Familial hemophagocytic lymphohistiocytosis is a genetic disorder of lymphocyte cytotoxicity that usually presents in the first two years of life and has a poor prognosis unless treated by ...hematopoietic stem cell transplantation. Atypical courses with later onset and prolonged survival have been described, but no detailed analysis of immunological parameters associated with typical versus atypical forms of familial hemophagocytic lymphohistiocytosis has been performed.
We analyzed disease manifestations, NK-cell and T-cell cytotoxicity and degranulation, markers of T-cell activation and B-cell differentiation as well as Natural Killer T cells in 8 patients with atypical familial hemophagocytic lymphohistiocytosis due to mutations in UNC13D and STXBP2.
All but one patient with atypical familial hemophagocytic lymphohistiocytosis carried at least one splice-site mutation in UNC13D or STXBP2. In most patients episodes of hemophagocytic lymphohistiocytosis were preceded or followed by clinical features typically associated with immunodeficiency, such as chronic active Epstein Barr virus infection, increased susceptibility to bacterial infections, granulomatous lung or liver disease, encephalitis or lymphoma. Five of 8 patients had hypogammaglobulinemia and reduced memory B cells. Most patients had a predominance of activated CD8(+) T cells and low numbers of Natural Killer T cells. When compared to patients with typical familial hemophagocytic lymphohistiocytosis, NK-cell cytotoxicity and NK-cell and CTL degranulation were impaired to a similar extent. However, in patients with an atypical course NK-cell degranulation could be partially reconstituted by interleukin-2 and cytotoxic T-cell cytotoxicity in vitro was normal.
Clinical and immunological features of atypical familial hemophagocytic lymphohistiocytosis show an important overlap to primary immunodeficiency diseases (particularly common variable immunodeficiency and X-linked lymphoproliferative syndrome) and must, therefore, be considered in a variety of clinical presentations. We show that degranulation assays are helpful screening tests for the identification of such patients.
Some rheumatologic disorders may initially manifest with central nervous system (CNS) affection, mimicking the clinical, magnetic resonance imaging, and cerebrospinal fluid findings of multiple ...sclerosis (MS). The MRZ reaction (MRZR), composed of the three respective antibody indices (AIs) against measles, rubella, and varicella zoster virus, has been found positive frequently in MS patients. However, it is unclear whether the MRZR is helpful to distinguish rheumatologic disorders with CNS involvement (RDwCNS) from MS.
The MRZR was evaluated in patients with RDwCNS (n = 23), MS (n = 46; age and sex matched to patients with RDwCNS), and other inflammatory autoimmune neurological diseases affecting the CNS (OIND; n = 48). Both the stringency levels that have been used in previous MRZR studies, MRZR-1 (≥ 1 of 3 AIs positive) and MRZR-2 (≥ 2 of 3 AIs positive), were applied.
There was no statistically significant difference in the prevalence of positive MRZR between patients with RDwCNS (MRZR-1: 13.0% and MRZR-2: 8.7%, respectively) and OIND (MRZR-1: 22.9% and MRZR-2: 8.3%, respectively). Compared to these two study cohorts, the MS group exhibited significantly higher prevalences of positive MRZR (MRZR-1: 82.6%, MRZR-2: 63.0%; p < 0.005 each).
Considering the high specificity of MRZR-2 for MS found in this study, MRZR-2 can be a useful diagnostic tool for distinguishing MS from RDwCNS or OIND.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study investigated the hypothesis that high-resolution MRI can reveal mural inflammatory changes of the superficial temporal artery in giant cell arteritis (GCA).
MRI of the temporal artery of ...20 patients with suspected GCA was performed on a 1.5-T scanner using a dedicated eight-element phased-array head coil. Contrast-enhanced multislice T1-weighted spin-echo sequences were acquired perpendicular to the orientation of the vessel, with a submillimeter spatial resolution of 0.2 x 0.3 mm and a slice thickness of 3 mm. Mural thickness and lumen diameter of the temporal artery were measured, and mural contrast enhancement was graded on a four-point scale by two radiologists. For all patients, the MRI results were compared with the findings of clinical examination and laboratory tests. In addition, biopsy samples of the temporal artery were taken from 16 of these patients.
MRI sharply demonstrated the superficial temporal artery, allowing an evaluation of its lumen and wall. Seventeen patients were GCA-positive according to criteria of the American College of Rheumatology. Of these 17, 16 had true-positive MRI findings and one had false-negative MRI findings. The 3 patients who were GCA-negative according to the American College of Rheumatology criteria had true-negative MRI findings. The mean thickness of the vessel wall and the lumen diameter were 0.88 +/- 0.23 mm and 0.78 +/- 0.29 mm, respectively, in GCA-positive patients and 0.57 +/- 0.25 mm and 0.7 +/- 0.1 mm, respectively, in GCA-negative patients.
High-resolution contrast-enhanced MRI of the temporal artery allowed visualization of the temporal artery and evaluation of possible inflammation of the vessel wall. Our initial results with this noninvasive technique agreed well with histologic results and with the clinical criteria of the American College of Rheumatology.
Introduction
Psoriasis (Pso) and psoriatic arthritis (PsA) can reduce the quality of life (QoL) and are known to be associated with depression. Within this study, we aimed to assess the burden of ...disease, functional capacity, quality of life, and depressive symptoms and identify factors predicting functional impairment and depression in patients with psoriatic disease.
Methods
A cross-sectional survey was conducted in a cohort of 300 patients with psoriatic disease including 150 patients from a university hospital dermatology outpatient clinic and 150 patients from a university hospital rheumatology outpatient clinic. Questionnaire-based assessment of signs of arthritis (Psoriasis Epidemiology Screening Tool; PEST), functional status (Functional Questionnaire Hannover; FFbH), quality of life (World Health Organization Quality of Life Brief Version; WHOQOL-BREF), and depressive symptoms (Patient health questionnaire 9; PHQ-9) and retrospective medical chart analysis were performed.
Results
Despite treatment, burden of disease was high. Joint pain was reported in multiple regions in patients with Pso (
n
= 111) and patients with PsA (
n
= 189), but with differences in frequency and distribution patterns of symptoms. Functional impairment in everyday life was independently associated with diagnosis of PsA (odds ratio OR 9.56,
p
= 0.005), depressive symptoms (OR 5.44,
p
< 0.001) and age (OR 1.04,
p
= 0.033). At least mild depressive symptoms were demonstrated in 54% and 69% of patients with Pso and PsA, respectively. In a logistic regression model, depressive symptoms were independently associated with functional impairment (OR 4.50,
p
= 0.003), axial complaints (OR 2.80,
p
= 0.030), diagnosis of psoriatic arthritis (OR 2.69,
p
= 0.046), and number of joint regions with complaints (OR 1.10,
p
= 0.032).
Conclusion
Functional impairment, QoL, and depressive symptoms are mutually interdependent. Early diagnosis of PsA and initiation of anti-inflammatory therapy are essential to avoid long-term damage, disability, and mental health complications. However, despite therapy many patients with PsA, and especially female patients, report a substantial residual disease burden due to their psoriatic disease which will need to be addressed by a more patient-centered approach.
Objective
Chronic back pain (CBP) constitutes one of the most common complaints in primary care and a leading cause of disability worldwide. CBP may be of mechanical or inflammatory character and may ...lead to functional impairment and reduced quality of life. In this study, we aimed to assess and compare burden of disease, functional capacity, quality of life and depressive symptoms in axial spondyloarthritis (axSpA) patients with orthopedic chronic back pain patients (OBP). We further aimed to identify factors associated with quality of life.
Methods
Cross-sectional survey of a cohort of 300 CBP patients including 150 patients from a University Hospital Orthopedic Back Pain Outpatient Clinic with OBP and 150 patients with confirmed axSpA from a University Hospital Rheumatology Outpatient Clinic. Questionnaire-based assessment of pain character (Inflammatory Back Pain, MAIL-Scale), functional status (FFbH, BASFI), quality of life (WHOQOL-Bref) and depressive symptoms (Phq9) and retrospective medical chart analysis.
Results
Both, OBP and axSpA patients reported on average intermediate pain levels of mostly mixed pain character. Both groups demonstrated a reduced health-related quality of life and the presence of depressive symptoms. However, axSpA patients reported a significantly better subjective quality of life, more satisfaction with their health status and better functional capacity compared to OBP patients (all
p
< 0.001). In a multivariate regression model, depressive symptoms, mechanical back pain, pain level and age were negative predictors of subjective quality of life, whereas functional capacity was a positive predictor.
Conclusion
Chronic back pain was associated with a high morbidity and reduced quality of life regardless of pain character. We identified multiple factors associated with reduced quality of life. Awareness and addressing of these factors may help to overcome unmet needs and improve quality of life for these patients.
ObjectivesAxial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) may have a profound impact on sleep and health-related quality of life. The aim of this study was to assess sleep quality and ...quality of life and determine associated factors in patients treated with spondyloarthritides (SpA).MethodsCross-sectional questionnaire-based assessment of sleep behaviour, quality of life, functional impairment and depression (Regensburg Insomnia Scale, WHO Quality of Life questionnaire, Funktionsfragebogen Hannover questionnaire, Beck Depression Inventory II, Patient health questionnaire 9) and retrospective medical chart analysis of a monocentric cohort of 330 patients with SpA (n=168 PsA and n=162 axSpA).Results46.6% of patients with SpA demonstrated abnormal sleep behaviour. Linear regression models showed HLA-B27 positivity, Bath Ankylosing Spondylitis Disease Activity Index, depressive symptoms, functional capacity and disease duration to be predictive of insomnia symptoms in axSpA, respectively, depressive symptoms, female sex and Disease Activity Score 28 in patients with PsA. Patients with unrestful sleep had a significantly reduced health-related quality of life (p<0.001) as well as significantly more depressive symptoms (p<0.001). Satisfaction with health was rated significantly lower (p<0.001), indicating poor sleep as a burden on general well-being.In particular, female patients had a significantly worse sleep quality with a prolonged sleep latency (p=0.009), increased sleep disturbances (p=0.014) and unrestful sleep (p<0.001) as well as a reduced physical and mental health-related quality of life (p=0.015, p<0.001) and more depressive symptoms (p=0.015).ConclusionDespite treatment, many patients with SpA demonstrate abnormal sleep behaviour with symptoms of insomnia and a reduced quality of life with significant differences between male and female patients. An interdisciplinary and holistic approach may be needed to address unmet needs.
Rheumatic diseases with involvement of the central nervous system (RDwCNS) may mimic multiple sclerosis (MS). Inversely, up to 60% of MS-patients have antinuclear autoantibodies (ANAs) and may be ...misdiagnosed as RDwCNS. The detection of antibodies against extractable nuclear antigens (ENA) and oligoclonal bands (OCB) are established valuable diagnostic tools in the differential diagnosis of RDwCNS and MS. The MRZ-reaction (MRZR) is defined by three antibody indices (AIs) against neurotropic viruses and is frequently positive in MS. To investigate the added value of MRZR combined with testing for antibodies against ENAs and OCB detection to distinguish RDwCNS from ANA positive MS.
MRZR was evaluated in RDwCNS (
= 40) and 68 ANA positive MS-patients. Two stringency levels, MRZR-1 and MRZR-2 (at least one respectively two of three AIs positive) were applied. Autoantibody testing included ANA plus ENA and anti-dsDNA antibodies, antiphospholipid antibodies, and anti-neutrophil cytoplasmic antibodies.
Most of the RDwCNS patients (
= 32; 80%) suffered from systemic lupus erythematosus. Within the RDwCNS group 20% had a positive MRZR-1 and 8.5% a positive MRZR-2 compared to 80.9 and 60%, respectively within the MS-group (
< 0.0001 for both comparisons). Oligoclonal bands were found in 28.6% of the RDwCNS patients and 94.3% of the MS-patients (
< 0.0001). Conversely, autoantibodies to specific nuclear antigens or phospholipids were found more frequently in RDwCNS. A positive MRZR in conjunction with the absence of ENA autoantibodies distinguished MS from RDwCNS with high specificity (97.5%).
We suggest combining MRZR, OCBs, and specific autoantibody diagnostics to differentiate RDwCNS from MS.
Objectives
Gastrointestinal manifestations are frequent in patients with common variable immunodeficiency (CVID), and some of the patients present with celiac-like features. Diagnosing celiac disease ...(CD) in CVID however is challenging, as autoantibody detection and histopathology of the small intestine cannot reliably discriminate between classic CD and a celiac-like disease in these individuals. For the development of classic gluten-sensitive CD a certain HLA haplotype involving the loci
DQA1*
and
DQB1*
and encoding two different HLA DQ heterodimers is the prerequisite. We aimed to determine the frequency of these haplotypes in CVID patients with suspected CD. Furthermore, we report on autoimmune manifestations and the lymphocyte phenotype in these patients.
Methods
By retrospective analysis data on gastrointestinal symptoms, diet, concurrent autoimmune diseases, and routine laboratory values were collected. CVID patients were classified according to their B-cell phenotype. Expression of
HLA-DQA1*
and
HLA-DQB1*
alleles were determined by genetic analysis.
Results
Twenty out of 250 CVID patients presented with a clinical phenotype resembling celiac disease. Four (20 %) out of these CVID patients carried the CD-associated HLA DQ2.5 or DQ8 heterodimer, while HLA DQ2.5 was present in 100 % of a CD control cohort. Gluten-free diet (GFD) resulted in a clinical and histological response in two out of four patients with HLA high-risk alleles for CD. The response could not be assessed in the remaining two patients, as these patients did not adhere sufficiently long to GFD. The percentage of autoimmune manifestations other than CD was high (50 %) in CVID patients presenting with a CD-like enteropathy, and most of these patients had an expansion of B-cells with low expression of CD21 (CD21low B-cells).
Conclusions
In CVID patients with suspected celiac disease typing of the HLA loci
DQA1
and
DQB1
can help to identify those that have a genetic susceptibility for CD. In CVID patients with a celiac-like phenotype but negative for CD-associated HLA-DQ markers, an autoimmune enteropathy (AIE) as part of an extended autoimmune dysregulation needs to be considered. This has important implications for further diagnostics and therapy of these patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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