Steven Vanderschueren

Cough is an underrecognized and atypical manifestation of giant cell arteritis (GCA), which may lead to diagnostic delay. Literature on cough in GCA is limited and lacks comprehensive data on clinical relevance. The aim of this study was to assess the frequency of cough at diagnosis in GCA patients and to compare clinical characteristics between those with and without cough. Consecutive patients diagnosed with GCA between 2000 and 2020 and followed for ≥ 12 months at the University Hospitals Leuven (Belgium) were included retrospectively. We included 398 GCA patients, of whom 72 (18%) reported cough. Patients with cough were slightly younger (69.8 vs 72.3 years, p = 0.019), more frequently had constitutional symptoms (94% vs 73%, p < 0.001), and less often had polymyalgia rheumatica (26% vs 50%, p < 0.001) or permanent visual loss (3% vs 19%, p < 0.001). They had higher C-reactive protein (86 vs 68 mg/L, p = 0.003) and erythrocyte sedimentation rate (80 vs 67 mm/h, p = 0.036), and lower haemoglobin (11.3 vs 11.8 g/dL, p = 0.008) and albumin (36.7 vs 38.4 g/L, p = 0.013). Positron emission tomography total vascular score (10 vs 5, p = 0.009) was higher in GCA patients with cough. Although time to first relapse was shorter (10 vs 13 months, p = 0.018), relapse probability [hazard ratio (HR) 1.15, 95% confidence interval (CI) 0.82-1.61, p = 0.420] and the probability of discontinuing glucocorticoids were similar (HR 1.10, 95% CI 0.80-1.50, p = 0.563). GCA patients with cough may represent a distinct phenotype associated with systemic inflammation and large-vessel involvement. Further prospective studies with standardized cough assessment are needed to clarify the role of cough in GCA.

Malnutrition evokes familiar images, such as a skinny patient with anorexia nervosa, an elderly patient with poor appetite or a cancer patient with cachexia. However, European Society for Clinical ...

Human deficiency of adenosine deaminase 2 (DADA2) is an autoinflammatory disease caused by pathogenic variants in ADA2 that lead to impaired deaminase activity. Recently, a lysosomal function of ADA2 has been proposed but an intracellular form of the protein has not yet been characterized. Here, we analyze protein expression of mutant ADA2 in human monocyte-derived macrophages from 10 DADA2 patients. We identify an intracellular low-molecular-weight (LMW) form of ADA2 that undergoes glycan trimming by α-mannosidases and is absent in DADA2 macrophages. Subcellular fractionation and immunofluorescence microscopy demonstrate that LMW-ADA2 is localized in the lysosomes. By overexpression of 34 ADA2 variants in HEK293T and U-937 cells, we show that absence of LMW-ADA2 strongly correlates with reduced deaminase activity and predicts variant pathogenicity. In conclusion, we describe a previously unreported intracellular hypoglycosylated form of ADA2 and establish the absence of this LMW-ADA2 as a cellular characteristic of DADA2. Thereby, we introduce a protein correlate of the recently described lysosomal form of ADA2. Summary: Ehlers et al. demonstrate that mutant ADA2 fails to undergo glycan processing beyond the ER leading to the absence of intracellular low-molecular-weight (LMW) ADA2 in DADA2 patients’ macrophages. LMW-ADA2 localizes to the lysosomes and can be generated from extracellular wild-type ADA2.

Previous studies have shown that patients with giant cell arteritis (GCA) who have vascular ¹⁸F-fluorodeoxyglucose (FDG) uptake at diagnosis are at increased risk for thoracic aortic complications. To measure the association between vascular FDG uptake at diagnosis and the change in aortic dimensions. Prospective cohort study. University Hospitals Leuven. 106 patients with GCA and FDG positron emission tomography (PET) imaging 3 days or less after initiation of glucocorticoids. Patients had PET and computed tomography (CT) imaging at diagnosis and CT imaging yearly for a maximum of 10 years. The PET scans were scored 0 to 3 in 7 vascular areas and summed to a total vascular score (TVS). The PET scan results were positive when FDG uptake was grade 2 or greater in any large vessel. The association between vascular FDG uptake and aortic dimensions was estimated by linear mixed-effects models with random intercept and slope. When compared with patients with a negative PET scan result, those with a positive scan result had a greater increase in the diameter of the ascending aorta (difference in 5-year progression, 1.58 mm [95% CI, 0.41 to 2.74 mm]), the diameter of the descending aorta (1.32 mm [CI, 0.38 to 2.26 mm]), and the volume of the thoracic aorta (20.5 cm³ [CI, 4.5 to 36.5 cm³]). These thoracic aortic dimensions were also positively associated with TVS. Patients with a positive PET scan result had a higher risk for thoracic aortic aneurysms (adjusted hazard ratio, 10.21 [CI, 1.25 to 83.3]). The lengthy inclusion and follow-up period resulted in missing data and the use of different PET machines. Higher TVS was associated with greater yearly increase in thoracic aortic dimensions. Performing PET imaging at diagnosis may help to estimate the risk for aortic aneurysm formation. None.

Deficiency of human adenosine deaminase type 2 (DADA2) is a complex systemic autoinflammatory disorder characterized by vasculopathy, immune dysregulation, and hematologic abnormalities. The most notable neurological manifestations of DADA2 are strokes that can manifest with various neurological symptoms and are potentially fatal. However, neurological presentations can be diverse. We here present a review of the neurological manifestations of DADA2 to increase clinical awareness of DADA2 as the underlying diagnosis. We reviewed all published cases of DADA2 from 1 January 2014 until 19 July 2022 found via PubMed. A total of 129 articles describing the clinical features of DADA2 were included in the analysis. Six hundred twenty-eight patients diagnosed with DADA2 were included in the review. 50.3% of patients had at least signs of one reported neurological event, which was the initial or sole manifestation in 5.7% and 0.6%, respectively. 77.5% of patients with neurological manifestations had at least signs of one cerebrovascular accident, with lacunar strokes being the most common and 35.9% of them having multiple stroke episodes. There is a remarkable predilection for the brain stem and deep gray matter, with 37.3% and 41.6% of ischemic strokes, respectively. Other neurological involvement included neuropathies, focal neurological deficits, ophthalmological findings, convulsions, and headaches. In summary, neurological manifestations affect a significant proportion of patients with DADA2, and the phenotype is broad. Neurological manifestations can be the first and single manifestation of DADA2. Therefore, stroke, encephalitis, posterior reversible encephalopathy syndrome, mononeuropathy and polyneuropathy, and Behçet’s disease-like presentations should prompt the neurologist to exclude DADA2, especially but not only in childhood.

Background: Sarcoidosis most commonly affects lungs and intrathoracic lymph nodes, but any other organ can be involved. In epidemiological studies, many occupational and environmental exposures have been linked to sarcoidosis but their relationship with the disease phenotype has barely been studied.Objective: To investigate how occupational and environmental exposures prior to diagnosis relate to organ involvement in patients with sarcoidosisMethods: We retrospectively studied patients seen at a sarcoidosis clinic between 2017 and 2020. Patients were included if they had a clinical presentation consistent with sarcoidosis and histologically confirmed epithelioid granulomas or had Löfgren syndrome. In a case–case analysis using multivariable logistic regression we calculated odds ratios (OR) of prespecified exposure categories (based on expert ascertainment) for cases with a given organ involvement versus cases without this organ involvement.Results: We included 238 sarcoidosis patients. Sarcoidosis limited to pulmonary involvement was associated with exposure to inorganic dust prior to diagnosis (OR 2.11; 95% confidence interval [CI] 1.11–4.17). Patients with liver involvement had higher odds of contact with livestock (OR 3.68; 95% CI 0.91–12.7) or having jobs with close human contact (OR 4.33; 95% CI 1.57–11.3) than patients without liver involvement. Similar associations were found for splenic involvement (livestock: OR 4.94, 95% CI 1.46–16.1; close human contact: OR 3.78; 95% CI 1.47–9.46). Cardiac sarcoidosis was associated with exposure to reactive chemicals (OR 5.08; 95% CI 1.28–19.2) or livestock (OR 9.86; 95% CI 1.95–49.0). Active smokers had more ocular sarcoidosis (OR 3.26; 95% CI 1.33–7.79).Conclusions: Our study indicates that, in sarcoidosis patients, different exposures might be related to different organ involvements—hereby providing support for the hypothesis that sarcoidosis has more than one cause, each of which may promote a different disease phenotype.