Primary immunodeficiencies (PIDs) are rare disorders of the immune system encompassing inborn errors of immunity. Primary antibody deficiencies constitute the largest group of PID with common ...variable immunodeficiency (CVID) being the most common symptomatic form. Combined immunodeficiencies (CID) accompanied by antibody deficiency can mimic CVID and these patients need the verification of the final diagnosis. Respiratory involvement, especially interstitial lung disease (ILD), poses a relevant cause of morbidity and mortality among patients with PID and in some cases is the first manifestation of immunodeficiency. In this study we present a retrospective analysis of a group of children with primary immunodeficiency and ILD - the clinical, radiological, histological characteristics, treatment strategies and outcomes. Eleven children with PID-related ILD were described. The majority of them presented CVID, in three patients CID was recognized. All patients underwent detailed pulmonary diagnostics. In eight of them histological analysis of lung biopsy was performed. We noted that in two out of 11 patients acute onset of ILD with respiratory failure was the first manifestation of the disease and preceded PID diagnosis. The most common histopathological diagnosis was GLILD. Among the analyzed patients three did not require any immunosuppressive therapy. All eight treated children received corticosteroids as initial treatment, but in some of them second-line therapy was introduced. The relevant side effects in some patients were observed. The study demonstrated that the response to corticosteroids is usually prompt. However, the resolution of pulmonary changes may be incomplete and second-line treatment may be necessary.
Hypersensitivity pneumonitis in children Wawszczak, Maria; Bielecka, Teresa; Szczukocki, Maciej
AAEM. Annals of Agricultural and Environmental Medicine/Annals of Agricultural and Environmental Medicine,
2021-Jun-14, Volume:
28, Issue:
2
Journal Article
Peer reviewed
Open access
Hypersensitivity pneumonitis (HP) is one of the most common forms of interstitial lung disease in children. Due to its common association with occupational environment, it used to be considered an ...exclusively adult disease; however, hypersensitivity pneumonitis also affects the paediatric population, and is often associated with exposure to antigens in the home environment and with the pastime activities of children.
The aim of the study is to present the current state of knowledge on hypersensitivity pneumonitis in children with a focus on the peculiarities of diagnostic investigation and management of the disease in this age group. The study includes a case report of the disease in a child.
In children, the most common factors causing HP are avian and fungal antigens present in the home environment. Diagnosis is based on the co-occurrence of characteristic clinical presentation, radiographic and pulmonary function tests findings, and a history of exposure to a potential triggering antigen. The main strategy in the management of HP is to eliminate the trigger factor with the use of a systemic corticosteroids therapy in severe or advanced cases.
Due to the risk of irreversible changes in the respiratory tract, an early diagnosis is very important. A quick identification of the trigger factor and its elimination from the patient's environment makes it possible to apply a less aggressive treatment, and to improve the patient's prognosis. Unfortunately, due to its infrequent occurrence, hypersensitivity pneumonitis is often not taken into account in a differential diagnosis of respiratory diseases in children, which leads to a delayed diagnosis despite the characteristic clinical presentation of the disease.
Children with nephrotic syndrome (NS) are at greater risk of infections than the general population, due to immunodeficiency in the course of the disease and the treatment. In this study we present 4 ...children (2 girls, 2 boys), mean age 7.6 ±5.1 years, with NS/proteinuria and latent tuberculosis in 3 children and lymph node tuberculosis in 1 child. The reasons for testing these children for tuberculosis (TB) were the evaluation of the epidemiological status before treatment with corticosteroids (GCS), leukopenia and the relapse of NS, and non-nephrotic proteinuria. The diagnosis of TB infection was based on positive IGRA (Interferon-Gamma Release Assay). Chest X-ray was normal in all the children. Chest CT scan revealed an enlargement of lymph nodes in 1 child. The children were treated with isoniazid (3 children) and isoniazid, rifampicin and pyrazinamide (1 child). Three children with idiopathic nephrotic syndrome were treated with prednisone. The child with non-nephrotic proteinuria was treated with enalapril. Proteinuria disappeared in all children during anti-TB treatment.
Pathogenic variants in genes encoding aminoacyl‐tRNA synthetases cause numerous disorders characterized by involvement of neurons, muscles, lungs and liver. Recently, biallelic FARSB defects have ...been shown to cause severe growth restriction with combined brain, liver and lung involvement (Rajab interstitial lung disease ILD with brain calcifications). Herein, for the first time, we present a patient with similar condition associated with biallelic mutations in FARSA (NM_004461.3: c.766T>C:p.Phe256Leu and c.1230C>A:p.Asn410Lys). Both detected FARSA variants are ultrarare and predicted to be damaging by in silico programs. Furthermore, they are both located in the active site of phenylalanyl‐tRNA synthetase (PheRS) with Asn410Lys directly affecting a residue forming the wall of the phenylalanine‐binding pocket. Clinical features shared between our patient and the FARSB syndrome include ILD with cholesterol pneumonitis, growth delay, hypotonia, brain calcifications with cysts and liver dysfunction. Our findings indicate that a disease similar to a syndrome associated with FARSB defects can also be caused by biallelic FARSA mutations. These findings are consistent with molecular structure of PheRS which is a tetramer including both FARSA and FARSB proteins.
Objective: The prevalence of allergic diseases has reached epidemic proportions in the Western world. Although farm-living has been associated with a lower prevalence of asthma and atopy, a marked ...increase in atopy among rural populations after accession to the European Union has been recently reported in Poland. Here, we aimed to investigate the effect of living environment on the prevalence of atopy and allergic diseases in Polish children. Methods: 400 schoolchildren aged 10-14 years from the capital city (223) and from traditional rural part of the country (177) were recruited from June to November 2011. Data on allergic diseases and symptoms were collected by means of questionnaire and physical examination. Atopy was assessed based on skin prick tests (SPTs) reactivity to inhalant allergens in 350 children. Results: A high discrepancy between the prevalence of allergic symptoms (46.7%) and doctor-diagnosed allergic diseases (25%) was demonstrated (p < 0.0001). Urban children had a higher overall prevalence of allergic diseases and atopy than children living in rural areas, 29.3% versus 17.1% (p = 0.007) and 33.5% versus 20% (p = 0.0045), respectively. However, no significant differences in the rates of particular allergic diseases were noted (p > 0.05). There was higher SPT positivity to trees, grass, corn, weeds, animal dander, and molds in urban children (p < 0.05). Conclusions: Our data support the protective effect of farm-living on the prevalence of atopy and overall allergic diseases, albeit not on particular allergic diseases, in children in Poland. The underlying mechanisms are not identified, but current socioeconomic changes may be responsible.
Objectives
To assess whether children ≤5 years of age, produce sufficient amounts of interferon gamma (IFN‐ɣ) in response to phytohaemagglutinin (mitogen), and Mycobacterium tuberculosis antigens (TB ...antigens) in the QuantiFERON‐TB Gold in‐Tube test (QFT‐GIT), (Cellestis Ltd., Australia). Working hypothesis: Is TB‐antigen‐induced IFN‐ɣ response in children ≤5 years sufficient to consider QFT‐GIT a possible tool for TB diagnostics? Study design, patient‐subject selection, and methods: We recruited children 0‐17 years old suspected of TB infection to this cross‐sectional study, in whom QFT–GIT and TST were performed. We analyzed the median IFN‐ɣ levels in mitogen and TB antigen tubes in children ≤5 years and >5 years, and the correlation between IFN‐ɣ level in both tubes and age.
Results
A total of 153 children were enrolled, age median was 7.8 (IQR:8), 45 (29.4%) aged ≤5 years (median 3.4, IQR:1.7), 108 > 5 years (median 10.55, IQR:5.93). In the mitogen tubes, the median IFN‐ɣ level was higher in children >5 years (median 17.87, IQR:2.1 vs 16.77, IQR:7.6), but surprisingly in the TB antigen tubes it was higher in the younger group (median 0.12, IQR:0.21vs 0.06, IQR:0.09, P = 0.04). We proved a positive correlation between IFN‐ɣ level and age in mitogen tubes (r = 0.18, P = 0.03) and a negative correlation in TB antigen tubes (r = −0.17, P = 0.04). In latent tuberculosis infection patients, the latter correlation was found to be even stronger (r = −0.39, P = 0.01).
Conclusions
The youngest children release sufficient amount of IFN‐ɣ in response to TB antigens thus QFT‐GIT might be a useful tool for TB diagnostics in this age group.
Tuberculosis morbidity rates in Poland have been gradually decreasing. Nevertheless, there are approximately 8 thousand cases being registered annually, which includes almost 3 thousand massively ...infectious patients. In the last 3 years, around 100 cases/year have been reported among children below 14 years of age. Infection with Mycobacterium tuberculosis should be considered in all patients who present symptoms suggesting tuberculosis, have had recent contact with a person suffering from lung tuberculosis or are planned to undergo an immunosuppressive treatment. HIV infected patients are also supposed to have screening tests for M. tuberculosis infection performed. For over a 100 years tuberculin skin test (TST) was the only test capable of confirming tuberculous infection. TST is based on the assessment of skin reaction to intracutaneous injection of tuberculin. Due to cross-reaction to the injected tuberculin in BCG vaccinated individuals, the correct interpretation of the test is difficult. Since 13 years new immunological assays have been available. They are based on detecting interferon gamma (Interferon Gamma Release Assay - IGRA) concentration in blood serum, which has previously been incubated with Mycobacterium tuberculosis antigens absent in the BCG strain. In infected individuals interferon gamma is intensively produced by memory cells in reaction to the contact with previously met Mycobacterium antigens. Many trials have proved IGRA's high sensitivity and, higher than TST, specificity. Recent guidelines promote the usage of IGRAs, even in children.
Bacillus Calmette-Guérin (BCG) is the only tuberculosis vaccine available and although it has been routinely used for more than 80 years, its protective effect varies depending on the age and the ...form of tuberculosis. Due to the close analogy between the vaccine strain and other species of the Mycobacterium tuberculosis complex, molecular methods are recommended for differential diagnosis of post-BCG complications. The aim of the study was to assess usefulness of molecular methods in diagnosis of post-BCG vaccine adverse events (VAEs).
M. tuberculosis complex strains obtained in 2011-2017 from 68 ill children were subjected to molecular analysis.
Molecular analysis of 68 strains showed 100% agreement between the results in the GenoType MTBC method and the multiplex PCR method. For the strains isolated from 45 patients with suspected VAE, M. bovis BCG was obtained, whereas the strains isolated from the remaining 23 children were identified as M. tuberculosis. The analysis confirmed the close relationship between the result of identification and the type of material as well as the patient's age.
The use of genetic methods enables quick and detailed diagnostics of infections caused by M. bovis BCG, which allows for the confirmation or exclusion of VAE.
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