Titanium wear from magnetically controlled growing rods (MCGRs) for the treatment of spinal deformities in children.

Magnetically controlled growing rods (MCGRs) are an effective treatment method for early-onset scoliosis (EOS). In recent years, increasing titanium wear was observed in tissue adjacent to implants and in blood samples of these patients. This study aims to investigate the potential correlation between amount of metal loss and titanium levels in blood during MCGR treatment as well as influencing factors for metal wear. In total, 44 MCGRs (n = 23 patients) were retrieved after an average of 2.6 years of implantation and analyzed using a tactile measurement instrument and subsequent metal loss calculation. Titanium plasma levels (n = 23) were obtained using inductively coupled plasma-mass spectrometry (ICP-MS). The correlation of both parameters as well as influencing factors were analyzed. Titanium abrasion on MCGRs was observed in the majority of implants. There was no correlation of metal implant wear or titanium plasma values to the duration of MCGR implantation time, number of external lengthening procedures, patient's ambulatory status, gender, weight or height. Material loss on the MCGRs showed a positive correlation to titanium blood plasma values. The present study is one of the first studies to analyze retrieved MCGRs using high-precision metrological techniques and compare these results with ICP-MS analyses determining blood titanium values.

[Fever in systemic lupus erythematosus: disease exacerbation or infection?] / Fieber bei systemischem Lupus erythematodes: Krankheitsschub oder Infektion?

The differential diagnosis of fever, especially in the context of autoimmune diseases is broad. Accordingly, the spectrum of diagnostic procedures is extensive and the therapeutic consequences are partly contradictory. Fever is basically the manifestation of an increased cell proliferation, such as classically seen in tumors, infections or autoimmune inflammation. Systemic lupus erythematosus (SLE) is one of the most multifaceted rheumatological diseases. Fever is one component of the new classification criteria which help to classify and possibly diagnose SLE. The differential work-up of fever is a special challenge for clinicians particularly in the context of the initial diagnosis of SLE or another autoimmune disease and also in the course of the disease in patients with autoimmune diseases. Based on a case report this article discusses differential diagnostic considerations and proposes a concrete differential diagnostic procedure. The patient's history is highlighted as an extremely important source of relevant information. Without claiming completeness various factors are listed, which help to differentiate fever as a consequence of SLE activity versus fever as a consequence of an infection.

[Surgical "no-touch" distraction technique to correct pediatric scoliosis]. / Operative "No-touch"-Techniken zur Korrektur kindlicher Skoliosen.

OBJECTIVE: Reduction and retention of the scoliotic curve in children with progressive spinal deformities. INDICATIONS: Progressive neuromyopathic scoliosis which cannot be controlled conservatively (especially by walking disability), and/or development of a thorax insufficiency syndrome (TIS). CONTRAINDICATIONS: Insufficient soft tissue coverage; body weight < 11.4 kg; body mass index (BMI) > 25 or >50 kg; missing osseous anchoring structures (ribs); adult skeleton (usually age < 12 years at surgery); severe spasticity. SURGICAL TECHNIQUE: Indirect correction and distraction of the spinal deformity by two extendable, paravertebral telescopic implants, anchored to the cranial ribs and the iliac crest; the spine is not compromised surgically. POSTOPERATIVE MANAGEMENT: Early functional therapy, no brace; multiple surgical (VEPTR®-system) or externally (magnetically controlled rods) controlled extensions per year. RESULTS: The surgical paravertebral "no-touch" technique for spine correction is particularly suitable for children with neuromyopathic scoliosis with a body weight > 11.4 kg. Our prospective group of children (n = 45), was treated with a combination of the classic vertical expandable prosthetic titanium rib (VEPTR®) anchored to the ribs and iliac crest combined with a magnetically controlled telescopic implant (MAGEC®). The primary correction of >50% was achieved, while progression was effectively prevented over years. In 495 outpatient lengthening procedures, the rate of implant-associated complications requiring surgery was 3.7%. Of the 45 children, 13 (29%) underwent surgical revision. With the proposed surgical "no-touch" technique for scoliosis correction of pediatric neuromyopathic deformities, an effective reduction of the scoliotic curve can be achieved and maintained. Advantages of the method are a partial retention of spinal flexibility and a reduction of spinal ossifications, which facilitates dorsal spondylodesis as the final treatment.

[Improvement of prognosis by timely treatment : Requirement: initial presentation within 6 weeks]. / Verbesserung der Prognose durch frühzeitige Therapie : Forderung: Erstvorstellung in 6 Wochen.

Rheumatoid arthritis (RA) is one of the most frequent chronic inflammatory rheumatic diseases and when untreated leads to chronic tissue destruction and increased mortality. Due to innovative systemic treatment strategies established over the last 20-25 years, the prognosis has considerably improved in terms of disease and socioeconomic burdens, symptoms, long-term prognosis, ability to work and mortality; however, as a rule a prerequisite is long-term and continuous treatment. A medicinal cure of RA is still not in view. For many patients this means the long-term use of very expensive medications. In addition to hemato-oncology, rheumatology has become the second most expensive discipline in Germany in terms of cost per patient. Convincing data from many studies imply that an early start of treatment within the first few weeks after clinical onset of symptoms improves the prognosis, reduces the necessity for expensive drugs and thereby considerably decreases medical costs. This results in the requirement that every patient with symptoms of arthritis must be seen by a rheumatologist within the first 6 weeks following initial manifestation of the disease. Such an improvement in treatment can only be achieved in Germany if the numbers of rheumatologists and trained healthcare professionals in practices such as clinics are considerably increased. This is not only in the interests of patients but also in the interests of the health insurance companies because the investment in the healthcare infrastructure with internistic rheumatologists will result in substantial economic benefits for the cost bearer. It must be the common task of all players in healthcare policy, cost bearers and internistic rheumatologists to provide optimal conditions in medical as well as economical terms.

Rituximab in routine care of severe active rheumatoid arthritis : A prospective, non-interventional study in Germany.

OBJECTIVE: To assess safety, effectiveness and onset of effect of rituximab (RTX) in routine clinical treatment of severe, active rheumatoid arthritis (RA). METHODS: Prospective, multi-centre, non-interventional study in rheumatological outpatient clinics or private practices in Germany. RTX-naïve adult patients were to receive RTX according to marketing authorisation and at their physician's discretion. Also according to their physician's discretion, patients could receive a second cycle of RTX (re-treatment = treatment continuation). Major outcome was the change in Disease Activity Score based on 28-joints count and erythrocyte sedimentation rate (DAS28-ESR) over 24 weeks and during 6 months of re-treatment. RESULTS: Overall, 1653 patients received at least one cycle RTX; 99.2% of these had received disease-modifying antirheumatic drugs (DMARD) pre-treatment and 75.5% anti-tumor necrosis factor(TNF)­α pre-treatment. After a mean interval of 8.0 months, 820 patients received RTX re-treatment. Mean DAS28-ESR decreased from 5.3 at baseline to 3.8 after 24 weeks (-1.5 [95% confidence interval, CI: -1.6; -1.4]), and from 4.1 at start of cycle 2 to 3.5 at study end (change from baseline: -1.8 [95% CI: -2.0; -1.7]). Improvements in DAS28-ESR and Health Assessment Questionnaire (HAQ) score occurred mainly during the first 12 weeks of RTX treatment, with further DAS28-ESR improvement until week 24 or month 6 of re-treatment. Improvements in DAS28-ESR and EULAR responses were more pronounced in seropositive patients. RF was a predictor of DAS28-ESR change to study end. Safety analysis showed the established profile of RTX. CONCLUSION: RTX was safe and effective in a real-life setting with rapid and sustained improvement in RA signs and symptoms.

A predominant Th1 polarization is present in synovial fluid of end-stage osteoarthritic knee joints: analysis of peripheral blood, synovial fluid and synovial membrane.

Thorough understanding of the complex pathophysiology of osteoarthritis (OA) is necessary in order to open new avenues for treatment. The aim of this study was to characterize the CD4+ T cell population and evaluate their activation and polarization status in OA joints. Fifty-five patients with end-stage knee OA (Kellgren-Lawrence grades III-IV) who underwent surgery for total knee arthroplasty (TKA) were enrolled into this study. Matched samples of synovial membrane (SM), synovial fluid (SF) and peripheral blood (PB) were analysed for CD3+ CD4+ CD8- T cell subsets [T helper type 1 (Th1), Th2, Th17, regulatory T cells] and activation status (CD25, CD69, CD45RO, CD45RA, CD62L) by flow cytometry. Subset-specific cytokines were analysed by cytometric bead array (CBA). SM and SF samples showed a distinct infiltration pattern of CD4+ T cells. In comparison to PB, a higher amount of joint-derived T cells was polarized into CD3+ CD4+ CD8- T cell subsets, with the most significant increase for proinflammatory Th1 cells in SF. CBA analysis revealed significantly increased immunomodulating cytokines [interferon (IFN)-γ, interleukin (IL)-2 and IL-10] in SF compared to PB. Whereas in PB only a small proportion of CD4+ T cells were activated, the majority of joint-derived CD4+ T cells can be characterized as activated effector memory cells (CD69+ CD45RO+ CD62L- ). End-stage OA knees are characterized by an increased CD4+ T cell polarization towards activated Th1 cells and cytokine secretion compared to PB. This local inflammation may contribute to disease aggravation and eventually perpetuate the disease process.

[Treatment and course of a man with systemic sclerosis before and after hematopoetic blood stem cell transplantation]. / Therapie und Verlauf bei einem Patienten mit systemischer Sklerose vor und nach Blutstammzelltransplantation.

HISTORY AND ADMISSION FINDINGS: A 66-year-old patient presented in our clinic with increasing painful swelling of his hands, whole body stiffness, weight loss and dyspnoea upon exercise. EXAMINATIONS: The physical examination revealed a marked skin sclerosis of hands, extremities and the face. Fist closure was impossible. Pulmonary CT scan showed lung fibrosis and ground glass opacities. Antinuclear antibodies and antibodies against Scl70 were positive. CRP, LDH, NT-Pro-BNP were elevated. DIAGNOSIS, TREATMENT AND COURSE: A diffuse cutaneous systemic sclerosis with an active interstitial pneumonia and lung fibrosis was diagnosed. Three pulses of cyclophosphamide 1.4 g every three weeks were ineffective to halt the progression of skin sclerosis, joint contractures and decline of pulmonary function. Mobilisation chemotherapy was initialized and blood stem cells were harvested. Blood stem cells were reinfused after myeloablative chemotherapy with melphalan. A maintainance therapy with mycophenolic acid was initiated after recovery of hematopoiesis. Six months after blood stem cell transplantation a decrease of skin sclerosis and an increasing recovery of joint mobility and physical strength was observed. CONCLUSION: Patients with a progressive systemic sclerosis and further risk factors should be treated with high-dose chemotherapy with blood stem cell transplantation before organ function is severely compromised. In cases with contraindications against cyclophosphamide or anti-thymocyte-globulin melphalan can be discussed as an alternative.

Familial Mediterranean fever in Germany: clinical presentation and amyloidosis risk.

OBJECTIVE: To characterize patients with familial Mediterranean fever (FMF) with and without AA amyloidosis living in Germany. METHOD: Clinical and genetic data from 64 FMF patients were analysed for amyloidosis risk factors. RESULTS: Fifty-five patients (85%) were of Turkish or Armenian origin. Thirty-one patients (48%) developed FMF symptoms before the age of 16 years. Sixteen patients (26%) became symptomatic after age 20. Symptoms reported were peritonitis (95%), fever (78%), pleuritis (59%), arthralgia (60%), arthritis (32%), erysipelas-like erythema (23%), and vasculitis (8%). FMF diagnosis was delayed for a median of 8.0 years. Genetic analysis confirmed M694V as the most prevalent Mediterranean fever (MEFV) gene mutation in 46 out of 59 patients (78%). M694V homozygosity was associated with an earlier FMF onset (median age 5.5 years, p = 0.0001) and a higher prevalence of peritonitis (p = 0.007) and pleuritis (p = 0.0007) compared to patients without an M694V mutation. AA amyloidosis was detected in 16 patients (25%) at a median age of 36.5 years and tended to be associated with a higher age at disease onset (p = 0.062) and a higher FMF activity score (p = 0.093). AA amyloidosis was significantly associated with a higher age at FMF diagnosis (p = 0.0022). CONCLUSIONS: Clinical symptoms of FMF-affected migrants living in Germany resemble those observed in their home country. In particular, patients with an onset of FMF symptoms after age 20 and a later FMF diagnosis have a high risk of AA amyloidosis. Symptomatic patients who originate from countries with a higher FMF prevalence should be screened for FMF and proteinuria.

[Rheumatoid arthritis: diagnostics and therapy 2012]. / Rheumatoide Arthritis: Diagnostik und Therapie 2012.

Rheumatoid Arthritis (RA) should be suspected if patients do not only complain of joint pain, but suffer from joint swelling, sensation of heat, hyperemia and warmth around the joints. An arthritic joint pain should be most prominent at night time or early in the morning and cause morning stiffness (> 30 min) of the joint, exercise will improve the symptoms. Diagnosis of RA will be even more likely if wrists, MCP- or PIP joints are affected. Serologic procedures will test for rheumatoid factor or anti-citrullinated antibodies (CCP Ab). One needs to keep in mind that positive results for rheumatoid factor or CCP Ab alone never proves the diagnosis of RA. After diagnosis therapy should be started immediately, recruiting physiotherapy, pain medication, corticosteroids and disease-modifying anti-rheumatic drugs (DMARDs), primarily methotrexate. At the latest after failure of two DMARDs biologics like TNF-α-blockers, an Interleukin-6-Receptor-antibody, a B-cell-specific antibody or a rather T-cell-specific biologic will be initiated. Aim of therapy is freedom of symptoms of an ongoing arthritis, low dosage of immunosuppressants (especially corticosteroids maximally 5 mg/day), stop of radiological progression and prevention of long term consequences of inflammation like myocardial infarction, stroke or lymphoma.

[Strategies for improved healthcare of people with the endemic disease rheumatism exemplified by rheumatoid arthritis]. / Strategien zur verbesserten Versorgung von Menschen mit der Volkskrankheit "Rheuma" am Beispiel der rheumatoiden Arthritis.

New therapeutic principles and considerable diagnostic advances have made it possible to define different rheumatic diseases and especially rheumatoid arthritis (RA) at an early stage and by starting an early and aggressive medication a considerable proportion of patients with RA will reach the status of low disease activity or even remission. With the additional development of composite measures to estimate the disease activity of RA, it was the goal of an international working group consisting of rheumatologists and patients to develop recommendations for treating rheumatoid arthritis in a similar way as for patients with hypertension or diabetes, with the aim to achieve remission as often as possible. This treat-to-target initiative has taken off in quite a number of different countries including Germany leading to discussions on how this initiative can be integrated into the specific national healthcare systems and what possibilities would exist for its implementation. To develop strategies for an improved healthcare of people suffering from rheumatic diseases and using RA as an example, action elements and postulates were developed which will be discussed in more detail in the present manuscript.

[Fever and arthritis: rheumatic or Whipple's disease?]. / Fieber und Arthritis: Entzündlich-rheumatische Erkrankung oder Morbus Whipple?

HISTORY AND CLINICAL FINDINGS: Five years ago a 52-year-old patient presented with arthritis of the small and large joints. Further symptoms were relapsing fever, unspecific gastrointestinal complaints with meteorism but no diarrhea, fatigue and impaired concentration. Subsequently increasing lower back pain developed. A lumbar-disc lesion was already known. INVESTIGATIONS: Inflammatory markers were elevated including leucocytosis. Gastroscopy with intestinal biopsies and colonoscopy remained without pathologic findings. Whipple's disease was excluded, but unspecific lymphozyte infiltration of the duodenal mucosa was described. Magnetic resconance imaging of the lumbar spine showed spondylodiscitis in L3/4 which was punctured, and polymerase chain reaction revealed Tropheryma whipplei DNA. Retrospectively, this was also found in the intestinal biopsies of three years ago. DIAGNOSIS, TREATMENT AND COURSE: After initial exclusion of Whipple's disease an unspecific systemic inflammatory disease had been presumed, and the patient had been treated with immunomodulatory therapies in alternating combinations. Steroids improved the symptoms but an increasing dosage of steroids was required. After the detection of Tropheryma whipplei and diagnosis of Whipple's disease the patient received ceftriaxon for a period of two weeks, subsequently cotrimoxazol for one year. Inflammatory activity decreased but unspecific symptoms remained almost unaffected. CONCLUSION: The differential diagnosis in patients with fever, elevated inflammatory markers and gastrointestinal symptoms must include Whipple's disease. A Tropheryma whipplei PCR from duodenal biopsies should be performed because of its higher sensitivity compared to histology alone.

[Amendment of the structural quality for inpatient rheumatology. A forward-looking concept]. / Neufassung der Strukturqualität der akut-stationären Rheumatologie. Ein zukunftsweisendes Projekt.

In 2010 a total of 9 guidelines on structural quality were endorsed by the Association of Rheumatology Clinics in Germany (VRA). These 9 structural criteria replace the regulations published in 2002 and were elaborated with the support of the German Rheumatology League. With guideline number 9 even the structural requirements for university hospitals are defined for the first time.Along with taking part in the quality project "Kobra" (continuous outcome benchmarking in rheumatology inpatient treatment) compliance with the new structural criteria constitutes a prerequisite for acquiring a quality certificate, which is awarded by an external institution.By this means the VRA sets the stage for its members to be prepared for future challenges and quality competition among hospitals. Furthermore, the provision of a high quality treatment for chronically diseased patients in rheumatology clinics will be effectively supported.

[Regulatory B cells and their role in maintaining peripheral tolerance]. / Regulatorische B-Zellen und ihre funktion im erhalt der peripheren toleranz.

The immune system is regulated by a variety of mechanisms that prevent overwhelming immune responses and a break in tolerance. There have been indications for some time that populations of B cells are also a part of this network and able to exert regulatory functions. Here we summarize current knowledge on this previously unrecognized B cell function and their potential role in protection against autoimmunity.

[Biomarkers collections: the future or a waste of resources?]. / Biomarkersammlungen: Zukunft oder Ressourcenverschwendung?

Disease biomarkers would aim at a more specific definition of diagnosis or subtype of a certain disease, as well as prognosis definition, including efficacy and side effects of certain therapeutics. Biomarkers could lead to a prognostically optimized definition of remission in the individual patient and thus to a more objective definition of therapeutic efficacy. Is this possible and does it make sense? Or would an extensive analysis of biomarkers to date lead to a costly overestimation of as yet not well established biologic parameters? Although we are currently unable to answer this question, many colleagues argue in favour of more in depth research for a better evaluation of biomarkers in many diseases. This could save money if we were able to predict the efficacy of expensive drugs such as immunobiologics. Biomarkers comprise cytometric information, data on protein expression and secretion, mRNA, microRNA or DNA, including epigenetic variants. Although much of these data already exist in the scientific literature, it is associated with problems in terms of feasibility (for cytometry and RNA analysis only on-site analysis is possible, while for DNA analysis central testing is also possible), costs and reproducibility (ethnic variability!). To date all biomarkers have only limited value in terms of the above-mentioned aims. The present review compiles "PROs and CONs" in a subjective way in order to provoke a discussion on the meaningfulness of biomarkers, while at the same time supporting and encouraging further research in this field.

[Ocular involvement in spondyloarthropathies: HLA B27 associated uveitis]. / Augenbeteiligung bei Spondyloarthritiden: HLA-B27-assoziierte Uveitis.

The most frequent extraarticular manifestation in spondyloarthropathies (SpA) is eye involvement, which is found in 30%-50% of patients. HLA B27 positive patients in particular--mostly those in the subgroup with ankylosing spondylitis--are affected. Prevalence of uveitis increases with duration of disease. Typical eye involvement is sudden-onset unilateral anterior uveitis (iridocyclitis). Most cases respond well to topical corticosteroids. Frequently relapsing or chronic cases may require oral corticosteroids in addition to classical immunosuppressive drugs and, to an increasing extent, also TNF-alpha inhibitors. In the case of the latter, monoclonal antibodies are preferred over receptor antagonists. Acute anterior uveitis may occur as a minimal variation or initial symptom of SpA. These patients should also be seen by a rheumatologist since undiagnosed SpA may be present in a significant percentage and should be included in therapeutic considerations.

[Radiographic healing of sarcoid bone erosion]. / Radiologische Heilung einer Erosion bei Knochensarkoidose.

Sarcoidosis is a systemic granulomatous disease that primarily affects the lung and other organs. Patients with dactylitis should be screened for abnormalities of the skin, eyes and lungs. Even in patients with normal-range ACE sarcoidosis could be confirmed by tissue biopsy. Treatment with methotrexate and steroids can relieve symptoms and stabilize the disease. In refractory cases leflunomide, azathioprine, hydroxychloroquine or antibodies against TNF-alpha can be additionally administered.

[Diagnostics and therapy of AA amyloidosis]. / Diagnostik und Therapie der AA-Amyloidose.

AA amyloidosis can be the consequence of any chronic inflammatory disorder. It is most commonly associated with chronic inflammatory rheumatic, pulmonary or gastrointestinal diseases, familial Mediterranean fever or other rare periodic syndromes. AA amyloidosis often affects the kidneys, gastrointestinal tract and the heart. Effective therapy of the underlying disease can normalize the inflammatory reaction and can slow or inhibit the deterioration of organ function if the diagnosis is made at an early stage of the disease. In rheumatoid diseases and in some periodic syndromes the use of antibodies against TNFalpha or IL-1 beta might be helpful. Patients with familial Mediterranean fever should regularly take colchicine to prevent attacks and to reduce the risk for development or progression of AA amyloidosis. Eprodisate is currently being investigated for AA amyloidosis and renal involvement.