[MICROSCOPIC POLYANGIITIS WITH VARIABLE PRESENTATION].

INTRODUCTION: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a group of rare diseases of systemic necrotizing vasculitis affecting small and medium-sized vessels and may be associated with the presence of anti- neutrophil cytoplasmic antibody. Vessels in different organs and systems are involved, leading to various clinical manifestations of the disease. We present 3 cases of microscopic polyangiitis which have been diagnosed and treated in one medical department for over 4 years. The first patient presented with a clinical picture resembling idiopathic pulmonary fibrosis (IPF) and the diagnosis of microscopic polyangiitis (MPA) was established only when acute renal failure appeared. With appropriate therapy, the renal function normalized but her respiratory status deteriorated and she died due to pulmonary infection. The second case presented with constitutional symptoms such as general weakness, weight loss, leg edema and elevated CRP. During the investigation, mononeuritis multiplex and then MPA were diagnosed. She was successfully treated. The third patient diagnosed with MPA presented as end stage renal failure and was treated by cyclophosphamide and rituximab. He did not receive cotrimoxazole that was recommended and was hospitalized for pneumocystis jirovecii pneumonia. Despite intensive therapy in the ICU by various antibiotics and mechanical ventilation, his condition deteriorated and the patient died.

The Powers of Flowers: Evaluating the Impact of Floral Therapy on Pain and Psychiatric Symptoms in Fibromyalgia.

BACKGROUND: Fibromyalgia is a syndrome of unknown etiology that is characterized by widespread pain, which severely impairs quality of life. Several forms of occupational and alternative therapy have demonstrated beneficial effects in fibromyalgia patients. OBJECTIVES: To assess the effects of participation in a floral design course on physical and psychiatric symptoms in a cohort of fibromyalgia patients. METHODS: This study was conducted as an observational study. Women diagnosed with fibromyalgia over the age of 18 were recruited to participate in one of two 12-week flower design (floristry) courses. Demographic details, disease activity indices, and anxiety and depression scores were calculated for all participants at baseline, week 12, and study completion. Physical and mental health of the two groups were compared throughout the study time-points. RESULTS: The study was completed by 61 female fibromyalgia patients who were included in the final analyses; 31 patients participated in the first floristry course and 30 in the second. Significant improvements in the 36-Item Short Form Survey physical and mental health components, visual analog scale, Fibromyalgia Impact Questionnaire, Hamilton Anxiety Rating Scale, and Hamilton Depression Rating Scale scores for the entire study population and for each group separately could be seen following participation in each floristry course. CONCLUSIONS: Participation in a floristry course may lead to a significant improvement in pain and psychiatric symptoms in fibromyalgia patients. These findings highlight the potential benefit of utilizing occupational therapy programs, such as a floristry course, for improving quality of life in fibromyalgia.

Social values as an independent factor affecting end of life medical decision making.

Research shows that the physician's personal attributes and social characteristics have a strong association with their end-of-life (EOL) decision making. Despite efforts to increase patient, family and surrogate input into EOL decision making, research shows the physician's input to be dominant. Our research finds that physician's social values, independent of religiosity, have a significant association with physician's tendency to withhold or withdraw life sustaining, EOL treatments. It is suggested that physicians employ personal social values in their EOL medical coping, because they have to cope with existential dilemmas posed by the mystery of death, and left unresolved by medical decision making mechanisms such as advanced directives and hospital ethics committees.

Ferritin and prolactin levels in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a common demyelnating disorder of the central nervous system (CNS) and ethiopathogenesis has yet to be fully elucidated. The disease may present in several clinical forms that are closely associated with disease morbidity. In recent years various environmental and hormonal factors have been implicated in the pathogenesis of autoimmunity. OBJECTIVES: To evaluate ferritin and prolactin levels in MS patients and their correlation with clinical manifestations of the disease. METHODS: Serum samples from 150 multiple sclerosis patients were evaluated for demographic characteristics, clinical parameters as well as prolactin and ferritin levels utilizing the Liaison chemiluminescent immunoassays (DiaSorin, Italy). Sera from 100 matched healthy donors were used as controls. RESULTS: Hyperprolactinemia was documented in 10 of 150 MS patients (6.7%) and hyperferritinemia in 12 (8%), both of which were significantly more common in this group compared with healthy controls (P < 0.01 and P = 0.02 respectively). Among female MS patients, elevated prolactin levels were related to the secondary-progressive type of disease (P = 0.05), whereas hyperferritinemia was associated with male gender (P = 0.03) and with the relapsing-progressive type of the disease (P = 0.02). An inverse association was found between hyperferritinemia and the relapsing-remitting type of MS in male patients (P = 0.05) CONCLUSIONS: Our results suggest a plausible association between these biomarkers and certain clinical types and gender among MS patients. Further studies combining clinical data, CNS imaging and these markers are warranted.

Hyperprolactinemia and autoimmune diseases.

The autoimmune diseases are more common in females. The sex hormones have an important role in this gender bias, mainly estrogen and prolactin (PRL) which modulate the immune response. PRL is secreted from the pituitary gland and other organs and cells mainly the lymphocytes. PRL has an immunostimulatory effect and promotes autoimmunity: PRL impairs the negative selection of autoreactive B lymphocytes occurring during B cell maturation into fully functional B cells. PRL has an anti-apoptotic effect, enhances proliferative response to antigens and mitogens and enhances the production of immunoglobulins and autoantibodies. Hyperprolactinemia (HPRL) is observed in multi-organ and organ specific autoimmune diseases like systemic lupus erythematosus (SLE) rheumatoid arthritis (RA), Sjogren's syndrome (SS), Hashimoto's thyroiditis (HT) and multiple sclerosis (MS). There is no consistent correlation between PRL levels and disease activity. Murine models and small studies in SLE patients suggest some role of dopamine agonists in the therapy of those diseases. The genetic factor may have a role in humans as in animal models. The PRL isoform has an important effect on the bioactivity on prolactin receptors (PRL-Rs).

Novel biomarkers in autoimmune diseases: prolactin, ferritin, vitamin D, and TPA levels in autoimmune diseases.

The development of autoimmune diseases may be influenced by hormonal, immunomodulatory, and metabolic pathways. Prolactin (PRL), ferritin, vitamin D, and the tumor marker tissue polypeptide antigen (TPA) were measured in autoimmune diseases: systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), polymyositis (PM), dermatomyositis (DM), multiple sclerosis (MS), autoimmune thyroid diseases, and antiphospholipid syndrome. Hyperprolactinemia (HPRL) was detected in 24% of PM patients, in 21% of SLE patients, in 6.7% of MS patients, 6% of RA patients, and in 3% of SSc patients. Hyperferritinemia was detected in 23% of SLE patients, 15% of DM patients, 8% of MS patients, and 4% of RA patients. The patients had relatively low levels of 25 OH Vitamin D: the average results (mean +/- SD) were between 9.3 +/- 4.4 to 13.7 +/- 7.1 ng/mL in the different diseases, while the 25 OH Vitamin D concentrations less than 20 ng/mL are regarded as deficient. TPA levels were in the same range of the controls, elevated only in SLE. HPRL, hyperferritinemia, hypovitaminosis D, and TPA levels did not correlate with SLE activity elevated levels of rheumatoid factor or anti-CCP antibodies in RA. HPRL, hyperferritinemia, and hypovitaminosis D have different immunological implications in the pathogenesis of the autoimmune diseases. Preventive treatment with vitamin D or therapy for HPRL with dopamine agonists, may be considered in certain cases. Hyperferritinemia may be used as an acute-phase reactant marker in autoimmune diseases mainly SLE. TPA may be used to indicate the tendency for malignancies.

Use of complementary and alternative medicine among patients attending rheumatology clinics in Israel.

BACKGROUND: Complementary and alternative medicine has recently attracted attention due to its widespread use. In a recent study in Israel, almost a half of CAM users in the general population used it for joint diseases or back pain. OBJECTIVE: To evaluate the prevalence of CAM use among patients with defined rheumatic diseases, and analyze the demographic features of CAM users, their reasons for using CAM and the use of specific CAM methods. METHODS: We conducted face-to-face structured interviews of 350 patients attending rheumatology clinics, regarding past or present use of CAM, specifying the various CAM types they used, and reasons for using CAM. Demographic data including age, gender, country of birth and origin, and level of education were also collected. RESULTS: Altogether, 148 patients reported using CAM (42%). In general, homeopathy and acupuncture were the most commonly used types (44% and 41% of the patients, respectively). The mean number of CAM methods per patient was 1.9 +/- 1.1. CAM was more commonly used by patients with advanced education (52% vs. 37% of patients with lower education, P= 0.007). Patients with rheumatoid arthritis used CAM significantly less than patients with other rheumatologic conditions (32% vs. 48%, P= 0.008). CONCLUSION: CAM use is influenced by level of education. The choice of the preferred CAM method among patients with rheumatic diseases seemed to follow the popular CAM methods in the general population, and was not specific to rheumatic diseases.

Intravenous immunoglobulin: adverse effects and safe administration.

Intravenous immunoglobulin (IVIg) is administered for various indications and generally considered a safe therapy. Most of the adverse effects (AEs) associated with IVIg administration are mild and transient. The immediate AEs include headache, flushing, malaise, chest tightness, fever, chills, myalgia, fatigue, dyspnea, back pain, nausea, vomiting, diarrhea, blood pressure changes, tachycardia, and anaphylactic reactions, especially in IgA-deficient patients. Late AEs are rare and include acute renal failure, thromboembolic events, aseptic meningitis, neutropenia, and autoimmune hemolytic anemia, skin reactions, and rare events of arthritis. Pseudohyponatremia following IVIg is important to be recognized. Renal failure, usually oliguric and transient, occurs mostly on using sucrose-containing products owing to osmotic injury. Among high-risk patients who have a previous renal disease, dehydration, diabetes mellitus, advanced age, hypertension, hyperviscosity, or are treated by other nephrotoxic medications, administration of a non-sucrose-containing IVIg product after accomplishing hydration, in a low concentration and a slow infusion rate while supervising urine output and kidney function, is recommended. Thromboembolic complications occur because of hyperviscosity especially in patients having risk factors including advanced age, previous thromboembolic diseases, being bedridden, diabetes mellitus, hypertension, dyslipidemia, or those receiving high-dose IVIg in a rapid infusion rate. Immediate AEs can be treated by the slowing or temporary discontinuation of the infusion and symptomatic therapy with analgesics, nonsteroidal anti-inflammatory drugs, antihistamines, and glucocorticoids in more severe reactions. Slow infusion rate of low concentration of IVIg products and hydration, especially in high-risk patients, may prevent renal failure, thromboembolic events, and aseptic meningitis.

Intravenous immunoglobulin and the kidney--a two-edged sword.

OBJECTIVES: To review the literature on the use and efficacy of intravenous immunoglobulin (IVIG) in glomerulonephritis and to evaluate the nephrotoxic effect of IVIG. METHODS: A structured literature search of articles published on the efficacy of IVIG in the treatment of nephritis between 1985 and 2003 was conducted. All articles dealing with lupus nephritis, IgA nephropathy, Henoch Schonlein purpura, antineutrophil cytoplasmic antibodies (ANCA) associated vasculitis, primary membranous glomerulonephritis, and primary chronic nephritis were reviewed. The same literature search was conducted for the nephrotoxic effects of IVIG. Two groups of patients were defined: (a) a group of patients with IVIG nephrotoxic effect published as case reports, and (b) a group of patients whose data were collected by the Food and Drug Administration (FDA). All existing data of both groups were pooled and compared. RESULTS: One hundred six patients with lupus nephritis were treated with IVIG. In most reports proteinuria, nephrotic syndrome, and values of creatinine clearance were improved. In 3 cases improvement in World Health Organization (WHO) class was noted, and in 2 cases a reduction of immune deposits was demonstrated. In the other forms of autoimmune nephropathy, although the number of reported cases was small, improvement was noted in most patients. Thirty-two reports entailing 78 patients with IVIG-induced nephrotoxicity were found and their data were compared with those of 88 patients reported to the FDA. No specific differences were noted between the 2 groups of patients, as their age and indications for using IVIG were similar. Most of the patients who developed renal toxicity (72% in the literature and 90% in the FDA group) received sucrose -containing IVIG products. A high percentage of patients (31% in the literature and 40% in the FDA group) required hemodialysis. Mortality occurred in 10 and 15%, respectively. Renal histology done in a minority of the cases demonstrated vacuolization and swelling of the proximal tubules consistent with osmotic injury. CONCLUSIONS: On one hand, there are encouraging reports on the efficacy of IVIG in different types of glomerulonephritis (mainly lupus nephritis) resistant to conventional therapy, but the exact success rate and clinical indications remain undetermined. On the other hand, IVIG and the kidney is a two-edged sword, since nephrotoxicity can be a serious rare complication of IVIG therapy. Products containing sucrose as a stabilizer are mainly associated with such injury through the mechanism of osmotic nephrosis. Preexisting renal disease, volume depletion, and old age are risk factors for such toxicity.

[Anti-cyclic citrullinated peptide antibodies as a diagnostic test for rheumatoid arthritis].

Early diagnosis of rheumatoid arthritis (RA) is important since aggressive therapy should begin at an early stage. Diagnosis is made on a clinical basis, supported by the determination of rheumatoid factor (RF). However, RF is also positive in healthy subjects, as well as in other autoimmune and infectious diseases. Two other diagnostic markers with a high specificity for RA, antiperinuclear factor (APF) and antikeratin antibodies (AKA), are not in general use because of technical difficulties. APF and AKA are antifilaggrin antibodies (AFA) that bind to determinants rich in the unusual amino acid citrulline, generated by posttranscriptional modification of arginine residues by the enzyme peptidylarginine deiminase (PAD). Enzymatic determination of recombinant filaggrin fragments produces linear peptides, which are recognized by RA-specific autoantibodies. After substitution of serine by cysteine, a cyclic peptide is formed. The conformational change mimics the original structure of the filaggrin and enhances the affinity of the antibodies. Recently, an anti-cyclic citrullinated peptide (anti-CCP) ELISA was developed. The sensitivity of this test is usually 51%-68%, with a specificity of about 96%-98% (significantly higher than that of RF). Together with RF, anti-CCP increases the ability to diagnose patients with early RA. The test might help to predict which patients will develop persistent disease with evidence of radiologic lesions. Implementation of the highly specific anti-CCP test in conjunction with RF would enable reliable early diagnosis in some cases and allow the initiation of aggressive therapy with disease modifying anti-rheumatic drugs (DMARDs).

Intravenous immune globulins (IVIg) treatment for organizing pneumonia in a selective IgG immune deficiency state.

We describe herein a 61-year-old woman who presented with fever, night sweats and cough. The diagnosis of pneumonia was established, but with symptom recurrence following antibiotic therapy, further diagnostics were performed. Biopsy via bronchoscopy revealed cryptogenic organizing pneumonia, and later on follow-up, a selective IgG immune deficiency was also diagnosed. Initial treatment of high-dose glucocorticoid therapy induced remission, but with dose reduction recurrence was observed. Intravenous immune globulin treatment was initiated and induced a successful clinical and radiological remission. Few cases of cryptogenic organizing pneumonia and hypogammaglobulinemia have been reported. To our knowledge, this is the fourth case described of cryptogenic organizing pneumonia with a hypogammaglobulinemia state and the first reported case of a selective immune deficiency state treated successfully with intravenous immune globulins.

Hyperferritinemia is associated with serologic antiphospholipid syndrome in SLE patients.

Ferritin may play a direct role on the immune system. We sought to determine if elevated levels of ferritin in lupus patients correlate with disease activity and organ involvement in a large cohort. Ferritin levels (gender and age adjusted) were assessed in 274 lupus serum samples utilizing the LIASON Ferritin automated immunoassay method. Significant disease activity was determined if European Consensus Lupus Activity Index (ECLAM)>2 or Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)>4. Utilizing an EXCEL database, we compared elevated ferritin levels to manifestations grouped by organ involvement, serology, and previous therapy. The patients were predominantly female (89%), median age was 37 years old, and disease duration was 10.6 ± 7.7 years. Hyperferritinemia was found in 18.6% of SLE patients. Compared to subjects with normal ferritin levels, a significantly greater proportion of patients with hyperferritinemia had thrombocytopenia (15.4% vs. 33.3%, p=0.003) and lupus anticoagulant (11.3% vs. 29.0%, p=0.01). Additionally, compared to normoferritinemic subjects, hyperferritinemic subjects had significantly higher total aCL (99.7 ± 369 vs. 30.9 ± 17.3 GPI, p=0.02) and aCL IgM antibody levels (75.3 ± 357.4 vs. 9.3 ± 10.3 GPI, p=0.02), and marginally lower aCL IgG antibody levels (9.2 ± 4.9 vs. 9.7 ± 3.9 GPI, p = 0.096). While the ECLAM score significantly correlated with hyperferritinemia (p=0.04), the SLEDAI score was marginally associated with hyperferritinemia (p = 0.1). Serositis was marginally associated with hyperferritinemia, but not with other manifestations. An association with serologic APS was encountered. Hyperferritinemia was associated with thrombocytopenia, lupus anticoagulant, and anti-cardiolipin antibodies suggest that it may be an early marker for secondary antiphospholipid syndrome in SLE patients.

Prolactin and autoimmunity.

Sex hormones, especially estrogen and prolactin (PRL), have an important role in modulating the immune response. PRL is secreted from the pituitary gland as well as other organs and cells particularly lymphocytes. PRL has an immune stimulatory effect and promotes autoimmunity. PRL interferes specifically with B cell tolerance induction, enhances proliferative response to antigens and mitogens and increases the production of immune globulins, cytokines and autoantibodies. Hyperprolactinemia (HPRL) in women present with clinical manifestations of galactorrhea, primary or secondary amenorrhea, delayed menarche or a change in the menses either in the amount or in the regularity. Furthermore in the last 2 decades multi-organ and organ specific autoimmune diseases like systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjogren's syndrome (SS), Hashimoto's thyroiditis (HT), multiple sclerosis (MS), psoriasis, hepatitis C patients, Behçet's disease, peripartum cardiomyopathy (PPCM) and active celiac disease were discussed to be associated with HPRL. There is data showing correlation between PRL level and diseases activity in few diseases. Genetic factors may have a role in humans as in animal models. The PRL isoforms based on the differences in the amino acid sequence and size of the cytoplasmic domain have an important effect on the bioactivity on prolactin receptors (PRL-Rs).