Risk factors for a first thrombotic event in antiphospholipid antibody carriers. A multicentre, retrospective follow-up study.

OBJECTIVES: To asses risk factors for a first thrombotic event in antiphospholipid antibody (aPL) positive carriers and evaluate the efficacy of prophylactic treatments. METHODS: Recruitment criteria were age 18-65 years, no history of thrombosis, positivity for lupus anticoagulant and/or IgG/IgM anticardiolipin antibody (aCL) on > or =2 occasions at least 6 weeks apart. Demographic, laboratory and clinical parameters were collected at enrolment and at the time of the thrombotic event. RESULTS: 370 patients/subjects (mean (SD) age 34 (9.9) years) were analysed retrospectively for a mean (SD) follow-up of 59.3 (45.5) months. Thirty patients (8.1%) developed a first thrombotic event during follow-up. Hypertension and medium/high levels of IgG aCL were identified by multivariate logistic regression analysis as independent risk factors for thrombosis. Thromboprophylaxis during high-risk and long-term periods was significantly protective. CONCLUSIONS: Hypertension or medium/high titres of IgG aCL are risk factors for a first thrombotic event in asymptomatic aPL carriers and primary prophylaxis is protective.

Bilateral femoral osteomyelitis with knee arthritis due to Salmonella enteritidis in a patient with systemic lupus erythematosus.

A bilateral knee septic arthritis due to Salmonella enteritidis developed in a female patient affected by long-standing systemic lupus erythematosus (SLE) with cardiac and renal involvement treated with immunosuppressants and corticosteroids. Because avascular necrosis and multiple osteomyelitic areas were detected at the same time in both right and left femoral condyles, an early localisation of Salmonella into the bone was assumed. Involvement of the joints was regarded as consequence of local dissemination of infection. Ampicilline (0.2 g/kg body weight daily for 2 months) plus ciprofloxacin (1.5 g daily for 12 months) and withdrawal of immunosuppressants appeared to be effective in preventing complications of infection.

Association of primary antiphospholipid syndrome with inherited activated protein C resistance.

A 65-year-old man had had arterial thromboses of the lower limbs and cerebral region for several years; tests revealed anticardiolipin, antiphosphatidylserine, anti-beta2-glycoprotein I antibodies, and lupus anticoagulant. As well, both phenotypic and genotypic resistance to activated protein C was found. Antiphospholipid antibodies have been reported to interfere in different ways with the functions of protein C; in our patient the simultaneous existence of inherited resistance to activated protein C could account for the thrombophilic status underlying the diffuse and serious arterial thromboses.

Clinical setting of patients with systemic sclerosis by serum autoantibodies.

Associations of antinuclear (ANA) and anticardiolipin (aCL) antibodies with clinical manifestations were analyzed in patients with systemic sclerosis (SSc). We studied 105 SSc patients: 28 had limited cutaneous SSc (lcSSc) involving fingers; 36 had intermediate cutaneous SSc involving limbs and face; 33 had diffuse cutaneous SSc (dcSSc) involving the trunk; 8 had a sclerosis sine scleroderma. Clinical manifestations and instrumental and laboratory findings were considered to calculate a disease score. Serum anticentromere (ACA), anti-topoisomerase I (anti-topo I) antibodies, and aCL (of IgG/IgA/IgM classes) were investigated by conventional methods. ACA positive patients (n=18), compared to ACA negative, showed higher prevalence of IcSSc (p < 0.001), lower prevalence of restrictive ventilatory defect (p=0.006), and lower disease score (p=0.008). Anti-topo I positive patients (n= 70) showed lower prevalence of lcSSc (p =0.001) compared to anti-topo I negative. In aCL positive patients (n=27) widespread skin and visceral involvement occurred more frequently than in aCL negative. The association with myocardial ischemia or necrosis (p=0.010) was significant. Occurrence of ACA excluded the coexistence of anti-topo I (p < 0.001), and aCL (p=0.037). aCL positive patients showed higher disease score in comparison with ACA positive patients (p=0.003). In conclusion ACA recognize patients with a mild disease. aCL in contrast to ACA are better than anti-topo I in recognizing the most severe pictures of SSc.

Clinical significance of anticardiolipin antibodies in patients with systemic sclerosis.

One hundred and three patients suffering from systemic sclerosis (SSc), with different extent of skin involvement, were retrospectively examined to investigate the correlations between clinical manifestations and anticardiolipin antibodies (aCL). aCL of IgG, IgA, and IgM classes were measured in the patients' sera by enzyme linked immunosorbent assay. aCL were found in 26 patients (25.2%). A significant association was found between aCL and myocardial ischaemia or necrosis (p = 0.011). No patient showed the clinical picture of the antiphospholipid syndrome. On the basis of clinical manifestations, a protocol for disease score was drawn. Patients with IgG-aCL and with IgA-aCL showed a disease score higher than aCL negative patients (p = 0.008 and p = 0.022 respectively). Thus, the finding of aCL can be considered a useful serological index for the most severe forms of SSc.

Avascular osteonecrosis in patients with SLE: relation to corticosteroid therapy and anticardiolipin antibodies.

Sixty-nine unselected SLE patients were studied to evaluate the prevalence of avascular osteonecrosis (AVN) and its relationship with steroid therapy and with anticardiolipin antibodies (aCL). All the patients were under treatment with corticosteroids. AVN occurred in seven occurred in seven of the 69 patients (10.14%) and was not related to corticosteroid intake. Seventeen of the 69 patients were also treated with methylprednisolone pulse therapy (MPPT) and cumulated the highest corticosteroid doses but none of them suffered from AVN. Excluding the 17 MPPT-treated SLE patients, corticosteroid intake was significantly higher in the AVN-SLE patients. Abnormal IgG and/or IgM aCL serum levels were found in two of the seven AVN-SLE patients and in 24 of the 62 non-AVN SLE, without a statistically significant difference. None of the seven AVN-SLE patients showed features of antiphospholipid syndrome. We conclude that in SLE patients a continuous high-dose steroid treatment may be considered a risk factor for AVN. On the contrary, MPPT regimen may reduce this risk. Anticardiolipin antibodies might represent an added factor which could play a role in some patients but not in all.

Spectrum of cardiac involvement in systemic lupus erythematosus: echocardiographic, echo-Doppler observations and immunological investigation.

Cardiac involvement was noninvasively evaluated in 75 consecutive patients with systemic lupus erythematosus (SLE) by two-dimensional and Doppler echocardiography. In 50/75 patients anticardiolipin antibodies (aCL) were also investigated. Major endocardial damage, characterized by the simultaneous presence of both anatomical and functional valvular involvement (AFVI), was observed in three patients with valvular vegetations and in five patients with combined valvular stenosis and/or regurgitation. Nine patients showed only an anatomic valvular involvement (AVI), expressed by a thickening of one or more valvular leaflets, without echo-Doppler findings of valvular dysfunction. Occurrence of major valvular involvement appears to be correlated with both longer disease duration (9.8 +/- 5.6 yrs in AFVI group vs 5.7 +/- 5.6 yrs in the remaining SLE patients; p < 0.001) and IgG aCL (chi-square = 5.546; p < 0.05). Left ventricular systolic function, evaluated by two-dimensional echocardiographic ejection fraction, was preserved in all patients (EF: 60 +/- 5%). Left ventricular diastolic function, as expressed by echo-Doppler transmitral flow indices of left ventricular filling, was subclinically impaired in 23 patients: only disease duration was significantly longer in these patients (7.7 +/- 5.9 yrs vs 4.9 +/- 4.8 yrs; p < 0.05). Our study demonstrated that cardiac involvement is quite frequent in SLE patients: the disease duration affects both endocardial and myocardial involvement; the anticardiolipin antibodies appear to be related to endocardial but not to myocardial damage.

A case of diffuse lupus encephalopathy successfully treated with high-dose intravenous methylprednisolone.

We report a case of systemic lupus erythematosus (SLE) in a young woman who presented a serious encephalopathy with respiratory distress and coma, after arbitrary interruption of oral corticosteroid therapy when her first pregnancy ended in abortion. The patient showed rapid improvement on methylprednisolone pulse therapy. The case suggests the utility of such a therapy in severe, non focal, CNS complications of SLE.

Longitudinal survey of anticardiolipin antibodies in systemic lupus erythematosus. Relationships with clinical manifestations and disease activity in an Italian series.

One hundred and two patients suffering from systemic lupus erythematosus were observed over 5-140 months. IgG and IgM anticardiolipin antibodies (aCL) were searched for by ELISA in 448 serum samples, and were found in 88 (86.3%) patients on at least one occasion. Changes of aCL levels and isotypes were recorded in most patients. In patients with medium (20-80 U. GPL and/or MPL) and high (> 80 U. GPL and/or MPL) aCL levels associations with thrombosis, neurological manifestations, cerebrovascular disease, prolonged aPTT, and thrombocytopenia were found. A highly significant statistical association was found between IgG aCL and the occurrence of active disease (p < 0.0001).

Evaluation of cardiac structures and function in systemic sclerosis by Doppler echocardiography.

Ventricular diastolic filling was investigated in a series of 51 consecutive patients with systemic sclerosis by means of Doppler echocardiography. Peak flow velocity in early (peak E) and late (peak A) diastole, E/A ratio, slope of the early diastolic flow velocity and isovolumic relaxation period were calculated. Nine out of the 51 patients showed abnormalities of ventricular filling dynamics in the absence of left ventricular systolic dysfunction at rest and after provocation. The abnormal diastolic filling pattern in these patients was detected in spite of the absence of systemic hypertension, left ventricular hypertrophy or other clinically evident myocardial disease. These diastolic abnormalities might represent an isolated evidence of the underlying myocardial fibrosis not yet clinically apparent.

[Clinico-developmental aspects in 44 cases of polymyositis/dermatomyositis]. / Aspetti clinico-evolutivi in 44 casi di polimiosite/dermatomiosite.

A retrospective study, paying particular attention to the clinical and evolutive aspects of the disease, was performed on 44 subjects affected by polymyositis/dermatomyositis (PM/DM) and hospitalized at the Institute of Medical Clinics of the 1st School of Medicine of Naples University. On the basis of the different clinical pictures, the cases were classified into the following groups: primary PM (4); primary DM (19); DM/PM associated with malignancy (6); childhood DM/PM (3); PM/DM associated with connective tissue disorders (12). Diagnosis was established in terms of the following criteria: a) symmetrical and mostly proximal bilateral muscle weakness (100%); b) elevation of serum enzymes (86.3%); c) electromyographic findings of myopathy sometimes with fibrillation potentials, increased insertional irritability and pseudo-myotonic discharges (93.1%); d) muscle biopsy changes compatible with a clinical form of polymyositis (83.3% out of 30 cases); e) dermatological manifestations including particularly pink or lilac edema-erythema over the periorbital areas, wine-red maculae, Gottron's sign, "poikiloderma vasculare atrophicans", telangiectasias and skin vasculitis (86.3%). An involvement of the extraneural apparatus and organs was present in 40 patients; the most damaged was the osteoarticular apparatus, followed by esophagus, lung, heart and kidney; such pathology was rarely present in the childhood form. A follow-up of the disease has been performed in 36 cases and the therapy consisted fundamentally of high dose corticosteroids (mostly prednisone), associated, in a minority of cases, with methotrexate. A clinical improvement was observed in most cases and a remission of the disease in part of the latter. However, a worsening of the illness was noticed only in the patients suffering from PM/DM associated with malignancy, and mortality rate was 11.1% in all.

[Neurological manifestations of systemic lupus erythematosus. Study of 53 cases]. / Manifestazioni neurologiche nel lupus eritematoso sistemico. Studio di 53 casi.

The Authors submitted 53 randomly selected patients affected by systemic lupus erythematosus (SLE) to neurologic evaluation to investigate the prevalence of neurologic manifestations, establish relationships to clinical and epidemiological findings and antinuclear antibodies and/or lupus anticoagulant (LAC), as well as to assess the usefulness of electroencephalogram (EEG), saccadic eye movements (SEM) analysis, brain computerized tomography (CT). Twenty-two patients (41.5%) had nervous system involvement on anamnestic and/or clinical examination: there were seizures in 5 patients, headache in 3, involuntary movements in 3, psychosis in 2 and cerebrovascular disorders in 9. The patients were subdivided into 2 groups, with neuro-SLE and without neuro-SLE, according to clinical and/or anamnestic evidence of nervous system involvement. There were no differences between the two groups of patients regarding disease duration, disease activity, presence of antinuclear antibodies and/or LAC. EEG and/or SEM and/or brain CT abnormalities were found in 38 cases, 18 of which had no clinical evidence of neuro-SLE. Instrumental evaluation can thus document subtle nervous dysfunction and offers the possibility of classification into: a) non-neuro-SLE; b) subclinical neuro-SLE; c) overt neuro-SLE.

Different antibody patterns and different prognoses in patients with scleroderma with various extent of skin sclerosis.

Ninety patients who fulfilled the ARA criteria for systemic sclerosis were divided into 6 groups on the basis of cutaneous areas of sclerosis. Anticentromere antibody (ACA) was found in 14 of 28 patients of the first 2 groups, the first group being pure sclerodactyly, and the second sclerodactyly plus minimal sclerotic lesions (eyelids, neck, armpits). In the other 4 groups (62 patients) in whom skin sclerosis was more diffuse, ACA was found in one case. Fluorescent antinuclear antibodies (FANA) with a diffusely grainy pattern, those with a nucleolar pattern and the anti-Scl-70 antibody were present in all 6 groups, but were significantly more frequent in the last 4 groups than in Groups 1 and 2. The cumulative survival rate as well as disease duration were found to be significantly longer in the first 2 groups designated "limited cutaneous systemic sclerosis," than in the 5th and 6th groups, i.e., patients in whom the trunk also was involved: "diffuse cutaneous systemic sclerosis." The cumulative survival rate and disease duration of patients with skin sclerosis of the face and limbs, but not of trunk, were not significantly different either from those of patients with limited cutaneous systemic sclerosis or from those of patients with diffuse cutaneous systemic sclerosis. Thus these patients show the same antibody pattern as diffuse cutaneous systemic sclerosis, but the prognosis not significantly different from the other 2 subsets. We suggest they constitute a distinct subset of systemic sclerosis for which we propose the name "intermediate cutaneous systemic sclerosis."

[Lupus-like connectivitis with severe hemorrhagic retinitis in a patient with total IgA deficiency]. / Lupusähnliche Konnektivitis mit schwerer hämorrhagischer Retinitis bei einem Patienten mit totalem IgA-Defizit.

Clinical report of a 23-year-old woman with total IgA-deficit, who had suffered for 2 years from a connective tissue disease similar to lupus erythematosus, with severe hemorrhagic retinitis but without any renal involvement.