Investigating the Effectiveness of a Carb-Free Oloproteic Diet in Fibromyalgia Treatment.

Fibromyalgia (FM), a chronic disease with a high incidence in women, poses a significant challenge for diagnosis and treatment, especially due to the absence of specific biomarkers and the multifaceted nature of its symptoms, which range from neuromuscular pain to mood disorders and intestinal dysbiosis. While diagnosis currently relies on rheumatological clinical evaluations and treatment options mainly focus on symptom management, FM seems to have possible links with systemic metabolic dysfunctions with a common inflammatory root. In this context, a new therapeutic avenue emerges: could a therapeutic nutritional approach be the missing piece of the puzzle? Indeed, diet therapies employed particularly for metabolic syndromes proved recently to be efficacious for correcting systemic dysmetabolism and a high number of chronic inflammation conditions. In particular, the very-low-calorie ketogenic diet (VLCKD) demonstrated therapeutic benefits in many disorders. In the present study, we aimed to investigate the specific effects of two dietary interventions, namely the oloproteic VLCKD and the low-glycemic insulinemic (LOGI) diet, on two groups of female FM patients (FM1 and FM2) over a 45-day period. Utilizing clinical and laboratory tests, as well as non-invasive NMR metabolomic analysis of serum, urine, and saliva samples, we sought to uncover how these dietary regimens impact the metabolic dysfunctions associated with FM.

Thalassemic trait prevalence in patients affected by psoriatic arthritis in anti-TNF treatment.

Thalassemic trait (Thal) is associated with rheumatic disease, particularly a mild form of seronegative polyarthritis resembling rheumatoid arthritis (RA), but not with other rheumatic diseases. The aim of this study was to estimate the frequency of Thal in patients with psoriatic arthritis (PsA) and to evaluate the efficacy of anti-tumor necrosis factor alpha (TNF-α) therapy in patients with PsA and Thal. We performed a retrospective study in 321 patients with PsA who started therapy with TNF-α blockers. For all patients included in the study, at baseline and every 3 months for the 1 year of follow up, data concerning PsA activity and ferritin levels were registered. In our group of PsA patients, a total of 27 (8%) with concomitant Thal were identified and included in the study. In patients without Thal, all variables improved significantly after 6 months of therapy, while in patients with Thal, the same variables showed a significant decrease after 12 months.: Our study shows that PsA is significantly associated with Thal, but further studies are needed to address this issue. The presence of Thal could be a negative predictor of achieving remission during treatment with TNF-α-blockers.

Untangling the web of systemic autoinflammatory diseases.

The innate immune system is involved in the pathophysiology of systemic autoinflammatory diseases (SAIDs), an enlarging group of disorders caused by dysregulated production of proinflammatory cytokines, such as interleukin-1ß and tumor necrosis factor-α, in which autoreactive T-lymphocytes and autoantibodies are indeed absent. A widely deranged innate immunity leads to overactivity of proinflammatory cytokines and subsequent multisite inflammatory symptoms depicting various conditions, such as hereditary periodic fevers, granulomatous disorders, and pyogenic diseases, collectively described in this review. Further research should enhance our understanding of the genetics behind SAIDs, unearth triggers of inflammatory attacks, and result in improvement for their diagnosis and treatment.

Biological treatments in Behçet's disease: beyond anti-TNF therapy.

Behçet's disease (BD) is universally recognized as a multisystemic inflammatory disease of unknown etiology with chronic course and unpredictable exacerbations: its clinical spectrum varies from pure vasculitic manifestations with thrombotic complications to protean inflammatory involvement of multiple organs and tissues. Treatment has been revolutionized by the progressed knowledge in the pathogenetic mechanisms of BD, involving dysfunction and oversecretion of multiple proinflammatory molecules, chiefly tumor necrosis factor- (TNF-) α, interleukin- (IL-) 1ß, and IL-6. However, although biological treatment with anti-TNF-α agents has been largely demonstrated to be effective in BD, not all patients are definite responders, and this beneficial response might drop off over time. Therefore, additional therapies for a subset of refractory patients with BD are inevitably needed. Different agents targeting various cytokines and their receptors or cell surface molecules have been studied: the IL-1 receptor has been targeted by anakinra, the IL-1 by canakinumab and gevokizumab, the IL-6 receptor by tocilizumab, the IL12/23 receptor by ustekinumab, and the B-lymphocyte antigen CD-20 by rituximab. The aim of this review is to summarize all current experiences and the most recent evidence regarding these novel approaches with biological drugs other than TNF-α blockers in BD, providing a valuable addition to the actually available therapeutic armamentarium.

Biological therapies for spondyloarthritis.

Biological therapies and new imaging techniques have changed the therapeutic and diagnostic approach to spondyloarthritis. In patients with axial spondyloarthritis, tumor necrosis factor α (TNFα) inhibitor treatment is currently the only effective therapy in patients for whom conventional therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) has failed. TNFα inhibitor treatment is more effective in preventing articular damage in peripheral joints than in axial ones. It is important to treat patients at an early stage of disease to reduce disease progression; moreover it is necessary to identify causes of therapy inefficacy in preventing joint damage in the axial subset.

Efficacy of tocilizumab in a patient with refractory psoriatic arthritis.

Psoriatic arthritis (PsA) is an inflammatory arthropathy, associated with skin and/or nail psoriasis and other possible systemic features. In the last years, PsA therapy has been revolutionized by the increasing knowledge in the pathogenetic mechanisms of the disease, involving dysfunction and oversecretion of multiple proinflammatory molecules, in particular tumor necrosis factor (TNF)-α. Hence, therapy of PsA refractory to disease-modifying antirheumatic drugs (DMARDs) relies mainly on the use of anti-TNF-α agents. However, since PsA can often be refractory also to these therapies, use of agents acting on other cytokines, such as interleukin (IL)-1 receptor targeted by anakinra, the IL-12/23 receptor by ustekinumab, the IL-17A by secukinumab, and the IL-6 receptor by tocilizumab, has been reported successfully. Herein we report a case of a refractory PsA patient successfully treated with the IL-6 receptor agent, tocilizumab. A review of the literature on the use of tocilizumab in PsA has been performed.

The enthesopathy of celiac patients: effects of gluten-free diet.

Celiac disease (CD) is a gluten-sensitive enthesopathy occurring in genetically predisposed individuals that is caused by a permanent intolerance to gluten. The major environmental factor associated with the risk of developing celiac-related complications is persistent exposure to dietary gluten. The aim of this study was to determine the prevalence of lower limb enthesopathy in CD patients at first diagnosis compared with CD patients on a gluten-free diet (GFD). Fifty-five untreated CD patients (group A) and 55 CD patients on a GFD from at least 1 year (group B), matched for age and sex, attending gastroenterology outpatient clinic of the University Federico II of Naples, were enrolled in this study. All patients underwent clinical and ultrasonography examination. Among group A, 27 (49.8 %) patients presented at least one entheseal alteration as compared with 15 patients (27.2 %) of group B (prevalence rate ratio 1.83, I.C. 95 % = 0.48-7.01; p < 0.001). The Glasgow ultrasound enthesitis scoring system (GUESS) was significantly higher in patients of group A than in patients of group B. In conclusion, our study shows that enthesopathy is more frequent in untreated CD subjects with positive anti-tissue transglutaminase antibodies title, as compared to those on GFD and absence of serum anti-tissue transglutaminase antibodies title.

The use of TNF-α blockers in psoriatic arthritis patients with latent tuberculosis infection.

Psoriatic arthritis (PsA) is an inflammatory arthropathy associated with skin and/or nail psoriasis. TNF-α is an essential cytokine for the host defense, and its depletion by treatment may facilitate the risk of infections or their reactivation. The aim of this study was to evaluate the efficacy and safety of TNF-α blockers in patients with PsA and concomitant latent tuberculosis infection (LTBI) comparing their outcome with non-infected PsA patients. This is a retrospective study in 321 patients with PsA, attending the Psoriatic Arthritis Clinic at the University Federico II of Naples, who had an inadequate response to DMARDs and started therapy with TNF-α blockers. We identified 40 patients with LTBI, who were included in this study along with 40 not infected PsA patients as control group. At baseline (T0) and every 3 months for 2 years (T2), data concerning PsA activity were registered. All patients underwent chest X-ray every 6 months (or 12 if appropriate). In each group, 22 patients were on etanercept therapy, 14 on adalimumab, and 4 on infliximab. Anti-TNF-α therapy was effective in both group of patients, and no statistically significant differences were found in the analysis of the study variables between the two groups from T0 to T2. No serious adverse events occurred in both groups, and no patient was withdrawn from therapy. Our experience suggests that anti-TNF-α treatment is effective and safe in PsA patients with concomitant LTBI. Therefore, neither LTBI nor chemoprophylaxis seems to influence the course of anti-TNF-α therapy.

JAK/STAT/PKCδ molecular pathways in synovial fluid T lymphocytes reflect the in vivo T helper-17 expansion in psoriatic arthritis.

Looking to the sustained psoriatic arthritis (PsA) joint as a model of local human inflammation, this study was designed to assess the T lymphocyte signal transduction pathways potentially involved in this chronic immune-mediated inflammatory process, as characterized by direct ex vivo analysis of T helper (Th)-17 T effector (Teff) cell phenotypes in synovial fluid (SF) and peripheral blood (PB) of clinically active PsA patients. The reverse-phase protein arrays (RPPA) technique was employed to identify STAT3, STAT1, JAK1, JAK2, PKCδ and ERK1/2 phosphoprotein levels on total T cell lysates in SF samples of PsA patients. Frequencies of T CD4(+)IL-17A-F(+) and T CD4(+)IL-23R(+) Th17 cells were quantified in SF and matched PB of PsA patients by flow cytometry and compared with PB of healthy controls (HC). Increased levels of JAK1, STAT3, STAT1 and PKCδ phosphoproteins were found in SF T cells of PsA patients, compared with PB of HC. The expansion of T CD4(+)IL-17A-F(+) cells, as well as of T CD4(+) cells expressing IL-23Rp19 (T CD4(+) IL-23R(+)), considered as the pathogenic phenotype of effector Th17 cells, was found to be confined to the joints of PsA patients, as the frequencies of both populations were significantly higher in SF than in matched PB, or in PB of HC. In conclusion, T lymphocyte signal transduction pathway mapping revealed an enhanced activation of JAK1/STAT3/STAT1 and PKCδ phosphoproteins that may drive the local inflammatory process, characterized by the in vivo expansion of T CD4(+)IL-17A-F(+) and T CD4(+)IL-23R(+) Th17 Teff cells in SF of clinically active joints of PsA patients.

Working the endless puzzle of hereditary autoinflammatory disorders.

Hereditary autoinflammatory disorders encompass manifold dysfunctions of innate immunity caused by mutations in genes coding for the main characters of the inflammatory scene: most of these conditions have an early onset, ranging from the first days of life to the first decades, and include hereditary periodic fevers, NLRP-related diseases, granulomatous and pyogenic syndromes, which are basically characterized by upturned inflammasome activity and overproduction of bioactive interleukin (IL)-1ß and other proinflammatory cytokines. The discovery of a causative link between autoinflammation and IL-1ß release has improved our understanding of the intimate mechanisms of innate immunity, and has likewise led to the identification of extraordinary treatments for many of these disorders.

Impact of 24-month treatment with etanercept, adalimumab, or methotrexate on metabolic syndrome components in a cohort of 210 psoriatic arthritis patients.

Psoriatic arthritis (PsA) is a chronic inflammatory condition, characterized by an excess of metabolic disorders. Metabolic syndrome (MetS) is a cluster of classic cardiovascular risk factors, due to an imbalance between pro- and anti-inflammatory adipokines. Tumor necrosis factor (TNF)-α is a pro-inflammatory adipocytokine mainly produced by monocytes and macrophages with a central role in inflammatory responses, but it also induces adipocytes apoptosis, promotes insulin resistance, and stimulates lipolysis. The aim of this study was to evaluate the impact of therapy with etanercept (ETN), adalimumab (ADA), and methotrexate (MTX) on MetS components in a cohort of PsA patients with a follow-up period of 24 months. A retrospective study has been conducted in a cohort of PsA patients. On the basis of the inclusion criteria, we identified the first 70 consecutive patients, respectively, on ADA, ETN, and MTX, for a total of 210 patients achieving PsARC criteria during the observation period. As part of the routine clinical practice, assessment of metabolic parameters and of disease activity was recorded at baseline (T0), at 12 months (T1), and at 24 months (T2). The results show that when the specific components of the MetS were considered, taking also into account by regression analysis the effect of the confounding factors, the patients on etN and ADA show a significant improvement of the metabolic syndrome components (in detail, waist circumference, triglycerides, high-density lipoprotein cholesterol, and glucose) as compared to the MTX group. In conclusion, these data suggest that the biologic treatment in PsA can no longer be taken into consideration only for its positive effect on articular and cutaneous symptoms but also on the various aspects of this complex picture.

Long-term safety of anti-TNF-α in PsA patients with concomitant HCV infection: a retrospective observational multicenter study on 15 patients.

Psoriatic arthritis (PsA) is an inflammatory arthropathy associated with skin and/or nail psoriasis. TNF-α, in addition to its pro-inflammatory role, is an essential cytokine for the host's defense, and its depletion by treatment may facilitate the risk of viral infections or their reactivation. The aim of this study was to evaluate the efficacy and safety of TNF-α blockers in PsA patients with concurrent hepatitis C virus (HCV) infection. This is a multicenter study carried out in four Italian centers specialized in the diagnosis and treatment of PsA. At baseline and after 6 (T6) and 12 months (T12) of therapy, data concerning PsA activity and liver tests were registered. A total of 15 PsA patients with concomitant HCV infection were included in the study. At baseline, 13 patients had low viral load, and liver enzyme tests were within the normal range. During the observation period, these values remained stable. On the other hand, at baseline, a high viral load with slightly increased values of AST and ALT was detected in one patient. At T6 and T12, these values decreased. The remaining patient, at baseline, had low viral load, but with slightly increased AST and ALT values that normalized during the observation period. This is the greatest sample size available in the literature on this topic. The data suggests that anti-TNF-α agents are effective and safe in PsA patients with concomitant HCV. We suggest that the use of anti-TNF-α agents, accompanied by close monitoring, could be a therapeutic option.

Simple clinical indicators for early psoriatic arthritis detection.

BACKGROUND: Diagnosis of psoriatic arthritis (PsA), in a period of 12 months from the onset of the first articular episode, permits of identifying the early form defined as "early PsA". The recognition of the disease in this phase leads to better outcome. The aim of this study was to identify peculiar clinical and/or laboratory findings that could be useful for the diagnosis of "early PsA". FINDINGS: Thirty-five patients with early onset of arthritis were observed. The following data were collected for each patient: family and personal history, physical examination, tender and swollen joint counts (TJC, SJC), tender entheseal count, presence of dactylitis and low back pain (LBP), and laboratory tests. Among the 35 total patients, 24 showed skin and/or nail psoriasis or a family history of psoriasis. The remaining 11 patients showed absence of concomitant or previous psoriasis and/or familiarity for psoriasis. The comparison between the two groups showed that patients with psoriasis had a significant presence of LBP, dactylitis and enthesitis than patients with psoriasis. CONCLUSIONS: The study confirms that the distinctive clinical findings of PsA is psoriasis, but also LBP, dactylitis and enthesitis have a relevant role in early identification. A low number of SJC and TJC are frequently observed in early phases of PsA than in other forms of early arthritis. These aspects could be mostly helpful when psoriasis is not detected or can follow arthritis in absence of familiar positivity, making difficult PsA diagnosis. In conclusion, careful medical history, clinical examination and first-level laboratory investigations are useful to characterize early phases of PsA.

Monogenic autoinflammatory syndromes: state of the art on genetic, clinical, and therapeutic issues.

Monogenic autoinflammatory syndromes (MAISs) are caused by innate immune system dysregulation leading to aberrant inflammasome activation and episodes of fever and involvement of skin, serous membranes, eyes, joints, gastrointestinal tract, and nervous system, predominantly with a childhood onset. To date, there are twelve known MAISs: familial Mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome, familial cold urticaria syndrome, Muckle-Wells syndrome, CINCA syndrome, mevalonate kinase deficiency, NLRP12-associated autoinflammatory disorder, Blau syndrome, early-onset sarcoidosis, PAPA syndrome, Majeed syndrome, and deficiency of the interleukin-1 receptor antagonist. Each of these conditions may manifest itself with more or less severe inflammatory symptoms of variable duration and frequency, associated with findings of increased inflammatory parameters in laboratory investigation. The purpose of this paper is to describe the main genetic, clinical, and therapeutic aspects of MAISs and their most recent classification with the ultimate goal of increasing awareness of autoinflammation among various internal medicine specialists.

Psoriatic arthritis: advances in pharmacotherapy based on molecular target.

The progress on the improved understanding of disease pathogenesis and molecular biology has changed the understanding of disease profiles, emphasizing aspects that simple clinical observation could not identify, and demarcating differences between clinical pictures that seemed to overlap. An example of this spectacular evolution is represented by psoriatic arthritis (PsA). This increase of knowledge on pathogenesis has led to an important impact on therapeutic approach. Therapies are now taken into account because their precise target is known. The authors describe treatment guidelines and revisit traditional therapies as well as innovative therapies in PsA.

The occurrence of lower limb enthesopathy in coeliac disease patients without clinical signs of articular involvement.

OBJECTIVE: Coeliac disease (CD) is a systemic autoimmune condition induced by gluten consumption in genetically predisposed people, affecting ∼1% of the general population. In the literature, there are many studies that report the association between CD and different kinds of arthritis. The aim of this study was to investigate the presence of entheseal abnormalities by US in patients with CD without clinical signs of articular involvement as compared with healthy control subjects. METHODS: Sixty patients with CD attending the gastroenterology outpatient clinic of the University Federico II of Naples and 60 healthy control subjects matched for age and sex were enrolled in this study. Coeliac patients and healthy controls underwent clinical and US examination. RESULTS: Among 60 CD patients, 24 (40%) presented at least one entheseal alteration as compared with 6 (10%) control subjects (P < 0.01). In CD patients, the entheseal site more frequently involved was patellar (distal and proximal), while in the healthy controls the enthesopathies were all localized at the Achilles tendon. CONCLUSION: In conclusion, the results of this study underline the ability of US to detect signs of subclinical enthesopathy and indicate the presence of a higher prevalence of subclinical enthesopathies in asymptomatic CD patients.

Osteoporosis and psoriatic arthritis.

Osteoporosis (OP) is a skeletal disorder characterized by compromised bone strength that predisposes to an increased risk of fracture. The prevalence of OP in the general population is very high as established in several studies, and OP represents one of the possible aspects of bone involvement in arthritis. In psoriatic arthritis this involvement is particularly complex because it affects not only mechanisms of bone loss but also of bone formation. We will discuss these aspects and the available epidemiological data.

New developments in magnetic resonance imaging of the nail unit.

The evolution of dedicated magnetic resonance imaging (MRI) musculoskeletal equipment allows new sequences and better images of the nail unit. The use of MRI has modified the imaging strategies used in treating inflammatory arthritis. In the case of psoriatic arthritis (PsA), the MRI study of the nail unit identifies nail involvement, which appears as an initial lesion for the induction of distal phalanx damage and consequently of distal interphalangeal joint arthritis. All patients with psoriasis, even in the absence of a clinically evident onychopathy, show characteristic MRI changes in the nail. This evidence could have a practical diagnostic value, because MRI study of the nail could document diagnosis in patients with undifferentiated spondyloarthropathies who have a barely evident psoriasis. We discuss the advantages and problems related to the use of low-field and high-field MRI in the study of the nail unit of patients with PsA.