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Systemic Mastocytosis (SM) comprises a heterogeneous group of disorders of mast cell proliferation. Infiltration, including skin and bone, of multiple mast cells may occur as cutaneous and systemic variants. A rare form of osteoporosis has been also described as expression of the skeletal involvement. Here, we describe a case of a 57-years-old woman with SM and, according to the clinical diagnosis, evaluate the possible mechanism underlying osteoporosis. Moreover, a review of the literature, particularly regarding the use of bisphosphonates in this rare disease is also presented.

Since anti-TNFalpha treatments were introduced in the therapy of rheumatoid arthritis, some cases of patients with drugs induced Lupus during clinical trials with infliximab treatment for rheumatoid arthritis (RA) were reported. We report three cases with history of refractory RA (two patients) and of psoriatic arthritis (one patient) with a diagnosis of Drug Induced Lupus, after treatment with infliximab, with different clinical features such as pericardial and pleural effusion, skin lesions and piastrinopenia and with autoantibody assessment. We also reviewed the development of anti nuclear and anti double-strand DNA antibodies and drug induced lupus in patients treated with anti-TNFalpha agents (infliximab, etanercept and adalimumab).

Cytokines such as TNF-alpha and IL-1beta play key roles in driving the inflammation and synovial cell proliferation that characterize rheumatoid arthritis (RA) joint destruction. It is, therefore, not surprising that therapies for RA have targeted these cytokines. While blockade of TNF-alpha or IL-1beta has been efficacious for many patients with RA, adequacy and maintenance of response are not universal, and increased risk of adverse events such as infections and malignancy remain a concern. Therefore, new targets in the treatment of RA continue to be examined. As interleukin-6 (IL-6) has been implicated in the pathogenesis of RA, blockade of its activity is of both scientific and clinical interest. Tocilizumab has been assessed in a number of studies in recent years, mainly in patients with rheumatoid arthritis. Data from randomized controlled clinical trials demonstrate the effectiveness of tocilizumab in improving the signs and symptoms of RA. In addition, it appears that such inhibition of IL-6 can have positive effects on functional status, an important outcome for RA patients. Finally, data suggest that treatment with this agent may also inhibit the progression of disease as assessed radiographically. Data from recent studies will help to refine the ultimate use of this novel approach to treatment, and help clinicians to optimize therapy using this approach.

Ischaemic optic neuropathy is a serious illness, with uncertain prognosis, which typically afflicts elderly patients. The patient complains of a reduction of monolateral visus. Massive involvement of the papilla with whitish oedema is associated with Horton arteritis. We report a clinical case which has responded rapidly to therapy with infliximab, an anti-TNFalpha agent, and we evaluate the literature.

Purpose of Review: Several biological agents have been introduced into the drug market and more are emerging. Adverse reactions to these agents have recently been classified into five different subtypes. Some of these reactions are frequent but without consequences for the patients. Others are less frequent but potentially life-threatening, and they include allergic reactions., Recent Findings: Hypersensitivity reactions are well described adverse drug reactions, corresponding to the ss-type of the newly proposed classification of adverse reactions induced by biological agents. We focus our search on tumor necrosis factor-alpha antagonists, as they represent a dramatic improvement in the therapy of both rheumatic and inflammatory bowel diseases and because adverse reactions have been closely scrutinized. We also add cases from our own experience. We found very few properly documented allergic reactions., Summary: Hypersensitivity reactions to tumor necrosis factor-alpha antagonists are not rare. Whether these manifestations have to be considered type beta or type gamma reactions is still a matter of debate. There is a need for allergological tests in vivo and in vitro.

Amyloidosis refers to the extracellular deposition of proteinaceous insoluble fibrils in various tissues, resulting in organ compromise. The most common form of amyloidosis occurs secondary to chronic inflammatory disease, in which AA fibrils, derived from the acute phase protein, serum amyloid-A (SAA). We evaluated the prevalence of AA with lip biopsy on 106 rheumatoid arthritis patients (according to 1988 ARA criteria), asymptomaticwith regard to amyloidosis (90 females, 16 males). On histological salivary gland samples we evaluated the presence of AA by an immunohistochemical method [Anti Human Amiloid clone MC-1 (DAKO, Italy)]. We observed a positivity of AA on 8/106 patients (5 F/3 M) 7.54%. When the total data were divided into three groups considering the different lenght of the disease (number of years) we observed the following prevalence data: group A, years of disease < 3, 2/45, 4.44% (F 1/M 1), group B, years of disease 3-5, 2/26, 7.69% (F 1/M 1), group C, years of disease > 5, 4/35, 11.42%. The statistical analysis showed a significative difference between group A and B (p < 0.025), between group B and C (p < 0.025) and between group A and C (p < 0.01). The 8 patients with AA positivity showed also an high disease activity in comparison with 98 negative patients: DAS 5.62 +/- 0.48 vs 4.36 +/- 0.79, DAS28 5.84 +/- 0.76 vs 4.48 +/- 0.87 (p < 0.05). Our data showed that secondary AA amyloidosis prevalence in asymptomatic Italian rheumatoid arthritis patients was 7.54%; moreover this complication was present in 4.44% of early rheumatoid arthritis patients.

TNF-alpha role in RA is confirmed by the improvement on joint inflammation and physical function and by the slowing of radiographic damage induced by TNF-alpha blockers, that also reduce Rheumatoid Factor (RF) and anti-CC-P titres. (1) To evaluate the effects of 3 TNF-alpha blockers on (a) disability (HAQ), disease activity (DAS28), acute phase reactants (ERS, CRP); (b) autoantibodies: IgM RF, anti-CCP abs. (2) To evaluate if anti-CCP abs could be useful for testing the efficacy of anti-TNF-alpha agents in the follow-up of RA patients. 34 patients with RA (25 F, 9 M; mean age: 59.1 +/- 12.1 years, mean disease duration: 9.6 +/- 2.3 years; 23/34 positive for anti-CCP abs, 19/34 for IgM RF) were enrolled: 18 received Etanercept (25 mg twice weekly subcutaneously), 8 received Infliximab (3 mg/kg intravenously every 8 weeks) and 8 Adalimumab (40 mg every 14 days). All the patients were evaluated for the above mentioned parameters at baseline (t0) and after 6 months of therapy (t6). Anti-TNF-alpha agents differently reduced HAQ and DAS28, ERS and CRP, RF and anti-CCP ab titres RA patients whose RF (14) and/or anti-CCP abs (17) titres were significantly lowered at the end of the study, at t6 presented a significant reduction in respect to t0 of VES, PCR, DAS28 and HAQ values (p < 0.05 for all comparison). This effect was not shown in patients in whose RF (5) and/or anti-CCP abs (6) titres were not reduced in respect to baseline. In RA, anti-TNF-alpha agents, especially Etanercept, reduce disability, disease activity and acute phase reactants expecially in patients showing reduction of RF and anti CC-P titres.

Almost 30-50% of patients on long-term therapy with glucocorticoids (GC), especially those affected by rheumatic diseases, develop glucocorticoid induced osteoporosis (GIOP) and osteoporosis-related fractures. To assess the effects of neridronate versus placebo on markers of bone resorption in rheumatic patients affected by GIOP (as defined by a T Score reduction > 2.5; mean BMD L2-L4), sixty-two female patients [age: 68.89 +/- 9.45 (mean +/- SD)] affected by different rheumatic diseases, like rheumatoid arthritis, polymyalgia rheumatica, Sjögren syndrome in treatment with a mean prednisone-equivalent daily dose of 6.44 +/- 2.4 mg/day, were enrolled in an open trial. The patients were divided in 2 groups: group A (26 patients) assuming daily calcium 1 g and vitamin D 800 UI and group B (36 patients) assuming daily calcium (1000 mg) and vitamin D (800 UI) and neridronate (25 mg im /30 days). The patients were evaluated for serum and urinary bone markers, basely (T0) and after 6 months of therapy (T6). After 6 months of therapy (T6), bone markers were significantly reduced in group B in respect to group A: OHPr - 41.64% (p < 0.001), D-Pyr - 34.96% (p < 0.001), NTX - 50.9% (p < 0.001). These preliminary data show that neridronate may be considered an useful agent for the treatment of GIOP in rheumatic patients.

A 67-year-old woman was hospitalized with recurrent fever, arthralgia and erythema of the arms and legs. She had suffered from bronchiectasis for the previous 4 years, and Pseudomonas was persistently detected in her sputum. During the course of her illness, she developed distal sensitive and motor polyneuropathy. Serum test was positive for myeloperoxidase and bactericidal/permeability-increasing protein antineutrophil cytoplasmic antibodies. Nerve biopsy showed vasculitis infiltration of the vasa nervorum. She started immunoglobulin therapy, and after methylprednisolone and pulse cyclophosphamide therapy once monthly for 6 months she showed a good response and a reduction in symptoms.

The aim of the study was to evaluate the composition and functional integrity of the various components of immune response in patients with rheumatoid arthritis (RA). We evaluated in 14 patients with RA with stable methotrexate therapy 12.5 mg/weekly, the number of peripheral mononuclear (PMN) cells lymphocytes, monocytes and the circulating levels of TNFalpha, IL-6 and IL-10 before and during adalimumab therapy 40 mg every other week for 6 months. No difference in baseline versus 6 months values between two treated group for PMN cells. Data about cytokines show a reduction for TNFalpha, IL-6 circulating levels and an increase for IL-10 circulating levels. Our data reveal that adalimumab doesn't reduce lymphocyte population and subsets such as CD14 or CD56 cells that have an important role against infections.

Background: The goal was to ascertain the prevalence of SLE in the population over 18 years of age in the Scandicci-Le Signe area of Florence, Italy, based on the records of general practitioners (GPs)., Material/methods: Twenty GPs screened 32,521 patients by administering the Lupus Screening Questionnaire (LQS) and found 30 patients with suspected or definite diagnosis of SLE. To confirm the diagnoses the patients were referred to a rheumatologist who conducted routine examinations and assessed antinuclear antibodies and SLE activity (ECLAM score)., Results: Total population >18 years of age in the three municipalities was 71,204 persons, with 42,474 in Scandicci, 15,368 in Lastra a Signa, and 13,362 in Signa. In 23/30 patients diagnosed with SLE the diagnosis was confirmed. Eleven of the 23 SLE patients were from Scandicci and 6 each from Lastra a Signa and Signa. An overall estimated prevalence of SLE of 71/100,000 (1/1408; 95% CI=49, 92) was found in the total population of the three municipalities. Scandicci (95% CI=42, 121) had a rate of 81/100.000, while Lastra a Signa (95% CI=32, 92) and Signa (95% CI=36, 94) had estimated rates of 62/100,000 and 65/100,000, respectively. Medium ECLAM score was 4.68+/-1.81 SD., Conclusions: This is the first epidemiological study on SLE prevalence in Italy. The prevalence and point prevalence are similar to other European studies. The LQS was also confirmed as an easy and reliable tool to assess SLE diagnosis in the Italian population.

We report a case of a 45-year-old man with an 8-month history of rheumatoid arthritis, who was treated with hydroxychloroquine 400 mg per day and 15 mg intramuscular methotrexate per week without reaching a good control of the disease. The patient was successfully treated with 3 mg/kg infliximab for 20 weeks. Before the last infusion, drug-induced lupus (DIL) was diagnosed based on the clinical features of fever > 37.5 degrees C, recurrence of active synovitis, myalgia, erythematosus rash, pericardial and pleural effusion, and of some laboratory findings (antinuclear antibodies 1:160 and anti double-strand DNA positive by DNA recombinant plasmid assay dsDNA). After infliximab discontinuation and the beginning of therapy with methylprednisolone, lupus symptoms resolved within 6 weeks. A new rheumatoid arthritis flare, occurring after 8 weeks, was controlled by methotrexate plus leflunomide. We also review the development of antinuclear and antidouble-strand DNA antibodies and drug-induced lupus in patients treated with anti-TNFalpha agents (infliximab, etanercept, and adalimumab).

Tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) is an autosomal dominant inherited condition of periodic fever and pain. TRAPS is caused by mutations of the TNFRSF1A gene localized at 12p13. The gene encodes extracellular region of the p55 TNF-alpha receptor, resulting in impaired cleavage and down-regulation of the membrane expressed form of the receptor, a diminished shedding of potentially antagonistic soluble form of the receptor and, as a consequence, an unbalanced TNF-alpha action. Most affected patients are from northern Europe. Fever, sterile peritonitis, pleural pain, arthralgia, myalgia, skin rash, and/or conjunctivitis occur during the syndrome episodes; some patients also develop systemic amyloidosis, with some differences among patients. An acute-phase response occurs during the episodes. We describe a case of a 23-year-old Moldavian woman, living in Italy presenting recurrent fever episodes with abdominal pain and skin rash. A biopsy showed small vessel vasculitis. The genetic analysis showed a TNFRSF1A gene (R92Q) mutation. In this paper we report also a literature review on this rare disease.