Background
Fabry disease (FD) is a rare inherited lysosomal storage disorder caused by the deficiency of the enzyme alpha-galactosidase A. This deficiency leads to an accumulation of ...glycosphingolipids leading to progressive and multisystemic disease, including renal, cardiac, and neurological damages. FD may also have neuro-otological and visual impairments, which can generate postural control alterations, inner ear, and vision being involved in this function. This study aimed to evaluate the impact of FD on postural control.
Methods
In total, fourteen adult patients (8 men/6 women, mean age = 37.6 ± 11.4 years) and two children (mean age = 11 years) with FD and 19 healthy adults (12 men/7 women, mean age = 36.5 ± 16.9 years) and two healthy children (mean age = 10.5 years) took part in this study. Postural control was evaluated by a sensory organization test combining three visual situations (eyes open, eyes closed, and sway referenced visual surround motion) with two platform situations (stable platform and sway referenced platform motion), aiming to calculate a composite equilibrium score (CES), a high score being representative of good postural control. Somatosensory (R
SOM
), visual (R
VIS
), and vestibular (R
VEST
) contributions to postural control were calculated, a low score reflecting a poor use of the indicated sensory input.
Results
The CES was lower in adult patients with FD compared with the healthy subjects (
p
< 0.001). R
VIS
(
p
= 0.001) and R
VEST
(
p
= 0.003) were lower in patients with FD compared with the control group, whereas no difference in R
SOM
was observed.
Conclusion
Inner ear and visual pathologies associated with the central nervous system impairments are factors of postural control impairments. Physical activities, which can also be rehabilitative, by maintaining or increasing the weight of proprioception, may help diminish dependency on altered sensorial inputs.
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Gain-of-function variants of JAK1 drive a rare immune dysregulation syndrome associated with atopic dermatitis, allergy, and eosinophilia.
This study sought to describe the clinical ...and immunological characteristics associated with a new gain-of-function variant of JAK1 and report the therapeutic efficacy of Janus kinase (JAK) inhibition.
The investigators identified a family affected by JAK1-associated autoinflammatory disease and performed clinical assessment and immunological monitoring on 9 patients. JAK1 signaling was studied by flow and mass cytometry in patients’ cells at basal state or after immune stimulation. A molecular disease signature in the blood was studied at the transcriptomic level. Patients were treated with 1 of 2 JAK inhibitors: either baricitinib or upadacitinib. Clinical, cellular, and molecular response were evaluated over a 2-year period.
Affected individuals displayed a syndromic disease with prominent allergy including atopic dermatitis, ichthyosis, arthralgia, chronic diarrhea, disseminated calcifying fibrous tumors, and elevated whole blood histamine levels. A variant of JAK1 localized in the pseudokinase domain was identified in all 9 affected, tested patients. Hyper-phosphorylation of STAT3 was found in 5 of 6 patients tested. Treatment of patients’ cells with baricitinib controlled most of the atypical hyper-phosphorylation of STAT3. Administration of baricitinib to patients led to rapid improvement of the disease in all adults and was associated with reduction of systemic inflammation.
Patients with this new JAK1 gain-of-function pathogenic variant displayed very high levels of blood histamine and showed a variable combination of atopy with articular and gastrointestinal manifestations as well as calcifying fibrous tumors. The disease, which appears to be linked to STAT3 hyperactivation, was well controlled under treatment by JAK inhibitors in adult patients.
Systemic capillary leak syndrome (Clarkson’s disease) is a rare entity characterized by recurrent and unpredictable attacks of capillary leakage of plasma fluid and proteins throughout the ...endothelium. Some cases are secondary. We describe the rare association between secondary capillary leak syndrome (SCLS) and autoimmune diseases.
We conducted a nationwide, retrospective, observational, and collaborative study throughout the hospital units of the Club des Rhumatismes et Inflammations network (CRI) between March and August 2015. Inclusion criteria were patients with (1) capillary leakage episodes characterized by edema and elevated hematocrit, low albumin count without proteinuria, or other cause of protein loss; and (2) definite autoimmune diseases according to international classification criteria.
The clinical and biological data of five patients (three women) were reviewed. Median age was 43.2 (17–55) years. Four patients had Sjögren syndrome. One of them also fulfilled the criteria for systemic sclerosis (n = 1). The fifth patient had polymyositis. During the 37.2 months of median follow-up (5.4–201), we recorded a total of 24 attacks, yielding an attack incidence of 91/100 patient-years. Laboratory tests revealed that three patients had anti-SSA/Ro antibodies. Only one patient had a monoclonal blood component (IgGκ). Three patients needed ICU support; one died during a flare.
We reported the first case series of a rare association of SCLS and autoimmune diseases, supporting the idea of some immune mediation in the pathogenesis of the former disease.
Introduction
Late‐onset Pompe disease (LOPD) is characterized by a progressive myopathy resulting from a deficiency of acid α‐glucosidase enzyme activity. Enzyme replacement therapy has been shown to ...be effective, but long‐term treatment results vary. Avalglucosidase alfa demonstrated non‐inferiority to alglucosidase alfa in a phase 3 study, allowing in France compassionate access for advanced LOPD patients unresponsive to alglucosidase alfa.
Methods
Data from the French Pompe registry were analyzed for patients who benefited from a switch to avalglucosidase alfa with at least 1 year of follow‐up. Respiratory (forced vital capacity FVC) and motor functions (Six‐Minute Walk Test 6MWT) were assessed before and 1 year after switching. Individual changes in FVC and 6MWT were expressed as slopes and statistical analyses were performed to compare values.
Results
Twenty‐nine patients were included (mean age 56 years, 11 years of prior treatment). The FVC and 6MWT values remained stable. The individual analyses showed a stabilization of motor worsening: –1 m/year on the 6MWT after the switch versus –63 m/year the year before the switch (i.e., a worsening of 33%/year before vs. an improvement of 3%/year later). Respiratory data were not statistically different.
Discussion
At the group level, gait parameters improved slightly with a stabilization of previous worsening, but respiratory parameters showed limited changes. At the individual level, results were discordant, with some patients with a good motor or respiratory response and some with further worsening.
Conclusion
Switching to avalglucosidase alfa demonstrated varied responses in advanced LOPD patients with failing alglucosidase alfa therapy, with a general improvement in motor stabilization.
Abstract Objectives Systemic capillary leak syndrome (Clarkson′s disease) is a rare entity characterized by recurrent and unpredictable attacks of capillary leakage of plasma fluid and proteins ...throughout the endothelium. Some cases are secondary. We describe the rare association between secondary capillary leak syndrome (SCLS) and auto-immune diseases. Methods We conducted a nation-wide, retrospective, observational and collaborative study throughout the hospital units of the CRI network (Club des Rhumatismes et Inflammations) between March and August 2015. Inclusion criteria were patients with 1) capillary leakage episodes characterized by edema and elevated hematocrit, low albumin count without proteinuria or other cause of protein loss; and 2) definite auto-immune diseases according to international classification criteria. Results The clinical and biological data of five patients (3 women) were reviewed. Median age was 43.2 (17 to 55) years. Four patients had Sjögren syndrome. One of these also fulfilled the criteria for systemic sclerosis (n=1). The fifth had polymyositis. During the 37.2 months of median follow-up (5.4 to 201) we recorded a total of 24 attacks, yielding an attack incidence of 91/100 patient-years. Laboratory tests revealed that three patients had anti-SSA/Ro antibodies. Only one had a monoclonal blood component (IgGκ). Three patients needed ICU supports; one died during a flare. Conclusion We reported the first case-series of a rare association of SCLS and autoimmune diseases, supporting the idea of some immune mediation in the pathogenesis of the former disease.
Abdominal pain is a common symptom underlying a variety of disorders with different prognoses. Neutrophilia or lymphopenia have been used as prognostic markers in several stress- or ...infection-mediated disorders. We studied the clinical relevance of the leukocyte differential in the initial workup of adult patients presenting with abdominal pain.
We reviewed all leukocyte differentials and medical records of 441 consecutive patients admitted for abdominal pain in an emergency department. Patients were matched by age and sex with controls and were assigned to 4 groups: functional disorders (group FUN), infectious medical disorders (group INF) and noninfectious medical disorders (group MED), and surgical disorders (group SUR). Patients of groups INF and SUR were pooled into group INF+SUR to predict severe illness, and this group was compared with others with nonsevere illness.
All patients exhibited neutrophilia, along with a neutrophil count that increased with illness severity. Lymphopenia, eosinopenia, and basopenia characterized patients of group INF+SUR. Neutrophilia, eosinopenia, and lymphopenia were independent predictors of the most severely affected patients. The association of a neutrophil count >9.0 × 10⁹/L with lymphopenia (<1.4 × 10⁹L) and eosinopenia (<0.04 × 10⁹/L) had a specificity of 94.9% (95% confidence interval, 91.2%-97.1%) for inclusion in group INF+SUR, although with a low sensitivity (27.5%).
Lymphocyte, eosinophil, and neutrophil counts should be considered in medical admissions of adults with abdominal pain. Lymphopenia associated with eosinopenia and significant neutrophilia is highly suggestive of a more severe illness.
Myotonic dystrophy type 1 (DM1) is a multisystemic disorder characterized by muscle weakness and multiple organ impairment, especially the eyes, lung, and heart. We conducted the current study to ...analyze the prevalence and intercorrelation among these disorders and their respective relationships with muscular disability. We assessed medical history, anthropometric data, lung volumes, arterial and venous blood samples, surface 12-lead electrocardiogram, echocardiography, ophthalmologic examination, and muscular impairment rating scale (MIRS) in 106 patients (48 male and 58 female) with DM1, aged 43.7 ± 12.8 years. Obesity, hypertriglyceridemia, and diabetes were found in respectively 25.6%, 47.6%, and 17.1% of patients. Disabling cataract was found in 43.4%, and was independently predicted by age and MIRS. Restrictive lung disease was noted in 34%, and was predicted by MIRS, CTG repeat expansion, and body mass index. Conduction disorders were found in 30.2% of patients and were predicted by left ventricular ejection fraction, MIRS, and CTG repeat expansion.We found significant relationships between cataract, restrictive lung disease, and conduction disorders: patients with cataract and those with conduction disorders exhibited more severe restrictive lung disease than the other patients. Conversely, the relative risk of restrictive lung disease was 2.42 (1% confidence interval CI, 1.06-5.51) in patients with cataract and 2.54 (1% CI, 1.26-5.07) in patients with conduction disorders. Multivariate analysis revealed that MIRS was the only independent predictor for conduction disorders and restrictive lung disease. MIRS ≥3 and MIRS ≥4 were the best simple cutoff values to predict, respectively, lung and cardiac involvements.To conclude, muscular disability, ophthalmologic, and cardiac and pulmonary involvement are strongly correlated. Particular attention should be given to these entities in patients with distal or proximal muscular weakness.
A diagnosis of sarcoidosis was evoked in a 61-year-old man on clinical and histologic bases. Nevertheless, a bile duct carcinoma was disclosed in association with the discovery of generalized ...sarcoid-like granulomas. This is only the third time that such an association has been described. HLA-B8, DR3, and DRw52 antigens were found, suggesting that altered immunologic mechanisms could play a role in the pathogenesis of this sarcoid-like reaction.
