Fig 2 - available from: Pediatric Rheumatology
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Chest CT findings in a 13-year-old female with trisomy 21 (Patient 4). Axial CT images through the upper (a) demonstrate ill-defined nodular ground glass opacities in the left upper lobe (arrows). Axial CT image through the lower chest (b) demonstrates innumerable tiny centrilobular nodules and septal thickening bilaterally
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Background
Respiratory conditions are the leading cause of hospitalization and death in children with Trisomy 21 (T21). Diffuse alveolar hemorrhage (DAH) occurs at higher frequency in children with T21; yet, it is not widely studied nor is there a standardized approach to diagnosis or management. The objective of this study was to identify children...
Context in source publication
Context 1
... possible resolving capillaritis. She received IV methylprednisolone and rituximab therapy followed by 2 years of IVIG and glucocorticoids. Repeat biopsy at 11 showed pulmonary hemosiderosis. At 13 and 16, she required ICU admission and IV glucocorticoids for DAH with influenza B and human metapneumovirus, respectively. She re-started rituximab (Fig. 2). BAL showed bloody fluid return. She remains on rituximab without recurrence of DAH 1 year later. Patient 5 was born at 26 weeks gestation and developed bronchopulmonary dysplasia, aspiration, hypothyroidism, aortic and tricuspid valve insufficiency, and mild PAH. She developed recurrent hemoptysis at age three and began daily ...
Citations
... Therefore, preventing and managing of the episode of alveolar hemorrhage is crucial to improve the prognosis of pediatric DAH. Respiratory infection has been found to be a trigger for the episode of alveolar hemorrhage in the pediatric DAH [5][6][7], which is not uncommon in clinical practice. Whereas, a further detailed study hasn't been conducted due to the rarity of the diseases and the limitations of the conventional detection techniques for the pathogens. ...
... So, reducing the episode of alveolar hemorrhage is an essential way to improve the prognosis of pediatric DAH. Respiratory infection is related to the episode of alveolar hemorrhage in the pediatric DAH [5][6][7]. The mechanism is still unknown. ...
Background Respiratory infection is a common trigger for the episode of alveolar hemorrhage in the pediatric diffuse alveolar hemorrahge (DAH). Whereas, a futher detailed study hasn’t been conducted. The aim of this study was to explore the etiological spectrum, clinical features, treatment strategies and outcomes of the respiratory infection induced episode of alveolar hemorrhage (RIIEAH) in the pediatric DAH. Methods The cases of pediatric DAH who had RIIEAH and a definite etiological diagnosis were included. A retrospective study was conducted. Results 1. A total of 16 cases with 21 RIIEAHs were included. Twelve RIIEAHs occurred at the unstable stage, 6 RIIEAHs occurred at the stable stage and 3 RIIEAHs occurred at the end stage. All the RIIEAHs with respiratory failure (n=5) and requirment of invasive mechanical ventilation (n=3) occurred at the unstable or end stage. 2. In the majority of the RIIEAHs (n=19), etiological diagnosis was identified by detecting the nucleic acid of the pathogens. Of these, bronchoalveolar lavage fluid was the most commonly used specimen in 12 RIIEAHs. The majority of the RIIEAHs (n=19) were caused by a single pathogen including mycoplasma pneumoniae (Mp) in 7 RIIEAHs, coronavirus (CoV) in 3 RIIEAHs, haemophilus influenzae (Hi) in 3 RIIEAHs, chlamydia pneumoniae in 2 RIIEAHs, human metapneumovirus in 2 RIIEAHs, acinetobacter baumannii in 1 RIIEAH and pueumocystis carinii in 1 RIIEAH. The rest 2 RIIEAHs were caused by the mixed pathogens including klebsiella pneumoniae and streptococcus pneumoniae in 1 RIIEAH, rhinovirus and CoV in 1 RIIEAH. 3. The majority of the RIIEAHs (n=19) presented with prodromal symptoms and most of them (n=15) occurred within 3 days from the prodromal symptoms. Either worsening anemia or hemoptysis was found in 13 RIIEAHs and dyspnea was found in 9 RIIEAHs. All the 12 RIIEAHs in which bronchosopy had been performed presented with bleeding on bronchoscopy. 4. An intensive glucocorticoid therapy was administrated in the 19 RIIEAHs and a targeted anti-infection treatment was administrated in the 11 RIIEAHs. The majority of the RIIEAHs (n=19) resolved, whereas there was 1 case death. Conclusions 1. RIIEAH could be caused by a varity of pathogens and could occur at any disease stage of pediatric DAH. 2. It usually occurred at the early stage of respiratory infection and presented with worsening anemia or hemoptysis. 3. Bronchoscopy had a good diagnostic value for RIIEAH and idenifying the etiology. 4. An intensive glucocorticoid therapy seemed to be effective and necessary.
... We picked this approach (as opposed to electron microscopy) due to its higher feasibility and higher throughput for analysis (enabling study of many multiciliated cells). 16,17 and 10 in mice. Note the majority of the genes are located on chr16 in mice which is triplicated in Dp(16)1/Yey (Dp16) mouse model. ...
... 16 Similarly, clinical evidence on recurrent pneumonias in people with trisomy 21 has been presented by multiple groups. [17][18][19][20] Our experiments uncovered an immune hyperreactivity at the lung airway epithelium level to IAV infection due to T21, which is consistent with elevated responsiveness of human immune cells with T21 to Type I IFN, 9 and Dp16 immune cells to both Type I and II IFN ligands. 21 Moreover, significant induction of monocyterecruiting chemokines in our studies may in part explain elevated levels of circulating intermediate (CD14 + CD16 + ) and nonclassical (CD14 -/dim CD16 + ) monocytes in DS 9 as secretion of CCL2, CCL3 and CCL4 from unchallenged mTECs is higher in Dp16 than the WT controls ( Figure 4C). ...
Individuals with Down syndrome (DS) clinically manifest severe respiratory illnesses; however, there is a paucity of data on how DS influences homeostatic physiology of lung airway, and its reactive responses to pulmonary pathogens. We generated well-differentiated ciliated airway epithelia using tracheas from wild-type and Dp(16)1/Yey mice in vitro, and discovered that Dp(16)1/Yey epithelia have significantly lower abundance of ciliated cells, an altered ciliary beating profile, and reduced mucociliary transport. Interestingly, both sets of differentiated epithelia released similar quantities of viral particles after infection with influenza A virus (IAV). However, RNA-sequencing and proteomic analyses revealed an immune hyperreactive phenotype particularly for monocyte-recruiting chemokines in Dp(16)1/Yey epithelia. Importantly, when we challenged mice in vivo with IAV, we observed immune hyper-responsiveness in Dp(16)1/Yey mice, evidenced by higher quantities of lung airway infiltrated monocytes, and elevated levels of pro-inflammatory cytokines in bronchoalveolar lavage fluid. Our findings illuminate mechanisms underlying DS-mediated pathophysiological changes in airway epithelium.
... In a recent literature review of treatment strategies for DAH patients, it was found that a patient with DAH and pulmonary infection had no recurrence of DAH after adding IVIG once a month to the treatment regimen of daily GC. [10] These results indicate that IVIG combined with other therapies is effective in SLE-DAH treatment. ...
... The overall incidence of DAH is unknown. In children with IPH, the incidence has been estimated to 0.24 -1.23 / million children per year but the incidence is highly elevated in children with trisomy 21 (3)(4)(5). The clinical presentation of DAH is very heterogenous from chronic cough and dyspnoea to haemoptysis, acute respiratory failure and severe anaemia (6)(7)(8). ...
Background
Paediatric diffuse alveolar haemorrhage (DAH) is a rare heterogeneous condition with limited knowledge on clinical presentation, treatment and outcome.
Methods
A retrospective, descriptive multicentre follow-up study initiated from the European network for translational research in children's and adult interstitial lung disease (Cost Action CA16125) and chILD-EU CRC (the European Research Collaboration for Children's Interstitial Lung Disease). Inclusion criteria were DAH of any cause diagnosed before the age of 18 years.
Results
Data of 124 patients from 26 centres (15 counties) were submitted, of whom 117 patients fulfilled the inclusion criteria. Diagnoses were idiopathic pulmonary haemosiderosis (n=35), DAH associated with autoimmune features (n=20), systemic and collagen disorders (n=18), immuno-allergic conditions (n=10), other childhood interstitial lung diseases (chILD) (n=5), autoinflammatory diseases (n=3), DAH secondary to other conditions (n=21) and nonspecified DAH (n=5). Median (IQR) age at onset was 5 (2.0–12.9) years. Most frequent clinical presentations were anaemia (87%), haemoptysis (42%), dyspnoea (35%) and cough (32%). Respiratory symptoms were absent in 23%. The most frequent medical treatment was systemic corticosteroids (93%), hydroxychloroquine (35%) and azathioprine (27%). Overall mortality was 13%. Long-term data demonstrated persistent abnormal radiology and a limited improvement in lung function.
Conclusions
Paediatric DAH is highly heterogeneous regarding underlying causes and clinical presentation. The high mortality rate and number of patients with ongoing treatment years after onset of disease underline that DAH is a severe and often chronic condition. This large international study paves the way for further prospective clinical trials that will in the long term allow evidence-based treatment and follow-up recommendations to be determined.
... Bronchial lavage fluid is hemorrhagic and is dominated by alveolar macrophages with the presence of hemosiderin [36]. There have been no cohort studies on sJIA-PH, and only two cases have been reported on a case-by-case basis, one with recurrent MAS and one with combined trisomy 21 [37,38]. It is essential to be aware of the potential for PH in patients with sJIA presenting with recurrent MAS, as dyspnea, iron deficiency anemia, and diffuse changes suggested by lung imaging may be present. ...
Juvenile idiopathic Arthritis (JIA) is a common rheumatic disorder in children that can cause multiple systems to be affected simultaneously, leading to severe clinical symptoms and a high mortality rate in those with pulmonary involvement. Pleurisy is the most common manifestation of pulmonary involvement. At the same time, other conditions, such as pneumonia, interstitial lung disease, occlusive bronchiectasis, and alveolar protein deposition, have been increasingly reported in recent years. This review aims to provide an overview of the clinical manifestations of JIA lung damage and the current treatment options to assist in identifying and treating JIA lung involvement.
... Other side-effects include osteoporosis, hypertension, opportunistic infections, elevated blood glucose levels, muscular atrophy/weakness, acne, weight gain, stomach irritation, and mood changes. Recently, rituximab (RTX) has been suggested as a treatment option for IPH, but published data are limited to few case reports with limited follow-up [8,9]. No randomized studies are available. ...
Idiopathic pulmonary hemosiderosis (IPH) is a rare, potentially life-threatening chronic disease. Steroids are the cornerstone of treatment, even though toxicity and side-effects are very common. Recently, rituximab (RTX) has been suggested as a treatment option, although evidence for its efficacy and long-term safety is lacking. We describe the disease course of two pediatric patients with IPH that were treated with RTX for over 4 years. Demographics, treatments, and clinical variables such as growth, infections, imaging follow-up by CT, and data from pulmonary function tests were retrospectively described. These are the first two cases described with a long-term follow-up of pediatric IPH patients treated with RTX. RTX was well-tolerated and prevented outbreaks of bleeding. In addition, RTX had a robust steroid-sparing effect resulting in the improvement of growth, pulmonary function, and CT abnormalities.
