Autoinflammatory Research Articles

Patients with Adult-Onset Still’s Disease in Germany: A Retrospective Analysis of Clinical Characteristics and Treatment Practices Ahead of the Release of the German Recommendations

Background/Objectives: Adult-onset Still’s disease (AOSD) is an autoinflammatory disorder that can be challenging to diagnose and manage. The aim of this study was to analyze retrospective data to provide insights into the clinical presentation, disease activity, and treatment patterns and outcomes of AOSD during routine clinical care prior to the release of new AOSD guidelines. Methods: This retrospective database analysis evaluated adult patients (≥18 years) with a diagnosis of AOSD who engaged in a clinical visit between 1 January 2010 and 31 December 2020. The evaluated outcomes included demographic characteristics, symptoms, disease activity, and treatment. Results: Our study included 120 patients (67 [55.8%] of whom were female) diagnosed with AOSD according to the Yamaguchi criteria at ten German rheumatology centers. The median (quartile [Q] 1, Q3) age was 51 (36, 62) years, and the median (Q1, Q3) time from diagnosis was 9 (4, 11) years. Approximately half (66 [55.0%]) had a polycyclic disease course. The most frequent symptoms at initial diagnosis were arthralgia (105 [87.5%]) and fever (86 [71.7%]), and these symptoms continued for a substantial proportion of patients at the current visit (35 [29.2%] and 22 [18.3%], respectively). High neutrophil and ferritin levels were also common. The mean Still Activity Score, a measure of disease activity, improved from 4.66 at initial diagnosis to 1.97 at the most recent visit. The treatments most frequently used at some point in the disease course were glucocorticoids (118 [98.3%]), interleukin (IL)-1 inhibitors (89 [74.2%]), and methotrexate (85 [70.8%]). The most common current treatments were IL-1 inhibitors (55 [45.8%]), followed by methotrexate (29 [24.2%}) and glucocorticoids (28 [23.3%]). Conclusions: Our cohort of patients with AOSD seen at German rheumatology clinics showed strong improvements in symptoms and disease activity from initial diagnosis, but a high symptom burden remained for some patients. Future studies may be able to build on our data to document the impact of new guidelines on treatment patterns.

Corticosteroids combined with low-dose methotrexate in the treatment of pemphigus vulgaris: A retrospective cohort study.

The treatment of pemphigus vulgaris (PV) often requires long-term systemic corticosteroids. Although new biologicals like rituximab are changing the landscape, traditional immunosuppressants still prevail in many underdeveloped areas. One such medication is methotrexate (MTX), which has been widely used in autoimmune and autoinflammatory diseases, but its role in treating pemphigus remains somewhat unclear and controversial. This study aimed to evaluate the effect and safety profile of using low-dose MTX in PV patients receiving glucocorticoids. PV patients who visited the Department of Dermatology, Peking University First Hospital from January 2010 to December 2021 were retrospectively screened. Based on different treatment regimens, patients were automatically divided into a corticosteroid monotherapy group and a corticosteroid combined with low-dose MTX group (MTX was administered at a dose of no more than15 mg per week, with a minimum duration of 8 weeks). All patients were followed up for 1 year. A total of 142 patients with PV were eligible for the study (100 in the corticosteroid monotherapy group and 42 in the corticosteroid combined with low-dose MTX group). The Kaplan-Meier curve indicated that the corticosteroid combined with low-dose MTX group achieved a 50% reduction in glucocorticoid use faster, with a P value of 0.0132, especially among patients who initially received more than 60 mg of steroids per day. The inclusion of MTX reduced the occurrence of hyperpilidemia. There was not sufficient evidence to determine if the addition of MTX was associated with more bacterial infection cases for certain. The inclusion of low-dose MTX in the corticosteroid treatment regimen for patients with PV, particularly those receiving high doses, can facilitate the reduction of glucocorticoid dosages and lower the incidence of hyperlipidemia, without increasing the risk of other adverse effects.

Investigation of Microvascular Involvement Through Nailfold Capillaroscopic Examination in Children with Familial Mediterranean Fever

Background and Objectives: Familial Mediterranean fever (FMF) is a lifelong autoinflammatory disease characterized by episodes of fever and aseptic polyserositis. Commonly associated with vasculitis, FMF’s impact on microcirculation was investigated by examining nailfold capillaries using capillaroscopy. Materials and Methods: This study included 32 female and 28 male FMF patients diagnosed according to the Tel Hashomer and Yalçınkaya criteria and a control group of 20 female and 10 male age-matched cases. Demographic characteristics, medical history (abdominal pain, fever, chest pain, and joint pain), and physical examination findings of the cases were assessed. FMF gene mutations, acute-phase reactants, urine analysis, and spot urine protein/creatinine ratios were evaluated. Nailfold capillaries were examined via capillaroscopy by the same dermatology specialist. Results: There was no significant age or gender difference between groups. The most common symptoms in the case group were abdominal pain (81.7%) and joint pain (65%). Pathological findings in capillaroscopy, such as microhemorrhages and avascular areas, were significantly more frequent in the FMF case group (p < 0.001; p < 0.001). Physiological findings, including hairpin-shaped capillaries and shortened loops, were significantly more common in the control group (p = 0.001; p = 0.034). No significant relationships were found between kidney involvement, subclinical inflammation, presence of microhemorrhages and avascular areas in capillaroscopy, and disease duration. Additionally, no significant differences were observed in capillaroscopic findings between those with exon-10 mutations in the MEFV gene and those with non-exon-10 mutations. Conclusions: In conclusion, our study demonstrated secondary microvascular findings due to inflammation in FMF patients using capillaroscopy, a cost-effective and safe tool.

Macrophage metabolic reprogramming: A trigger for cardiac damage in autoimmune diseases.

Macrophage metabolic reprogramming has a central role in the progression of autoimmune and auto-inflammatory diseases. The heart is a major target organ in many autoimmune conditions and can sustain functional and structural impairments, potentially leading to irreversible cardiac damage. There is mounting clinical evidence pointing to a link between autoimmune disease and cardiac damage. However, this association remains poorly understood, and numerous patients do not receive appropriate preventive measures, which poses serious cardiovascular risks and significantly impacts their quality of life. This review discusses the relationship between macrophage metabolic reprogramming and cardiac damage in patients with autoimmune diseases and the role of adaptive immunity in macrophage reprogramming. It also provides an overview of the immunosuppressive therapies used at present. Exploiting the properties of macrophage reprogramming could lead to development of novel treatments for patients with autoimmune-related cardiac damage.

Comparative study of radio-clinical parameters in pediatric forms of fibrous dysplasia and chronic recurrent multifocal osteomyelitis.

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory disease with clinical and radiological symptoms that overlap with fibrous dysplasia (FD), particularly in children. This study aimed to compare the clinical and radiological features of craniofacial CRMO and FD in a pediatric population. Seven children with CRMO and 14 with FD were retrospectively identified in our tertiary centre between 2012 and 2022. Their clinical, radiological, and biological (when available) data were collected. Two experienced radiologists reviewed imaging modalities following a standardized form, including characteristics of the lesions, soft-tissue involvement, and signal abnormalities (MRI). Swelling and pain were common symptoms in the CRMO group (7/7 and 5/5, respectively), compared with 11/14 and 2/14 patients in the FD group. Imaging (CT scan) comparisons revealed a predominance of erosive lesions, cortical interruption, periosteal apposition, and soft-tissue involvement in CRMO compared with FD (4/5 vs 0/6, p1=0.01; 5/5 vs 1/6, p2=0.01; 5/5 vs 0/6, p3=0.002; and 4/5 vs 0/6, p4=0.02, respectively). Hyperosteosis was mainly associated with FD lesions (6/6 vs 2/5, p=0.06). Knowledge of the clinical and radiographic differences between CRMO and FD could help clinicians to differentiate between the two diseases.

Chromosome aberrations and autoimmunity: Immune-mediated diseases associated with 18p deletion and other chromosomal aberrations.

Recent advances in genomic methodologies have significantly enhanced our understanding of immune-mediated rheumatic diseases. Specific structural variants (SVs), such as substantial DNA deletions or insertions, including chromosomal aberrations, have been implicated in diseases of immune dysregulation. Regrettably, SVs are frequently overlooked in next-generation sequencing (NGS) targeted-gene panels, whole exome sequencing (WES) and whole genome sequencing (WGS). In view of a case of chromosome 18p deletion syndrome, characterized by hypogammaglobulinemia and an autoinflammatory phenotype, we provide a comprehensive review on chromosome aberrations associated with multiple immune-mediated conditions, highlighting the clinical aspects of the various chromosome aberrations associated with immune-mediated diseases. Further investigations and development of functional tests should contribute to elucidate the mechanistic connection between chromosome aberrations and Primary Immune Regulatory Disorders (PIRD), bringing novel perspectives in the field of autoinflammatory and autoimmune diseases.

Carboxyaminotriazole: A bone savior in collagen-induced arthritis-Halting osteoclastogenesis via interleukin-1β downregulation.

Rheumatoid arthritis (RA), a prevalent autoimmune disease, features inflammation and bone erosion, correlating with osteoclast hyperactivation and enhanced responsiveness to inflammatory factors. Reducing osteoclast formation and inflammatory mediator expression might avert bone erosion in RA. Carboxyaminotriazole (CAI) holds potential for treating autoinflammatory disorders and impeding cancer-related bone metastases. Yet, its bone-protective role and mechanism remain elusive. This study targets to explore the impacts and underlying mechanisms of CAI in preventing bone erosion in RA. A collagen-induced arthritis (CIA) rat model was utilized to evaluate the anti-RA potential of CAI. CCK-8, TRAP staining, TRAP activity assay, pit formation assay, RT-qPCR, Western blotting, immunofluorescence, and ELISA, were conducted to assess the effects and potential mechanisms of CAI in the management of RA. CAI not only reduces inflammatory symptoms, but it also offers superior bone protection compared to methotrexate (MTX) and works synergistically with MTX, the preferred anchoring agent for the treatment of RA. In vitro studies show that CAI inhibits osteoclast differentiation and function, as well as the expression of specific genes, by inhibiting NF-κB/MAPK pathways and reducing IL-1β levels. The deletion of Il-1 and the application of IL-1β inhibitors suggest that CAI retards osteoclastogenesis through the downregulation of IL-1β. CAI may have therapeutic value in treating RA-related bone erosion, likely due to its inhibition of overactive osteoclasts by suppressing the NF-κB/MAPK pathways and the subsequent expression of IL-1β.

The effect of tonsillectomy on clinical manifestations in Familial Mediterranean fever.

Familial Mediterranean fever (FMF) is the most prevalent genetic autoinflammatory disease worldwide. There are several novel advancements in pathophysiology, genetic testing, diagnosis, comorbidities, disease-related damage, and treatment strategies. This study aimed to assess the effect of tonsillectomy on FMF disease severity and activity. This prospective randomized cohort study was conducted on 43 patients diagnosed with FMF and chronic tonsillitis, who were divided randomly into two groups: Group I, a case group including 23 patients subjected to tonsillectomy and medical treatment using colchicine; Group II, a control group consisting of 20 cases receiving only colchicine. The monthly frequency of the attacks and average duration of the three symptoms, such as fever, abdominal/chest pain, and musculoskeletal pain in days, were evaluated and recorded. A highly significant reduction in the monthly frequency of attacks, duration of fever, abdominal/chest pain, and musculoskeletal pain was observed three months after management in both study groups (p<0.00001 for all). Evaluation of the values of both groups revealed a significant increase in the degree of change for the duration of fever, abdominal/chest pain in Group I relative to Group II (p=0.0003 and 0.006 respectively) and a significant increase in the degree of change for musculoskeletal pain in Group II relative to Group I (p=0.007). Survival analysis showed a nonsignificant difference between the two groups regarding the resolution of fever, abdominal/chest pain, and musculoskeletal pain at 12, 18, and 24 months (p=0.26, 0.08, and 0.42, respectively) CONCLUSION: Tonsillectomy operation combined with colchicine resulted in a greater but nonsignificant decrease in the monthly frequency of the FMF attacks and a significant greater decrease in the duration of fever and abdominal/chest pain compared with the use of colchicine alone. Further research is recommended to confirm these results on a larger scale.

Can Peritoneal Biopsy Diagnose Atypical Cases of Familial Mediterranean Fever?: A Case Report.

Familial Mediterranean Fever (FMF) is a prevalent inherited monogenic autoinflammatory disease that predominantly affects populations from the Mediterranean basin. It is typically characterized by the recurrence of fever episodes and abdominal pain accompanied by recurrent short-lived inflammatory attacks that usually resolve spontaneously within 1-3 days. It is uncommon to see ascites with large amounts of peritoneal fluid as a manifestation of FMF. A 36-year-old Arab female presented with generalized abdominal pain and bloating. No family history of FMF. Analysis of peritoneal fluid identified low-grade ascites. A CT scan was performed, which did not reveal any suspicious lesions. Laparoscopic surgery was undertaken to rule out the differential diagnoses and obtain a peritoneal biopsy, even though the periton had a normal visual appearance. Histopathological examination of the biopsy specimens was compatible with a diagnosis of FMF, after other differential diagnoses were ruled out. The patient showed significant improvement within a month of taking colchicine. The ascites resolved progressively and completely, affirming the FMF diagnosis. The occurrence of chronic ascites in a patient requires the consideration of FMF among the differential diagnoses. A diagnosis of FMF can also be suspected through a peritoneal biopsy, which may be sufficient for diagnosis without the need for genetic testing. Additionally, the patient's response to colchicine therapy can be considered for confirmation, as demonstrated in our case. Future research should focus on considering the inclusion of peritoneal biopsy among the diagnostic criteria for FMF particularly in cases with non-specific presentations.

Next generation sequencing for autoinflammatory diseases: diagnostic insights from an eight-gene panel

Next generation sequencing for autoinflammatory diseases: diagnostic insights from an eight-gene panel

Clinical implications of human Parvovirus B19 infection on autoimmunity and autoimmune diseases.

Parvovirus B19 (B19V) is a human pathogen from the Parvoviridae family that primarily targets and replicates in erythroid progenitor cells (EPCs). While its symptoms are typically self-limiting in healthy individuals, B19V can cause or exacerbate autoimmune diseases in vulnerable patients. This review integrates the involvement of B19V in the development and worsening of several autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), hematological disorders (thalassemia, anemia, and thrombocytopenia), vasculitis, antiphospholipid syndrome (APS), dermatological disease (systemic sclerosis, psoriasis), autoimmune thyroid disease, myocarditis, and myasthenia gravis, and autoinflammatory disease of adult-onset Still's disease (AOSD). B19V contributes to autoimmunity and autoimmune disease onset and progression through mechanisms such as molecular mimicry, immune system disruption, and chronic infection. By summarizing findings from in vitro experiments, clinical case studies, seroprevalence data, and biopsy results, this review highlights the critical connection between B19V and autoimmune disease development. Recognizing the role of B19V in the early diagnosis and management of these conditions is essential, as its presence may influence the disease course and severity. Greater awareness among healthcare professionals and the public is necessary to address the impact of B19V, leading to more accurate diagnoses and better-informed treatment approaches for autoimmune diseases linked to the virus.

Long-Term Safety and Effectiveness of Canakinumab in Patients with MKD/HIDS: Interim Analysis of the RELIANCE Registry.

Interim analysis of the long-term safety and effectiveness of canakinumab, at a patient level, in the mevalonate kinase deficiency/hyperimmunoglobulin-D syndrome (MKD/HIDS) cohort of the RELIANCE registry. From June 2018, the RELIANCE registry enrolled paediatric (aged ≥ 2years) and adult patients (aged ≥ 18years) with MKD/HIDS who were receiving canakinumab as part of their routine medical care. Safety, physician- and patient-reported measures of disease activity and dosing patterns were evaluated at baseline and every 6months until end-of-study visit. At the analysis cut-off date of December 2022, eight patients with MKD/HIDS were enrolled. Five (62.5%) were children (< 18years) and five (62.5%) were female. The median patient age was 8.0 (range 2.0-39.0)years, and all patients were pre-treated with canakinumab prior to enrolment (median duration of canakinumab treatment: 3.8years). Canakinumab was well tolerated, with seven (87.5%) patients reporting 48 adverse events (incidence rate/100 patient years: 218.1). No serious adverse drug reactions were reported. Patients continued to receive vaccinations during long-term treatment with canakinumab. Disease activity, evaluated by physician-reported (physician's global assessment, disease remission, C-reactive protein, serum amyloid A, erythrocyte sedimentation rate) and patient-reported (autoinflammatory disease activity index diary, disease activity, fatigue, impact on social life) measures, was generally well controlled throughout the study. Over 50.0% of patients maintained disease remission from baseline to month 24, and medians of all inflammatory markers remained within normal limits throughout the study. Most patients received higher than the recommended starting dose of canakinumab throughout the study. Data from this interim analysis of a unique registry of patients with a rare disease support the long-term safety and effectiveness of the IL-1-blocking agent canakinumab for the treatment of MKD/HIDS.

Nucleic acid triggers of autoimmunity and autoinflammation.

The key role of nucleic acid sensing receptors in the development of autoimmune and autoinflammatory diseases is becoming increasingly apparent. Activation of these sensors has been attributed to the failure of professional scavenger cells to adequately clear cell debris, in many cases due to defective scavenger receptors. However, as now summarized in this review, numerous gain-of-function mutations in the nucleic acid sensing receptors, or in molecules that regulate sensor activity, have now been evaluated in gene-targeted murine strains, and critical components of their downstream pathways have been identified as therapeutic targets. In addition, we are beginning to understand how DNases and RNases play crucial roles in both generating and eliminating the distinct ligands that engage the various nucleic acid sensors. Murine models of disease have further provided important insights regarding the function of and synergy between individual endosomal and cytosolic receptors, as well as cell type restricted functions.

P-994. Cellular and humoral immunological profile of Human T-Lymphotropic Virus type I (HTLV-1) in a pediatric case series

Abstract Background Human T- lymphotropic Virus type 1 (HTLV-1) is a powerful oncovirus. In South America there is a high incidence of cases in countries such as Brazil, Peru and Colombia, mainly affecting the indigenous and Afro-descendant population. In children, the main clinical findings are dermatological manifestations followed by lung disease, opportunistic coinfections, and autoinflammatory disorders. The main target of HTLV-1 is CD4+ T lymphocytes, which are the regulators of the acquired immune response, but It’s also capable of infecting CD8+ T lymphocytes, B cells, dendritic cells and synovial cells. The purpose of this study is to describe the humoral and cellular immunological profile in pediatric patients diagnosed with HTLV-1 in a reference center in Cali, Colombia.Table 1.Characterization of cellular immunity in pediatric patients diagnosed with HTLV1 (n = 6)BL: B lymphocyte, TL: T lymphocyte Source: Self elaboration Methods This is an observational, descriptive, retrospective cross-sectional study carried out between January 2017 and March 2021.Table 2.Characterization of humoral immunity in pediatric patients diagnosed with HTLV1 (n = 16) Results Nineteen patients were included in this study with a median age at diagnosis of 94 months, most of them were schoolchildren (52.6%), 50% of patients had elevated B lymphocytes (CD19), and 50% of them had normal range cytotoxic T lymphocytes (CD8+) and helper T lymphocytes (CD4) (Table 1 and graph 1). None of the patients had decreases in serum immunoglobulins (IgM, IgG, IgE and IgA) (Table 2 and graph 2)Graph 1.Cellular immunological profile (n=6) Conclusion HTLV-1 immunosuppression is not mediated by low levels of lymphocyte subpopulations in the pediatric population.Graph 2.Humoral immunological profile (n=16) Disclosures All Authors: No reported disclosures

Emerging Immunotherapies for Disease Modification of Type 1 Diabetes.

Type 1 diabetes mellitus (T1DM) is characterized by the progressive, autoimmune-mediated destruction of β cells. As such, restoring immunoregulation early in the disease course is sought to retain endogenous insulin production. Nevertheless, in the more than 100 years since the discovery of insulin, treatment of T1DM has focused primarily on hormone replacement and glucose monitoring. That said, immunotherapies are widely used to interdict autoimmune and autoinflammatory diseases and are emerging as potential therapeutics seeking the preservation of β-cell function among those with T1DM. In the past 4 decades of diabetes research, several immunomodulatory therapies have been explored, culminating with the US Food and Drug Administration approval of teplizumab to delay stage 3 (clinical) onset of T1DM. Clinical trials seeking to prevent or reverse T1DM by repurposing immunotherapies approved for other autoimmune conditions and by exploring new therapeutics are ongoing. Collectively, these efforts have the potential to transform the future of diabetes care. We encapsulate the past 40 years of immunotherapy trials, take stock of our successes and failures, and chart paths forward in this new age of clinically available immune therapies for T1DM.

Case report: Therapeutic use of bortezomib in a patient with Schnitzler syndrome

Schnitzler syndrome (SchS) is a rare acquired systemic autoinflammatory disorder, characterized by chronic urticarial rash and immunoglobulin M (IgM) monoclonal gammopathy. Anti-interleukin-1 (IL-1) therapies have been shown to be more effective in managing the clinical symptoms of SchS compared to anti-IL-6 therapies. In this case report, we present a male patient with urticarial rash, fever, and arthralgia. Laboratory tests identified the presence of IgMκ monoclonal protein, and the absence of IL-1β in serum. Whole exome sequencing (WES) did not reveal any pathological variants associated with monogenic autoinflammatory diseases or the MYD88 L265P mutation. He met the diagnostic criteria for SchS and was treated with bortezomib, leading to a significant improvement in clinical symptoms and a decline in IgMκ monoclonal protein levels. The patient tolerated the treatment well. This case suggests that bortezomib may be considered as a potential treatment option for SchS, in addition to anti-IL-1 therapies and bruton tyrosine kinase (BTK) inhibitors.

P-27 H SYNDROME: CASE REPORT

Abstract Introduction H Syndrome is an autosomal recessive disorder characterized by cutaneous hyperpigmentation, hypertrichosis, and induration with numerous systemic manifestations. The syndrome is caused by mutations in SLC29A3, a gene located on chromosome 10q23, which encodes the human equilibrative transporter 3 (hENT3). H syndrome is a rare autoinflammatory syndrome with pleiotropic manifestations that affect multiple organ systems. We are presenting first possible case of H syndrome reported in Iraq up to our knowledge. Clinical Case A 14 year old Iraqi boy presented with abnormal lower limb hyperpigmentation, and symmetrical, indurated plaques with marked hypertrichosis over medial aspect of thighs and legs. The skin hyperpigmentation was not itchy and did not involve the feet and knees. This hyperpigmentation had been present for several months. The patient was known to have type 1 diabetes mellitus (DM) since 5 years of age and was treated with insulin with fair control, although without features of advanced microvascular diabetic complications. The patient had deafness and he was wearing a hearing aid device recently. Laboratory analysis showed normal kidney and liver function and normal blood counts but with subclinical hypothyroidism and surprisingly positive serology for celiac disease and this feature was not reported in the few documented cases in the literature. Conclusion This rare syndrome of skin hyperpigmentation, diabetes and deafness may represent the first reported case of H syndrome in Iraq and occurrence of celiac disease is another manifestation that could be part of this syndrome.Figure 1:Hyperpigmentation

An Autoethnographic Account of Familial Mediterranean Fever: A Turkish Patient's Discovery of Spiritual Meaning.

Familial Mediterranean Fever (FMF) is a genetic autoinflammatory disorder characterized by recurrent febrile episodes that are accompanied by pain in the abdomen, chest, or joints caused by peritonitis, pleuritis, skin lesions, arthritis, and pericarditis. This original article aims to provide an analytic autoethnographic account of a Turkish patient's experience of FMF, with a focus on the discovery of spiritual meaning. In addition to discussing the grief reactions to a loss of health, the article uses self-reflexive discourse and narrative-based analysis to explore four stages of discovery of spiritual meaning through FMF: "omnipotent me," "God's punishment," "God's test," and "God's mercy." The article provides an in-depth look at the experience of FMF, a chronic and lifelong disease, through a spiritual lens and offers suggestions for mental health professionals and rheumatologists providing holistic treatment to FMF patients that might improve treatment adherence.

Healthcare Resource Utilization Among Patients With Generalized Pustular Psoriasis: The Impact of Flares and Disease Severity.

Generalized pustular psoriasis (GPP) is a rare, chronic, often unpredictable, severe multisystemic autoinflammatory skin disease from which patients can experience flares, episodes of widespread eruptions of painful, sterile pustules often accompanied by systemic symptoms. The impact of GPP flares and underlying GPP severity on the healthcare resource utilization (HCRU) is not well characterized. To quantify HCRU among US GPP patients by flare status and underlying severity. Outpatient electronic health record (EHR) data (2017-2023) from the OMNY Health platform were linked with claims. Patients were indexed at first EHR GPP diagnosis code and followed for 1 year. GPP flares were identified from a previously developed algorithm. All-cause hospitalizations, emergency department/urgent care (ED/UC), and outpatient visits were summarized by flare status and underlying severity. Pharmacy and total gross charges were described by number of flares. A total of 335 patients were included. Patients who flared in the follow-up period (n = 205) had more hospitalizations than patients who did not flare (n = 130; 12.2% vs 6.9%; mean: 0.26 vs 0.09). ED/UC visits were similar between groups (22.9% vs 27.7%; mean: 0.54 vs 0.45), while outpatient visits were greater among patients who did not flare (69.8% vs 78.5%; mean: 5.37 vs 6.56). For patients with 0, 1, and ≥2 flares with HCRU, mean pharmacy charges ($19,887, $25,180, and $57,674, respectively) and total gross charges ($29,196, $40,079, and $52,940, respectively) increased monotonically. GPP patients who flared and had more severe disease had greater HCRU and charges.

Clinical and Imaging Characteristics of Posterior Scleritis in Children

ABSTRACT Background Posterior scleritis (PS) is a rare phenotype of scleritis. Comprehensive epidemiological studies on PS in children are limited. We aimed to report on its clinical and imaging features in one of the largest pediatric series to date. Methods Retrospective review of medical files. Results Included were 12 children (7 girls, mean±SD age at diagnosis 13.75 ± 3.3 years,18 eyes, mean follow-up ±SD of 46.7 ± 45.9 months). All patients presented with eye pain followed by headache. Papillitis was the most common presenting sign (16 eyes, 88.9%). Seven patients (58%) showed laboratory markers of systemic inflammation. One patient had periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA). In 2 other patients, Behҫet disease and inflammatory bowel disease were diagnosed subsequently. Initial echography showed increased posterior scleral thickness (mean±SD 2.9 ± 0.68 mm) with a significant reduction four ± 2 months later (mean±SD 1.85 ± 0.62 mm). Retinal nerve fiber layer (RNFL) was thickened in all examined eyes (mean±SD 136.2 ± 28.4 µm) at presentation and it significantly decreased with treatment (109.8 ± 8.2 µm two months later). In 5 patients (42%), diagnosing PS was prompted by Brain imaging. PS was part of orbital inflammatory syndrome in 4 patients (33.3%). All patients were treated with systemic steroids and 91% required steroid-sparing agent. Adalimumab was added in 2 patients. A chronic course was observed in 63.6%. Remission was achieved in 4 patients. Mean±SD presenting LogMAR VA was 0.23 ± 0.3 with marked improvement to 0.04 ± 0.07 one month later. Conclusion Searching for an associated autoinflammatory/autoimmune disease is an important step in patients’ triaging. B-scan ultrasound remains the gold standard test. OCT proved to be of practical importance in delineating the magnitude of RNFL thickness and could serve as a potential imaging biomarker of disease activity.