Occult HBV infection may negatively impact on drug survival in patients with rheumatoid arthritis on treatment with a first biologic drug. An appraisal from the Biologic Apulian Registry (BIOPURE).

We performed a retrospective analysis to evaluate the survival on first line biologic drug of rheumatoid arthritis (RA) patients with potential occult HBV infection (pOBI). We analysed longitudinal data of 486 consecutive RA patients starting a first biological drug in a time frame from 1st January 2008 to 31st December 2014. Demographic and disease related characteristics were collected at baseline and at the last observation visit. Baseline serological markers of HBV infection and causes of treatment discontinuation were also recorded. Primary endpoint was the influence of pOBI on drug survival, estimated by Kaplan-Meier life table analysis. Estimates hazard ratios (HRs) of drug discontinuation, adjusted for disease characteristics, biological drug class and HBcAb status were computed by Cox-regression models. The retention rate was significantly lower in pOBI positive patients (58.2%) when compared to pOBI negative ones (67.8%) and this data was confirmed also when only discontinuation due to ineffectiveness was considered (pOBI positive 66.4% vs pOBI negative 75.3%, long rank 7.93, p=0.005). Cox regression models showed a significant association between HBcAb-neg (HR 0.58, 0.41-0.84), higher ESR-DAS28 at baseline (HR 1.07, 1.03-1.11) or RF/ACPA-neg (HR 1.46, 1.04-2.06) and drug discontinuation. Occult HBV infection seems to influence negatively the effectiveness of biological therapies in RA patients.

The entity of thermal-crush-avulsion hand injury (hot-press roller burns) treated with fast acting debriding enzymes (nexobrid): literature review and report of first case.

Hand burns are present in >60% of all burn cases and in fire mass casualty incidents even up to 100%. Most trauma and especially burns may be detrimental to the complex and delicate structures of the hand by direct injury, indirect BICS (Burn Induced Compartment Syndrome and interstitial high pressure) or by delayed or faulty treatment. BICS represents a special threat as the increasing swelling and oedema of the small diameter hand and forearm will exert pressure on the capillary/venous system, eventually ending in irreversible damage to the skin, nerves, muscle and vascular bed. Immediate release of constricting skin by incisional escharotomy and sometimes fasciotomy may arrest this vicious cycle: escharotomy is simple for experienced hand or burn surgeons, but they are not always present at the primary treatment site. The diagnosis of BICS is not simple either, as the direct measurement of interstitial/compartment pressure is rarely done. Burns caused by hot rollers such as industrial linen ironing machines are especially traumatic as besides the "simple" thermal burn, the hot rollers exert immense crushing pressure to the hand caught between the rollers. Over the last few years, several publications have described the role of a newly approved Bromelain derived enzymatic debriding agent (NexoBrid) for burns in general and hand burns in particular, and its ability to resolve or prevent BICS. We present a rare severe thermal/crush hand injury case where we were able to successfully treat the patient with NexoBrid enzymatic debridement-escharotomy.

Une atteinte des mains est observée dans plus de 60% des brûlures, et dans quasiment tous les cas de catastrophes. La plupart des traumaitismes, en particulier les brûlures, peuvent être délétères pour les structures complexes et délicates de la main. Ceci peut être dû à la brûlure elle même, à un syndrome compartimental (SC), à un traitement tardif ou mal conduit. Le SC est particulièrement dangereux dans les espaces ténus de l'avant bras et de la main. L'augmentation de pression consécutive à l'oedème obère la microcirculation, entraînant au bout du compte des lésions cutanées, nerveuses, vasculaires et musculaires irréversibles. La libération immédiate des tissus ainsi comprimés par incision de décharge cutanée voire aponévrotomie peut interrompre le cercle vicieux. Il s'agit d'un geste simple pour des chirurgiens spécialisés, malheureusement pas toujours disponibles sur le site du traitement initial. Le diagnostic de SC n'est pas toujours aisé si la mesure directe des pressions tissulaires n'est pas réalisée. Les brûlures dues à des rouleaux chauffés comme ceux des presses à repasser industrielles car, outre le dégagement de chaleur, les rouleaux exercent une pression intense sur la main coincée entre eux. Depuis quelques années, plusieurs articles on décrit le rôle d'un nouvel agent de débridement enzymatique à base de bromélaïne (Nexobrid) pour le traitement des brûlures dont celles des mains ainsi que ses capacité à prévenir et traiter les SC. Nous présentons ici un cas de main de presse avec utilisation, couronnée de succès, de Nexobrid.

Management of cutaneous discomfort in patients with scleroderma: a clinical trial.

Systemic sclerosis (scleroderma) is a disease of unknown cause, the hallmark of which is induration of the skin. This bad condition of the skin influences negatively the quality of life of patients with scleroderma. The aim of the study was to verify the efficacy of two formulations, specifically designed to wash, moisturize and soothe the scleroderma skin. An independent, randomized, double blind, controlled trial was conducted in the Department of Rheumatology of "A. Galateo" Hospital in San Cesario di Lecce. Forty-six women affected by scleroderma, and treated with Iloprost every month, were divided into two groups: group 1 followed a specific treatment with cleansing formulation only, group 2 followed a combined treatment with the cleansing solution and the moisturizing solution. In addition, a third group was evaluated: 14 women, who did not undergo intravenous Iloprost therapy, were treated simultaneously with the cleansing formulation and the moisturizing formulation. The three treatments lasted for 4 weeks. Reduction in trans epidermal water loss (TEWL), increase in moisturization of the stratum corneum, reduction in Skin Score and improvement in quality of life were assessed. Very significant improvement in quality of life occurred in each group. Group 2 obtained very significant improvement in hydration and reduction in skin score and TEWL. The study showed that the daily use of both formulations proved to be effective in washing, hydrating and soothing the skin of patients with scleroderma, especially in association with Iloprost therapy.

"Twice-a-month" clodronate 200 mg IM: a new dosing regimen and improved therapy adherence in the treatment of postmenopausal osteoporosis.

INTRODUCTION: The identification of therapeutic strategies aimed both at preventing and treating osteoporosis and osteoporotic fractures has become increasingly important; in particular, it is essential to promote adequate patient adherence to treatment. The primary aim of this study was to evaluate the effects on lumbar and femoral bone mass density (BMD) after two different intramuscular (IM) dosing regimens of clodronate (CLD), a bisphosphonate shown to be efficacious in reducing the incidence of both vertebral and nonvertebral fractures. Secondary aims were the assessments of bone resorption markers, safety, tolerability, pain, and patient compliance. METHODS: Sixty women with postmenopausal osteoporosis were randomized to two groups: group A (CLD 100 mg IM weekly for 12 months), and group B (CLD 200 mg IM every 2 weeks for 12 months). All patients received 1 g of calcium supplemented with 800 IU vitamin D(3), orally, once daily for 12 months Lumbar and femoral BMD, measured by DEXA Norland XR-36 (Norland Co., Fort Atkinson, WI), and bone turnover markers were assessed at baseline and at 12 months. Each patient was administered a visual analog scale of pain at baseline and after 6 and 12 months of treatment. RESULTS: A significant increase of BMD in both groups and in both skeletal sites was observed at 12 months versus baseline. In group A (n=28), lumbar BMD increased by 3.5% and femoral BMD by 2.1%; in group B (n=32), lumbar and femoral BMD rose by 3.4% and 2.2%, respectively. No difference was observed between groups. Bone resorption markers significantly reduced from baseline. Pain significantly improved as early as after 6 months of therapy and even more after 12 months, although no significant difference between the two groups was observed. The most common side effect was pain at the injection site, particularly in group B. Six patients in group A discontinued treatment and failed adherence to the therapeutic protocol. Conversely, no patient from group B discontinued therapy. CONCLUSION: In agreement with published data, in our two groups of patients, therapy with IM CLD at the doses of 100 mg/week and 200 mg/2 weeks was shown to be effective in increasing BMD, without differences between the two dosing regimens in all assessed efficacy parameters. Therefore, the "twice-a-month" regimen with 200 mg IM CLD may well promote an improved adherence with the same clinical efficacy and safety profile.

Two cases of distal extremity swelling with pitting oedema in psoriatic arthritis: the different pathological mechanisms.

In psoriatic arthritis, swelling and pitting oedema may be caused by different pathogenic mechanisms: on one hand, the involvement of tenosynovial structures; on the other hand, the involvement of lymphatic vessels, which may be rarely implicated by the inflammatory process. This different involvement is responsible for a different response to therapy and a different clinical outcome. In fact, patients with inflammation of the tenosynovial structures and normal lymphatic drainage have a more favourable clinical outcome and response to pharmacologic treatment, whilst patients affected by psoriatic arthritis with chronic lymphatic vascular damage are characterized usually by resistance of oedema to therapy. In this study, we report two cases of psoriatic arthritis with distal extremity swelling and pitting oedema. In the first patient, the swelling and pitting oedema were associated with lymphatic obstruction, as detected by lymphoscintigraphy. In the second, the predominant involvement of the tenosynovial structures, as shown by magnetic resonance, with normal lymphatic flow, may have been the cause of arthritis with oedema. These different pathogenetic mechanisms were associated with different response to therapy. Nevertheless, oedema was resistant to therapy in both patients probably because of other unknown factors, which influence therapy and clinical outcome.

Combined effect of Neridronate and specific antibiotic therapy in a case of tuberculous spondylodiscitis.

Because of the increased incidence of tuberculosis (TB) in recent years, infective spondylitis is still a major problem in the world. In skeletal TB the spine is the most often involved and lumbosacral spine involvement is rare. Nowadays early diagnosis and new medical treatment can reduce the incidence of the serious skeletal sequelae and the number of surgery procedures in spinal TB. We present a case of TB spondylodiscitis characterized by a rapid and progressive clinical and radiological improvement after treatment with Neridronate and chemotherapic drugs. Our data suggest that in the treatment of the TB spondylodiscitis the combined use of these drugs is a good alternative to stimulate bone reparative process to the chemotherapy alone. To our knowledge this is first case of a patient with TB discitis treated with Neridronate. Further studies are necessary to confirm the effectiveness of Neridronate treatment added to antiTB drugs in spondylodiscitis.

IgA nephropathy in systemic lupus erythematosus.

Renal involvement in systemic lupus erythematosus (SLE) is a typical manifestation of the disease. The occurrence of non-lupus nephritis in SLE patients has rarely been reported; we describe the case of a woman suffering from SLE and IgA nephropathy (IgAN). Although IgAN and lupus nephritis share some common physiopathological characteristics, their laboratory and histopathologic findings and the extra-renal clinical manifestations are different and support a different pathogenesis. Our case highlights the importance of renal biopsy in lupus patients with urinary alterations since a correct diagnosis would permit the most appropriate treatment to be started, thus avoiding unnecessary immunosuppressive treatments.

Corticosteroids, a review.

Recent studies have shown a strong correlation between the nervous, endocrine and immune systems. Knowledge of how these systems interact is important for understanding the pathogenesis of autoimmune diseases such as rheumatoid arthritis (RA) and to open new therapeutic perspectives. New theories suggest that in RA there is an inappropriate response of the hypothalamic-pituitary-adrenal axis to the increase in pro-inflammatory cytokines, resulting in a corticosteroid (CS) insufficiency state. While recent observations have questioned the positive effect of CS on the progression of joint damage, efficacious new drugs such as anti-TNF have attracted attention to agents without the side effects of CS. Cartilage oligomeric matrix protein, a new biohumoral marker, has recently led to a re-evaluation of CS in RA therapy.

Lymphocytes and synovial fluid fibroblasts support osteoclastogenesis through RANKL, TNFalpha, and IL-7 in an in vitro model derived from human psoriatic arthritis.

Psoriatic arthritis (PsA) is an inflammatory joint disease, characterized by extensive bone resorption, whose mechanisms have not been fully elucidated. Thus, in the present study we investigated the involvement of RANKL, TNFalpha, and IL-7 in the osteoclastogenesis of PsA patients. In vitro osteoclastogenesis models, consisting of unfractionated and T-cell-depleted mononuclear cells from peripheral blood (PBMCs) and synovial fluid (SFMCs) of 20 PsA patients as well as from healthy donors were studied. Freshly isolated T and B cells from PBMCs and T cells and fibroblasts from SFMCs of PsA patients were subjected to RT-PCR to detect the levels of RANKL, TNFalpha, and IL-7. Osteoclastogenesis was studied in the presence of RANK-Fc, anti-TNFalpha, and anti IL-7 functional antibodies. We demonstrate that lymphocytes and fibroblasts support osteoclast (OC) formation in PsA patients through the production of osteoclastogenic cytokines. In particular, OC formation was completely abolished in unstimulated T cell-depleted PBMC cultures, and reduced by approximately 70% in unstimulated T cell-depleted SFMC cultures. Freshly isolated T cells from PBMCs and SFMCs of PsA patients overexpressed RANKL and TNFalpha, while fibroblasts from synovial fluid produced only RANKL. We show that the presence of RANK-Fc and/or anti-TNFalpha functional antibodies reduced OC formation. Moreover, T and B cells from PBMCs as well as T cells and fibroblasts from SFMCs expressed IL-7 mRNA. Finally, the anti-IL-7 functional antibody significantly reduced osteoclastogenesis. Our results suggest that fibroblasts, B and T lymphocytes support OC formation by producing RANKL, TNFalpha, and IL-7, contributing to the aggressive bone resorption in PsA patients.

Psoriatic arthritis and Klinefelter syndrome: case report.

Psoriatic arthritis (PsA) is a well-known disease characterized by psoriasis and inflammatory joint disease, with distinct clinical and radiological features to differentiate it from other arthropathies. Whereas many cases of coexistence of arthritis and other autoimmune disorders with chromosomal abnormalities have been reported, the occurrence of PsA and Klinefelter syndrome has not been reported previously. A case of Klinefelter syndrome and PsA was reported. This case report emphasizes the role played by sex hormones and chromosomal abnormalities in the pathogenesis of autoimmune disorder, and to our knowledge, this is an uncommon case of a patient with Klinefelter syndrome who developed PsA.

Cervical myelopathy caused by periodontoid synovial pannus in a patient with psoriatic arthritis: a case report.

The atlantoaxial subluxation and the formation of a synovial periodontoid pannus are associated with rheumatoid arthritis causing mechanical compression of the spinal cord and cervical myelopathy. Atlantoaxial subluxation is very rare in psoriatic arthritis (PsA). Even more rare is the formation of a periodontoid synovial pannus associated with PsA and signs of myelopathy. In this report, cervical myelopathy caused by periodontoid synovial pannus in PsA is described.

Pubic symphysis sclerosis in psoriatic arthritis. Case report.

Pubic symphysis sclerosis is a very interesting event in psoriatic arthritis (PsA). PsA is a cronical arthritis, associated with psoriasis, classified with seronegative spondyloarthrities. There are 5 clinical PsA patterns: an oligoarticular pattern, characterized by asymmetrical involvement of metacarpophalangeal and interphalangeal joints of hands and feet, as well as ankles and knees; a polyarticular pattern; a pattern characterized by involvement of distal interphalangeal joints; an arthritis mutilans pattern, characterized by acro-osteolysis of distal phalanxes; a pattern with spondylitic involvement. Although pubic involvement in PsA is not described in literature, a lot of authors describe the presence of erosive and/or sclerotic osteitis pubis in seronegative spondyloarthrities, without a more accurate subclassification. In seronegative spondyloarthrities sclerotic involvement of pubic symphysis has been described in patients suffering from ankylosing spondylitis for 5-10 years. A case of pubic symphysis sclerosis, evident on radiographs and detected also by magnetic resonance, which shows also a pattern of oedema and enhancement, with increased signal intensity on pubic symphysis in T2-weighted images, after the contrast agent was injected in the bone marrow, is reported in a woman affected by PsA. Pubic symphysis sclerosis is atypical in PsA and may be considered, by analogy with ankylosing spondylitis, the final result of repairing mechanisms of the previous erosive changes.

[Fibromyalgic syndrome: new perspectives in rehabilitation and management. A review]. / La sindrome fibromialgica: le nuove prospettive riabilitativo-terapeutiche. Review.

Fibromyalgia is a chronic syndrome, characterized by widespread body pain and pain at specific tender points, whose etiology and pathogenesis is still unknown. Patient can also exhibit a range of other symptoms including irritable bowel syndrome, chest pain, anxiety, fatigue, sleep disturbance, headache. The prevalence of fibromyalgia ranges from 1-3% in the general population, and the condition is more common among female than males. Contrary to the situation a few years ago, the most widely accepted hypothesis now evoke central nervous system mechanisms, whose local functions could influence also periferical microvascular activity at tender points. There are many findings supporting the hypothesis of different endogenic and exogenic factors that lead to chronic local hypoxia in muscle tissue. Currently, therapy is polipragmatic and is aimed at reducing the pain. A range of medical treatment had been used to treat fibromyalgia. Pharmacological therapy aims to enhance the pain threshold and to support sleep. Nonpharmaceutical treatment modalities, such as exercise, massage, idrotherapy can be helpful. Future studies should investigate the possible benefits of new strategies that may combine the effects of hot pool water, stretching exercises, massage and relaxation benefits of balneotherapy.