Clinical laboratory assessment and predictability of the periodontal inflammation development in children with undifferentiated connective tissue disease

Relevance. The development of multiple organ lesions in undifferentiated connective tissue disease leads to secondary immunodeficiency, which triggers oral homeostasis disruption and activates periodontal pathogens, which produce anti-inflammatory cytokines, which trigger the mechanisms of periodontal destruction. Purpose – to establish the relationship between undifferentiated connective tissue disease in children and their predisposition to periodontal inflammation and destruction.Materials and methods. The study examined the patients, aged 15 to 17 years old, of the endocrinological department of the Children's Clinical Hospital of N. N. Burdenko Voronezh State Medical University. All examined children had the same diagnosis of undifferentiated connective tissue disease. The control group consisted of 15 children with healthy periodontium. Silness-Loe plaque index (Loe H., Silness J., 1962) at the gingival margin assessed the children periodontal status. Mühlemann bleeding index (Mühlemann H.R., Son S., 1971) [19] evaluated the bleeding. The study measured the intensity and extension of the inflammatory reaction by the cytological changes in the periodontium according to the Page and Schroeder model (Page R.C. and Schroeder M. E., 1976). The enzyme immunoassay kits from eBioscince determined the level of pro-inflammatory cytokines: interleukin (IL-1β), interferon-gamma (IFN-γ) and transforming growth factor (TGF-β1) in the oral fluid; and the anti-inflammatory cytokine, receptor antagonist interleukin IL-1 (IL-1ra), was measured using Invitrogen kit in strict accordance with Multiskan FC microplate photometer instructions (Thermo Scientific).Results. Children periodontal status evaluation did not reveal any pronounced clinical manifestations of the inflammation that could cause concern and complaints of bleeding gums. Thus, the Silness-Loe plaque index at the gingival margin was 1.70 ± 0.07 (control group 1.10 ± 0.03), the Mühlemann gingival sulcus bleeding index in children with undifferentiated connective tissue disease was 2.10 ± 0.05 (control group 0). The results of the oral fluid cytokine count in patients with undifferentiated connective tissue disease demonstrated a tendency for pro-inflammatory cytokine increase and anti-inflammatory cytokine decrease, in contrast to the control group.Conclusions. Thus, the qualitative composition of pro-inflammatory cytokines – interleukin (IL-1β), interferongamma (IFN-γ) and transforming growth factor (TGF-β1), interleukin IL-1 receptor antagonist (IL-1ra) in the oral fluid, in combination with clinical diagnostic methods in periodontal practice, can reliably predict the predisposition of people with undifferentiated connective tissue disease to periodontal inflammation and destruction. Medical checkup in children with undifferentiated connective tissue disease mainly aims to carry out comprehensive treatment and preventive measures to preserve the functions of the dental system. As children periodontal service is not allocated in the register of medical specialties in the Russian Federation, pediatric periodontal patients are followed-up in the periodontally healthy groups. However, it is evident today that periodontal passports are necessary, which indicate a genetic predisposition to inflammatory periodontal diseases.

Is axillary botulinum toxin efficient in controlling secondary Raynaud’s phenomenon? A case report

Raynaud’s phenomenon when secondary to underlying systemic disease such as systemic sclerosis occurs early in the disease course and progression can bring significant morbidity such as pain, digital ulceration, and necrosis. Standard medical therapies are aimed at promoting distal arterial vasodilation but are often inadequate in managing Raynaud’s phenomenon. Options for refractory cases include surgical and chemical sympathectomy with Botulinum neurotoxin type A (BoNT/A) hand injections but the latter can be associated with transient hand weakness. We describe the case of a 35-year-old woman with undifferentiated connective tissue disease, Raynaud’s phenomenon, and concomitant primary focal axillary hyperhidrosis for which she received axillary BoNT/A therapy every 6 months who noted significant improvement in her Raynaud’s phenomenon and hand arthralgias for 5 months following the axillary injections. This effect remained durable after 24 months of therapy. This improvement in Raynaud’s phenomenon after axillary BoNT/A has not been previously described.

CLINICAL SIGNIFICANCE OF LAMININ AND ELASTINE LEVELS IN CHILDREN WITH UNDIFFERENTIATED CONNECTIVE TISSUE DISEASE

This research aims to study levels of laminin and elastine in 64 children with undifferentiated connective tissue disease (UCTD). All the children underwent clinical, laboratory and instrumental examination. It was found that changes in the levels of laminin and elastin are directly related to the severity of UCTD in children. Thus, clinical values of laminin and elastin levels can serve as additional criteria of UCTD severity. Using them, along with early detection of the phenotypic and visceral signs, helps prevent the development of severe forms of the disease.

POS0715 QUANTIFYING THE PSYCHOSOCIAL IMPACT OF UNDIFFERENTIATED CONNECTIVE TISSUE DISEASE (UCTD)

Background:Only half of patients diagnosed with SLE fulfill classification criteria; the rest have “SLE-like” illnesses such as UCTD. SLE patients are known to experience impaired health-related quality of life (HRQoL) and significant anxiety, depression, and fatigue,1 yet the psychosocial aspects of UCTD are less established. In a qualitative study, we found that most UCTD patients had engaged in psychotherapy and felt additional support was needed.2Objectives:Using multiple validated instruments, this study aims to quantify the psychosocial impact of UCTD.Methods:The Hospital for Special Surgery UCTD and Overlap Registry includes UCTD patients aged ≥ 18 years with ANA ≥ 1:80 and ≥ 1 sign or symptom of rheumatic disease who do not fulfill classification criteria for a defined CTD. We administered the 36-Item Short Form Health Survey (SF-36), General Anxiety Disorder-7 (GAD-7), Beck Depression Inventory (BDI), and Fatigue Severity Scale (FSS) to all patients to assess HRQoL, anxiety, depression, and fatigue. Instruments were scored based on established algorithms and results were summarized using predefined scales and severity thresholds.Results:The composite questionnaire was administered to 85 UCTD patients and completed by 75 (97.3% female, 60% white, mean age ± SD 48.8 ± 13.6 years). The SF-36 Physical Component Summary mean score was 37.8 and Mental Component Summary mean score was 41.1. Across the 8 SF-36 subscales, mean scores were lowest for role limitations due to physical health (39.3) and vitality (39.7) and highest for physical functioning (67.2), role limitations due to emotional health (67.1), and mental health (67.1). Approximately half of UCTD patients reported anxiety (GAD-7 ≥ 6); 20% had moderate/severe anxiety (GAD-7 ≥ 10). The prevalence of depression (BDI ≥ 14) was 26.7%; 13.3% had moderate/severe depression (BDI ≥ 20). Fatigue (FSS ≥ 3) was reported by 82.8% of patients (median FSS score of 4.7) [Table 1].Table 1.Psychosocial Survey Scores of Patients with Undifferentiated Connective Tissue Disease (n=75)36-Item Short Form Health Survey (SF-36)Range 1-100 – Mean (SD)*Physical Component Summary∘Physical functioning∘Role-Physical∘Bodily PainoGeneral Health38.2 (11.2)67.2 (26.3)39.3 (46.3)49.5 (22.1)42.9 (21.5)Mental Component Summary∘Vitality∘Social Functioning∘Role-EmotionaloMental Health41.3 (10.7)39.7 (21.7)59.3 (25.9)67.1 (41.9)67.1 (18.3)Generalized Anxiety Disorder-7 (GAD-7)Range 0-21 – N (%)**None [0-5]Mild [6-10]Moderate [11-15]Severe [16-21]38 (50.7)22 (29.3)14 (18.7)1 (1.3)Beck Depression Inventory (BDI)Range 0-63 – N (%)**Minimal [0-13]Mild [14-19]Moderate [20-28]Severe [29-63]55 (73.3)10 (13.3)7 (9.3)3 (4.0)Fatigue Severity Scale (FSS) Range 1-7 – Median (IQR)**4.7 (1.5)*Higher number indicates better health state. **Higher number indicates greater severity.Conclusion:UCTD patients have significantly impaired HRQoL and a high prevalence of anxiety, depression, and fatigue, suggesting substantial psychosocial impact of UCTD comparable to that reported in SLE.3,4 Impaired HRQoL in UCTD is driven to similar degrees by aspects of physical and mental health. In future studies, we will compare age- and sex- matched UCTD to SLE patients and longitudinally evaluate psychosocial metrics alongside clinical trajectories.References:[1]Dietz B, Katz P, Dall’Era M, et al. Major depression and adverse patient-reported outcomes in systemic lupus erythematosus: Results from a prospective longitudinal cohort. Arthritis Care Res. 2021;73(1):48-54.[2]Siegel CH, Kleinman J, Barbhaiya M, et al. The psychosocial impact of undifferentiated connective tissue disease on patient health and well-being: A qualitative study. J Clin Rheumatol. In press.[3]Gu M, Cheng Q, Wang X, et al. The impact of SLE on health-related quality of life assessed with SF-36: A systemic review and meta-analysis. Lupus. 2019;28(3):371-382.[4]Zhang L, Fu T, Yin R, Zhang Q, Shen B. Prevalence of depression and anxiety in systemic lupus erythematosus: A systematic review and meta-analysis. BMC Psychiatry. 2017;17(1).Acknowledgements:This project was supported by the Barbara Volcker Center for Women and Rheumatic Diseases and the Robin J. Sillau Memorial Research Fund for Connective Tissue Disease. Dr. Barbhaiya is supported by the Rheumatology Research Foundation Investigator Award.Disclosure of Interests:None declared

Kingella kingae Intrauterine Infection: An Unusual Cause of Chorioamnionitis and Miscarriage in a Patient with Undifferentiated Connective Tissue Disease

Kingella kingae is a Gram-negative coccobacillus belonging to the Neisseriaceae family. In children less than 4 years old, K. kingae invasive infection can induce septic arthritis and osteomyelitis, and more rarely endocarditis, meningitis, ocular infections, and pneumonia. In adults, it may be a cause of endocarditis. To date, K. kingae acute chorioamnionitis (AC) leading to preterm rupture of membranes (PPROM) and miscarriage has never been reported. Herein, we describe a case of intrauterine fetal death (IUFD) at 22 weeks’ gestation due to K. kingae infection occurred in a patient affected by undifferentiated connective tissue disease (UCTD) in lupus erythematosus systemic (LES) evolution with severe neutropenia. K. kingae was isolated in placental subamnionic swab and tissue cultures as well as fetal ear, nose, and pharyngeal swabs. Placental histological examination showed necrotizing AC and funisitis. In the fetus, neutrophils were observed within the alveoli and in the gastrointestinal lumen. Maternal medical treatment for UCTD was modified according to the K. kingae invasive infection. In the event of IUFD due to AC, microbiological cultures on placenta and fetal tissues should always be carried out in order to isolate the etiologic agent and target the correct medical treatment.