OBJECTIVES: We sought to define the clinical features that distinguish DOCK8 deficiency from other forms of HIES and CIDs, study the mutational spectrum of DOCK8 deficiency, and report on the frequency of specific clinical findings.
METHODS: Eighty-two patients from 60 families with CID and the phenotype of AR-HIES with (64 patients) and without (18 patients) DOCK8 mutations were studied. Support vector machines were used to compare clinical data from 35 patients with DOCK8 deficiency with those from 10 patients with AR-HIES without a DOCK8 mutation and 64 patients with signal transducer and activator of transcription 3 (STAT3) mutations.
RESULTS: DOCK8-deficient patients had median IgE levels of 5201 IU, high eosinophil levels of usually at least 800/μL (92% of patients), and low IgM levels (62%). About 20% of patients were lymphopenic, mainly because of low CD4(+) and CD8(+) T-cell counts. Fewer than half of the patients tested produced normal specific antibody responses to recall antigens. Bacterial (84%), viral (78%), and fungal (70%) infections were frequently observed. Skin abscesses (60%) and allergies (73%) were common clinical problems. In contrast to STAT3 deficiency, there were few pneumatoceles, bone fractures, and teething problems. Mortality was high (34%). A combination of 5 clinical features was helpful in distinguishing patients with DOCK8 mutations from those with STAT3 mutations.
CONCLUSIONS: DOCK8 deficiency is likely in patients with severe viral infections, allergies, and/or low IgM levels who have a diagnosis of HIES plus hypereosinophilia and upper respiratory tract infections in the absence of parenchymal lung abnormalities, retained primary teeth, and minimal trauma fractures.
OBJECTIVES: The aim of this study is to assess the role of Granulocyte Macrophage-Colony Stimulating Factor (GMCSF) in asthmatic airway hyper-responsiveness associated with RSV infections.
MATERIALS AND METHODS: Forty five asthmatic cases and 45 healthy individuals were studied in a cross-sectional design. All asthmatics underwent symptom score assessment.GMCSF concentrations in sputum and RSV-IgM/IgG in serum samples were measured for all participants by Enzyme Linked Immuno-Sorbent Assay (ELISA).
RESULTS: The GM-CSF concentration level was significantly higher in asthmatics (270.27± 194.87pg/mL) especially among moderate and severe disease with mean concentration of 197.33±98.47 and 521.08± 310.04 respectively, compared to healthy controls (22.20±21.27 pg/ mL) (p =0.0001). The sputum level of GM-CSF in asthmatics is highly significant associated with positive anti-RSV IgG sera which represents 35/45(77.8%) with mean GM-CSF concentration of (276.99± 86.42) compared with controls at about 31/45 (68.9%) with GM-CSF mean concentration of (22.84±23.47). On the other hand, positive anti-RSV IgM in asthma cases was 8 out of 45(17.8 %) with GM-CSF mean concentration of (307.25± 306.65). Furthermore, GM-CSF sputum level was significantly correlated with eosinophil count especially in moderate and severe asthma.
CONCLUSIONS: This study revealed that GM-CSF level is associated with eosinophilia and indicates asthma severity that might be evident during RSV infection .The distinctive GM-CSF features observed in the sputum from asthmatics with RSV may be useful as a diagnostic methods to help match patients with antibody therapy.
OBJECTIVES: Our study aimed to characterize the clinical, immunological and virological features of confirmed dengue patients in Sri Lanka during the outbreak in 2017 when unusual manifestations of severe dengue were observed.
STUDY DESIGN: Sera from 295 patients who were admitted to Teaching Hospital Kandy, Kandy, Sri Lanka between March 2017- January 2018 were subjected to NS1 antigen, IgM and IgG ELISAs, virus isolation, conventional and real time RT-PCR and next generation sequencing.
RESULTS: Primary and secondary infections were detected in 48.5 % and 51.5 % of the study population, respectively. Two hundred twenty five DENV strains were isolated (219 DENV-2, one DENV-3, two DENV-4, two mixed infections of DENV-2 and -3 and one mixed infection of DENV-2 and -4). Unusual and severe manifestations such as encephalitis, encephalopathy, liver failure, kidney failure, myocarditis, Guillain-Barré syndrome and multi-organ failure were noted in 44 dengue patients with 11 deaths. The viraemia levels in patients with primary infection and unusual manifestations were significantly higher compared to those in patients with secondary infection. A new clade of DENV-2 Cosmopolitan genotype strains was observed with the strains closely related to those from China, Malaysia, Indonesia, Singapore and Taiwan.
CONCLUSIONS: The new clade of DENV-2 cosmopolitan genotype observed in Sri Lanka in 2017 caused an unprecedented, severe dengue outbreak. The emergence of DENV-3 and DENV-4 in the 2017 outbreak might cause future outbreaks in Sri Lanka.
RESULTS: The diagnosis was made based on clinical findings and in addition, with the support of the evidence of Bartonella hensalae IgG and/or IgM. Small retinal white lesions were the most common ocular findings in this series of patients (82.6% of eyes, 76.9% of patients). Neuroretinitis was the second most common finding (47.8% of eyes, 69.2% of patients), followed by exudative retinal detachment involving the macula (34.8% of eyes, 53.8% of patients) and Parinaud's oculoglandular syndrome (17.4% of eyes, 23.1% of patients). Other findings like isolated optic disc oedema without macular star (8.7% of eyes, 15.4% of patients) and vitritis (4.3% of eyes, 7.7% of patients) were also observed. Ten patients (76.9%) had bilateral ocular involvement. Most of the patients were young, immunocompetent and had systemic symptoms like fever prior to their ocular symptoms. The visual acuity (VA) at initial presentation ranged from 6/6 to hand movement (mean, 6/20), and at final visit 6/6 to 6/60, (mean, 6/9). 91.7% of patients were treated with antibiotics. Only 2 patients received oral corticosteroids together with antibiotics due to very poor vision on presentation. The visual prognosis of ocular bartonellosis is generally good with 16 (88.9%) of 23 eyes having VA of 6/12 or better at final follow-up visit.
CONCLUSION: Small foci of retinal white lesions were the most common manifestation of ocular bartonellosis in this series, followed by neuroretinitis, though an array of other ocular findings may also occur. Therefore, we should consider bartonella infection as a possible differential diagnosis in those patients.