Multinational evidence-based recommendations on how to investigate and follow-up undifferentiated peripheral inflammatory arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative.

OBJECTIVE: To develop evidence-based recommendations on how to investigate and follow-up undifferentiated peripheral inflammatory arthritis (UPIA). METHODS: 697 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2008-9 consisting of three separate rounds of discussions and modified Delphi votes. In the first round 10 clinical questions were selected. A bibliographic team systematically searched Medline, Embase, the Cochrane Library and ACR/EULAR 2007-2008 meeting abstracts. Relevant articles were reviewed for quality assessment, data extraction and synthesis. In the second round each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed. RESULTS: A total of 39,756 references were identified, of which 250 were systematically reviewed. Ten multinational key recommendations about the investigation and follow-up of UPIA were formulated. One recommendation addressed differential diagnosis and investigations prior to establishing the operational diagnosis of UPIA, seven recommendations related to the diagnostic and prognostic value of clinical and laboratory assessments in established UPIA (history and physical examination, acute phase reactants, autoantibodies, radiographs, MRI and ultrasound, genetic markers and synovial biopsy), one recommendation highlighted predictors of persistence (chronicity) and the final recommendation addressed monitoring of clinical disease activity in UPIA. CONCLUSIONS: Ten recommendations on how to investigate and follow-up UPIA in the clinical setting were developed. They are evidence-based and supported by a large panel of rheumatologists, thus enhancing their validity and practical use.

Measurement of damage in 210 Mexican patients with systemic lupus erythematosus: relationship with disease duration.

The Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index is a validated instrument specifically designed to ascertain damage in SLE; this instrument has been applied mainly to Caucasians and African-American SLE patients. The objective of this study was to assess damage using the SLICC/ACR Damage Index in Mexican SLE patients. The SLICC/ACR Damage Index was applied to 210 consecutive SLE patients with disease of variable duration. The SLICC/ACR Damage Index was assessed by review of hospital clinical records, interview and physical examination. One hundred and seventeen (55.5%) patients had some damage. The proportion of patients with damage increased significantly with disease duration (33% at 1-60 months, 66% at 61-120 months and 70% at > or = 121 months, P < 0.001). The main organ systems involved were musculoskeletal (osteonecrosis), neuropsychiatric (neuropathy, seizures), gonadal (amenorrhea prior to age 40 years), ocular (cataracts), renal (glomerular filtration < 50%) and peripheral vascular (permanent damage by venous thrombosis). Damage was frequent, increased over time, particularly for ocular, renal, musculoskeletal and gonadal. Patients who experienced damage were older, had a longer disease duration, a greater number of ACR criteria at diagnosis, and were more likely to have renal involvement and antibodies to dsDNA. The damage occurred in many different domains and started to develop early after disease onset. Mexican patients had more peripheral vascular and gonadal involvement compared with published data from non-Hispanic SLE populations.

Does serum rheumatoid factor have an influence on the clinical picture of ankylosing spondylitis?

OBJECTIVE: To describe the influence of serum rheumatoid factor (RF) on the clinical and radiological picture of definite ankylosing spondylitis (AS). METHODS: In a retrospective chart review of 281 AS patients typed for RF, the clinical picture of RF positive patients (Group 1) was compared with RF negative patients (Group 2); mode of onset, disease duration, and treatment were recorded. All patients were examined to determine their clinical status; the blood cell count. HLA-B27, serum IgG, IgM, IgA, and erythrocyte sedimentation rate (ESR) were determined, and radiological studies of the entire spine, pelvis and affected peripheral joints were carried out. In patients from Group 1 the HLA-DR was also determined. RESULTS: Fifteen of 281 patients (8 men, 7 women) with AS were RF+ (1:64 to 1:1024) (5.3%) and 11 were HLA-B27+. Seven patients in Group 1 had spine involvement and chronic arthritis of the knees. Four out of these 7 were tested for DR, and none was positive; in 6, AS and rheumatoid arthritis (RA) coexisted, 2 were DR1 and 2 were DR4 (test not carried out in 2). In two others we found spinal involvement only, and one of them had both DR1 and DR4. The onset of AS was similar in both groups. Group 1 was characterized by a chronic disease of moderate intensity with chronic arthritis of the metacarpophalangeal and proximal interphalangeal joints (p = 0.0008 and p = 0.04, respectively), no valvulopathy (p = 0.04) and fewer uveitis sequelae (p = 0.007) than Group 2. The ESR (p = 0.01), IgG (p = 0.008) and IgM (p = 0.0001) were higher in Group 1 than in Group 2. CONCLUSIONS: The presence of RF in AS is associated with a chronic disease of moderate intensity with chronic peripheral arthritis and fewer extra-articular manifestations. The presence of RF, not always associated with HLA-DR, seems to affect the course of AS and does not necessarily indicate an association with RA.

Ultraviolet-A1 (340-400 nm) irradiation therapy in systemic lupus erythematosus.

Ultraviolet-A1 (UV-A1) wavelengths have been found effective in mitigating signs and symptoms of disease activity in systemic lupus erythematosus (SLE) but studies have been uncontrolled. To rigorously assess the effectiveness and safety of daily low-dose UV-A1 irradiation as a therapeutic agent in this disorder we enrolled 26 women with SLE in an 18-week two-phase study. During the initial six-week prospective, double-blind, placebo-controlled phase, the patients were divided into two groups; Group A was exposed to 60kJ/m2 of UV-A1 (340-400 nm) irradiation within a sunbed five days a week for three weeks and Group B was exposed for an equal amount of time to visible light of greater than > 430 nm (placebo). Each group was then crossed over for exposure to the other source for three weeks. During the second phase-2 weeks-patients and physicians were unblinded and patients were irradiated with progressively decreasing levels of UV-A1 only. Twenty-five patients completed the six-week placebo-controlled phase of the study and eighteen patients participated for the entire 18 weeks. In Group A the systemic lupus activity measure (SLAM) score improved significantly after three weeks of five-day-a-week UV-A1 irradiation (P < 0.05), regressing to baseline during the three weeks of placebo irradiation. Improvement recurred and progressed with six weeks of three-day-a-week UV-A1 irradiation (P < 0.05). Group B patients responded negligibly to the three weeks of visible light, more sharply to UV-A1, and as with Group A, maximally to the six weeks of three-day-a-week UV-A1 (P < 0.01). With twice- and then once-weekly UV-A1 irradiation the SLAM scores worsened slightly. All patients decreased their drug use. Anti-double-stranded DNA antibodies (anti-dsDNA) decreased significantly (P < 0.05) and anti-nuclear antibodies non-significantly. Side effects were negligible. Visible light had no significant effect. In conclusion, low-dose UV-A1 irradiation effectively, comfortably, and without apparent toxicity diminished signs and symptoms of disease activity in SLE.

Eosinophilic hepatitis: a new feature of the clinical spectrum of the eosinophilia-myalgia syndrome.

The eosinophilia-myalgia syndrome associated with L-tryptophan-containing products is highlighted by eosinophilia, incapacitating myalgias, and diverse multisystemic manifestations. In addition to involvement of the skin, skeletal muscle, and peripheral nerves, visceral damage has been quite prominent, particularly affecting the lungs, the heart, and the liver. Hepatic involvement has been manifested by altered liver tests but is clinically silent. We report the unique case of a woman with this syndrome who developed abdominal pain, a clinical picture of hepatitis and chronically abnormal liver tests. Histologic examination of the liver disclosed eosinophilic hepatitis with piecemeal necrosis. The occurrence of clinically overt hepatic involvement has not been reported previously. Potential mechanisms of liver damage in eosinophilia-myalgia syndromes are discussed.

Clinical findings in symptomatic women with silicone breast implants.

We report the clinical findings in a series of women with silicone breast implants (SBI) and rheumatic disease. These findings represent the first 50 patients seen at the University of South Florida Medical Clinic between March 1977 and January 1991. The average age was 44 years with a range of 30 to 66 years. The most common clinical findings included chronic fatigue, muscle pain, joint pain, joint swelling, and lymphadenopathy. Seventeen women with an average Steinbrocker functional class of 1.8 decided not to remove the implants. An average of 14 months later, follow-up showed no change in their condition. Thirty-three women, with an average functional class of 2.5 underwent implant removal. Twelve of the 33 had documented implant rupture. During an average follow-up of 22 months after implant removal, 24 women improved clinically, 8 did not change, and 1 worsened. We believe this series supports a relationship between silicone breast implants and rheumatic disease signs and symptoms. Although this report is not a definitive epidemiological study, findings suggest that physicians should inform women about the possible benefit of implant removal.

Intravenous cyclophosphamide pulses in the treatment of pyoderma gangrenosum associated with rheumatoid arthritis: report of 2 cases and review of the literature.

Pyoderma gangrenosum is a chronic ulceronecrotic inflammatory cutaneous disorder that can be associated with diseases such as rheumatoid arthritis (RA). No definitive treatment exists for this condition; steroids have been the mainstay of therapy, and the addition of immunosuppressives has been advocated. We describe 2 patients with pyoderma gangrenosum occurring in the setting of RA who, in addition to steroids, received pulse intravenous cyclophosphamide and had a remarkably good and lasting response. This is the first report of such a therapeutic approach. The pertinent literature is discussed. We conclude that pulse cyclophosphamide is another possible therapy for pyoderma gangrenosum.

Gonococcal arthritis.

Disseminated gonococcal infection is a preventable communicable disease. It is an important cause of arthritis in sexually active adults. Prompt recognition and treatment of this common disease results in cure and eliminates unnecessary diagnostic procedures and prolonged hospitalization.

Lack of immunosuppressive effect of low-dose oral methotrexate on lymphocytes in rheumatoid arthritis.

Whether methotrexate (MTX) is effective in rheumatoid arthritis (RA) because of immunosuppressive and/or anti-inflammatory mechanisms of action is controversial. Many lines of investigation point to the latter. We evaluated DNA synthesis in peripheral blood lymphocytes (PBL) from 33 RA patients on oral MTX (7.5-15 mg/wk) and in 30 healthy controls by flow cytometric cell cycle analysis (CCA). DNA synthesis was also evaluated with a thymidilate synthetase activity assay (TSA) (3H-deoxyuridine incorporation) in 12 patients and 21 controls (12 on MTX and NSAID, and 9 healthy subjects). The patients had taken MTX for at least 3 months and were in different stages of clinical activity. There were no significant differences in TSA or in the cell cycle phase distributions (especially the S phase) between treated RA patients and controls. These data suggest that low-dose oral MTX does not inhibit DNA synthesis and therefore does not have an immunosuppressive effect on lymphocytes from patients with RA.

Refractory nephrotic syndrome in lupus nephritis: favorable response to indomethacin therapy.

The effects of indomethacin on urinary protein excretion, levels of serum albumin and renal function were studied prospectively in six patients with systemic lupus erythematosus (SLE) and refractory nephrotic syndrome due to lupus nephritis. Two had membranoproliferative glomerulonephritis, two had diffuse proliferative glomerulonephritis, and one each had mesangioproliferative and membranous glomerulonephritis. All experienced a considerable reduction in urinary protein excretion and an increase in serum albumin. Indomethacin was discontinued in two patients because of side effects, and proteinuria recurred to pretreatment levels. The decrease of proteinuria continued during long-term treatment in three patients. Indomethacin did not cause a permanent decline in renal function. Our results suggest that therapy with indomethacin may be beneficial for the treatment of refractory nephrotic syndrome in selected SLE patients. However, because of potential side effects the administration of indomethacin should be monitored closely.

Prevention of anticardiolipin antibody-related pregnancy losses with prednisone and aspirin.

PURPOSE: Prevention and treatment of pregnancy loss associated with the antiphospholipid syndrome (APS) are controversial. Successful pregnancies have been reported with prednisone and low-dose aspirin in patients with lupus anticoagulant and anticardiolipin antibodies (aCL), but failure has also been reported. The purpose of this prospective study was to define the efficacy of such combination therapy in the prevention of pregnancy loss related to aCL. PATIENTS AND METHODS: Consecutive pregnant patients with a minimum of one pregnancy loss and at least two positive aCL determinations more than 3 months apart, and in whom other causes of pregnancy loss were ruled out, were included in the study. aCL concentrations were determined by enzyme-linked immunosorbent assay before and during therapy. Patients received prednisone, at a dosage of 40 mg/d, for 4 weeks. The dose was then tapered down 10 mg every 4 weeks, and then to a maintenance dose of 5 mg/d. They also received aspirin, 81 mg/d, throughout the pregnancy. Babies were evaluated during the pregnancy by measurement of fetal heart rate and ultrasonography, and after the delivery by measurement of weight and Apgar scores, and, in some cases, by arterial gasometry. RESULTS: Eleven patients with a mean (+/- SD) age of 33.2 +/- 5.01 years were included. Prior to therapy, the rate of live-born babies was 15.6% (32 previous fetal losses and 5 live-born babies), and, after therapy, it was 100% (12 pregnancies and 12 live-born babies). There were no significant adverse effects to either mothers or babies. All the patients had positive aCL determinations. Nine patients had positive IgG aCL. The levels of the antibodies decreased during treatment in these nine patients. IgM aCL determinations were positive in nine patients. The levels of this isotype decreased in eight patients (90%) during treatment. CONCLUSIONS: Treatment with prednisone and aspirin appears to be efficacious, safe, and economic in the prevention of pregnancy loss and fetal growth retardation in patients with aCL.

Psoriatic arthritis: clinical response and side effects to methotrexate therapy.

In the last decade, methotrexate (MTX) has emerged as a useful second line agent for a variety of arthritides. However, there still exists some reluctance for its wider use mainly because of concerns about its liver side effects. We describe our clinical experience with this drug in psoriatic arthritis (PsA). The study group included 24 men and 16 women, with a mean age of 47 years (16-75), with oligoarticular (13) or polyarticular (27) involvement, with a mean disease duration of 12 years (1-36). Patients received a mean dose of 11.2 mg of MTX orally/week during a mean period of 34 months (6-132). Seven had been previously treated with other second line agents. Thirty-eight patients had an excellent or good response. In them, the erythrocyte sedimentation rate dropped in a mean of 38 mm/h. Only 2 patients had a rather poor response. Two patients discontinued the medication because of side effects: leukopenia in one and stomatitis in the other. Eleven patients presented with liver test abnormalities: 3 mild, 6 moderate and 2 severe. Seven patients had 11 liver biopsies. Except for one, none had evidence of cirrhosis or inflammation. Indeed, no changes were observed in the histopathology in those with repeated biopsies. The case reported as cirrhosis occurred very early in the course of MTX therapy. He continued taking MTX treatment without further deterioration of liver chemistry and/or histology. It is concluded that MTX is an effective and safe agent in PsA. Results also indicate that it is not necessary to perform liver biopsies on a routine basis.

Hyperprolactinemia in systemic lupus erythematosus: association with disease activity.

This study was designed to determine the prevalence and clinical significance of hyperprolactinemia in systemic lupus erythematosus (SLE) and other rheumatic diseases. Basal levels of prolactin were determined in 130 nonselected sera from patients with rheumatic diseases including 45 with SLE, 31 with rheumatoid arthritis, 23 with osteoarthritis, 18 with fibromyalgia, and 13 with polymyalgia rheumatica. Serum samples of 28 healthy subjects were used as normal controls. Serum prolactin was measured by radioimmunoassay. ANA, anti-DNA, RNP, Sm, Ro, La, and anticardiolipin antibodies were determined by standard techniques. Elevated serum levels of prolactin (PRL greater than 20 ng/ml) were found in a subset of SLE patients. In addition, a direct correlation with clinical disease and serological (ANA) activity was also found. These findings suggest a potential role for this immunoregulatory hormone in SLE pathogenesis.

There is an association between human immunodeficiency virus infection and spondyloarthropathies.

The presence of inflammatory musculoskeletal manifestations during the course of human immunodeficiency virus (HIV) infection is well established. A wide spectrum of rheumatic disorders have been reported since the first reports of Reiter's syndrome with HIV infection. Other reported associations include forms of arthropathies, psoriatic arthritis, Sjögren's syndrome, polymyositis-dermatomyositis, vasculitis, and septic arthritis.

Treatment of the eosinophilia-myalgia syndrome.

The eosinophilia-myalgia syndrome (EMS) is a unique entity associated with products that contain L-tryptophan (L-trp). Studies of the underlying etiopathogenic processes are underway. EMS is a distinct syndrome, but shares features with eosinophilic fasciitis and other variants of systemic sclerosis. A wide spectrum of clinical manifestations has been described, but there is no consensus regarding treatment. We report the clinical and laboratory features of 12 patients. All were treated with nonsteroidal antiinflammatory drugs (NSAIDs) and analgesics with transient or minimal effect. Two received D-penicillamine (DP) and colchicine, with minimal improvement; one had no response to azathioprine (AZA). Eleven received corticosteroids and had improvement of general symptoms, arthralgias, arthritis, myalgias, skin changes, eosinophilia, and leukocytosis. Nevertheless, all but the latter two findings recurred when corticosteroids were tapered. Seven patients who were unresponsive to the former treatments received low-dose pulse oral methotrexate. Six exhibited continued improvement after a mean follow-up of 4.5 months, with good drug tolerance. Corticosteroids were tapered and, in some instances, discontinued without relapse or complications. One patient improved but later died of aspiration pneumonia. We conclude that methotrexate (MTX) is a therapeutic alternative for patients with severe or refractory EMS.