Psoriatic arthritis (PsA) is a chronic inflammatory joint disease with heterogeneous clinical presentation and unpredictable course but often with a tendency to irreversible joint damage. Joint damage can occur early in the disease also in the absence of significant clinical signs of arthritis. These observations and the current availability of effective treatments in controlling skin and joint disease underline the importance of early diagnosis of PsA. The use of specific questionnaires for screening patients at risk of psoriatic arthritis, knowledge of new classification criteria for PsA and especially the proper use of new imaging techniques are all important steps in achieving the goal of early diagnosis of PsA. The dermatologist may play a key role in this regard supported, when necessary, by the collaboration of the rheumatologist and radiologist.

The differences in systemic T-cell responses between patients with psoriatic arthritis (PsA) and patients with cutaneous psoriasis (Ps) are still largely unknown. To determine differential features that could be used to distinguish PsA from Ps, we compared the cytokine secretion profile of circulating T cells in patients with PsA, patients with cutaneous Ps and control subjects. We determined Th1, Th2 and Th17 cytokine secretion of anti-CD3-stimulated peripheral blood mononuclear cells (PBMCs) using a cytokine bead array. Normality of data distribution was assessed by the Shapiro-Wilk test, and statistical significance was calculated by the Mann-Whitney test. Phenotypic characterization of circulating T cells was performed by fluorescence-activated cell sorting analysis. We found that the major systemic differences distinguishing PsA from cutaneous Ps were the increased secretion of interleukin (IL)-2 by -CD3-stimulated PBMCs and a higher percentage of circulating CD3+ T cells expressing the proliferation marker CD71 in PsA. These results indicate IL-2 as a possible biomarker of PsA, and suggest a role of circulating T cells with high proliferative capacity in the pathogenesis of PsA.

We examined the effect of the protein kinase C-selective inhibitor AEB071 (sotrastaurin) on neutrophil functions in vitro. Pre-incubation with AEB071 at concentrations similar to those reached during in vivo therapy significantly reduced cell capacity to migrate toward three different chemo-attractants and to produce superoxide anions (O 2 ) in response to phorbol myristate acetate (PMA) or to iV-formyl-methionyl-leucyl-phenylalanine (fMLP). AEB071 also significantly inhibited the O − 2 “overproduction induced by fMLP in neutrophils primed with tumor necrosis factor alpha (TNF-α) or granulocyte/macrophage-colony stimulating factor (GM-CSF). This inhibition was not linked to fMLP-receptor down-regulation since the drug had no effect on either fMLP-receptors or fMLP-induced CD11b membrane expression. When the activity of AEB071 was compared to that of the conventional protein kinase C (PKC) inhibitor Gö6850 (which, like sotrastaurin, inhibits classical and novel PKC isoforms), Gö6976 (an inhibitor of α and β PKC isoforms) and rottlerin (a prevailing δ PKC isoform inhibitor), AEB071 at an equimolar concentration of 3 μM (close to the maximum drug concentration reached in patients treated with AEB071) caused significantly more inhibition on both chemotactic response and superoxide production. These in vitro findings suggest that neutrophils may offer a cellular target for AEB071 activity in vivo.

Amicrobial pustulosis associated with autoimmune diseases (APAD) is a clinical entity which was described only recently and few cases are reported in the literature. This condition is characterized by recurrent acute onset with pustular lesions predominantly involving skin folds, genitals, scalp and external auditory canals of young women. The etiopathogenesis of APAD is unknown and the most effective therapeutic treatment seems to be systemic corticosteroids. We describe the case of a 16-year old female patient suffering from APAD successfully treated with cyclosporine A.

Previous reports have suggested an increased risk of psoriasis in MS patients. Worsening of dermatologic lesions during interferon therapy has been rarely reported, but activation of psoriatic arthritis has not been described until now. The following is a case report. A 37-year-old woman affected by relapsing–remitting multiple sclerosis had severe worsening of cutaneous psoriasis and activation of psoriatic arthritis during interferon beta treatment. The symptoms resolved after therapy discontinuation. This case further supports that activation of psoriasis might be a rare side effect of IFNB therapy and suggests careful evaluation of concomitant morbidity to allow a patient-oriented treatment strategy.

Osteonecrosis of the jaw (ONJ) is a well-known devastating side effect of parenteral bisphosphonate therapy for cancer. Several ONJ cases have been reported in patients taking oral bisphosphonates for osteoporosis or Paget's disease. Even if the number of cases of ONJ in patients taking oral bisphosphonates are still rare compared to the total exposure, rheumatologists treating bone diseases with bisphosphonates must be aware of this new complication, allowing for prevention and early diagnosis. The patients must be informed on the benefit/risk of bisphosphonate therapy and, when necessary and possible, alternative therapy for postmenopausal osteoporosis should be considered. The need for the patient to be dentally fit and to maintain this state forever should be part of the informed consent for bisphosphonate treatment. It is uncommon for rheumatologists to ask about dental problems but this new bisphosphonate- associated complication highlights the need for this to change. In this paper we review the literature available on this newly described bisphosphonate-induced complication with particular emphasis on ONJ cases related to the use of oral bisphosphonates.

We evaluated the effect of efalizumab on neutrophil and monocyte functions. The in vitro pre-incubation with efalizumab concentrations similar to those reached during in vivo therapy almost completely saturated CD11a binding sites without affecting the membrane expression of CD11b, CD128a or CD128b. There was a significant reduction in the chemotactic activity of the pre-treated cells toward three different chemo-attractants, whereas their phagocytic capacity and production of oxygen radicals remained unchanged. One month after the administration of efalizumab to five patients with psoriasis (T1) circulating neutrophil counts increased by 34% from pre-therapy (T0) with no change in the number of monocytes. In the same patients the CD11a binding sites on phagocytes were >90% saturated, and there was also a significant down-modulation on neutrophils (44% of T0) and monocytes (63% of T0). In line with in vitro results, efalizumab treatment caused a significant deficiency in the chemotactic properties of neutrophils and monocytes, but no changes in phagocytosis, oxidative burst, production of pro-inflammatory cytokines or the membrane expression of CD11b, CD128a and CD128b. Our findings suggest that neutrophils and monocytes may be among the targets of efalizumab activity in patients with psoriasis.

TNF-alpha is a crucial cytokine in the establishment and maintenance of inflammation in multiple autoimmune and non-autoimmune disorders. A number of large placebo-controlled trials have shown that infliximab, a chimeric monoclonal antibody against TNF-alpha, is effective and well-tolerated in patients with Crohn's disease and rheumatoid arthritis (RA) and has become a widely used treatment for these diseases. More recent controlled trials have also shown the effectiveness of TNF-alpha blockers in psoriasis, psoriatic arthritis, and ankylosing spondylitis. The results of clinical trials, open-label studies, and case studies indicate that TNF inhibitors (alone or in combination with other protocols) look very promising for the treatment of a variety of other conditions, including uveitis, sarcoidosis, Sjogren's syndrome (SS), Behcet's syndrome, vasculitis, and graft versus host disease. There is a rationale for using TNF blockade even in systemic lupus erythematosus, a prototype of autoantibody-mediated disease, and a pilot study seems to confirm this potential effective approach. The neutralisation of TNF might therefore play a role in the treatment of many autoimmune and non-autoimmune disorders other than Crohn's disease or RA.We here review the current and prospective roles of infliximab in the treatment of autoimmune diseases and other conditions that do not currently have FDA or EMEA approval. (c) 2004 Elsevier B.V. All rights reserved.

The thorax and spine house many vital organs and are in constant motion throughout our lives, from basic respiration through to support and movement during locomotion. This chapter provides an overview of a number of skeletal indicators of behaviour used by bioarchaeologists to attempt to understand various biological and social aspects of past humans and our fossil relatives. By understanding healthy skeletal variation of the human spine and thorax and how this compares to fossil hominins and extant non-human apes, we can identify traits related to our location to help us trace the origin of bipedalism, which was a vital part of human evolution. Further, investigating pathological lesions and deformations in the thorax can indicate important cultural practices in the past, such as clothing fashion, medical interventions, subsistence-related activities, rituals, interpersonal violence, and abuse. All of this information provides unique and valuable insights into human behaviours populations, allowing bioarchaeologists to use the thorax and spine to reconstruct what life was like for people in the past.

We report a patient with longstanding systemic lupus erythematosus (SLE) who developed pure red cell aplasia (PRCA). This condition is rare in connective tissue diseases and is reported in 32 previous cases of SLE in literature. Our patient recovered, apparently in response to treatment with high dosage of corticosteroids, but relapse occurred when the prednisone dosage was tapered down to 10 mg/day. The patient was successfully treated with cyclosporin A with no recurrence of the disease in the last 2 years.

OBJECTIVEIn the dynamic organization of sleep, cyclic alternating pattern (CAP) expresses a condition of instability of the level of vigilance that manifests the brain's fatigue in preserving and regulating the macrostructure of sleep. We evaluated the presence of CAP in patients with fibromyalgia (FM) compared to healthy controls.METHODSForty-five patients with FM (42 women) were studied and compared with 38 healthy subjects (36 women) matched for age, sex, and body mass index. Entry criteria were diagnosis of FM according to 1990 American College of Rheumatology criteria; willingness to participate in the study; and having no other diagnosis of autoimmune, neoplastic, or other possible causes of secondary diffuse musculoskeletal pain. Patients in the study underwent polysomnography recordings and a sleep questionnaire. Hypersomnolence was evaluated according to the Epworth Sleepiness Scale.RESULTSFM patients had less sleep efficiency (sleep time/time in bed) than controls (79 +/- 10 vs 89 +/- 6; p < 0.01), a higher proportion of stage 1 non-rapid eye movement (non-REM) sleep (20 +/- 5 vs 12 +/- 5; p < 0.001), and twice as many arousals per hour of sleep (9.7 +/- 3.3 vs 4.1 +/- 1.9; p < 0.01). The CAP rate (total CAP time/non-REM sleep time) was significantly increased in FM patients compared to controls (68 +/- 6% vs 45 +/- 11%; p < 0.001). CAP rate seemed to correlate with the severity of clinical symptoms in FM patients (tender points index; p < 0.01) and with less efficiency of sleep (p < 0.01).CONCLUSIONThe increase of CAP rate indicates a worse quality of sleep in patients with FM. These data are strongly correlated to the severity of symptoms.

OBJECTIVE:Since the early activation antigen CD69 has been implicated in the pathogenesis of some inflammatory diseases, we evaluated the expression of the molecule on peripheral blood (PB) and synovial fluid (SF) neutrophils obtained from RA patients and its possible correlation with PB and SF cytokine concentration.METHODS:CD69 membrane expression (and CD11b as control marker) was assessed by indirect immunofluorescence and flow cytometry analysis on purified PB and SF neutrophils. Cytokine levels (GM-CSF, IFN-gamma, TNF-alpha) in plasma and SF supernatants were measured by ELISA.RESULTS:CD69 was absent on control neutrophils, while it was expressed on PB neutrophils from RA patients although no detectable GM-CSF, IFN-gamma or TNF-alpha was observed in their plasma. CD69 expression was still more evident on SF neutrophils from RA patients; 59% had detectable levels of INF-gamma in their SF while GM-CSF and TNF-alpha were detectable in SF from 95% and 33% of RA patients, respectively. However, no correlation was observed between cytokine concentrations and CD69 expression on SF neutrophils. SF but not PB neutrophils from RA patients expressed increased amounts of CD11b when compared to control PB neutrophils without any correlation with CD69 membrane expression.CONCLUSION:The activation antigen CD69 is significantly expressed on PB and SF neutrophils from RA patients. However, the mechanism(s) of induction and its possible role in the pathogenesis of RA remain to be defined.