ERN GENTURIS clinical practice guidelines for the diagnosis, surveillance and management of people with Birt-Hogg-Dubé syndrome.

Birt-Hogg-Dubé syndrome (BHD syndrome) is an autosomal dominant multisystem disorder with variable expression due to pathogenic constitutional variants in the FLCN gene. Patients with BHD syndrome are predisposed to benign cutaneous fibrofolliculomas/trichodischomas, pulmonary cysts with an associated risk of spontaneous pneumothorax, and renal cell carcinoma. A requirement for updated International consensus recommendations for the diagnosis and management of BHD syndrome was identified. Based on a comprehensive literature review and expert consensus within the fields of respiratory medicine, urology, radiology, dermatology, clinical oncology and clinical genetics, updated recommendations for diagnosis, surveillance and management in BHD syndrome were developed. With the widespread availability of FLCN genetic testing, clinical scenarios in which a diagnosis should be considered and criteria for genetic testing were defined. Following a clinical and/or molecular diagnosis of BHD syndrome, a multidisciplinary approach to disease management is required. Regular renal cancer surveillance is recommended in adulthood and life-long, but the evidence base for additional tumour surveillance is limited and further research warranted. Recommendations for the treatment of cutaneous, pulmonary and renal manifestations are provided. Awareness of BHD syndrome needs to be raised and better knowledge of the clinical settings in which the diagnosis should be considered should enable earlier diagnosis. Further details, including areas for future research topics are available at: https://www.genturis.eu/l=eng/Guidelines-and-pathways/Clinical-practice-guidelines.html .

Update on cryptogenic organizing pneumonia.

Cryptogenic organizing pneumonia (COP) is a form of idiopathic interstitial pneumonia that results from the pulmonary reaction to various unidentified injuries. Secondary organizing pneumonia is diagnosed when the triggering factor has been identified; it is mainly caused by infections, toxic substance exposure, drugs, connective tissue diseases, malignancies, autoimmune diseases, bone marrow, or organ transplantation, and radiotherapy. There has been an increase in the number of reports of drug-induced organizing pneumonia (OP). New biological therapies, interferon, monoclonal antibodies, anti-interleukin antibodies, and PD1/PDL-1 inhibitors may induce this specific pulmonary reaction. The classical form of COP is usually subacute and does not manifest as severe disease. Patients maintain sufficient respiratory function, and treatment with steroids is usually effective. Several specific forms of OP (e.g., the cicatricial variant or acute fibrinous type) have distinct clinical and histological features, require higher doses of immunosuppressive drugs, and have a worse prognosis. In the era of administering steroid-sparing therapies for the treatment of interstitial lung diseases, connective tissue dases, and other conditions, it is important to emphasize this type of therapy for patients with COP.

Eosinophilic granulomatosis with polyangiitis - Advances in pathogenesis, diagnosis, and treatment.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare disease characterized by eosinophil-rich granulomatous inflammation and necrotizing vasculitis, pre-dominantly affecting small-to-medium-sized vessels. It is categorized as a primary antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) but also shares features of hypereosinophilic syndrome (HES); therefore, both vessel inflammation and eosinophilic infiltration are suggested to cause organ damage. This dual nature of the disease causes variable clinical presentation. As a result, careful differentiation from mimicking conditions is needed, especially from HES, given the overlapping clinical, radiologic, and histologic features, and biomarker profile. EGPA also remains a diagnostic challenge, in part because of asthma, which may pre-dominate for years, and often requires chronic corticosteroids (CS), which can mask other disease features. The pathogenesis is still not fully understood, however, the interaction between eosinophils and lymphocytes B and T seems to play an important role. Furthermore, the role of ANCA is not clear, and only up to 40% of patients are ANCA-positive. Moreover, two ANCA-dependent clinically and genetically distinct subgroups have been identified. However, a gold standard test for establishing a diagnosis is not available. In practice, the disease is mainly diagnosed based on the clinical symptoms and results of non-invasive tests. The unmet needs include uniform diagnostic criteria and biomarkers to help distinguish EGPA from HESs. Despite its rarity, notable progress has been made in understanding the disease and in its management. A better understanding of the pathophysiology has provided new insights into the pathogenesis and therapeutic targets, which are reflected in novel biological agents. However, there remains an ongoing reliance on corticosteroid therapy. Therefore, there is a significant need for more effective and better-tolerated steroid-sparing treatment schemes.

COVID-19 in patients with pulmonary alveolar proteinosis: a European multicentre study.

Adult PAP patients experience similar #COVID19 rates to the general population, and high rates of hospitalisation and deaths, underscoring their vulnerability and the need for measures to prevent infection. The impact of iGM-CSF must be considered. https://bit.ly/3M0wKnZ.

Novel folliculin gene mutations in Polish patients with Birt-Hogg-Dubé syndrome.

BACKGROUND: Birt-Hogg-Dubé syndrome (BHDS) is a rare, autosomal dominant, inherited disease caused by mutations in the folliculin gene (FLCN). The disease is characterised by skin lesions (fibrofolliculomas, trichodiscomas, acrochordons), pulmonary cysts with pneumothoraces and renal tumours. We present the features of Polish patients with BHDS. MATERIALS AND METHODS: The first case of BHDS in Poland was diagnosed in 2016. Since then, 15 cases from 10 families have been identified. Thirteen patients were confirmed via direct FLCN sequencing, and two according to their characteristic clinical and radiological presentations. RESULTS: BHDS was diagnosed in 15 cases (13 women and 2 men) from 10 families. The mean ages at the time of first pneumothorax and diagnosis were 38.4 ± 13.9 and 47.7 ± 13 years, respectively. Five patients (33%) were ex-smokers (2.1 ± 1.37 packyears), and 10 (67%) had never smoked cigarettes. Twelve patients (83%) had a history of recurrent symptomatic pneumothorax. Three patients had small, asymptomatic pneumothoraces, which were only detected upon computed tomography examination. All patients had multiple bilateral pulmonary cysts, distributed predominantly in the lower and middle, peripheral, and subpleural regions of the lungs. Generally, patients exhibited preserved lung function. Skin lesions were seen in four patients (27%), one patient had renal angiomyolipoma, and one had bilateral renal cancer. Different mutations of the FLCN gene were identified (mainly in exon 6), with two novel heterozygous variants: c.490delA p.(Arg164GlyTer13) and c.40delC p.(His14ThrsfTer41). CONCLUSIONS: All analysed patients with BHDS presented with lung lesions and with less frequent skin and renal lesions than previously reported in other populations. In addition, more frequent mutations located in exon 6 were detected, and two novel FLCN gene mutations were identified.

Decreased Volume of Lateral and Medial Geniculate Nuclei in Patients with LHON Disease-7 Tesla MRI Study.

Leber's hereditary optic neuropathy (LHON) is a maternally inherited genetic disorder leading to severe and bilateral loss of central vision, with a young male predilection. In recent years, multiple studies examined structural abnormalities in visual white matter tracts such as the optic tract and optic radiation. However, it is still unclear if the disease alters only some parts of the white matter architecture or whether the changes also affect grey matter parts of the visual pathway. This study aimed at improving our understanding of morphometric changes in the lateral (LGN) and medial (MGN) geniculate nuclei and their associations with the clinical picture in LHON by the application of a submillimeter surface-based analysis approach to the ultra-high-field 7T magnetic resonance imaging data. To meet these goals, fifteen LHON patients and fifteen age-matched healthy subjects were examined. A quantitative analysis of the LGN and MGN volume was performed for all individuals. Additionally, morphometric results of LGN and MGN were correlated with variables covering selected aspects of the clinical picture of LHON. In comparison with healthy controls (HC), LHON participants showed a significantly decreased volume of the right LGN and the right MGN. Nevertheless, the volume of the right LGN was strongly correlated with the averaged thickness value of the right retinal nerve fiber layer (RNFL). The abnormalities in the volume of the LHON patients' thalamic nuclei indicate that the disease can cause changes not only in the white matter areas constituting visual tracts but also in the grey matter structures. Furthermore, the correlation between the changes in the LGN volume and the RNFL, as well as the right optic nerve surface area located proximally to the eyeball, suggest some associations between the atrophy of these structures. However, to fully confirm this observation, longitudinal studies should be conducted.

Recommendations for Lung Ultrasound in Internal Medicine.

A growing amount of evidence prompts us to update the first version of recommendations for lung ultrasound in internal medicine (POLLUS-IM) that was published in 2018. The recommendations were established in several stages, consisting of: literature review, assessment of literature data quality (with the application of QUADAS, QUADAS-2 and GRADE criteria) and expert evaluation carried out consistently with the modified Delphi method (three rounds of on-line discussions, followed by a secret ballot by the panel of experts after each completed discussion). Publications to be analyzed were selected from the following databases: Pubmed, Medline, OVID, and Embase. New reports published as of October 2019 were added to the existing POLLUS-IM database used for the original publication of 2018. Altogether, 528 publications were systematically reviewed, including 253 new reports published between September 2017 and October 2019. The new recommendations concern the following conditions and issues: pneumonia, heart failure, monitoring dialyzed patients' hydration status, assessment of pleural effusion, pulmonary embolism and diaphragm function assessment. POLLUS-IM 2020 recommendations were established primarily for clinicians who utilize lung ultrasound in their everyday clinical work.