Armando Malcata

Contribution for new genetic markers of rheumatoid arthritis activity and severity: sequencing of the tumor necrosis factor-alpha gene promoter

The objective of this study was to assess whether clinical measures of rheumatoid arthritis activity and severity were influenced by tumor necrosis factor-alpha (TNF-α) promoter genotype/haplotype markers. Each patients disease activity was assessed by the disease activity score using 28 joint counts (DAS28) and functional capacity by the Health Assessment Questionnaire (HAQ) score. Systemic manifestations, radiological damage evaluated by the Sharp/van der Heijde (SvdH) score, disease-modifying anti-rheumatic drug use, joint surgeries, and work disability were also assessed. The promoter region of the TNF-α gene, between nucleotides -1,318 and +49, was sequenced using an automated platform. Five hundred fifty-four patients were evaluated and genotyped for 10 single-nucleotide polymorphism (SNP) markers, but 5 of these markers were excluded due to failure to fall within Hardy-Weinberg equilibrium or to monomorphism. Patients with more than 10 years of disease duration (DD) presented significant associations between the -857 SNP and systemic manifestations, as well as joint surgeries. Associations were also found between the -308 SNP and work disability in patients with more than 2 years of DD and radiological damage in patients with less than 10 years of DD. A borderline effect was found between the -238 SNP and HAQ score and radiological damage in patients with 2 to 10 years of DD. An association was also found between haplotypes and the SvdH score for those with more than 10 years of DD. An association was found between some TNF-α promoter SNPs and systemic manifestations, radiological progression, HAQ score, work disability, and joint surgeries, particularly in some classes of DD and between haplotypes and radiological progression for those with more than 10 years of DD.

White blood cell count abnormalities and infections in one-year follow-up of 124 patients with SLE.

The purpose of our study was to evaluate the frequency of leukocyte count abnormalities in a large cohort of SLE patients and its association with infection. To make this evaluation, we studied consecutive patients with SLE diagnosis and prospectively followed them in the Coimbra Lupus Cohort. Data about white blood cell count abnormalities and infection during one‐year follow‐up were obtained. The presence of leukopenia, lymphopenia, and neutropenia was registered for one‐year period. Infections were classified as severe or mild. We found that of the 124 patients who were included (91.1% female, mean age 41.2, mean disease duration 11.1), mild infections occurred in 43.5%, and severe in 3.2% of the patients. Twelve percent, 41.1%, and 4.8% of the patients had persistent leukopenia, lymphopenia, and neutropenia, respectively. Fourteen percent received a pneumococcal vaccination. Patients with neutropenia had a significantly higher number of infections (P= 0.033). Thus, our study showed that neutropenia was associated with an increased risk of infection during this one‐year follow‐up. Infections were frequent, but most of them were mild.

Anaphylaxis to mefenamic acid in a patient with new onset of systemic lupus erythematosus.

Many studies have addressed the frequency of drug allergy (DA) in systemic lupus erythematosus (SLE) patients. Some studies suggest that there may be an increased risk in these patients while others do not confirm this. The conflicting results may be due to differences in definition of drug allergy; in the means of ascertaining allergic manifestations; and in the choice of controls. SLE patients are more frequently exposed to drugs, which, ‘‘per se’’, represent a risk factor for drug allergy. Prompt recognition of DA, particularly anaphylaxis, is crucial, as it may be life-threatening and the appropriate treatment cannot be delayed. In a patient with SLE, the differential diagnosis of drug allergy is challenging. Features such as rash, fever and cytopenia may result from drug allergy but may also be part of SLE manifestations. Furthermore, drugs like sulphonamides are well known to exacerbate, or even induce SLE. The authors report a case of a 32-year-old Caucasian female housewife who presented at the emergency room with rash, diffuse myalgias, dry mouth, paraesthesia and dizziness. The symptoms started 90 minutes after taking a 250 mg tablet of mefenamic acid. She was thought to have an allergic drug reaction and was treated with intramuscular clemastin and IV methylprednisolone 250 mg. She was alert, her blood pressure was 100/57 mmHg, her heart rate was 124 per minute and her temperature was normal. Despite receiving clemastin and methylprednisolone, two hours later she had a clinical deterioration starting with generalised pruritus and worsening of generalised exanthema, myalgias and arthralgias. She rapidly developed angio-oedema and anaphylactic shock. Her temperature was 37.4 1C, her blood pressure dropped to 73/45 mmHg and her heart rate was 120 per min. She was given dopamine, epinephrine and 250 mg of IV methylprednisolone and intravenous fluids. Blood cell count revealed a haemoglobin level of 7.9 g/dl [11.5–16.5], a white blood cell count of 5.4 10/mL [4–11], prothrombin time 22 s [13], d-dimers of 7.17 mg/L [0–0.6], fibrinogen of 2.6 g/L [2–5.0], SGPT 219 U/l [5 55]; SGOT 337 U/l [5–34]; SGGT 15 U/l [9–36], total bilirubin 0.8 mg/dl

Increased prevalence of allergic sensitisation in rheumatoid arthritis patients treated with anti-TNFalpha

INTRODUCTION Tumour necrosis factor alpha (TNFalpha) has emerged as a therapeutic target in chronic inflammatory disorders characterised by a Th1 type immune response, such as rheumatoid arthritis (RA). The presence of allergic disease in these patients could be influenced both by the presence of RA and anti-TNFalpha therapy. Our aim was to evaluate the prevalence of sensitisation to airborne allergens and allergic disease in RA patients, with and without anti-TNFalpha treatment. METHODS RA patients with (N=20) and without (N=20) anti-TNFalpha therapy (groups T and R) were enrolled. Healthy controls (N=60, group C) were randomly selected from the general population. All participants answered a standardised questionnaire to assess the prevalence of allergic disease and had skin prick tests (SPT) with a standard panel of airborne allergen extracts. RESULTS Significant differences were found in the prevalence of positive SPT between groups T and R (70% vs 35%, p=0.027) and groups T and C (70% vs 36.7%, p=0.009), but not between groups R and C. The prevalence of allergic disease was similar in the three groups. Groups T and R had similar gender and age distribution, disease duration, disease activity score (DAS28), erythrocyte sedimentation rate and serum C-reactive protein. CONCLUSIONS Increased prevalence of sensitisation to airborne allergens in RA patients treated with anti-TNFalpha was found. The clinical impact of the positive SPT following anti-TNFalpha initiation has now to be assessed.

Milwaukee shoulder (and knee) syndrome

An 80-year-old woman presented with a 1-month history of bilateral shoulder pain and swelling (figure 1). There was no history of any trauma. Physical examination showed limited and painful active and passive range of motion of the shoulders and a valgus deformity of the knees. Anteroposterior X-rays of the shoulders and knees were performed (figure 2). Shoulder ultrasound revealed exuberant subacromial bursitis (figure 3) associated with complete rotator cuff tear bilaterally. Bursa aspiration yielded a haemorrhagic non-inflammatory fluid and hydroxyapatite crystals were identified with alizarin red staining (figure 4). Synovial fluid culture was …

Educational needs of patients with rheumatoid arthritis

Only three patients received pain assessment within 4 h of admission. No patients were assessed regularly regarding the location and intensity of their pain. More than one third of patients did not receive any PRN analgesics. Patients of 80 years of age or older received a smaller number of doses of PRN analgesics than their younger counterparts. The number of doses of PRN analgesics received by patients following pain assessment was significantly greater than that received by patients without pain assessment. More than 60% of nurses reported that they were aware of the method of assessing pain in the elderly, and more than three quarters said that ‘‘administration of analgesia around-the-clock’’ is better than ‘‘administration as required’’. Of the barriers for optimal pain management, the one that created the most challenge was ‘‘difficulty communicating with patients’’.