Rituximab induces resolution of recurrent diffuse alveolar hemorrhage in a patient with primary antiphospholipid antibody syndrome.

Diffuse alveolar hemorrhage (DAH) is a rare manifestation of primary antiphospholipid antibody syndrome (APS). We describe a patient with primary APS and refractory recurrent episodes of DAH. The patient was admitted 15 times due to recurrent episodes of DAH in a period of 18 months. Multiple immunosuppressive drugs did not improve his condition. Two years after his presentation, he was treated with rituximab (two doses of 1 g, 2 weeks apart). Six months later, the attacks of DAH have gradually disappeared. In a follow-up of more than 2 years after he received rituximab, the patient has had no further admissions due to DAH. Levels of antiphospholipid antibodies were measured during follow-up of 4 years. Anti-ß2 glycoprotein IgG titer decreased to normal 6 months after therapy but anticardiolipin (aCL) antibody titer increased. We conclude that rituximab caused a dramatic clinical response in this patient. Anti-ß2 glycoprotein IgG correlated better with the clinical response in this patient than aCL.

Secondary syphilis presenting as SAPHO syndrome features.

The SAPHO syndrome may evolve following low virulent infections. This report describes a patient who developed a clinical syndrome that complied with the formal diagnostic criteria of the SAPHO following an infection with syphilis. His clinical manifestations gradually resolved following antibiotic therapy. This interesting association underlines the pathogenic circumstances linking infections and various rheumatic conditions. It is less evident whether resolution of the symptoms was ascribed to the eradication of the bacteria or perhaps due to cessation of the auto-inflammatory reaction to the infection induced. In our description we suggest a correlation between infection with Treponema pallidum and the induction of SAPHO syndrome.

Physical activity protects male patients with post-traumatic stress disorder from developing severe fibromyalgia.

OBJECTIVES: Fibromyalgia syndrome (FMS) has been associated with various psychiatric and other, ill-defined disorders. We recently showed that fibromyalgia is more prevalent in men suffering from combat-related Post Traumatic Stress Disorder (PTSD). In this paper we analyze the relationship between engagement in physical activity, the psycho-metric traits of PTSD and the future development of FMS. METHODS: Fifty-five male patients, all known to have combat-related PTSD, were investigated for the presence of fibro-myalgia according to the American College of Rheumatology (ACR) criteria. Each patient completed questionnaires characterizing his quality of sleep, and the Sheehan Disability Scale measuring performance in the familial, social and vocational spheres. Additionally, each of the enrollees was interviewed by an experienced psychiatrist, who then completed a Clinician Administered PTSD Scale, a Clinical Global Impression Scale, and calculated an SF-36 score. Each patient was asked whether he exercised often, occasionally or not at all. The data was analyzed by the chi2 test and by ANOVA. RESULTS: PTSD patients who also suffered from FMS had a more severe form of disease as measured by the Clinician Administered PTSD Scale (CAPS) score, 88.2 +/- 14.0 (n = 28) compared to 97.6 +/- 13.2 of patients with PTSD and FMS (n = 27) (p = 0.013, F(d.f 2)-6.61, ANOVA test). Interestingly, engaging in physical exercise was also associated with less severe disease. When the patients were analyzed based on their tender point count (0-5, 6-10, or > 11), the number of tender points decreased with increasing physical activity (p = 0.02, chi2(d.f.-4) = 11.3). CONCLUSION: Physical exercise in male patients with combat-related PTSD provides protection from the future development of fibromyalgia. Furthermore, physical activity is related in this group of patients to a better perception of their quality of life.

Attitudes of medical practitioners towards "Do Not Resuscitate" orders.

When the desires of a patient are unknown or cannot be ascertained, cardio-pulmonary resuscitation (CPR) is the default procedure. Explicit, Do Not Resuscitate (DNR), orders are required to prevent implementation of CPR. We studied the response of general medical internists in specific clinical situations demanding consideration of DNR orders and respect for patient preferences; their current practice regarding slow codes and participation in CPR attempts considered futile provide information as to how often they discuss DNR issues with patients or families. Eighty-five internists attending the monthly meeting of the Internal Medicine Forum participated in the study. The physicians demonstrated their consent to participate by accepting a remote transmitter that elicited a response 2-3 minutes following the presentation of case vignettes or practice-related questions. The survey showed that 73% of the physicians agreed to assign a DNR order for a terminally ill patient unable to express her preferences. Only 55% agreed to do the same for a competent patient who specifically requested that CPR be withheld in the event of a cardiopulmonary arrest (p<0.05). 77% reported to have performed CPR, at least three times, in situations where they expected no benefit. 59% affirmed that their team had performed a partial CPR (slow code) at least once. Only 28% discussed the subject of DNR with patients or family more than 5 times a year. Paternalism, disregard for patients' preferences and poor communication skills influence normative behaviour in end-of-life decision-making.

Alveolar hemorrhage in cryoglobulinemia--an indicator of poor prognosis.

OBJECTIVE: Alveolar vasculitis is an unusual event in the course of cryoglobulinemia (CG). The inflammatory process involving the alveolar capillary walls may result in severe alveolar hemorrhage and consequently lead to a grave outcome. The objective of this study was to evaluate the occurrence of this unusual finding in CG. METHODS: We reviewed the records of all patients with CG who developed acute alveolitis, registered their associated clinical and laboratory parameters and evaluated the possible impact these parameters may have on their prognosis. In addition we scanned the Medline for similar cases. RESULTS: Of the 125 patients with CG who were hospitalized in our medical center during the last 23 years, 4 (3.2%) developed alveolar hemorrhage. All patients exhibited extreme fatigue, fever with clinical and radiological evidence of alveolitis. Of the 4 new cases, 1 had type II CG and 3 had type III CG. Of our 4 patients, 3 developed concomitant acute renal failure necessitating hemodialysis. A literature survey resulted in 6 additional cases. All 10 patients experienced acute respiratory insufficiency and eight had at least one episode of hemoptysis. In the other 2 patients the bronchoalveolar lavage (BAL) fluid contained hemosiderin laden macrophages. Five of the 10 patients had concomitant hepatitis C virus (HCV) infection; 2 patients were seen prior to modern identification of the HCV; however, liver abnormalities were not described. Of the 10 patients 5 patients had type II CG and 5 others had type III. Of the 7 patients in whom outcome was available, 6 died from their illness. Acute renal failure or exacerbation of antecedent glomerular disease occurred in 8 patients. CONCLUSIONS: Alveolitis is a rare manifestation of CG, presenting as an overwhelming systemic illness and portends a poor prognosis with a high mortality rate.

Hyperacute renal failure as the initial presentation of systemic lupus erythematosus.

SLE nephritis is usually a slow process that may lead to renal failure many years after its first presentation. Success of different therapeutic modalities in preventing renal failure is therefore evaluated and compared only after many years of treatment. Lately, this conservative philosophy has been challenged with the acknowledgment of collapsing glomerulopathy (CG), a recent recognized clinical-pathological entity, characterized by rapidly progressive renal failure. Despite this ominous description we present an unusual case of a patient who presented with systemic lupus erythematosus (SLE) and clinical and pathological findings of CG, who completely remitted several weeks after commencing immunosuppressive therapy with intravenous cyclophosphamide and prednisolone.

Methotrexate related adverse effects in patients with rheumatoid arthritis are associated with the A1298C polymorphism of the MTHFR gene.

BACKGROUND: There is an association between C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene and methotrexate related toxicity. OBJECTIVE: To examine the relations between the recently described A1298C polymorphism of the MTHFR gene, plasma homocysteine, methotrexate toxicity, and disease activity in patients with rheumatoid arthritis. DESIGN: A cross sectional study on 93 methotrexate treated patients with rheumatoid arthritis, comprising a clinical interview and physical examination to determine disease activity and methotrexate related adverse reactions. Genotype analysis of the MTHFR gene was carried out and fasting plasma homocysteine and serum folate concentrations were measured. The data were analysed using univariate analysis. Allele and genotype distributions were compared with those of a healthy control group. RESULTS: The frequency of the 1298CC genotype (24.7%) in the rheumatoid study group was greater than expected in the general population (12.8%, p<0.001). This genotype was associated with a significantly low rate of methotrexate related side effects. The odds ratio for side effects in patients with wild type 1298AA genotype v 1298CC genotype was 5.24 (95% confidence interval, 1.38 to 20). No correlation of disease activity variables or plasma homocysteine with MTHFR A1298C and C677T polymorphisms was observed. CONCLUSIONS: 1298CC polymorphism was more common in methotrexate treated rheumatoid patients than expected in the population, and was associated with a reduction in methotrexate related adverse effects. The A1298C polymorphism of the MTHFR gene may indicate a need to adjust the dose of methotrexate given to patients with rheumatoid arthritis.

SAPHO syndrome treated with pamidronate: an open-label study of 10 patients.

BACKGROUND: In recent years the SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis and osteitis) has been encountered more frequently. However, clinical evidence indicating superiority of a specific therapeutic modality is still absent. Pamidronate, a second-generation bisphosphonate, has a pronounced effect on bone metabolism by suppressing bone resorption. We report our clinical experience with intravenous pamidronate in SAPHO syndrome. METHODS: Between the years 1999 and 2003 we treated 10 patients with the SAPHO syndrome who did not respond to NSAIDs, oral corticosteroids, colchicine, methotrexate, sulphasalazine or infliximab. All patients were treated with 60 mg pamidronate, given intravenously within an hour. In cases of no response a subsequent dose was given within a month and if there was a partial response an additional infusion was given after 4 months. The primary endpoint was the disappearance of recurrent bouts of bone pain, osteitis or hyperostosis, or recurrent synovitis. Reduction of the frequency of attacks by 50% was regarded as a partial response. RESULTS: Seven of the patients were females and three were males. The age at diagnosis ranged from 26 to 68 yr. All patients had axial or peripheral arthritis and cutaneous involvement; three had severe acne, eight had pustulosis and two had concomitant psoriasis vulgaris. Hyperostosis of the anterior chest wall involving either sternocostal or sternoclavicular joints, as seen on technetium 99 bone scintigraphy, was detected in all patients. Complete remission was observed following therapy in six patients, three others partially responded and only one patient had no response. Two patients needed four cycles of pamidronate infusion, one patient needed three, six needed two infusions and one patient remitted following a single pamidronate infusion. In all but one patient pamidronate was effective in preventing recurrent bouts of pustulosis. CONCLUSION: Pamidronate seems to be a very effective mode of therapy for patients with the SAPHO syndrome, by promoting remission in all components of the disorder, such as bone, joint and skin involvement, and ceases the bouts that characterize this disorder.

Safety of low dose methotrexate in elderly patients with rheumatoid arthritis.

Weekly low dose methotrexate is an established treatment for rheumatoid arthritis, but its use in elderly people has not been adequately examined. The aim of this study was to evaluate its safety in elderly patients with rheumatoid arthritis. A retrospective review of the clinical records of rheumatoid arthritis patients over the age of 65 attending a rheumatology unit was conducted. Eligible patients were followed for at least two years and treated with methotrexate in a dose of 7.5 mg/week while being maintained on concurrent treatment. Thirty three patients were studied. Their mean age was 78.8 years; 32 were female and one was male. Treatment was discontinued in four patients, two because of raised serum liver enzymes and two because of gastrointestinal irritation. No serious adverse events were reported. After two years, haemoglobin levels increased from a mean (SD) of 12.4 (1.3) g/dl to 13.0 (1.1) g/dl (r = 0.226, p < 0.005). The white blood count was significantly reduced from 7.9 (1.8) x 10(9)/l to 6.8 (1.7) x 10(9)/l (r = 0.184, p < 0.05). No episodes of neutropenia or agranulocytosis were observed. There was a non-significant decrease in platelet count. The erythrocyte sedimentation rate decreased from 56.8 (30.8) to 35.2 (24.6) mm/h (r = 0.246, p < 0.01). In conclusion, low methotrexate treatment in elderly patients appears to be safe. Routine determination of serum liver enzymes and renal function may reduce individual risk.

CLINHAQ scale--validation of a Hebrew version in patients with fibromyalgia. Clinical Health Assessment Questionnaire.

Assessment of health status in patients with rheumatic disease, including fibromyalgia (FM), using structured questionnaires has become an important approach to evaluate treatment and outcome. The objectives of this study were to validate a translated version of the Clinical Health Assessment Questionnaire (CLINHAQ) to be used by Hebrew-speaking populations, and specifically to evaluate its usefulness in fibromyalgia syndrome (FM). The CLINHAQ was translated into Hebrew and administered to 90 women with FM along with the Hebrew versions of the Fibromyalgia Impact Questionnaire (FIQ) and the Quality of Life (QOL) Scale. The CLINHAQ includes scales of functional disability, helplessness, anxiety and depression, as well as assessment of current health status and satisfaction with this. All subjects were asked about the presence and severity (assessed by visual analogue scale) of current FM symptoms (pain, fatigue, anxiety etc.); a count of 18 tender points was conducted by thumb palpation, and tenderness thresholds were measured by dolorimetry. Test-retest reliability was assessed by Pearson correlation coefficients, and internal consistency was evaluated with Cronbach's alpha coefficient of reliability. Construct validity was tested by correlating the CLINHAQ items with measures of symptom severity, count of tender point, tenderness thresholds, physical functioning measured by FIQ, and with a score of QOL. Test-retest reliability coefficients ranged from 0.82 to 0.99, and Cronbach's alpha coefficients from 0.725 to 0.929. Significant moderate to high correlations were obtained between most subscales of CLINHAQ and measures of physical functioning, quality of life and severity of FM symptoms. In conclusion, the CLINHAQ is a reliable and valid instrument for measuring health status and physical functioning in Israeli women with FM.

The use of oral pilocarpine in xerostomia and Sjögren's syndrome.

OBJECTIVES: To analyze the role of oral pilocarpine in the treatment of xerostomia of Sjogren's syndrome (SS). METHODS: The medical literature was reviewed for all studies using oral pilocarpine to treat xerostomia caused by SS or radiotherapy registered in the MedLine Silver Platter database from 1966 to 1998. RESULTS: All the studies identified excluded elderly individuals with cardiac or pulmonary disease. Patients with postradiation xerostomia and incomplete resection of the salivary glands were more likely to benefit from oral pilocarpine when there was sufficient residual glandular function than patients with radical surgery for head and neck cancer (HNC). However, patients with SS and other inflammatory disorders seemed to benefit from oral pilocarpine, when compared with patients with postradiation xerostomia. The optimal dose of oral pilocarpine, which was less likely to cause side effects, was 5 mg four times daily. A recent multi-center study in SS patients suggests that oral pilocarpine is effective and safe for long-term administration. Although some studies did not show evidence for increased salivary gland secretion rate as measured by sialometry, symptoms improved, perhaps because of increased secretion from the minor salivary glands or better conditioning of the oral mucosa. CONCLUSIONS: Oral pilocarpine is likely to benefit patients with SS by reducing the symptoms of xerostomia, even if the salivary gland secretion rate does not increase. Further controlled studies are needed in patients with SS and should include elderly patients with cardiovascular disease treated with moderate doses of oral pilocarpine.