M. Rudwaleit

Clinical response to discontinuation of anti-TNF therapy in patients with ankylosing spondylitis after 3 years of continuous treatment with infliximab

We analyzed the clinical response and the time to relapse after discontinuation of continuous long-term infliximab therapy in patients with ankylosing spondylitis (AS). After 3 years of infliximab therapy, all AS patients (n = 42) discontinued treatment (time point (TP)1) and were visited regularly for 1 year in order to assess the time to relapse (TP2). Relapse was defined as an increase to a value ≥ 4 on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and a physicians global assessment ≥ 4 according to the recommendations of the Assessments in Ankylosing Spondylitis (ASAS) working group. After 52 weeks, 41 of the 42 patients (97.6%) had to be reinfused because of relapse. The mean change in the BASDAI between TP1 and TP2 was 3.6 ± 1.7 and that in the physicians global assessment was 4.4 ± 1.8 (both P < 0.001). The mean time to relapse was 17.5 weeks (± 7.9 weeks, range 7 to 45). Ten patients (24%) showed a relapse within 12 weeks and 38 patients (90.5%), within 36 weeks. After 52 weeks, only one patient had remained in ongoing remission without further treatment with anti-tumor-necrosis factor. Patients who were in partial remission according to the ASAS criteria and those with normal C-reactive protein levels at the time point of withdrawal had longer times to relapse after discontinuation of the treatment. Retreatment with infliximab was safe and resulted in clinical improvement in all patients to a state similar to that before the treatment was stopped. Discontinuation of long-term therapy with infliximab eventually led to relapse of disease activity in all patients but one.

Low T cell production of TNFα and IFNγ in ankylosing spondylitis: its relation to HLA-B27 and influence of the TNF-308 gene polymorphism

OBJECTIVE To test the hypothesis that ankylosing spondylitis (AS) is a T helper cell type 2 polarised disease by quantifying the T cell cytokines interferon γ (IFNγ), interleukin 4 (IL4), tumour necrosis factor α (TNFα), and IL10 at the single cell level in patients with AS in comparison with healthy HLA-B27 negative and HLA-B27 positive controls. METHODS Peripheral blood mononuclear cells from 65 subjects (25 HLA-B27 positive patients with active AS, 18 healthy HLA-B27 positive controls, and 22 healthy HLA-B27 negative controls) were stimulated with phorbol myristate acetate/ionomycin for six hours, surface stained for CD3 and CD8, intracellularly stained for the cytokines IFNγ, TNFα, IL4, and IL10, and analysed by flow cytometry. TNFα production was related to the genotype of the TNFα promoter at the -308 and -238 polymorphisms. RESULTS In peripheral blood the percentage of TNFα+ T cells was significantly lower in HLA-B27 positive patients with AS (median 5.1% for CD4+ T cells) than in healthy HLA-B27 negative controls (median 9.5%; p=0.008). Surprisingly, the percentage of TNFα+ T cells was also significantly lower in healthy HLA-B27 positive controls (median 7.48%) than in healthy HLA-B27 negative controls (p=0.034). Furthermore, the percentage of IFNγ+ T cells was lower in patients with AS and in healthy HLA-B27 positive controls than in healthy HLA-B27 negative controls (p=0.005 and p=0.003, respectively). The percentage of IL10+/CD8+ T cells was higher in patients with AS than in both control groups. In HLA-B27 positive subjects, TNF1/2 heterozygosity at -308 (n=6) was associated with a higher percentage of TNFα+ T cells than TNF1/1 homozygosity (n=25; median 9.97%v 5.11% for CD4+ T cells; p=0.017). In contrast, in HLA-B27 negative controls (n=18) there was no such genotype/phenotype correlation (median 9.4%v 10.6%). CONCLUSIONS The lower T cell production of TNFα and IFNγ shown at the single cell level in HLA-B27 positive patients with AS and healthy HLA-B27 positive controls may contribute to the increased susceptibility of HLA-B27 positive subjects to develop AS. Preliminary genotype-phenotype correlations suggest that in HLA-B27 positive subjects TNF2 at -308 or a linked gene results in higher TNFα production and, therefore, might be a marker for a protective haplotype.

Association of genotypes affecting the expression of interleukin‐1β or interleukin‐1 receptor antagonist with osteoarthritis

OBJECTIVE The majority of cytokines and growth factors known to be involved in cartilage metabolism are synthesized by the chondrocytes themselves. They are up-regulated in osteoarthritic (OA) cartilage, resulting in 2 opposite phenotypes, TNFalpha(high) and TNFalpha(low), that are characterized by an elevated number of tumor necrosis factor alpha (TNFalpha)-positive and interleukin-1beta (IL-1beta)-positive chondrocytes, respectively. To establish a hierarchy among the cytokines and growth factors expressed in articular chondrocytes, this study investigated cytokine genes for known polymorphisms that may contribute to the deregulated expression in OA cartilage. METHODS Polymerase chain reaction techniques were performed either in a thermal cycler using standard methods or in a light cycler to analyze the frequencies of the TNFalpha (-308), IL-1 receptor antagonist (IL-1Ra) (intron 2), IL-1beta (exon 5), and IL-6 (-174) polymorphisms in 61 OA patients and 254 randomly chosen controls. RESULTS For the TNFalpha(low) phenotype, a statistically significant association was found with the less frequent allele of IL-1beta, which carries a single-basepair substitution in exon 5 and may contribute to the characteristic increase in IL-beta-positive chondrocytes. In contrast, the TNFalpha(high) phenotype was significantly associated with the less frequent allele of IL-1Ra, which carries two 86-bp repeats in the second intron and is assumed to lead to an elevated expression of the antagonist. CONCLUSION These results point to an association between the IL-1beta polymorphism and the TNFalpha(high) phenotype and between the IL-1Ra polymorphism and the TNFalpha(low) phenotype found in OA. Both associations suggest that IL-1beta may be more important than TNFalpha for the regulation of cytokine and growth factor expression in articular chondrocytes.

Multispecific CD4+ T Cell Response to a Single 12-mer Epitope of the Immunodominant Heat-Shock Protein 60 of Yersinia enterocolitica in Yersinia-Triggered Reactive Arthritis: Overlap with the B27-Restricted CD8 Epitope, Functional Properties, and Epitope Presentation by Multiple DR Alleles

Yersinia heat-shock protein 60 (Ye-hsp60) has recently been found to be a dominant CD4 and CD8 T cell Ag in Yersinia-triggered reactive arthritis. The nature of this response with respect to the epitopes recognized and functional characteristics of the T cells is largely unknown. CD4+ T cell clones specific for Ye-hsp60 were raised from synovial fluid mononuclear cells from a patient with Yersinia-triggered reactive arthritis. and their specificity was determined using three recombinant Ye-hsp60 fragments, overlapping 18-mer synthetic peptides as well as truncated peptides. Functional characteristics were assessed by cytokine secretion analysis in culture supernatants after specific antigenic stimulation. Amino acid positions relevant for T cell activation were detected by single alanine substitutions within the epitopes. Fragment II comprising amino acid sequence 182–371 was recognized by the majority of clones. All these clones were specific for peptide 319–342. Th1 clones and IL-10-secreting clones occurred in parallel, sometimes with the same fine specificity. The 12-mer core epitope 322–333 is a degenerate MHC binder and is presented to some T cell clones in a “promiscuous” manner. This epitope is almost identical with a B27-restricted CTL epitope of Ye-hsp60. Cross-reactivity of Ye-hsp60-specific T cell clones with self-hsp60 was not observed. In conclusion, an interesting Ye-hsp60 T cell epitope has been identified and characterized. It remains to be determined whether this epitope is also relevant in other reactive arthritis patients.

Validierung einer deutschen Version des Fragebogens BASDAI zur Messung der Krankheitsaktivität bei ankylosierender Spondylitis

Zusammenfassung.Zielsetzung: Das Ziel der vorliegenden Arbeit war die Validierung einer deutschen Übersetzung des “Bath Ankylosing Spondylitis Disease Activity Index” (BASDAI). Patienten und Methoden: Die Testung der Validität der deutschen Version des BASDAI erfolgte mit Daten einer Kohorte von 134 Patienten mit ankylosierender Spondylitis (AS). Hierzu wurde der BASDAI mit arztseitig erfassten Parametern verglichen: globales Urteil zur Krankheitsaktivität, C-reaktives Protein (CRP), Blutsenkungsgeschwindigkeit (BSG), Beweglichkeit der Wirbelsäule (BASMI), sowie Gelenkschwellung und Enthesitis (ja/nein). Darüber hinaus erfolgten Gegenüberstellungen mit Selbsteinschätzungen der Patienten zu Schmerzen, funktioneller Beeinträchtigung (BASFI) und Lebensqualität (SF-12). Die diskriminative Validität wurde durch Vergleiche der BASDAI-Scores von Subgruppen unterschiedlicher Krankheitsschwere geprüft. Die Änderungssensitivität wurde anhand von Verlaufsdaten einer Plazebo-kontrollierten Studie zur Wirksamkeit des Tumornekrosefaktor (TNF) α-Antagonisten Infliximab bei 70 Patienten mit aktiver und schwerer AS untersucht. Ergebnisse: Die deutsche Übersetzung des BASDAI erwies sich als gut verständlich. Nach Rückübersetzung entsprach die englische Version dem englischen Original. Es bestätigte sich, dass die 6 Einzelfragen sowohl unterschiedliche Aspekte der Erkrankung abbilden als auch deutliche Zusammenhänge zwischen den Einzelkomponenten wie Stärke der Morgensteifigkeit und Rückenschmerzen (r = 0,697) oder Stärke und Dauer der Morgensteifigkeit (r = 0,647) aufzeigen können. Die gute interne Konsistenz der 6 Komponenten (Cronbachs Alpha=0,82) bestätigte die Subsummierung der Komponenten zu einem Gesamtscore “Krankheitsaktivität”. Hohe Korrelationen mit dem globalen Arzturteil (r = 0,659), der globalen Einschätzung der Schmerzstärke durch den Patienten (r = 0,789), mit funktioneller Beeinträchtigung (BASFI; r = 0,752) und ein signifikanter Zusammenhang zu der Höhe des CRP und der BSG unterstreichen, dass der BASDAI Krankheitsaktivität misst. Im Vergleich von Patientensubgruppen unterschiedlicher Krankheitsschwere und Krankheitsmanifestationen zeigte der BASDAI gute diskriminative Fähigkeiten. In einer Therapiestudie bildete er die gute Wirksamkeit von Infliximab überzeugend ab (Effektstärke 1,18). Schlussfolgerung: Mit der deutsche Übersetzung des BASDAI steht ein gut verständliches, einfach anzuwendendes, zuverlässiges und änderungssensitives Instrument zur Erfassung der Krankheitsaktivität bei ankylosierender Spondylitis zur Verfügung.Summary.Objective: The purpose of this study was the validation of a German translation of the Bath Ankylosing Spondylitis Index (BASDAI). Patients and methods: The German translation of the BASDAI was validated using data of 134 patients with ankylosing spondylitis (AS) from a spondyloarthropathy cohort. For validation the BASDAI was compared with parameters assessed by physicians (physicians global, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), spinal mobility (BASMI), swollen joints, enthesitis (yes or no)), and parameters assessed by patients themselves (pain, function (BASFI) and quality of life (SF-12)). The discriminative validity was analyzed by comparison of BASDAI scores of patients subgroups who have different levels of disease severity. The sensibility to change was analyzed by using follow-up data of a clinical trial on efficacy of the anti-tumor necrosis factor (TNF) α agent infliximab in 70 AS-patients with active and severe disease. Results: The German translation of the BASDAI was easy to understand, the translation back to English corresponded well with the original English version. The 6 questions of the BASDAI represent different aspects of disease but correlated also well with each other (r < 0.65). There was a good internal consistency for all 6 questions (Cronbachs Alpha 0.82), strong correlations to the physicians global (r = 0.659), pain (r = 789), function (BASFI; r = 0.752) and to CRP and ESR confirming that the BASDAI assesses a comprehensive picture of patients disease activity. For subgroups of patients with different levels of disease severity or with different manifestations the BASDAI showed good discriminative properties. The BASDAI was sensitive to change during treatment with infliximab (effect size 1.18). Conclusion: The German translation of the BASDAI is easy to use, reliable, and sensitive to change for the assessment of disease activity in AS.

Severe Calciphylaxis in a Renal Patient on Long-Term Oral Anticoagulant Therapy

The pathogenesis of calciphylaxis, a potentially life-threatening condition, is not well understood. Several factors such as end-stage renal disease (azotemia), hyperparathyroidism, hyperphosphatemia, hypercalcemia, a high calcium-phosphate product, and the use of steroids and cytotoxic drugs after kidney transplantation are believed to interact in calciphylaxis. Recently, hypercoagulability due to functional protein C deficiency has been suggested to play a pathogenic role in this condition. Here, we present a renal transplant patient, with secondary hyperparathyroidism and on long-term oral anticoagulant therapy, who developed calciphylaxis with severe skin necrosis of her legs. The patients condition improved dramatically after total parathyroidectomy. Hypercoagulability, therefore, does not appear to have played a significant role in this case of calciphylaxis.

Bildgebende Verfahren in der Rheumatologie: Bildgebung bei der Psoriasisarthritis (PsA)

ZusammenfassungDie Standardmethode der Bildgebung bei der Psoriasisarthritis ist die konventionelle Radiologie, mit der sowohl bei gleichzeitiger Darstellung zahlreicher Gelenke die verschiedenen Befallsmuster der Erkrankung wie auch die knöchernen Veränderungen am einzelnen Gelenk bei hoher Ortsauflösung hervorragend dargestellt werden können. Von der RA unterscheidet sich die PsA durch häufigen Endgelenksbefall, Asymmetrie, strahlförmigen Befall, Oligoarthritis aber auch symmetrische Polyarthritis. Am einzelnen Gelenk findet sich ein Nebeneinander von Destruktion bis hin zur Mutilation und Proliferation mit Protuberanzen, periostalem Knochenanbau und oft auch Ankylose. Knochenan- und -abbau betreffen charakteristischerweise nicht nur die Gelenkregion sondern auch die Knochenschäfte mit Verdickung einerseits und konzentrischem Abbau bis zur Osteolyse andererseits. Für die Quantifizierung der Veränderungen bei klinischen Studien werden für die RA entwickelte Scoringmethoden eingesetzt. Bisher gibt es erst eine für die PsA entwickelte und validierte Methode, die sowohl Destruktion wie Proliferation berücksichtigt. Im Unterschied zur konventionellen Radiologie können mit der MRT wie auch der Sonographie die an den Weichteilen (Gelenkkapsel, Sehnenscheiden, Sehneninsertionen) ablaufenden entzündlichen Prozesse dargestellt und so auch eine Aussage über die momentane Aktivität der Erkrankung gemacht werden. Die prinzipiell unspezifische Szintigraphie kann allenfalls zum Auffinden klinisch stummer Entzündungsherde herangezogen werden.Der relativ häufige Achsenskelettbefall unterscheidet sich von der ankylosierenden Spondylitis (AS) allenfalls durch eine häufiger unilaterale Sacroiliitis, Asymmetrie der Syndesmophyten und Auftreten von Parasyndesmophyten. Während das konventionelle Röntgen die knöchernen Folgen der Entzündung sichtbar macht, erlaubt die MRT auch eine Aussage über akut entzündliche Veränderungen an den Sacroiliacalgelenken und den Wirbelkörpern.SummaryConventional radiography is still the standard method of imaging in PsA since it displays many joints at the same time, thereby allowing different types of joint involvement to be recognized. Moreover, thanks to the high resolution of radiography, bony changes in a single joint are depicted in a brilliant way. Several features of psoriatic arthritis allow the distinction from rheumatoid arthritis, including the frequent involvement of the distal interphalangeal joints, asymmetry of joint involvement, axial involvement of finger joints, oligoarticular involvement; however, symmetric polyarthritis is also possible. At the level of the single joint, there are signs of severe destructive changes potentially leading to mutilation and at the same time signs of periostal bone proliferation and ankylosis may be present. Bony proliferation and/or osteolysis are not restricted to the joint region but can affect also the total phalanx with bone apposition or concentric osteolysis which may lead to a complete disappearance of phalanxes. For purposes of quantification of radiographic changes scoring methods are used that were originally developed for rheumatoid arthritis. So far, there is only one validated scoring method that was specifically designed for PsA and that takes into account both features of PsA, damage as well as proliferation of bone.In contrast to conventional radiography, MRI and sonography are able to visualize inflammatory processes within the soft tissue (joint capsules, tendon sheaths, tendon insertions, etc.), allowing an estimation of disease activity. Scintigraphy is nonspecific and can only be used to detect clinically silent inflammatory spots.The relatively frequent spinal (axial) involvement is similar to that seen in ankylosing spondylitis. However, unilateral sacroiliitis, asymmetry of syndesmophytes and development of parsyndesmophytes may distinguish PsA from ankylosing spondylitis. While conventional radiography demonstrates the bony consequences of inflammation in the spine, MRI also shows the active inflammatory changes in sacroiliacal joints and vertebrae.Conventional radiography is still the standard method of imaging in PsA since it displays many joints at the same time, thereby allowing different types of joint involvement to be recognized. Moreover, thanks to the high resolution of radiography, bony changes in a single joint are depicted in a brilliant way. Several features of psoriatic arthritis allow the distinction from rheumatoid arthritis, including the frequent involvement of the distal interphalangeal joints, asymmetry of joint involvement, axial involvement of finger joints, oligoarticular involvement; however, symmetric polyarthritis is also possible. At the level of the single joint, there are signs of severe destructive changes potentially leading to mutilation and at the same time signs of periostal bone proliferation and ankylosis may be present. Bony proliferation and/or osteolysis are not restricted to the joint region but can affect also the total phalanx with bone apposition or concentric osteolysis which may lead to a complete disappearance of phalanxes. For purposes of quantification of radiographic changes scoring methods are used that were originally developed for rheumatoid arthritis. So far, there is only one validated scoring method that was specifically designed for PsA and that takes into account both features of PsA, damage as well as proliferation of bone. In contrast to conventional radiography, MRI and sonography are able to visualize inflammatory processes within the soft tissue (joint capsules, tendon sheaths, tendon insertions, etc.), allowing an estimation of disease activity. Scintigraphy is nonspecific and can only be used to detect clinically silent inflammatory spots. The relatively frequent spinal (axial) involvement is similar to that seen in ankylosing spondylitis. However, unilateral sacroiliitis, asymmetry of syndesmophytes and development of parsyndesmophytes may distinguish PsA from ankylosing spondylitis. While conventional radiography demonstrates the bony consequences of inflammation in the spine, MRI also shows the active inflammatory changes in sacroiliacal joints and vertebrae.

Epidemiologie und Versorgung im Bereich der Spondylarthropathien

Zusammenfassung Zu den bedeutendsten entzündlich rheumatischen Erkrankungen werden die Spondylarthropathien neben der rheumatoiden Arthritis gezählt. Ihre Prävalenz wurde lange unterschätzt. Heute ist bekannt, dass sie als Gesamtgruppe nahezu ebenso häufig wie die rheumatoide Arthritis vorkommen. Hauptvertreter der Spondylarthropathien in der westlichen Welt sind die ankylosierende Spondylitis (AS) und die undifferenzierte Spondylarthropathie (uSpA). Die Diagnose insbesondere der frühen Formen ist schwierig. Bislang ist die Datenlage zur sozioökonomischen Situation jedoch spärlich, und die Therapiemöglichkeiten limitiert. In den letzten Jahren sind Fortschritte auf diesem Gebiet gemacht worden, erste sozioökonomische Untersuchungen und Daten über die Krankeitsbelastung, aber auch bessere diagnostische Möglichkeiten stehen für die Frühdiagnose zur Verfügung. In jüngster Zeit gibt es vielversprechende Therapieansätze u.a. seit die gute Wirksamkeit von TNF-alpha-Blockern nachgewiesen werden konnte. Weitere Untersuchungen zu dieser unterschätzten Erkrankungsgruppe sind notwendig und erfolgen innerhalb des Kompetenznetzes Rheumatologie.Summary Within the group of inflammatory rheumatic diseases, spondyloarthropathy is the most common diagnosis after rheumatoid arthritis. Its prevalence was long underestimated. Ankylosing spondylitis (AS) and undifferentiated spondyloathropathy (uSpA) are the most common subgroups in western countries. There are still difficulties in diagnosis especially of the early forms of the spondyloarthropathies. Data of socioeconomics and therapeutic options are limited. In more recent times, researchers have started to investigate the burden of disease and the socioeconomic aspects. Better diagnostic options are available and promising new therapeutic agents, especially TNF-alpha blocking agents, have been investigated. However, further studies are urgently needed for this underestimated group of diseases and are currently being performed inside the German rheumatology network.

[Imaging methods in rheumatology: imaging in psoriasis arthritis (PsA)].

ZusammenfassungDie Standardmethode der Bildgebung bei der Psoriasisarthritis ist die konventionelle Radiologie, mit der sowohl bei gleichzeitiger Darstellung zahlreicher Gelenke die verschiedenen Befallsmuster der Erkrankung wie auch die knöchernen Veränderungen am einzelnen Gelenk bei hoher Ortsauflösung hervorragend dargestellt werden können. Von der RA unterscheidet sich die PsA durch häufigen Endgelenksbefall, Asymmetrie, strahlförmigen Befall, Oligoarthritis aber auch symmetrische Polyarthritis. Am einzelnen Gelenk findet sich ein Nebeneinander von Destruktion bis hin zur Mutilation und Proliferation mit Protuberanzen, periostalem Knochenanbau und oft auch Ankylose. Knochenan- und -abbau betreffen charakteristischerweise nicht nur die Gelenkregion sondern auch die Knochenschäfte mit Verdickung einerseits und konzentrischem Abbau bis zur Osteolyse andererseits. Für die Quantifizierung der Veränderungen bei klinischen Studien werden für die RA entwickelte Scoringmethoden eingesetzt. Bisher gibt es erst eine für die PsA entwickelte und validierte Methode, die sowohl Destruktion wie Proliferation berücksichtigt. Im Unterschied zur konventionellen Radiologie können mit der MRT wie auch der Sonographie die an den Weichteilen (Gelenkkapsel, Sehnenscheiden, Sehneninsertionen) ablaufenden entzündlichen Prozesse dargestellt und so auch eine Aussage über die momentane Aktivität der Erkrankung gemacht werden. Die prinzipiell unspezifische Szintigraphie kann allenfalls zum Auffinden klinisch stummer Entzündungsherde herangezogen werden.Der relativ häufige Achsenskelettbefall unterscheidet sich von der ankylosierenden Spondylitis (AS) allenfalls durch eine häufiger unilaterale Sacroiliitis, Asymmetrie der Syndesmophyten und Auftreten von Parasyndesmophyten. Während das konventionelle Röntgen die knöchernen Folgen der Entzündung sichtbar macht, erlaubt die MRT auch eine Aussage über akut entzündliche Veränderungen an den Sacroiliacalgelenken und den Wirbelkörpern.SummaryConventional radiography is still the standard method of imaging in PsA since it displays many joints at the same time, thereby allowing different types of joint involvement to be recognized. Moreover, thanks to the high resolution of radiography, bony changes in a single joint are depicted in a brilliant way. Several features of psoriatic arthritis allow the distinction from rheumatoid arthritis, including the frequent involvement of the distal interphalangeal joints, asymmetry of joint involvement, axial involvement of finger joints, oligoarticular involvement; however, symmetric polyarthritis is also possible. At the level of the single joint, there are signs of severe destructive changes potentially leading to mutilation and at the same time signs of periostal bone proliferation and ankylosis may be present. Bony proliferation and/or osteolysis are not restricted to the joint region but can affect also the total phalanx with bone apposition or concentric osteolysis which may lead to a complete disappearance of phalanxes. For purposes of quantification of radiographic changes scoring methods are used that were originally developed for rheumatoid arthritis. So far, there is only one validated scoring method that was specifically designed for PsA and that takes into account both features of PsA, damage as well as proliferation of bone.In contrast to conventional radiography, MRI and sonography are able to visualize inflammatory processes within the soft tissue (joint capsules, tendon sheaths, tendon insertions, etc.), allowing an estimation of disease activity. Scintigraphy is nonspecific and can only be used to detect clinically silent inflammatory spots.The relatively frequent spinal (axial) involvement is similar to that seen in ankylosing spondylitis. However, unilateral sacroiliitis, asymmetry of syndesmophytes and development of parsyndesmophytes may distinguish PsA from ankylosing spondylitis. While conventional radiography demonstrates the bony consequences of inflammation in the spine, MRI also shows the active inflammatory changes in sacroiliacal joints and vertebrae.Conventional radiography is still the standard method of imaging in PsA since it displays many joints at the same time, thereby allowing different types of joint involvement to be recognized. Moreover, thanks to the high resolution of radiography, bony changes in a single joint are depicted in a brilliant way. Several features of psoriatic arthritis allow the distinction from rheumatoid arthritis, including the frequent involvement of the distal interphalangeal joints, asymmetry of joint involvement, axial involvement of finger joints, oligoarticular involvement; however, symmetric polyarthritis is also possible. At the level of the single joint, there are signs of severe destructive changes potentially leading to mutilation and at the same time signs of periostal bone proliferation and ankylosis may be present. Bony proliferation and/or osteolysis are not restricted to the joint region but can affect also the total phalanx with bone apposition or concentric osteolysis which may lead to a complete disappearance of phalanxes. For purposes of quantification of radiographic changes scoring methods are used that were originally developed for rheumatoid arthritis. So far, there is only one validated scoring method that was specifically designed for PsA and that takes into account both features of PsA, damage as well as proliferation of bone. In contrast to conventional radiography, MRI and sonography are able to visualize inflammatory processes within the soft tissue (joint capsules, tendon sheaths, tendon insertions, etc.), allowing an estimation of disease activity. Scintigraphy is nonspecific and can only be used to detect clinically silent inflammatory spots. The relatively frequent spinal (axial) involvement is similar to that seen in ankylosing spondylitis. However, unilateral sacroiliitis, asymmetry of syndesmophytes and development of parsyndesmophytes may distinguish PsA from ankylosing spondylitis. While conventional radiography demonstrates the bony consequences of inflammation in the spine, MRI also shows the active inflammatory changes in sacroiliacal joints and vertebrae.

T cell response to human HSP60 and yersinia 19 kDa in ankylosing spondylitis and rheumatoid arthritis: no evidence for a causal role of these antigens in the pathogenesis

The pathogenesis of two important inflammatory rheumatic diseases, rheumatoid arthritis (RA) and ankylosing spondylitis (AS), is not clear. In both diseases an immune response against an unknown autoantigen may have a crucial role.1,2 It has been repeatedly suggested that heat shock proteins (HSP) play a part in various autoimmune diseases such as RA, diabetes, and multiple sclerosis,3 based on high interspecies sequence homologies, inducible tissue expression, and a strong immunogenicity. On the other hand, some studies indicate that HSP may even be protective in arthritis.4 The 19 kDa urease β subunit of yersinia is regarded as a major immunodominant protein for both T cell and antibody responses in patients with yersinia induced reactive arthritis.5 Because 20–30% of HLA-B27+ patients with yersinia induced reactive arthritis develop the full picture of AS after 10–20 years,6 it is an obvious question to ask whether a T cell response against the yersinia-specific 19 kDa protein is also detectable in patients with AS. …