Disease progression in systemic sclerosis-overlap syndrome is significantly different from limited and diffuse cutaneous systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc)-overlap syndromes are a very heterogeneous and remarkable subgroup of SSc-patients, who present at least two connective tissue diseases (CTD) at the same time, usually with a specific autoantibody status. OBJECTIVES: To determine whether patients, classified as overlap syndromes, show a disease course different from patients with limited SSc (lcSSc) or diffuse cutaneous SSc (dcSSc). METHODS: The data of 3240 prospectively included patients, registered in the database of the German Network for Systemic Scleroderma and followed between 2003 and 2013, were analysed. RESULTS: Among 3240 registered patients, 10% were diagnosed as SSc-overlap syndrome. Of these, 82.5% were female. SSc-overlap patients had a mean age of 48±1.2 years and carried significantly more often 'other antibodies' (68.0%; p<0.0001), including anti-U1RNP, -PmScl, -Ro, -La, as well as anti-Jo-1 and -Ku antibodies. These patients developed musculoskeletal involvement earlier and more frequently (62.5%) than patients diagnosed as lcSSc (32.2%) or dcSSc (43.3%) (p<0.0001). The onset of lung fibrosis and heart involvement in SSc-overlap patients was significantly earlier than in patients with lcSSc and occurred later than in patients with dcSSc. Oesophagus, kidney and PH progression was similar to lcSSc patients, whereas dcSSc patients had a significantly earlier onset. CONCLUSIONS: These data support the concept that SSc-overlap syndromes should be regarded as a separate SSc subset, distinct from lcSSc and dcSSc, due to a different progression of the disease, different proportional distribution of specific autoantibodies, and of different organ involvement.

Giant cell arteritis: diagnostic accuracy of MR imaging of superficial cranial arteries in initial diagnosis-results from a multicenter trial.

PURPOSE: To assess the diagnostic accuracy of contrast material-enhanced magnetic resonance (MR) imaging of superficial cranial arteries in the initial diagnosis of giant cell arteritis ( GCA giant cell arteritis ). MATERIALS AND METHODS: Following institutional review board approval and informed consent, 185 patients suspected of having GCA giant cell arteritis were included in a prospective three-university medical center trial. GCA giant cell arteritis was diagnosed or excluded clinically in all patients (reference standard [final clinical diagnosis]). In 53.0% of patients (98 of 185), temporal artery biopsy ( TAB temporal artery biopsy ) was performed (diagnostic standard [ TAB temporal artery biopsy ]). Two observers independently evaluated contrast-enhanced T1-weighted MR images of superficial cranial arteries by using a four-point scale. Diagnostic accuracy, involvement pattern, and systemic corticosteroid ( sCS systemic corticosteroid ) therapy effects were assessed in comparison with the reference standard (total study cohort) and separately in comparison with the diagnostic standard TAB temporal artery biopsy ( TAB temporal artery biopsy subcohort). Statistical analysis included diagnostic accuracy parameters, interobserver agreement, and receiver operating characteristic analysis. RESULTS: Sensitivity of MR imaging was 78.4% and specificity was 90.4% for the total study cohort, and sensitivity was 88.7% and specificity was 75.0% for the TAB temporal artery biopsy subcohort (first observer). Diagnostic accuracy was comparable for both observers, with good interobserver agreement ( TAB temporal artery biopsy subcohort, κ = 0.718; total study cohort, κ = 0.676). MR imaging scores were significantly higher in patients with GCA giant cell arteritis -positive results than in patients with GCA giant cell arteritis -negative results ( TAB temporal artery biopsy subcohort and total study cohort, P < .001). Diagnostic accuracy of MR imaging was high in patients without and with sCS systemic corticosteroid therapy for 5 days or fewer (area under the curve, ≥0.9) and was decreased in patients receiving sCS systemic corticosteroid therapy for 6-14 days. In 56.5% of patients with TAB temporal artery biopsy -positive results (35 of 62), MR imaging displayed symmetrical and simultaneous inflammation of arterial segments. CONCLUSION: MR imaging of superficial cranial arteries is accurate in the initial diagnosis of GCA giant cell arteritis . Sensitivity probably decreases after more than 5 days of sCS systemic corticosteroid therapy; thus, imaging should not be delayed. Clinical trial registration no. DRKS00000594 .

Evaluation of a 32-channel versus a 12-channel head coil for high-resolution post-contrast MRI in giant cell arteritis (GCA) at 3T.

The aim of this study was to evaluate the diagnostic value of a 32-channel head coil for the characterization of mural inflammation patterns in the superficial cranial arteries in patients with giant cell arteritis (GCA) compared to a standard 12-channel coil at 3T MRI. 55 patients with suspected GCA underwent high resolution T1-weighted post-contrast MRI at 3T to detect inflammation related vessel wall enhancement using both coils. To account for different time delays between contrast agent injection and sequence acquisition, the patients were divided into two cohorts: 27 patients were examined with the 32-channel coil first and 28 patients with the 12-channel coil first. Images were evaluated by two blinded readers with regard to image quality, artifact level and arteries' inflammation according to a standardized ranking scale; furthermore signal-to-noise ratio (SNR) measurements were performed at three locations. Identification of arteries' inflammation was achieved with both coils with excellent inter-observer agreement (κ=0.89 for 12-channel and κ=0.96 for 32-channel coil). Regarding image grading, the inter-observer variability was moderate for the 12-channel (κ=0.5) and substantial for the 32-channel coil (κ=0.63). Significantly higher SNR and improved image quality (p<0.01) were obtained with the 32-channel coil in either coil order. Image quality for depiction of the superficial cranial arteries was superior for the 32-channel coil. For standardized GCA diagnosis, the 12-channel coil was sufficient.

MRI displays involvement of the temporalis muscle and the deep temporal artery in patients with giant cell arteritis.

PURPOSE: To assess deep temporal artery and temporalis muscle involvement in patients with giant cell arteritis (GCA). MATERIAL AND METHODS: Ninety-nine patients who received magnetic resonance imaging (MRI) and superficial temporal artery biopsy (TAB) were included in this study. Patients with positive TAB (n = 61) were defined as GCA patients, those with negative TAB (n = 38) as the GCA-negative reference group. Contrast-enhanced T1w-images were acquired utilizing 1.5 T and 3 T MRI. Two radiologists assessed the images. Mural contrast-hyperenhancement and wall thickening of the deep temporal artery and hyperenhancement of the muscle were defined as inflammation. MRI results were correlated with jaw claudication in 70 patients. RESULTS: The two observers found temporalis muscle involvement in 19.7 % (n = 12) and 21.3 % (n = 13) of GCA patients. It occurred bilaterally in 100 %. Specificities were 92/97 % and sensitivities were 20/21 %. Deep temporal artery involvement was found in 34.4 % (n = 21) and 49.2 % (n = 30) and occurred bilaterally in 80/90.5 %. Specificities were 84/95 % and sensitivities were 34/49 %. Both structures were affected simultaneously in 18/21.3 %. Jaw claudication correlated moderately with inflammation of the temporalis muscle (r = 0.31; p < 0.05) and the deep temporal artery (r = 0.38; p = 0.01). CONCLUSION: MRI visualizes changes in the temporalis muscle and the deep temporal artery in GCA. Moderate correlation of clinical symptoms with MRI results was observed. KEY POINTS: • Approximately 20 % of GCA patients presented with temporalis muscle inflammation. • A total of 34-49 % of GCA patients presented with vasculitis of the deep temporal artery. • In approximately 20 % of GCA patients, both structures were simultaneously involved. • Involvement of both structures correlated moderately with presence of jaw claudication. • MRI is a suitable tool for the assessment of vasculitis and muscle inflammation.

Self-reported symptoms of pain and depression in primary fibromyalgia syndrome and rheumatoid arthritis.

BACKGROUND: Primary fibromyalgia syndrome (FMS) is associated with substantial psychiatric comorbidity. The aim of the present study was to investigate the interrelationship between self-reported symptoms of depression and pain in FMS compared with rheumatoid arthritis (RA). METHODS: In a cross-sectional study, 100 patients with FMS and 50 patients with RA were compared with regard to depression and psychopathology using the Symptom Check List (SCL-27). Group comparisons were calculated by parametric and non-parametric tests. The association between pain intensity and depression was determined by correlation analyses and multivariate statistical procedures (CATREG). RESULTS: Pain intensity was significantly higher in FMS compared with RA. FMS patients also scored significantly higher on all subscales of the SCL-27 including the depression scale and the General Symptom Index (GSI) (P < 0.001). These group differences remained stable even after correcting for pain intensity. Correlation analyses revealed an association between pain intensity and depression in FMS but not in RA (R = 0.419, P < 0.001). CONCLUSION: FMS patients in tertiary referral centers suffer from higher levels of pain intensity than RA patients. Depression predicts levels of pain in FMS but not in RA and is therefore an important target of intervention.

Effects of early corticosteroid treatment on magnetic resonance imaging and ultrasonography findings in giant cell arteritis.

OBJECTIVE: To compare the impact of initial corticosteroid treatment on high-resolution MRI and colour-coded duplex sonography (CCDS) findings in patients with GCA (temporal). METHODS: Sensitivity and specificity of CCDS and high-resolution contrast-enhanced MRI studies of 59 patients with suspected GCA were retrospectively analysed. Patients were grouped according to the duration of steroid treatment before imaging: 0-1 day, 2-4 days and >4 days. In 41 patients, imaging results were compared with findings of temporal artery biopsy (TAB). RESULTS: Sixty-one per cent (36/59) of patients were diagnosed with GCA. TAB findings were positive in 59% (24/41). The compared results of TAB sensitivity of CCDS and MRI under steroid treatment of 0-1 day were 92% and 90%, 2-4 days 80% and 78% and >4 days 50% and 80%, respectively. The compared results of the final clinical diagnosis sensitivity of CCDS and MRI under steroid treatment of 0-1 day was 88% and 85%, 2-4 days 50% and 64% and >4 days 50% and 56%, respectively. CONCLUSION: Sensitivity of a first-time CCDS or an MRI for detection of GCA rapidly decreases under corticosteroid treatment. Therefore imaging of patients with suspected GCA should be performed as soon as possible, preferably within the first days of treatment.

Involvement of the ophthalmic artery in giant cell arteritis visualized by 3T MRI.

OBJECTIVES: To retrospectively analyse inflammatory involvement of the ophthalmic arteries in patients with GCA utilizing high-resolution MRI. METHODS: A cohort of 50 patients with GCA who had been examined by 1.5 or 3T high-field MRI was analysed retrospectively in a consensus reading for possible involvement of the ophthalmic arteries. In 43 patients, entire orbits were within the field of view. In all cases, the superficial cranial arteries displayed mural inflammation in post-contrast T1-weighted spin-echo (SE) images. MRI results were compared with ophthalmological findings, subjective visual symptoms and laboratory values, i.e. CRP and ESR. RESULTS: We observed mural contrast enhancement of the ophthalmic arteries in 20/43 patients (46%). Bilateral involvement was seen in 14, unilateral enhancement in six cases. Fifteen patients had ophthalmic vascular diseases: nine had anterior ischaemic optic neuropathy (AION), one posterior ischaemic optic neuropathy (PION), four revealed central retinal artery occlusion (CRAO) and one patient presented with narrowing of the retinal arteries. Funduscopy detected no arteritis-related changes in 22 cases. Of those patients who were MRI positive, seven had ophthalmological disease. Twenty-six patients complained of visual symptoms including amaurosis fugax, vision loss, diplopia or eye pain. CONCLUSIONS: High-resolution MRI detects mural contrast enhancement consistent with inflammatory changes in the superficial cranial and extracranial arteries and additionally in the ophthalmic arteries. This provides insight in vasculitic orbital involvement during one single investigation.

No association between systemic sclerosis and C77G polymorphism in the human PTPRC (CD45) gene.

OBJECTIVE: The functional variant C77G (rs17612648) of PTPRC (CD45) was described to confer risk for systemic sclerosis (SSc) in German Caucasians. We analyzed this association in an independent, larger German cohort. METHODS: We genotyped 171 cases and 179 controls. Cases were subgrouped according to sex, autoantibody profiles, or clinical subsets. RESULTS: No association of SSc with C77G was detected in the whole dataset, in subgroups, or in combined analyses with a previous study. CONCLUSION: The results do not confirm PTPRC C77G as a general and independent risk factor for development of SSc.

Multiple chemical sensitivity syndrome (MCS)--suggestions for an extension of the U.S. MCS-case definition.

PURPOSE: To validate and extend the US case definition for the Multiple Chemical Sensitivity Syndrome (MCS) from 1999 by a systematic literature-review. DATA SOURCE: MEDLINE-research from 1997 to August 2003, research in the Cochrane-Library in August 2003, earlier reviews since 1997. STUDY SELECTION: Headings and abstracts were screened by one reviewer. All references dealing with multiple chemical sensitivities (MCS) which covered topics of interest such as symptom-profiles, differential diagnostic procedures, etc. were included in the analysis. DATA EXTRACTION AND SYNTHESIS: Topic-specific data extraction and synthesis was done by one reviewer. Data interpretation was discussed by all other authors. RESULTS: Out of 1429 references 36 publications proved to be suitable for the review. The results can be summarized as follows: exposure-related symptoms associated with self-reported multiple chemical sensitivities can be divided into non-specific complaints of the central nervous system--CNS (main characteristics) and functional disturbances in other organ systems (optional complaints). There is a significant overlap of MCS, CFS and fibromyalgie. At present no standards for a diagnostic procedure based on the criteria outlined above are existing CONCLUSIONS: MCS should only be diagnosed in patients who are mainly suffering from exposure-related non-specific complaints of the Central nervous system. The suggested diagnostic procedure follows the guidelines for CFS which are extended by diagnostic clarification of functional disturbances in other organ systems.

Human IgG1/IgG3 cryoglobulin suggesting lack of allelic exclusion.

Immunoglobulins undergoing cold-dependent precipitation are known as cryoglobulins. A type I cryoglobulin after Brouet et al. from serum of a patient with severe cutaneous vasculitis and membranoproliferative glomerulonephritis was purified by reversible temperature-dependent precipitation and analyzed using FPLC, Western blotting and peptide sequencing. The isolated cryoglobulin consisted of a single complex of a molecular weight of above 210kDa observed under non-reducing conditions in SDS-polyacrylamide gel electrophoresis (PAGE). Under reducing conditions, this complex resolved into three bands, two of which were reminiscent of Ig heavy (HC) chains and one of Ig-light chains (LC). The FPLC-purified type I cryoglobulin showed reversible precipitation analyzed by spectrophotometry. Delineation of the peptides involved in complex formation by immunoblot analysis and peptide sequencing revealed IgG3-V(H)4/Igkappa-VkappaIII/JkappaII and IgG1/V(H)3 molecules with evidence of somatic mutation. Coomassie blue-staining suggested that molar amounts of the IgG3-heavy chain were much higher than that of the IgG1-heavy chain. Treatment with SDS and boiling did not disrupt the unusually high molecular weight Ig complex. Pre-treatment of the cryoglobulin in 6M guadinium hydrochloride followed by gel filtration chromatography suggested covalent association of the IgG3, IgG1 and Igkappa molecules. Therefore, it might be that the cryoglobulin was produced by a single plasma B cell clone which passed immunological check-points in terms of B cell selection in the bone marrow in the absence of allelic exclusion, class switching and affinity maturation by somatic mutation.

[Ocular syphilis]. / Augenbefunde bei Syphilis.

BACKGROUND: Syphilis has distinctly increased in the last decades. It is necessary to know the different eye changes in syphilis. PATIENTS: In four patients, between 34 and 71 years of age, typical as well as unusual syphilitic eye changes were found. In three patients diagnosis was made due to the inflammatory eye changes. RESULTS: An iritis was found in two patients (62 and 34 years old). In addition, the 62-year-old patient showed the unusual fundus picture of both vasculitis and neuroretinitis, with macular exudates and swelling of the optic disk. A venous occlusion, a rare sign in syphilis, was diagnosed in a 55-year-old patient. A 71-year-old patient revealed the characteristic finding of a placoid chorioretinitis. All four patients showed a swelling of the optic disk. CONCLUSION: Syphilis should be suspected even in older patients with an uncertain origin of uveitis, optic nerve disease, pupillary changes, or eye motility disturbances giving rise to carry out serologic tests in patients with the suspected diagnosis.