[Non-steroidal anti-inflammatory drugs and cyclooxygenase-2-specific inhibitors]. / Nichtsteroidale Antiphlogistika und Cyclooxygenase-2-spezifische Hemmsubstanzen.

The discovery of two isoenzymes of cyclooxygenase--COX-1 and COX-2--in the late eighties was followed by an intensive looking for drugs, which inhibit specifically COX-2 and have no influence on COX-1. After some years of trial and error it is now possible to measure the inhibition-capacity--e.g. of Rofecoxib, Celecoxib and all the conventional NSAIDs--in a human blood assay. New insights into localisation, expression and physiological function of COX-2 followed. We now are able to differentiate between "conventional" NSAIDs and COX-2 specific inhibitors (CSI, COXIBS), as a new class of substances. CSI firstly inhibit COX-1/COX-2 to a different extent and in a different manner. Secondly they have a different profile concerning unwanted--especially gastrointestinal--side effects. Further experiences and investigations have to confirm and establish this positive risk/benefit ratio.

[Vitamin E in active arthroses and chronic polyarthritis. What is the value of alpha-tocopherol in therapy?]. / Vitamin E bei aktivierten Arthrosen und chronischen Polyarthritiden. Welchen Stellenwert hat Alpha-Tocopherol in der Therapie?

Known and recognized mechanisms of action of alpha-tocopherols are the grounds for the use of vitamin E in activated arthrosis or rheumatoid arthritis. This is also supported by the positive clinical results obtained in double-blind studies. On this basis, a change in the evaluation of these substances has taken place in recent years. Initially characterised as "unorthodox", "unconventional" or "additive" therapy, the term now applied tends to be "adjuvant-accepted" therapy. The results of double-blind studies and clinical empiricism support the following hyperthesis: The pathogenetic substrate "free oxygen radicals" increases quantitatively from activated arthrosis to (bland, mild) chronic polyarthritis. This could explain the graded differentiated antioxidative (or hypothetically the "central-analgesic") effects of alpha-tocopherols. While there still is no causal treatment with the alpha-tocopherols-pain alleviation and anti-inflammatory effect-are similar to those achieved with non-steroidal antiinflammatory drugs, the potency of which, however, is superior.

[Atypical course in (eosinophilic) fasciitis]. / Atypischer Verlauf einer (eosinophilen) Fasziitis.

A 22-year old male patient developed--following a short phase of monarthritis--the symptoms of a symmetric, polysynoviatic, discrete erosive rheumatoid arthritis, thus fulfilling five of seven ACR criteria. Initially as well as persisting during the course of the disease the palpable swelling of synovitis showed a coarse character. The radiological progression at the hands during an interval of eight years being only minimal the loss of functions, up to contraction of joints (left hip) augmented considerably during that time. Neither rheumatoid factor or antinuclear antibodies nor evident eosinophilia or hypergammaglobulinaemia could be proved or verified. In 1994 muscle biopsy led to the diagnosis "fasciitis with low-graded eosinophilia". Anamnestic, clinical and radiological signs and data as well as the course of the disease and assessing of differential diagnoses are presented and discussed.

[Chronic polyarthritis--treatment with alternative medicine. How frequent is (self-) therapy with alternative methods?]. / Chronische Polyarthritis--Behandlung ausserhalb der Schulmedizin. Wie häufig ist die (Eigen-) Therapie mit alternativen Verfahren?

Between 1987 and 1992, we carried out an initial survey of 535, and second and third surveys of 552, patients with chronic polyarthritis, with the aim of obtaining information about paramedical and unconventional treatments and drugs used by those patients to self-treat their conditions. Some 32 to 64% had tried acupuncture, homeopathy and a number of obscure procedures (iridoscopy, cupping, and ozone treatment). Unconventional methods--use of vitamin E, enzymes, dietary measures--predominated. Over the years, the use of paramedical methods and drugs decreased, but the number of patients living on a diet (no pork, sausages or offal, but vegetarian food) remained constant. Attempts to separate the tares from the wheat, are reflected by the nomenclature: so-called unconventional therapies have the potential of becoming recognized forms of treatment. This appears to be the case with dietary measures and the use of vitamin E.

[Does methotrexate induce "rheumatoid nodules"? Case report and discussion of the literature]. / Induziert Methotrexat "Rheumaknoten"? Kasuistik und Diskussion der Literatur.

A 58-year-old woman with chronic polyarthritis rapidly developed a large number of rheumatic nodules under treatment with methotrexate. A comparison with other cases reported to date showed that the sudden onset of such nodules after initiation of treatment, and their disappearance again after discontinuation of the drug make the causal relationship highly likely. Although the predominantly anti-inflammatory actions of methotrexate control the chronic polyarthritis in almost all cases so far reported, they are unable to prevent the primarily immunological tissue necrosis (rheumatic nodules) and may even promote their development through the liberation of adenosine. Only in very rare cases does the severity or localisation of the nodules--e.g. vasculitis, pulmonary or cardial manifestation--necessitate the discontinuation of methotrexate.

[Differential diagnosis of "rheumatoid nodules"]. / Differentialdiagnose von "Rheumaknoten".

Rheumatic nodules occur in some 20 to 25% of cases of chronic polyarthritis, and need special diagnostic, in particular differential diagnostic, consideration. They have to be differentiated from numerous other nodules in rheumatoid and non-rheumatoid diseases. To achieve this, palpation, a knowledge of the preferred sites, and the use of such technical means as laboratory and x-ray investigations are all useful.

[Current aspects of D-penicillamine and pregnancy]. / Aktuelles zu D-Penicillamin und Schwangerschaft.

Although the outcome of most pregnancies is normal under D-penicillamine a teratogenic effect of the drug is known from animal studies. A few cases of children with birth defects whose mothers received D-penicillamine during pregnancy are reported in the literature. Whether D-penicillamine therapy should be performed throughout pregnancy or whether it should be interrupted depends on the disease to be treated. While in patients with morbus Wilson, continuous treatment with D-penicillamine is justified, it is advisable to interrupt the therapy during pregnancy in patients with rheumatoid arthritis.

Arthrosis or osteoarthritis: do these terms imply therapy with pure analgesics or non-steroidal antirheumatic agents?

In contrast to German-speaking regions, where the expression "arthrosis" is used, English-speaking countries prefer the term "osteoarthritis". The syllable "itis" indicates quantitatively variable inflammation which is present in each phase of the disease. In choosing the right expression one must also include new concepts of arthrosis regarding aetiology and pathogenesis as well as the quantitative aspect of inflammation. Since most arthrotic patients are now treated with non-steroidal anti-inflammatory drugs, the question of the anti-inflammatory effect of each of these drugs is just as important as the question of their analgesic activity and neutrality for chondrocytes. Bearing in mind that some kinds of arthrotic pain are not induced by inflammation mediators, treatment with pure analgesic drugs would be advantageous. The latest concept of the pathogenesis of arthrosis involving interleukin, rounds the problem off. Perhaps the difficulty lies therein, in that nowadays we are unable to quantify the inflammatory aspect of inflammation. Only when we are in a position to determine pathogenetically-damaging agents in their negative potential and their proportional quantity, will we be able to answer the question, "osteoarthrosis or osteoarthritis?"

[Controversial and so-called alternative therapeutic approaches]. / Umstrittene und sogenannte ausserschulische Therapieansätze.

In spite of intensive research, it has not yet been possible to produce a complete explanation of the aetiology and pathology of rheumatoid arthritis (R.A.). Therapeutic measures are possible in many phases of the pathogenetic concept, and often produce good, modifying results, improving the course of the disease. No causal therapy of R.A. exists--we do not know the aetiology of this disease. Frustration with conventional medicine on the one side, and the predominating spirit of the times on the other--back to biological methods and the old forms of therapy--are the reasons why chronic polyarthritics drift into the sphere of para-medicine. In the judgement of para-medical methods, "risk/benefit relationship", "superfluous and no longer up-to-date", "controversial--absence of scientific evidence", "controversial", and "controversial--not scientifically acceptable" present some of the decision criteria. Treatment with mussel extracts, beta-sitosterins, THX, and substitution with various substances, as well as anthroposophically-oriented high-potency homeopathy, are to be allocated to the "controversial--not scientifically acceptable" category. If one weighs up the "risk/benefit relationship" of cell therapy, this treatment concept also cannot be supported. Moreover, precisely documented scientific results of this form of therapy do not exist. Methods standing on scientifically-hypothetically interesting ground, but which were tested on too small a group and cannot yet be accepted as sufficiently proven, are therapy with Vitamin E, the use of Thymopoietin, in which, for example, dose-finding and mode of application are not yet firmly established, and therapy with enzyme mixtures. Interferon results, initially extolled in the lay press, have not been confirmed in the most recent studies. Thymopoietin treatments, via the laborious road to the correct application (oral, subcutaneous, intramuscular, intravenous as bolus, intravenous--fractionated), show encouraging successes. As tissue-localized immune complexes (which sort?) play a role in the pathogenesis of R.A., but enzyme mixtures, apart from the problems of absorption, only influence circulating immune complexes, and moreover, in many diseases neither the aetiology nor the pathogenesis is connected with the immune complexes, this therapy concept can be regarded neither as causal nor as scientifically guaranteed. In summary: from the start-point that healing is the ideal aim, it has been forgotten that there are many human sufferings which medicine can ease and ameliorate, but not yet cure.(ABSTRACT TRUNCATED AT 400 WORDS)

[Changes in the cervical spine in chronic polyarthritis]. / Veränderungen der Halswirbelsäule bei chronischer Polyarthritis.

In 93 patients with classical chronic polyarthritis (rheumatoid arthritis) (at least five ARA-criterias) there were inflammatory lesions of dens epistropheus in 48.4%, ventral atlantoaxial subluxations in 25.8%, lateral atlantoaxial dislocations in 14% and pseudobasilary invagination in 5.4%. Step-ladder-subluxation between C 2/C 7 was found in 31.2%, discitis in 12.5% and spondylarthritis in 38% of cases. Inflammatory signs of the cervical spine were correlated to the Steinbrocker-Grade IV, ANA level 1:40 and the degree of Waaler-Rose. The correlation between long standing steroid-therapy and signs of cervical involvement during c.p.--specially in C1/C2--is found to be proven. There are connections between the duration of c.p. (more than 10 years) and manifestation of cervical spine lesions, further, in a protective sense between longstanding gold therapy and cervical spine lesions.

HLA-DR4 in ankylosing spondylitis with different patterns of joint involvement.

Fifty patients with ankylosing spondylitis (AS) confined to the spine and sacroiliac joints were compared with 50 cases of AS complicated by various patterns of non-axial joint involvement. Radiological and clinical features were evaluated and HLA-DR4 typing was carried out. This antigen was found in 16% of 200 normal individuals in 18% of patients suffering from exclusively axial AS, and in 54% of patients with additional purely peripheral joint involvement (wrist, finger, ankle, toe). The possibility that HLA-DR4 represents a non-specific marker for peripheral arthritis in patients with ankylosing spondylitis is discussed.

[Ankylosing spondylitis with and without peripheral joint involvement. The significance of HLA-DR4 in the diagnosis, disease risk and pathogenesis]. / Spondylitis ankylosans mit und ohne periphere Gelenkbeteiligung. Die Bedeutung von HLA-DR4 für Diagnostik, Erkrankungsrisiko und Pathogenese.

50 patients with ankylosing spondylitis without any peripheral arthritis are compared with 50 cases of ankylosing spondylitis complicated by arthritis of different kind. Radiological and clinical features were evaluated and assessed. HLA-DR4 typing was carried out. This antigen was found in 16% of 200 normal individuals, in 18% of all patients with ankylosing spondylitis confined to the spinal column, and in 54% of patients with only peripheral arthritis (wrist, finger, ankle, toe joints). The conclusion that HLA-DR4 represents nonspecific evidence for peripheral arthritis in patients with ankylosing spondylitis is discussed.

[Polymyalgia arteriitica (rheumatica)]. / Polymyalgia arteriitica (rheumatica).

The polymyalgia arteritica (PMA) is a systemic disease characterized by symmetrical muscle pain of the shoulder and/or pelvic girdle and a highly inflammatory constellation of non-specific inflammation parameters. The symptoms in the mostly elderly patients may perfectly imitate a malignancy of syndrome. Besides showing arthralgia and arthritis nearly 50% of cases will develop an arteritis localized most frequently at the arteria temporalis. Decisive diagnostic criteria are muscle pain in the shoulder/pelvis girdle and a markedly raised erythrocyte sedimentation rate. Other diagnostic classification, laboratory findings, X-ray, non-invasive techniques such as sonography are of no use in assessment of the diagnosis. Successful treatment provides corticosteroid therapy applied in a circadian rhythm. The alternating therapy lately often recommended does not completely suppress the symptoms. Obligatory is a warning against a too early stop of therapy as well as too low corticosteroid dosage. Exclusive non-steroidal antirheumatic therapy not only is not sufficient but will prove dangerous (arteritis). Although limiting itself after a duration of about 2 to 10 years, even without treatment, the PMA must not be labelled as benign due to its risk of arteritis.