Paul Klee’s gastrointestinal maladies: A series of historical and clinical vignettes, part IV

2021 ◽  
pp. 239719832110192
Author(s):  
Richard M Silver
Keyword(s):  
Systemic Sclerosis ◽  
Present Evidence ◽  
Paul Klee ◽  
Swiss German ◽  
Clinical Vignettes ◽  
Gi Symptoms

Paul Klee (1879–1940), the 20th century Swiss-German artist, suffered and died from complications of systemic sclerosis (SSc, scleroderma). In a series of clinical and historical vignettes the various symptoms and complications of Klee’s scleroderma are described. Here, I present evidence of Klee’s multiple gastrointestinal (GI) symptoms and the significant impact they had on the quality of his life.

scholarly journals FRI0233 IMPACT AND ADHERENCE TO THE MEDITERRANEAN DIET IN SYSTEMIC SCLEROSIS ITALIAN PATIENTS: CORRELATION WITH GASTROINTESTINAL SYMPTOMS, MOOD DISTURBANCES AND QUALITY OF LIFE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 700.2-700
Author(s):  
G. De Luca ◽  
G. Natalello ◽  
G. Abignano ◽  
C. Campochiaro ◽  
D. Temiz Karadağ ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Systemic Sclerosis ◽  
Mediterranean Diet ◽  
Dietary Habits ◽  
Anxiety And Depression ◽  
Research Support ◽  
Work Impairment ◽  
Gi Symptoms ◽  
The Mediterranean

Background:Gastrointestinal involvement(GI) is a common feature of systemic sclerosis(SSc) and can be highly disabling, representing a major cause of morbidity and reduced quality of life(QoL). The impact of dietary habits on GI symptoms, mood and QoL has not been extensively evaluated.Objectives:To evaluate the adherence to the Mediterranean Diet(MD) in an Italian multicenter cohort of SSc patients, and its impact on GI symptoms and other disease features, depression, anxiety and overall QoL.Methods:Consecutive SSc(ACR/EULAR2013) patients from 4 Italian cohorts were enrolled. Dietary habits and adherence to the MD were assessed using the 14-item MEDAS and QueMD questionnaires. Presence and severity of depressive/anxious symptoms and QoL were evaluated with the Hospital Anxiety and Depression Scale(HADS) and the SSc-HAQ(S-HAQ). GI symptoms were assessed with the Reflux Disease Questionnaire(RDQ) and the UCLA SCTC GI Tract 2.0 questionnaire(USG). Associations with patients’ lifestyle, disease characteristics, and nutritional status were explored.Results:265 patients (94.7% females; age 55.8±13.6years; disease duration 9.1±7.0years; diffuse SSc 31.8%; Scl70 + 35.8%;ulcers 23.4%;ILD 29.4%;BMI 23.7±4.4 Kg/m2; obese 11.3%,overweight 23.4%,underweight 4.9%) were enrolled.Overall MD adherence was moderate(7.5±1.9) according to MEDAS and it correlated with QueMD score(4.53±1.96)(R=.371,p<0.001). MD adherence was optimal in 39 patients(14.7%), more frequently from Central-Southern Italy(p=0.036); 189 patients(71.3%) had a good and 37(14.0%) a poor MD adherence.GI symptoms were moderate/severe according to USG in 37(14.0%) patients(USG:0.41±0.40), and heartburn was the most common GI symptom(35.2%). The prevalence of significant anxiety and depression was 24.1% and 17.0%.An inverse correlation was found between MD adherence and mood disturbances at HADS(MEDAS; R=-0.181,p=0.04), work impairment(QueMD;R=-0.247,p=0.005) and reduced QoL, both for GI (constipation at USG: R=-0.133,p=0.032) and general S-HAQ items(bowel:R=-0.181,p=0.04;severity R=-0.202,p=0.01;Raynaud:R=-0.217,p<0.001;ulcers: R=-0.207,p=0.01). MD adherence directly correlated with lung function(MEDAS;R=0.181,p=0.023 for FVC and R=0.170,p=0.03 for DLCO). Patients with MD optimal adherence had lower HADS depression(p=0.04) and S-HAQ scores(HAQ,p=0.04; Raynaud,p=0.005; ulcers,p=0.02) and lower work impairment and lost work time(p=0.03). No significant correlation emerged between MD adherence and BMI, or specific symptoms. Depression and anxiety directly correlated with the severity of reported upper GI symptoms according to both scales (RDQ-GERD:R=0.261,p=0.001; USG:R=0.263,p<0.001) and general S-HAQ items (HAQ: R=0.136,p=0.032;severity R=0.233,p<0.001;bowel: R=0.135,p=0.04;breath: R=0.133,p=0.03; ulcers: R=0.132,p=0.037). Results were confirmed after exclusion of psychiatric(11.7%) and fibromyalgic(15.5%) patients.Conclusion:Unsatisfactory MD adherence is associated with a low mood, impaired QoL, work impairment, GI and vascular symptoms in Italian SSc patients. The promotion of a healthy lifestyle could positively impact on QoL and disease status of SSc patients.References:[1]Gnagnarella P, et a. NMCD 2018. DOI: 10.1016/j.numecd.2018.06.006[2]Jaeger VK et al. PLoS One, 2016.[3]Dinu M et al. Eur J Clin Nutr 2018. doi: 10.1038/ejcn.2017.58.[4]Khanna D, et al.Arthritis Rheum. 2009. doi: 10.1002/art.24730.Acknowledgments:GILSDisclosure of Interests:Giacomo De Luca Grant/research support from: SOBI, Speakers bureau: SOBI, Novartis, Pfizer, MSD, Celgene, Gerlando Natalello: None declared, Giuseppina Abignano: None declared, Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Duygu Temiz Karadağ: None declared, Maria De Santis: None declared, Elisa Gremese Speakers bureau: Abbvie, BMS, Celgene, Jannsen, Lilly, MSD, Novartis, Pfizer, Sandoz, UCB, Silvia Laura Bosello Speakers bureau: Abbvie, Pfizer, Boehringer, Lorenzo Dagna Grant/research support from: Abbvie, BMS, Celgene, Janssen, MSD, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, SG, SOBI, Consultant of: Abbvie, Amgen, Biogen, BMS, Celltrion, Novartis, Pfizer, Roche, SG, and SOBI

Was Paul Klee’s scleroderma an occupational disease? A series of historical and clinical vignettes, part III

2020 ◽  
Vol 5 (2) ◽  
pp. 85-89
Author(s):  
Richard M Silver
Keyword(s):  
Heavy Metals ◽  
Systemic Sclerosis ◽  
Environmental Factors ◽  
20Th Century ◽  
Occupational Disease ◽  
Susceptible Host ◽  
Paul Klee ◽  
Clinical Vignettes ◽  
Self Tolerance ◽  
Potential Factors

Paul Klee (1879–1940), one of the most influential artists of the 20th century, died at 60 years of age from complications of systemic sclerosis (scleroderma). The precipitating event(s) of Klee’s scleroderma, as in most cases, will never be known. Among various potential factors, exposure to heavy metals, crystalline silica, and organic solvents—acting alone or in combination—can now be considered potential factors in the onset of Klee’s disease. By altering and modulating epigenetic determinants in a genetically susceptible host, these and other environmental factors may have led to perturbations of self-tolerance and inflammation culminating in Klee’s scleroderma.

scholarly journals Paul Klee's illness – a series of historical and clinical vignettes

2017 ◽  
Vol 2 (3) ◽  
pp. 135-136 ◽  
Author(s):  
Richard M. Silver
Keyword(s):  
Systemic Sclerosis ◽  
Raynaud Phenomenon ◽  
Paul Klee ◽  
Clinical Vignettes ◽  
Historical Figure

Paul Klee (1879-1940) is undoubtedly the most notable historical figure to have suffered from systemic sclerosis (scleroderma). In this, the first in a series of vignettes on Klee's illness, I will explore a likely early feature of his condition - Raynaud phenomenon. In subsequent vignettes I will highlight other features of Klee's condition.

scholarly journals Paul Klee’s illness—a series of historical and clinical vignettes, part II

2019 ◽  
Vol 5 (1) ◽  
pp. 3-5
Author(s):  
Richard M Silver
Keyword(s):  
Systemic Sclerosis ◽  
20Th Century ◽  
Fine Art ◽  
Important Lesson ◽  
Paul Klee ◽  
Clinical Vignettes ◽  
Human Aspects ◽  
Musculoskeletal Manifestations ◽  
Medical Perspective

Viewing and analyzing fine art from a medical perspective increases our appreciation of the artist’s suffering and teaches an important lesson of the human aspects of medicine. Paul Klee (1879–1940), one of the most influential artists of the 20th century, died at the age of 60 from complications of systemic sclerosis (scleroderma). In this second, in a series of clinical vignettes, I discuss the musculoskeletal manifestations of systemic sclerosis and how they may have influenced the life and art of Paul Klee.

scholarly journals POS0329 GASTROINTESTINAL INVOLVEMENT IN SYSTEMIC SCLEROSIS: PATHOGENETIC ROLE OF GUT MICROBIOME, CYTOKINES AND ADIPOKINES

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 392.1-392
Author(s):  
E. Pigatto ◽  
M. Schiesaro ◽  
M. Caputo ◽  
M. Beggio ◽  
P. Galozzi ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Gut Microbiome ◽  
Serum Levels ◽  
High Serum ◽  
Healthy Population ◽  
Gastrointestinal Involvement ◽  
Degrading Bacteria ◽  
Gi Symptoms ◽  
Low Levels ◽  
The Impact

Background:Gastrointestinal (GI) involvement is very common in patients with Systemic Sclerosis (SSc). The pathophysiology of GI manifestations has not yet been defined. Cell-mediated immunological reactions appear to lead to endothelial damage resulting in fibrosis. The risk of developing malnutrition reinforces the need to better understand GI pathophysiology in these patients.Objectives:The study aimed to evaluate GI symptoms (GIT 2.0) and malnutrition status (MUST) and to determine specific bacterial changes in gut microbiome by investigating the possible presence of positive hot spots in bacterial species in SSc patients and their potential role in the disease progression. We also evaluated serum levels of adipokines and cytokines involved in the pathogenesis of SSc and their role, in addition to gut microbiome, in predicting the onset of GI involvement and malnutrition in SSc patients.Methods:We enrolled 25 scleroderma patients (EULAR/ACR 2013 criteria). UCLA-SCTC GIT 2.0 questionnaire to evaluate GI symptoms and MUST to investigate the risk of malnutrition were used. Gut microbiome was analyzed and the samples were subjected to extraction for the 16S rRNA gene (Earth Microbiome Project and the NIH-Human Microbiome Project). The microbiome was investigated at phenotypic and genotypic level. Serum levels of cytokines and adipokines (adiponectin and leptin) were evaluated by ELISA.Results:79.9% of patients had GERD and 63.5% abdominal distension at GIT 2.0 questionnaires. 48% of patients had moderate risk of malnutrition (MUST=2) and 12% had high risk (MUST=3). Gut microbioma: 19 patients (76%) had low similarity and 11 (44%) low diversity compared to the healthy population. The prevailing enterotypes of gut microbiome was Bacteroides (80%) and Prevotella (20%). The genotypic evaluation showed a reduced concentration of: gluten-digesting (Lactobacillus); lactose-digesting (Faecalibacterium); vitamin K-producing (Enterococcus, Desulfovibrio and Veillonella); acetaldehyde-degrading bacteria. 24 patients (96%) showed a reduction in bacteria devoted to maintaining weight control (Bifidobacterium and Ruminococcus). The patients had an altered intestinal permeability with less mucolytic bacteria (Bacteroides) and reduced production of LPS (Enterobacter and Escherichia). Low levels of butyrate (Eubacterium and Clostridium), acetate and propionate were found for SCFA-producing bacteria. Potentially pathogenic bacteria were also investigated: Salmonella was found in 14 (56%), Klebsiella in 9 (36%) and Enterococcus Faecalis in 3 (12%) patients. 11 (44%) patients had elevated serum levels of IL10 and IL12; 4 (16%) had high value of leptin. Correlation was found in patients who had a reduced concentration of gluten-digesting bacteria and MUST. Elevated MUST was correlated with serological increase in IL17A and IFN-α. Serum levels of IL12 and IL10 were found to correlate with specific bacteria alterations: high concentration of acetaldehyde-producing bacteria and low levels of acetaldehyde-degrade bacteria (also correlated with high serum levels of IL6), mucolytic bacteria and producers of hydrogen sulphide, acetate and propionate. Finally, reduced levels of mucolytic bacteria and acetate producing bacteria correlated with high serum leptin levels.Conclusion:The relationship between the gut microbiome and SSc seems to be multifactorial. In our study genotypic changes of gut microbioma might play a role in damaging the permeability of the mucosa and increasing risk of malnutrition. The evaluation of gut microbiome and cytokine profile is probably going to be of value in the follow-up of SSc. However, further studies are needed to clarify the impact of GI dysbiosis on the immune system in SSc.References:[1]Patrone V. et al. Gut microbiota profile in systemic sclerosis patients with and without clinical evidence of gastrointestinal involvement, Sci Rep. 2017; 7: 14874Disclosure of Interests:None declared

scholarly journals Improved gastrointestinal profile with diroximel fumarate is associated with a positive impact on quality of life compared with dimethyl fumarate: results from the randomized, double-blind, phase III EVOLVE-MS-2 study

2021 ◽  
Vol 14 ◽  
pp. 175628642199399 ◽  
Author(s):  
Annette Wundes ◽  
Sibyl Wray ◽  
Ralf Gold ◽  
Barry A. Singer ◽  
Elzbieta Jasinska ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Medication Use ◽  
Dimethyl Fumarate ◽  
Daily Activities ◽  
Phase Iii ◽  
Symptomatic Medication ◽  
Gi Symptoms ◽  
Symptom Intensity ◽  
The Impact

Background: Diroximel fumarate (DRF) is a novel oral fumarate approved for relapsing forms of multiple sclerosis (MS). DRF demonstrated significantly improved gastrointestinal (GI) tolerability versus dimethyl fumarate (DMF) with fewer days of Individual Gastrointestinal Symptom and Impact Scale (IGISIS) scores ⩾2, GI adverse events (AEs), and treatment discontinuations due to GI AEs. Our aim was to evaluate the impact of GI tolerability events on quality of life (QoL) for patients with relapsing–remitting MS who received DRF or DMF in EVOLVE-MS-2. Methods: A post hoc analysis was conducted in patients who were enrolled in the randomized, blinded, 5-week, EVOLVE-MS-2 [ClinicalTrials.gov identifier: NCT03093324] study of DRF versus DMF. Patients completed daily IGISIS and Global GISIS (GGISIS) eDiary questionnaires to assess GI symptom intensity and interference with daily activities and work. Results: In total, 504 patients (DRF, n = 253; DMF, n = 251) received study drug and 502 (DRF, n = 253; DMF, n = 249) completed at least one post-baseline questionnaire. With DRF, GI symptoms were less likely to interfere ‘quite a bit’ or ‘extremely’ with regular daily activities [IGISIS: DRF, 9.5% (24/253) versus DMF, 28.9% (72/249)] or work productivity [GGISIS: DRF, 6.1% (10/165) versus DMF, 11.3% (18/159)]. DRF-treated patients had fewer days with ⩾1 h of missed work (DRF, 43 days, n = 20 versus DMF, 88 days, n = 26). DMF-treated patients reported highest GI symptom severity and missed work at week 2–3 shortly after completing the titration period, which coincided with the majority of GI-related treatment discontinuations [58.3% (7/12)]. GI tolerability AEs [DRF, 34.8% (88/253); DMF, 48.2% (121/251)], concomitant symptomatic medication use [DRF, 19.3% (17/88) versus DMF, 30.6% (37/121)], and GI-related discontinuations (DRF, 0.8% versus DMF, 4.8%) were lower with DRF versus DMF. Conclusions: The improved GI tolerability with DRF translated into clinically meaningful benefits to QoL, as patients experienced less impact on daily life and work and required less concomitant symptomatic medication use. Trial registration: [ClinicalTrials.gov identifier: NCT03093324]

scholarly journals ILD-specific health-related quality of life in systemic sclerosis-associated ILD compared with IPF

2020 ◽  
Vol 7 (1) ◽  
pp. e000598
Author(s):  
Michael T Durheim ◽  
Anna-Maria Hoffmann-Vold ◽  
Tomas M Eagan ◽  
Arnt-Ove Hovden ◽  
May Brit Lund ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Function ◽  
Forced Vital Capacity ◽  
Vital Capacity ◽  
Health Related Quality ◽  
Related Quality ◽  
Health Related

IntroductionIdiopathic pulmonary fibrosis (IPF) and systemic sclerosis-associated interstitial lung disease (SSc-ILD) are fibrotic ILDs with divergent disease populations. Little is known about health-related quality of life (HRQL) in SSc-ILD relative to IPF.MethodsWe used the Kings Brief Interstitial Lung Disease Questionnaire (K-BILD) to compare HRQL in a cross-sectional study of 57 patients with IPF and 29 patients with SSc-ILD. Analysis of covariance was used to adjust for age, gender and lung function.ResultsThe unadjusted mean K-BILD score was 63.1 (95% CI 57.1 to 69.1) among patients with SSc-ILD, as compared with 54.7 (51.8–57.5) among those with IPF (p=0.005). However, this difference in HRQL was attenuated after adjustment for age, gender and lung function. In a multivariable model, only forced vital capacity was associated with K-BILD scores. K-BILD scores were correlated with both forced vital capacity and with other relevant HRQL measures, regardless of ILD diagnosis.DiscussionPatients with SSc-ILD may have better ILD-specific quality of life than patients with IPF, but this difference appears to be driven primarily by better lung function. These results underscore the impact of lung function on HRQL in fibrotic ILD and the utility of K-BILD to assess HRQL in SSc-ILD.

scholarly journals An open-label study to evaluate biomarkers and safety in systemic sclerosis patients treated with paquinimod

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Roger Hesselstrand ◽  
Jörg H. W. Distler ◽  
Gabriela Riemekasten ◽  
Dirk M. Wuttge ◽  
Marie Törngren ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Type I ◽  
Type I Ifn ◽  
Open Label ◽  
Reactive Protein ◽  
Before And After ◽  
Modified Rodnan Skin Score ◽  
Skin Biopsies ◽  
Rank 2

Abstract Objectives To evaluate the changes in disease-related biomarkers and safety of paquinimod, an oral immunomodulatory compound, in patients with systemic sclerosis (SSc). Methods In this open-label, single-arm, multicenter study, SSc patients with a rapidly progressive disease received paquinimod for 8 weeks. Blood and skin biopsies were collected at baseline, during treatment, and at follow-up for the analyses of type I interferon (IFN) activity, chemokine (C-C motif) ligand 2 (CCL2), and the number of myofibroblasts. The safety of paquinimod was evaluated throughout the study. Results Nine SSc patients were enrolled and completed the study treatment with paquinimod at 3 mg/day for 8 weeks. After the treatment, a reduction of type I IFN activity in the plasma from one patient with elevated baseline IFN activity was recorded. A trend towards reduced IFN activity in the skin after treatment was also observed in patients. The serum level of CCL2 was reduced in 7 of 9 patients after paquinimod treatment. There was a median reduction of 10% of the number of myofibroblasts in skin biopsies at week 8 compared to baseline. No change in modified Rodnan skin score and quality of life was detected in the study. Reported adverse events (AEs) were mild to moderate and expected with the most common being arthralgia (n = 3) and headache (n = 3), and C-reactive protein (CRP) increase. Conclusions Analysis of biomarkers before and after treatment suggest reduced type I IFN activity and reduced number of myofibroblasts in lesional skin. Paquinimod was overall well tolerated with mild to moderate and expected AEs. Trial registration ClinicalTrials.gov, NCT01487551. Registered on 7 September 2011

scholarly journals THU0632-HPR DETERMINANTS OF HAPPINESS AND QUALITY OF LIFE IN PEOPLE WITH SYSTEMIC SCLEROSIS: A STRUCTURAL EQUATION MODELLING APPROACH

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 561.1-561
Author(s):  
T. Santiago ◽  
E. Santos ◽  
A. C. Duarte ◽  
P. Martins ◽  
M. Sousa ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Systemic Sclerosis ◽  
Disease Activity ◽  
Personality Traits ◽  
Structural Equation Modelling ◽  
Structural Equation ◽  
Effective Control ◽  
Equation Modelling ◽  
Disease Impact

Background:In recent years more attention has been given to patients reported outcomes (PROs). Systemic sclerosis (SSc) is no exception. As there is no effective treatment or cure to SSc, it is important to recognize the relevance to patients of the different features of the disease to improve quality and enjoyment of life: the ultimate targets of therapy. Remarkably lacking in PROs is the evaluation of the overall perspective of subjective well being, equivalent to ‘happiness’ or “positive psychological dimensions”.Objectives:To examine the determinants of happiness and quality of life (QoL) in patients with SSc with emphasis on disease activity, disease impact and personality traits.Methods:This is an observational, cross-sectional and multicenter study from six rheumatology clinics in Portugal. A total of 113 patients with SSc with a complete set of data on disease activity, disease impact, personality, quality of life and happiness were included.Structural equation modelling (latent variable structural model) was used to estimate the association between the variables using a maximum likelihood estimation with Satorra-Bentler’s correction and performed with STATA® 15.0. Two hypotheses were pursued: H1 – Disease activity and impact of disease are negatively associated to overall QoL and happiness; H2 – ‘Positive’ personality traits are related to happiness both directly and indirectly through perceived disease impact.Results:Results obtained in the structural equation measurement model indicated a good fit [χ2/df=1.44; CFI=0.93; TLI=0.90; RMSEA=0.06] and supported all driving hypotheses (Figure 1). Happiness was positively related to ‘positive’ personality (β=0.45, p=0.01) and, to a lesser extent, negatively related with impact of disease (β=-0.32; p=0.01). This impact, in turn, was positively related to EUSTAR activity score (β=0.37; p<0.001) and mitigated by ‘positive’ personality traits (β=-0.57; p<0.001). Impact of disease had a much stronger relation with QoL than with happiness (β=-0.78, p<0.001). Quality of life and happiness had no statistically significant relationship.Conclusion:Optimization of Qol and happiness in people with SSc requires effective control of the disease process. Personality and its effects upon the patient´s perception of the disease impact, seems to play a pivotal mediating role in these relations and should deserve paramount attention if happiness and enjoyment of life is taken as the ultimate goal of health care.Disclosure of Interests:Tânia Santiago: None declared, Eduardo Santos: None declared, Ana Catarina Duarte: None declared, Patrícia Martins: None declared, Marlene Sousa: None declared, Franscisca Guimarães: None declared, Soraia Azevedo: None declared, Raquel Ferreira: None declared, Miguel Guerra: None declared, Ana Cordeiro Consultant of: Ana Cordeiro has acted as a consultant for Roche, Speakers bureau: Ana Cordeiro has received speaker fees from Boehringer Ingelheim, Lilly, and Vitoria, Inês Cordeiro: None declared, Sofia Pimenta: None declared, Patrícia Pinto: None declared, Maria Joao Salvador: None declared, José Antonio P. da Silva Grant/research support from: Pfizer, Abbvie, Consultant of: Pfizer, AbbVie, Roche, Lilly, Novartis

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