High prevalence of Pneumocystis jirovecii colonization among patients with autoimmune inflammatory diseases and corticosteroid therapy.

BACKGROUND: Patients with autoimmune inflammatory diseases (AID) account for 13-36% of Pneumocystis pneumonia (PCP) cases in human immunodeficiency virus (HIV)-negative patients. Up to 88% of PCP cases in HIV-negative patients are associated with prior steroid treatment. Pulmonary colonization with Pneumocystis in HIV-negative patients is associated with corticosteroid therapy in up to 75% of cases. The aim of this study was to detect the prevalence and risk factors of pulmonary colonization with Pneumocystis jirovecii in patients with AID receiving corticosteroid therapy in comparison with healthy control persons. METHODS: We investigated induced sputa of 102 patients with AID on current corticosteroid treatment and of 117 healthy controls for the presence of P. jirovecii using polymerase chain reaction (PCR). RESULTS: Twenty-nine patients (28.5%) with AID were colonized with P. jirovecii compared to three healthy controls (2.6%) [p < 0.001, odds ratio (OR) 15.10, 95% confidence interval (CI) 4.43-51.38]. In patients with AID, age over 60 years was significantly associated with colonization (p = 0.015, OR 3.19, 95% CI 1.27-7.94). Multivariate analysis showed age to be independently associated with the colonization of P. jirovecii (95% CI 1.002-1.092). Neither duration nor dose of corticosteroid therapy nor immunosuppressive co-medication had a significant influence on P. jirovecii colonization. CONCLUSION: Patients with AID, especially those over 60 years of age, display a high prevalence of colonization with P. jirovecii. Clinicians should be aware of this and ensure that they consider the possibility of PCP when pulmonary symptoms arise in these patients.

IgG1 and IgG4 are the predominant subclasses among auto-antibodies against two citrullinated antigens in RA.

OBJECTIVE: Antibody subclasses reflect specific immunological processes and may be indicative of the underlying pathological pattern in an autoimmune disease like RA. We therefore quantified anti-cyclic citrullinated peptides (CCP) and anti- citrullinated vimentin (MCV) IgG subclass titres in RA patients and compared them with the respective titres of antibodies directed against the varicella zoster virus (VZV) and to total serum titres. METHODS: Sera of 77 patients fulfilling the ACR criteria for RA were collected. An IgG subclass-specific ELISA system was then established and combined with commercially available MCV, CCP and VZV pre-coated microtitre plates. RESULTS: Even though IgG1 is the predominant subclass among antibodies against CCP and MCV in RA patients, IgG4 is second with respect to titres and frequencies. This increase in IgG4 among RA-specific antibodies is independent of disease duration and does not reflect a general skewing of the immune response in these patients as overall serum titres and antibodies directed against VZV show a normal distribution of IgG1, IgG2, IgG3 and IgG4. CONCLUSION: Elevated IgG4 titres are specific for auto-antibodies against citrullinated antigens in RA and are indicative of a Th2-biased environment during the generation of auto-reactive plasma cells. We discuss here an indirect role for IgG4 auto-antibodies in hindering the elimination of auto-reactive B and plasma cells and thus driving the autoimmune process.

Neuroendocrine perturbations in fibromyalgia and chronic fatigue syndrome.

A large body of data from a number of different laboratories worldwide has demonstrated a general tendency for reduced adrenocortical responsiveness in CFS. It is still not clear if this is secondary to CNS abnormalities leading to decreased activity of CRH- or AVP-producing hypothalamic neurons. Primary hypofunction of the CRH neurons has been described on the basis of genetic and environmental influences. Other pathways could secondarily influence HPA axis activity, however. For example, serotonergic and noradrenergic input acts to stimulate HPA axis activity. Deficient serotonergic activity in CFS has been suggested by some of the studies as reviewed here. In addition, hypofunction of sympathetic nervous system function has been described and could contribute to abnormalities of central components of the HPA axis. One could interpret the clinical trial of glucocorticoid replacement in patients with CFS as confirmation of adrenal insufficiency if one were convinced of a positive therapeutic effect. If patient symptoms were related to impaired activation of central components of the axis, replacing glucocorticoids would merely exacerbate symptoms caused by enhanced negative feedback. Further study of specific components of the HPA axis should ultimately clarify the reproducible abnormalities associated with a clinical picture of CFS. In contrast to CFS, the results of the different hormonal axes in FMS support the assumption that the distortion of the hormonal pattern observed can be attributed to hyperactivity of CRH neurons. This hyperactivity may be driven and sustained by stress exerted by chronic pain originating in the musculoskeletal system or by an alteration of the CNS mechanism of nociception. The elevated activity of CRH neurons also seems to cause alteration of the set point of other hormonal axes. In addition to its control of the adrenal hormones, CRH stimulates somatostatin secretion at the hypothalamic level, which, in turn, causes inhibition of growth hormone and thyroid-stimulating hormone at the pituitary level. The suppression of gonadal function may also be attributed to elevated CRH because of its ability to inhibit hypothalamic luteinizing hormone-releasing hormone release; however, a remote effect on the ovary by the inhibition of follicle-stimulating hormone-stimulated estrogen production must also be considered. Serotonin (5-HT) precursors such as tryptophan (5-HTP), drugs that release 5-HT, or drugs that act directly on 5-HT receptors stimulate the HPA axis, indicating a stimulatory effect of serotonergic input on HPA axis function. Hyperfunction of the HPA axis could also reflect an elevated serotonergic tonus in the CNS of FMS patients. The authors conclude that the observed pattern of hormonal deviations in patients with FMS is a CNS adjustment to chronic pain and stress, constitutes a specific entity of FMS, and is primarily evoked by activated CRH neurons.

Hormonal pertubations in fibromyalgia syndrome.

The symptomatology characterizing fibromyalgia (FM) comprises three systems: the musculoskeletal system with widespread muscular pain, neuroendocrine disorders, and psychological distress including depression. Though the most prominent symptom of FM is pain in defined points of the musculoskeletal system, the numerous other somatoform and psychological disorders suppose a common primary disturbance which we consider to originate within higher levels of the central nervous system. Recent studies of the entire endocrine profile of FM patients following a simultaneous challenge of the hypophysis with corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone, growth hormone-releasing hormone, and luteinizing hormone-releasing hormone support the hypothesis that an elevated activity of CRH neurons determines not only many symptoms of FM but may also cause the deviations observed in the other hormonal axes. Hypothalamic CRH neurons thus may play a key role not only in "resetting" the various endocrine loops but possibly also nociceptive and psychological mechanisms as well.

Thyroid disorders in female patients with ankylosing spondylitis.

The association between rheumatological and thyroid disorders has long been known, the most common being the association of rheumatoid arthritis and autoimmune thyroiditis. Little is known as to possible thyroid involvement in ankylosing spondylitis (AS). In 22 female patients with AS and 22 healthy age-matched control subjects parameters of thyroid gland function, rheumatic activity, as well as a subtle drug anamnesis of the rheumatic medication, and an ultrasonographic examination of the thyroid gland were determined. Thyroid function was tested by intravenous injection of 400 microg thyrotropin-releasing hormone (TRH). In parallel basal levels of reverse-T3 (rT3), calcium and anti-thyroid antibodies were estimated. In the AS-group an enlarged thyroid volume was seen in 10 cases, basal FT4, FT3 and TT3 were significantly lower, TSH and TT4 were found to be in the normal range and rT3 was significantly increased. The prevalence of anti-thyroid antibodies was significantly higher in the AS-group. The AS-patients responded as well as the controls with thyroid hormone secretion to TRH, within an observation period of 2 hours. No differences were observed in TSH response. Free serum calcium showed in both groups no significant difference. To summarize our results, female patients with AS showed a

Short-term treatment of primary fibromyalgia with the 5-HT3-receptor antagonist tropisetron. Results of a randomized, double-blind, placebo-controlled multicenter trial in 418 patients.

We investigated the efficacy and tolerability of short-term treatment with tropisetron, a selective, competitive 5-HT3-receptor antagonist in fibromyalgia. The trial was designed as a prospective, multicenter, double-blind, parallel-group, dose-finding study. We randomly assigned 418 patients suffering from primary fibromyalgia to receive either placebo, 5 mg, 10 mg or 15 mg tropisetron once daily for 10 days. Clinical response was measured by changes in pain score, visual analog scale, tender point count and ancillary symptoms. Responders were prospectively defined as patients showing a 35% or higher reduction in pain score. Treatment with 5 mg tropisetron resulted in a significantly higher response rate (39.2%) than placebo (26.2%) (p < 0.05). In the visual analog scale, the group administered 5 mg tropisetron showed a significant improvement (p < 0.05) and the group administered 10 mg tropisetron showed a nonsignificant clinical benefit. The number of painful tender points was significantly reduced (p = 0.002) in the 5 mg tropisetron group. Regarding ancillary symptoms, the 5 mg tropisetron group showed a significant improvement (p < 0.05) in sleep and dizziness. The patients' overall assessment of efficacy was significantly higher for 5 mg (p = 0.016) and 10 mg (p = 0.002) tropisetron than for placebo. The safety and tolerability of tropisetron was good; gastrointestinal tract symptoms were the most frequently reported adverse events. Short-term treatment of fibromyalgia patients with 5 mg tropisetron for 10 days proved to be efficacious and well tolerated. In this study a bell-shaped dose-response curve was seen.

Autoantibodies in autoimmune diseases.

The occurrence of autoantibodies is a common feature of autoimmune diseases. This review is intended to give an overview of the most important autoantibodies and their role in diagnosis, disease activity and prognosis in rheumatoid arthritis (RA), systemic lupus erythematodes (SLE) and multiple sclerosis (MS). Whereas in RA and SLE these antibodies are meaningful for diagnosis and partially for the prognosis of the disease, the situation is quite different in the case of MS. Up to date, no specific antibody is known to be exclusively present in the serum or cerebrospinal fluid (CSF) of MS-patients compared to the respective fluids of healthy individuals. Nevertheless, there are some antigens that are reported to be bound significantly more often by MS-patients' serum or CSF than by comparable samples of healthy volunteers. In addition to the importance of several autoantibodies for diagnosis of the respective disease, the serum concentration of certain antibodies in RA and SLE is associated with therapy response. Since therapy with biologicals (e. g. TNF-alpha blockade, B-cell depletion) is expensive, monitoring these autoantibodies seems to be an additional useful tool for early identification of therapy responders or non-responders.

Spots, blots, peaks and chips: proteomic approaches in autoimmune diseases.

During the past five years, investigations employing a variety of proteomic technologies have yielded a wealth of information on a number of autoimmune disorders. Animal models of autoimmune disease have been examined and have provided clues that can be useful in elucidating molecular pathways and mechanisms that play a role in autoimmune disorders. Human sera and body fluids have been analyzed and have resulted in the identification of autoantibodies that can be used as diagnostic markers in specific autoimmune diseases, and proteomic fingerprints of tissues and body fluids have resulted in the identification of individual proteins or patterns of protein expression that are deregulated in autoimmune diseases. The information provided by these proteomic studies are of diagnostic and therapeutic potential. This review provides an overview of the approaches used in the proteomic analyses of autoimmune disease.

Neuroendocrine and hormonal perturbations and relations to the serotonergic system in fibromyalgia patients.

The symptomatology of the fibromyalgia syndrome (FMS) often resembles an alteration in central nervous set points at least in three systems. The patients suffer under chronic pain in the region of the locomotor system, presumably reflecting a disturbed central processing of pain. Anxiety and depression often characterizes the clinical picture. Almost all of the hormonal feedback mechanisms controlled by the hypothalamus are altered. Characteristic for FMS patients are the elevated basal values of ACTH, follicle-stimulating hormone (FSH), and cortisol as well as lowered basal values of insulin-like growth factor 1 (IGF-1, somatomedin C), free triiodothyronine (FT3), and oestrogen. In FMS patients, the systemic administration of the relevant releasing hormones of corticotropin-releasing hormone (CRH), growth hormone-releasing hormone (GHRH), thyreotropin-releasing hormone (TRH), and luteinizing hormone-releasing hormone (LHRH) leads to increased secretion of ACTH and prolactin, whereas the degree to which TSH can be stimulated is reduced. The stimulation of the hypophysis with LHRH in female FMS patients during their follicular phase results in a significantly reduced LH response. All in all, the typical alterations in set points of hormonal regulation that are typical for FMS patients can be explained as a primary stress activation of hypothalamic CRH neurons caused by the chronic pain. In addition to the stimulation of pituitary ACTH secretion, CRH activates somatostatin on the hypothalamic level, which in turn inhibits the release of GH and TSH on the hypophyseal level. The lowered oestrogen levels could be accounted for both via an inhibitory effect of the CRH on the hypothalamic release of LHRH or via a direct CRH-mediated inhibition of the FSH-stimulated oestrogen production in the ovary. Serotonin (5HT), precursors like tryptophan (5HTP), drugs which release 5HT or act directly on 5HT receptors stimulate HPA axis, indicating a stimulatory serotonergic influence on HPA axis function. Therefore activation of the HPA axis may reflect an elevated serotonergic tonus in the central nervous system of FMS patients.

Neuromediator and hormonal perturbations in fibromyalgia syndrome: results of chronic stress?

Since the first comprehensive description of the symptoms of FMS by Yunus et al (1981), numerous investigations have confirmed that FMS is a clinical entity. However, the aetiology of the syndrome is still not fully elucidated. It seems, however, logical to place the origin of the disorder in the muscle. Muscle pain, especially at the muscle-tendon junctions, fatigue and stiffness are the first symptoms. A malfunction of energy metabolism has been detected in part of the muscle fibres. However, it has to be considered that the muscle is not an isolated entity. Its activity is controlled by segmentally arranged motor units of the ventral horn of the spinal cord in response to proprioceptive afferent signals arising in the muscle spindles or in other sensory elements including nociceptors. Together with supraspinal descending inputs, the spinal motor neurone pool is the common final pathway for segmental and suprasegmental inputs, making the motor system extremely powerful for adaptive adjustments but also vulnerable if deficits occur in either of these input levels. A second, recently discovered abnormality seen in FMS is a lowered serotonin level in peripheral and most likely also central structures. The underlying mechanism seems to be defective absorption of the precursor amino acid tryptophan from the gut. Serotonin is involved centrally in the regulation of the sleep pattern, and at the spinal level it acts as a 'gain setter' of motoneurone excitability and suppresses signal transmission of noxious stimuli in dorsal horn neurones. Either of these two disturbances, muscle energy depletion or serotonin deficiency, could by itself evoke many of the symptoms of FMS, and their combined appearance will perpetuate the disease. Depressed levels of somatomedin C, caused by a deficit of stage 4 sleep-dependent release of GH, might represent an additional factor in preventing proper development or repair of myoskeletal structures. Malabsorption of certain amino acids, possibly due to a genetic disorder of gut transport mechanisms, may constitute an additional deleterious factor. The abnormalities found in the HPA and HPT axis may be seen as an attempt of the organism to restore homeostasis. The stimulus eliciting this counter-regulatory reaction may be pain or other afferent signals which normally do not reach the central nervous system. It is doubtful whether the unspecific activation of the HPA axis in a non-inflammatory disease is beneficial.(ABSTRACT TRUNCATED AT 400 WORDS)

Thyroid function in patients with fibromyalgia syndrome.

Thyroid function was tested in 13 female patients with primary fibromyalgia syndrome (FS) and 10 healthy age matched controls by intravenous injection of 400 micrograms thyrotropin-releasing hormone (TRH). Basal thyroid hormone levels of both groups were in the normal range. However, patients with primary FS responded with a significantly lower secretion of thyrotropin and thyroid hormones to TRH, within an observation period of 2 h, and reacted with a significantly higher increase of prolactin. Total and free serum calcium and calcitonin levels were significantly lower in patients with primary FS, while both groups exhibited parathyroid hormone levels in the normal range.

Correlation of IL-6 with the classical humoral disease activity parameters ESR and CRP and with serum cortisol, reflecting the activity of the HPA axis in active rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic inflammatory disease with elevated levels of proinflammatory cytokines in peripheral blood, especially IL-6, but also IL-1 alpha and TNF alpha, for example, in different concentrations, depending on disease activity. A disturbed circadian rhythm of cortisol secretion and an overall elevated cortisol release in active RA, depending on disease activity, is known. The presented study examined correlations of IL-6 as the most important systemic mediator of the acute phase response in active RA with classical humoral disease activity parameters, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and with serum cortisol. We investigated 64 active RA patients, previously untreated with glucocorticoids. IL-6 was measured by ELISA from Pharmingen (San Diego), ESR by the method of Westergren and CRP by nephelometry (Behring Marburg, Germany). Cortisol was measured in 34 of these patients, using a fluorescence-polarization immunoassay (FPIA) from Abbott. We found correlations of IL-6 with CRP (p < 0.001, Spearman Rank Test, rs = 0.75), with ESR (p < 0.001, rs = 0.62) and with serum cortisol (p = 0.019, rs = 0.401). ESR and CRP correlate (p < 0.001, rs = 0.8) and cortisol also correlates with ESR (p = 0.002, rs = 0.52) and CRP (p < 0.001, rs = 0.57). IL-6 as an important systemic mediator of inflammation in RA correlates closely with CRP, as it induces its production, and with ESR. These three parameters correlate well with serum cortisol, which is increased in active RA, depending on disease activity. Thus, IL-6 is an important disease activity parameter in RA that is closely related to both the classical humoral disease activity and the HPA axis.

Nociception, pain, and antinociception: current concepts.

The physiology of nociception involves a complex interaction of peripheral and central nervous system (CNS) structures, extending from the skin, the viscera and the musculoskeletal tissues to the cerebral cortex. The pathophysiology of chronic pain shows alterations of normal physiological pathways, giving rise to hyperalgesia or allodynia. After integration in the spinal cord, nociceptive information is transferred to thalamic structures before it reaches the somatosensory cortex. Each of these levels of the CNS contain modulatory mechanisms. The two most important systems in modulating nociception and antinociception, the N-methyl-D-aspartate (NMDA) and opioid receptor system, show a close distribution pattern in nearly all CNS regions, and activation of NMDA receptors has been found to contribute to the hyperalgesia associated with nerve injury or inflammation. Apart from substance P (SP), the major facilitatory effect in nociception is exerted by glutamate as the natural activator of NMDA receptors. Stimulation of ionotropic NMDA receptors causes intraneuronal elevation of Ca2+ which stimulates nitric oxide synthase (NOS) and the production of nitric oxide (NO). NO as a gaseous molecule diffuses out from the neuron and by action on guanylyl cyclase, NO stimulates in neighboring neurons the formation of cGMP. Depending on the expression of cGMP-controlled ion channels in target neurons, NO may act excitatory or inhibitory. NO has been implicated in the development of hyperexcitability, resulting in hyperalgesia or allodynia, by increasing nociceptive transmitters at their central terminals. Among the three subtypes of opioid receptors, mu- and delta-receptors either inhibit or potentiate NMDA receptor-mediated events, while kappa opioids antagonize NMDA receptor-mediated activity. Recently, CRH has been found to act at all levels of the neuraxis to produce analgesia. Modulation of nociception occurs at all levels of the neuraxis, thus, eliciting the multidimensional experience of pain involving sensory-discriminative, affective-motivational, cognitive and locomotor components.

[The expert assessment of fibromyalgia]. / Zur Begutachtung der Fibromyalgie.

Research on fibromyalgia over the last ten years has focused on the broad variety of pathogenetic aspects of a pain amplification syndrome. This emphasizes pain as the leading symptom. The sociomedical implications are obvious and considerable, and therefore fibromyalgia has increasingly become the subject of expert assessments. The expert assessment should not discuss the existence or non-existence of fibromyalgia, but evaluate the individual impairments, disabilities and handicaps which may lead to an individual degree of dysfunctioning.

Endocrine aspects of paediatric rheumatic diseases.

Compared to the now numerous studies on the endocrinology of rheumatic diseases in adults, only a small number of studies has been published on children with rheumatic diseases. Prolactin has been most extensively investigated, showing interesting parallels with the findings in adults with rheumatological diseases. Thus, analogous to adult RA most forms of JRA or JCA (with the exception of ANA-positive JRA with uveitis) appear to show, if anything, low to normal levels of prolactin. Since the prolactin levels in adult RA depend on the inflammatory activity, and the physiological prolactin secretion decreases in chronic stress (especially sleep disorders), these results are most likely to be explained as reactive non-specific mechanisms in the stress of the disease. However, specific mechanisms are also being discussed to explain the low prolactin levels in adult RA. The results of prolactin measurements in juvenile SLE, juvenile ankylosing spondylitis and ANA-positive JRA with a raised incidence of uveitis, contrast with this. These conditions sometimes show significantly higher prolactin levels compared to healthy controls. A correlation of the increase of prolactin concentration with the inflammatory activity has been described for juvenile ankylosing spondylitis. These results correlate well with those of adult forms such as diseases of the seronegative spondyloarthropathies type, SLE and iridocyclitis. Raised prolactin concentrations are also found in these diseases. The inflammation promoting and immunostimulatory effects of prolactin found especially in animal experiments are confirmed clinically in these diseases by reports of successful treatments with the prolactin inhibitor, bromocriptine. The results available up to now for human growth hormone in JRA and JCA tend to be comparable with the results for prolactin in these form of paediatric rheumatological diseases. Besides normal values above, all lowered concentrations are measured for this hormone. Apart from other non-specific factors, its diminished secretion is mainly determined by the inflammatory activity of the disease. Low levels of growth hormone are likely to be a significant factor in the growth retardation in children with inflammatory rheumatological diseases. Up to now, the small number of investigations on gonadotrophins and the sex hormones in juvenile SLE and various forms of JRA published have not as yet yielded unequivocal results. The endocrine aspects of paediatric rheumatological diseases are thus still incompletely elucidated. However, there are many promising avenues for further fruitful research in this field.

[Essential cryoglobulinemic vasculitis with severe peripheral neuropathy and neurogenic muscular atrophy -- inducing remission by cascade filtration]. / Essentielle kryoglobulinämische Vaskulitis mit hochgradiger peripherer Neuropathie und neurogener Muskelatrophie -- Remissionsinduktion mittels Differenzialfiltrationsapherese.

We report on a 60 year old patient with peripheral neuropathy, neurogenic muscular atrophy, skin ulcers, arthritis and weakness. Detection of cryoglobulins in association with typical clinical symptoms, exclusion of hepatitis C and any other disease led to a rare diagnosis: essential cryoglobulinemic vasculitis. The case demonstrates not only the difficult diagnostic process but also the problems of an adequate and effective therapy. Since the usual immunosuppressive treatments such as methotrexate, high dose corticosteroid and intermittent intravenous pulse cyclophosphamide therapy (Austin's scheme) failed, we performed plasmapheresis (cascade filtration), which brought about an immediate and long-term remission. Besides discussing various types of plasmapheresis procedures and potential pathophysiological mechanisms, we point out that this therapy could find an early use in severe essential cryoglobulinemic vasculitis because of its excellent risk/benefit ratio.

Secretory pattern of GH, TSH, thyroid hormones, ACTH, cortisol, FSH, and LH in patients with fibromyalgia syndrome following systemic injection of the relevant hypothalamic-releasing hormones.

To study the hormonal perturbations in FMS patients we injected sixteen FMS patients and seventeen controls a cocktail of the hypothalamic releasing hormones: Corticotropin-releasing hormone (CRH), Thyrotropin-releasing hormone (TRH), Growth hormone-releasing hormone (GHRH), and Luteinizing hormone-releasing hormone (LHRH) and observed the hormonal secretion pattern of the pituitary together with the hormones of the peripheral endocrine glands. We found in FMS patients elevated basal values of ACTH and cortisol, lowered basal values of insulin-like growth factor I (IGF-I) and of triiodothyronine (T3), elevated basal values of follicle-stimulating hormone (FSH) and lowered basal values of estrogen. Following injection of the four releasing-hormones, we found in FMS patients an augmented response of ACTH, a blunted response of TSH, while the prolactin response was exaggerated. The effects of LHRH stimulation were investigated in six FMS patients and six controls and disclosed a significantly blunted response of LH in FMS. We explain the deviations of hormonal secretion in FMS patients as being caused by chronic stress, which, after being perceived and processed by the central nervous system (CNS), activates hypothalamic CRH neurons. CRH, on the one hand, activates the pituitary-adrenal axis, but also stimulates at the hypothalamic level somatostatin secretion which, in turn, causes inhibition of GH and TSH at the pituitary level. The suppression of gonadal function may also be attributed to elevated CRH by its ability to inhibit hypothalamic LHRH release, although it could act also directly on the ovary by inhibiting FSH-stimulated estrogen production. We conclude that the observed pattern of hormonal deviations in FMS patients is a CNS adjustment to chronic pain and stress, constitutes a specific entity of FMS, and is primarily evoked by activated CRH neurons.

Dynamic thermography of the knee joints in rheumatoid arthritis (RA) in the course of the first therapy of the patient with methylprednisolone.

Thermography in rheumatology is most often used in a static manner: after having fulfilled the conditions of standardized preparation of the patient in a cold examination room one or more thermograms are taken in standard positions for the respective joints. In our hospital the thermograms are more or less supplementary. The main examination result is a rewarming curve of the skin over the knee joints. The rewarming is provoked by dry cooling of the skin for one minute. Calculation of the slope of the rewarming curve and plotting the slope on a logarithmic scale shows two different rewarming processes in the skin overlying inflamed joints. The faster one is the rewarming by the arterial blood flow in the skin and the slower one is an additional rewarming by a pathological venous skin blood flow originating from deeper tissues under the skin. One has to suppose that the occurrence of excessive nitric oxide production in inflamed tissues is responsible for this pathological venous skin blood flow. Until now only nine patients receiving for the first time methylprednisolone could be included in a therapy study. Therefore only slight indications can be seen in the results. Whereas the erythrocyte sedimentation rate (ESR [mm/h] becomes more homogeneous (lower confidence interval CI 95) over the course of the treatment with decreasing drug dose, the thermal signs of inflammatory activity as measured by dynamic thermography have greater CI 95 values at the end than at the beginning of the treatment under study. This indicates that not all patients had sufficient antiinflammatory medication with the final 6 mg/d of methylprednisolone as measured by dynamic thermography but not by ESR or CRP.