Search

Background: Tumor necrosis factor (TNF) antagonists have been reported as an efficient third-line therapy for sarcoidosis but there is no data regarding patients who do not respond to this treatment. Objective: To report the characteristics, the outcome and the response to therapy of patients with sarcoidosis resistant to TNF antagonists. Methods: Patients from the French STAT (Sarcoidosis Treatment with Anti-TNF) registry who were classified as non-responders and who were followed-up for >1 year were included. The response to further therapies was classified as complete response, or partial response, and the others were classified as non-responders. Results: Among the 132 patients from the registry, 14 were considered as non-responders to anti-TNF. Nine patients (66% of women; mean age 48 years) were analyzed. The mean number of organs involved was 4.2. Seven patients were previously treated with more than 2 immunosuppressive treatments. The mean duration of the anti-TNF treatment was 9 months (range, 3-24). After a mean follow-up duration of 58 months (median, 35; range, 19-128) a complete response was observed in 2/9 cases, a partial response in 5/9 cases, and 2/9 cases were considered as non-responders. In all but one patient, the immunosuppressant that allowed the clinical response had previously been used. Furthermore, the dosage was not necessarily increased to gain efficacy. Non-responders were treated by corticosteroids only because of their comorbidities or noncompliance. Conclusion: In patients who do not respond to TNF antagonists, previously used immunosuppressants may be useful. Excluding a differential diagnosis, assessing compliance and testing for anti-drug antibodies should be systematic. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 371-375)

Extrapulmonary sarcoidosis occurs in 30-50% of cases of sarcoidosis, most often in association with pulmonary involvement, and virtually any organ can be involved. Its incidence depends according to the organs considered, clinical phenotype, and history of sarcoidosis, but also on epidemiological factors like age, sex, geographic ancestry, and socio-professional factors. The presentation, symptomatology, organ dysfunction, severity, and lethal risk vary from and to patient even at the level of the same organ. The presentation may be specific or not, and its occurrence is at variable times in the history of sarcoidosis from initial to delayed. There are schematically two types of presentation, one when pulmonary sarcoidosis is first discovered, the problem is then to detect extrapulmonary localizations and to assess their link with sarcoidosis, while the other presentation is when extrapulmonary manifestations are indicative of the disease with the need to promptly make the diagnosis of sarcoidosis. To improve diagnosis accuracy, extrapulmonary manifestations need to be known and a medical strategy is warranted to avoid both under- and over-diagnosis. An accurate estimation of impairment and risk linked to extrapulmonary sarcoidosis is essential to offer the best treatment. Most frequent extrapulmonary localizations are skin lesions, arthritis, uveitis, peripheral lymphadenopathy, and hepatic involvement. Potentially severe involvement may stem from the heart, nervous system, kidney, eye and larynx. There is a lack of randomized trials to support recommendations which are often derived from what is known for lung sarcoidosis and from the natural history of the disease at the level of the respective organ. The treatment needs to be holistic and personalized, taking into account not only extrapulmonary localizations but also lung involvement, parasarcoidosis syndrome if any, symptoms, quality of life, medical history, drugs contra-indications, and potential adverse events and patient preferences. The treatment is based on the use of anti-sarcoidosis drugs, on treatments related to organ dysfunction and supportive treatments. Multidisciplinary discussions and referral to sarcoidosis centers of excellence may be helpful for difficult diagnosis and treatment decisions.

Background Genetic testing is proposed for suspected cases of monogenic pulmonary fibrosis, but clinicians and patients need specific information and recommendation about the related diagnosis and management issues. Because multidisciplinary discussion (MDD) has been shown to improve accuracy of interstitial lung disease (ILD) diagnosis, we evaluated the feasibility of a genetic MDD (geneMDD) dedicated to the indication for and interpretation of genetic testing. The geneMDD group met monthly and included pediatric and adult lung specialists with ILD expertise, molecular and clinical geneticists, and one radiologist. Hematologists, rheumatologists, dermatologists, hepatologists, and pathologists were also invited to attend. Results Since 2016, physicians from 34 different centers in 7 countries have participated in the geneMDD. The medical files of 95 patients (53 males) have been discussed. The median age of patients was 43 years [range 0–77], 10 were ≤ 15 years old, and 6 were deceased at the time of the discussion. Among 85 analyses available, the geneMDD considered the rare gene variants pathogenic for 61: 37 variants in telomere-related genes, 23 variants in surfactant-related genes and 1 variant in MARS. Genetic counseling was offered for relatives of these patients. The geneMDD therapeutic proposals were as follows: antifibrotic drugs (n = 25), steroids or immunomodulatory therapy (n = 18), organ transplantation (n = 21), watch and wait (n = 21), or best supportive care (n = 4). Conclusion Our experience shows that a dedicated geneMDD is feasible regardless of a patient’s age and provides a unique opportunity to adapt patient management and therapy in this very rare condition.

To describe the current knowledge on indications for sarcoidosis treatment.Despite the lack of evidence-based recommendations, the sarcoidosis community has adopted the concept of starting systemic anti-inflammatory treatment because of potential danger (risk of severe dysfunction on major organs or death) or unacceptable impaired quality of life (QoL). On the contrary, while QoL and functionality are patients' priorities, few studies have evaluated treatment effect on patient-reported outcomes. The awareness of long-term corticosteroids toxicities and consequences on QoL and the emergence of novel drugs have changed therapeutic management. Second-line therapy, mainly methotrexate and azathioprine, are indicated for corticosteroids sparing or corticosteroids-resistant sarcoidosis. TNF-α inhibitors are a useful third-line therapy in chronic refractory disease. In addition to organ-targeted treatment, efforts should also be taken for treating nonorgan-specific symptoms, such as physical training for fatigue, and various disease complications.Clinicians should offer a tailored treatment for each patient and ensure a holistic multidisciplinary approach, including pharmacological and nonpharmacological interventions. Patient-centered communication is critical to drive shared decisions, in particular for the tricky situation of isolated impaired QoL as the unique therapeutic indication. Once treatment is decided, clinicians should define a clear therapeutic plan, including goals and instruments to assess response.

(1) Background: Systemic granulomatosis developed in a context of malignancy has already been reported. Our objective was to describe the clinical, radiological, functional, biological, and evolutive characteristics of sarcoidosis-like cancer-associated granulomatosis (SLCAG) and to compare them to those of sarcoidosis. (2) Methods: 38 patients with a biopsy-proven SLCAG developed after a diagnostic of malignancy were included. The control group consisted of sarcoidosis patients matched for age, sex, and radiologic stage. Clinical, biological, physiological, radiological, and outcome data were collected. (3) Results: The mean age of SLCAG patients was 51 ± 14 years. They were diagnosed within 15 ± 14 months of the cancer diagnosis (breast cancer most frequently). All SLCAG patients presented a thoracic involvement, extrathoracic locations were observed in 32% of subjects. SLCAG was more often asymptomatic than sarcoidosis (p &lt, 0.0001). During follow-up, systemic treatment was less often required in SLCAG than in sarcoidosis (58% vs. 32%, p = 0.04 respectively) and SLCAG were characterized by a significantly less severe progression profile according to the Sarcoid Clinical Activity Classification, with a complete recovery more frequent at 5 years (p = 0.03). (4) Conclusion: This case-control study shows that SLCAG differs from sarcoidosis with a significantly more benign course. These results might argue for true differences in the physiopathology, which remain to be elucidated.

International audience; BackgroundLow income, a known prognostic indicator of various chronic respiratory diseases, has not been properly studied in idiopathic pulmonary fibrosis (IPF). We hypothesize that a low income has an adverse prognostic impact on IPF.MethodsPatients were selected from the French national prospective cohort COFI. Patients’ income was assessed through the median city-level income provided by the French National Institute of Statistics and Economic Studies according to their residential address. Patients were classified in two groups as “low income” vs. “higher income” depending on whether their annual income was estimated to be < or ≥18 170 €/year (the first quartile of the income distribution in the study population). The survival and progression-free survival (PFS) of the groups were compared by a log-rank test and a Cox model in multivariate analysis.Results200 patients were included. The average follow-up was 33.8 ± 22.7 months. Patients in the low income group were significantly more likely to be of non-European origin (p < 0.006), and to have at least one occupational exposure (p < 0.0001), and they tended to have a higher cumulative exposure to fine particles PM2.5 (p = 0.057). After adjusting for age, gender, forced vital capacity at inclusion, geographical origin, and occupational exposure having a low-income level was a factor associated with a worse PFS (HR: 1.81; CI95%: 1.24–2.62, p = 0.001) and overall survival (HR: 1.49; CI95%: 1.0006–2.23, p = 0.049).ConclusionsLow income appears to be a prognostic factor in IPF. IPF patients with low incomes may also be exposed more frequently to occupational exposures.

IntroductionInterstitial lung diseases (ILDs) can be caused by mutations in the SFTPA1 and SFTPA2 genes, which encode the surfactant protein (SP) complex SP-A. Only 11 SFTPA1 or SFTPA2 mutations have so far been reported worldwide, of which five have been functionally assessed. In the framework of ILD molecular diagnosis, we identified 14 independent patients with pathogenic SFTPA1 or SFTPA2 mutations. The present study aimed to functionally assess the 11 different mutations identified and to accurately describe the disease phenotype of the patients and their affected relatives.MethodsThe consequences of the 11 SFTPA1 or SFTPA2 mutations were analysed both in vitro, by studying the production and secretion of the corresponding mutated proteins and ex vivo, by analysing SP-A expression in lung tissue samples. The associated disease phenotypes were documented.ResultsFor the 11 identified mutations, protein production was preserved but secretion was abolished. The expression pattern of lung SP-A available in six patients was altered and the family history reported ILD and/or lung adenocarcinoma in 13 out of 14 families (93%). Among the 28 SFTPA1 or SFTPA2 mutation carriers, the mean age at ILD onset was 45 years (range 0.6–65 years) and 48% underwent lung transplantation (mean age 51 years). Seven carriers were asymptomatic.DiscussionThis study, which expands the molecular and clinical spectrum of SP-A disorders, shows that pathogenic SFTPA1 or SFTPA2 mutations share similar consequences for SP-A secretion in cell models and in lung tissue immunostaining, whereas they are associated with a highly variable phenotypic expression of disease, ranging from severe forms requiring lung transplantation to incomplete penetrance.

International audience; Scedosporiosis/lomentosporiosis is a devastating emerging fungal infection. Our objective was to describe the clinical pattern and to analyze whether taxonomic grouping of the species involved was supported by differences in terms of clinical presentations or outcomes. We retrospectively studied cases of invasive scedosporiosis in France from 2005 through 2017 based on isolates characterized by polyphasic approach. We recorded 90 cases, mainly related to Scedosporium apiospermum (n = 48), S. boydii/S. ellipsoideum (n = 20), and Lomentospora prolificans (n = 14). One-third of infections were disseminated, with unexpectedly high rates of cerebral (41%) and cardiovascular (31%) involvement. In light of recent Scedosporium taxonomic revisions, we aimed to study the clinical significance of Scedosporium species identification and report for the first time contrasting clinical presentations between infections caused S. apiospermum, which were associated with malignancies and cutaneous involvement in disseminated infections, and infections caused by S. boydii, which were associated with solid organ transplantation, cerebral infections, fungemia, and early death. The clinical presentation of L. prolificans also differed from that of other species, involving more neutropenic patients, breakthrough infections, fungemia, and disseminated infections. Neutropenia, dissemination, and lack of antifungal prescription were all associated with 3-month mortality. Our data support the distinction between S. apiospermum and S. boydii and between L. prolificans and Scedosporium sp. Our results also underline the importance of the workup to assess dissemination, including cardiovascular system and brain. Lay Summary Scedosporiosis/lomentosporiosis is a devastating emerging fungal infection. Our objective was to describe the clinical pattern and to analyze whether taxonomic grouping of the species involved was supported by differences in terms of clinical presentations or outcomes.

Objective: There are a number of factors that go into a recommendation to treat non-tuberculous mycobacterial lung infection (NTM-LI). The purpose of the study is to validate consensus recommendations on clinical considerations before treating a NTM-LI. Methods: We engaged respiratory physicians of the "Mycobacterioses" working group, part of the research and teaching group in pulmonology and infectious diseases (GREPI), on behalf of the SPLF (Societe de Pneumologie de Langue Francaise) in a Delphi survey concerning three areas of interest for physicians before they had to decide to treat (Diagnosis, Definition of the level of severity and Clinical assessment before deciding to treat) in order to create a decision algorithm. Each assertion was subjected to rating and free comments by these experts via an online questionnaire. The scores were weighted by the number of patients seen each year by the experts. The assertions having obtained a weighted average greater than 9/10 were validated. Otherwise they were subject to re-evaluation during round 2 until reaching 9/10. Results: A total of 37 experts responded. At first round, 9/38 assertions obtained a strong agreement (median ≥7 and 80% of responses >7). Other assertions from all domains, in particular the definition of the level of severity, were revised and new assertions added for submission to scoring in round 2. Fifty-one assertions were finally assessed. Agreement was strong in 78% of the assertions (40/51); moderate in 22% (11/51). There was no disagreement. Conclusion: We obtained a consensus from physicians about clinical considerations before deciding to treat NTM-LI and we propose a decision algorithm to guide a treatment decision.

Introduction Pulmonary fibrosing sarcoidosis is associated with increased mortality. This study was aimed to explore the prognosis value of a panel of parameters for predicting mortality. Methods This retrospective study included 216 patients with confirmed stage 4 pulmonary sarcoidosis. Stage 4 diagnosis date served as baseline. The following information was systematically present at baseline: epidemiological characteristics; treatments; pulmonary function; composite physiologic index (CPI); systolic pulmonary artery pressure at echocardiography; pulmonary fibrosis extent, main pulmonary artery/ascending aorta diameters ratio (MPAD/AAD) and MPAD/body surface area (BSA) measured and calculated using computed tomography, Walsh's algorithm based on CPI, lung fibrosis extent and MPAD/AAD ratio, and modified Walsh's algorithm with MPAD/BSA replacing MPAD/AAD allowed to estimate good or bad prognosis profiles. The primary outcome of the study was all cause mortality and lung transplantation. The value of baseline parameters was tested as predictors of mortality using univariate and multivariate analyses. Results Median follow-up was 105 months. There were 41 deaths and 5 transplantations. At multivariate analysis, survival was independently predicted by several parameters including CPI, lung fibrosis extent, pulmonary hypertension at echography or MPAD/BSA ratio, Walsh's algorithm, and geographic origin. The modified Walsh's algorithm was most highly predictive. Conclusion Survival was best predicted by geographic origin, lung fibrosis extent, PH at echography or MPAD/BSA ratio, as well as by various scores among them the modified Walsh's algorithm had very high predictive value thanks to MPAD/BSA ratio which accurately predicted mortality.

Interstitial lung diseases (ILDs) can be caused by mutations in theThe consequences of the 11For the 11 identified mutations, protein production was preserved but secretion was abolished. The expression pattern of lung SP-A available in six patients was altered and the family history reported ILD and/or lung adenocarcinoma in 13 out of 14 families (93%). Among the 28This study, which expands the molecular and clinical spectrum of SP-A disorders, shows that pathogenic

Multiple problems may be encountered during the diagnosis of sarcoidosis: at first diagnose sarcoidosis in an appropriate clinical setting, secondly, identify any manifestation to be linked to sarcoidosis at diagnosis work-up and during evolution; thirdly, recognize "danger" in sarcoidosis and parasarcoidosis syndromes, and finally, diagnose sarcoidosis recovery. Diagnosis is often delayed as presentation may be diverse, non-specific, or atypical. Diagnosis of sarcoidosis is based on three criteria: a compatible presentation; evidence of non-caseating granulomas and exclusion of any alternative diagnosis. However, even when all criteria are fulfilled, the probability of sarcoidosis diagnosis varies from definite to only possible depending upon the presence of more or less characteristic radio-clinical and histopathological findings and on the epidemiological context. Bilateral hilar lymphadenopathy and/or diffuse lung micronodules mainly along lymphatics are the most frequent highly suggestive findings. Evidence of granulomas relies on superficial biopsies of clinically suspected lesion when present or most often by bronchial endoscopy. The diagnosis of sarcoidosis may be difficult in absence of thoracic or skin manifestations and may require the benefit of hindsight before being definitive. Differential diagnoses, mainly tuberculosis, must be considered. The diagnosis of events during evolution relies on serial clinical, pulmonary function, radiographic evaluation and on extrapulmonary manifestations work-up, including electrocardiogram and blood biology. Affected organs need to be related to sarcoidosis using an appropriate diagnostic assessment instrument. To declare the recovery of sarcoidosis, all manifestations must have disappeared spontaneously or after 3-5 years post-treatment without relapse.

Resume La sarcoidose est une granulomatose de cause inconnue avec une atteinte pulmonaire quasi-constante et une evolution difficile a predire. Le diagnostic est retenu dans un triple contexte devant un tableau clinico-radiologique le plus souvent evocateur, la mise en evidence de granulomes typiques sans necrose caseeuse par des biopsies de lesions superficielles, per-endoscopiques bronchiques ou encore ganglionnaires mediastinales sous controle echoendoscopique et l’exclusion des autres causes de granulomatose pouvant donner un meme tableau. La corticotherapie constitue le traitement de premiere ligne en cas d’indication therapeutique, situation rencontree chez la moitie des patients. Les traitements de deuxieme et de troisieme ligne sont respectivement les agents cytotoxiques et les biomedicaments anti-TNF-α. Les formes pulmonaires severes — fibrose sarcoidienne, hypertension pulmonaire, stenoses bronchiques et greffe aspergillaire — sont les premieres causes de morbi-mortalite. Les enjeux dans l’atteinte pulmonaire sont de ne pas meconnaitre un diagnostic alternatif, de savoir quand et comment traiter les patients et de cibler au mieux ceux a risque de developper des formes severes.

Resume Introduction La toxicite musculaire aigue de la corticotherapie est une complication rare, caracterisee par un deficit myogene diffus et une rhabdomyolyse, reversible a l’arret de la corticotherapie. Observation Nous rapportons l’observation d’une femme prise en charge en reanimation pour une crise d’asthme severe ayant developpe une rhabdomyolyse sous corticoides a forte dose. Cette rhabdomyolyse est apparue au quinzieme jour avec un pic de CPK a 28 160 UI/L (n Conclusion Cette myopathie necrosante aigue declenchee par la corticotherapie a forte dose est une complication de mecanisme multifactoriel, et survient presque exclusivement au cours des crises d’asthme severes en reanimation.

Introduction Chronic back pain (CBP) is a frequent complaint in patients with sarcoidosis, which challenges the clinician as multiples causes may potentially underlie this symptom. Interestingly, some reports suggest that the coexistence of sarcoidosis and spondyloarthritis (SpA) may be frequent. This study aimed to determine the prevalence of axial radiographic and non-radiographic SpA in patients with sarcoidosis and CBP and assess the association between patient characteristics and SpA. Methods This cross-sectional study enrolled 64 patients with a diagnosis of sarcoidosis and CBP. Patients describing CBP underwent a full spine MRI and radiography. All patients with inflammatory CBP underwent complementary sacroiliac joint MRI. The diagnosis of axial SpA was based on the Assessment of SpondyloArthritis International Society classification criteria. Results Among the 64 patients (49 women) with sarcoidosis and CBP, 29 had inflammatory pain; 15/64 had a diagnosis of SpA (23.4% [95% CI: 13.7–35.6], 14/29 (48.3% [95% CI: 29.5–67.5] of those with inflammatory back pain). MRI sacroiliitis was found in 13 patients. On both univariate and multivariate analysis, SpA diagnosis was associated with inflammatory CBP (OR=28.5, 95% CI: 1.91–425.4) and sarcoidosis limited to the thorax (OR=6.74, 95% CI: 1.08–42.1). SpA was associated with young age (p = 0.0093) and male sex (p = 0.021) only on univariate analysis. Besides, 12/64 patients (18.8%, 95% CI: 10.1–30.5) had a diagnosis of sarcoidosis spine bone lesions, 7/64 (10.9%, 95% CI: 4.5–21.2) symptomatic vertebral fracture and 30/64 (46.9%, 95% CI: 34.3–59.8) degenerative spine. Conclusions The prevalence of SpA is increased in sarcoidosis patients with inflammatory back pain. The systematic use of spine and sacroiliac MRI in this subgroup is justified. The association between other patient features and SpA needs further confirmation.

Regulator of telomere length 1 (RTEL1) mutations have been evidenced in 5–9% of familial pulmonary fibrosis; however, the phenotype of patients with interstitial lung disease (ILD) and RTEL1 mutations is poorly understood.Whole exome sequencing was performed in 252 probands with ILD and we included all patients with ILD and RTEL1 mutation. RTEL1 expression was evaluated by immunochemistry in the lungs of controls, as well as in RTEL1 and telomerase reverse transcriptase (TERT) mutation carriers.We identified 35 subjects from 17 families. Median age at diagnosis of ILD was 53.1 years (range 28.0–80.6). The most frequent pulmonary diagnoses were idiopathic pulmonary fibrosis (n=20, 57%), secondary ILD (n=7, 20%) and unclassifiable fibrosis or interstitial pneumonia with autoimmune features (n=7, 20%). The median transplant-free and overall survival periods were 39.2 months and 45.3 months, respectively. Forced vital capacity at diagnosis was the only factor associated with decreased transplant-free survival. Extra-pulmonary manifestations were less frequent as compared to other telomere-related gene mutation carriers. A systematic analysis of the literature identified 110 patients with ILD and RTEL1 mutations (including this series) and confirmed the heterogeneity of the pulmonary phenotype, the prevalence of non-idiopathic diseases and the low prevalence of extra-pulmonary manifestations.Immunohistochemistry showed that RTEL1 was expressed by bronchial and alveolar epithelial cells, as well as by alveolar macrophages and lymphocytes, but not by fibroblasts.

Resume Objectifs Decrire les lesions broncho-pulmonaires residuelles et evaluer l’interet de la tomodensitometrie (TDM) en fin de traitement d’une tuberculose pulmonaire. Materiels et methodes Analyse des TDM thoraciques initiales et de fin de traitement de 56 patients avec tuberculose pulmonaire selon une grille de lecture incluant les lesions parenchymateuses et des voies aeriennes. Les donnees TDM de fin de traitement ont ete analysees en fonction des donnees cliniques, mycobacteriologiques et du TDM initial. Resultats Des lesions actives (cavite a paroi epaisse et/ou micronodules centrolobulaires) persistaient chez 24 patients (43 %) apres un traitement moyen de 7 mois. La persistance de ces signes d’activite etait correlee initialement a la presence d’un syndrome cavitaire (p = 0,027), a une atteinte bronchique predominant en sous-segmentaire, a une extension plus importante des micronodules (p = 0,024) et a des bronchectasies (p = 0,04). Ces lesions residuelles n’etaient pas associees a un risque plus eleve de rechute. Conclusion La persistance de signes d’activite sur la TDM de fin de traitement d’une tuberculose ne correspond pas obligatoirement a une absence de guerison mais a un retard radiologique. Cette imagerie est neanmoins utile pour faire le bilan des sequelles de l’arbre bronchique, voire estimer le risque de complications ulterieures.

Objective: To compare the efficacy of methotrexate (MTX) and mycophenolate mofetil (MMF) in the prevention of relapses in neurosarcoidosis. Methods: We conducted a retrospective multicenter study including patients who received MTX or MMF for the treatment of histologically proven neurosarcoidosis. The efficacy of the immunosuppressive drug was assessed by determining the time to relapse. Results: Forty patients with a diagnosis of neurosarcoidosis (24 men, 16 women, median age at diagnosis 43.5 years) who received at least 3 months of MTX (n = 32) or MMF (n = 14) were included. The immunosuppressive drug was always associated with steroids. The rate of relapse was 47% in the MTX group (0.2 relapses per year of exposure) and 79% in the MMF group (0.6 relapses per year of exposure) (p = 0.058). The median time to relapse was significantly shorter in the MMF group (11 months) compared with the MTX group (28 months) (p = 0.049). Adverse events occurred in 11 patients during MTX therapy and in 1 patient during MMF therapy (p = 0.12). Conclusions: Relapses of neurosarcoidosis occur frequently, despite the use of an immunosuppressive drug in addition to corticosteroids. MTX significantly increases the survival time without relapse compared to MMF and should be preferred over MMF for the treatment of neurosarcoidosis. This study provides Class IV evidence that for patients with neurosarcoidosis taking steroids, MTX is superior to MMF in reducing the risk of relapse.

Sarcoidosis is a systemic disease of unknown cause with very diverse presentation, outcome, severity and need for treatments. While some presentations may be very typical, for many patients, the presentation is nonspecific, with shared associations with other diseases at times being by far more frequent or misleading, which can be a cause of significant delay and often several consultations before a diagnosis of sarcoidosis can be confirmed. This is particularly the case when pulmonary manifestations are in the forefront. The diagnosis relies on three well-known criteria. In clinical practice, these criteria are not easily implemented, particularly by physicians without expertise in sarcoidosis, which can lead to a risk of either under- or over-diagnosis. Qualifying the presentation according to sarcoidosis diagnosis is essential. However, it is often not easy to classify the presentation as typical versus compatible or compatible versus inconsistent. Further investigations are needed before any other hypothesis is to be considered. It is important to detect events and to determine whether or not they are indicative of a flare of sarcoidosis. Eventually, treatment needs to be related to the correct indications. The evaluation of the efficacy and safety of treatments is crucial. To address such issues, we present five emblematic cases that illustrate this.

Genetic testing is proposed for suspected cases of pulmonary fibrosis of genetics origin but clinicians and patients need advice about the related diagnostic and management issues. Because multidisciplinary team (MDT) has been shown to improve accuracy of ILD diagnosis, we evaluated the feasibility of an MDT dedicated to the indication and interpretation of genetic testing. The MDT met monthly, included pneumologists experts in ILD in adults, children, geneticists, radiologist. Hematologists, rheumatologists, dermatologists, hepatologists, and pathologists were also invited to attend. Since 2016, 70 patients (37 males, 33 females) were discussed, from 31 different centers (7 countries). Mean age was 46.4 years [0-71] including 3 patients The MDT therapeutic proposals were: antifibrotic drugs (n=23), best supportive care (n=4), surgical lung biopsy (n=2), steroids (n=7), lung transplantation (n=16), or watch and wait (n=9). Our experience shows that a dedicated MDT with genetic analysis is feasible including patients of all ages and provides a unique opportunity to improve knowledge and to adapt patient management and therapy.

Background: Heterozygous mutations in the SFTPA1 and SFTPA2 genes, encoding the surfactant protein SP-A1 and SP-A2 have been associated with rare forms of familial IIP and lung adenocarcinoma. We previously described 11 new heterozygous SFTPA1 and SFTPA2 variations in 13 unrelated patients including one newborn. The study aims to analyze the pathogenicity of those variations. Methods: We first analyzed the intrafamilial segregation of the identified variations with IIP and lung cancer. The production and the secretion of the mutant proteins were subsequently studied in HEK293T cells transiently expressing the SP-A proteins carrying the variations. Finally, SP-A expression was assessed on lung tissues of the patients. Results: In the studied families (38 adults, 3 children), the variations segregated with either IIP and/or lung cancer (37%) with an incomplete penetrance of the disease phenotype. The mean age at onset of the IIP was 45 years (0-68). Nine of the variations were located in the highly conserved carbohydrate recognition domain of the protein. In vitro, the mutant proteins were produced but their secretion was absent (n=9) or altered (n=2). The lung expression of SP-A studied in 3 unrelated patients showed an increased expression of SP-A in the cytoplasm of hypertrophic type 2 alveolar cells. Discussion and conclusion: The 11 identified SFTPA1 and SFTPA2 variations are pathogenic. They are associated with IIP and with an increased risk of lung cancer. They were identified mainly in adults but also in children. The pathophysiological consequences of their abnormal secretion/expression remain to be elucidated.

AIM To compare combined 2-[18F]-fluoro-2-deoxy- d- glucose (FDG)-positron-emission tomography (PET) and cardiac magnetic resonance imaging (CMR) for the diagnosis and therapy monitoring of cardiac sarcoidosis (CS). MATERIALS AND METHODS Eighty patients with sarcoidosis and a suspicion of CS who underwent PET and CMR were included retrospectively. PET was undertaken after a low-carbohydrate–high-fat diet in all patients using a combined 16-section PET/computed tomography (CT) camera. PET was considered positive (PET+) in cases of focal or multifocal FDG uptake. CMR was considered positive (CMR+) in cases of subepicardial late gadolinium enhancement (LGE). A subgroup of 50 patients (50/80) was monitored during therapy and classified as responders or non-responders. RESULTS Eighty-two percent of patients with PET+ (9/11) also had CMR+ imaging, with good spatial agreement (kappa=0,79; 95% confidence interval [CI]: 0.65–0.94). Twenty-seven percent (22/80) had residual physiological FDG uptake, with a standardised uptake value (SUV) not significantly different compared to the SUV from pathological uptake (6.4 versus 6 respectively, p=0,92). The clinical response was more frequent in patients with baseline PET+ compared to baseline PET– (80% versus 45%, p=0.07). PET findings improved in all cases under treatment (7/7), whereas LGE improved in only 33% of patients (3/9). CONCLUSION Due to high risk of false-positive or undetermined findings, PET might be performed as a second-line study in cases of LGE, to assess inflammatory load. In addition, PET seems suitable to predict and assess response under therapy.

Regulator of telomere length 1 (

CD4(+) regulatory T (Treg) cells expressing CD25 and the transcription factor forkhead box P3 (FOXP3) are indispensable for immunological self-tolerance and homeostasis. FOXP3(+)CD25(+)CD4(+) T cells in humans, however, are heterogeneous in function and differentiation status, including suppressive or nonsuppressive cells as well as resting or activated Treg cells. We have searched for cell surface markers specific for suppression-competent Treg cells by using a panel of currently available monoclonal antibodies reactive with human T cells. We found that CD15s (sialyl Lewis x) was highly specific for activated, terminally differentiated, and most suppressive FOXP3(high) effector Treg (eTreg) cells and able to differentiate them in various clinical settings from nonsuppressive FOXP3(+) T cells secreting inflammatory cytokines. For example, CD15s(+)FOXP3(+) eTreg cells were increased in sarcoidosis, whereas it was nonsuppressive CD15s(-)FOXP3(+) T cells that were expanded in lupus flares. FOXP3(+) cells induced from conventional CD4(+) T cells by T-cell receptor stimulation hardly expressed CD15s. CD15s(+)CD4(+) T-cell depletion was sufficient to evoke and enhance in vitro immune responses against tumor or viral antigens. Collectively, we have identified CD15s as a biomarker instrumental in both phenotypic and functional analysis of FOXP3(+)CD4(+) T-cell subpopulations in health and disease. It allows specific targeting of eTreg cells, rather than whole FOXP3(+)CD4(+) T cells, in controlling immune responses.

In common variable immunodeficiency, lung manifestations are related to different mechanisms: recurrent pneumonias due to encapsulated bacteria responsible for diffuse bronchiectasis, diffuse infiltrative pneumonia with various patterns, and lymphomas, mostly B cell extranodal non-Hodgkin type. The diagnosis relies on significant serum Ig deficiency and the exclusion of any primary or secondary cause. Histopathology may be needed. Immunoglobulin (IgG) replacement is crucial to prevent infections and bronchiectasis. IgG4-related respiratory disease, often associated with extrapulmonary localizations, presents with solitary nodules or masses, diffuse interstitial lung diseases, bronchiolitis, lymphadenopathy, and pleural or pericardial involvement. Diagnosis relies on international criteria including serum IgG4 dosage and significantly increased IgG4/IgG plasma cells ratio in pathologically suggestive biopsy. Respiratory amyloidosis presents with tracheobronchial, nodular, and cystic or diffuse interstitial lung infiltration. Usually of AL (amyloid light chain) subtype, it may be localized or systemic, primary or secondary to a lymphoproliferative process. Very rare other diseases due to nonamyloid IgG deposits are described. Among the various lung manifestations of dysregulated states of humoral immunity, this article covers only those associated with the common variable immunodeficiency, IgG4-related disease, amyloidosis, and pulmonary light-chain deposition disease. Autoimmune connective-vascular tissue diseases or lymphoproliferative disorders are addressed in other chapters of this issue.

Background: The surfactant protein A (SP)-A is a collectin implicated in surfactant homeostasis, local alveolar immune response, and epithelial repair after lung injury. SP-A is encoded by the SFTPA1 and SFTPA2 genes. The aim of this study was to search for mutations in SFTPA1 and SFTPA2 in adult patients with ILD. Methods: All SFTPA1 and SFTPA2 exons and flanking intronic sequences were analyzed in a large prospective study population of 160 apparently unrelated ILD patients with no telomerase, SFTPC or ABCA3 mutations. Results: 86 patients were diagnosed with a familial form of ILD, of whom 20 presented an association with a familial lung cancer. 63 patients were Discussion and conclusion: Altered SP-A expression may contribute to ILD pathophysiology. Data reported herein indicate that patients with ILD and a personal or familial lung cancer, and/or

Importance Evidence for the long-term efficacy and safety of anti–tumor necrosis factor α agents (anti-TNF) in treating cutaneous sarcoidosis is lacking. Objective To determine the efficacy and safety of anti-TNF in treating cutaneous sarcoidosis in a large observational study. Design, Setting, and Participants STAT (Sarcoidosis Treated with Anti-TNF) is a French retrospective and prospective multicenter observational database that receives data from teaching hospitals and referral centers, as well as several pneumology, dermatology, and internal medicine departments. Included patients had histologically proven sarcoidosis and received anti-TNF between January 2004 and January 2016. We extracted data for patients with skin involvement at anti-TNF initiation. Main Outcomes and Measures Response to treatment was evaluated for skin and visceral involvement using the ePOST (extra-pulmonary Physician Organ Severity Tool) severity score (from 0 [not affected] to 6 [very severe involvement]). Epidemiological and cutaneous features at baseline, efficacy, steroid-sparing, safety, and relapses were recorded. The overall cutaneous response rate (OCRR) was defined as complete (final cutaneous ePOST score of 0 or 1) or partial response (ePOST drop ≥2 points from baseline but >1 at last follow-up). Results Among 140 patients in the STAT database, 46 had skin involvement. The most frequent lesions were lupus pernio (n = 21 [46%]) and nodules (n = 20 [43%]). The median cutaneous severity score was 5 and/or 6 at baseline. Twenty-one patients were treated for skin involvement and 25 patients for visceral involvement. Reasons for initiating anti-TNF were failure or adverse effects of previous therapy in 42 patients (93%). Most patients received infliximab (n = 40 [87%]), with systemic steroids in 28 cases (61%) and immunosuppressants in 32 cases (69.5%). The median (range) follow-up was 45 (3-103) months. Of the 46 patients with sarcoidosis and skin involvement who were treated with anti-TNF were included, median (range) age was 50 (14-78) years, and 33 patients (72%) were women. The OCRR was 24% after 3 months, 46% after 6 months, and 79% after 12 months. Steroid sparing was significant. Treatment was discontinued because of adverse events in 11 patients (24%), and 21 infectious events occurred in 14 patients (30%). Infections were more frequent in patients treated for visceral involvement than in those treated for skin involvement (n = 12 of 25 [48%] vs n = 2 of 21 [9.5%], respectively; P = .02). The relapse rate was 44% 18 months after discontinuation of treatment. Relapses during treatment occurred in 35% of cases, mostly during anti-TNF or concomitant treatment tapering. Conclusions and Relevance Anti-TNF agents are effective but suspensive in cutaneous sarcoidosis. The risk of infectious events must be considered.

Introduction Les biotherapies anti-TNFα (infliximab et adalimumab, principalement) sont utilisees pour traiter les sarcoidoses severes et/ou refractaires. L’etude STAT a montre une reponse clinique dans 64 % des cas, principalement pour les atteintes neurologiques, cardiaques, cutanees, et ORL [1] . Il n’y a, cependant, pas de donnees concernant le profil et le devenir des patients non repondeurs aux anti-TNFα. Objectif Decrire les patients non repondeurs inclus dans le registre national francais des sarcoidoses traitees par anti-TNFα (STAT). Patients et methodes Etude de cohorte retrospective a partir d’un appel a observations national en juillet 2014. Etaient inclus les patients atteints de sarcoidose histologiquement prouvees et/ou de neurosarcoidose probable selon la classification de Zajicek consideres comme non-repondeurs aux anti-TNFα. Resultats Parmi 132 patients, 14 patients etaient identifies comme refractaires aux anti-TNFα. Cinq patients ont ete exclus (un deces, 3 donnees manquantes, 1 diagnostic final alternatif). L’âge median des 9 patients inclus, (6 femmes) etait de 48 ans (29–70) a l’initiation des anti-TNFα. La maladie atteignait en moyenne 4,2 organes et les patients avaient recu en moyenne 2 traitements immunosuppresseurs (IS) avant les anti-TNFα. Huit patients avaient recus de l’infliximab et un patient avait recu 3 anti-TNFα differents. Quatre patients recevaient un IS en meme temps que les anti-TNFα. La duree mediane de traitement anti-TNFα etait de 7 mois (3–24). Apres un suivi median de 35 mois (19–128) post-traitement anti-TNFα, 2 patients avaient finalement une reponse complete, 5 avaient une reponse partielle et 2 avait une maladie evolutive. Les patients recevaient en moyenne 2 nouvelles lignes de traitements IS. Les traitements de premiere ligne etaient le methotrexate (n = 5) et le cyclophosphamide (n = 2). Dans 6 cas, la reponse clinique etait obtenue avec un traitement IS recu anterieurement par le patient. Conclusion Dans les sarcoidoses refractaires, les immunosuppresseurs conservent leur utilite meme en cas d’echec des anti-TNFα.

Introduction Les causes de PID fibrosantes predominant aux lobes superieurs sont connues pour etre variees dans la litterature, mais elles sont mal decrites. Parmi elles, la fibroelastose pleuroparenchymateuse (FEPP) a ete recemment individualisee comme une entite bien definie. Notre etude avait pour objectif de determiner la prevalence des PID predominant aux lobes superieurs, la repartition de leurs etiologies, leurs caracteristiques et leur pronostic. Methodes Etude retrospective monocentrique basee sur une cohorte de 1132 patients ayant une PID chronique fibrosante adresses entre 2006 et 2016. Etaient exclus les cas de sarcoidose d’evolution fibrosante dont le diagnostic etait deja connu avant la prise en charge dans le service. Resultats Quatre-vingt-sept patients avaient une predominance aux lobes superieurs sur la tomodensitometrie (TDM) thoracique, soit une prevalence de 7,69 %. La gamme diagnostique apres une discussion multidisciplinaire etait la suivante : sarcoidose : n = 21, FEPP : n = 19, pneumopathie d’hypersensibilite (PHS) : n = 15, PID inclassable : n = 11, PID du fumeur : n = 6, silicose : n = 5 ; et autres diagnostics : n = 10. Les quatre groupes les plus prevalents ont ete compares (sarcoidose, FEPP, PHS, et PID inclassable). Les patients avec une FEPP avaient un antecedent familial de PID significativement plus frequent (7/19, 37 %), un IMC plus bas, la survenue plus frequente de pneumothorax et/ou de pneumomediastins (8/19, 42 %) et pas de fixation a la tomographie par emission de positrons. Sur la TDM, les masses de fibrose, les adenopathies et la predominance centrale etaient plus frequentes en cas de sarcoidose. Les FEPP avaient plus souvent une perte de volume, une asymetrie, des condensations sous pleurales et un thorax plus plat. Les lobules clairs distinguaient les PHS. Le declin annuel de la capacite vitale etait moins marque dans la sarcoidose. La survie de la FEPP etait significativement plus mauvaise que celle des autres groupes ( p = 0,02), estimee a 60 % a 5 ans, en particulier en presence d’une PID associee des bases. Conclusion Certaines caracteristiques cliniques et radiologiques aident a differencier les principales causes de PID fibrosantes predominant aux lobes superieurs. La frequence des formes familiales doit inciter a faire une recherche genetique chez les patients ayant une FEPP, dont le pronostic est sombre.

Introduction Le diagnostic de sarcoidose cardiaque est difficile et crucial car il engage le pronostic vital. Plusieurs societes savantes ont propose des criteres diagnostiques s’appuyant sur des cohortes heterogenes, notamment le Japanese Ministry of Health and Welfare (JMWH) et l’Heart and Rythm Society (HRS). Le but etait d’evaluer l’apport d’une discussion multidisciplinaire (DMD) pour la mise en evidence de l’atteinte cardiaque par rapport aux criteres diagnostiques JMWH et HRS, de determiner la performance diagnostique des differents examens et d’analyser les facteurs predictifs d’evenements cardiaques severes (ECS). Methodes Entre mars 2015 et fevrier 2018, une DMD a confronte les donnees cliniques, electrocardiographiques (ECG), du Holter ECG, de l’echographie cardiaque, de l’imagerie par resonnance magnetique cardiaque (IRMc) et de la tomographie a emission de positons (TEP-scanner) dediee chez tous les patients consecutifs ayant une suspicion de sarcoidose cardiaque suivis dans le service de pneumologie de l’hopital Avicenne. Resultats La DMD a retenu une atteinte cardiaque chez 26 des 105 patients discutes (24,7 %) contre 8 patients (7,6 %) et 40 patients (38 %) en appliquant les criteres JMWH et HRS, respectivement. Des investigations complementaires de controle ou necessaires a l’exclusion d’un diagnostic differentiel ont ete demandees dans 18 cas. La presence de symptomes cliniques et/ou electriques et/ou echographiques evocateurs d’une atteinte specifique avait une sensibilite (Se) de 65 % et une specificite (Sp) de 36 %. La Se et la Sp de l’IRMc etaient de 92 % et 86 %, et de 40 % et 94 % pour le TEP scanner. Au terme d’un suivi de 23,4 ± 1,6 mois, 13 patients ont presente des evenements cardiaques severes. Les facteurs predictifs de leur survenue en analyse multivariee etaient l’atteinte cardiaque retenue en DMD (HR = 17 [1,61–187]) et celle selon les criteres JMWH (HR = 3,77 [1,093–13,01]). Dans les cas de sarcoidose cardiaque confirmee, l’existence d’une fixation myocardique au TEP-scanner etait correlee aux evenements cardiaques severes. (p Conclusion Le diagnostic de sarcoidose cardiaque pose en DMD, plus precis que celui base sur les criteres d’une societe cardiologique (HRS 2014), est plus associe aux evenements cardiaques severes. Cette etude souligne la necessite d’adapter l’algorithme diagnostique a la population pneumologique et le role d’une approche multi-modale combinant IRMc et TEP-scanner lors d’une DMD.

The off-label use of TNF antagonists in refractory sarcoidosis is increasingly reported but data on their efficacy and safety are still insufficient.To report on efficacy and safety of TNF antagonists in severe and refractory sarcoidosis.Examination of retrospective demographic, clinical, therapeutic, and adverse event data on 132 sarcoidosis patients (58% women; mean (min-max) age = 45.5 (14-78) years) given TNF antagonists (mainly infliximab, 91%) and investigation of response-linked factors.The overall clinical response (complete and partial) rate was 64%. TNF-antagonist efficacy (i.e., significant decrease of the ePOST score) was noted in cases with neurologic, heart, skin, and upper respiratory tract involvements. No significant difference in efficacy was found between anti-TNF used alone and TNF with immunosuppressant. The use of anti-TNF allowed reducing prednisone dosage at end of follow-up (p0.001). Adverse events were observed in 52% of the patients; they included infections (36%) and allergic reactions (8%) and required treatment interruption in 31 cases (23%). When TNF antagonists were interrupted, 13 patients experienced relapses within 14 months on average (median follow-up: 20.5 months).TNF antagonists were efficacious in about two-thirds of patients with severe/refractory sarcoidosis but their use led to a high rate of adverse events.

A diagnosis of PPFE is linked to pathogenic variants in three different telomere-related genes http://ow.ly/eGOq30aPkgx

Rationale New approaches to define factors underlying the immunopathogenesis of pulmonary diseases including sarcoidosis and tuberculosis are needed to develop new treatments and biomarkers. Comparing the blood transcriptional response of tuberculosis to other similar pulmonary diseases will advance knowledge of disease pathways and help distinguish diseases with similar clinical presentations. Objectives To determine the factors underlying the immunopathogenesis of the granulomatous diseases, sarcoidosis and tuberculosis, by comparing the blood transcriptional responses in these and other pulmonary diseases. Methods We compared whole blood genome-wide transcriptional profiles in pulmonary sarcoidosis, pulmonary tuberculosis, to community acquired pneumonia and primary lung cancer and healthy controls, before and after treatment, and in purified leucocyte populations. Measurements and Main Results An Interferon-inducible neutrophil-driven blood transcriptional signature was present in both sarcoidosis and tuberculosis, with a higher abundance and expression in tuberculosis. Heterogeneity of the sarcoidosis signature correlated significantly with disease activity. Transcriptional profiles in pneumonia and lung cancer revealed an over-abundance of inflammatory transcripts. After successful treatment the transcriptional activity in tuberculosis and pneumonia patients was significantly reduced. However the glucocorticoid-responsive sarcoidosis patients showed a significant increase in transcriptional activity. 144-blood transcripts were able to distinguish tuberculosis from other lung diseases and controls. Conclusions Tuberculosis and sarcoidosis revealed similar blood transcriptional profiles, dominated by interferon-inducible transcripts, while pneumonia and lung cancer showed distinct signatures, dominated by inflammatory genes. There were also significant differences between tuberculosis and sarcoidosis in the degree of their transcriptional activity, the heterogeneity of their profiles and their transcriptional response to treatment.

Backgroung: This study investigated the efficacy and safety of TNF antagonists in sarcoid uveitis in unselected cases. Design: This is a multicentre study on patients with sarcoidosis who received TNF antagonists in pneumology and internal medicine departments in France. We present here the subgroup of patients with biopsy-proven sarcoid uveitis included in the nationwide registry STAT (Sarcoidosis treated with TNF AnTagonists). Results: Among the 132 patients included in this multicenter study, 18 patients with refractory uveitis were treated as a first-line TNF antagonist with infliximab (n=14), adalimumab (n=3) and certolizumab (n=1). Before anti-TNF initiation, the median duration of sarcoidosis was 42 months and 83% of the patients have been treated with at least one immunosuppressive drug. Six patients switched for a second-line TNF antagonist. After a mean time under treatment of 29 months, the treatment resulted in a significant decrease of the ophthalmic extrapulmonary Physician Organ Severity Tool (ePOST) (mean score: 4.2 vs. 2.6) scores and a steroid sparing effect (29.4±20.7 vs. 6.2±5.2 mg/d). Overall, the ophthalmic response, either complete or partial, was 67%. Nine patients (50%) presented adverse events, including severe infectious complications in 5 patients, which required anti-TNF treatment interruption in 6 cases (33%). Among the 7 responder patients who discontinued anti-TNF therapy, 71% relapsed. Finally, 12 patients (67%) could continue TNF antagonist treatment. Conclusions: TNF antagonists were efficient in 67% of biopsy-proven refractory sarcoid uveitis. Severe adverse events, mainly infectious complications, were frequent. The high frequency of relapses after anti-TNF-α discontinuation requires a close patient follow-up thereafter. (Sarcoidosis Vasc Diffuse Lung Dis 2017; 34: 74-80)

Resume La biopsie pulmonaire chirurgicale a sa place dans le diagnostic etiologique des pneumopathies infiltrantes diffuses aigues et chroniques. Cet article resume les indications actuelles, les incidences therapeutiques, les differentes techniques operatoires et les risques per- et postoperatoires de cette methode diagnostique. Les differentes controverses et problemes lies a la procedure sont egalement presentes.

Introduction La sarcoidose cardiaque (SC) represente environ 85 % des deces lies a la sarcoidose au Japon et 13–25 % en Amerique du Nord. L’objectif est d’evaluer l’efficacite et la tolerance du traitement par anti-TNFα dans la SC. Patients et methodes A partir d’une cohorte multicentrique francaise de patients atteints d’une sarcoidose extra-thoracique, nous avons retrospectivement analyse les dossiers de patients ayant les criteres d’inclusion suivants : (1) une sarcoidose extra-thoracique prouve histologiquement, (2) un diagnostic de SC base sur le consensus de la Heart Rhythm Society de 2011, et (3) qui ont recu un traitement par anti-TNFα. La reponse au traitement par anti-TNFα a ete analysee sur les symptomes/signes cliniques cardiaques, et les anomalies d’imageries cardiaques. Les repondeurs complets sont definis par une amelioration/normalisation de tous les examens anormaux a l’inclusion. Resultats Vingt patients ont ete analyses. 50 % avaient des douleurs thoraciques et/ou une insuffisance cardiaque, 71,4 % des anomalies ECG, 70 % des anomalies sur l’IRM cardiaque, 41,7 % au scanner TEP FDG 18, 41,7 % sur la scintigraphie au thallium, et 35,7 % a l’echographie cardiaque transthoracique. La SC etait refractaire a la corticotherapie associee aux immunosuppresseurs (methotrexate [n = 19/20], cyclophosphamide [n = 10/20], azathioprine [n = 6/20], ou mycophenolate mofetyl [n = 3/20]). Apres un suivi moyen de 44,4 mois, 25 % des patients avaient une reponse complete et 50 % une reponse partielle. Un epargne cortisonique etait obtenue, la corticotherapie orale passant de 23,3 mg/j a l’inclusion a 11,9 mg/j a la derniere visite (p Conclusion Le traitement par anti-TNFα a permis d’obtenir une reponse complete et partielle pour 75 % patients atteints de sarcoidose cardiaque refractaire aux immunosuppresseurs, avec une epargne cortisonique significative. Les evenements indesirables ont mene a un arret des anti-TNFα chez 20 % des patients.

Introduction La sarcoidose (S) est une granulomatose rare, multisystemique d’etiologie inconnue qui debute dans 70 % des cas entre 25 et 45 ans. Elle est tres rare avant 15 ans et apres 70 ans. Les objectifs de ce travail sont de decrire les particularites cliniques, therapeutiques et evolutives de la sarcoidose du sujet âge. Patients et methodes Analyse retrospective, multicentrique de 78 cas de S du sujet âge, la limite de 6 ans repondant a la definition de l’OMS du sujet âge. Resultats La population est caucasienne dans 81 %. La sex-ratio femme/homme est de 1,51. L’âge du diagnostic de S se situe entre 65 et 74 ans dans 76 % des cas, entre 75 et 84 ans dans 20 % et 4 % ont 85 ans ou plus. Dans pres de 50 % des cas, il existait une ou plusieurs maladies associees (HTA, diabete, neoplasie…). Le delai diagnostic est inferieur a 1 an dans 81 %. Une asthenie, un amaigrissement et/ou des signes respiratoires ont ete revelateurs respectivement dans 56 %, 15 % et 27 % des cas. Le nombre d’organes atteints n’excedait pas 3 dans 86 %. Les localisations preferentielles sont mediastino-pulmonaires (51 %) et oculaires (31 %). Des atteintes cutanees, ganglionnaires, neuromusculaires, osseuses et cardiaques ont ete notees dans moins de 10 % des cas. Une preuve histologique a ete obtenue dans 82 % des cas (nombre de sites biopsies variant de 1 a 4). Lors de la premiere poussee, seuls 25 patients (32 %) ont ete traites, soit en monotherapie (12/32) (prednisone [12], methotrexate [3], plaquenil [1], cyclophosphamide [1], clarithromycine [1]) soit en bitherapie (8/32) : (prednisone + methotrexate [6] ou azathioprine [1]). Une ou plusieurs rechutes ont ete notees dans 44 % des cas (jusqu’a 8). Celles-ci ont entraine des adaptations therapeutiques aboutissant a un traitement immunosuppresseur chez 63 patients (81 %) soit en monotherapie (33/63), soit en bitherapie voire en tritherapie immunomodulatrice (30/63). La duree moyenne du suivi est de 69 mois (12 a 204 mois). Au terme de ce suivi, 49 patients sont traites (63 %) : 37 sont sous monotherapie immunosuppressive (prednisone : 29 ; methotrexate : 1, plaquenil : 2, clarithromycine : 2) et 12 recoivent une association prednisone plus methotrexate (5), azathioprine (1), cyclophosphamide (1), mycophenolate mofetil (2), anti-TNFα (1), plaquenil (2). Une evolution favorable sans traitement n’a ete notee que dans 19 % des cas. L’evolution lors de la derniere visite est marquee par une remission avec ou sans sequelles dans 87 %, une maladie active dans 13 % des cas. Deux patients sont decedes, seul un deces est lie a la sarcoidose. Des effets secondaires ou comorbidites ont ete notes chez 30 % des patients, dont 14 etaient indemnes avant la prise en charge de la S, principalement de l’hypertension arterielle et/ou une fibrillation auriculaire (10 cas), de l’osteoporose (4 cas) un diabete non insulino-requerant (2 cas), cataracte (2 cas) et des cancers (4). Conclusion La sarcoidose du sujet âge est rare et par consequent peu evoquee dans les services de medecine interne ou de geriatrie. Les signes cliniques ne different pas de ceux du sujet jeune, en dehors de signes generaux plus marques. Meme si le diagnostic est evoque, il faut eliminer les diagnostics differentiels habituels. Les investigations et l’approche therapeutique doivent etre superposables a celle du sujet jeune, compte tenu du taux faible d’evolution spontanement favorable.

Introduction Les symptomes de la fibrose pulmonaire idiopathique (FPI) sont specifiques et peuvent conduire a un retard diagnostique potentiellement deletere. En effet, la FPI necessite une prise en charge globale et specialisee pour l’introduction precoce des traitements anti-fibrosants (pirfenidone et nintedanib), l’accessibilite optimale a la transplantation pulmonaire (TP), et la gestion des comorbidites et facteurs de risque cardiovasculaires frequents. Le but de cette etude etait de decrire le reseau de soin emprunte depuis l’apparition des symptomes jusqu’au diagnostic, et d’evaluer l’association entre le delai diagnostique et la survie. Methodes Il s’agit d’une analyse retrospective concernant les patients ayant une FPI incidente, suivis a l’hopital Avicenne et inclus dans la cohorte nationale prospective COFI. Resultats Soixante-cinq patients ont ete inclus dont 54 hommes et 76,9 % fumeurs (actifs ou sevres) ; l’âge median etait de 67,1 ans (Q1–Q3 = 60,7–72,4). Au total, 67,7 % des patients avaient consulte spontanement pour des symptomes, alors que la decouverte de la FPI etait fortuite dans 32,3 % des cas. Le delai median entre le debut des symptomes et la premiere consultation etait de 5,6 mois (Q1–Q3 = 1,4–18,0). Avant le diagnostic, la mediane du nombre total de consultation etait de 4 (Q1–Q3 = 2–5), le nombre median de praticiens consultes etait de 2 (Q1–Q3 = 1–2), et 30,9 % des patients avaient beneficie d’au moins trois scanners thoraciques. Le delai diagnostique median (defini comme le delai entre l’apparition des premiers symptomes et l’inclusion dans la cohorte COFI) etait de 1,6 ans (Q1–Q3 = 0,9–2,5). Il etait d’autant plus long que les patients avaient une comorbidite respiratoire ( p = 0,001) et etaient jeunes ( p = 0,044). En revanche, il n’y avait pas de lien entre le delai diagnostique et la fonction respiratoire, le score scanographique de fibrose, ou, le score GAP au moment de l’inclusion. La mediane de survie globale sans TP etait de 2,8 ans. Aucune association significative n’a ete mise en evidence entre le delai diagnostique et la survie globale sans TP ( p = 0,65), la survie sans evenement ( p = 0,48), la survie liee a la FPI ( p = 0,72), ou la survie non liee a la FPI ( p = 0,92). Conclusion Cette etude confirme l’existence d’une errance diagnostique chez les patients ayant une FPI, entrainant un retard de prise en charge en centre specialise. Cependant, il ne semble pas y avoir d’association entre le delai diagnostique et la severite initiale de la maladie ou la survie.

Introduction L’aspergillose pulmonaire chronique (APC) complique les formes fibro-kystiques de sarcoidose. La contribution respective de chacune de ces maladies dans la mortalite de ces patients n’est pas claire. Methodes Etude retrospective monocentrique des APC sur sarcoidose pris en charge entre 1981 et 2015 dans le service de pneumologie de l’hopital Avicenne. Resultats Soixante-cinq patients (42 hommes, 22 afro-caribeens) ont ete inclus. L’âge moyen etait de 41,4 ± 13,5 et 48,3 ± 11,9 ans au diagnostic de sarcoidose et d’APC, respectivement. Tous les patients, sauf un avaient une forme fibro-kystique de sarcoidose au diagnostic d’APC. Un tiers des patients rapportaient une exposition professionnelle a des poussieres et moisissures. Au diagnostic d’APC, 43 patients (69 %) recevaient des corticosteroides. Au diagnostic, l’APC etait classee en forme chronique cavitaire (n = 27), aspergillome simple (n = 17) et overlaps (n = 10), 11 cas n’etant pas classables. La plupart des patients avaient une forme pulmonaire severe de sarcoidose au diagnostic d’APC attestee par l’alteration fonctionnelle respiratoire severe et la prevalence de l’hypertension pulmonaire (31 %), du score CPI > 40 (66 %) et des formes de mauvais pronostic selon l’algorithme de Walsh (66 %). Les patients recevaient des traitements lourds avec, en plus du traitement de la sarcoidose, des anti-fongiques (n = 55), une arterio-embolisation bronchique (n = 11 ; 22 procedures), chirurgie (n = 11), des antihypertenseurs pulmonaires (n = 6) et une transplantation pulmonaire (n = 2). Vingt-huit patients (43 %) sont decedes (âge moyen : 56,4) au cours du suivi (7,2 ± 6,1 ans). Les causes de deces etaient une hemoptysie fatale (n = 3), une cause respiratoire (n = 14), une defaillance cardiaque droite (n = 9) et une cause inconnue (n = 2). La survie globale etait de 73,7 % et 61 %, respectivement a 5 ans et 10 ans. L’APC contribuait directement au deces dans 4 cas alors que la majorite des deces etait en lien avec la sarcoidose pulmonaire severe sous-jacente. Les facteurs predictifs de deces etaient l’âge, le diabete, l’existence d’une hypertension pulmonaire, les valeurs basses de CVF et de DLCO, l’extension de la fibrose, le score CPI et l’algorithme de Walsh, mais pas le type d’APC. Conclusion Cette etude a permis de decrire la presentation des APC sur sarcoidose. Le pronostic est sombre. La mortalite est liee a la severite de la maladie pulmonaire sous-jacente plutot qu’a l’APC elle-meme.

Background: Acute exacerbation is a substantial cause of death in patients with idiopathic pulmonary fibrosis with poorly described prognostic factors. Objectives: To review the features associated with acute exacerbation of idiopathic pulmonary fibrosis and assess its prognostic factors. Methods: Thirty-seven occurrences of acute exacerbation of idiopathic pulmonary fibrosis were retrospectively reviewed in the medical records of 27 patients. Clinical presentation, radiographic studies, pulmonary function tests, laboratory data, treatment, and outcome were analyzed. Results: Acute exacerbation of idiopathic pulmonary fibrosis occurred more frequently between December and May (75.7%) than between June and November (24.3%) (p = 0.01). In-hospital mortality was 27% and median survival was 4.2 months (range 0.2–36.6). Significant differences between nonsurvivors and survivors included the time elapsed between their admission and the initiation of treatment for acute exacerbation (6 vs. 3.1 days, p = 0.04), lactate dehydrogenase levels at admission (801 vs. 544.6 IU/l, p = 0.002), impairment of the prior forced vital capacity (51.2 vs. 65%, p = 0.01) and diffusing capacity for carbon monoxide (21.7 vs. 34%, p = 0.01). Furthermore, the evolution of gas exchange in the first 10 days after the initiation of treatment was associated with in-hospital and long-term mortality. Conclusions: Acute exacerbations of idiopathic pulmonary fibrosis are more frequent during winter and spring. The time between admission and initiation of treatment is a new reported prognostic factor that should be investigated further. This finding highlights the need for a fast diagnostic approach that should probably be standardized. Early gas exchange modifications reflect the response to treatment and predict the prognosis.

Introduction Certaines granulomatoses, locales ou systemiques, surviennent dans un contexte tumoral, dans un delai variable par rapport au cancer. Les caracteristiques de ces granulomatoses associees aux cancers (GAC) sont mal connues. Le but de cette etude etait de comparer les presentations cliniques, fonctionnelle, radiologique et evolutive des GAC a celles de la sarcoidose. Methodes Il s’agit d’une etude retrospective cas-temoin realisee dans 2 centres parisiens. Au, total, 43 patients presentant une granulomatose prouvee histologiquement dans un contexte tumoral ont ete inclus et compares a 43 patients suivis pour une sarcoidose, apparies sur l’âge, le sexe, le nombre d’organes atteints et pour les atteintes thoraciques isolees, le stade radiographique. Les donnees cliniques, biologiques, fonctionnelles et radiologiques au cours du suivi ont ete recueillies. Resultats L’âge moyen des patients GAC etait de 51 ± 13 ans (m ± DS). La granulomatose, de diagnostic concomitant a celui de cancer dans 41 % des cas, survenait dans un delai de 22 ± 33 mois apres ce dernier, le plus souvent un cancer du sein. La localisation preferentielle de l’atteinte granulomateuse etait thoracique, mediastinale (88 %) et/ou parenchymateuse (53 %). Des atteintes extrathoraciques etaient notees chez 37 % des GAC, touchant le plus souvent un seul organe (76 % des cas). Les GAC etaient le plus souvent asymptomatiques (63 %, p Conclusion Cette etude cas-temoin comparant GAC et sarcoidose a permis de montrer que le profil clinique, fonctionnel et evolutif de la granulomatose etait moins severe dans le premier cas, necessitant un moindre recours au traitement. Ces resultats pourraient plaider en faveur de differences physiopathologiques, qui restent a elucider, entre ces deux entites.