Interferon beta 1a anaphylaxis, a case report. Standardization of non-irritating concentration for allergy skin tests.

Multiple sclerosis is a disease with a potentially severe prognosis and epidemiologically increasing. Interferon beta 1a is a very useful maintenance therapy widely used by neurologists. In the literature, there are several case reports of  hypersensitivity reactions. In this case report we describe an anaphylactic IgE mediated reaction to interferon beta 1a. We also describe, for the first time in the medical literature, the non-irritating concentration (NIC) to be used for skin tests.

Aspirin challenge/desensitisation before coronary stenting in subjects with history of hypersensitivity. A pragmatic approach.

BACKGROUND: Aspirin hypersensitivity may represent a major problem in patients with ischemic coronary disease who need a stenting procedure. In those patients, clinically unsettled reasonably quick desensitisation procedures are needed. In our study we attempted to select the most suitable procedure on the basis of characteristics and severity of ASA hypersensitivity. METHODS: Thirty patients with a history of mild reactions to anti-inflammatory doses of aspirin (> 325 mg) were considered at low risk and underwent a tolerance test in 5 steps. Thirty-one patients, with a history of severe reactions to anti-platelet doses of aspirin 0 mg) underwent a slow desensitisation in 12 steps, reaching a cumulative dose of 150 mg ASA in 220 minutes. RESULTS: In the first group, 29 patients tolerated the challenge. One developed urticaria, thus underwent challenge/desensitisation and achieved tolerance. In the second group, 3 patients did not tolerate the procedure and had to discontinue. CONCLUSION. Our approach to aspirin hypersensitivity in patients needing coronary stenting, based on a severity stratification, allowed to achieve an effective tolerance to aspirin in the majority of subject in a reasonable short time.

Long-term chikungunya infection clinical manifestations after an outbreak in Italy: a prognostic cohort study.

OBJECTIVES: Following a Chikungunya (CHIKV) outbreak in Italy, a cohort study was conducted to describe the infection long-term clinical course and outcome. METHODS: Persons identified through active and passive surveillance as confirmed or possible CHIKV cases during the outbreak were enrolled and interviewed by trained public health nurses, between 4-5 and 12-13 months following the acute stage. Patients reporting persistent clinical symptoms were evaluated by rheumatologists. Serum samples were obtained and anti-CHIKV specific IgG and IgM immune responses detected. Only confirmed cases who completed the follow-up were analysed. RESULTS: Out of 250 patients, 66.5% still reported myalgia, asthenia or arthralgia (most frequent sign) after 12 months. Functional ability, measured by the ROAD index, was more impaired for lower extremities (3.75; Inter Quartile Range - IQR 4.4), and the activities of daily living (average 4.2; IQR 5). Variables independently associated with the presence of joint pain at 12-13 months were increasing age, and history of rheumatologic diseases). Elderly, females, and persons with history of rheumatologic diseases had higher anti-CHIKV IgG titres at 12-13 months. CONCLUSIONS: This study confirms, in an unselected population, that the long-lasting burden of CHIKV infection is significant.

Improvement of shrimp allergy after sublingual immunotherapy for house dust mites: a case report.

The appropriateness of house dust mite specific immunotherapy in patients allergic to shrimps still remains unclear We present a clinical case as an immunological model for the strong sensitization to tropomyosin with symptoms of anaphylaxis due to shrimps and coexisting asthma due to house dust mite. The improvement in respiratory symptoms for house dust mite and in the food challenge for shrimps during mite immunotherapy with a known and high dosage of tropomyosin suggests the hypothesis that efficacy of mite immunotherapy in food allergy to tropomyosin may be dose dependent.

A case of fatal biphasic anaphylaxis secondary to multiple stings: adrenalin and/or a longer observation time could have saved the patient?

We report the case of an atopic male, 76 years old, with post-myocardial infarction ischaemic cardiopathy, arterial hypertension and a history of insect-sting induced large local reactions who died because of a biphasic anaphylaxis subsequent to multiple Vespid stings (about 15). Within approximately ten minutes after the stings he developed urticaria, extended erythema and hypotension (90/60 mmHg), measured by a family member. The objective physical examination by the emergency doctor at the patient's home revealed an orticarioid reaction and erythema of the back and neck, an unaffected respiratory apparatus and CNS, normal pupils, a pulse rate of 74, normal blood pressure ranging from 120/70 to 130/60 mmHg. The patient was administered antihistamine and corticosteroid through parenteral route. During the 45' observation period at the patient's home the urticaria subsided but not to completion. Approximately 40 minutes after the emergency doctor left, the urticaria reoccurred, angioedema of the neck and worsening asthenia developed. The patient died, despite attempts to resuscitate him by the emergency doctor that had been called out again. A post-mortem examination revealed generalised eodema of the lungs, brain, glottis, and bowels due to the severe characteristic systemic compromise of anaphylaxis. The Authors discuss whether an early use of adrenalin and/or a longer observation time could have saved the patient.

Five-year follow-up of 165 Italian patients with undifferentiated connective tissue diseases.

OBJECTIVE: To study those conditions with a proven or hypothesised immunologic pathogenesis and denominated under a working definition of undifferentiated connective tissue diseases (UCTD). METHODS: A multicentre prospective study was organised involving 10 tertiary referral centers of internal medicine in Italy, with the aim of describing the natural history of UCTD and the prevalence of its different clinical and immunological manifestations. RESULTS: After a five-year follow-up period, data on 165 patients were available for analysis. UCTDs occur mainly in females in their fourth decade of life. Articular and mucocutaneous features and Raynaud's phenomenon represent the most common findings. Nevertheless, we also detected a relatively high incidence of permanent major organ damage. Regarding the immunologic parameters, we documented some conflicting results in the correlation between serologic abnormalities and clinical features. In 10 patients UCTD evolved to a major disease, generally systemic lupus erythematosus or Sjögren's syndrome. CONCLUSION: A low rate of evolution to a defined autoimmune disease, the limited use of steroid or immunosuppressive therapy, and a favourable course in the majority of cases are the main characteristics of patients with UCTDs.

[Nailfold capillary microscopy in patients with antiphospholipid syndrome]. / La capillaroscopia periungueale in pazienti con sindrome da immunità anti fosfolipidica.

In this paper we tried to define the capillaroscopic pattern of anti phospholipid syndrome able to differentiate between the primary (PAPS) and the systemic lupus erythematosus-associated form (SLE-APS) and to be a predictive marker of thrombotic manifestations. Eight PAPS and five SLE-APS patients were studied. In each patient the evaluation was based on anti cardiolipin antibody levels, nailfold capillaroscopy, retinal fluorangiography and transcranial doppler sonography. Statistical analysis has been performed using chi 2 analysis. Morphological alterations of capillary loops, venular visibility and sludging of blood were often observed in both groups. While we found in higher prevalence a variability of capillary loop length in PAPS patients, the SLE-APL group significantly differed for the presence of microhaemorrhages (p < 0.001). When we evaluated the clinical history, a marked microcirculatory damage was related with the occurrence of thrombotic manifestations in the PAPS patients. Anti cardiolipin antibody levels, retinal fluorangiography and transcranial doppler sonography did not correlate with clinical history in either group. In conclusion, nailfold capillaroscopy can be usefully employed in the differentiation between primary and SLE-associated anti phospholipid syndrome, and it can help to identify the patients at higher risk of thrombotic disease.

Terminal complement complex in synovial tissue from patients affected by rheumatoid arthritis, osteoarthritis and acute joint trauma.

The C5b-9 complex (Terminal Complement Complex-TCC) is the final product of the terminal complement pathway. In this study, using the monoclonal antibody MCaE11 (specific for a C9 neoantigen) and an immunohistochemical technique, we examined the TCC deposits in synovial tissues from 4 patients affected by rheumatoid arthritis (RA) and 6 patients affected by osteoarthritis (OA). Synovial tissues from 8 patients affected by acute joint trauma were examined as controls. Furthermore, plasma TCC levels were measured in 44 RA patients and 51 controls, using the above mentioned antibody and a sandwich ELISA. Eight synovial fluids were also included in this study. Abundant TCC deposits were detected in the cytoplasm of the synovial lining cells and of large stromal mononuclear cells in all the RA and in 3 out of 6 OA synovial tissues characterized by histological signs of inflammation. No TCC deposits were found in non-inflamed synovial tissues from patients with joint trauma. In agreement with previous observations, the TCC plasma levels found were significantly higher in RA patients than in controls, but no difference was seen between patients with active and non-active disease. The mean TCC level was significantly higher in the synovial fluid than in the plasma, but no correlation emerged between these two series of values. This study shows that: a) the plasma level of TCCs cannot serve as an indicator of disease activity in RA; b) the TCC deposits in synovial tissue correlate well with the extent of inflammatory synovitis, irrespective of whether the synovitis is rheumatoid or osteoarthritic in nature.

Juvenile rheumatoid arthritis patients manifest immune reactivity to the mycobacterial 65-kDa heat shock protein, to its 180-188 peptide, and to a partially homologous peptide of the proteoglycan link protein.

Immune reactivity to the 65-kDa mycobacterial heat shock protein (hsp65) has been associated with arthritis in rats and humans. In this report we evaluated patients with juvenile rheumatoid arthritis for such immunity. A high proportion of affected children showed both antibody and T lymphocyte responses to hsp65 and to two related peptides: the nonapeptide 180-188 sequence of hsp65 and a partially homologous peptide of the cartilage proteoglycan link protein. The titer of circulating antibodies was generally higher in patients with clinically active disease. In contrast to the juvenile rheumatoid arthritis patients, patients with adult rheumatoid arthritis tended to have lower responses of their peripheral blood T lymphocytes to the whole hsp65 molecule. Moreover, the adult rheumatoid arthritis patients did not respond to the peptides. Thus, there appear to be immunological differences between juvenile and adult forms of rheumatoid arthritis related to hsp65 reactivity.

MR imaging of rheumatoid hand lesions: comparison with conventional radiology in 31 patients.

The purpose of this study was to evaluate the diagnostic accuracy of magnetic resonance imaging (MRI) in rheumatoid arthritis (RA) by comparing MRI with conventional radiology (CR) findings and by correlating these findings with the clinical and serological profile of the disease. The hands of 31 patients (24 females, 7 males) affected by classical RA were studied using a Magnetom 1.0 T tomograph. Coronal, axial, and/or sagittal SE T1 and GE (FLASH 2D FL: 70 degrees-15 degrees) images were obtained in all patients. Moreover, in 7 patients the MRI study was performed after i.v. injection of Gd DTPA contrast medium (0.2 mM/kg). Ten healthy volunteers were also studied as controls. In all patients a conventional radiological study was performed as well as a clinical and serological investigation. Two blinded observers evaluated the MRI and CR findings and checked 15 elementary pathological lesions, assigning an MRI and a CR score to each patient. MRI provided higher accuracy than CR in detecting rheumatoid soft tissue changes and minimal skeletal lesions, while the opposite was true for severe skeletal lesions. No correlations emerged between the MRI/CR findings and clinical and serological data. This study suggests that MRI and CR are complementary techniques in the evaluation of the anatomical changes in RA.

Complement deficiency and antibody profile in survivors of meningococcal meningitis due to common serogroups in Italy.

A collaborative survey was carried out in Italy on a group of 59 subjects with a past history of meningococcal meningitis. The aim was to evaluate the prevalence of complement deficiencies, the serogroup of meningococci responsible for the disease and other possible immune abnormalities associated with the infection. Complement analysis allowed the detection of 10 cases (17%) with deficiencies of the terminal components, and in particular six cases of C8 beta, three of C7 and one of C6 defect. Half of the subjects with complement deficiencies had recurrences of meningitis and developed the infection at an older age in comparison with the control group with normal complement activity. The meningococcal C strain was the most diffuse (68%) and infected all the complement-deficient subjects. Evaluation of the antibody response to meningococcal capsular polysaccharides (PS) showed that only 42.5% of the individuals with group C had antibodies as opposed to 83% and 100% of the patients with meningitis due to group A and B, respectively. In all 59 subjects serum Ig as well as IgG subclasses were present, at normal levels for the age. Vaccination of seven out of the 24 subjects without detectable anti-meningococcal PS antibodies with the sole PS A+C induced a normal response in six of them, including a subject with complement defect. In the subject who did not respond to the antigen, the antibodies against the ubiquitous pneumococcal PS type 14 were also lacking, whereas anti-tetanus toxoid (TT) antibodies were normally present. From these data we may conclude the following: (1) the high prevalence (17%) of late complement components defect among survivors of meningococcal meningitis is also confirmed in the Italian population; (2) the serogroup C, responsible for the infections in all the cases with late complement components defect, is highly recirculating in Italy and apparently less immunogenic; (3) specific vaccination with meningococcal PS is a valid prophylaxis in subjects with lack of specific antibodies as well as in subjects with complement defect.

MHC gene products and anticardiolipin antibodies in systemic lupus erythematosus results of a multicenter study. SLE Study Group.

Anticardiolipin antibodies (aCL) and HLA-DR antigens were determined in 314 central European patients with systemic lupus erythematosus (SLE). Both HLA-DR4 and DR7 were increased in aCL-positive patients, and aCL were significantly associated with DRw53. The association between DRw53 and aCL was also apparent in those 17 patients with SLE and the anticardiolipin syndrome. There was no association between aCL and HLA-DQ or C4 alleles in SLE.

Low number of complement C3b/C4b receptors (CR1) on erythrocytes from patients with essential mixed cryoglobulinemia, systemic lupus erythematosus and rheumatoid arthritis: relationship with disease activity, anticardiolipin antibodies, complement activation and therapy.

Our aim was to assess whether the amount of complement C3b/C4b receptors (CR1) on erythrocytes shows a correlation to disease activity in various connective tissue diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and essential mixed cryoglobulinemia (EMC). Using an anti-CR1 monoclonal antibody, 26 patients with SLE, 34 with RA and 22 patients with EMC were investigated for erythrocyte CR1 expression. The control group consisted of 30 healthy individuals. The mean number of CR1/erythrocyte in the control group was 568 +/- 197 (range 174-1060), significantly higher than studied (EMC:379 +/- 248; p = 0.0005;SLE 147 +/- 56, p less than 0.0001; RA 298 +/- 177, p less than 0.0001). In patients with RA and in SLE, but not in patients with EMC, the number of CR1 numbers and anticardiolipin antibody (aCl) titers (r2 = 0.493; p = 0.034). A statistically significant correlation between CR1 numbers and CH50 values was found in patients with SLE, while in 3 patients with RA 4 months of therapy with cyclosporine A led to a further 30% reduction in CR1 number. Our conclusions are that (a) the decreased expression of erythrocyte CR1 is apparently a common feature of patients with various connective tissue diseases; (b) several acquired factors such as disease activity, complement activation, aCl and drugs may contribute to the loss of CR1 from erythrocytes; (c) in patients with RA and SLE, but not in patients with EMC, CR1 enumeration on erythrocytes may serve as a variable for clinical monitoring.

5-Methylcytosine content of DNA in blood, synovial mononuclear cells and synovial tissue from patients affected by autoimmune rheumatic diseases.

The percentage of 5-methylcytosine (m5Cyt) has been determined in peripheral blood, synovial mononuclear cells and synovial tissue from patients affected by various rheumatic autoimmune diseases. The determination was performed by reversed-phase high-performance liquid chromatography. Fifteen controls were compared to twenty-one patients affected by rheumatoid arthritis and to nine patients affected by systemic lupus erythematosus. The mean percentage of m5Cyt in normal individuals was significantly higher than in the rheumatoid arthritis and systemic lupus erythematosus patients. In addition, patients with active disease showed lower values than patients in remission. This finding is in agreement with the hypothesis that DNA hypomethylation may play a role in the pathogenesis of the autoimmune diseases, resulting in altered oncogene expression. Therapy with cyclosporin A led to a decrease in the percentage of m5Cyt in three rheumatoid arthritis patients, but a rebound was observed when the cyclosporin A was suspended. The percentage of m5Cyt in the DNA of synovial tissue from four rheumatoid arthritis patients and five patients with osteoarthritis was similar; this observation confirms that, in addition to disease-specific and disease activity-specific variations, the percentage of m5Cyt may also show tissue-specific variations.

[Magnetic resonance of the rheumatoid hand]. / La risonanza Magnetica nella mano reumatoide.

The purpose of this study was to evaluate MRI diagnostic accuracy in rheumatoid arthritis (RA), to compare MRI and radiological findings and to correlate these findings with the clinical and serological profile of the disease. The hands of 24 patients (20 females, 4 males) affected with typical RA (ARA criteria) were studied using a tomograph Magnetom 1.0 T Siemens. Two patients affected with RA refractory to conventional second-line drugs who received a bolus of methylprednisolone (1 g) were studied before and after such treatment. The hands of healthy volunteers were examined as controls. Besides MRI study all patients underwent: (1) radiological examination of the hands performed with a standard technique and (2) clinical and serological investigation aimed at characterizing diseases activity and extent. The radiographic and MRI findings were evaluated by two different observers who found 15 pathological elementary lesions and assigned a MRI and a radiological score to each patient. MRI exhibited significantly higher accuracy than radiography in evaluating rheumatoid soft-tissue changes and in detecting minimal skeletal lesions, while severe skeletal lesions were better detected by radiology. No correlation was found between pathological MRI findings, radiological results and clinical or serological data. A significant drop in soft-tissue effusion was observed after methylprednisolone pulse in two patients. This study confirms MRI potential in the study of rheumatoid joint lesions and in the early detection of minimal soft-tissue changes. Its use appears to be suitable for accurate monitoring of RA patients under specific therapy.

Tenoxicam and ketoprofen level monitoring with high performance liquid chromatography in patients affected by rheumatoid arthritis.

A new reversed-phase high-performance liquid chromatography (HPLC) technique was employed in order to monitor the plasma Tenoxicam (TNX) levels in 13 patients affected by rheumatoid arthritis who were participating in a short-term, controlled, randomized, double-blind TNX (20 mg once a day) vs Ketoprofen (KPF) study. The HPLC method described by Sutterwhite was used to measure the KPF levels in plasma samples from 10 rheumatoid patients assigned to the treatment with this drug (100 mg twice a day). The mean (+/- 1 SD) steady-state plasma TNX concentration was 11.138 +/- 3.55 micrograms/ml. Twelve out of 13 patients had a drug level within the steady-state range and 8 out of these 12 patients showed clinical improvement. A synovial fluid TNX concentration slightly lower than plasma levels (11.04 vs 13.58 micrograms/ml), and TNX synovial tissue levels remarkably lower than plasma levels (1.02 vs 3.5 and 0.85 vs 4.1 micrograms/ml) were observed in three further rheumatoid patients. The mean plasma concentration of KPF (+/- 1 SD) was 3.23 +/- 2.68 micrograms/ml and only two patients showed drug levels within the therapeutic range. In some cases the lack of compliance with the treatment regimen was proved in both groups, and an explanation for the poor efficacy of the drug was provided. A positive clinical result was reached in some of the patients with low drug plasma levels, in both the TNX and KPF groups. Gastrointestinal side-effects were observed in 4 patients from both groups, 2 within the therapeutic range and 2 below. This finding confirms that several variables, in addition to the plasma drug concentration, condition the efficacy and side-effects of an NSAID.

Interleukin-2, soluble interleukin-2 receptor and tumor necrosis factor in sera from patients with rheumatoid arthritis.

Interleukin-2 (IL-2), soluble interleukin-2 receptor (IL-2R) and tumor necrosis factor (TNF) have been measured in sera from 47 patients affected by classic rheumatoid arthritis (RA) using an enzyme-linked immunosorbent assay. The patients were divided into 4 groups as follows: group A, 18 patients with inactive disease; group B, 19 patients with active disease under treatment with non-steroidal antiinflammatory drugs (NSAID) and second-line drugs; group C, 5 patients with active disease under treatment with NSAID and cyclosporine A (CSA) for at least 4 months; group D, 5 patients in the same condition as patients of group C, but treated with azathioprine (AZA) instead of CSA. IL-2 was undetectable in all patients except two, both characterized by active disease. Soluble IL-2R levels were above the upper limit of the normal range in most of the patients studied, but the mean value ( +/- 1 SD) was significantly higher in patients of group B (1,288 +/- 421 U/ml) than in patients of group A (686 +/- 205 U/ml) and group C (842 +/- 414 U/ml). In two patients affected by active RA treated with pulse methylprednisolone therapy (1 g/day for 3 alternate days) the values of soluble IL-2R dropped from 948 to 662 U/ml and from 660 to 518 U/ml, respectively. No statistically significant correlation was observed between the serum level of IL-2R and the RF titre or percentage of C1q-binding activity, respectively. TNF was found within the normal range in all patients except one, who was characterized by active arthritis, high number of rheumatoid skin nodules and extremely high RF titre.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclosporin effect on sodium and potassium transport across erythrocytes in rheumatoid arthritis.

The aim of the present work was to evaluate the action of cyclosporin (CsA) both in vivo and in vitro on the active sodium transport across the erythrocyte membrane of rheumatoid arthritis (RA) patients. The in vivo study was performed on 20 patients affected by refractory RA and treated with CsA (5 mg/kg/die) or with azathioprine (2 mg/kg/die) before and after 7 days' therapy. The control group was formed of 25 healthy subjects. RA patients before treatment showed increased intra-erythrocyte Na+ concentration and decreased Na+, K+ ATPase activity in comparison with normal subjects. A rise in the activity of the sodium pump and a reduction in the intra-erythrocyte Na+ concentration were observed after cyclosporin treatment, but not after azathioprine. The in vitro study was performed on intact RBCs and on erythrocyte membranes from 15 healthy subjects and from 12 patients affected by classical RA, in the presence or absence of CsA (0.5-1-2 micrograms/ml). CsA (0.5 micrograms/ml) increased the Na+, K+ ATPase activity in intact RBCs and in erythrocyte membranes from both groups of subjects. Intracellular Na+ was decreased only in erythrocytes from RA patients after addition of 0.5 micrograms/ml CsA. A direct action of CsA on the membrane hydrophobic environment of the Na+, K+ ATPase is hypothesized on the basis of the present results.

Use of high-dose intravenous immunoglobulin in systemic lupus erythematosus: report of three cases.

Three patients with life-threatening manifestations of systemic lupus erythematosus (SLE), unresponsive to conventional high-dose corticosteroid and/or immunosuppressive therapy were treated with intravenous polyspecific IgG (IVIG). Following IVIG infusion, lupus encephalitis in the first patient quickly resolved and the impressive improvement of the clinical status was associated with a transient increase in C1q-binding activity. The daily infusion of IgG had to be suspended after three days in the second patient with encephalitis and nephritis, because the renal function rapidly deteriorated; subsequently, six plasma exchanges led to an almost complete recovery. Finally, leukocyte and platelet counts increased and remained within normal range following IgG therapy in the third patient having SLE-associated leuko- and thrombocytopenia. In all three patients a decrease in anti-DNA antibody levels and an increase in total complement hemolytic activity were detected after therapy.