LGR5 expressing skin fibroblasts define a major cellular hub perturbed in scleroderma.

Systemic sclerosis (scleroderma, SSc) is an incurable autoimmune disease with high morbidity and mortality rates. Here, we conducted a population-scale single-cell genomic analysis of skin and blood samples of 56 healthy controls and 97 SSc patients at different stages of the disease. We found immune compartment dysfunction only in a specific subtype of diffuse SSc patients but global dysregulation of the stromal compartment, particularly in a previously undefined subset of LGR5+-scleroderma-associated fibroblasts (ScAFs). ScAFs are perturbed morphologically and molecularly in SSc patients. Single-cell multiome profiling of stromal cells revealed ScAF-specific markers, pathways, regulatory elements, and transcription factors underlining disease development. Systematic analysis of these molecular features with clinical metadata associates specific ScAF targets with disease pathogenesis and SSc clinical traits. Our high-resolution atlas of the sclerodermatous skin spectrum will enable a paradigm shift in the understanding of SSc disease and facilitate the development of biomarkers and therapeutic strategies.

[THE PREVALENCE OF POSITIVE POWER DOPPLER SIGNALS BY MUSCULOSKELETAL ULTRASOUND OF HANDS IN SCLERODERMA PATIENTS].

BACKGROUND: Musculoskeletal ultrasound is increasingly used in the evaluation of joint inflammation. Power Doppler can identify increased hyperemia which indicates inflammation. OBJECTIVES: To measure the prevalence and level of positive Power Doppler signals at the hand joints of scleroderma patients. METHODS: Ten scleroderma patients were examined by ultrasound of the dominant hand. Power Doppler signals were measured at the wrist as well as the metacarpophalangeal joints (MCPS), proximal interphalangeal joints (PIPS) and distal interphalangeal joints (DIPS) at the second to fifth fingers. Clinical information regarding age, gender, disease duration, level of involvement (limited or diffuse) and skin score were collected. The data were taken from a larger ultrasound study from UCLA University that examined the validation of ultrasound in scleroderma. RESULTS: Mean age was 51.7 years and 70% were females; 212 joints were examined. Positive Power Doppler signals were found in 30% of patients and were mostly low grade. Power Doppler signals were found in 3.3% of the joints of scleroderma patients. DISCUSSION: Level of Power Doppler signals which probably reflects the level of joint inflammation was low in the scleroderma patients and its prevalence was low.

Adalimumab-induced autoimmune hepatitis.

Antitumor necrosis factor antibodies are widely used in the treatment of autoimmune diseases. We describe the occurrence of autoimmune hepatitis in a patient treated with adalimumab, a fully human IgG antibody against tumor necrosis factor, for psoriatic arthritis. The patient made a full recovery after discontinuation of adalimumab and treatment with steroids. This is the first reported case of adalimumab-induced autoimmune hepatitis.

High percentages and activity of synovial fluid NK cells present in patients with advanced stage active Rheumatoid Arthritis.

Rheumatoid Arthritis (RA) causes chronic inflammation of joints. The cytokines TNFα and IFNγ are central players in RA, however their source has not been fully elucidated. Natural Killer (NK) cells are best known for their role in elimination of viral-infected and transformed cells, and they secrete pro-inflammatory cytokines. NK cells are present in the synovial fluids (SFs) of RA patients and are considered to be important in bone destruction. However, the phenotype and function of NK cells in the SFs of patients with erosive deformative RA (DRA) versus non-deformative RA (NDRA) is poorly characterized. Here we characterize the NK cell populations present in the blood and SFs of DRA and NDRA patients. We demonstrate that a distinct population of activated synovial fluid NK (sfNK) cells constitutes a large proportion of immune cells found in the SFs of DRA patients. We discovered that although sfNK cells in both DRA and NDRA patients have similar phenotypes, they function differently. The DRA sfNK secrete more TNFα and IFNγ upon exposure to IL-2 and IL-15. Consequently, we suggest that sfNK cells may be a marker for more severely destructive RA disease.

Validation of Sonography findings of synovitis and tenosynovitis of hands and wrists in patients with systemic sclerosis.

Objectives: Validating musculoskeletal ultrasound features of the joints and tendons of the hands in a large scleroderma cohort. Methods: A total of 81 scleroderma patients participated in this prospective, cross-sectional study. Grayscale and power Doppler musculoskeletal ultrasound images of 13 joints and 5 tendons of the wrist and hand were obtained. Clinical assessment included modified Rodnan skin thickness score, joint count, and Scleroderma Health Assessment Questionnaire. Face validity, content validity, construct validity, and feasibility were assessed. Results: Mean age was 53.8 years (range 22-80), 76.5% were females, and disease duration ranged from 0.25 to 29 years. Mean length of the examination was 36 min. Scleroderma Health Assessment Questionnaire-Disability Index correlated with musculoskeletal ultrasound erosions (r = 0.5, p = 0.0003). Skin score correlated with tendinitis grayscale (r = 0.26, p = 0.02). Intra-reader correlation coefficient for musculoskeletal ultrasound was 0.96 for the joints and could not be calculated for tendons because there were too few positive findings. When tendon changes existed, percent of agreement was 77.7%-83.3%. Conclusion: Musculoskeletal ultrasound of 13 joints and 5 tendons of the hands and wrist has face and content validity. Construct validity was shown for the tendons and erosion scores. Feasibility and reliability were partially validated.

Severe Epstein-Barr virus-associated hemophagocytic syndrome in six adult patients.

BACKGROUND: EBV associated hemophagocytic syndrome (HPS) is an aggressive and potentially life-threatening condition. So far, most EBV associated HPS has been characterized mainly in infants and children in Asian countries. RESULTS: Here, we report six cases of EBV associated HPS occurring in previously healthy adults in a non-endemic area within a short period of 3 years. All patients presented with fever, hepatosplenomegaly and pancytopenia as well as disturbed liver function tests and coagulopathy. Half were diagnosed as having lymphoma. While EBV-specific serological assays were non-diagnostic in four of the six patients, the presence of EBV DNA in plasma allowed the diagnosis of EBV associated HPS in all patients. CONCLUSION: EBV associated HPS may be more prevalent in non-Japanese adults than was previously considered. Screening for hemophagocytic syndrome, in adults as well as in children, should include real-time PCR for EBV.

The Rate of Adherence to Antiarthritis Medications and Associated Factors among Patients with Rheumatoid Arthritis: A Systematic Literature Review and Metaanalysis.

OBJECTIVE: Reported adherence in rheumatoid arthritis (RA) varies widely (10.5-98.5%). Variability may result in part from different methods used to measure adherence. Our aims were to quantify adherence to antiarthritis medications for each method and to identify variability and associated factors. METHODS: The systematic literature review examined PubMed, the Cochrane central database, and article reference lists from 1970 to November 2014. Papers with medication adherence data (disease-modifying antirheumatic drugs, steroids, and nonsteroidal antiinflammatory drugs) in adult patients with RA or data on associated factors were included. Adherence rate was recorded for each method. Random-effect metaanalysis estimated adherence for different evaluation methods. RESULTS: Adherence rate was 66% (95% CI 0.58-0.75). There were no differences in adherence among different measurement methods (interview, questionnaires, etc.). Regression analysis showed that adherence decreases during followup. Among 100 possible factors potentially effecting adherence, 7 adherence-associated factors were found in at least 2 different studies. These were the use of infliximab compared with etanercept or methotrexate (MTX), use of MTX compared to sulfasalazine or to etanercept, belief in the necessity of the medications, older age, and white race. CONCLUSION: Overall adherence rate was 66%. We suggest that readers appraise adherence studies according to the medications evaluated, the validity of the method, and the scales and cutpoints.

Age-related accelerated tapping response in healthy population.

Different types of rapid tapping responses were described in the finger-tapping test. The "Hastening phenomenon" was described as an abnormal motor response in patients with Parkinson's disease. Accelerated tapping has been shown in a healthy elderly sample. It is not clear whether accelerated tapping relates to the hastening phenomenon or characterizes normal aging. We hypothesized that this sample of 21 healthy elderly people showed increased accelerated tapping but not hastening phenomenon. To assess this hypothesis, 20 healthy young and 21 elderly subjects performed a tapping test, requiring responses from 1 to 6 Hz. The healthy elderly sample showed increased accelerated tapping but not increased "hastening phenomenon." We conclude that Accelerated tapping may represent age-related motor processes unlike the hastening phenomenon characterizing Parkinson's disease.

Severe malnutrition due to systemic lupus erythematosus associated protein losing enteropathy.

Systemic lupus erythematosus most often targets organs such as joints, serosa, skin, bone marrow, and the kidneys. Gastrointestinal complications are uncommon, and among these, protein losing enteropathy is particularly rare. We present a young woman who suffered from chronic abdominal pain and diarrhea, developed severe malnutrition, and was eventually diagnosed with systemic lupus erythematosus and associated protein losing enteropathy.

Pulmonary hemorrhage in antiphospholipid antibody syndrome.

OBJECTIVE: To characterize the clinical manifestations of patients with antiphospholipid antibody syndrome (APS) and pulmonary hemorrhage (PH). METHODS: We performed a retrospective, single-center analysis of patients with APS who were followed up from 1980 to 2011. Of these patients, only those who fulfilled the Sydney criteria for APS were included. Patients with APS that manifested with PH were called the PHAPS group. The rest of the patients with APS served as controls. Clinical manifestations were compared between the PHAPS group and controls. RESULTS: Sixty-three patients fulfilled the criteria for APS. Thirteen experienced PH and were included in the PHAPS group. Seventy-five percent of the patients with PHAPS and 22% of the controls had mitral valve disease (p = 0.001). Central nervous system (CNS) involvement (cerebrovascular accident, seizures) was present in 61% and 16% of the patients with PHAPS and controls, respectively (p = 0.001). Skin involvement (livedo reticularis, chronic leg ulcers) was present in 54% and 8% of the patients with PHAPS and controls (p = 0.001). Pregnancy morbidity occurred in 87.5% and 32.5% of the patients with PHAPS and controls (p = 0.005). Ninety-two percent and 83% of the patients with PHAPS had high-titer immunoglobulin γ (IgG) anticardiolipin and ß(2)-glycoprotein I IgG antibodies compared to 43% and 30% of the controls (p = 0.002, p < 0.001, respectively). CONCLUSION: Patients with PHAPS were more likely than controls to have mitral valve disease, skin disease, CNS involvement, and pregnancy morbidity as well as high-titer APS. PHAPS seems to be a unique subgroup of all patients with APS.