Rheumatologic Disorders Research Articles

IMPACT OF DEPRESSION IN LOWERING THE QUALITY OF LIFE AMONG PATIENTS WITH RHEUMATIC MUSCULOSKELETAL DISORDERS ATTENDING A TERTIARY HOSPITAL IN NORTHERN NIGERIA

Background: Rheumatic musculoskeletal disorder is a group of inflammatory disorders affecting one or more joints of the body causing pain, swelling, stiffness, and loss of joint functions. They constitute the second most common cause of disability worldwide when measured by years lived with disability (YLDs). Rheumatologic disorders may precipitate psychological distress, including depressive disorders. Depression is presently the fourth leading cause of the global burden of disease. The comorbidity of these disorders may negatively impact the quality of life. Most studies on depression among rheumatoid patients have focused on determinants rather than the role of depressive disorder in lowering quality of life. This study determined the impact of depression in lowering the quality of life of rheumatoid disease patients. Methods: A cross-sectional descriptive study of randomly selected 151 participants, using a systematic random sampling method was used. The Socio-demographic and clinical questionnaire, MINI, and WHO Quality of Life were administered to them. Result: The majority of the participants were females (56.3%), and more than half were above 40 years (59.7%). About two-thirds had poor quality of life with a score of less than mean±1SD. The prevalence rate of depressive disorder was 14.6%. Poor quality of life was significantly associated with gender (t= 2.111, p=0.038), marital status (t= 3.228, p= 0.002), level of education (t= -3.551, p= 0.001), and living alone (t= 2.025, p= 0.045). Depression was found to be an independent contributor to poor quality of life. Conclusion: Depression is common among rheumatoid patients. There is a need to screen for and treat depression among these patients to improve their quality of life.

Incidental findings involving the temporomandibular joint on computed tomography and magnetic resonance imaging.

The temporomandibular joint (TMJ) is frequently imaged in head and neck computed tomography (CT) and magnetic resonance imaging (MRI) studies. Depending on the indication for the study, an abnormality of the TMJ may be an incidental finding. These findings encompass both intra- and extra-articular disorders. They may also be related to local, regional or systemic conditions. Familiarity with these findings along with pertinent clinical information helps narrow the list of differential diagnoses. While definitive diagnosis may not be immediately apparent, a systematic approach contributes to improved discussions between clinicians and radiologists and better patient management.

Acute limb ischemia in an adolescent with COVID-19 and systemic scleroderma: a case report

BackgroundJuvenile Scleroderma is a rare autoimmune disease of the connective tissue. Its concurrence with COVID-19 can lead to limb ischemia as both disease entities are pro-inflammatory and pro-thrombotic. To date, there is no case report describing the symptomatology and course of disease in patients with juvenile Scleroderma and COVID-19.Case presentationAn adolescent with acute limb ischemia presented with a history of generalized hypo-and-hyperpigmented skin lesions and mild, non-productive cough. She tested positive for SARS-CoV-2 on nasopharyngeal swab RT-PCR. Further work-up revealed elevated anti-phospholipid antibodies, anti-nuclear antibody, and D-dimer; low Protein S activity; and evidence of peripheral arterial disease on imaging studies. She was started on peripheral vasodilators, Methotrexate, and anticoagulation. Close monitoring of the affected limbs and other organs involved was done. Control of limb ischemia was achieved after 4 months of regular Cyclophosphamide infusion. Continued multi-disciplinary care was ensured for this patient.ConclusionThere is evolving knowledge about the interplay of COVID-19 hyperinflammatory state and rheumatologic disorders. COVID-19 is thought to exacerbate cutaneous manifestations of autoimmune disorders via antigen protein mimicry and cytokine imbalance. Moreover, COVID-19 is characterized by complex hematopathologic processes that put a patient in a hypercoagulable state. Elevated D-dimer can be seen in both COVID-19 and systemic sclerosis owing to their pro-thrombotic sequela. There is scarcity of data on the association of Protein S activity with COVID-19 and systemic sclerosis. More studies need to be carried out to ultimately arrive at a consensus on thrombosis prophylaxis for patients with Scleroderma and COVID-19.

Hemophagocytic lymphohistocytosis in trisomy 21: successful treatment with interferon inhibition

BackgroundHemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition of immune dysregulation primarily driven by the cytokine interferon gamma. It can be either a genetic or acquired disorder associated with infection, malignancy, and rheumatologic disorders. Trisomy 21 can express a wide range of phenotypes which include immune dysregulation and shares inherent pathophysiology with a group of disorders termed interferonopathies. Knowledge of this overlap in seemingly unrelated conditions could provide a basis for future research, and most importantly, alternative therapeutic interventions in acute life threatening clinical scenarios. Herein, we describe two patients with trisomy 21 presenting with HLH that was refractory to conventional treatment. Both patients were successfully managed with novel interventions targeting the interferon pathway.Case presentationWe describe a 17-month-old male and 15-month-old female with trisomy 21 presenting with a myriad of signs and symptoms including fever, rash, cytopenias, and hyperferritinemia, both ultimately diagnosed with HLH. Each had relapsing, refractory HLH over time requiring several admissions to the hospital receiving conventional high dose corticosteroids and interleukin-1 inhibition therapy. Successful steroid-free remission was achieved after targeting interferon inhibition with emapalumab induction followed by long-term maintenance on baricitinib.ConclusionTo our knowledge, these are the first reported cases of relapsed, refractory HLH in patients with trisomy 21 successfully treated with emapalumab and transitioned to a steroid-sparing regimen with oral baricitinib for maintenance therapy. Trisomy 21 autoimmunity and HLH are both thought to be driven by interferon gamma. Targeting therapy toward interferon signaling in both HLH and autoimmunity in trisomy 21 may have potential therapeutic benefits. Further investigation is needed to determine if trisomy 21 may predispose to the development of HLH given this common pathway.

Factors Associated with in-Hospital Mortality in Patients with Hemophagocytic Lymphohistiocytosis: A 5-Year Analysis from the National Inpatient Sample

Background: Haemophagocytic lymphohistiocytosis (HLH) is an aggressive, life-threatening syndrome caused by a robust and excessive immune response leading to multi-organ failure. HLH can be due to a myriad of etiologies that range from primary disorders related to genetic defects or secondary to infections, autoimmune conditions, malignancies, etc. HLH has been broadly recognized in the pediatric population. Most of the clinical guidelines and evidence are based on this population; thus, more literature is needed amongst the adult population, especially on what factors increase mortality. Therefore, our study aims to evaluate factors associated with mortality in HLH Among Hospitalized Patients in the US using a Large Nation-wide Database. Methods: We performed a retrospective survey analysis of the National Inpatient Sample (NIS) using ICD10-CM and PCS codes to identify adult patients hospitalized with a primary or secondary diagnosis of HLH between October 2015 and December 2019. We compared patients who survived the illness as a control group versus patients who died during the hospitalization. A comparison was done between demographic variables including age, race, sex, median income, among other factors. Data regarding past medical history was also included. The most common causes of HLH were queried and compared between the two groups. Lastly, we performed a final comparison between multiple inpatient complications and outcomes between the two groups. We used qui-square and fisher exact test for categorical variables and student t-test or Mann-Whitney U test for continuous variables. All analysis was done using R studio utilizing the survey package. Results: Data from 8,660 admissions with HLH were included, of which 21% of patients died during the hospitalization. Patients with HLH who died tended to be males (61%), slightly older at age 53 years, and a higher percentage of white patients (55%), though not statistically significant than those who did not die. On the other hand, increased mortality was associated with hematological malignancies (37% vs 24%, p<0.05), baseline chronic kidney, heart, and liver disease. Additionally, these patients were also more likely to develop renal failure, non-septic shock, and pneumonia. Interestingly, patients with rheumatological disorders had statistically lower deaths (13% vs 17% p<0.05). Patients in the lowest percentile of income had the highest percentage of deaths at 30% and the highest percentile of income had a lower percentage of deaths at 22%. The length of inpatient stay was significantly longer in patients who died (18 vs 14 days, p<0.05). In terms of location, larger academic hospitals had higher mortality (77% vs 71%, p=0.02), with no difference between regions. Conclusions: This nationwide data analysis demonstrates the high mortality rates that persist in patients with HLH. Our study contributes to the growing literature on HLH, an intricate and complex topic that is not yet fully understood. Increased attention should be placed on the older population with pre-existent co-morbidities as well as patients with hematological malignancies and low socioeconomic status who are at potentially higher risk of death, to elucidate the mechanisms leading to poor outcomes and potential treatments of this condition. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Incidence and Factors Associated with Hemophagocytic Lymphohistiocytosis Among Hospitalized Patients in the US Using a Large Nation-Wide Database

Background Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening condition triggered by an excessive inflammatory response leading to multiorgan failure with high mortality rates. Early diagnosis and treatment are imperative for survival. However, the diversity in etiologies and clinical presentations make it very challenging to diagnose. HLH has been widely described in the pediatric population. While it is being increasingly recognized in adults, the current knowledge of epidemiological characteristics is limited. The aim of our study is to evaluate the incidence and factors associated with HLH among hospitalized patients in the US using a large nationwide database. Methods We performed a retrospective analysis with the National Inpatient Sample (NIS) using ICD10-CM and PCS codes to identify adult patients hospitalized with a primary or secondary diagnosis of HLH between October 2015 and December 2019. We described patient characteristics including location, charges, length of stay (LOS), associated diagnosis, and inpatient complication variables. We used R studio survey package to analyze survey data included in the NIS to account for the sampling weight and obtain accurate estimates of the included population. Lastly, we included a graph to describe the annual trend of HLH admissions and mortality. Results Data from 8,660 admissions with HLH were included, of which 1785 (21%) patients died during the hospitalization. Patients with HLH tended to be males (56%), with a mean age of 48 years, fifty five percent of the population were white, 17% black, 15% Hispanic, and 7.3% Asian. Associated diagnosis included DLBCL (9.1%), other Non-Hodgkin lymphoma (4.3%), Hodgkin lymphoma (3.8%), Leukemia (4.2%), NK-Cell lymphoma (2%), Viral infections (11.56%), fungal infections (17.85%), bacterial infections (1.16%), and rheumatological disorders (18.51%). Most patients were hospitalized in larger hospitals (74%). A higher percentage of patients were admitted in the South (34%), followed by West (23%), Northeast (22%), and Midwest (20%), with a mean hospitalization cost of $ 251,283. An increasing trend was noted in admissions for HLH. However, the mortality rate has remained stable, despite the recent approval of the interferon-gamma monoclonal antibody emapalumab-lzsg in November of 2018. Conclusions HLH in adults is an increasingly identified disorder that remains a challenging and critical condition. This nationwide data analysis demonstrates its geographical distribution and the persistently high mortality associated with it. Further studies are needed to improve early diagnosis, help understand its pathophysiology to identify patients at risk, and allow for improved treatment. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Frequency of Thrombosis in Covid-19 Patients Compared to Non-Covid-19 Sepsis Patients Admitted to the Intensive Care Unit

The COVID-19 pandemic to date is responsible for 6.39 million deaths and has devastated economies and healthcare infrastructure worldwide. In mid-January 2021 in the United States, more than 28,000 Covid-19 patients were admitted to the intensive care unit (ICU) at a given time. Systemic activation of coagulation may be a part of the pathophysiology of COVID-19. Numerous studies have demonstrated that the hypercoagulable state associated with COVID-19 infection may be associated with adverse outcomes and mortality. Historically, studies have also demonstrated high rates of thrombotic events among patients with sepsis. Whether the associated increase in thrombotic events results from COVID-19 specific infection or a general severe infection response is unknown. Understanding the relative contribution of venous thromboembolism (VTE) in COVID-19 severe disease helps risk stratify and clarify thromboembolism management from sepsis guidelines. Moreover, different VTE rates may indicate COVID-19-specific mechanisms warranting further investigation. To delineate the role of VTE in COVID-19 ICU admission and outcomes and to elucidate the pathophysiology of COVID-19 hypercoagulability, we evaluated the rate of thrombotic events across ICU patients with COVID-19 disease and compared the rate with all patients with non-COVID-19 sepsis or septic shock. This retrospective cohort study was approved by the USF Institutional Review Board. A chart review was performed of patients 18 years or older admitted to the ICU at Tampa General Hospital between January 1, 2020, to December 31, 2020, with a diagnosis of COVID-19 or sepsis secondary to other organisms. Sepsis criteria was defined as non-Covid-19 systemic infection and at least two of the following: 1) Temperature >38C or <36C; 2) heart rate >90 3) respiratory rate >20 or PaCO2<32; 4) WBC >12,000 or <4000, or >10% bands. Patients' data were collected, including age, body mass index (BMI), malignancy, heart failure, respiratory failure, rheumatologic disorders, diabetes mellitus type 2 (DM2), and history of hypercoagulable events and incidence of a thrombotic event. Our study evaluated 2,752 patients admitted to the ICU. We found no statistically significant difference in the thrombotic event incidence in COVID-19 patients in the ICU [n=540] compared to non-COVID-19 patients [n=2,212] (15.6 % versus 18.2%, p-value 0.15). Based on these results, further study is required to lower the rate of VTE in COVID-19 and non-COVID-19 sepsis patients admitted to the ICU. It is reasonable to consider similar thromboembolism guidelines between COVID-19 and sepsis. However, comparing additional ICU outcomes such as mortality rates and length of stay is warranted.

PRMT5 Inhibition Reduces Autoinflammation in a Murine Model of Secondary Hemophagocytic Lymphohistiocytosis

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare but frequently fatal autoinflammatory syndrome characterized by dysregulated immune activation, excessive production of proinflammatory cytokines and hyperactivation of T cells and macrophages leading to tissue damage. Primary HLH occurs due to predisposing genetic mutations in the perforin/granzyme pathway, while secondary HLH can be triggered by infections, rheumatologic disorders, or malignancies. HLH has a poor overall prognosis despite appropriate therapy, and new avenues targeting pathologic disease mechanisms are urgently needed. The protein arginine methyltransferase 5 (PRMT5) enzyme has been identified as an important mediator in inflammatory T cell subsets in autoimmune disease and graft versus host disease. We hypothesized that PRMT5 activity is relevant to inflammation loops that drive autoinflammation observed in HLH. Methods: We explored inhibition of type II protein arginine methyltransferase enzyme, PRMT5, in a murine model of secondary HLH. HLH was triggered in C57BL/6-J mice (Jackson Laboratories) by repeated injections of CpG 1826 (Integrated DNA Technologies) and an IL-10 receptor-blocking antibody (clone 1B1.3A; Bio X Cell) on days 0, 2, 4, and 7. Injected mice were left untreated or were treated with ruxolitinib 90 mg/kg (validated treatment of HLH) orally twice daily, starting on Day 4, or increasing doses of oral inhibitor of PRMT5, PRT382 (0.25, 1 or 2 mg/kg daily), starting on Day 0. Mice were weighed daily. On day 9, mice were euthanized and analyzed for spleen and liver weight, serum IFNγ levels and immune profiling of lymphoid and myeloid splenocyte subsets. Splenocytes were left unstimulated, or stimulated with lipopolysaccharide (LPS, myeloid cell stimulation) or CD3/CD28-directed antibodies (T cell stimulation) and analyzed by flow cytometry. Data analysis was performed by unsupervised ViSNE clustering in Cytobank software. Statistical analysis was performed by unpaired t test. Results: We observed that 1 mg/kg PRT382 lessened the hallmarks of secondary HLH, compared to the untreated HLH cohort, including weight loss (21% reduction, p-value 0.2746), the development of splenomegaly (71% reduction, p-value <0.001) and hepatomegaly (61% reduction, p-value <0.05), similarly to ruxolitinib (p-values <0.01, <0.001, and 0.0795, respectively). Furthermore, mice with untreated HLH showed a 17X increase in serum IFNγ levels compared to controls (p-value <0.01), while mice treated with ruxolitinib showed a 10X increase (p-value <0.05 compared to controls, 0.2577 compared to untreated HLH), and mice treated with 1 mg/kg PRT382 showed undetectable serum IFNγ (p-value 0.2104 compared to controls, <0.01 compared to untreated HLH). Flow cytometric analysis of mouse splenocytes showed that HLH stimulated the expansion of neutrophils (CD11b+/Ly6Clo/Ly6G+) and inflammatory monocytes (CD11b+/Ly6C+/Ly6G-). Ruxolitinib partially counteracted this expansion. PRT382 inhibited expansion of these myeloid cell subsets in a dose-dependent manner and also limited production of IFNγ and TNFα by myeloid cells in response to stimulation with LPS in presence of Golgi blockade with Brefeldin A. Furthermore, PRT382 limited the upregulation of CD25 on the surface of T cells in response to T cell stimulation, although no change in cytokine production by T cells was observed. Conclusions: PRMT5 inhibition counteracts pro-inflammatory features of pathologic hyper-inflammation driven by myeloid immune cell subsets in a model of secondary HLH. This may represent a novel avenue for urgently needed immune modulatory targeted treatment of HLH. Studies of PRMT5 expression and targeting in models of primary HLH are underway.

Vesiculobullous diseases, connective tissue and rheumatological disorders

This section reviews the emergency presentations of autoimmune blistering diseases, connective tissue and rheumatological disorders as well as common pitfalls associated with their diagnosis and management

Immune-related adverse events in patients with pre-existing autoimmune rheumatologic disease on immune checkpoint inhibitor therapy

IntroductionImmune checkpoint inhibitors (ICIs) enhance the immune system’s ability to target and destroy cancer cells, but this non-specific immune overactivation can result in immune-related adverse events (irAEs). Patients with underlying autoimmune diseases were excluded from the original ICI clinical trials because of the theoretical risk of irAEs. This study aimed to evaluate the risk of irAEs in patients with pre-existing rheumatologic diseases on ICIs, impact of anti-rheumatic therapy on irAEs, and malignancy outcomes.MethodsWe performed a retrospective chart review of patients with a pre-existing rheumatologic diagnosis receiving ICIs at the University of North Carolina from 2014 to 2019. Risk differences (RD) and asymptotic 95% confidence intervals (95% CIs) using a continuity correction along with odds ratios (OR) and exact 95% CIs were produced between pre-specified risk factors and flares of the underlying rheumatologic disease and/or irAEs. Kaplan–Meier survival estimates for time to unfavorable cancer response between subsets of patients were compared using the log-rank test.ResultsWe identified 45 patients receiving an ICI with an underlying rheumatologic diagnosis, including 22 with rheumatoid arthritis (RA). Overall, 13 patients (29%) had a flare of their autoimmune disease, 20 patients (44%) had a new-onset irAE, and 27 (60%) had either a flare or new-onset irAE. Patients with RA had higher risk of flares compared to those with other rheumatologic disorders (45% vs 13%, RD 32%, 95% CI 2.0–56.8); all RA flares were ≤ grade 2 and treated in the outpatient setting. Concurrent treatment of the rheumatologic disease at the start of ICI therapy was not associated with a reduced risk of flare (OR 0.86, 95% CI 0.19–3.76) or new onset irAE (OR 3.21, 95% CI 0.83–13.6) compared to those not on anti-rheumatic medications. Anti-rheumatic therapy did not impact time to unfavorable malignancy outcome (p = 0.52).ConclusionThe majority of our study cohort experienced a flare or new onset irAE with ICI treatment. Treatment with anti-rheumatic therapy did not prevent disease flares or new onset irAEs, but did not negatively impact malignancy outcomes. Research is needed to determine safe anti-rheumatic therapy options to prevent flares and irAEs that do not interfere with malignancy outcomes.

Characteristics and Limitations of Video-capillaroscopy in Reconstructive Microsurgery for Different Histologic Components of Flaps.

Indocyanine green, ultrasonography, and handheld Doppler can be used to evaluate blood flow at the donor and recipient site during microvascular reconstruction. However, these methods do not provide direct visualization and assessment of real-time blood flow. Video-capillaroscopy has been shown to be useful in clinical practice to assess microcirculation in rheumatologic disorders. In this report we used video-capillaroscopy to assess different tissue components involved in microvascular surgery. Seven patients who underwent head and neck oncologic microvascular reconstruction between November 2021 and February 2022 were included in this study. Video-capillaroscopy (GOKO-BscanZD, GOKO Imaging Devices Co., Ltd., Japan) was used to evaluate the donor-site and recipient-site tissue components. Optimal red blood cell movement was graded with a score of four, while no flow was graded with a score of 0. Seven myocutaneous flaps and seven recipient sites were evaluated. For the donor-site, our analysis demonstrated a significantly higher video-capillaroscopy quality for skin (3.43), adipose tissue (3.7) and perforators (3.7) when compared with muscle (0.429), muscle fascia (0.857), and de-epithelialized skin (1) (P < 0.001). For the recipient-site, a significantly higher video-capillaroscopy quality for skin (2.7), adipose tissue (3.5), and the periosteum (2.1) was noted when compared with muscle (0) (P < 0.001). Video-capillaroscopy efficiency is limited in the muscular component and injured (de-epithelialized) skin surface areas of flaps. Herein, we provide evidence that assessment of flap perfusion with video-capillaroscopy can be reliably achieved in the skin, periosteum, perforators, and adipose tissue. Video-capillaroscopy is expected to be applied for intraoperative real-time blood flow evaluation.

High-resolution ultrasound of peripheral neuropathies in rheumatological patients: An overview of clinical applications and imaging findings.

Peripheral neuropathies are surprisingly common and can be associated with a number of conditions, including rheumatological diseases. Whether the co-existence of peripheral neuropathies with rheumatological disorders is coincidental or related to a common pathogenic mechanism, these disabling conditions can affect the outcome of rheumatological patients and should be targeted with specific treatment. The clinical presentation of peripheral neuropathy can be multifaceted and difficult to recognize in polysymptomatic patients. However, physicians adopting state-of-art diagnostic strategies, including nerve imaging, may improve the detection rate and management of neuropathies. In particular, a diagnostic approach relying exclusively on clinical history and nerve conduction studies may not be sufficient to disclose the etiology of the nerve damage and its anatomical location and thus requires integration with morphological studies. High-Resolution Ultrasound (HRUS) is increasingly adopted to support the diagnosis and follow-up of both joint disorders in rheumatology and peripheral neuropathies of different etiologies. In this review, the different types of nerve disorders associated with the most common syndromes of rheumatological interest are discussed, focusing on the distinctive sonographic features.

Role of Rehabilitation in Comprehensive Management of Juvenile Idiopathic Arthritis: When and How?

Juvenile idiopathic arthritis (JIA), the most common chronic rheumatological disorder in children, can result in significant disability and poorer health-related quality of life. Rehabilitation aimed at pain management, optimizing musculoskeletal function, improving endurance and achieving independence in activities of daily living, and participation in age-appropriate activities, is a vital component in the comprehensive management of children with this condition. Rehabilitation strategies depend on the phase of the disease and focus on pain alleviation in the active phase and improving mobility and function in the inactive phase. Rehabilitation in JIA is multidisciplinary and includes exercise therapy, physical modalities, orthotic and assistive devices, and gait training. Exercise therapy has demonstrated improvement in muscle strength, bone mineral density, exercise capacity, and quality of life, without negative consequences of pain or exacerbation of arthritis. Common exercise interventions for children with JIA include mobilization, strengthening, aerobic exercises, Pilates-based exercises, aquatic therapy, and recreation. Physical modalities such as thermotherapy, cryotherapy, electrotherapy, ultrasound, and low-power laser therapy are commonly employed. Orthotic devices play an important role in joint protection, prevention and reduction of joint deformities, and assistance with function and gait. Assistive devices are prescribed to improve functional ability and independence in activities of daily living in children with disabilities. There have been recent advances in the field of rehabilitation with the advent of robotics, virtual reality, and telerehabilitation.

Long-term safety and efficacy of fecal microbiota transplantation in 74 children: A single-center retrospective study.

BackgroundFecal microbiota transplantation (FMT) is an effective treatment for intestinal and extra-intestinal disorders. Nonetheless, long-term safety and efficacy remain major challenges for FMT applications. To date, few long-term follow-up studies have been published on FMT in children.MethodsRetrospective reviewed the medical charts of 74 patients who underwent 508 FMT courses between August 2014 and July 2019 at our medical center. All the FMT procedures followed uniform standards. Baseline characteristics pre-FMT and follow-up data were collected at 1, 3, 6, 12, 36, 60, and 84 months after FMT. All potential influencing factors for adverse events (AEs) were analyzed and assessed using regression analyses.ResultsA total of 70 (13.7%) short-term AEs occurred in twenty-six patients (35.1%). Most AEs (88.5%) occurred within 2 days post-FMT. A total of 91.4% of the AEs were self-limiting. Ulcerative colitis (UC) and within four times of FMT were associated with a higher rate of AEs (p = 0.028 and p = 0.021, respectively). The primary clinical remission rate after FMT was as high as 72.9%. Twenty-five children were followed for more than 5 years after FMT. The clinical remission rates gradually decreased over time after FMT. During follow-up, none of the patients developed autoimmune, metabolic, or rheumatologic disorders or tumor-related diseases. However, nine children developed rhinitis, five developed rhinitis, were underweight, and six developed constipation.ConclusionsFMT is a safe and effective treatment for dysbiosis in children. The long-term efficacy of FMT for each disease decreased over time. Moreover, multiple FMTs are recommended 3 months post-FMT for recurrent diseases.

SINGLE CAVITARY LUNG LESION IN A HEALTHY YOUNG MALE

SINGLE CAVITARY LUNG LESION IN A HEALTHY YOUNG MALE

Hemophagocytic Lymphohistiocytosis.

Hemophagocytic Lymphohistiocytosis.

Hemophagocytic Lymphohistiocytosis after ChAdOx1 nCoV-19 Coronavirus Vaccination in a Patient with no Known Comorbidities

Hemophagocytic lymphohistiocytosis (HLH) is an inflammatory condition where there is marked cytopenia and large-scale activation of macrophages and CD8+ cytotoxic T cells. HLH may be of two types – primary HLH caused by genetic abnormalities and secondary HLH due to infections, malignancies, autoimmune disorders, rheumatologic disorders, and metabolic dysfunctions. We describe a case of HLH following the first dose of the ChAdOx1 nCoV-19 Corona Virus vaccine. In this patient, there was no clear precipitant of HLH. The most probable explanation could be intense immune activation by vaccine constituents producing aberrant activation of inflammatory cytokines. There were no signs of infection or malignancy. Since our patient was clinically stable, his symptoms had resolved and HLH parameters had improved, no HLH-specific therapy was given.

Type I interferon signature as a possible new marker for stratification of patients with juvenile idiopathic arthritis.

The interferon score (IS) quantifies the expression of interferon-stimulated genes in peripheral blood, providing an indirect estimate of interferon-mediated inflammation in rheumatological disorders. This study explores the clinical significance of IS among a cohort of patients affected by juvenile idiopathic arthritis (JIA) and its relevance to disease stratification and prognosis. All patients referred to the Rheumatology Service of the Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy, with a diagnosis of JIA (2001 ILAR criteria) were consecutively recruited. Systemic JIA was excluded. Demographic, clinical and laboratory data were collected for each patient in a structured database. Categorical variables were expressed as numbers (%) and compared by the χ2 test or Fisher's exact test. Principal Component Analysis (PCA) was performed with clinical and laboratory data. Forty-four patients were recruited (35 F, 9 M): 19 polyarticular, 13 oligoarticular, 6 oligoarticular-extended, 5 psoriatic and 1 enthesitis-related arthritis. Sixteen had a positive IS (≥3). Increased IS correlated with a higher number of involved joints ≥5 (p=0.013), increased erythrocyte sedimentation rate (ESR) (p=0.026) and hypergammaglobulinaemia (p=0.003). PCA highlighted a subgroup of patients who shared high levels of IS, ESR, C-reactive protein, hypergammaglobulinaemia, JADAS-27, polyarticular involvement and family history of autoimmunity. Although based on a small case series, our results may support the role of IS in better defining a subgroup of JIA subjects with stronger autoimmune features. The possible relevance of these results for therapeutic stratification remains to be explored.

Rheumatological and Musculoskeletal Complications in Diabetes Patients

Musculoskeletal disorders are common in individuals with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). It is associated with significant morbidity and hampered quality of life. Hyperglycemia-induced aberrant levels of insulin or insulin growth factors may lead to neuropathic complications, which enhances pain through central sensitization. Evidence suggests that diabetes is associated with numerous musculoskeletal disorders and inefficient control of diabetes may cause persistent musculoskeletal pain over time. Neuropathic joints are commonly observed in the foot and ankle of patients. Diabetic polyneuropathy, rheumatoid arthritis (RA)-associated pain are other complications. In diabetic patients with osteoarthritis (OA), factors including advanced glycation end-stage products (AGEs) and markers of oxidative stress could contribute to pain associated with low-grade inflammation. In obese individuals with T2DM, uncontrolled glycemic status can lead to mechanical stress-induced calcification and ossification of ligaments, and oxidative damage. In individuals with diabetes and OA, synovitis in the tissues is evidenced by the presence of higher levels of prostaglandins, leukotrienes, and adipokines. The pathogenesis of cheirarthritis remains largely unknown and is attributed to increased AGE, chronic hyperglycemia, dysregulated function of extracellular and some intracellular proteins. Advancing age, hormonal changes during adolescence, disorderly secretion of growth hormone and insulin-like growth factor-1 (IGF-1) are other possible contributing factors. Early assessment and strict control of diabetes can prevent other long-term micro and macrovascular complications. These measures can reduce the term of enduring pain and morbidity in susceptible individuals. This article reviews the prevailing knowledge and the mechanistic role of underlying diabetes on rheumatological and musculoskeletal disorders. J Endocrinol Metab. 2022;12(4-5):117-124 doi: https://doi.org/10.14740/jem811

Identification of specific causes of myelopathy in a large cohort of patients initially diagnosed with transverse myelitis

Background and objectivesIdentifying the etiologic diagnosis in patients presenting with myelopathy is essential in order to guide appropriate treatment and follow-up. We set out to examine the etiologic diagnosis after comprehensive clinical evaluation and diagnostic work-up in a large cohort of patients referred to our specialized myelopathy clinic, and to explore the demographic profiles and symptomatic evolution of specific etiologic diagnoses. MethodsIn this retrospective study of patients referred to the Johns Hopkins Myelitis and Myelopathy Center between 2006 and 2021 for evaluation of “transverse myelitis”,the final etiologic diagnosis determined after comprehensive evaluation in each patient was reviewed and validated. Demographic characteristics and temporal profile of symptom evolution were recorded. ResultsOf 1193 included patients, 772 (65%) were determined to have an inflammatory myelopathy and 421 (35%) were determined to have a non-inflammatory myelopathy. Multiple sclerosis/clinically isolated syndrome (n = 221, 29%) and idiopathic myelitis (n = 149, 19%) were the most frequent inflammatory diagnoses, while spinal cord infarction (n = 197, 47%) and structural causes of myelopathy (n = 108, 26%) were the most frequent non-inflammatory diagnoses. Compared to patients with inflammatory myelopathies, patients with non-inflammatory myelopathies were more likely to be older, male and experience chronic symptom evolution (p < 0.001 for all). Hyperacute symptom evolution was most frequent in patients with spinal cord infarction (74%), while chronic symptom evolution was most frequent in patients with structural causes of myelopathy (81%), arteriovenous fistula or arteriovenous malformation (81%), myelopathy associated with rheumatologic disorder (71%), and sarcoidosis-associated myelopathy (61%). ConclusionsPatients initially diagnosed with “transverse myelitis” are eventually found to have a more specific inflammatory or even non-inflammatory cause, potentially resulting in inappropriate treatment and follow-up. Demographic characteristics and temporal profile of symptom evolution may help inform a differential diagnosis in these patients. Etiological diagnosis of myelopathies would provide better therapeutic decisions.