. Methods: In all, 164 AR patients with or without asthma, aged 6–17 years, who have undergone SPTs prior to the pandemic and after October 1, 2021 (18th month of the pandemic), were evaluated retrospectively. The wheal size of allergens in performed SPTs during and prior to the pandemic were compared. Detected changes in allergen sensitivities via SPT results were compared with changes in the disease severity parameters (AR severity, asthma severity, and the number of asthma exacerbations per year), frequency of upper respiratory tract infections and antibiotic use, laboratory parameters, demographic characteristics, and visual analogue scores (VAS). Results: House dust mites (HDMs), cat, pollen, Artemisia, and Cupressus sensitization increased in AR patients during the Coronavirus disease 2019 (COVID-19) pandemic. HDM, mold, and pollen wheal diameters increased in SPTs. Proportion of polysensitization increased during the pandemic, compared to pre-pandemic period (9.1% vs 3%; P < 0.001), and number of non-sensitized patients decreased during the pandemic period compared to the pre-pandemic period (7.9% vs 22.6%; P < 0.001). An increase in HDM sensitivity in SPTs was correlated with VAS for nasal blockage, and an increase in cat sensitivity was correlated with VAS for all nasal symptoms. Conclusion: We believe that inhalant allergen sensitization might have been affected by the lifestyle changes of patients during the pandemic. Hence, it is important to evaluate patients for allergen sensitization, especially patients with moderate/severe AR, to revise disease control measurements (AU)

Assessment of intracellular zinc levels in infants with food protein-induced allergic proctocolitis.

BACKGROUND: Food protein-induced allergic proctocolitis (FPIAP) is characterized by bloody stools in well-appearing infants. Zinc is a micronutrient that plays a crucial role in immune modulation and is essential for cellular function during immune response. Although there are studies on the assessment of intracellular zinc levels in allergic diseases, no data is available on erythrocyte zinc levels of patients with FPIAP. OBJECTIVE: This study aimed to assess the erythrocyte zinc levels of children with allergic proctocolitis and compare zinc levels with clinical and demographic characteristics. METHODS: This was a case-control study that prospectively compared 50 patients with FPIAP and 50 healthy children without malnutrition. The erythrocyte zinc levels of children were determined using atomic absorption spectrophotometry. RESULTS: Fifty patients with FPIAP, including 28 (51%) girls, with median age of 7.1 ± 2.9 (3-14) months and 50 healthy children, including 26 (53.1%) girls, with median age of 7.7 ± 2.8 (3-13) months were included in the study. Seventy percent (n = 35) of the patients with FPIAP started to have symptoms while they were exclusively breastfeeding. Offending allergen foods were cow's milk (78%), egg (40%), sesame (10%), hazelnut (8%), almond (6%), beef (6%), and peanuts (6%, n = 3). Intracellular (erythrocyte) zinc levels in patients with FPIAP were lower than in the healthy control group (495.5 ± 134 µg/dL, 567.3 ± 154.4 µg/dL, respectively, P = 0.01). Patients with FPIAP aged younger than 6 months had lower intracellular zinc levels compared with those aged above 6 months (457 ± 137 µg/dL; 548 ± 112 µg/dL, respectively, P = 0.01). There was no relationship between zinc levels and time of symptom onset, presence of concomitant disease, being allergic to multiple foods, and family history of atopy (P > 0.05). CONCLUSIONS: FPIAP is a food allergy with limited information on its pathogenesis. Considering the beneficial effects on gastrointestinal system epithelia, zinc may be involved in the pathogenesis of FPIAP. Future comprehensive prospective research on this subject is of importance.

Assessment of intracellular zinc levels in infants with food protein–induced allergic proctocolitis

Background: Food protein–induced allergic proctocolitis (FPIAP) is characterized by bloody stools in well-appearing infants. Zinc is a micronutrient that plays a crucial role in immune modulation and is essential for cellular function during immune response. Although there are studies on the assessment of intracellular zinc levels in allergic diseases, no data is available on erythrocyte zinc levels of patients with FPIAP. Objective: This study aimed to assess the erythrocyte zinc levels of children with allergic proctocolitis and compare zinc levels with clinical and demographic characteristics. Methods: This was a case–control study that prospectively compared 50 patients with FPIAP and 50 healthy children without malnutrition. The erythrocyte zinc levels of children were determined using atomic absorption spectrophotometry. Results: Fifty patients with FPIAP, including 28 (51%) girls, with median age of 7.1 ± 2.9 (3–14) months and 50 healthy children, including 26 (53.1%) girls, with median age of 7.7 ± 2.8 (3–13) months were included in the study. Seventy percent (n = 35) of the patients with FPIAP started to have symptoms while they were exclusively breastfeeding. Offending allergen foods were cow’s milk (78%), egg (40%), sesame (10%), hazelnut (8%), almond (6%), beef (6%), and peanuts (6%, n = 3). Intracellular (erythrocyte) zinc levels in patients with FPIAP were lower than in the healthy control group (495.5 ± 134 µg/dL, 567.3 ± 154.4 µg/dL, respectively, P = 0.01). Patients with FPIAP aged younger than 6 months had lower intracellular zinc levels compared with those aged above 6 months (457 ± 137 µg/dL; 548 ± 112 µg/dL, respectively, P = 0.01). There was no relationship between zinc levels and time of symptom onset, presence of concomitant disease, being allergic to multiple foods, and family history of atopy (P > 0.05). Conclusions: FPIAP is a food allergy with limited information on its pathogenesis (AU)

Cut-Off Values of Specific IgE and Skin Prick Test to Predict Oral Food Challenge Positivity in Children with Cow's Milk Allergy.

OBJECTIVE: The cut-off values for the skin prick test diameters and cow's milk-specific IgE measurements are used to predict the result of the oral food challenge test for the diagnosis of cow's milk allergy. This study aimed to determine the diagnostic values of skin prick test and cow's milk-specific IgE according to age groups and compare the diagnostic powers of these 2 methods. MATERIALS AND METHODS: In total, 153 children who had a preliminary diagnosis of cow's milk allergy were evaluated. Group A (n = 90) consisted of cow's milk allergy patients whose diagnosis was confirmed by a positive oral food challenge or a history of anaphylaxis. Group B (n = 63) was composed of patients with a negative oral food challenge. The demographic, clinical, and laboratory findings of 2 groups were compared. RESULTS: The cut-off points for cow's milk-specific IgE and cow's milk-skin prick test were determined as >2.12 kUA/L and >5 mm, respectively. The area under the curve was 0.844 for cow's milk-skin prick test (sensitivity 73%, specificity 84%) and 0.745 for cow's milk-specific IgE (sensitivity 67%, specificity 86%). The diagnostic power of skin prick test was determined to be higher when compared to cow's milk-specific IgE (P = .02). According to the predicted probability curves, decision points for cow's milk-specific IgE and cow's milk-skin prick test with 95% probability were determined as follows, respectively: for ≤24 months: 22 kUA/L, 11.3 mm; for >24 months: 44.1 kUA/, 15.1 mm. The lowest cut-off value with a positive predictive value of 95% and a specificity of 96% was found in patients 3.3 kUA/L) Conclusion: The use of high probability diagnostic values of communities for specific IgE and skin prick test along with a significant clinical history may provide accurate and rapid diagnosis of cow's milk allergy and facilitate patient follow-up.

Immunologic changes during desensitization with cow's milk: How it differs from natural tolerance or nonallergic state?

BACKGROUND: Oral immunotherapy (OIT) is a novel allergen-specific treatment for food allergies. OBJECTIVE: To investigate the effect of OIT on blocking antibodies, T cell regulation, and cytokine response during immunoglobulin (Ig)E-mediated cow's milk allergy (CMA) treatment. METHODS: A total of 59 children with IgE-mediated CMA who were followed in pediatric allergy outpatient clinic and 18 healthy children were included. The children were evaluated in the following 4 groups: OIT group, elimination group (patients receiving dairy elimination diet), tolerance group (patients who developed tolerance), and healthy control group. Milk-specific IgE, IgG4, and IgA levels, cow's milk induration diameters in skin prick test, CD4 + CD25 + FoxP3 + Treg cell percentages, messenger RNA (mRNA) expressions, and interleukin (IL)-10, transforming growth factor-beta (TGF-ß), IL-2, IL-4, and IL-13 cytokine levels were compared between the groups. RESULTS: The mean age of the patients was 42.6 ± 39 (6-201) months, and 63.6% (n = 49) of the patients were girls. We observed an increase in total IgE levels (P = .02), a decrease in cow's milk sIgE (P = .08, NS), and an increase in cow's milk component (ß-lactoglobulin and casein) specific IgA (P < .05) and IgG4 (P < .001) levels at 2 months after the maintenance phase of OIT. In addition, the immune response after OIT treatment, which had a 100% clinical success rate, was notable for similar CD4 + CD25 + FoxP3 + cell percentages (P = .8), and increased IL-10 (P = .04) levels and increased but statistically nonsignificant TGF-ß levels (P = .17) compared with those before treatment. FoxP3 mRNA expression was similar to that of patients who developed natural tolerance. Pretreatment and post-treatment FoxP3 mRNA-FoxP3 flow cytometric expressions were positively correlated with TGF-ß concentrations in the OIT group. CONCLUSION: A successful immune response to OIT was found, possibly through the blockage of IgE-mediated allergen presentation by blocking antibodies, marked IL-10 cytokine response, and TGF-ß response. FoxP3 mRNA expression was similar to the natural tolerance mechanism, but more studies are needed.

Could Age and Oral Challenge Outcomes Identify High-Risk Patients During Cow's Milk Oral Immunotherapy?

Objective: Severe immunglobuline E (IgE)-mediated reactions during oral immunotherapy (OIT) are major obstacles to treatment. The present study aimed to evaluate and identify clinical and laboratory biomarkers of adverse events during OIT among children with cow's milk (CM) allergy. Study Design: Eighty-six children older than 36 months who had undergone OIT with milk were enrolled. Clinical data, oral food challenge (OFC) test results, and laboratory data were recorded retrospectively. Results: The median duration of the build-up phase of OIT was 19 weeks (min 10-max 40) and the duration of the maintenance phase was 86.5 (min 1-max 132) months. A total of 11,767 CM doses were administered during the build-up phase and adverse reactions were seen in 62 (73.8%) patients with reactions registered for 157 doses among 11,767 (1/75 doses). The number of reactions during the maintenance phase was 41 (47.6%) in 24 (27.9%) patients. There was a significant reduction in the number of reactions (P = 0.000) between the build-up phase and maintenance phase. Adverse reactions and anaphylaxis were higher for patients who had cough during OFC (P = 0.003, P = 0.002, respectively) during the build-up phase and also during the maintenance phase too (P = 0.000). Evaluation for all reactions and anaphylaxis (during build-up and maintenance) with Kaplan-Meier and Cox regression analysis showed class IV-VI of CM-specific immunoglobulin E (sIgE), casein-sIgE and cough during OFC were significantly associated with increased probability of reaction and anaphylaxis. Younger age at onset of OIT was associated with risk reduction (0.017). Conclusion: Laboratory data and reactions during the OFC (especially cough) can help to identify high-risk patients during OIT.

Effects of Cow's Milk Components, Goat's Milk and Sheep's Milk Sensitivities on Clinical Findings, and Tolerance Development in Cow's Milk Allergy.

OBJECTIVE: Cow's milk (CM) contains some proteins capable of causing an allergic reaction in a sensitized individual and one of the most common causes of food allergy in childhood. Most of the patients will develop tolerance by the age of 3. In this study, we aimed to evaluate sensitivity to CM allergen components as well as goat's milk (GM) and sheep's milk cross reactions in cow's milk allergic (CMA) patients and to figure out the risk factors for tolerance non-development. METHODS: This is a retrospective cross-sectional study including 66 patients for IgE-mediated CMA with mean age of 38 months. We evaluated the patients in two groups: Group 1 (n=50): Patients who have no tolerance in oral food challenge test; Group 2 (n= 16): Patients who were found tolerant to CM after elimination diet. Cow's milk-spesific IgE(sIgE), α-lactalbumin(ALA)-sIgE, ß-Lactoglobulin(BLG)-sIgE, casein-sIgE, goat's milk-sIgE, sheep's milk-sIgE, skin prick tests(SPTs) with CM and GM, eosinophils in peripheral blood were all compared between two groups. RESULTS: In the whole group, goat's milk-sIgE and sheep's milk-sIgE were positive in 84.8% and ALA-sIgE, BLG-sIgE, casein-sIgE were positive in 69.7%, 62.7%, 77.3% of the patients, respectively. Two groups were similar in terms of age at onset and diagnosis, gender, median elimination period, total IgE levels, cow's milk-sIgE and eosinophilia (p>0.05). Mean wheal diameters of CM and GM in SPT (p<0.001), goat's milk-sIgE (p=0.03), sheep's milk-sIgE (p=0.01) were significantly higher in Group 1. Cow's milk-sIgE showed a positive correlation with total IgE (p=0.001), eosinophilia percentage (p=0.04), CM wheal diameter in SPT (p=0.001), casein-sIgE (p<0.001), goat's milk-sIgE (p<0.001), sheep's milk-sIgE (p<0.001) in Group 1. Patients with respiratory symptoms and history of anaphylaxis had higher cow's milk-SPT, cow's milk-sIgE, casein-sIgE, goat's milk-sIgE, sheep's milk-sIgE levels(p<0.05). Gastrointestinal and skin symptoms showed no relation with laboratory findings. Any patient with a history of anaphylaxis did not develop tolerance. CONCLUSIONS: As with cow's milk-sIgE levels and high induration diameters in SPT; high casein-sIgE, sheep's milk-sIgE and goat's milk-sIgE levels are also risk factors for persistence of CMA. Anaphylaxis, as a first reaction, may also be a risk factor. High cow's milk-sIgE, casein-sIgE, sheep's milk-sIgE, goat's milk-sIgE levels are associated with respiratory symptoms.

Proven Food-Induced Acute Urticaria and Predictive Factors for Definitive Diagnosis in Childhood.

BACKGROUND: Urticaria can be the only sign of a food allergy or can be seen together with other signs and symptoms of a food allergy. OBJECTIVE: To determine the demographic, etiologic, and clinical features of food-induced acute urticaria in childhood. METHODS: Patients suspected of food-induced acute urticaria were included in this prospective cross-sectional multicenter study. RESULTS: Two hundred twenty-nine urticaria cases were included in this study. Seventeen patients who did not meet the inclusion criteria of the study were excluded. Of the 212 included cases, 179 (84.4%) were diagnosed with definitive food-induced acute urticaria. The most common foods causing acute urticaria were cow's milk, hen's eggs, and nuts in 56.4, 35.2, and 19% of cases, respectively. The positive predictive value of a history of milk-induced acute urticaria together with a milk-specific IgE >5 kU/L for cow's milk-induced acute urticaria was 92% (95% CI: 81-96%). A history of cow's milk-induced and/or hen's egg-induced acute urticaria was consistent with a definitive diagnosis of food-induced urticaria (Chen's kappa: 0.664 and 0.627 for milk and eggs, respectively). Urticaria activity scores were higher in patients with food-induced acute urticaria (p = 0.002). CONCLUSION: Cow's milk, hen's eggs, and nuts were the most common allergens in the etiology of childhood food-induced acute urticaria. Although the urticaria activity score provides guidance for diagnosis, an oral food challenge is often essential for the definitive diagnosis of a patient with a history of food-induced acute urticaria.

Oral Immunotherapy for Cow's Milk Allergy: Five Years' Experience from a Single Center in Turkey

Background: Oral immunotherapy for cow's milk allergy is an effective treatment option because of its ability to increase the threshold for clinical reactions. Aims: To present our experience of oral immunotherapy for cow's milk allergy in the pediatric allergy outpatient clinic, and to evaluate the long-term efficacy of oral immunotherapy and risk factors for adverse reactions during oral immunotherapy. Study Design: Single-center retrospective cohort study. Methods: Forty-two patients with Immunoglobulin-E-mediated cow's milk allergy who complied with the oral immunotherapy protocol were evaluated in this study. The treatment consisted of a rapid escalation phase with an oral food challenge step that included milk doses. During the build-up phase, increasing quantities of cow's milk were administered until the patient was able to consume 200 mL of cow's milk daily. Results: The mean age of starting the oral immunotherapy was 40.2±3.2 (range, 36-156) months, and 54.8% (n=23) of the patients were males. The mean duration of the build-up phase was 18.1±5.6 (range, 9-41) weeks, and the mean maintenance phase was 29.1±11.6 (range, 12-63) months. During the oral immunotherapy, 36 adverse reactions (78% mild and 22% moderate) occurred in 16 (38%) patients. There were no differences in the age of starting the oral immunotherapy (p=0.19), cow's milk-specific Immunoglobulin-E levels (p=0.17), and cumulative provocative doses of oral food challenges (p=0.78) between the two groups of patients with and without adverse reactions. The wheal diameters to cow's milk were higher in the group with adverse reactions (p=0.03). There was no difference in the oral immunotherapy onset age between patients with and without a history of anaphylaxis (p=0.38). The patients with a history of anaphylaxis had more adverse reactions (p=0.04) and a higher number of reactions during the oral immunotherapy (p=0.01), and a higher mean duration of the up-dosing phase (p=0.04) compared with patients without anaphylaxis. Conclusion: Oral immunotherapy is a treatment option in patients with cow's milk allergy because of its high efficacy. Adverse reactions occur in about 40% of cases and are mostly mild. It should be administered with caution to patients with a history of anaphylaxis and a higher wheal diameter to cow's milk in the skin prick test.

Successful Desensitization Protocol in an Infant Following Anaphylaxis Secondary to Recombinant Factor VIIa.

Background: Recombinant factor VIIa (rFVIIa) is a highly purified recombinant protein. It is approved for the treatment and prevention of bleeding episodes associated with congenital factor VII deficiency, congenital hemophilia with inhibitors, and Glanzmann's thrombasthenia. The most commonly reported adverse events are thrombolytic in nature. In this report, we present a successful desensitization protocol administered to an infant with a history of anaphylaxis to rFVIIa. Case: A male infant with a history of gingival bleeding at the age of 6 months was diagnosed with factor VII deficiency with a factor VII level of 1%. His sister also had diagnosis of factor VII deficiency. Our patient was hospitalized at 10 months of age with generalized petechiae and bloody stools. Twenty minutes after administration of rFVIIa, he developed anaphylaxis that responded to epinephrine and supportive care. Subsequently he was evaluated at the allergy clinic, where a skin prick test with rFVIIa was negative. However, the intradermal skin test, applied with 1/1,000 (1 µg/1 mL, 0.1 mL) dilution of rFVIIa, showed induration of 8 mm (positive reaction). Because there is no alternative treatment for factor VII deficiency, we developed a successful 13-step desensitization protocol with rFVIIa (NovoSeven®). Desensitization was performed an additional 2 times using the same protocol, one of which was for a head injury and the other for a swollen knee since the period between the doses was ∼3 months. Conclusion: Allergic reactions, such as anaphylaxis can occur without prior exposure. This can be due to the high molecular weight and structural property of the biological agent. In this report, we present an effective desensitization protocol for an infant with a history of anaphylaxis to rFVIIa. Desensitization protocols in this age group should be carried out in a medical facility and with specialized staff and equipment prepared to care for anaphylaxis.

Familial inheritance and screening of first-degree relatives in common variable immunodeficiency and immunoglobulin A deficiency patients.

Common variable immunodeficiency (CVID) and immunoglobulin A deficiency (IgAD) are the most prevalent primary immunodeficiency disorders. High rates of familial inheritance have been described in CVID and IgAD, but it is unknown in different ethnic populations. We aimed to determine the prevalence of familial cases and whether they showed more severe clinical characteristics than sporadic ones in Turkish patients. A total of 40 CVID and 70 IgAD patients and their 251 first-degree relatives (FDRs) were evaluated. Demographic, clinical, and laboratory data were reviewed. A familial case was defined as a patient with at least one affected FDR (A-FDR). The rate of parental consanguinity was 19.1%. There were 37 familial cases (37/110) (33.6%) with at least one A-FDR. There were 48 A-FDRs who had immunoglobulins lower than age-related normals (48/251) (19.1%). Pulmonary infections were significantly higher in familial cases. To our knowledge, this study includes the highest number of CVID/IgAD patients and their FDRs in literature. Familial cases are at least 30% of the IgAD and CVID patients, and they have more frequent lower respiratory tract infections than sporadic ones, so these patients have to be evaluated depending on their being familial or sporadic for better management. The risk of carrying any immunologic alterations in relatives of patients with IgAD and CVID is approximately 20%. Although most A-FDRs are asymptomatic, considering the risk of progression to CVID by age, we highly recommend routine screening for FDRs.

A successful desensitization protocol for horse-derived antithymocyte globulin in severe aplastic anemia.

BACKGROUND: Horse antithymocyte globulin (h-ATG) (ATGAM(®) ) is the first choice of treatment in very severe patients with aplastic anemia who do not have any HLA matched sibling donor. h-ATG is a heterologous serum that may cause anaphylaxis. Alternative treatment strategies must be planned in case of hypersensitivity. Desensitization must be considered in patients without an alternative treatment of choice. We aimed to present the h-ATG desensitization protocol and consider its effectiveness in patients with aplastic anemia who are hypersensitized with h-ATG and do not have an alternative treatment of choice. METHODS: Skin prick tests were performed with non-diluted solution in eight very severe patients with aplastic anemia who are followed up in Ege University Children's Hospital. Although skin prick test was found negative in these eight patients, different dilution h-ATG intradermal tests were performed and found positive in all patients. h-ATG desensitization program was started to these hypersensitized patients. RESULTS: Desensitization program was started to six male and two female very severe patients with aplastic anemia whose ages were between seven and 19 yr (median: 12.9 yr). All of the patients completed the desensitization program. While local reaction was seen in two patients, systemic reaction was seen in one patient and late reaction was seen in one patient during and after desensitization program. CONCLUSION: A successful desensitization program with h-ATG in children with aplastic anemia is presented. Even though there is not an exposure before to such high allergy potential heterologous serum, skin tests should be performed and desensitization must be started to patients who are hypersensitized to h-ATG. As the expected effectiveness of the treatment is so much, the desensitization protocol can be carried out safely and effectively with trained stuff although allergic reactions can be seen.

A novel disease-causing CD40L mutation reduces expression of CD40 ligand, but preserves CD40 binding capacity.

Mutations in CD40 ligand (CD40L) that permit residual CD40L expression typically impair binding of CD40. We report a male patient who presented with recurrent bacterial respiratory tract infections, normal IgM, decreased IgG, absent IgA levels, and CD40L expression at ~50% of the level observed in the normal control. He subsequently developed autoimmunity, inflammatory bowel disease, severe opportunistic infections suggestive of a combined immunodeficiency, and a cervical spine schwannoma. Whole exome sequencing of the patient's genomic DNA revealed a novel missense mutation (p.H47Y) in CD40L. Although this mutation was predicted to be benign in silico, flow cytometry at 13 years of age demonstrated markedly decreased CD40L expression (~32% of normal control) that retained the capacity to bind soluble CD40-Ig, suggesting that the mutation impairs CD40L surface expression without affecting its affinity for CD40. This case highlights the variability in the clinical evolution and phenotype of CD40L deficiency.

Brucellosis presenting with pancytopenia due to hemophagocytic syndrome.

Reactive hemophagocytic syndrome is clinically characterized by fever, hepatosplenomegaly, pancytopenia, and coagulopathy, and is histologically characterized by excessive proliferation and activation of histiocytes or macrophages. It can occur with systemic infections, immunodeficiency, or underlying malignancy. Brucellosis is one of the rare causes of hemophagocytosis. Herein we report an 11-year-old male with pancytopenia due to hemophagocytosis during the course of brucellosis that responded favorably to therapy. Although rare, hemophagocytosis should be considered as a possible cause of pancytopenia in patients with brucellosis, especially in regions where brucellosis is frequently encountered.