Arthritis Syndrome Research Articles

Choroidal, retinal, and optic nerve changes in rheumatoid arthritis and primary sjogren's syndrome patients: comparıson with each other and healthy subjects.

The present study aims to evaluate the optic nerve, macula, and choroidal changes in both rheumatoid arthritis (RA) and primary Sjögren's syndrome (SjS) patients, and to compare these findings with age-matched healthy volunteers. This study included 46 RA patients, 33 primary SjS patients, and 37 age-matched healthy volunteers. All of the patients underwent a thorough ophthalmological examination, during which measurements of the retinal nerve fiber layer (RNFL), ganglion cell layer(GCL), and subfoveal choroidal thickness (CT) were taken using OCT (optical coherence tomography). The measurements taken from the right eye of each patient were used to compare among the groups. RNFL thickness in superior quadrant was found to be statistically significantly thinner in the eyes with RA when compared to the control group (p = 0.022). In the nasal quadrant, the RNFL thickness was significantly thinner in patients with primary SjS compared to healthy individuals (p = 0.036). Also, the temporal quadrant RNFL was significantly thinner in RA patients than in the primary SjS patients (p = 0.033). GCL thickness was observed to be thinner in all quadrants of both RA and primary SjS groups compared to the control group. However, the difference was not found to be statistically significant. Subfoveal CT was observed to be thicker in RA and SjS groups compared to the control group, but this difference was also not statistically significant. Systemic autoimmune diseases like RA and primary SjS can lead to a decrease in RNLF and GCL thickness, which can impair visual acuity even in the absence of ocular symptoms. Therefore, monitoring changes in the optic nerve, retina, and choroid layer are crucial in these patients.

Complications of operatively treated distal radial fractures.

Distal radial fractures represent the most common fractures of the upper extremity. Operative treatment is performed for approximately one-third of distal radial fractures in the adult population. Complications following operative treatment of distal radial fractures vary depending on the treatment modality and can be stratified into preoperative and postoperative complications. Complications can occur in the near, intermediate and long term. The most common complications seen are tendon irritation and rupture, chronic regional pain syndrome (CRPS), carpal tunnel syndrome, ulnar or radial neuropathy, compartment syndrome, malunion, inadequate fixation or loss of fixation, symptomatic hardware, post-traumatic arthritis, stiffness and infection. Careful planning, treatment and patient selection can help to mitigate these complications.Level of evidence: V.

Identification and genetic correlation of avian reoviruses to the currently used vaccines in Egypt

A variety of illnesses, including arthritis, tenosynovitis, stunted growth, and malabsorption syndrome, are caused by Avian Reoviruses (ARVs), which have become more prevalent in Egypt during recent years and resulted in significant economic losses. This study investigated 27 suspected samples collected from 14 broiler breeders and 13 broilers suffering from immunosuppression, decreased body weight, and diarrhea. Fourteen samples tested positive based on RT-PCR, and the virus could be isolated from ten samples in Specific Pathogen Free (SPF) embryonated chicken eggs. Ten isolates were subjected to molecular and genetic analysis of the S1 gene (sigma C) and S2 gene (sigma A). The amino acid identity of the S1 gene revealed that these viruses are closely related to the viruses that were identified in Israel during 2020 (91.8%-97.2% identity) and belonged to the genetic cluster 5 (genotype 5), which also includes some viruses that are circulating in the United States and Canada. They also showed weak similarity (48.9%-50.2%) with the available vaccine strains in the Egyptian field that belong to cluster 1, genotype 1. The S2 gene showed amino acid homology of 91.7%-98.2% with the current vaccine used in Egypt. However, the Egy-Reo-7-2021 virus had the lowest similarity (84.2%-87.6%) to the available vaccine. It is hypothesized that the difference between field and vaccine strains may have contributed to the failure of current vaccinations to produce protective immunity against current ARV strains circulated in Egypt, which made the disease a problem to the poultry industry. Developing homologous vaccines and evaluating their potency and efficacy are required in Egypt.

Kawasaki Disease-Associated Cytokine Storm Syndrome.

Kawasaki disease (KD) is a hyperinflammatory syndrome manifesting as an acute systemic vasculitis characterized by fever, nonsuppurative conjunctival injection, rash, oral mucositis, extremity changes, and cervical lymphadenopathy. KD predominantly affects young children and shares clinical features and immunobiology with other hyperinflammation syndromes including systemic juvenile idiopathic arthritis (sJIA) and multisystem inflammatory syndrome in children (MIS-C). Cytokine storm syndrome (CSS) is an acute complication in ~2% of KD patients; however, the incidence is likely underestimated as many clinical and laboratory features of both diseases overlap. CSS should be entertained when a child with KD is unresponsive to IVIG therapy with recalcitrant fever. Early recognition and prompt institution of immunomodulatory treatment can substantially reduce the mortality and morbidity of CSS in KD. Given the known pathogenetic role of IL-1β in both syndromes, the early use of IL-1 blockers in refractory KD with CSS deserves consideration.

Clinical Image: Eczema herpeticum in a patient with rheumatoid arthritis and dry eye syndrome.

Clinical Image: Eczema herpeticum in a patient with rheumatoid arthritis and dry eye syndrome.

An Overview of Growth Factors as the Potential Link between Psoriasis and Metabolic Syndrome.

Psoriasis is a chronic, complex, and immunologically mediated systemic disease that not only affects the skin, but also the joints and nails. It may coexist with various other disorders, such as depression, psoriatic arthritis, cardiovascular diseases, diabetes mellitus, and metabolic syndrome. In particular, the potential link between psoriasis and metabolic syndrome is an issue worthy of attention. The dysregulation of growth factors could potentially contribute to the disturbances of keratinocyte proliferation, inflammation, and itch severity. However, the pathophysiology of psoriasis and its comorbidities, such as metabolic syndrome, remains incompletely elucidated. Growth factors and their abnormal metabolism may be a potential link connecting these conditions. Overall, the objective of this review is to analyze the role of growth factor disturbances in both psoriasis and metabolic syndrome.

Recent Insights in Pyrin Inflammasome Activation: Identifying Potential Novel Therapeutic Approaches in Pyrin-Associated Autoinflammatory Syndromes.

Pyrin is a cytosolic protein encoded by the MEFV gene, predominantly expressed in innate immune cells. Upon activation, it forms an inflammasome, a multimolecular complex that enables the activation and secretion of IL-1β and IL-18. In addition, the Pyrin inflammasome activates Gasdermin D leading to pyroptosis, a highly pro-inflammatory cell death. Four autoinflammatory syndromes are associated with Pyrin inflammasome dysregulation: familial Mediterranean fever, hyper IgD syndrome/mevalonate kinase deficiency, pyrin-associated autoinflammation with neutrophilic dermatosis, and pyogenic arthritis, pyoderma gangrenosum, and acne syndrome. In this review, we discuss recent advances in understanding the molecular mechanisms regulating the two-step model of Pyrin inflammasome activation. Based on these insights, we discuss current pharmacological options and identify a series of existing molecules with therapeutic potential for the treatment of pyrin-associated autoinflammatory syndromes.

High Dose Cyclophosphamide for the Treatment of Severe Immune Checkpoint Inhibitor Related Adverse Events.

Immune-related adverse events (irAEs) are a group of autoimmune syndromes that arise following therapy with immune checkpoint inhibitors (ICIs) and are characterized by disinhibition of cell-mediated immunity and decreased self-tolerance. First line treatment of irAEs is typically steroids. Severe irAEs that are refractory to steroids can be life threatening and treatment protocols are an area of unmet need. Standardized clinical guidelines for management of severe corticosteroid refractory irAEs are currently not available and thus are an area of unmet need. We present two patients who were treated with nivolumab and subsequently developed steroid refractory irAEs in the forms of transverse myelitis, arthritis, and peri-engraftment respiratory distress syndrome. Treatment with a single high dose of cyclophosphamide resulted in rapid and sustained clinical improvements in two patients experiencing steroid refractory irAEs following ICI therapy. Cyclophosphamide may benefit patients with wide spectrum of irAEs while having a favorable toxicity profile.

Association between Leukocyte Cell-Derived Chemotaxin 2 and Metabolic and Renal Diseases in a Geriatric Population: A Pilot Study.

LECT2 is not a routine diagnostic marker for any disease, but it has been associated with many pathologies, including systemic amyloidosis, rheumatoid arthritis, diabetes, atherosclerosis, and metabolic syndrome. With human aortic sections (n = 22) and sera from geriatric subjects (n = 79), we analyzed the relationships that could be observed between this protein and other parameters related to metabolic diseases. As a result, we observed a relatively high (r~0.8, p < 0.05) positive correlation between SRA and LECT2 and a negative correlation between EGFR and LECT2 (r~-0.4, p < 0.05). We observed LECT2 expression in macrophages, myocytes, and other aortic cells, with a tendency to be overexpressed in developed atherosclerotic plaques. We conclude that LECT2 exerts its chemotactic effects not only as a protein synthesized in the liver and secreted and circulating in the blood but also as a locally expressed protein within atherosclerotic plaque development. The LECT2-EGFR correlation suggests an association of this protein with loss of normal renal function. This fact can be associated with LECT2 amyloidosis, although it should be verified whether in the geriatric population there is indeed a widespread accumulation of LECT2 with the progression of aging or whether it is rather a marker of general deterioration of renal function.

Identification and validation of novel biomarkers for cold-dampness syndrome of rheumatoid arthritis based on integration of multiple bioinformatics methods

This study aims to identify the novel biomarkers of cold-dampness syndrome(RA-Cold) of rheumatoid arthritis(RA) by gene set enrichment analysis(GSEA), weighted gene correlation network analysis(WGCNA), and clinical validation. Firstly, transcriptome sequencing was carried out for the whole blood samples from RA-Cold patients, RA patients with other traditional Chinese medicine(TCM) syndromes, and healthy volunteers. The differentially expressed gene(DEG) sets of RA-Cold were screened by comparison with the RA patients with other TCM syndromes and healthy volunteers. Then, GSEA and WGCNA were carried out to screen the key DEGs as candidate biomarkers for RA-Cold. Experimentally, the expression levels of the candidate biomarkers were determined by RT-qPCR for an independent clinical cohort(not less than 10 cases/group), and the clinical efficacy of the candidates was assessed using the receiver operating characteristic(ROC) curve. The results showed that 3 601 DEGs associated with RA-Cold were obtained, including 106 up-regulated genes and 3 495 down-regulated genes. The DEGs of RA-Cold were mainly enriched in the pathways associated with inflammation-immunity regulation, hormone regulation, substance and energy metabolism, cell function regulation, and synovial pannus formation. GSEA and WGCNA showed that recombinant proteasome 26S subunit, ATPase 2(PSMC2), which ranked in the top 50% in terms of coefficient of variation, representativeness of pathway, and biological modules, was a candidate biomarker of RA-Cold. Furthermore, the validation results based on the clinical independent sample set showed that the F1 value, specificity, accuracy, and precision of PSMC2 for RA-Cold were 70.3%, 61.9%, 64.5%, and 81.3%, respectively, and the area under the curve(AUC) value was 0.96. In summary, this study employed the &quot;GSEA-WGCNA-validation&quot; integrated strategy to identify novel biomarkers of RA-Cold, which helped to improve the TCM clinical diagnosis and treatment of core syndromes in RA and provided an experimental basis for TCM syndrome differentiation.

Clinical Manifestations.

Perturbations in immune pathways are strongly associated with Alzheimer's disease. A positive association between autoimmune diseases and frontotemporal dementia has been reported. We explored whether early onset Alzheimer's disease (EOAD) would associate with autoimmune diseases. We compared 313 patients with EOAD from the Mayo Clinic Florida, Alzheimer's Disease Research Center (ADRC) Registry with matched cognitively normal controls (NC) based on age (+/- 2 years) and gender at 1:2 ratio. NC were derived from Mayo Clinic Biobank Project, Rochester (N = 313) and the Mayo Clinic Study of Aging (N = 313). Data abstraction was performed by trained statisticians using ICD 9&10 codes corresponding to 40 specified autoimmune diseases and/or documentation of specified immunomodulatory treatment. Data was also abstracted via retrospective record review. We further reviewed clinical records from EOAD patients with neuropathologically confirmed Alzheimer's disease patients enrolled in the ADRC (n = 10). Each autoimmune disease type was compared between cases and controls using Fisher's exact test. All tests were two-sided with alpha level set at 0.05 for statistical significance. Continuous variables were summarized as median (range) while categorical variables were reported as frequency (percentage). The prevalence of autoimmune disease in the general population was based off Hayter & Cook, 2012 and Roberts & Erdei, 2020. All data abstraction was done blinded to the clinical diagnosis and baseline demographics. Autoimmune disease history was abstracted from 949 patient records (313 EOAD, 10 pathologically-confirmed EOAD, 626 NCI). The median age was 57 years-old. (EOAD range 28,65 yrs.; NC 30,66 yrs.). Autoimmune thyroiditis (p = 0.0008), ulcerative colitis (p = 0.011, psoriasis (<0.0001), rheumatoid arthritis (p = 0.0005), and Raynaud's syndrome (p = 0.0021) were less prevalent in patients with EOAD compared to NC. Furthermore, patients with EOAD had a lower prevalence of immune mediated hematologic disorders. Patients with EOAD have a lower prevalence of autoimmune diseases than NC. Immune activation identified in early onset AD patients may be unrelated to autoimmunity. Findings should be explored in late onset AD patients.

Genetic mutations in pyoderma gangrenosum, hidradenitis suppurativa, and associated autoinflammatory syndromes: Insights into pathogenic mechanisms and shared pathways.

Pyoderma gangrenosum (PG), hidradenitis suppurativa (HS), and the associated autoinflammatory syndromes, including pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome, PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome, pyoderma gangrenosum, acne, and hidradenitis suppurativa (PASH) syndrome, and pyogenic arthritis, pyoderma gangrenosum, acne, and suppurative hidradenitis (PAPASH) syndrome are dermatological conditions characterized by chronic inflammation and tissue damage. Recent advances in genetic research have identified specific mutations associated with these disorders, shedding light on their underlying pathogenic mechanisms. This review aims to summarize the current knowledge of identified mutations and presumed pathophysiology in PG, HS, and the associated autoinflammatory syndromes.

Efficacy and safety of 5-aminolevulinic acid in adult-onset Still's disease: A preclinical study in mice and a pilot study in humans

The study aimed to investigate the therapeutic effects of 5-aminolevulinic acid/sodium ferrous citrate (5-ALA/SFC) on adult-onset Still's disease (AOSD), specifically focusing on arthritis and macrophage activation syndrome (MAS). We used mouse models to assess the impact of 5-ALA/SFC on collagen-induced arthritis (CIA) and MAS induced by synthetic oligonucleotides containing CpG motifs (CpG-S-ODN). Additionally, we conducted a pilot study with AOSD patients receiving prednisolone (PSL) treatment and 5-ALA/SFC administration to evaluate its efficacy and safety. The 5-ALA/SFC group exhibited significantly lower joint scores in CIA mice. In CpG-S-ODN-treated mice, 5-ALA/SFC administration led to reduced hemophagocytosis and splenomegaly. The anti-inflammatory properties of 5-ALA/SFC were attributed to the suppression of CCL4 and CXCL10 production in monocytes and the induction of M2 macrophages. AOSD patients treated with 5-ALA/SFC demonstrated successful PSL tapering without adverse events. Collectively, the administration of 5-ALA/SFC showed promising potential in ameliorating arthritis and MAS in AOSD patients.

Pyogenic Arthritis, Pyoderma Gangrenosum and Acne (PAPA) and PAPA-Like Syndromes: Systematic Review of the Literature

Pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome is a rare autosomal dominant autoinflammatory disorder caused by mutations in the PSTPIP1/CD2BP1 gene. We systematically reviewed 93 patients with PAPA and PAPA-like syndrome. Most patients were male (65.9%) mainly born to non-consanguineous parents. The median (IQR) age at the onset of symptoms and diagnosis was 6.0 (2.0- 8.0) and 25.0 (7.0-32.0) years, respectively. 62.5% of patients were presented with arthropathies and septic arthritis was the most common (54.2%) initial diagnosis. Joint disorders were the most common findings (n=71, 78.9%) starting at the median (IQR) age of 4.0 (2.0-8.0) years, mainly in the knee (56.5%), ankle (36.9%), and elbow (47.8%). Skin involvement (62 (66.7%)) initially presented at a median (IQR) age of 12.0 (20.-10.0) years and included pyoderma gangrenosum (n=41, 44.1%), acne (n=43, 46.2%), and nodulocystic acne (n=19, 20.4%). There was a stronger association between skin manifestations and the development of the classic triad (P&lt;0.001) compared to joint disorders (P=0.05) and patients with lower age of onset were more prone to the progression of the complete triad (P=0.18). Corticosteroids (n=45, 50.0%) with or without anakinra (33.3%) were the treatments applied in the majority of patients. PAPA/PAPA-like syndromes involve mainly non-axial joints in early childhood and later skin in the second decade of life. Only 26.4% of the patients manifested the classical triad of PAPA syndrome. There is no clear genotype-phenotype association in these disorders. More studies are required to investigate the therapeutic options in PAPA/PAPA-like syndromes.

Tmem178 Negatively Regulates IL-1β Production Through Inhibition of the NLRP3 Inflammasome.

Inflammasomes modulate the release of bioactive interleukin (IL)-1β. Excessive IL-1β levels are detected in patients with systemic juvenile idiopathic arthritis (sJIA) and cytokine storm syndrome (CSS) with mutated and unmutated inflammasome components, raising questions on the mechanisms of IL-1β regulation in these disorders. To investigate how the NLRP3 inflammasome is modulated in sJIA, we focused on Transmembrane protein 178 (Tmem178), a negative regulator of calcium levels in macrophages, and measured IL-1β and caspase-1 activation in wild-type (WT) and Tmem178-/- macrophages after calcium chelators, silencing of Stim1, a component of store-operated calcium entry (SOCE), or by expressing a Tmem178 mutant lacking the Stromal Interaction Molecule 1 (Stim1) binding site. Mitochondrial function in both genotypes was assessed by measuring oxidative respiration, mitochondrial reactive oxygen species (mtROS), and mitochondrial damage. CSS development was analyzed in Perforin-/- /Tmem178-/- mice infected with lymphocytic choriomeningitis virus (LCMV) in which inflammasome or IL-1β signaling was pharmacologically inhibited. Human TMEM178 and IL1B transcripts were analyzed in data sets of whole blood and peripheral blood monocytes from healthy controls and patients with active sJIA. TMEM178 levels are reduced in whole blood and monocytes from patients with sJIA while IL1B levels are increased. Accordingly, Tmem178-/- macrophages produce elevated IL-1β compared with WT cells. The elevated intracellular calcium levels after SOCE activation in Tmem178-/- macrophages induce mitochondrial damage, release mtROS, and ultimately promote NLRP3 inflammasome activation. In vivo, inhibition of inflammasome or IL-1β neutralization prolongs Tmem178-/- mouse survival in LCMV-induced CSS. Down-regulation of TMEM178 levels may represent a marker of disease activity and help identify patients who could benefit from inflammasome targeting.

Clinical and genetic analysis of the first Mexican patient with a diagnosis of pyogenic sterile arthritis, pyoderma gangrenosum and acne (PAPA) syndrome.

Our report discusses the first Mexican patient with a clinical and molecular diagnosis of pyogenic sterile arthritis, pyoderma gangrenosum and acne syndrome. In addition, a literature review of the clinical and molecular spectrum of the disease is included.

Molecular diagnostic yield for Blau syndrome in previously diagnosed juvenile idiopathic arthritis with uveitis or cutaneous lesions.

Diagnostic pitfalls often arise in the community because of potentially misleading similarities between juvenile idiopathic arthritis (JIA) and Blau syndrome, an immune-related disorder caused by NOD2 gene mutations. It remains unclear in which population and to what extent next-generation sequencing techniques can aid in diagnosis. We evaluated clinical usefulness of targeted next-generation sequencing in previously diagnosed JIA. Participants were required to have symptoms and signs suspected of Blau syndrome, including at least uveitis or cutaneous lesions in addition to arthritis. Targeted sequencing was conducted on NOD2 gene to detect diagnostic variants classified as pathogenic or likely pathogenic for Blau syndrome. We assessed the molecular diagnostic yield and clinical implications for patient care. Between 1 May 2008 and 1 June 2021, sequencing data were accrued from 123 previously diagnosed JIA (median age: 5 years; female: 62.6%). Targeted NOD2 sequencing yielded a positive molecular diagnosis of Blau syndrome in 21.1% (95% CI: 14.9%, 29.2%), encompassing six heterozygous missense mutations classified as pathogenic variants. Among those receiving a molecular diagnosis, changes in clinical management and treatment were considered as having occurred in 38.5%. Nine predictors were identified as being associated with a higher diagnostic yield, providing clinical clues to suspect the possibility of Blau syndrome. Among some patients with paediatric-onset arthritis complicated with uveitis or cutaneous lesions, reassessment of the diagnosis of JIA may be warranted. Targeted NOD2 sequencing established the molecular diagnosis of Blau syndrome in nearly one-fifth of these cases and provided clinically relevant information for patient-care decisions.

Prevalence and Spectrum of Autoimmune Diseases Among Patients with Telomere Biology Disorder

Introduction Telomeres are the protective ends of linear chromosomes that prevent DNA degradation with each replication. Premature attrition or dysfunction of telomeres due to an inherited defect in a telomere maintenance gene results in a spectrum of phenotypes collectively known as telomere biology disorders (TBD). To date, 18 genes have been implicated in TBD. Disease phenotypes are variable including bone marrow failure, immunodeficiency, myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), idiopathic pulmonary fibrosis (IPF), liver cirrhosis, nail dystrophy, and premature graying of hair. Short telomeres have been observed in patients with autoimmune disorders (AID) and have been shown to increase the risk of AID. Furthermore, TBD have been associated with T cell dysfunction and exhaustion, mechanisms which may predispose to autoimmune phenotypes. Given the potential relationship between short telomeres and immune dysregulation, we hypothesize that the prevalence of AID may be increased in patients with a diagnosis of TBD. The aim of this study is to describe the prevalence and spectrum of AID in a cohort of patients with TBD. Methods Health record data were reviewed for 34 adult patients with confirmed TBD treated at the University of Wisconsin-Madison. A TBD diagnosis was established for patients who had a compatible clinical history plus either critically short lymphocyte telomere lengths (&amp;lt;1 st percentile for age as measured by FlowFISH) or one or more pathogenic/likely pathogenic variant(s) in a gene known to cause TBD. Demographics, rheumatologic history, serologies, and family history were collected. AID were included if diagnoses were made by a rheumatologist or other appropriate specialist with clinical features, physical exam findings, and/or serologies meeting diagnostic criteria per subspecialty guidelines. Results Eight of 34 patients (23.5%) with TBD had a concomitant diagnosis of a primary autoimmune condition. Specific AID included inflammatory bowel disease, Graves' disease, Hashimoto's thyroiditis, rheumatoid arthritis, scleroderma, and Sjogren's syndrome (Table 1). Two patients had autoimmune cytopenias, including steroid-responsive immune thrombocytopenic purpura and pure red cell aplasia (PRCA). Patient 8 was diagnosed with PRCA mixed with spur cell anemia prior to transplant, and bone marrow biopsy showed pure erythroid hypoplasia without evidence of malignancy. He responded to treatment with steroids and immunosuppression. Of the eight patients with a primary autoimmune condition, two had pathogenic/like pathogenic variants, two had rare variants of uncertain significance, and four had no detectable variants in a telomere associated gene. Twenty-three patients (67.6%) had a first- or second-degree relative with an autoimmune disorder. Conclusions An AID, as defined by strict diagnostic criteria per subspecialty guidelines, was present in 23.5% of patients with TBD defined by conservative diagnostic criteria. The spectrum of AID was diverse, including two patients with autoimmune hematologic disorders, and the majority had a family history of various AID. Thus, TBD may be associated with an increased prevalence of AID, though confirmation in a larger cohort of genetically defined TBD patients is needed. In the absence of a causative genetic lesion, diagnosis of a TBD based on critically short telomeres in those with multisystem autoimmune disorders with features that overlap TBD phenotypes can be challenging. Screening for AID as part of routine TBD comprehensive assessments as well as offering germline genetic testing for individuals with primary autoimmune disease with a compatible TBD phenotypes and studies to determine the mechanistic relationship between telomere length and autoimmunity are warranted.

Immunoglobulin G4-Related Lesions in Autoimmune Diseases: Unusual Presentations at Atypical Sites-A Tale of 2 Cases with Literature Review.

Immunoglobulin G4-related disease (IgG4-RD) coexisting with clinically apparent autoimmune diseases, such as rheumatoid arthritis (RA) or antiphospholipid syndrome (APS), is a rarely documented combination in the scientific literature. In this case-based review, we present 2 intriguing cases with preexisting autoimmune diseases, namely, RA and primary APS, who exhibited coexistent IgG4- related lesions at unusual sites. The first case pertains to a patient with known RA who presented with an encasing mass in the esophagus leading to stricture, with histopathological diagnosis of IgG4-RD.The second patient, diagnosed with primary APS, experienced breathlessness, and imaging revealed a right atrial mass. Histopathological examination of the mass confirmed IgG4-RD. Notably, both patients demonstrated significant clinical improvement upon initiation of steroid therapy. Rheumatoid arthritis patients commonly exhibit elevated levels of IgG4 in their sera; however, RA with coexisting IgG4-RD is rarely reported in the literature. Similarly, APS with IgG4-related lesions is exceedingly rare. Although there are few case reports and series on esophageal and cardiac IgG4-RD, the occurrence of such unusual location of IgG4-related lesions in the context of known autoimmunity is presented here for the first time.

Hereditary angioedema in older adults: Understanding the patient perspective

BackgroundHereditary angioedema (HAE) is a rare condition characterized by potentially fatal, recurrent episodes of painful swelling. Whereas there are limited studies evaluating the quality of life of individuals with HAE, none have evaluated the impact of HAE on older adults. ObjectiveTo evaluate the effect of HAE on older adults through qualitative methodology. MethodsA group of 3 physicians with extensive research and clinical experience in HAE developed a focus group guidebook highlighting issues of importance to older adults. A total of 17 patients with HAE (type I or II) aged 60 years and older participated in focus groups. Three independent reviewers coded each focus group transcript using a thematic saturation approach. ResultsReviewers identified 7 core themes from the focus groups. The themes identified encompassed the following: (1) challenges with securing medications and insurance concerns; (2) the experience of living with HAE before the advent of newer and more effective therapeutic options; (3) a worsening of HAE attack frequency and severity with aging; (4) the effects of comorbid conditions such as arthritis, memory loss, and irritable bowel syndrome; (5) changes in HAE with menopause; and (6) changing perspective on HAE with age, the effect of HAE on interpersonal relationships including the decision to have children, and goals for future care and research including support groups and a desire to be included in clinical trials. ConclusionOlder adults with HAE have specific challenges and concerns that may be unique compared with younger populations. Health care providers should address these to provide optimal care.