scholarly journals Interstitial lung disease in an adolescent child associated with a novel STAT5B mutation-a case report

2021 ◽  
Author(s):  
Samriti Gupta ◽  
Anita Mandal ◽  
Kana Jat ◽  
Sushil Kabra
Keyword(s):  
Growth Hormone ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Novel Mutation ◽  
Pulmonary Involvement ◽  
Poor Growth ◽  
Whole Exome ◽  
Common Causes ◽  
Growth Hormone Insensitivity ◽  
Cd8 Cell

STAT5B protein is an important component of signalling pathway for growth hormone and IL-2 mediated responses. Mutation in STAT5B gene has been reported to be associated with growth hormone insensitivity, immunodeficiency and autoimmunity. Chronic pulmonary involvement is also one component of the disorder. We describe a case an adolescent girl who suffered with poor growth and loose stools since 1 year of age and was subsequently diagnosed with celiac disease and hypothyroidism. She developed features of interstitial lung disease (ILD) which were progressively worsening. Common causes of ILD were ruled out on investigations. She underwent whole exome sequencing and found to be positive for a novel mutation in STAT5B gene on exon 16. On further evaluation, she had growth hormone insensitivity and CD8 cell deficiency. This case highlights that in a child with chronic pulmonary involvement with features suggestive of growth hormone insensitivity, immunodeficiency and autoimmunity, evaluation for STAT5B mutation should be thought of.

scholarly journals Management of Myositis-Associated Interstitial Lung Disease

Medicina ◽  
2021 ◽  
Vol 57 (4) ◽  
pp. 347
Author(s):  
Tomoyuki Fujisawa
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Current Knowledge ◽  
Strong Predictor ◽  
Calcineurin Inhibitors ◽  
Pulmonary Involvement ◽  
Trna Synthetase ◽  
Evidence Based Guidelines ◽  
Substantial Heterogeneity

Idiopathic inflammatory myopathies, including polymyositis (PM), dermatomyositis (DM), and clinically amyopathic DM (CADM), are a diverse group of autoimmune diseases characterized by muscular involvement and extramuscular manifestations. Interstitial lung disease (ILD) has major pulmonary involvement and is associated with increased mortality in PM/DM/CADM. The management of PM-/DM-/CADM-associated ILD (PM/DM/CADM-ILD) requires careful evaluation of the disease severity and clinical subtype, including the ILD forms (acute/subacute or chronic), because of the substantial heterogeneity of their clinical courses. Recent studies have highlighted the importance of myositis-specific autoantibodies’ status, especially anti-melanoma differentiation-associated gene 5 (MDA5) and anti-aminoacyl tRNA synthetase (ARS) antibodies, in order to evaluate the clinical phenotypes and treatment of choice for PM/DM/CADM-ILD. Because the presence of the anti-MDA5 antibody is a strong predictor of a worse prognosis, combination treatment with glucocorticoids (GCs) and calcineurin inhibitors (CNIs; tacrolimus (TAC) or cyclosporin A (CsA)) is recommended for patients with anti-MDA5 antibody-positive DM/CADM-ILD. Rapidly progressive DM/CADM-ILD with the anti-MDA5 antibody is the most intractable condition, which requires immediate combined immunosuppressive therapy with GCs, CNIs, and intravenous cyclophosphamide. Additional salvage therapies (rituximab, tofacitinib, and plasma exchange) should be considered for patients with refractory ILD. Patients with anti-ARS antibody-positive ILD respond better to GC treatment, but with frequent recurrence; thus, GCs plus immunosuppressants (TAC, CsA, azathioprine, and mycophenolate mofetil) are often needed in order to achieve favorable long-term disease control. PM/DM/CADM-ILD management is still a therapeutic challenge for clinicians, as evidence-based guidelines do not exist to help with management decisions. A few prospective clinical trials have been recently reported regarding the treatment of PM/DM/CADM-ILD. Here, the current knowledge on the pharmacologic managements of PM/DM/CADM-ILD was mainly reviewed.

AB0528 CHARACTERIZATION OF ANTI-MPO POSITIVE INTERSTITIAL LUNG DISEASE. CLINICAL-SEROLOGIC AND RADIOLOGIC FEATURES AND SURVIVAL

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1561-1562
Author(s):  
G. Cassone ◽  
G. Dei ◽  
G. Sambataro ◽  
A. Manfredi ◽  
S. Cerri ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
Interstitial Pneumonia ◽  
Usual Interstitial Pneumonia ◽  
Pulmonary Involvement ◽  
Antineutrophil Cytoplasmic Antibodies ◽  
Anca Associated Vasculitis ◽  
Radiologic Features

Background:Prevalence of anti-neutrophil cytoplasmic antibody (ANCA) in patient with idiopathic pulmonary fibrosis (IPF) ranges from 1 to 35%, mainly anti-MPO. The presence of ANCA positivity seems to be a poorer prognostic factor in patient with IPF, and some of these patients will develop clinical vasculitis (7-23%).Unfortunately, the majority of the available studies on this topic are retrospective and the real natural history of the disease remains poorly understood.Objectives:Aim of the study was to investigate the clinical, serological and radiologic features of patients with interstitial lung disease (ILD) and positivity for anti-MPO, and to evaluate the survival of this population compared with IPF patients.Methods:We retrospectively analysed 30 patients with ILD and anti-MPO antibodies, without diagnosis of vasculitis, from 3 different rheumatology-pulmonology Italian Center.For each patient, clinical, radiologic and serological data were evaluated. Treatments were also collected, both immunosuppressants or antifibrotic agents.Finally, survival of ILD-MPO patients and of 90 unselected idiopathic pulmonary fibrosis (IPF) patients was compared.Results:Thirty patients were enrolled in the study (see table for the characteristics of the patients).Fibrosing pneumonia was described in 73.3% of patients (usual interstitial pneumonia [UIP] in 19 patients), and 10 patients (33.3%) received antifibrotic drugs, all with UIP pattern. Of interest, 7 patients were treated with immunosuppressants (azathioprine, cyclophosphamide, mycophenolate mofetil), independently by the ILD pattern and 21 (70%) low dosage of steroids.After a median period of 23.5 months (range 11-111), 7 patients developed an ANCA associated vasculitis, while other 3 developed other rheumatic diseases.Finally, when compared with IPF, ILD-MPO patients had a better survival (81.2%±0.9 vs 54.7±0.7 for ILD-MPO and IPF, respectively; p=0.045)Conclusion:ILD positive for anti-MPO antibodies are still a not definite condition. We need larger population to identify possible markers for the evolution in an ANCA associated vasculitis, to define the prognosis of disease and the better therapeutic approach.References: :[1]Mohammad AJ, et al. Pulmonary Involvement in Antineutrophil Cytoplasmic Antibodies (ANCA)-associated Vasculitis: The Influence of ANCA Subtype. J Rheumatol. 2017;44:1458-67Table.Serological, clinical and radiological features of anti-MPO + interstitial lung diseaseNumber30Males/female15/15Median age (years + IQR)68 (17)Median follow-up (months + IQR)39.5 (61)Smoke36.70%ILD pattern Usual interstitial pneumonia63.30% Nonspecific interstitial pneumonia16.70% Hipersensitivity pneumonia10% Other fibrosing pneumonia10%Median FVC (% + IQR)83 (23)Median DLCO (% + IQR)53 (28)Clinical features Raynaud’s phenomenon7.70% Sicca syndrome0 Arthralgias20% Arthritis3.40%Serology Antinuclear antibodies30.80% Anti-extractable nuclear antibodies (ENA)8% Anti-SSA4% Rheumatoid factor21.40%Therapy Immusuppressants23.30% Anti-fibrotic drugs33.30%Disclosure of Interests:None declared

scholarly journals Interpretation of autoantibody positivity in interstitial lung disease and lung-dominant connective tissue disease

2013 ◽  
Vol 39 (6) ◽  
pp. 728-741 ◽  
Author(s):  
Daniel Antunes Silva Pereira ◽  
Alexandre de Melo Kawassaki ◽  
Bruno Guedes Baldi
Keyword(s):  
Interstitial Lung Disease ◽  
Connective Tissue ◽  
Lung Disease ◽  
Connective Tissue Disease ◽  
Current Knowledge ◽  
Pulmonary Involvement ◽  
Pathophysiological Role ◽  
History Of

The initial evaluation of patients with interstitial lung disease (ILD) primarily involves a comprehensive, active search for the cause. Autoantibody assays, which can suggest the presence of a rheumatic disease, are routinely performed at various referral centers. When interstitial lung involvement is the condition that allows the definitive diagnosis of connective tissue disease and the classical criteria are met, there is little debate. However, there is still debate regarding the significance, relevance, specificity, and pathophysiological role of autoimmunity in patients with predominant pulmonary involvement and only mild symptoms or formes frustes of connective tissue disease. The purpose of this article was to review the current knowledge of autoantibody positivity and to discuss its possible interpretations in patients with ILD and without clear etiologic associations, as well as to enhance the understanding of the natural history of an allegedly new disease and to describe the possible prognostic implications. We also discuss the proposition of a new term to be used in the classification of ILDs: lung-dominant connective tissue disease.

scholarly journals Heme oxygenase-1 deficiency presenting with interstitial lung disease and hemophagocytic flares

2020 ◽  
Author(s):  
Alice S. Chau ◽  
Bonnie L. Cole ◽  
Jason S. Debley ◽  
Kabita Nanda ◽  
Aaron B.I. Rosen ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Heme Oxygenase ◽  
Autosomal Recessive Disorder ◽  
Clinical Findings ◽  
Heme Oxygenase 1 ◽  
Compound Heterozygous ◽  
Biliverdin Reductase ◽  
Frame Shift ◽  
Whole Exome

Abstract Background Heme oxygenase-1 (HMOX1) catalyzes the metabolism of heme into carbon monoxide, ferrous iron, and biliverdin. Through biliverdin reductase, biliverdin becomes bilirubin. HMOX1 -deficiency is an exceedingly rare autosomal recessive disorder with hallmark features of direct antibody negative hemolytic anemia with normal bilirubin, hyperinflammation and features indicating hemophagocytosis lymphohistiocytosis. Clinical findings have included asplenia, nephritis, hepatitis, and evidence of vasculitis. Pulmonary features and evaluation of the immune response have been limited. Results Here, we present the fifth reported case in literature of a young boy who remarkably also presented with chronic respiratory failure due to nonspecific interstitial pneumonia in addition to infection-triggered recurrent hyperinflammatory flares notable for hemolysis without hyperbilirubinemia, immunodeficiency, hepatomegaly with mild transaminitis, asplenia, leukocytosis, thrombocytosis, joint pain and features of macrophage activation with negative autoimmune serologies. Lung biopsy revealed cholesterol granulomas. He was found post-mortem by whole exome sequencing to have a compound heterozygous paternal frame shift a paternal frame shift HMOX1 c.264delCTGG (p.L89Sfs*24) and maternal splice donor HMOX1 (c.636+2 T>A) consistent with HMOX1 deficiency. Western blot analysis confirmed lack of HMOX1 protein upon oxidant stimulation of the patient cells. Conclusions Here, we describe a phenotype expansion for HMOX1-deficiency to include not only asplenia and hepatomegaly, but also interstitial lung disease with cholesterol granulomas and inflammatory flares with hemophagocytosis present in the bone marrow.

scholarly journals Shared genetic predisposition in rheumatoid arthritis-interstitial lung disease and familial pulmonary fibrosis

2017 ◽  
Vol 49 (5) ◽  
pp. 1602314 ◽  
Author(s):  
Pierre-Antoine Juge ◽  
Raphaël Borie ◽  
Caroline Kannengiesser ◽  
Steven Gazal ◽  
Patrick Revy ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Interstitial Lung Disease ◽  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
European Ancestry ◽  
Whole Exome ◽  
Burden Test ◽  
Excess Number ◽  
Familial Pulmonary Fibrosis

Despite its high prevalence and mortality, little is known about the pathogenesis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Given that familial pulmonary fibrosis (FPF) and RA-ILD frequently share the usual pattern of interstitial pneumonia and common environmental risk factors, we hypothesised that the two diseases might share additional risk factors, including FPF-linked genes. Our aim was to identify coding mutations of FPF-risk genes associated with RA-ILD.We used whole exome sequencing (WES), followed by restricted analysis of a discrete number of FPF-linked genes and performed a burden test to assess the excess number of mutations in RA-ILD patients compared to controls.Among the 101 RA-ILD patients included, 12 (11.9%) had 13 WES-identified heterozygous mutations in the TERT, RTEL1, PARN or SFTPC coding regions. The burden test, based on 81 RA-ILD patients and 1010 controls of European ancestry, revealed an excess of TERT, RTEL1, PARN or SFTPC mutations in RA-ILD patients (OR 3.17, 95% CI 1.53–6.12; p=9.45×10−4). Telomeres were shorter in RA-ILD patients with a TERT, RTEL1 or PARN mutation than in controls (p=2.87×10−2).Our results support the contribution of FPF-linked genes to RA-ILD susceptibility.

scholarly journals OP0167 THE ROLE OF LUNG ULTRASOUND IN THE DIAGNOSIS OF INTERSTITIAL LUNG DISEASE IN CHILDREN WITH DERMATOMYOSISTIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 100.3-100
Author(s):  
R. Dertkgil ◽  
C. Cappello ◽  
S. Dertkigil ◽  
R. Marini ◽  
S. Appenzeller
Keyword(s):  
Computed Tomography ◽  
High Resolution ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Gold Standard ◽  
Lung Ultrasound ◽  
Pulmonary Involvement ◽  
High Resolution Computed Tomography ◽  
B Lines ◽  
Transthoracic Ultrasound

Background:Dermatomyositis is a multi organ autoimmune disease wich is commonly complicated with interstitial lung disease. Chest high-resolution computed tomography (HRCT) is still considered the diagnostic gold standard for interstitial lung disease and is quantification, however he increasing use of lung ultrasound may play an important role in the future.Objectives:The aim of our study was to determine the diagnostic value of lung ultrasound in the detection and progression of interstitial pulmonary disease in patients with dermatomyositis.Methods:Twenty two subjects with dermatomyositis diagnosed according to the American College of Rheumatology criteria were enrolled (6 males, 16 females; mean age: 15,8 ± 8.8 years; range: 6 to 29 years). All subjects underwent high resolution computed tomography followed by transthoracic ultrasound for comet tail sign detection and pleural irregularity in order to predict the degree of interstitial lung disease. The modified transthoracic ultrasound assessment was performed at 06 thoracic regions each side. The Warrick score was calculated according standard high-resolution chest computed tomography images that were evaluated independently from each other by two thoracics radiologists.Results:A significantly positive correlation between transthoracic ultrasound and the severity of pulmonary involvement, as seen by the number of B lines (Spearman ‘s correlation coefficient = 0.80, p < 0.001), and the number of positive areas (regions wih more than 3 B lines) (Spearman ‘s correlation coefficient = 0.75, p < 0.001) were found. When compared with high-resolution chest computed tomography as the gold standard method, the sensitivity, specificity, of transthoracic ultrasound was 96.4%, 83,3% respectively. Addicionally the number of B lines (sum of 35 or more B lines) and a number of B lines positive areas (7 or more regions with at least 3 B lines) cut of allowed to discriminate the inflamatory pattern (ground glass) to those with structural pattern (honeycomb and pulmonary cysts).Conclusion:Our study showed that transthoracic ultrasound comet tails scoring system could be useful in the assessment of the pulmonary involvement in patients with dermatomyositis, and should be considered as a primary screening exam to exclude lung involvement, rather than routine chest CT scans in assimptomatic patients.Disclosure of Interests:None declared

scholarly journals Interstitial Lung Disease of the UIP Variant as the Only Presenting Symptom of Rheumatoid Arthritis

2015 ◽  
Vol 2015 ◽  
pp. 1-5
Author(s):  
Abhinav Agrawal ◽  
Braghadheeswar Thyagarajan ◽  
Sidney Ceniza ◽  
Syed Hasan Yusuf
Keyword(s):  
Rheumatoid Arthritis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Joint Pain ◽  
Previous History ◽  
Usual Interstitial Pneumonia ◽  
Pulmonary Involvement ◽  
Chronic Inflammatory Disease ◽  
The Body ◽  
Organ Systems

Rheumatoid arthritis is a chronic inflammatory disease primarily manifesting with symptoms of joint pain. It also involves multiple organ systems in the body, including the lungs. Interstitial lung disease (ILD) is the most common form of pulmonary involvement in rheumatoid arthritis (RA). Without the typical symptoms such as chronic joint pain, establishing the diagnosis of RA could be quite challenging and a high index of suspicion is thereby required to diagnose ILD in patients with RA, thereby delaying treatment and increasing morbidity and mortality. We report a case of a 67-year-old Hispanic male with no previous history of rheumatoid arthritis or symptoms of typical joint pain who comes to the hospital only with the chief complaints of progressive worsening of shortness of breath for a duration of 6 months and was eventually diagnosed with ILD of the usual interstitial pneumonia variant with serologies positive for rheumatoid arthritis.

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