Anti-inflammatory effects of infliximab and methotrexate on peripheral blood and synovial fluid mononuclear cells: ex vivo study.

OBJECTIVE: To investigate the effects of methotrexate (MTX) and the tumour necrosis factor inhibitor infliximab (IFX) on immune cells derived from peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) of inflammatory arthritis patients. METHOD: Phytohaemagglutinin (PHA)-induced proliferation of healthy donors' PBMCs and synovial intermediate monocytes (CD14+CD16+ cells) in SFMCs derived from psoriatic arthritis (PsA) and rheumatoid arthritis (RA) patients was determined by flow cytometry following co-culture with IFX and MTX. PHA-induced interferon-γ (IFN-γ) production in PBMCs was measured by enzyme-linked immunosorbent assay. The drugs' effect on mRNA expression in SFMCs was determined by quantitative polymerase chain reaction. RESULTS: The combination of IFX 10 µg/mL + MTX 0.1 µg/mL had the strongest inhibitory effect on PBMC proliferation (91%), followed by MTX 0.1 µg/mL (86%) and IFX 10 µg/mL (49%). In PHA-stimulated PBMCs, IFN-γ production was reduced by IFX 10 µg/mL, MTX 0.1 µg/mL, and IFX 10 µg/mL + MTX 0.1 µg/mL by 68%, 90%, and 85%, respectively. In SFMCs, IFX 10 µg/mL significantly reduced CD14+CD16+ cells compared to medium (PsA 54%, p < 0.01; RA 46%, p < 0.05), while MTX had no effect on this population. IFX + MTX led to a similar suppression of CD14+CD16+ cells as achieved by IFX alone. The drugs had different impacts on SFMC gene expression. CONCLUSION: Both IFX and MTX effectively inhibited PBMC proliferation and IFN-γ production, but only IFX reduced synovial monocytes and pro-inflammatory gene expression in SFMCs, suggesting a differential impact of IFX and MTX on critical inflammatory cell populations ex vivo.

Increased incidence of Susac syndrome: a case series study.

BACKGROUND: Susac syndrome (SuS) is a rare condition characterized by a clinical triad of sensorineural hearing loss, branch artery occlusion and encephalopathy. This study reports an increased incidence of SuS in Israel. We describe the clinical characteristics of these patients, diagnostic procedures and the use and subsequent outcomes of newly published treatment guidelines. METHODS: This is a single center retrospective study. Patients who were diagnosed with SuS between July 2017 and August 2018 were enrolled in this study. RESULTS: Seven patients were diagnosed with SuS according to the diagnostic criteria in a time period of 13 months. The annual incidence was recently evaluated in Austria to be 0.024/100000, therefore, our case series represent at least a 5.4- fold increase in the annual incidence of SuS expected in Israel and a 7-fold increase in the annual incidence expected in our medical center. Mean time from the onset of the symptoms to diagnosis was three weeks and follow-up time was twenty four months. Recent exposure to cytomegalovirus was serologically evident in three patients and one patient had high titer of anti-streptolysin antibody. All patients underwent brain MRI, fluorescein angiography and audiometry. All patients were treated according to the newly recommended guidelines. All patients achieved clinical and radiological stability. CONCLUSIONS: We report of an increased incidence of SuS in Israel. Infectious serological findings may imply a post infectious mechanism. The use of the recommended diagnostic procedures reduced the time to diagnosis. Newly published treatment guidelines led to favorable clinical outcomes.

Heparanase is expressed in adult human osteoarthritic cartilage and drives catabolic responses in primary chondrocytes.

OBJECTIVES: The chondrocytes' pericellular matrix acts as a mechanosensor by sequestering growth factors that are bound to heparan sulfate (HS) proteoglycans. Heparanase is the sole mammalian enzyme with HS degrading endoglycosidase activity. Here, we aimed to ascertain whether heparanase plays a role in modulating the anabolic or catabolic responses of human articular chondrocytes. METHODS: Primary chondrocytes were incubated with pro-heparanase and catabolic and anabolic gene expression was analyzed by quantitative polymerase chain reaction (PCR). MMP13 enzymatic activity in the culture medium was measured with a specific fluorescent assay. Extracellular regulated kinase (ERK) phosphorylation was evaluated by Western blot. Human osteoarthritis (OA) cartilage was assessed for heparanase expression by reverse-transcriptase PCR, by Western blot and by a heparanase enzymatic activity assay. RESULTS: Cultured chondrocytes rapidly associated with and activated pro-heparanase. Heparanase induced the catabolic genes MMP13 and ADAMTS4 and the secretion of active MMP13, and down-regulated the anabolic genes ACAN and COL2A1. PG545, a HS-mimetic, inhibited the effects of heparanase. Heparanase expression and enzymatic activity were demonstrated in adult human osteoarthritic cartilage. Heparanase induced ERK phosphorylation in cultured chondrocytes and this could be inhibited by PG545, by fibroblast growth factor 2 (FGF2) neutralizing antibodies and by a FGF-receptor inhibitor. CONCLUSIONS: Heparanase is active in osteoarthritic cartilage and induces catabolic responses in primary human chondrocytes. This response is due, at least in part, to the release of soluble growth factors such as FGF2.

Implementation of recommendations for the screening of hydroxychloroquine retinopathy: poor adherence of rheumatologists and ophthalmologists.

The American Academy of Ophthalmology published in 2011 revised recommendations regarding screening for hydroxychloroquine (HCQ) toxicity. We aimed to assess implementation of these recommendations by rheumatologists and ophthalmologists. A questionnaire regarding screening practices for HCQ toxicity was distributed among all members of the Israeli societies of Rheumatology and Ophthalmology. A total of 128 physicians responded to the questionnaire (rheumatologists: 60, ophthalmologists: 68). Only 5% of the rheumatologists and 15% of the ophthalmologists are aware of ophthalmologic assessments recommended for baseline and follow-up evaluation. When an abnormal test is detected, even if inappropriate for HCQ toxicity screening, 60% of the responders recommend cessation of therapy. Only 13% of the responders recommend first follow-up after five years for patients without risk factors; the remainder recommend more frequent testing. Ninety-six percent of the responders are not aware of all of the known risk factors for HCQ toxicity. Use of inappropriate tests to detect HCQ retinal toxicity may lead to unnecessary cessation of beneficial treatment with risk of disease flare, while lack of consideration of risk factors may put patients at risk for toxicity. These results emphasize the importance of implementing the recommendations to ensure safe and effective use of this drug.

Systemic lupus erythematosus exacerbation following cessation of belimumab treatment.

OBJECTIVES: Belimumab has recently been approved for the treatment of systemic lupus erythematosus (SLE) refractory to standard therapy. Following one case of an SLE flare after cessation of belimumab, we hypothesized that this might lead to a rebound phenomenon and possible exacerbation of SLE. METHOD: Members of the Israeli Society of Rheumatology were contacted by e-mail and asked to report cases of an SLE flare following cessation of belimumab treatment. RESULTS: Three cases of SLE patients who experienced a severe SLE flare following cessation of belimumab therapy were reported. In all cases, belimumab was given as treatment for active mucocutaneous manifestations and/or polyarthritis with improvement in all three patients, one of whom achieved disease remission. In all three cases, patients experienced a severe flare in previously uninvolved major organ systems, including one case of class IV lupus nephritis accompanied by a new-onset severe headache with elevated cerebrospinal fluid (CSF) protein and white matter lesions on brain magnetic resonance imaging (MRI), one case of severe pneumonitis and haemolytic anaemia, and one case of a systemic flare, fatigue, arthritis, and severe abdominal pain. CONCLUSIONS: Belimumab therapy has been shown to be beneficial in the management of active SLE, mostly in patients with mucocutaneous and musculoskeletal manifestations. We suggest a possible rebound effect following cessation of belimumab that could be due to an increase in B-cell activating factor (BAFF) levels and lead to a disease flare. Future assessment of BAFF levels in patients stopping belimumab therapy and clinical correlation may support this hypothesis. Further studies are needed to confirm this observation.

Decreased diffusion capacity on lung function testing in asymptomatic patients with systemic lupus erythematosus does not predict future lung disease.

BACKGROUND: In a previous study performed 9 ± 3.6 years ago, 74 asymptomatic patients with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS) underwent lung function testing. A significantly low diffusion capacity (DLCO) ranging from 45% to 70% was recorded in 28 of the 74 (37.8%) patients who were all free of respiratory symptoms. AIM: The aim of this report is to assess the clinical importance and the predictive value of a low DLCO in asymptomatic patients with SLE or APS. METHODS: Asymptomatic patients with SLE and/or APS who were found to have a low DLCO in the previous study were contacted. Of the 28 patients, 15 were recruited and reevaluated in the current study (SLE with APS (n = 7), SLE without APS (n = 7); primary APS (n = 1)). A full history, physical examination, nail bed capillaroscopy, current laboratory tests and full lung function tests including DLCO were performed. RESULTS: During a surveillance period of 9 ± 3.6 years, none of the patients developed lung disease. Diffusion capacity corrected for alveolar volume (DLCO/VA) improved in the study group during this period from 60.4% ± 7.0 to 76.1% ± 11.2 (p < 0.0001). Lung function tests including total lung capacity (TLC) and forced expiratory volume in one second (FEV1) remained within normal limits. Capillaroscopy studies did not reveal changes compatible with scleroderma in any of the patients. CONCLUSION: Low DLCO findings on lung function testing does not have a positive predictive value for the development of future lung disease in patients with SLE, with or without APS, who are free of respiratory symptoms. Our results suggest that a finding of low DLCO in asymptomatic patients with SLE, with or without APS, does not necessarily require further evaluation and imaging and may improve spontaneously over time. Further studies in a larger group of patients are needed to validate these findings.

Influenza vaccination is safe and effective in patients suffering from fibromyalgia syndrome.

The fibromyalgia syndrome (FMS) is considered to result from the exposure of a genetically susceptible individual to various triggers, such as physical trauma, stress, viral infections etc. A possible role of vaccination in FMS etiology has been suspected. Our objective was to evaluate the efficacy and safety of influenza vaccination in FMS patients. Nineteen FMS patients underwent physical and dolorimetric examinations and answered the fibromyalgia impact questionnaire (FIQ), the widespread pain index (WPI) checklist and the symptoms severity scale (SSS), which are part of the 2010 diagnostic criteria. Thirty-eight healthy subjects were recruited as controls. All participants were vaccinated with the inactivated split virion influenza vaccine. Serum was collected for antibody titration. Six weeks after vaccination, sera were tested by hemagglutination (HI) against A/California (H1N1), A/Perth (H3N2) and B/Brisbane. Humoral response was defined as either a fourfold or greater increase in titer, or an increase from a non-protective baseline level of <1/40 to a level of 1/40. No severe vaccination reactions were observed. No significant change was observed between WPI, SSS and FIQ values before and after vaccination, indicating no worsening of FMS symptoms. Vaccine immunogenicity: Six weeks after vaccination, FMS patients showed a significant increase in geometric mean titers of HI antibody. The rates of sero-protection increased from 22.9% for H1N1 to 89.5% post-vaccination. A significant increase in HI antibody titers was also demonstrated among healthy controls. Influenza vaccination was both safe and effective in FMS patients. In view of these results, FMS patients should be encouraged to undergo influenza vaccination according to the standard WHO recommendations.

EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases.

OBJECTIVES: To develop evidence-based European League Against Rheumatism (EULAR) recommendations for vaccination in patients with autoimmune inflammatory rheumatic diseases (AIIRD). METHODS: A EULAR task force was composed of experts representing 11 European countries, consisting of eight rheumatologists, four clinical immunologists, one rheumatologist/clinical immunologist, one infectious disease physician, one nephrologist, one paediatrician/rheumatologist and one clinical epidemiologist. Key questions were formulated and the eligible spectrum of AIIRD, immunosuppressive drugs and vaccines were defined in order to perform a systematic literature review. A search was made of Medline from 1966 to October 2009 as well as abstracts from the EULAR meetings of 2008 and 2009 and the American College of Rheumatology (ACR) meetings of 2007 and 2008. Evidence was graded in categories I-IV, the strength of recommendations was graded in categories A-D and Delphi voting was applied to determine the level of agreement between the experts of the task force. RESULTS: Eight key questions and 13 recommendations addressing vaccination in patients with AIIRD were formulated. The strength of each recommendation was determined. Delphi voting revealed a very high level of agreement with the recommendations among the experts of the task force. Finally, a research agenda was proposed. CONCLUSION: Recommendations for vaccination in patients with AIIRD based on the currently available evidence and expert opinion were formulated. More research is needed, particularly regarding the incidence of vaccine-preventable infectious diseases and the safety of vaccination in patients with AIIRD.

Protective effect of eotaxin-2 inhibition in adjuvant-induced arthritis.

Eotaxin-2 is a potent chemoattractant for eosinophils, basophils and T helper type 2 (Th2) lymphocytes. The eotaxin-2/CCL24 receptor CCR3 is expressed in human brain, skin, endothelium and macrophages. The aim of the current study was to evaluate the protective effect of a monoclonal anti-eotaxin-2 antibody on the development of adjuvant-induced arthritis in rats (AIA). Adjuvant arthritis was induced in Lewis rats by intradermal injection of incomplete Freund's adjuvant +Mycobacterium tuberculosis. Rats were treated by intraperitoneal (i.p.) injection with three monoclonal antibodies against eotaxin-2 (G7, G8, D8) three times per week. Controls were treated with total mouse immunoglobulin G (IgG), methotrexate (MTX) or phosphate-buffered saline (PBS). Arthritis severity was evaluated by measuring ankle swelling, arthritic score, whole animal mobility and body weight. Sample joints were obtained for pathological evaluation and postmortem X-ray of ankle joints was performed to document erosions. Significant inhibition of arthritis was observed in rats treated with anti-eotaxin-2 antibodies compared to those treated with immunoglobulin or PBS. Inhibition was manifest in ankle diameter, arthritic score and mobility score. The antibody marked D8 showed the greatest efficacy. The effect was observed both in animals treated before the appearance of arthritis and in those where treatment was begun after development of joint inflammation. Combined treatment with D8 and MTX caused additional protection. Significant reduction of inflammation in D8-treated animals was also demonstrated in pathological and X-ray examinations. Inhibition of eotaxin-2 by monoclonal antibodies has a significant protective effect in adjuvant arthritis. These results may introduce a novel therapeutic target in rheumatoid arthritis and additional inflammatory joint disorders.

Decreased levels of CCR3 in CD4+ lymphocytes of rheumatoid arthritis patients.

OBJECTIVES: To evaluate the expression of CCR3 receptors as well as CCR3 agonists, including eotaxin-2 and RANTES, among patients suffering from rheumatoid arthritis and healthy controls, as a possible pathogenetic mechanism in inflammatory joint disease. METHODS: Twenty-two patients and 13 healthy controls were recruited and clinically evaluated. CCR3 expression on CD4+ lymphocytes and mononuclear cells was evaluated by FACS analysis after staining with human CD4 APC (bioscience) and human CCR3 (CD193)PE. Levels of eotaxin-2 and RANTES were analysed by ELISA. RESULTS: A significant decrease was observed in the level of CD4+ cells expressing the CCR3 receptor in serum of RA patients (0.96+/-0.5) as compared with healthy controls (1.48+/-0.6) (p<0.05). A significant decrease in serum eotaxin-2 levels was evident among RA patients suffering from active disease, defined by a DAS-28 score above 5.5, compared with RA patients with lower activity scores (2.1+/-1.6 vs. 7.0+/-5.1; p=0.01). A significant decrease was evident in the number of CCR3 expressing Monocytes among RA patients treated with steroids and anti TNF-a medications as compared with RA patients not receiving such treatment. CONCLUSIONS: CCR3 is differentially expressed on inflammatory cells in RA, while eotaxin-2, a potent CCR3 agonist, is differentially expressed in active disease. Anti-inflammatory medications may down-regulate CCR3 expression in RA. The CCR3-CCR3 agonist pathway may thus have a pathogenic role in RA and may be a future target for novel treatment modalities.

Vaccination against influenza in patients with rheumatoid arthritis: the effect of rituximab on the humoral response.

OBJECTIVE: To assess the effect of rituximab on the efficacy and safety of influenza virus vaccine in patients with rheumatoid arthritis (RA). METHODS: The study group comprised patients with RA treated with conventional disease-modifying drugs with or without rituximab. Split-virion inactivated vaccine containing 15 microg haemagglutinin/dose of B/Shanghai/361/02 (SHAN), A/New Caledonian/20/99 (NC) (H1N1) and A/California/7/04 (CAL) (H3N2) was used. Disease activity was assessed by the number of tender and swollen joints, duration of morning stiffness and evaluation of pain on the day of vaccination and 4 weeks later. CD19-positive cell levels were assessed in rituximab-treated patients. Haemagglutination inhibition (HI) antibodies were tested and response was defined as a greater than fourfold rise 4 weeks after vaccination or seroconversion in patients with a non-protective baseline level of antibodies (<1/40). Geometric mean titres (GMT) were calculated in all subjects. RESULTS: The participants were divided into three groups: RA (n = 29, aged 64 (12) years), rituximab-treated RA (n = 14, aged 53 (15) years) and healthy controls (n = 21, aged 58 (15) years). All baseline protective levels of HI antibodies and GMT were similar. Four weeks after vaccination, there was a significant increase in GMT for NC and CAL antigens in all subjects, but not for the SHAN antigen in the rituximab group. In rituximab-treated patients, the percentage of responders was low for all three antigens tested, achieving statistical significance for the CAL antigen. Measures of disease activity remained unchanged. CONCLUSION: Influenza virus vaccine generated a humoral response in all study patients with RA and controls. Although the response was significantly lower among rituximab-treated patients, treatment with rituximab does not preclude administration of vaccination against influenza.

Auto-antibody profiles in patients with active pulmonary tuberculosis.

OBJECTIVES: To determine the prevalence of a wide array of auto-antibodies in patients with tuberculosis (TB) compared with healthy controls. MATERIALS AND METHODS: Forty-seven consecutive patients (age 47 +/- 21 years, 29 males) with recently diagnosed active pulmonary tuberculosis (PTB) and 39 healthy controls were enrolled. Data collected on a questionnaire included clinical features of the disease, duration of symptoms, presence of fever, cough, arthralgia, myalgia, sicca symptoms and others. Serum samples were collected from the patients' before initiating TB treatment, frozen at -20 degrees C and tested for antinuclear antibodies (ANA), anti-ds DNA, anti-Sm, anti-RNP, anti-Ro, anti-La, and anti-cardiolipin (ACA) (IgG and IgM). RESULTS: Rheumatic symptoms were relatively rare: arthralgia (n = 2), myalgias (n = 2), and eye (n = 1) and mouth dryness (n = 4). The TB patients' mean serum levels of anti-ds DNA, anti-Sm, anti-RNP, anti-SSA (anti-Ro), and anti-ACA-IgM were significantly increased compared with controls (P < 0.05 for all). A significantly higher proportion of TB patients had increased pathological levels of anti-ds DNA (32% vs. 2.5%), anti-Sm (38% vs. 0%), anti-RNP (15% vs. 0%), anti-Ro (64% vs. 10%), anti-ACA-IgG (59% vs. 0%) and anti-ACA-IgM (47% vs. 7.7%) (P < 0.05 for all). CONCLUSIONS: Patients with active TB have significantly increased titres of various auto-antibodies, including highly specific serological markers, such as anti-Sm. RELEVANCE: Differential interpretation of serological studies of patients with systemic manifestations should consider the possibility of PTB.

Perceived efficacy among patients of various methods of complementary alternative medicine for rheumatologic diseases.

OBJECTIVE: The purpose of this cross-sectional survey was to obtain and analyze data on self-perceived efficacy of different types of complementary alternative medicine (CAM) by patients with various rheumatologic conditions. METHODS: Patients followed in rheumatology outpatient clinics were screened for the use of CAM. Patients reporting the use of CAM were asked to participate in face-to-face structured interviews, specifying the various CAM types they used, and grading their subjective impression of efficacy of each CAM type on a scale of 1-10. RESULTS: 350 consecutive patients were screened and 148 reported using CAM. In general, homeopathy and acupuncture were the most commonly used CAM types (44% and 41% of the CAM users, respectively). The mean number of different CAM methods used by a CAM user was 1.9 +/- 1.1. Patients with fibromyalgia used significantly more CAM methods (2.7 +/- 1.4, p = 0.005). On patients' self-perceived efficacy scale of 1-10, the mean score of the whole group was 5.3 +/- 3.2. Acupuncture and homeopathy achieved significantly higher self-perceived efficacy scores in CAM users with spondylo-arthropathies and osteoarthritis, respectively, when compared to some of the other disease groups. Satisfaction was lowest among CAM users with rheumatoid arthritis, vasculitis and connective tissue diseases. CONCLUSION: In general, CAM users were less than moderately satisfied with self-perceived-efficacy of CAM therapies. However efficacy of specific CAM methods differed significantly among patients in different disease groups.

Clinical and immunological study of 7 patients with minocycline-induced autoimmune phenomena.

PURPOSE: Prolonged treatment with minocycline for acne vulgaris has been associated with the development of arthralgia, arthritis, and other autoimmune phenomena. We characterized the clinical, laboratory, and immunological profiles of seven patients with this syndrome. SUBJECTS AND METHODS: Clinically the patients were studied with special emphasis on prior minocycline treatment, presenting symptoms, physical findings, course, and outcome. Laboratory tests included fluorescent antinuclear and antineutrophil cytoplasmic (ANCA) antibodies, as well as antibodies to myeloperoxidase, bactericidal permeability increasing protein, elastase, cathepsin G, lactoferrin, cardiolipin, and histone. RESULTS: All 7 patients presented with polyarthritis or arthralgia, morning stiffness, and fever after 6 to 36 months of minocycline treatment. The skin was involved in five patients (three with livedo reticularis and two with subcutaneous nodules). Two patients had chronic active hepatitis. Increased titers of perinuclear ANCA (p-ANCA) were detected in all seven patients; five patients had fluorescent antinuclear antibodies, two had antihistone autoantibodies and one had anticardiolipin antibodies. Antigenic characterization of p-ANCA disclosed antibodies to bactericidal permeability increasing protein in one patient, to elastase in three patients, and to cathepsin G in five patients. Symptoms resolved in five patients upon discontinuation of minocycline; the other two patients were treated with corticosteroids and also achieved remissions. CONCLUSION: Minocycline-induced autoimmune syndrome is characterized by reversible polyarthralgia or arthritis, morning stiffness, fever, frequent skin involvement, occasional chronic active hepatitis, and increased titers of p-ANCA with various minor p-ANCA-related antigens.

Minocycline-induced autoimmune syndromes: an overview.

OBJECTIVE: To increase awareness of minocycline-induced autoimmune syndromes. METHODS: Review of relevant publications from the American and European literature. RESULTS: Four minocycline-induced syndromes have been described in 82 patients: serum sickness, drug-induced lupus, autoimmune hepatitis, and vasculitis. Aside from sporadic cases of serum sickness, all other syndromes occurred in patients treated for acne. Drug-induced lupus and hepatitis were by far the most common events (66 cases). Except for serum sickness, which presented shortly (mean, 16 days) after minocycline, the autoimmune syndromes manifested after protracted use (mean, 25.3 months). As expected, the patients with acne were young (mean, 19.7 years). The most frequent symptoms were arthralgia, followed by arthritis, fever, and rash (73, 45, 38, and 29 patients, respectively). Serologically, antinuclear antibodies were the most common finding (63 positive of 68 tests); perinuclear anti-neutrophilic cytoplasmic antibodies (pANCA), when assayed, were similarly frequent (20 of 24 tests). Surprisingly, anti-histone antibodies were uncommon, even among patients with drug-induced lupus (4 of 31 tests). The clinical and serological features of the separate syndromes may overlap. The diagnostic value of pANCA, as well as its possible role in minocycline-induced autoimmunity, are discussed. CONCLUSIONS: Minocycline has the potential to evoke a variety of clinical and serological autoimmune expressions. The number of published reports may underestimate the frequency of this condition, which should be suspected and investigated in young patients with autoimmune manifestations.

Watermelon stomach following and preceding systemic sclerosis.

OBJECTIVES: To report two patients with watermelon stomach associated with systemic sclerosis (SSc) and review the literature on that subject. METHODS: We describe the clinical presentation, course and outcome of our two patients and reviewed the medical literature registered in the MedLine PubMed database from 1966 to 1999 by using the key words watermelon stomach, gastric antral vascular ectasia, systemic sclerosis, scleroderma. RESULTS: The two patients presented with microcytic hypochromic anemia. Esophagogastroscopy showed multiple linear vascular malformations in the antrum compatible with watermelon stomach. They responded to Nd-Yag laser therapy with resolution of the lesions and improvement of the anemia. Patient 1 had a history of diffuse SSc while patient 2 developed limited SSc 2 years after the diagnosis of watermelon stomach. A literature review disclosed 16 documented case reports of watermelon stomach associated with SSc, 14 of whom were women. In most cases, watermelon stomach occurred in patients with established SSc but in some it antedated it by several years. In many cases, other autoimmune syndromes such as hypothyroidism, primary biliary cirrhosis, and Sjögren's syndrome were present. The presenting symptom was iron deficiency anemia, which in 11 cases was severe enough to require blood transfusions. Nine patients were successfully treated with several transendoscopic treatments, four required surgical intervention, and in three treatment was not specified. CONCLUSION: Although watermelon stomach is a rare syndrome, it is recognized as a cause of persistent bleeding in patients with SSc. Awareness of this condition may increase its recognition and treatment.

Polymyalgia rheumatica in patients with ankylosing spondylitis: a report of 5 cases.

OBJECTIVE: To report the cases of 5 elderly male patients with ankylosing spondylitis (AS) who developed polymyalgia rheumatica (PMR). MATERIALS AND METHODS: The files of 5 patients with AS who developed PMR were retrospectively reviewed. The demographic, clinical, laboratory characteristics and outcome of these patients were summarized. RESULTS: All 5 patients were male, 65-80 years old at the time of their PMR diagnosis. The diagnosis of AS was made simultaneously based on clinical and radiological data; the age at onset of symptoms retrospectively attributable to AS was 20-40 years in three cases, while in the two other patients it could not be determined. The patients presented with typical symptoms of PMR and responded to steroid treatment. HLA B27 was found in three cases, while HLA DR did not show a consistent pattern. CONCLUSIONS: The coexistence of AS and PMR could be more than coincidental. Further screening of both patient populations is needed to assess the true extent of this preliminary observation.

Restrictive lung disease due to diaphragmatic dysfunction in systemic lupus erythematosus. Two case reports.

Two patients with systemic lupus erythematosus and unexplained dyspnea are described. Both had severe dyspnea and a restrictive lung function pattern without any apparent specific pathology. Both patients initially responded to corticosteroids and/or immunosuppression; one patient, however, relapsed and eventually died. Many factors may contribute to this syndrome, including diaphragmatic dysfunction, splinting of the diaphragm, pleuritis, atelectasis and respiratory muscle dysfunction. This syndrome, which may respond to steroids or immunosuppressive treatment, must be considered in SLE patients with dyspnea lacking a concrete underlying cause.