Tag: lupus

Autonomic symptom burden, comorbidities and quality of life in women with Hypermobility Spectrum Disorders and hypermobile Ehlers-Danlos syndrome

Abstract:

Background: Hypermobility Spectrum Disorders (HSD) and hypermobile Ehlers-Danlos syndrome (h-EDS) are multisystemic connective tissue disorders involving joint hypermobility and numerous other manifestations. Autonomic dysfunction, chronic pain, and chronic fatigue are known comorbidities of HSD and h-EDS that can affect patient quality of life (QoL), but there are limited data on the severity of autonomic symptoms, prevalence of comorbid conditions and QoL in patients with HSD/h-EDS.

Methods: We utilized the Composite Autonomic Symptom Scale (COMPASS-31) to assess autonomic symptom severity, Short-Form 36 (SF-36) to assess QoL, and the Beck Depression Inventory Second Edition (BDI-II) in a cohort of women with physician-diagnosed HSD or h-EDS, who completed these questionnaires anonymously.

Results: 84 women (mean age of 37.1 ± 8.4 years) completed the study. 58.3 % reported having physician-diagnosed postural orthostatic tachycardia syndrome (POTS), 32.1 % had mast cell activation syndrome (MCAS), 54.8 % had migraine, 26.2 % had myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and 98.8 % reported experiencing chronic pain. Importantly, 25 % of patients reported having all three diagnoses: HSD/h-EDS, POTS and MCAS. Mean COMPASS-31 score was 54.45 (range 18.79-80.93), indicating severe autonomic dysfunction, which was significantly higher than in patients with multiple sclerosis, diabetic neuropathy, scleroderma, and psoriatic arthritis as shown in prior studies. Mean SF-36 score was 32.38 (SD = 22.91) indicating poor QoL, which was worse than in patients with POTS, multiple sclerosis, rheumatoid arthritis, and lupus as determined by prior studies.

Conclusions: This study demonstrates that women with HSD/h-EDS experience severe autonomic dysfunction, chronic pain, chronic comorbid conditions and reduced QoL. More than half of participants in this cohort had POTS and migraine, with one in four having a clinical triad of HSD/h-EDS, POTS and MCAS.

Source: Collins Hutchinson ML, Liang E, Fuster E, Blitshteyn S. Autonomic symptom burden, comorbidities and quality of life in women with Hypermobility Spectrum Disorders and hypermobile Ehlers-Danlos syndrome. Auton Neurosci. 2025 Oct 14;262:103356. doi: 10.1016/j.autneu.2025.103356. Epub ahead of print. PMID: 41118678. https://pubmed.ncbi.nlm.nih.gov/41118678/

Ignored, dismissed, and minimized: Understanding the harmful consequences of invalidation in health care-A systematic meta-synthesis of qualitative research

Abstract:

The upsurge in the prevalence of contested, ambiguous, and difficult-to-diagnose illnesses presents challenges for clinicians who too often respond by invalidating patients’ symptoms. Although numerous qualitative studies have reported the effects of invalidation on patients’ psychological and behavioral outcomes, this body of research has not been systematically reviewed. Informed by Linehan’s (1993) conceptualization of invalidation, this systematic review elucidated the negative consequences, of symptom invalidation, or the dismissal or minimization of a person’s experiences with illness.

We reviewed 151 qualitative reports representing 11,307 individuals with Ehlers-Danlos syndrome, endometriosis, fibromyalgia syndrome, Gulf War syndrome, irritable bowel syndrome, long COVID, multiple chemical sensitivity, myalgic encephalomyelitis/chronic fatigue syndrome, postural orthostatic tachycardia syndrome, systemic lupus erythematosus, and vulvodynia.

Consistent with Linehan’s theorizing, thematic analysis identified four broad classes of consequences: induced emotional states and beliefs (e.g., shame, suicidality), induced health care emotional states and beliefs (e.g., health care-related anxiety and trauma), induced health care behavior (e.g., health care system avoidance), and diagnostic delay.

Informed by these findings, we developed a novel conceptual model explaining how symptom invalidation leads to these consequences and thereby undermines health outcomes. Future work should explore the proposed conceptual model and identify theoretically informed interventions and policies aimed at preventing symptom invalidation to improve psychological, behavioral, and health outcomes. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Source: Bontempo AC, Bontempo JM, Duberstein PR. Ignored, dismissed, and minimized: Understanding the harmful consequences of invalidation in health care-A systematic meta-synthesis of qualitative research. Psychol Bull. 2025 Apr;151(4):399-427. doi: 10.1037/bul0000473. PMID: 40310228. https://psycnet.apa.org/fulltext/2026-10154-001.html (Full text)

Exploring the shared mechanism of fatigue between systemic lupus erythematosus and myalgic encephalomyelitis/chronic fatigue syndrome: monocytic dysregulation and drug repurposing

Abstract:

Background: SLE and ME/CFS both present significant fatigue and share immune dysregulation. The mechanisms underlying fatigue in these disorders remain unclear, and there are no standardized treatments. This study aims to explore shared mechanisms and predict potential therapeutic drugs for fatigue in SLE and ME/CFS.

Methods: Genes associated with SLE and ME/CFS were collected from disease target and clinical sample databases to identify overlapping genes. Bioinformatics analyses, including GO, KEGG, PPI network construction, and key target identification, were performed. ROC curve and correlation analysis of key targets, along with single-cell clustering, were conducted to validate their expression in different cell types. Additionally, an inflammation model was established using THP-1 cells to simulate monocyte activation in both diseases in vitro, and RT-qPCR was used to validate the expression of the key targets. A TF-mRNA-miRNA co-regulatory network was constructed, followed by drug prediction and molecular docking.

Results: Fifty-eight overlapping genes were identified, mainly involved in innate immunity and inflammation. Five key targets were identified (IL1β, CCL2, TLR2, STAT1, IFIH1). Single-cell sequencing revealed that monocytes are enriched with these targets. RT-qPCR confirmed significant upregulation of these targets in the model group. A co-regulatory network was constructed, and ten potential drugs, including suloctidil, N-Acetyl-L-cysteine, simvastatin, ACMC-20mvek, and camptothecin, were predicted. Simvastatin and camptothecin showed high affinity for the key targets.

Conclusion: SLE and ME/CFS share immune and inflammatory pathways. The identified key targets are predominantly enriched in monocytes at the single-cell level, suggesting that classical monocytes may be crucial in linking inflammation and fatigue. RT-qPCR confirmed upregulation in activated monocytes. The TF-mRNA-miRNA network provides a foundation for future research, and drug prediction suggests N-Acetyl-L-cysteine and camptothecin as potential therapies.

Source: Zheng D, Li X, Wang P, Zhu Q, Huang Z, Zhao T. Exploring the shared mechanism of fatigue between systemic lupus erythematosus and myalgic encephalomyelitis/chronic fatigue syndrome: monocytic dysregulation and drug repurposing. Front Immunol. 2025 Jan 7;15:1440922. doi: 10.3389/fimmu.2024.1440922. PMID: 39845969; PMCID: PMC11752880. https://pmc.ncbi.nlm.nih.gov/articles/PMC11752880/ (Full text)

Autoantibody production is enhanced after mild SARS-CoV-2 infection despite vaccination in individuals with and without long COVID

Abstract:

Long COVID patients who experienced severe acute SARS-CoV-2 infection can present with humoral autoimmunity. However, whether mild SARS-CoV-2 infection increases autoantibody responses and whether vaccination can decrease autoimmunity in long COVID patients is unknown.

Here, we demonstrate that mild SARS-CoV-2 infection increases autoantibodies associated with systemic lupus erythematosus (SLE) and inflammatory myopathies in long COVID patients with persistent neurologic symptoms to a greater extent than COVID convalescent controls at 8 months post-infection. Furthermore, high titers of SLE-associated autoantibodies in long COVID patients are associated with impaired cognitive performance and greater symptom severity, and subsequent vaccination/booster does not decrease autoantibody titers.

In summary, we found that mild SARS-CoV-2 infection can induce persistent humoral autoimmunity in both long COVID patients and healthy COVID convalescents, suggesting that a reappraisal of vaccination and mitigation strategies is warranted.

Source: Visvabharathy L, Zhu C, Orban ZS, Yarnoff K, Palacio N, Jimenez M, Lim PH, Penaloza-MacMaster P, Koralnik IJ. Autoantibody production is enhanced after mild SARS-CoV-2 infection despite vaccination in individuals with and without long COVID. medRxiv [Preprint]. 2023 Apr 12:2023.04.07.23288243. doi: 10.1101/2023.04.07.23288243. PMID: 37090595; PMCID: PMC10120795. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10120795/ (Full text)

Silicone breast implants and depression, fibromyalgia and chronic fatigue syndrome in a rheumatology clinic population

Abstract:

INTRODUCTION: Silicone breast implants (SBI) may induce systemic autoimmune disease as part of autoimmune syndrome induced by adjuvants (ASIA). This syndrome bears similarities to fibromyalgia and chronic fatigue syndrome (CFS). We sought to determine whether there are any associations between SBI and depression, fibromyalgia and CFS in a rheumatology clinic population.

METHODS: The electronic files of rheumatology clinic patients at the Royal Adelaide Hospital between 2000 and 2017 were searched for patients who had received SBI prior to rheumatological diagnosis. Demographics, diagnosis, implant history and whether the patient had depression, fibromyalgia or CFS were recorded. Controls were rheumatology clinic patients, half of whom had systemic sclerosis (SSc) and the other half had systemic lupus erythematosus (SLE). They were matched to cases 3:1 for age (within 2 years) and gender.

RESULTS: Thirty patients had received SBI (mean age 47.9, 100% female). Twelve had a diagnosis of depression, 6 of fibromyalgia and 3 of CFS. Implant rupture was not associated with any of these (p = 1). There was no difference in the incidence of depression (p = 1), fibromyalgia (p = 0.76) or CFS (p = 0.3) between cases and SLE controls. When compared with SSc controls, there were significantly more patients with fibromyalgia and/or CFS in the case group (20.0% of cases vs 2.2% of SSc controls, p = 0.01) but no difference in depression (p = 0.12).

CONCLUSION: Fibromyalgia and CFS are more common in patients with silicone implants than SSc controls but not SLE controls. Prospective study of development of depression, fibromyalgia and CFS in recipients of SBI is required.

Source: Khoo T, Proudman S, Limaye V. Silicone breast implants and depression, fibromyalgia and chronic fatigue syndrome in a rheumatology clinic population. Clin Rheumatol. 2019 Jan 31. doi: 10.1007/s10067-019-04447-y. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/30706290

The “anti-Ki” syndrome: major clinical features

Abstract:

OBJECTIVE: To describe the major clinical features of patients with high titers of anti-Ki antibodies.

METHOD AND RESULTS: Four of 172 patients with connective tissue diseases showed high titers (> 1/256) of anti-Ki antibodies. In these four patients, (1) the common clinical findings were alopecia, disabling chronic fatigue, muscle weakness, tenosynovitis, dry mouth, and abnormal glucose tolerance test; (2) anti-Ki antibodies were positive not only in patients with sicca lupus, but also in those with nonsicca lupus. In this case, anti-insulin receptor antibody was positive and there was a regulatory insufficiency of the pituitary. (3) Symptoms of anti-Ki antibodies share many clinical and laboratory features of chronic fatigue syndrome and fibromyalgia, that is, they may share either a common etiologic agents or a common pathogenetic pathway or both.

CONCLUSION: “Anti-Ki antibody” syndrome may be a subset of sicca lupus.

 

Source: Matsunaga K. The “anti-Ki” syndrome: major clinical features. Rinsho Byori. 1993 Aug;41(8):882-7. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/8371504