Study on the possible role of the -174G>C IL-6 promoter polymorphism in predicting response to rituximab in rheumatoid arthritis.

OBJECTIVE: Identification of genetic biomarkers of response to biologics in rheumatoid arthritis (RA) is a relevant issue. The -174G>C interleukin-6 (IL-6) promoter polymorphism was investigated in RA patients treated with rituximab (RTX), being IL-6 a key cytokine for B cell survival and proliferation, thus possibly implicated in rituximab efficacy. METHODS: The study was conducted in a real-life retrospective cohort of 142 unselected RA patients (120F/22M) treated with RTX and referred to 7 rheumatologic centres in the north of Italy. One hundred and thirteen (79.6%) patients were rheumatoid factor (RF)-positive and 112 (78.9%) were anti-CCP antibodies positive. The response to therapy was evaluated at the end of the sixth month after the first RTX infusion, by using both the EULAR criteria (DAS28) and the ACR criteria. The IL-6 -174G>C promoter polymorphism was analyzed by RFLP following previously reported methods. RESULTS: Lack of response to RTX at month +6 by EULAR criteria was more prevalent in RA patients with the IL-6 -174 CC genotypes (9/21, 42.8%), than in the GC/GG patients (23/121, 19.0%) (OR 3.196, 95% CI=1.204-8.485; p=0.0234). Similar results were found when evaluating the response by ACR criteria. No differences were found in RA duration, baseline DAS28, baseline HAQ, RF status, anti-CCP status according to the different IL-6 -174 genotypes. CONCLUSION: IL-6 promoter genotyping may be useful to better plan treatment with RTX in RA. Larger replication studies are in course to confirm these preliminary results.

Sexual dysfunction in multiple sclerosis: a case-control study. I. Frequency and comparison of groups.

Sexual dysfunction is a very important but often overlooked symptom of multiple sclerosis. To investigate the type and frequency of symptoms of sexual dysfunction in patients suffering from multiple sclerosis, we performed a case-control study comparing 108 unselected patients with definite multiple sclerosis, 97 patients with chronic disease and 110 healthy individuals with regard to sexual function, sphincteric function, physical disorders impeding sexual activity and the impact of sexual dysfunction on social life. Information has been collected from a face-to-face structured interview performed by a doctor of the same gender as the patient. The disability, the cognitive performances, the psychiatric conditions and the psychological profile of patients and controls have been assessed. Sexual dysfunction was present in 73.1% of cases, in 39.2% of chronic disease controls and in 12.7% of healthy controls (P<0.0001). Male cases reported symptoms of sexual dysfunction more frequently than female cases (P<0.002). Symptoms of sexual dysfunction more commonly reported in patients with multiple sclerosis were anorgasmia or hyporgasmia (37.1%), decreased vaginal lubrication (35.7%) and reduced libido (31.4%) in women, and impotence or erectile dysfunction (63.2%), ejaculatory dysfunction and/or orgasmic dysfunction (50%) and reduced libido (39.5%) in men. Seventy-five per cent of cases, 51.5% of chronic disease controls and 28.2% of healthy controls (P<0.0001) experienced symptoms of sphincteric dysfunction. In conclusion, a substantial part of our sample of patients with multiple sclerosis reported symptoms of sexual and sphincteric dysfunction. Both sexual and sphincteric dysfunction were significantly more common in patients with multiple sclerosis than in either control group. Our findings suggest that a peculiar damage of the structures involved in sexual function is responsible for the dysfunction in patients with multiple sclerosis, but the highly significant lower frequency of symptoms of depression and anxiety in healthy controls may also imply a possible causative role of psychological factors.

[Antiphospholipid antibody syndrome: a case report. Clinical considerations]. / La sindrome da anticorpi antifosfolipidi: descrizione di un caso. Considerazioni cliniche.

The association of thrombosis, recurrent abortion, thrombocytopenia and antiphospholipid antibodies defines a recently discovered syndrome known as "antiphospholipid syndrome". The mentioned autoantibodies are directed against the negatively charged phospholipids of the clotting cascade and can be detected by the phospholipid-dependent prolongation of some coagulation tests "in vitro". Despite these results "in vitro", patients suffering from this syndrome present a hypercoagulable state, of which these antibodies seem to be the "marker" or intimately connected in some way with the highly complex coagulation mechanisms resulting in thrombotic occlusions. The following case of antiphospholipid syndrome also showed the typical manifestations of some other symptoms such as neurological and ocular diseases and a chronic cardiomyopathy with severe ventricular dysfunction, which could not be ascribed to any detectable vascular occlusions. This made our case original and much more interesting and induced us to make clear its "expanded" clinical manifestations that, as recently reported in literature, may now be included under the broad umbrella of the antiphospholipid syndrome.

[Treatment of amyloidosis with dimethyl sulfoxide (DMSO)]. / Trattamento dell'amiloidosi con dimetilsulfossido (DMSO).

In this study we have investigated the role of oral dimethylsulfoxide (DMSO) therapy in 2 patients with primary amyloidosis (AL) and in 2 patients with secondary amyloidosis (AA) to long-standing rheumatoid arthritis. DMSO treatment produced no beneficial effects in the patients with idiopathic amyloidosis. Instead the patients with secondary amyloidosis experienced a subjective improvement, a decrease of inflammatory activity of the rheumatoid arthritis and an unequivocal improvement of renal function following 3-6 months of DMSO therapy. No serious side effects of DMSO were observed except for unpleasant breath odour. We conclude that a treatment with oral DMSO may prolong life of patients with secondary amyloidosis.

[Computerized tomography of the spine in the evaluation of multiple myeloma]. / La tomografia computerizzata del rachide nella valutazione del mieloma multiplo.

Computed Tomography (CT) of the spine was performed on 17 patients with myeloma in order to assess the role of the technique in recognizing and evaluating the extent of the lesions. Myelomatous lesions followed two patterns at CT: first of all, multiple focal lesions, whose density is either solid, liquid, or fatty; second, an extensive pattern involving the spongiosa of the vertebra, including the posterior arch. CT detected more lesions than conventional radiology; furthermore, the extent of the lesions was much better demonstrated by CT. CT should thus be performed: a) in case of pain and/or neurological findings in negative radiological examinations; b) to evaluate the extent of myelomatous lesions (mainly in the spine); c) in solitary myeloma CT may be performed on different bone segments with clinical symptomatology but normal X-ray findings.

Bone scintigraphy in the diagnosis of pulmonary calcification in multiple myeloma.

We present a case of multiple myeloma in which pulmonary calcification was clinically shown by bone scintigraphy and subsequently confirmed at autopsy. It is suggested that, in patients with myeloma, radionuclide bone scanning may be of value for differentiating deposits in the lung due to calcification from those due to other types of pulmonary infiltration revealed by chest X-rays. A thorough review of the relevant literature is presented.

Different morphologic aspects and clinical features in massive hepatic amyloidosis.

4 cases of massive hepatic amyloidosis are reported with special reference to their clinical profiles and histologic features. On the basis of these data, two different clinical and histologic courses of the disease can be distinguished. 2 patients showed marked hepatomegaly without cholestasis, whereas in the other 2 the clinical picture was characterized by much less pronounced hepatomegaly, but by severe and progressive intrahepatic cholestasis. The time course of the disease seems to be different in the two forms, the cholestatic form being more rapidly fatal than the other.