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Children's Interstitial Lung Disease (ChILD): Differential Diagnoses & Workup
Updated: Sep 11, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Differential Diagnoses
Other Problems to Be Considered
Other connective tissue disorders
Congenital heart disease
Pulmonary venoocclusive disorders
Immunodeficiency
Pediatric AIDS
Workup
Laboratory Studies
General diagnostic approach
The process and pace of evaluation depends on several factors and no single algorithm applies to the diverse clinical settings in which interstitial lung disease (ILD) can occur. Considerations influencing the diagnostic approach include age at presentation, immunocompetence, chronicity, severity of disease, duration of illness, family history, and trend toward improvement. For example, the full-term newborn with respiratory failure is approached differently from the young child with tachypnea of insidious onset and hypoxemia with feeding or sleep. As outlined below, some types of ILD may be diagnosed on the basis of genetic testing, and laboratory studies may provide clues for others, particularly in association with systemic disorders. Although chest CT patterns may suggest certain diagnoses, many forms of ILD require surgical lung biopsy for definitive diagnosis.
- CBC count and differential: Anemia and reticulocytosis are seen in pulmonary hemorrhage. Polycythemia may be seen in chronic hypoxia. Peripheral eosinophilia suggests parasitic disease, hypersensitivity, eosinophilic syndromes, or other immune dysfunction.
- Urinalysis may indicate coincident glomerulonephritis in patients with pulmonary-renal syndromes.
- Stool hemoccult results may be positive in patients with idiopathic pulmonary hemorrhage or inflammatory bowel disease.
- Sweat chloride test and cystic fibrosis (CF) genotyping may be required to exclude CF
- Serologic testing for Mycoplasma pneumoniae may be used.
- Fungal serologic testing may be used.
- Respiratory viral studies may be used.
- Markers of inflammation, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, may be elevated in inflammatory disorders.
- Workup for immunodeficiency includes testing for immunoglobulins, immunoglobulin G (IgG), IgG subclasses, specific antibodies to vaccine antigens (tetanus, diphtheria, polyvalent pneumococcal vaccine, and Haemophilus influenzae type B), complement (C3, C4, CH50), and lymphocyte subsets
- Anergy skin test panel should be considered
- Lymphocyte markers may be useful.
- Immunoglobulin E (IgE) may be used to evaluate for parasitic disease, allergic bronchopulmonary aspergillosis (ABPA), and eosinophilic syndromes.
- Human immunodeficiency virus (HIV) testing is indicated if LIP, P carinii pneumonia (PCP), or disseminated histoplasmosis is present.
- Markers of rheumatic disorders, including rheumatoid factor (RF), antinuclear antibody (ANA)/anti–double-stranded DNA (anti-dsDNA) antibody, antineutrophil cytoplasmic antibodies (ANCAs), and anti–basement membrane antibodies, should be measured to determine connective tissue disease or autoimmune etiologies.
- ACE levels and/or lysozyme may be elevated in patients with sarcoidosis, but these are neither sensitive nor specific.
- Serum precipitin results may be positive in patients with hypersensitivity pneumonitis but do not prove disease causality.
- Genetic testing for SFTPB and ABCA3 mutations should be performed in infants with unexplained severe neonatal respiratory distress, particularly if a family history of respiratory disease is known. Testing for SFTPC and ABCA3 mutations should be considered in infants and children with children’s interstitial lung disease (ChILD) syndrome, particularly if they exhibit digital clubbing, diffuse ground glass opacities, or "honeycomb" changes on high-resolution CT (HRCT) or if they have a family history of chronic lung disease. Clinical genetic testing for these disorders is available through Clinical Laboratories Improvement Act (CLIA)-certified diagnostic laboratories.
- Serum and urine amino acids may be measured if metabolic conditions, such as lysinuric protein intolerance, are not suspected.
- KL-6 is a high-molecular-weight protein produced by type II pneumocytes and bronchial epithelial cells, especially during their regeneration. Unfortunately, outside of Japan, testing is only available on a limited research basis.
- KL-6 functions as a chemoattractant for fibroblasts
- High levels of serum KL-6 reflect an active fibroblastic process affecting the pulmonary interstitium or bronchioles. Elevated serum KL-6 levels have been found in different types of ILD, bronchopulmonary dysplasia (BPD), severe measles pneumonia, and ILD associated with juvenile dermatomyositis.20,21
- KL-6 appears to have high sensitivity (93.9%) and high specificity (96.3%) for IDL in adults and correlates with disease severity.22
Imaging Studies
Chest radiography
Chest radiographs are often the first imaging study performed for evaluation of possible ILD. Although they rarely allow for a specific diagnosis, they can be useful in identifying other causes of respiratory symptoms that may present similarly to ILD.23,24 Findings on plain chest images may be normal in the presence of active disease and abnormal in the absence of symptoms. Numerous radiographic patterns are associated with ILD, including ground-glass opacities; reticular, nodular, or reticulonodular infiltrates; and honeycombing. The ground-glass appearance is consistent with active alveolitis, and honeycombing is consistent with advanced fibrosis.
Radiographic findings are usually described as interstitial infiltrates, although predominantly nodular (alveolar) and mixed reticulonodular patterns have been described, as have nonspecific findings (hyperinflation).
CT scanning
CT scanning, specifically high-resolution CT (HRCT), provides a noninvasive means for determining the patterns, extent and distribution of changes associated with ILD. The imaging appearance of diffuse abnormalities include ground-glass attenuation, a tree-in-bud appearance, lobular airtrapping, reticular attenuations, and centrilobular nodules.25 CT is especially useful in demarcating the most appropriate areas for tissue biopsy.
Disadvantages of HRCT include the need for sedation in uncooperative infants and the relatively high radiation exposure. Newer, more rapid acquisition algorithms have somewhat decreased these problems. Long and colleagues have developed a method by using combination of sedation and controlled ventilation with a face mask providing a controlled pause in respiration to allow scanning of the lung with 1-mm sections.26 Without controlled ventilation, respiratory motion may mimic ground glass opacities, and dependent atelectasis may occur mimicking parenchymal changes. When possible, both inspiratory and expiratory images should be obtained, as expiratory images can be important to assess for air-trapping and to evaluate extent of ground-glass opacity. Whether serial HRCT provides any benefit in monitoring disease progression or response to therapy is unclear.
In a study of HRCT in 20 children with ILD, specific patterns were correlated with certain types of pathology, with little overlap.27 Regions with hyperlucency, with or without bronchiectasis, were well correlated with airspace localizing diseases, such as bronchiolitis obliterans or bronchocentric granulomatosis. Septal thickening was correlated with lymphangiomatosis and pulmonary capillary hemangiomatosis. Ground-glass changes were seen in infiltrative ILD, such as DIP, hypersensitivity pneumonitis, and LIP. A characteristic CT pattern appears to be associated with NEHI (figure 3).28 Consolidative patterns were seen in aspiration syndromes, BOOP (figure 5), and vasculitides. Characteristic thin-walled, heterogeneous cysts, alternating with small nodules, were seen only in patients with LCH.
In another study, investigators evaluated the ability of expert readers to correctly diagnose pediatric diffuse lung disease with HRCT.24 The correct first-choice diagnosis of ILD was made in 61%, and the conditions correctly diagnosed with greatest frequency were alveolar proteinosis, idiopathic pulmonary hemosiderosis, and pulmonary lymphangiectasia.
Studies in a small number of patients with neuroendocrine cell hyperplasia of infancy (NEHI) or bronchiolitis obliterans suggest that characteristic HRCT patterns are often noted in these entities.28,29
Barium swallow studies
Barium swallow studies or radionuclide "milk" scans may demonstrate evidence of gastroesophageal reflux or aspiration.
Echocardiography
Echocardiography should be included in the initial diagnostic workup. Special attention should be paid to depiction of all 4 pulmonary veins, because partial anomalous pulmonary venous return may be present in patients with respiratory distress and chest radiograph findings of interstitial infiltrates. Evidence of pulmonary hypertension (based on the tricuspid regurgitant jet velocity) and right ventricular hypertrophy may be evident.
Nuclear scintigraphy
Certain radionuclides (specifically 67Ga) accumulate preferentially in areas of active lung inflammation; therefore, they may be useful both in delineating areas of active inflammation and in monitoring disease progression. However, in adult IPF, results of 67Ga scanning are not correlated with disease activity or response to treatment.
Other Tests
Pulse oximetry
Decreased oxyhemoglobin saturation more often reflects ventilation-perfusion mismatching, rather than diffusion abnormalities, because of the remodeling of distal airspaces characteristic of most childhood ILD. In early stages of ILD, oxyhemoglobin saturation may be relatively normal at rest but may worsen dramatically with exercise or sleep.
Most children with more advanced ILD present with hypoxemia. In adults, the degree of arterial desaturation correlates with severity of fibrosis, pulmonary hypertension, and survival. In children, pulmonary hypertension is a more important predictor of poor prognosis than desaturation.
Pulmonary function testing
In children and adolescents who can perform spirometry and plethysmography, total lung capacity (TLC), forced vital capacity (FVC), and FEV1 are all reduced, consistent with restrictive physiology. Although TLC maybe reduced, functional residual capacity (FRC) and residual volume (RV) are often normal or elevated, resulting in increased FRC/TLC and RV/TLC ratios. Airflow limitation, as indicated by a reduced FEV1/FVC ratio, is present in as many as one half of children with ILD. Compliance of the respiratory system (Crs) is reduced.
Diffusing capacity for carbon monoxide is usually low, although this value often returns to normal when corrected for lung volume and hemoglobin. In pulmonary hemorrhage syndromes, diffusing capacity may be elevated because of the affinity of carbon monoxide for sequestered hemoglobin.
Infant PFTs can be safely performed in sedated infants at a large number of pediatric centers. Results of PFTs in infants, if available, usually show reduced Crs using both multiple occlusion and end inspiratory occlusion techniques, and PFTs have been used to monitor the response to treatment in some studies.
Results of arterial blood gas analysis may be normal, but typical changes include decreased arterial partial pressure of oxygen (PaO2) and respiratory alkalosis.
Exercise testing
In children old enough to cooperate, exercise testing may reveal exercise-related desaturation, even when oxyhemoglobin saturation is normal during rest. Exercise testing, or a 6-minute walk test, may provide an objective indicator of disease progression.
pH probe testing
pH or impedance probe testing may be required to demonstrate gastroesophageal reflux (GER), predisposing patients to aspiration. GER may occur as a secondary complication of ILD.
Electrocardiography
ECG readings may show evidence of cor pulmonale, specifically right atrial and ventricular enlargement, and right axis deviation.
Procedures
Bronchoalveolar lavage
Bronchoscopy with BAL is useful in diagnosing certain conditions in the differential diagnosis of ILD, including alveolar proteinosis, aspiration syndromes, pulmonary hemosiderosis, and various infections. Occasionally, results of cytologic analysis may be diagnostic, for example, when Langerhans cells are present, indicating histiocytosis. Most authorities believe BAL should precede biopsy.
Problems with the use of BAL include the lack of a standardized methodology in children, the paucity of reference values for differential cell counts, the variability of BAL findings at different times in a disease course, and the lack of correlation between BAL and histologic findings.
Fluid should be sent for differential cell counts, culturing and special staining for bacteria (including mycobacteria) and fungi, cytologic analysis (including oil red O staining for lipid-laden macrophages and staining for hemosiderin), pepsin levels, and viral diagnostic studies. Analysis of lymphocyte markers in BAL is controversial in adults and has not been standardized in children.
BAL findings can be diagnostic of PAP, demonstrating cloudy or milky appearance of the fluid with periodic acid-Schiff (PAS)–positive amorphous debris. Increased eosinophils (>30% of total) are consistent with eosinophilic pneumonia syndromes, whereas predominant lymphocytosis can be associated with hypersensitivity pneumonitis. CD1a-positive cells are diagnostic for Langerhans' cell histiocytosis.30
Lung biopsy
Analysis of tissue obtained during lung biopsy is the best way to make a definitive diagnosis if it cannot be established by noninvasive means. Much of the classification of ILD, especially in disorders of unknown cause, is based on histopathology (see Histologic Findings). To maximize the diagnostic yield, a pediatric lung biopsy protocol has been developed and supported by the ChILD Pathology Cooperative Group.31 However, a diagnosis is not reached in all patients, even after biopsy is performed.
The number of biopsy procedures performed and the method used (eg, open vs thoracoscopic) have little influence on diagnostic yield. The biopsy sample should be taken from a region of involvement: if diffuse involvement is found, any site except the tip of the right middle lobe or lingua is appropriate.
Open lung biopsy has been the traditional approach. Open biopsy allows for the collection of an optimal amount of tissue from areas most likely to enable a diagnosis. Diagnostic yield may be enhanced if HRCT is used to direct the biopsy sites. Communication between the clinician, surgeon, pathologist, and radiologist before biopsy is useful and appropriate for determining biopsy sites and prioritizing use of the tissue.
Compared with open lung biopsy, thoracoscopic biopsy shortens surgical time, duration of chest tube placement, and hospital stay without substantially altering the diagnostic yield. The choice between thoracoscopic and open approaches should be left to the consulting surgeon.
Transbronchial biopsy is increasingly performed in older pediatric patients because of its use after lung transplantation. Small pediatric bronchoscopes do not allow biopsy forceps to pass. Although this may be an option with newer models, tissue yield is less than that obtained with open or thoracoscopic lung biopsy, and, may not be sufficient for accurate diagnosis of chILD.31 One group compared the diagnostic value of different techniques for lung biopsy. Specific diagnosis were made in 50%, 60%, and 53% of patients who underwent transbronchial, video-assisted, and open lung biopsy, respectively.8,4
Regardless of the method used, biopsy samples should be processed for bacterial, fungal, and mycobacterial cultures and staining, including special staining, light microscopy, immunofluorescence, and electron microscopy. Immunostains, such as bombesin for NEHI and vimentin for PIG, may aid in the diagnosis of specific forms of ILD.16
Cardiac catheterization
This procedure should be considered in any child with noninvasive evidence of pulmonary hypertension but especially in children with a history of hemoptysis or absence of crackles on examination. These findings have been correlated with pulmonary venoocclusive disease.
Histologic Findings
Histologic findings on routine hematoxylin and eosin staining remain the criterion standard for the diagnosis and classification of many types of ILD and may indicate the underlying cause, if a cause is present, or may suggest associated systemic illnesses (eg, noncaseating granulomas characteristic of granulomatous infections or sarcoidosis). However, this area has been rife with confusion because of different classification schemes, inexact nomenclature, and important differences between children and adults. Consultation with pathologists experienced in chILD is critical and ideally should be sought before biopsy specimens are obtained.
ILD classification systems
Several classification systems have been developed for adults. The American Thoracic Society (ATS) classification of the differential diagnoses of IPF is as follows:32
- UIP (required for IPF)
- DIP
- RBILD
- NSIP
- AIP
- BOOP
- LIP
- Pulmonary histiocytosis X
- UIP pattern with likely underlying cause (eg, asbestosis, connective tissue disease, hypersensitivity pneumonitis)
- Nonclassifiable
These are of questionable relevance to child, because particular patterns may have differing diagnostic and prognostic significance in adults and children. A classification system for infants with ILD based on a multicenter retrospective review of histopathology has recently been published, which divides child entities into "disorders more prevalent in infancy," "disorders not unique to infancy," and "unclassified disorders."5 Most of the histologic patterns and associated clinical manifestations are described below.
Childhood Interstitial Lung Disease Syndromes That Manifest in Infancy
Neuroendocrine Cell Hyperplasia of Infancy (NEHI)In 2005, Deterding et al reported a case series of 15 patients with a clinical picture of persistent tachypnea, crackles, and hypoxemia.33 The clinical picture is consistent with what was previously termed persistent tachypnea of infancy. About 85% of the patients were born at full term, and none of those born prematurely had a history of chronic lung disease. In those infants, chest radiographs revealed hyperinflation; hyperinflation and a ground-glass appearance were revealed on HRCT. Lung biopsy did not reveal a characteristic histologic pattern, and interstitial involvement was minimal. They observed mild, nonspecific changes, including airway smooth muscle hyperplasia, increased alveolar macrophages, and increased airway clear cells. Immunostaining of the cells demonstrated strong staining for bombesin and serotonin, which identified these cells as pulmonary neuroendocrine cells (PNECs).
Neuroendocrine cell hyperplasia of infancy (NEHI)
(A) Chest high-resolution CT (HRCT) scanning (at total lung capacity) in a 6-month-old infant with tachypnea, hypoxemia, and failure to thrive. Sharply defined areas of ground glass opacity are seen most prominent in the right middle lobe and lingual. Diffuse air-trapping was seen on expiratory images (not shown). No additional abnormalities were identified.
(B) Hematoxylin and eosin staining of the lung biopsy reveals near-normal lung architecture.
(C) Bombesin immunostaining reveals increased numbers of neuroendocrine cells.
Clinical improvement was inconsistent, but no pulmonary-related deaths were reported, suggesting that prognosis for children with NEHI is generally good. The authors suggested that NEHI and chronic idiopathic bronchiolitis of infancy might constitute the same entity.33 ,34
Follicular bronchitis/bronchiolitis
In 2 case series similar to those described above, infants presented with tachypnea, fine crackles, and chronic cough by age 6 weeks.35,36 Lung biopsy findings demonstrated follicular lymphocytic infiltration surrounding and infiltrating the bronchial walls. All patients improved gradually over several years.
Follicular bronchiolitis
(A) Chest high-resolution CT (HRCT) scan from a 6-year-old infant with common variable immunodeficiency with history of anemia, thrombocytopenia, recurrent pneumonia, chronic cough, and exercise intolerance. Mosaic attenuation is present diffusely throughout the lungs. Extensive hilar and mediastinal lymphadenopathy is also present. Air-trapping was seen on expiratory images (not shown).
(B) Lung histopathology demonstrates severe airway-centric lymphocytic inflammation with reactive follicles, which infiltrates and obscures most bronchioles.
In follicular bronchitis/bronchiolitis, the HRCT appearance is similar to that seen in NEHI, but biopsy findings differ because airway inflammation is not prominent or consistent in NEHI. In addition, PNECs are not described in follicular bronchiolitis.34,28
Cellular interstitial pneumonitis/pulmonary interstitial glycogenosis (PIG)
Several case reports and small series have described infants with tachypnea since birth and diffuse lung infiltrates. Lung biopsy findings revealed interstitial proliferation of histiocytic type cells with minimal to no infiltration. In general, the clinical picture improved gradually.34 In 2002, Canakis et al reported 7 neonates presenting with chronic ILD.37 Lung biopsy findings demonstrated a histopathologic appearance similar to that of cellular interstitial pneumonitis, with spindle-shaped cells containing PAS-positive material. Electron microscopy demonstrated primitive interstitial cells with abundant cytoplasmic glycogen. The authors suggested that these cells represent a developmental abnormality. PIG is likely a more complete description of cellular interstitial pneumonitis.
Chronic pneumonitis of infancy
This is not to be confused with cellular interstitial pneumonitis. Several reports described infants with severe lung disease and chest radiographic findings including ground-glass opacities, volume loss, and hyperinflation. Biopsy findings revealed alveolar septal thickening, prominent pneumocyte hyperplasia, and alveolar exudates with numerous macrophages along with rare eosinophils and cholesterol clefts. This condition had a high mortality rate, and some cases were associated with genetic abnormalities of surfactant function.38,34
Genetic abnormalities of surfactant function
The typical histologic pattern for SP-B deficiency is interstitial thickening, abundant type II cell hyperplasia, and eosinophilic PAS-positive granular material in the alveolar space. The eosinophilic granular material is typical of PAP. Immunohistochemical staining demonstrates absence of SP-B.39,17
Adults with SP-C deficiency can have biopsy findings consistent with those of UIP, DIP, or NSIP.34 ,40 Studies suggest that a mutation in SFTPC gene may cause the production and accumulation of an abnormal protein, resulting in injury to the respiratory epithelium.41 ,17
The histopathology of ABCA3 deficiency can widely vary and appears to be age-dependent, with infants manifesting patterns consistent with PAP, chronic pneumonitis of infancy or DIP, and older children manifesting features of NSIP.7 The only well-documented case of UIP in a child was an adolescent with ABCA3 deficiency.9
Histologic Patterns of Interstitial Lung Disease not Limited to Children
DIPIn adults, DIP is a rare finding usually seen in cigarette smokers. The histologic pattern is uniform and diffuse. Alveoli are filled with accumulations of macrophages, which were originally believed to be desquamated alveolar epithelial cells, hence the name. DIP is associated with ground-glass changes on HRCT scans.
In children, DIP is not as rare a histologic pattern as it is in adults and is associated with ILD in the first year of life, sometimes with symptoms present at birth. This pattern is seen in some of the SDMs, such as ABCA3 deficiency. Unlike DIP in adults, in whom this pattern is associated with smoking history, steroid responsiveness and a favorable prognosis, DIP in children is one of the few specific ILD diagnoses associated with a significantly increased risk of death. In one large series from 1998, Fan et al reported a markedly increased mortality rate in patients with DIP compared with patients with other childhood ILDs.42
NSIP
NSIP is a confusing term (a specific pattern despite the inclusion of “nonspecific”) for a microscopically homogeneous pattern of inflammation and fibrosis, although gross involvement may be patchy. Honeycomb changes are rare. Patchy ground-glass attenuations are depicted on HRCT scans.
Nonspecific interstitial pneumonitis.
(A) Chest high-resolution CT (HRCT) scanning from a 10-year-old with systemic sclerosis and progressive exercise intolerance.
(B) Lung biopsy showed multiple abnormalities including a relatively diffuse interstitial process with mild chronic inflammation, abundant fibroblastic tissue and patchy dense interstitial fibrosis. Accumulation of alveolar macrophages is seen in the airspaces, with rare foci of organizing pneumonia. Pulmonary arteries demonstrated focal intimal hyperplasia and medial hypertrophy, and the pleura contains patchy chronic inflammation. This overall constellation of findings is generally classified as mixed cellular and fibrotic nonspecific interstitial pneumonia (NSIP) and is a pattern most commonly seen in the setting of underlying collagen vascular disease.
In one series of 64 patients, 5 patients were younger than 20 years. This pattern is associated with improved survival rates. Severity appears to be associated with the extent of fibrosis seen on histologic analysis. NSIP can be associated with ABCA3 deficiency, with known or suspected connective tissue diseases, and with environmental exposures.
AIP
AIP is the pattern associated with the entity Hamman and Rich originally described in 1944.43 The histologic pattern is one of diffuse active fibrosis (many proliferating fibroblasts, little collagen) with uniform alveolar septal thickening. Features of acute lung injury or diffuse alveolar damage (DAD) are present, such as hyaline membranes, acute inflammation, and bronchial epithelial atypia. The clinical picture is one of acute fulminant idiopathic ARDS. The mortality rate is high (60%), and progression is rapid (months). This clinical and histologic entity has been reported in children as young as 7 years.
BOOP/COP
BOOP is not technically an interstitial disease because the pathology is primarily intraluminal in distal airspaces, but BOOP may be difficult to clinically and radiographically distinguish from other ILDs. Upon histopathologic evaluation, BOOP appears as patchy areas of granulation tissue in conducting airways and alveolar ducts with inflammation (primarily macrophages) in the surrounding alveoli. In affected areas, the appearance is uniform without significant distortion of lung parenchyma. Buds of myofibroblasts in collagenous stroma (Masson bodies) may extend into adjacent airspaces, demonstrating a characteristic butterfly pattern.
Bronchiolitis obliterans.
(A) Chest CT scanning from an 8-year-old demonstrates irregular large mosaic regions of ground-glass opacity and air-trapping, as well as the presence of peribronchial thickening and bronchiectasis.
(B) Pathology demonstrates focal areas of fibrosis with polypoid plugs of fibroblastic cells and fibrin filling distal bronchioles and airspaces (hematoxylin and eosin).
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Organizing pneumonia may also be a secondary finding in other forms of ILD. Because the term BOOP is often misused, and because bronchiolar involvement is minimal in as many as one third of adults, COP is now the preferred term.
LIP
LIP is characterized by monotonous, diffuse, lymphoplasmacytic cell infiltrates in the interstitium and distal airspaces. Mononuclear cells and histiocytes are also seen. Occasionally, lymphoid aggregates are seen in a lymphatic or angiocentric distribution. LIP is often a pulmonary manifestation of AIDS in children. In addition, LIP is associated with Sjögren syndrome, chronic active hepatitis, and JRA. EBV-genomic DNA occasionally can be identified in LIP. Lymphoproliferative diseases, lymphomas, and underlying immunodeficiency must be considered.
Pulmonary LCH
LCH, or histiocytosis X, is predominantly interstitial on histologic analysis, with features of centrally scarred, stellate nodules with a polymorphic infiltrate containing characteristic Langerhans cells. The lungs are involved in approximately 10-40% of children with LCH, but few children present with isolated lung disease. In adults, pulmonary involvement is clearly related to smoking.
UIP
UIP is characterized by a heterogeneous appearance at low magnification, with alternating areas of normal lung, inflammation, fibrosis, and honeycomb changes, which are most prominent in the peripheral subpleural areas. Fibrotic areas contain dense collagenous deposits and characteristic foci of proliferating fibroblasts (fibroblastic foci), which have negative prognostic importance. There is only one well-characterized report of UIP in a child, and adolescent with ABCA3 deficiency.9
Nonclassifiable patterns
Clinical specimens that cannot be classified into one of the described patterns represent a substantial percentage of childhood ILD. Some of these may represent sampling error. Occasionally, important histologic information derived from portions of lung that may appear grossly normal. Remember that NSIP, despite its name, is a specific histologic pattern and distinct from nonclassifiable ILD.
Staging
No widely used staging system is available for ChILD, which is appropriate because the spectrum of possible final diagnoses is large.
In adults, a scoring system is available for IPF, based on clinical, radiographic, and pathologic findings (ie, CRP scoring system).
Fan devised a simple scoring system for ChILD. A score of 5 indicates the worst outcome, with a 38% survival rate at 60 months. A score of 2, 3, or 4 indicates a survival rate of 76%. Data from Cox proportional hazards modeling suggested a 140% increase in risk of death with each unit increase in score.
The Fan scoring system is as follows (1998):42
- Asymptomatic
- Symptomatic with normal oxyhemoglobin saturation
- Symptomatic with nocturnal or exercise-induced desaturation
- Desaturation at rest
- Pulmonary hypertension
More on Children's Interstitial Lung Disease (ChILD) |
| Overview: Children's Interstitial Lung Disease (ChILD) |
 Differential Diagnoses & Workup: Children's Interstitial Lung Disease (ChILD) |
| Treatment & Medication: Children's Interstitial Lung Disease (ChILD) |
| Follow-up: Children's Interstitial Lung Disease (ChILD) |
| Multimedia: Children's Interstitial Lung Disease (ChILD) |
| References |
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Further Reading
Keywords
children’s interstitial lung disease, ChILD, ILD, diffuse infiltrative lung disease, pulmonary disease, lung disease, interstitial disease, idiopathic pulmonary fibrosis, IPF, nonidiopathic interstitial pulmonary fibrosis, usual interstitial pneumonia, UIP, desquamative interstitial pneumonia, DIP, bronchiolitis obliterans with interstitial pneumonia, BIP, lymphoid interstitial pneumonia, lymphocytic interstitial pneumonia, LIP, giant cell interstitial pneumonia, giant-cell interstitial pneumonia, GIP, respiratory bronchiolitis interstitial lung disease, RBILD
nonspecific interstitial pneumonia, NSIP, bronchiolitis obliterans organizing pneumonia, BOOP, cryptogenic organizing pneumonia, COP, cryptogenic fibrosing alveolitis, CFA, pulmonary histiocytosis X, eosinophilic granuloma, Langerhans cell histiocytosis, LCH, acute interstitial pneumonia, AIP, idiopathic BOOP, nonclassifiable ILD, neuroendocrine cell hyperplasia of infancy, NEHI, pulmonary interstitial glycogenosis, PIG, idiopathic interstitial pneumonia, cryptogenic fibrosing alveolitis, chronic pneumonitis of infancy, cellular interstitial pneumonitis
