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Histological features of patient no. 1 shows a sub-pleural elastotic fibrosis highlighted by the orcein elastic stain, that marks the alveolar walls elastosis () and the intra-alveolar fibrosis ( ) (H&E, 100×; Orcein, 40×).
Source publication
Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a recently described rare entity, characterized by pleural and subpleural parenchymal fibrosis and elastosis mainly in the upper lobes. The etiology and pathophysiology are unknown. The prognosis is poor, with no effective therapies other than lung transplantation. IPPFE should be properly iden...
Context in source publication
Context 1
... with bronchopleural fistula and subcutaneous emphysema. Histological evaluation showed marked thickened visceral pleura and prominent predominantly elastic sub-pleural fibrosis with mild, patchy lymphoplasmacytic inflammatory infiltrate; orcein stain showed that the elastosis was within the alveolar walls, marking the intra-alveolar fibrosis (Fig. 2). Despite the prescription of azathioprine (2 mg/kg/day), the patient is clinically and functionally worse after 20 months of follow-up: FVC 1.63 L (82% predicted), FEV1 1.44 L (89% predicted), FEV1/FVC 89.5%, TLC 3.28 L (80% predicted), DLco 1.66 mL/min/mmHg (26% ...
Citations
... Similarly to the reported cases, clinical presentation is not specific, with the most common symptoms consisting of exertional dyspnoea of insidious onset, dry cough and weight loss 1,8,9,10,11 . Chronic dull pleuritic pain 1,8,9,10 , recurrent lung infections 8 and platythorax due to upper lobes fibrosis 1,9,10,12 may also occur. ...
Pleuroparenchymal fibroelastosis (PPFE) is a rare and recently described interstitial pneumonia. It consists of progressive fibrosis involving the pleura and subpleural lung parenchyma, predominantly in the upper lobes, with defined and reproducible clinical, radiological and histopathological criteria. No effective treatment has yet been shown to modify the natural course of the disease, which vary greatly in the literature. Several conditions have been associated with PPFE, including connective tissue diseases (CTD). The authors present two cases of female patients with a CTD (rheumatoid arthritis and limited cutaneous systemic sclerosis, respectively) who presented with typical bilateral upper lobe thickening in chest-HRCT. In the first case, diagnosis was based on "definite" radiological and histopathological criteria for PPFE, while in the second case diagnosis was established on clinical grounds after discussion in a multidisciplinary team meeting. The authors present these cases of CTD-associated PPFE in order to raise awareness of this entity among clinicians.
... However, it was first described in the Japanese literature by Amitani et al. [2] under the name idiopathic pulmonary upper lobe fibrosis. However, it may not be as rare as it was described, and PPFE has been recognized increasingly worldwide during the past years [3]. It is mainly characterized by predominant upper lobe fibrosis [4]. ...
Introduction Pleuropulmonary fibroelastosis (PPFE) is a rare
type of interstitial lung disease (ILD); however, it may not be
as rare as it was described. PPFE has been recognized
increasingly worldwide during the past years.
Patients and methods The study was held in the Chest
Department, Kasr Al-Ainy hospitals, during the period from
January 2015 till June 2018. Seventy patients were included
and divided into two main groups. Group 1 included 36 cases
with PPFE, diagnosed either radiologically alone or combined
with histopathological examination of lung biopsy. Group 2
included 34 cases of hypersensitivity pneumonitis (HP) as
controls. Group 1 was further subdivided into two subgroups:
group A included patients with 19 PPFE without any other
pattern of ILD, and group B included 17 cases of PPFE
associated with other forms of ILD. Clinical assessment, BMI,
and high-resolution computed tomography chest were done.
The inner anteroposterior diameter (APD) and transverse
diameter (TD) of the chest wall were measured, and the ratio
between them was calculated.
Results Significant female predominance was observed.
Both groups of PPFE presented at earlier age than the HP
group. Patients with PPFE had a lower body weight and BMI
than HP group. There was a significant reduction in the APD
and TD in both groups of PPFE than HP group.
Conclusion Thirty-six cases with PPFE presented either
alone or in association with other forms of ILD. Significant
reduction in their chest wall APD in comparison with TD was
observed, giving a characteristic flat shape of the chest.
Further evaluation of this phenomena and its explanation is
required.
... However, it was first described in the Japanese literature by Amitani et al. [2] under the name idiopathic pulmonary upper lobe fibrosis. However, it may not be as rare as it was described, and PPFE has been recognized increasingly worldwide during the past years [3]. It is mainly characterized by predominant upper lobe fibrosis [4]. ...
Abstract Introduction Pleuropulmonary fibroelastosis (PPFE) is a rare type of interstitial lung disease (ILD); however, it may not be as rare as it was described. PPFE has been recognized increasingly worldwide during the past years. Patients and methods The study was held in the Chest Department, Kasr Al-Ainy hospitals, during the period from January 2015 till June 2018. Seventy patients were included and divided into two main groups. Group 1 included 36 cases with PPFE, diagnosed either radiologically alone or combined with histopathological examination of lung biopsy. Group 2 included 34 cases of hypersensitivity pneumonitis (HP) as controls. Group 1 was further subdivided into two subgroups: group A included patients with 19 PPFE without any other pattern of ILD, and group B included 17 cases of PPFE associated with other forms of ILD. Clinical assessment, BMI, and high-resolution computed tomography chest were done. The inner anteroposterior diameter (APD) and transverse diameter (TD) of the chest wall were measured, and the ratio between them was calculated. Results Significant female predominance was observed. Both groups of PPFE presented at earlier age than the HP group. Patients with PPFE had a lower body weight and BMI than HP group. There was a significant reduction in the APD and TD in both groups of PPFE than HP group. Conclusion Thirty-six cases with PPFE presented either alone or in association with other forms of ILD. Significant reduction in their chest wall APD in comparison with TD was observed, giving a characteristic flat shape of the chest. Further evaluation of this phenomena and its explanation is required.
... [3][4][5] First described 25 years ago, [6] PPFE is now considered a distinct entity that may be familial, idiopathic, or associated with pathological conditions such as hypersensitivity pneumonitis (HP), pneumoconiosis, bone marrow or lung transplant, drug-induced lung toxicity, and connective tissue diseases. [6][7][8][9][10][11][12] PPFE may coexist with different radiological and histological ILD patterns: usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), granulomatous lung diseases, and chronic hypersensitivity pneumonitis (HP). [13] Radiological PPFE has also been reported in patients with recurrent respiratory infections, which is in line with the theory that repeated inflammatory stimuli may trigger the disease. ...
Pleuroparenchymal fibroelastosis (PPFE) is a rare new interstitial lung disease (ILD) characterized by the fibrotic thickening of the visceral pleura and subadjacent parenchymal areas of the upper lobes This study reveals that patients with ILD-SSc associated with chest HRCT evidence of PPFE require close and recurrent follow-up with periodic evaluation of lung function parameters, DLCO and chest HRCT. Rheumatologists should be aware of this new radiological finding which is accompanied by a negative prognosis, especially when associated with a progressive course. Patients with this radiological pattern need to be monitored with particular attention.
... (37) A sua etiologia é desconhecida, sendo que para além das formas idiopáticas pode estar em contexto de outras patologias, como as doenças do tecido conjuntivo ou serem secundárias a toxicidade pulmonar por drogas. (38)(39)(40)(41)(42) Por outro lado, encontram-se frequentemente associadas a outras IIP como a UIP ou a NSIP. (39,40) A LIP é extremamente rara como forma idiopática, sendo habitualmente observada num contexto secundário no âmbito da síndrome de Sjögren. ...
... 288patients were stratified by chronic stable or chronic progressive disease(38). ...
Introduction
A genetic background may be involved in the susceptibility, clinical presentation and different clinical courses in interstitial lung diseases (ILD), such as sarcoidosis. The protein expressions of some genetic polymorphisms are associated with relevant pathologic pathways that sometimes, due to its association with a particular disorder, can be used as a diagnostic biomarker.
Aim
To evaluate the relationship between sarcoidosis and the most relevant associated polymorphisms described - ANXA11 rs1049550 C/T SNP, the BTNL2 rs2076530 G/A SNP, and HLA class I/II alleles - in a portuguese population, exploring gene-gene interactions regarding sarcoidosis outcomes. We also investigated the expression of CD103 in bronchoalveolar lavage fluid (BALF) T-lymphocytes in sarcoidosis comparatively with other ILD, namely hypersensitivity pneumonitis, and evaluated its relevance as a BALF diagnostic marker. We also intended to explore the value of serum metalloproteinases (MMP) 1 and 7 levels in the differential diagnosis of ILD.
Material and Methods
151 Caucasian patients from North region of Portugal were genotyped for BTNL2 rs2076530 G/A SNPs and HLA class I/II alleles and 208 for the annexin A11 (ANXA11) rs1049550 C/T (R230C) SNP. A control group of 150 healthy subjects were also genotyped for BTNL2 rs2076530 G/A SNPs and HLA class I/II alleles and other 197 for ANXA11 rs1049550 C/T SNP. Samples were genotyped for ANXA11 rs1049550 C/T and BTNL2 rs2076530 G/A SNPs using TaqMan Real-Time PCR Assays and for HLA class I/II alleles using PCR sequence specific primers. Allele frequencies were compared with Chi-square test in a univariate analysis (or the Fisher exact test when appropriate) and with logistic regression in a multivariate analysis. A total of 86
patients with ILD who underwent BALF as part of their initial diagnostic work-up, were enrolled into 3 groups: sarcoidosis (n-41), HP (n-22) and other ILD (n-23). Area under the receiver operating characteristic (ROC) curve (AUC) was used to describe the performance of CD103 for sarcoidosis diagnosis. MMP-1/7 serum levels were measured using Luminex xMAP technology in 139 patients- 47 IPF, 36 non-IPF Usual Interstitial Pneumonia (UIP), 14 idiopathic Nonspecific Interstitial Pneumonia (iNSIP), 29 secondary NSIP (secNSIP), 13 stage IV sarcoidosis- and 20 healthy controls, compared using the Mann-Whitney U test.
Results
BTNL2 rs206530 A allele frequencies (Respiratory Medicine 2012, 106: 1771-7) were significantly higher in sarcoidosis with no linkage disequilibrium with HLA-DRB1 alleles, except in the subgroup of patients with Löfgren syndrome where the determinant allele was HLA-DRB1*03. The A allele was also increased in those with isolated thoracic disease, with no differences regarding radiological stages or disease evolution. HLA-DRB1*03, besides the association with Löfgren syndrome was significantly related with disease resolution. The frequency of the annexin A11 rs1049550*T allele (Tissue Antigens, 2013, 82: 186–91) was significantly lower in sarcoidosis than in controls (33.2 vs 44.9%, P <0.001), independently of the subgroup of patients with Löfgren syndrome. Odds ratio of 0.52 and 0.44 were obtained, respectively for carriers of one (CT) and two (TT) copies normalized to the CC wild-type genotype (P <0.001). Regarding evolution, considering 2 years of evolution, only the HLA DRB1*03 allele was significantly associated with disease resolution (21.2% vs 4.9% for chronic disease; RR = 0.35; P < 0.01 after Bonferroni correction). In the logistic regression models evaluating the association between HLA alleles and chronic sarcoidosis adjusted for rs1049550 and rs2076530, only DRB1*03 was statistically significant associated with disease resolution. No significant interactions were found in any of the logistic regression analyses (BMC Pulmonary Medicine, 2015, submit.).
Sarcoidosis patients presented a significantly reduced CD103 expression in BALF T lymphocytes, more pronounced in the CD4+ subset (Respir Medicine 2012, 106: 1014-20). The BALF CD103+CD4+/CD4+ ratio for a cutoff point of 0.45 was associated with a better diagnostic performance for sarcoidosis (AUC: 0.86 [95% confidence interval (95% CI): 0.78-0.94]; sensitivity: 81%; specificity: 78%), even for those with a CD4+/CD8+ ratio <3.5 (AUC: 0.79 [95% CI: 0.64-0.93]; sensitivity: 75%; specificity: 78%). In comparison with sarcoidosis, hypersensitivity pneumonitis patients had a significantly higher number of CD4+CD103+ and CD8+CD103+ lymphocytes (Int Arch Occup Environ Health 2015, 88:167–73). MMP-1 was significantly higher in IPF than non-IPF UIP (P=.042) and sarcoidosis (P = .027). MMP-7 was significantly higher in IPF than controls (P < .001), non-IPF UIP (P = .003), secNSIP (P < .001), and sarcoidosis (P < .001). AUC for IPF versus other ILD was 0.63 (95%CI, 0.53-0.73) for MMP-1, 0.73 (95%CI, 0.65-0.81) for MMP-7, and 0.74 (95%CI, 0.66-0.82) for MMP-1/MMP-7 combined. Sensitivity and specificity for MMP-7 cutoff=3.91 ng/mL was 72.3% and 66.3%, respectively, Positive Predictive Values=52.3% and Negative Predictive Values=82.4% (Respiratory Medicine 2015, 109: 1063-1068).
Conclusions
Our findings confirm the association of BTNL2 rs2076530 A allele with sarcoidosis susceptibility in the Caucasian population. Moreover, we found independent genetic risk factors in clinically distinct disease phenotypes: BTNL2 rs2076530 A allele in patients with isolated pulmonary disease or without Löfgren syndrome, and HLA-DRB1*03 in Löfgren syndrome or disease resolution. We also confirmed that the annexin A11 rs1049550*T allele exerts a significant protective effect on sarcoidosis susceptibility. Regarding disease evolution, only DRB1*03 was associated with disease resolution after 2 years’ follow-up, with no statistically significant interactions with the other studied genes. The significant lower expression of CD4+CD103 in
sarcoidosis patients is consistent with a peripheral origin of these cells, favoring the hypothesis of redistribution from the peripheral blood and compartmentalization into the lung and showed a high potential as a diagnostic marker, namely in those with a BALF CD4+/CD8+ ratio <3.5 and in comparison with hypersensitivity pneumonitis. Serum MMP-1 and specially MMP-7 serum levels were significantly higher
in IPF than in non- IPF UIP, the main entity in its differential diagnosis, suggesting a potential use as reliable IPF serum biomarker.
... PPFE is a rare, underdiagnosed and increasingly recognised disorder with unique clinical, radiological and pathological features [1][2][3][4][5][6][7][8][9][10][11]21]. It has been defined as a distinct IIP entity in the English literature by Frankel et al. [5] and was recently included in the International Multidisciplinary Classification of the Idiopathic Interstitial Pneumonias of the American Thoracic Society/European Respiratory Society in the category of rare IIP [9]. ...
Objectives:
Pleuroparenchymal fibroelastosis (PPFE) is a rare idiopathic interstitial pneumonia (IIP) with variable clinical and radiological features. Diagnosis is based on histology obtained by surgical lung biopsy, which is associated with significant mortality and morbidity. This study aims to briefly review PPFE and discuss the role of CT-guided transthoracic core lung biopsy (TTB) in its diagnosis.
Materials/methods:
Four cases of PPFE diagnosed at our institution with TTB are reported and discussed.
Results:
Clinical, radiological and histological features are in agreement with the previous literature cases. TTB provided the diagnosis in all cases. Iatrogenic pneumothorax was the main complication in all patients. Placement of a chest tube was needed in three patients. An overlap between PPFE and other interstitial lung diseases (ILD) was documented.
Conclusion:
PPFE is an underdiagnosed IIP, so radiologist awareness of it needs to be widespread in patients with fibrosis with apical-caudal distribution. Coexistence of different lung diseases strengthens the idea of a predisposing factor. TTB proved to be a good diagnostic tool and can be considered the first choice for invasive assessment of these patients. PFFE has a variable course with no established therapeutic options; therefore a multidisciplinary team is crucial in the approach to patients with ILD.
Main messages/teaching points:
• PPFE should be considered in the differential diagnosis of fibrosis with apical-caudal distribution. • CT-guided TTB can be considered the first choice for invasive assessment of PPFE. • Site of biopsy has to be chosen carefully in order not to miss PPFE. • Coexistence of different lung diseases strengthens the idea of a predisposing factor. • A multidisciplinary team is crucial in the approach to patients with ILD.
... This publication had a second case of IPPFE which had a persistent pneumothorax after a VATS biopsy, as in our case. Both the cases published by Redondo et al. [8] were complicated by a pneumothorax post CT guided biopsy. It has been suggested that the increased deposition of elastin fibres in the lung is responsible for the easy development of pneumothorax. ...
Idiopathic pleuroparenchymal fibroelastosis is a rare idiopathic interstitial pneumonia. It was first described in 2004 and subsequently included in the ATS/ERS classification of idiopathic interstitial pneumonia in 2013. There have been few cases reported so far. The diagnostic criteria is still emerging and its etiology is being questioned. We report a case of pleuroparenchymal fibroelastosis probably idiopathic, the first of its kind to be reported from India, and a brief review of the literature.
Pleuroparenchymal fibroelastosis (PPFE) is a rare and recently described distinct pattern of lung apical fibrosis involving the upper lobe parenchyma and pleural dome.
PPFE has definable and reproducible clinical, radiological and histopathological criteria, which allowed its classification as independent interstitial lung disease. Several factors
have been associated with PPFE, such as chemotherapy, especially with alkylating agents. The authors present a case of a 34‑year‑old female with a previous history of Hodgkin
lymphoma treated with first-line chemotherapy (doxorubicin, bleomycin, vinblastine, and dacarbazine). The patient had no other known comorbidities or relevant exposure to lung irritants. A total of 2 years after completing cancer treatment, the patient developed clinical and radiological features of PPFE. Given their previous history of malignancy, a biopsy of the lesion was obtained, which confirmed the diagnosis of PPFE.
The authors present this case to raise awareness of this disease and to demonstrate that PPFE can develop months to years following chemotherapy treatment. Moreover, to date, none of these chemotherapy agents have been associated with the development of PPFE.
Background
Krebs von den Lungen‐6 (KL‐6) is a high‐molecular‐weight (200kDa) glycoprotein proposed as a diagnostic biomarker for differentiating interstitial lung disease (ILD). Systemic sclerosis (SSc) is a rare immune‐mediated disorder, and ILD is the leading cause of morbidity and mortality. Pleuroparenchymal fibroelastosis (PPFE) has been described to have a poor prognosis in SSc‐ILD patients. This study undertook to compare serial changes in KL‐6 in SSc‐ILD patients with and without PPFE, to verify its prognostic value as a disease biomarker.
Materials and Methods
Twenty‐five SSc‐ILD patients (median IQR, 62 (56‐58); 20% males) were retrospectively enrolled. 12 SSc‐ILD patients (48%) had also a radiological diagnosis of PPFE. Serum KL‐6 concentrations were measured by KL‐6 reagent assay (Fujirebio Europe, Ghent, Belgium).
Results
Serum KL‐6 measurements were increased in SSc‐ILD patients with and without PPFE compared with healthy controls (P < .0001). Comparative analysis of the rate of variation of KL‐6 over the 6 years of follow‐up was performed by serial two‐yearly KL‐6 measurements: Δ1(t1‐t0), Δ2(t2‐t1) and Δ3(t3‐t2). In SSc‐ILD patients with PPFE pattern, Δ3 was significantly different than those without PPFE pattern (P = .0020). Serum KL‐6 levels were significantly different (P = .0455) either at Δ2 and Δ3 in the PPFE group. In SSc‐ILD patients with PPFE, at t3 serum KL‐6 concentrations were inversely correlated with FEV1 (r = −.76; P = .037) and FVC percentages (r = −.79; P = .028).
Conclusion
These results suggest that serial measurements of KL‐6 in the follow‐up of these patients may help to monitor disease progression. In real life, in SSc‐ILD patients PPFE should be always evaluated at CT and when present should suggest a tight follow‐up to monitor its evolution.
