In 9-20% of cases, Sjögren's syndrome is associated with various respiratory symptoms. The most typical manifestations are chronic interstitial lung disease (ILD) and tracheobronchial disease. The ...most common manifestation of ILD is nonspecific interstitial pneumonia in its fibrosing variant. Other types of ILD, such as organising pneumonia, usual interstitial pneumonia and lymphocytic interstitial pneumonitis, are rare. Their radiological presentation is less distinctive, and definitive diagnosis may require the use of transbronchial or surgical lung biopsy. Corticosteroid therapy is the mainstay of ILD treatment in Sjögren's syndrome, but the use of other immunosuppressive drugs needs to be determined. ILD is a significant cause of death in Sjögren's syndrome. Tracheobronchial disease is common in Sjögren's syndrome, characterised by diffuse lymphocytic infiltration of the airway. It is sometimes responsible for a crippling chronic cough. It can also present in the form of bronchial hyperresponsiveness, bronchiectasis, bronchiolitis or recurrent respiratory infections. The management of these manifestations may require treatment for dryness and/or inflammation of the airways. Airway disease has little effect on respiratory function and is rarely the cause of death in Sjögren's syndrome patients. Rare respiratory complications such as amyloidosis, lymphoma or pulmonary hypertension should not be disregarded in Sjögren's syndrome patients.
Objective
To investigate a new therapeutic strategy, with rapid corticosteroid dose tapering and limited cyclophosphamide (CYC) exposure, for older patients with systemic necrotizing vasculitides ...(SNVs; polyarteritis nodosa PAN, granulomatosis with polyangiitis Wegnener's GPA, microscopic polyangiitis MPA, or eosinophilic GPA Churg‐Strauss EGPA).
Methods
A multicenter, open‐label, randomized controlled trial comprising patients ≥65 years old and newly diagnosed as having SNV was conducted. The experimental treatment consisted of corticosteroids for ∼9 months and a maximum of six 500‐mg fixed‐dose intravenous (IV) CYC pulses, every 2–3 weeks, then maintenance azathioprine or methotrexate. The control treatment included ∼26 months of corticosteroids for all patients, combined with 500 mg/m2 IV CYC pulses, every 2–3 weeks until remission, then maintenance for all patients with GPA or MPA and for those with EGPA or PAN with a Five‐Factors Score (FFS) of ≥1. Randomization used a 1:1 ratio computer‐generated list and was performed centrally with sealed opaque envelopes. The primary outcome measure was ≥1 serious adverse event (SAE) occurring within 3 years of followup. Secondary outcome measures included remission and relapse rates.
Results
Among the 108 patients randomized, 4 were excluded (early consent withdrawal or protocol violation). Mean ± SD age at diagnosis was 75.2 ± 6.3 years. Analysis at 3 years included 53 patients (21 GPA, 21 MPA, 8 EGPA, and 3 PAN) in the experimental arm and 51 patients (15 GPA, 23 MPA, 6 EGPA, and 7 PAN) in the conventional arm. In total, 32 (60%) versus 40 (78%) had ≥1 SAE (P = 0.04), most frequently infections; 6 (11%) versus 7 (14%) failed to achieve remission (P = 0.71); 9 (17%) versus 12 (24%) died (P = 0.41); and 20 (44%) of 45 versus 12 (29%) of 41 survivors in remission experienced a relapse (P = 0.15).
Conclusion
For older SNV patients, an induction regimen limiting corticosteroid exposure and with fixed low‐dose IV CYC pulses reduces SAEs in comparison to conventional therapy, and does not affect the remission rate. Three‐year relapse rates remain high for both arms.
To measure the prevalence of different types of pulmonary hypertension (PH) and to identify patients with systemic sclerosis (SSc) at highest risk in a multicenter European sample, with a ...metaanalysis of relevant studies.
Consecutive patients with SSc recruited at 11 French and Italian centers underwent detailed evaluations, including Doppler echocardiography, chest computed tomography, pulmonary function tests, and right-heart catheterization (RHC), to detect the presence and causes of PH. A metaanalysis was performed, including data from 4 other studies.
Among 206 patients in whom it was suspected, PH was confirmed by RHC in 83 patients (7%). Precapillary PH was found in 64 patients (5%), of whom 42 had pulmonary arterial hypertension (PAH) and 22 had PH secondary to interstitial lung disease (ILD). RHC identified 17 patients (1%) with postcapillary PH secondary to left-heart disease. Patients with DLCO/alveolar volume < 70% were more likely to have precapillary PH (87.5% vs 42%; p < 0.0001). Precapillary and postcapillary PH were associated with advanced age (68 ± 14 vs 59 ± 12 yrs, p < 0.0001, and 74 ± 16 vs 61.5 ± 10 yrs, p < 0.0001, respectively). The metaanalysis of 3818 patients showed a prevalence of precapillary PH of 9% (95% CI 6%-12%) and identified advanced age, longer disease duration, and limited cutaneous disease subset as risk factors for this condition.
The prevalence of precapillary PH in our multicenter study of SSc was 5%, and in the metaanalysis 9%. Our observations support use of RHC to confirm the presence of precapillary PH suspected by noninvasive testing. We also identified patients at high risk who should be carefully monitored.
Background: Identification of underlying diseases is crucial for secondary hyperhidrosis management, but data are lacking to guide appropriate investigation.
Objective: To describe aetiologies of ...recurrent sweating in a hospital setting and the diagnostic performance parameters of their respective clinical/biological features.
Patients and Methods: We performed a monocentric evaluative study in a tertiary care centre. Patients with recurrent generalised sweating were selected via the Clinical Data Warehouse (CDW) by screening all electronic hospital documents from the year 2018 using a keyword-based algorithm. All in and out-patients aged ≥ 18 years having reported recurrent sweating for at least 2 weeks in 2018 were included, with a minimum one-year follow-up after symptoms' onset.
Results: A total of 420 patients were included. Over 130 different aetiologies were identified; 70 patients (16.7%) remained without diagnosis. Solid organ cancers (14.3% with 13 lung cancers), haematologic malignancies (14.0% with 35 non-Hodgkin's lymphomas) and Infectious Diseases (10.5% including 13 tuberculosis) were the most frequent diagnoses. Other aetiologies were gathered into inflammatory (16.9%) and non-inflammatory (27.6%) conditions. To distinguish non-inflammatory and undiagnosed hyperhidrosis from other causes, fever had a specificity of 94%, impaired general condition a sensitivity of 78%, and C-reactive protein (CRP) > 5.6 mg/l a positive predictive value of 0.86. Symptoms' duration over 1 year was in favour of non-infectious and non-malignant causes (94% specificity).
Conclusions: We identified fever, impaired general condition, duration, and CRP as helpful orientation parameters to assess the need for complementary explorations for hyperhidrosis. The study provides a diagnostic algorithm for the investigation of recurrent sweating.
KEY MESSAGES
In a hospital setting, malignancies and infections are the most frequently associated diseases, but 1/5 remain without diagnosis.
Fever is a specific but not sensitive sign to distinguish inflammatory conditions.
Over 1 year duration of symptoms significantly reduce the probability of malignancy or infection as the underlying diagnosis.
Data on the clinical spectrum and therapeutic management of noninfectious mixed cryoglobulinemia vasculitis (CryoVas) in the era of hepatitis C virus screening are lacking. We analyzed data from 242 ...patients with noninfectious mixed CryoVas included in the French multicenter CryoVas survey. Baseline manifestations were purpura (75%), peripheral neuropathy (52%), arthralgia or arthritis (44%), glomerulonephritis (35%), cutaneous ulcers (16%), and cutaneous necrosis (14%). A connective tissue disease was diagnosed in 30% and B-cell non-Hodgkin lymphoma in 22%, whereas the CryoVas was considered to be essential in 48%. With the use of Cox-marginal structural models, rituximab plus corticosteroids showed the greater therapeutic efficacy compared with corticosteroids alone and alkylating agents plus corticosteroids to achieve complete clinical, renal, and immunologic responses and a prednisone dosage < 10 mg/d at 6 months. However, this regimen was also associated with severe infections, particularly when high doses of corticosteroids were used, whereas death rates did not differ between the therapeutic regimens. The role of each of these strategies remains to be defined in well-designed randomized controlled trials.
Systemic sclerosis (SSc) is a severe and highly heterogeneous disease. The modified Rodnan skin score (mRSS) is a widely used tool for the assessment of the extent and degree of skin thickness. This ...study aimed to identify the classes of patients with early similar skin thickening trajectories without any a priori assumptions and study their associations with organ involvement and survival.
From the French SSc national cohort, patients with a disease duration of less than 2 years at inclusion and with at least 2 mRSS available within the first 4 years of follow-up were enrolled. Classes of patients with similar mRSS trajectories were identified based on a latent class mixed model. The clinical characteristics and survival rate were compared between the obtained classes.
A total of 198 patients fulfilled the inclusion criteria, with a total of 641 mRSS available. The median disease duration and follow-up were 0.8 (interquartile range 0.4; 1.2) and 6.3 (3.8; 8.9) years, respectively. Individual trajectories of mRSS were highly heterogeneous between patients. Models with 1-6 latent classes of trajectories were sequentially assessed, and the 5-class model represented the best fit to data. Each class was characterized by a unique global trajectory of mRSS. The median disease duration did not differ significantly between classes. Baseline organ involvement was more frequent in classes with significant change over time (classes 2-5) than in class 1 (low baseline mRSS without significant change over time). Using Cox regression, we observed a progressively increasing risk of death from classes 1 to 5.
Early identification of clinical phenotype based on skin thickening trajectories could predict morbi-mortality in SSc. This study suggested that mRSS trajectories characterization might be pivotal for clinical practice and future trial designs.
High-resolution computed tomography (HRCT) may lack sensitivity for the early detection of interstitial lung disease associated with systemic sclerosis (SSc-ILD). Lung ultrasound is an emerging ...technique for the diagnosis of SSc-ILD. This cross-sectional study aimed to describe the prevalence of ultrasound interstitial syndrome in SSc patients with normal HRCT and pulmonary function tests (PFT).
Thirty SSc patients with normal HRCT, FVC > 80% predicted and DLCO > 70% predicted were included. Echocardiography and PFT including impulse oscillometry and cardiopulmonary exercise testing were performed. Lung ultrasound was analyzed by two blinded operators. Patients were classified into two groups, according to the presence or absence of ultrasound interstitial syndrome, defined as the sum of B-lines in all thoracic areas ≥10 and/or pleural line thickness >3 mm on at least one thoracic area and/or a pleural line irregularity score >16%.
Ultrasound interstitial syndrome was present in 12 patients (40%). Inter-reader agreement for the diagnosis of ultrasound interstitial syndrome defined by the Kappa coefficient was 0.93 (95%CI 0.79-1.00). Patients with ultrasound interstitial syndrome were younger (37 years vs. 53 years,
= 0.009), more often had pitting scars (
= 7/12 vs. 3/18,
= 0.045) and had lower FVC (102 vs. 110% pred,
= 0.009), TLC (114 vs. 122% pred,
= 0.042) and low-frequency respiratory system reactance (Xrs5 Z-score 0.16 vs. 1.02,
= 0.018), while pulmonary gas exchange was similar.
Ultrasound interstitial syndrome was detected in 12/30 SSc patients with normal HRCT and PFT. Patients with ultrasound interstitial syndrome had differences in lung function consistent with reduced respiratory compliance, suggesting minimal and/or early suspected SSc-ILD.
Rheumatoid arthritis (RA) is a chronic inflammatory joint disease causing articular cartilage and bone destruction. Since irreversible joint destruction can be prevented by intervention at the early ...stages of disease, early diagnosis of RA is important. In this study, we identified new autoantibodies in the sera of patients with early (less than one year) RA.
We screened the sera of 20 RA patients with disease duration less than one year, 19 RA patients with disease duration more than five years and 23 controls on 8,268 human protein arrays. We confirmed the validity of protein array detection by ELISA assays. We then performed epitope mapping with overlapping 15-mers to analyze RA sera reactivity.
WIBG (within BGCN homolog (Drosophila)), GABARAPL2 (GABA(A) receptor associated protein like 2) and ZNF706 (zinc finger protein 706) proteins are preferentially recognized by autoantibodies from early RA patients. Of interest, autoantibodies to WIBG are very specific for early RA. Indeed, 33% of early RA patients' sera recognize WIBG versus 5% of RA patients with disease duration more than 5 years and 2% of controls. We identified three linear peptides on WIBG GABARAPL2 and ZNF706 that are preferentially recognized by sera of early RA patients.
We identified new autoantibodies associated with RA with disease duration less than one year. These autoantibodies could be used as diagnosis markers in RA patients.
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