Systematic review and meta-analysis of the prognosis and prognostic factors of interstitial pneumonia with autoimmune features.

OBJECTIVE: To clarify the prognosis and prognostic factors of interstitial pneumonia with autoimmune features (IPAF) in comparison to idiopathic pulmonary fibrosis (IPF), the most common idiopathic interstitial pneumonia, and connective tissue disease-associated interstitial pneumonia (CTD-IP). DESIGN: A systematic review and meta-analysis. DATA SOURCES: Electronic databases such as Medline and Embase were searched from 2015 through 6 September 2019. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Primary studies that comparatively investigated the prognosis or prognostic factors of IPAF were eligible. DATA EXTRACTION AND ANALYSIS: Two reviewers extracted relevant data and assessed the risk of bias independently. A meta-analysis was conducted using a random-effects model. The quality of presented evidence was assessed by the Grades of Recommendation, Assessment, Development, and Evaluation system. RESULTS: Out of a total of 656 records retrieved, 12 studies were reviewed. The clinical features of IPAF were diverse between studies, which included a radiological and/or pathological usual interstitial pneumonia (UIP) pattern of between 0% and 73.8%. All studies contained some risk of bias. There was no significant difference of all-cause mortality between IPAF-UIP and IPF in all studies, although the prognosis of IPAF in contrast to IPF or CTD-IP varied between studies depending on the proportion of UIP pattern. Among the potential prognostic factors identified, age was significantly associated with all-cause mortality of IPAF by a pooled analysis of univariate results with a hazard ratio (HR) of 1.06 (95% confidence interval (CI) 1.04 to 1.07). The adjusted effect of age was also significant in all studies. The quality of presented evidence was deemed as very low. CONCLUSION: There was no significant difference of all-cause mortality between IPAF-UIP and IPF. Age was deemed as a prognostic factor for all-cause mortality of IPAF. The findings should be interpreted cautiously due to the low quality of the presented evidence. PROSPERO REGISTRATION NUMBER: CRD42018115870.

Immunistochemical Analysis of the Expression of TGFß, Galectin-1, Vimentin, and Thrombospondin in Gastric Cancer Associated with Systemic Undifferentiated Connective Tissue Dysplasia.

We performed immunohistochemical analysis of the expression of TGFß, galectin-1, vimentin, and thrombospondin in the mucosa in gastric cancer of diffuse and intestinal type associated with systemic undifferentiated connective tissue dysplasia. In diffuse gastric cancer, both with and without association with connective tissue dysplasia, a higher level of expression of TGFß, galectin-1, vimentin, and thrombospondin in the tumor was detected in comparison with the perifocal and tumor zones in intestinal gastric cancer, which may reflect the pathogenetic peculiarities of the two histotypes of gastric cancer. Intestinal type of gastric cancer associated with connective tissue dysplasia is characterized by a high level of expression of galectin-1 and vimentin in the perifocal zone and TGFß in the tumor zone. The pattern of expression of the studied markers can reflect both the pathogenetic peculiarities of the two histotypes of gastric cancer and peculiar expression of some growth factors, cytoskeleton proteins, and matrix-cell proteins associated with undifferentiated connective tissue dysplasia which may contribute to epithelial-mesenchymal transition.

Systemic sclerosis-rheumatoid arthritis overlap syndrome complicated with Sweet's syndrome.

Herein, we report a case of a 34-year-old woman with systemic sclerosis (SSc)-rheumatoid arthritis (RA) overlap syndrome (OS) complicated with Sweet's syndrome. OS has been defined as entities satisfying classification criteria of at least two connective tissue diseases (CTD) occurring at the same or at different times in the same patient. The CTD include RA, SSc, systemic lupus erythematosus (SLE), polymyositis, and dermatomyositis. Sweet's syndrome also known as acute febrile neutrophilic dermatosis was first described by Robert Sweet in 1964. Sweet's syndrome is characterized by fever, neutrophilia, erythematous skin lesions, and a diffuse dermal infiltrate of mature neutrophils. There are sets of associations that we will discuss in this article between OS and Sweet's syndrome.

Overlap of interstitial pneumonia with autoimmune features with undifferentiated connective tissue disease and contribution of UIP to mortality.

BACKGROUND AND OBJECTIVE: Criteria for interstitial pneumonia with autoimmune features (IPAF) were recently established for research purposes in a joint statement from the European Respiratory Society (ERS) and American Thoracic Society (ATS). We reviewed the utility of these criteria in patients previously diagnosed as broadly defined undifferentiated connective tissue disease (UCTD) and noted overlapping IPAF findings. Additional review was given to IPAF patients with usual interstitial pneumonia (UIP) on histopathology or radiology in terms of survival and outcome. METHODS: Patients with prior UCTD-interstitial lung disease (ILD) were screened by ERS/ATS criteria for IPAF. Clinical data along with all-cause mortality were collated and compared with selected idiopathic pulmonary fibrosis (IPF) patients from the same study period. Survival was compared between IPAF subgroups with and without UIP features. RESULTS: One hundred and one UCTD-ILD subjects (91%) evaluated from 2005 to 2012 also met strict criteria for IPAF. Frequent clinical findings included Raynaud's phenomenon, positive anti-nuclear antibody (ANA) and non-specific interstitial pneumonia (NSIP) pattern on chest computed tomography (CT). Nineteen had features of UIP either on histopathology or CT imaging. As compared with IPF, IPAF patients had overall better survival except in those with UIP features. CONCLUSION: Current IPAF criteria encompassed the majority of broadly defined UCTD-ILD and included those with UIP findings. Survival compared with IPF in those with UIP was similar. Further studies are necessary to refine IPAF definitions for clinical use and guide directed management strategies.

Pulmonary Aspergillus Overlap Syndromes.

BACKGROUND: Broadly, there are three main categories in pulmonary aspergillosis: chronic forms of aspergillosis; allergic bronchopulmonary aspergillosis; and invasive aspergillosis (IPA). IPA has been further subdivided into angioinvasive and airway-invasive aspergillosis. Aspergillus overlap syndromes is defined as the occurrence of more than one form aspergillus disease in a single individual. OBJECTIVES: To help clinicians correctly deal with AOS. METHODS: Retrospectively study the clinical findings of nine patients presenting with AOS. RESULTS: Four cases were diagnosed as angioinvasive aspergillosis complicated with ABPA, three cases as IPA overlap aspergilloma, and two cases as ABPA with AWIA. All the patients presented with cough and expectoration. In three patients with IPA overlap aspergilloma, two had hemoptysis, two had wheezing and fever. All of patients with IPA overlap ABPA had wheezing, dyspnea, and fever, three had sputum plugs, two had hemoptysis, and five patients had mucopurulent discharge and rhonchi in auscultation. Their total IgE ranged from 129 to 2124 IU/ml (676.5 ± 557.33 IU/ml). Fungal culture in sputum showed A. Fumigatus in three patients. All the six patients with IPA overlap ABPA applied steroid therapy and antifungal therapy. Three of them received two or more antifungal drugs successively, and three received combinational therapy. All the patients improved except one diagnosed ABPA overlap IPA. CONCLUSIONS: Clinical manifestation of AOS is not typical. Poor first-line therapeutic effects and complicated diagnosis criteria require clinicians to be aware of AOS when facing patients with aspergillosis.

European Dermatology Forum S1-guideline on the diagnosis and treatment of sclerosing diseases of the skin, Part 1: localized scleroderma, systemic sclerosis and overlap syndromes.

The term 'sclerosing diseases of the skin' comprises specific dermatological entities, which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present guideline focuses on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, current strategies in the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 1 of this guideline provides clinicians with an overview of the diagnosis and treatment of localized scleroderma (morphea), and systemic sclerosis including overlap syndromes of systemic sclerosis with diseases of the rheumatological spectrum.

Primary anetoderma with undifferentiated connective tissue disease.

Anetoderma is a rare benign elastolytic disorder that is characterized by focal loss of elastin fibers on histopathology and is often recalcitrant to treatment. We present a case of a patient with a 20-year history of pruritic and painful hyperpigmented atrophic papules clustered on the neck, axillae, inframammary folds, and right medial thigh. Although the histopathologyof her axillary lesions was consistent with anetoderma, her clinical presentation is unusual given the extent of involvement, reported pain and pruritus, and sharp demarcation of the distribution. The diagnosticuncertainty of this case led to added difficulty in management of a disease that is already notoriously difficult to treat and may significantly impact patient's quality of life.

CXCL4 in undifferentiated connective tissue disease at risk for systemic sclerosis (SSc) (previously referred to as very early SSc).

The aim of the study was to evaluate CXCL4 levels in undifferentiated connective tissue disease at risk for SSc (UCTD-SSc-risk) and confirm its increase and investigate its prognostic value. Serum CXCL4 levels were measured in 45 patients and 24 controls. CXCL4 was significantly higher in UCTD-SSc-risk patients than in controls. It resulted higher in patients with a shorter disease duration and in those lacking capillaroscopic alterations. We confirm that CXCL4 levels are increased in UCTD-risk-SSc patients. Further studies are needed to investigate the role of CXCL4 assessment in UCTD-risk-SSc.