Ocular Involvement in Systemic Lupus Erythematosus: The Experience of Two Tertiary Referral Centers.

PURPOSE: To assess the prevalence of the ocular manifestations related to the disease and/or ascribable to the administration of potentially toxic drugs in a cohort of 98 patients with systemic lupus erythematosus (SLE). METHODS: Retrospective, observational study reporting the experience of two tertiary referral centers. RESULTS: Overall, an ocular involvement was detected in 29 patients (29.6%), sometimes preceding of months the diagnosis of SLE, more often revealed at diagnosis or throughout its course. More than a single ocular manifestation was found in 20 of the 29 patients with ophthalmological findings (68.9%). The array of ocular morbidity included, in a decreasing order of frequency, cataracts, keratoconjunctivitis sicca, glaucoma, discoid lesions of eyelids, episcleritis, retinopathy, vortex keratopathy, choroidopathy and retinal detachment, central retinal vein occlusion, and hydroxychloroquine-induced toxic maculopathy. CONCLUSIONS: It is advised that a multidisciplinary team for the diagnosis and treatment of SLE should regularly include the presence of an ophthalmologist.

Cancer-related coagulopathy (Trousseau's syndrome): review of the literature and experience of a single center of internal medicine.

Venous thromboembolism (VTE) occurs roughly in one out of five cancer patients and is the second cause of death in this population. When all cancer patients are considered together, a sevenfold increased risk for VTE has been calculated. Over the last 20 years, a number of risk factors have been recognized. These have been used in several risk assessment models aimed at identifying high-risk patients who are therefore candidates for thromboprophylaxis. An easily applicable and reliable risk score is based on the cancer site, hemoglobin levels, pre-chemotherapy platelet and leukocyte counts as well as body mass index. The additional measurement of two biomarkers, namely D-dimer and soluble P-selectin, may improve estimates of the cumulative VTE probability. A variable incidence of VTE has been determined in patients with specific types of malignancy, with the highest odds in those with pancreatic cancer followed by head and neck tumors. In terms of histotype, the risk of VTE is significantly higher in patients with adenocarcinoma than in those with squamous cell carcinoma and in patients with high-grade versus low-grade tumors. Cancer therapy may also be responsible for VTE; specifically, the presence of an indwelling central venous catheter, immunomodulatory drugs such as thalidomide and lenalidomide, monoclonal antibodies, such as bevacizumab, erythropoiesis-stimulating agents and hormonal therapy with tamoxifen place patients at higher risk. The pathogenesis of cancer-related VTE is poorly understood but is likely to be multifactorial. "Virchow's triad," comprising stasis consequent to a decreased blood flow rate, an enhanced blood clotting tendency such as accompanies inflammation and growth factor expression, and structural modifications in blood vessel walls, is thought to play a central role in the induction of VTE. The prophylaxis and treatment of VTE are based on well-established drugs such as vitamin K antagonists and unfractionated and low-molecular-weight heparins as well as on an expanding group of new oral anticoagulants, including fondaparinux, rivaroxaban, apixaban and dabigatran. Furthermore, aspirin has been shown to prevent arterial thrombosis and to reduce the rate of major vascular events. Guidelines for the general management of VTE in cancer patients and in those with an indwelling central venous catheter have been recently developed with the aim of selecting the most rational therapeutic approach for each clinical situation. The main features of VTE based on our own observations of 92 cancer patients and 159 patients with non-neoplastic disease are briefly described herein.

Waldenström's macroglobulinemia. An overview of its clinical, biochemical, immunological and therapeutic features and our series of 121 patients collected in a single center.

Waldenström's macroglobulinemia (WM) is defined as a B-cell lymphoproliferative disorder characterized by lymphoplasmacytic infiltration of the bone marrow associated with a monoclonal IgM component in the serum. Its clinical presentation is marked by diffuse clonal cell expansion, as well as by the physical and chemical properties of the monoclonal component, its autoantibody activity and possible tissue deposition. Initiation of treatment is not determined by the monoclonal IgM level, nor the extent of bone marrow infiltration, but confined to symptomatic patients. Their median overall survival ranges from 5 to 10 years. Poor outcome predictors include advanced age, low hemoglobin levels, low platelet count, high ß2-microglobulin and high concentration of the serum monoclonal component. First-line therapeutic approaches include alkylating agents (chlorambucil, melphalan, cyclophosphamide), nucleoside analogs (fludarabine, cladribrine), and rituximab, whether singly or combined. Thalidomide-based regimens and bortezomib have also been assessed, and new agents such as bendamustine and everolimus are being investigated. We review these general features and describe our series of 121 patients with clearly established WM.

Long-term survival in multiple myeloma: a single-center experience.

In patients with multiple myeloma the median overall survival is now approaching 5 years, following the introduction of autologous stem cell transplantation and targeted therapies. However, patients receiving conventional chemotherapy who have survived 10 years or longer have been repeatedly reported in the literature. From 723 patients with multiple myeloma seen in our department from January 1981 to June 2007, we selected 21 long-term (> or =10 years) survivors (2.9%) who had been treated with conventional chemotherapy. Potentially favourable prognostic factors, common to most patients, were: age < or =65 years; response to first-line chemotherapy; absence of Bence-Jones proteinuria; prolonged duration of response or stable disease irrespective of the primary regimen; maintenance therapy with interferon-alpha. The use of prognostic factors to identify a subset of low-risk patients could be of assistance in the selection of targeted treatments and the elucidation of poorly known features of myeloma biology.

Calciphylaxis in a patient with POEMS syndrome without renal failure and/or hyperparathyroidism. A case report.

POEMS (Crow-Fukase) syndrome is a rare plasma cell lymphoproliferative disorder associated with polyneuropathy (P), organomegaly (O), endocrinopathy (E), monoclonal (M) gammopathy and skin (S) abnormalities. The latter are usually not specific and include hyperpigmentation, hypertrichosis, cutaneous angioma and skin-thickening. A 45-year-old Italian woman was admitted to hospital because of muscle weakness, marked fatigue and paresthesia of the upper and lower extremities. Two and a half years earlier, a POEMS syndrome had been diagnosed on the basis of a history of organomegaly and mild lymphadenopathy, IgA-lambda monoclonal gammopathy, hypothyroidism, severe lower and upper limb sensory-motor peripheral neuropathy and a single osteosclerotic lesion in the left humerus. Eight weeks later, she developed skin lesions bioptically shown to be due to calciphylaxis-induced cutaneous vasculitis. To our knowledge, this is the first case of POEMS syndrome with this peculiar type of vasculitis. The absence of predisposing conditions, namely renal failure, hyperparathyroidism or clotting disorders renders the pathogenetic mechanism(s) of this severe type of vasculitis more intriguing.