Publications by authors named "Joerg Henes"

46 Publications

Atrioventricular conduction delay in the second trimester measured by fetal magnetocardiography.

J Immunol Res 2014 16;2014:753953. Epub 2014 Jan 16.

Centre for Interdisciplinary Clinical Immunology, Rheumatology and Auto-Inflammatory Diseases and Department of Internal Medicine II (Oncology, Hematology, Immunology, Rheumatology, Pulmonology), University Hospital, 72076 Tuebingen, Germany.

Introduction: Fetal AV block in SSA/Ro pregnancies is generally not seen before 18-week gestation and onset is rare after 28-week gestation. If complete AV block appears, it is believed to be irreversible. The purpose of the study was to evaluate precise electrophysiological AV conduction from 18-week gestation onwards.

Patients And Methods: 21 fetuses of pregnant women with collagen vascular diseases were included in the study group and 59 healthy fetuses served as controls. In addition to fetal echocardiography, fetal magnetocardiography (fMCG) was used to investigate precise electrophysiological fetal cardiac time intervals (fCTIs).

Results: The PR segment (isoelectric segment between the end of the P wave and the start of the QRS complex) was significantly prolonged (P < 0.036 2nd trimester, P < 0.023 3rd trimester) in both trimesters within the study group. In fetuses less than 23-week gestational age, a nearly complete separation was found, where a PR segment of 60 ms or greater completely excluded control fetuses. All other fCTIs did not differ significantly. None of the fetuses progressed to a more advanced heart block.

Conclusion: Slight antibody effects in pregnancy, leading to PR segment prolongation, can already be seen from 18-week gestation onwards by fMCG. Serial fetal Doppler echocardiography and additional fMCG can be useful methods to measure early and precise AV conduction time, to achieve best surveillance for these high-risk pregnancies.
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December 2014

Autologous stem cell transplantation with thiotepa-based conditioning in patients with systemic sclerosis and cardiac manifestations.

Rheumatology (Oxford) 2014 May 22;53(5):919-22. Epub 2014 Jan 22.

University Hospital Tübingen, Department of Internal Medicine II, Otfried-Mueller-Str. 10, D-72076 Tübingen, Germany.

Objective: The aim of this study was to find a new and less cardiotoxic conditioning regimen for high-dose chemotherapy and autologous stem cell transplantation (aSCT) in patients with severe SSc and pre-existing cardiac involvement.

Methods: Six patients with cardiac involvement were treated for SSc with a conditioning regimen including reduced-dose CYC plus the non-cardiotoxic alkylant thiotepa. All patients received an implantable cardioverter defibrillator (ICD) before aSCT. The response at months 6 and 12 was measured according to reduction of the modified Rodnan skin score (mRSS). CT histography was used to monitor pulmonary manifestations, as were echocardiography, N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin for the cardiac involvement. Cardiac events were defined as death or hospitalisation due to heart failure or appropriate discharge of the ICD.

Results: Between December 2008 and May 2012, four male and two female patients with a median age of 41 years received aSCT. The median mRSS significantly decreased from 26.5 to 18 and 17.5 at month 6 and 12, respectively. The total lung volume also significantly improved. Within the median follow-up of 1.6 years (range 1-3.8) two patients experienced a relapse of SSc, which results in a progression-free survival rate of 66.6%. Three patients experienced ICD discharge.

Conclusion: For patients with SSc and cardiac involvement, the use of thiotepa and reduced-dose CYC is feasible and effective. The rate of ICD discharge underlines the need for protection in these endangered patients. This preliminary experience allowed us to use this regimen for our currently recruiting prospective trial (NCT01895244).
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May 2014

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

Ann Rheum Dis 2015 Apr 3;74(4):730-7. Epub 2014 Jan 3.

Department of Dermatology, Cologne University Hospital, Cologne, Germany.

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.
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April 2015

High prevalence of psoriatic arthritis in dermatological patients with psoriasis: a cross-sectional study.

Rheumatol Int 2014 Feb 10;34(2):227-34. Epub 2013 Oct 10.

Centre for Interdisciplinary Clinical Immunology, Rheumatology and Auto-inflammatory Diseases (INDIRA), Tuebingen, Germany,

The exact prevalence of psoriatic arthritis (PsA) among patients with psoriasis is still not conclusive. Data in the literature vary between 5.8 and 30 %. Objective of this study was to gain more information on the prevalence of PsA among patients with psoriasis in Germany. Between 09/2010 and 05/2011, consecutive patients from dermatological private practices and a university hospital with psoriasis were asked to fill out the validated German Psoriatic Arthritis Diagnostic (GEPARD) Questionnaire. Patients who answered ≥4 questions with "yes" were invited to come for a rheumatological check up. Those patients who refused a rheumatological examination were counted as "absence of PsA". Laboratory tests for inflammatory markers as well as the severity of skin manifestations were assessed. The diagnosis of PsA was made according to the CASPAR criteria, and imaging was performed in addition. A total of 404 questionnaires were evaluated; 50.5 % answered ≥4 questions positively; 19.3 % had a history of PsA confirmed by a rheumatologist; and in 10.9 %, PsA or spondyloarthritis was newly diagnosed during the present study. This leads to an overall prevalence of PsA in patients with psoriasis of 30.2 %. The frequency of psoriatic arthritis in the present study is higher than expected from previous studies in Germany. The prevalence is consistent with findings of a large observational survey from Scandinavia. Using the CASPAR criteria and imaging in all patients, certainty of the diagnosis is very high. The GEPARD Questionnaire is a helpful tool to identify people at risk for psoriatic arthritis.
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February 2014

Atrioventricular conduction delay in fetuses exposed to anti-SSA/Ro and anti-SSB/La antibodies: a magnetocardiography study.

Clin Dev Immunol 2012 20;2012:432176. Epub 2012 Dec 20.

Department of Neonatology, University Children's Hospital Tuebingen, 72076 Tuebingen, Germany.

Background: The presence of anti-SSA/Ro and anti-SSB/La antibodies during pregnancy is associated with fetal congenital heart block (CHB), which is primarily diagnosed through fetal echocardiography. Conclusive information about the complete electrophysiology of the fetal cardiac conducting system is still lacking. In addition to echocardiography, fetal magnetocardiography (fMCG) can be used. fMCG is the magnetic analogue of the fetal electrocardiogram (ECG).

Patients And Methods: Forty-eight pregnant women were enrolled in an observational study; 16 of them tested positive for anti-SSA/Ro and anti-SSB/La antibodies. In addition to routine fetal echocardiography, fMCG was used. Fetal cardiac time intervals (fCTIs) were extracted from the magnetic recordings by predefined procedures. ECGs in the neonates of the study group were performed within the first month after delivery.

Results: The PQ segment of the fCTI was significantly prolonged in the study group (P = 0.007), representing a delay of the electrical impulse in the atrioventricular (AV) node. Other fCTIs were within normal range. None of the anti-SSA/Ro and/or anti-SSB/La fetuses progressed to a more advanced heart block during pregnancy or after birth.

Conclusion: The study identified a low-risk population within antibody positive mothers, where PQ segment prolongation is associated with a lack of progression of the disease.
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August 2013

Enteric-coated mycophenolate sodium for progressive systemic sclerosis--a prospective open-label study with CT histography for monitoring of pulmonary fibrosis.

Clin Rheumatol 2013 May 10;32(5):673-8. Epub 2013 Jan 10.

Centre for Interdisciplinary Clinical Immunology, Rheumatology and Auto-inflammatory Diseases--INDIRA and Department of Internal Medicine II (Hematology, Oncology, Immunology, Rheumatology, Pulmology), University Hospital, Otfried-Mueller-Str. 10, 72076 Tuebingen, Germany.

The purpose of this study was to assess the impact of enteric-coated mycophenolate sodium (EC-MPS) on skin and pulmonary manifestations of patients with progressive systemic sclerosis (Ssc). A prospective, open-label single-centre trial with EC-MPS 2 × 720 mg/day over 12 months and a long-term follow-up of 50 months were conducted. Modified Rodnan skin score (mRSS) was used to assess the skin and pulmonary function tests to assess the pulmonary involvement. In order to quantify the extent of alveolitis/fibrosis via densitometry, the high attenuation value, median lung density and percentiles of lung tissue densities were obtained by high-resolution computed tomography. Eleven patients were included. Three patients had to stop medication before month 6 (2× side effects, 1× progression). For the remaining eight patients, the median mRSS was non-significantly reduced from 13.5 at baseline to 11 at month 12. According to the CT histography, median lung density and high attenuation values remained stable. However, the course of percentiles -200 to -300 and particularly -300 to -400 Hounsfield units slightly increased in seven of eight patients after 12 months, suggesting worsening of pulmonary involvement. Accordingly, median diffusing capacity for carbon monoxide showed a tendency to decline (75.1 % vs. 70.2) while forced vital capacity non-significantly improved (78.0 vs. 85.5 %) during the study. Four patients are still on EC-MPS without clinical signs of progression after 50 months follow-up. EC-MPS showed non-significant improvement of the skin. Pulmonary fibrosis remained stable with only a slight tendency towards progression which might be ascribed to the medication as well as the natural course of the disease. CT histography appears to be a sensitive method for the detection of progression of pulmonary fibrosis and therefore should be considered for further studies in Ssc.
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May 2013

Reduced pretreatment ovarian reserve in premenopausal female patients with Hodgkin lymphoma or non-Hodgkin-lymphoma--evaluation by using antimüllerian hormone and retrieved oocytes.

Fertil Steril 2012 Jul 16;98(1):141-4. Epub 2012 May 16.

University Women's Hospital, Department of Gynaecological Endocrinology and Reproductive Medicine, Tübingen, Germany.

Objective: To study whether the ovarian reserve in female lymphoma patients is already reduced before the start of chemotherapy.

Design: Age-matched control study.

Setting: Women's university hospital.

Patient(s): Female patients aged <40 years with the initial diagnosis of lymphoma (study group) were compared with age-matched healthy volunteers (control group). Eighty-four female patients with breast cancer and 64 patients with lymphoma who underwent ovarian hormonal stimulation as a fertility-preserving method before the start of chemotherapy.

Intervention(s): Measurement of antimüllerian-hormone (AMH) levels. Ovarian hormonal stimulation to retrieve oocytes.

Main Outcome Measure(s): AMH levels of the lymphoma patients and the healthy volunteers were compared. Numbers of retrieved oocytes after hormonal stimulation in patients with breast cancer and those with lymphoma were compared.

Result(s): Female lymphoma patients have significantly lower AMH levels than healthy age-matched controls: mean value of AMH was 2.06 ng/mL in the study group versus 3.20 ng/mL in the control group. Analysis of the stimulation results showed that in significantly younger patients with lymphoma, significantly fewer oocytes could be retrieved in comparison to those with breast cancer.

Conclusion(s): Ovarian reserve is reduced in female patients affected by lymphoma even before the start of chemotherapy. Proper counseling and implementation of fertility-preserving methods is highly recommended.
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July 2012

Fertility preservation in women with vasculitis: experiences from the FertiPROTEKT network.

Clin Exp Rheumatol 2012 Jan-Feb;30(1 Suppl 70):S53-6. Epub 2012 May 10.

Centre for Interdisciplinary Clinical Immunology, Rheumatology and Autoimmune Diseases - INDRA and Department of Internal Medicine II (Oncology, Haematology, Immunology, Rheumatology, Pulmonology), University of Tuebingen, Germany.

Objectives: Fertility preservation is not only important for malignant diseases but should also be offered to patients with autoimmune diseases (AID) like vasculitides, prior to cyclophosphamide therapy. No recommendations are available for patients with AID.

Methods: Analysis from the Fertiprotekt registry of all female patients with age <40 and the diagnosis of a vasculitis. The number of counselled patients, their diagnosis and age, the number of children before the start of therapy as well as the fertility preservation treatment chosen were evaluated.

Results: From January 2007 to November 2011, 47 patients with the diagnosis AID were counselled at 17 of the 69 Fertiprotekt centres. 80.9% decided for at least one of the offered preservation methods. Ovarian cryopreservation was performed in 6 patients, 36 patients opted for GnRH-analogue treatment. Two patients decided for a stimulation therapy for cryopreservation of oocytes.

Conclusions: Regarding the experiences from the registry and the literature gonadotropin releasing hormone analogues are evaluated best and recommended to most of the patients with AID. Cryoconservation of ovarian tissue is a promising option. Stimulation for oocyte cryopreservation can be offered to patients with vasculitis. A combination of the methods might have the biggest preservative effect.
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August 2012

Optimization of autologous stem cell transplantation for systemic sclerosis -- a single-center longterm experience in 26 patients with severe organ manifestations.

J Rheumatol 2012 Feb 15;39(2):269-75. Epub 2012 Jan 15.

Centre for Interdisciplinary Clinical Immunology, Rheumatology and Auto-inflammatory Diseases and Department of Internal Medicine II, University Hospital Tuebingen, Tuebingen, Germany.

Objective: Autologous stem cell transplantation (aSCT) for systemic sclerosis (SSc) has been shown to be effective in recent reports. This aggressive approach and the disease itself are associated with a high mortality. We report our experiences in 26 consecutive patients.

Methods: Between 1997 and 2009, 26 patients were scheduled for aSCT. Our standard transplant regimen consists of cyclophosphamide (CYC) and granulocyte colony-stimulating factor (GCSF) for mobilization and CYC plus antithymocyte globulin for conditioning before the retransfusion of CD34 selected stem cells. The major outcome variable was the response to treatment [reduction of modified Rodnan skin score (mRSS) by 25%] at Month 6. Secondary endpoints were the transplant-related mortality and the progression-free survival.

Results: Significant skin and lung function improvement of the mRSS was achieved in 78.3% of patients at Month 6. The overall response rate was 91%, as some patients improved even after Month 6. Three patients died between mobilization and conditioning treatment, 2 due to severe disease progression and 1 whose death was considered treatment-related (i.e., GCSF or CYC toxicity). Depending on definitions, transplant-related mortality was 4% and treatment-related mortality 11%. Seven patients experienced a relapse during the 4.4 years of followup. The progression-free survival was 74%. Four patients died during followup and the most frequent causes of death were pulmonary and cardiac complications of SSc.

Conclusion: aSCT led to significant improvement in most patients with SSc. The procedure requires further optimization; hence we are modifying our screening and treatment strategy. To minimize infectious complications, CYC for mobilization and GCSF were reduced. We intensified our screening for cardiac involvement and modified our conditioning regimen in case of cardiac involvement.
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February 2012

Safety and clinical outcomes of rituximab therapy in patients with different autoimmune diseases: experience from a national registry (GRAID).

Arthritis Res Ther 2011 May 13;13(3):R75. Epub 2011 May 13.

Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Klinikstr 6-8, 97070 Würzburg, Germany.

Introduction: Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard-of-care. The objective of this study was to evaluate the safety and clinical outcomes of rituximab in several standard-of-care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin's lymphoma in a real-life clinical setting.

Methods: Patients who received rituximab having shown an inadequate response to standard-of-care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune Diseases. The main outcome measures were safety and clinical response, as judged at the discretion of the investigators.

Results: A total of 370 patients (299 patient-years) with various autoimmune diseases (23.0% with systemic lupus erythematosus, 15.7% antineutrophil cytoplasmic antibody-associated granulomatous vasculitides, 15.1% multiple sclerosis and 10.0% pemphigus) from 42 centres received a mean dose of 2,440 mg of rituximab over a median (range) of 194 (180 to 1,407) days. The overall rate of serious infections was 5.3 per 100 patient-years during rituximab therapy. Opportunistic infections were infrequent across the whole study population, and mostly occurred in patients with systemic lupus erythematosus. There were 11 deaths (3.0% of patients) after rituximab treatment (mean 11.6 months after first infusion, range 0.8 to 31.3 months), with most of the deaths caused by infections. Overall (n = 293), 13.3% of patients showed no response, 45.1% showed a partial response and 41.6% showed a complete response. Responses were also reflected by reduced use of glucocorticoids and various immunosuppressives during rituximab therapy and follow-up compared with before rituximab. Rituximab generally had a positive effect on patient well-being (physician's visual analogue scale; mean improvement from baseline of 12.1 mm).

Conclusions: Data from this registry indicate that rituximab is a commonly employed, well-tolerated therapy with potential beneficial effects in standard of care-refractory autoimmune diseases, and support the results from other open-label, uncontrolled studies.
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May 2011

Assessment of synovitis in erosive osteoarthritis of the hand using DCE-MRI and comparison with that in its major mimic, the psoriatic arthritis.

Acad Radiol 2011 Jul 21;18(7):804-9. Epub 2011 Mar 21.

Department of Diagnostic and Interventional Radiology, University Hospital Tuebingen, Hoppe-Seyler-Str. 3, 72076 Tuebingen, Germany.

Rationale And Objectives: To investigate the diagnostic value of high-resolution dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for assessment of synovitis in erosive osteoarthritis (EOA) of the hand and compare the results with those acquired in its potential mimic, the psoriatic arthritis (PsA).

Materials And Methods: Twenty-six patients (17 PsA, 9 EOA) were examined at 3 T. The time course of synovial contrast uptake was measured by ROI analysis using a three-dimensional encoded spoiled gradient-echo sequence. Characteristic parameters of synovial uptake curves (time to peak [TTP], peak value, mean transit time [MTT], area under the curve [AUC], and maximum upslope) of PsA and EOA patients were compared using gamma variate analysis and calculation of the late relative enhancement 15 minutes after contrast administration.

Results: Enhancement curves of PsA and EOA patients paralleled each other at comparable levels in the early phase after contrast injection without statistical difference in the following calculated characteristic curve parameters: TTP, peak value, MTT, AUC, and maximum upslope. However, significant difference was found in the late relative enhancement 15 minutes after contrast injection (P = .0275) with higher values in EOA patients.

Conclusion: DCE-MRI provides assessment of synovitis in both patients with EOA and PsA. Interestingly, synovial enhancement characteristics were comparable for the most part in these two disorders. However, late enhancement might help in differentiation which is essential for guiding therapy.
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July 2011

Cyclophosphamide for large vessel vasculitis: assessment of response by PET/CT.

Clin Exp Rheumatol 2011 Jan-Feb;29(1 Suppl 64):S43-8. Epub 2011 May 11.

Department of Internal Medicine II, University Hospital Tuebingen, Germany.

Objectives: Glucocorticosteroids (GC) are the standard treatment for large vessel vasculitis, but some patients are refractory. Cyclophosphamide (CYC) has been shown to be effective in autoimmune diseases.

Methods: The study consisted of a retrospective analysis of 10 patients with active large vessel arteritis who received pulse CYC after failure of GC or because of organ threatening stenosis. CYC pulse therapy was started with a dose of 750mg/m² body surface every 3 weeks and increased if necessary. Clinical response was assessed by the Birmingham Vasculitis Activity Score (BVAS), the C-reactive protein and the erythrocyte sedimentation rate (ESR). PET/CT was performed at baseline and during treatment to determine disease activity.

Results: The median BVAS at the time of the initial PET/CT was 6.5 (5-13). The median ESR was 42mm/h (6-94mm/h), and the medium CRP was 4.6mg/dl (0.18-11.8mg/dl). All but one patient experienced a complete clinical remission during CYC treatment after a median of 10 cycles. PET/CT confirmed the efficacy of the treatment by normalisation of FDG uptake during therapy. One patient with persisting inflammation was lost to follow-up. One patient experienced a relapse after 21 months. The remaining 8 patients are still in remission with low-dose GC and a maintenance therapy (azathioprine, methotrexate or mycophenolate) after a median follow-up of 45 months.

Conclusions: Pulse cyclophosphamide is effective in patients with large vessel vasculitis resistant to glucocorticosteroids. The high rate of sustained response in our patients suggests that treatment decisions based on clinical parameters combined with PET/CT may have a beneficial effect on the clinical outcome.
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August 2011

Rituximab and concomitant leflunomide for the treatment of rheumatoid arthritis.

Rheumatol Int 2010 Mar 12;30(5):709-12. Epub 2009 Dec 12.

Department of Internal Medicine II (Oncology, Haematology, Immunology, Rheumatology, Pulmology), University Hospital Tuebingen, Otfried-Mueller-Str. 10, 72076, Tuebingen, Germany.

Rituximab has only been approved in combination with methotrexate for the treatment of rheumatoid arthritis. As some patients have intolerance to methotrexate, alternative co-therapies are needed. This method involved retrospective analysis of ten patients treated with a combination of rituximab and leflunomide. Primary outcome measures were the DAS28 response at month 6 and the time to relapse. The median initial DAS 28 of 5.7 (3.2-7.2) was reduced to 3.5 (1.9-6.1) at month 6. 70% of the patients achieved a good or moderate response, whereas 30% showed no response. Two patients had to stop leflunomide due to adverse effects. Two patients had to reduce the leflunomide dose to 10 mg/day. 5/8 patients experienced a relapse after a median of 10 (6-30) months and were successfully re-treated with rituximab. This small case series suggests that leflunomide might offer an alternative DMARD combination option for the treatment of RA with rituximab.
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March 2010

Anaphylactic shock in a young woman with abnormal liver scans.

Liver Int 2009 Feb 26;29(2):265. Epub 2008 Sep 26.

Department of Internal Medicine II (Oncology, Haematology, Immunology, Rheumatology, Pulmology), University Hospital Tuebingen, Tuebingen, Germany.

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February 2009