Wrist ultrasound analysis of patients with early rheumatoid arthritis

In the present study, we evaluated 42 wrists using the semi-quantitative scales power Doppler ultrasound (PDUS) and gray scale ultrasound (GSUS) with scores ranging from 0 to 3 and correlated the results with clinical, laboratory and radiographic data. Twenty-one patients (17 women and 4 men) with rheumatoid arthritis according to criteria of the American College of Rheumatology were enrolled in the study from September 2008 to July 2009 at Universidade Estadual de Campinas (UNICAMP). The average disease duration was 14 months. The patients were 66.6% Caucasians and 33.3% non-Caucasians, with a mean age of 42 and 41 years, respectively. A dorsal longitudinal scan was performed by ultrasound on the radiocarpal and midcarpal joints using GE LOGIQ XP-linear ultrasound and a high frequency (8-10 MHz) transducer. All patients were X-rayed, and the Larsen score was determined for the joints, with grades ranging from 0 to V. This study showed significant correlations between clinical, sonographic and laboratory data: GSUS and swollen right wrist (r = 0.546), GSUS of right wrist and swelling of left wrist (r = 0.511), PDUS of right wrist and pain in left wrist (r = 0.436), PDUS of right wrist and C-reactive protein (r = 0.466). Ultrasound can be considered a useful tool in the diagnosis of synovitis in early rheumatoid arthritis mainly when the anti-cyclic citrullinated peptide and rheumatoid factor are negative, and can lead to an early change in the therapeutic decision.

Serum 25-hydroxyvitamin D and biochemical markers of bone metabolism in patients with juvenile idiopathic arthritis

Our objective was to evaluate the concentrations of serum 25-hydroxyvitamin D [25(OH)D], serum calcium, serum phosphorus, alkaline phosphatase, and parathormone (PTH) in patients with polyarticular juvenile idiopathic arthritis (JIA) and to associate them with disease duration and activity, bone mineral density and use of medications. In a cross-sectional and controlled study, 30 patients with polyarticular JIA were evaluated and compared to 30 healthy individuals matched for age and gender. Clinical status, anthropometry, laboratory markers in both patients and controls, and bone mineral density, only in the patients, were measured. Of the 30 patients included in the study, 23 (76.7%) were female and 16 (53.3%) non-Caucasian; mean age was 14 years (range = 4 to 20 years). Mean disease duration was 5 years (range = 1 to 12 years). The mean concentrations of serum albumin-corrected calcium (9.04 ± 0.41 mg/dL) and alkaline phosphatase (153.3 ± 100.1 IU) were significantly lower in patients with JIA than in controls (P < 0.0001 and P = 0.001, respectively). No differences in 25(OH)D, PTH or serum phosphorus were observed between JIA and control subjects. Regarding 25(OH)D concentration, 8 patients (26.7%) and 5 controls (16.7%) had 25(OH)D concentrations compatible with deficiency (lower than 20 ng/mL) and 14 patients (46.7%) and 18 controls (60%) had concentrations compatible with insufficiency (20-32 ng/mL). These values were not associated with disease activity, use of medications or bone mineral density. We observed a high frequency of 25(OH)D insufficiency and deficiency in the study sample. The compromised bone metabolism emphasizes the importance of follow-up of JIA patients.

Human parvovirus B19 infection: clinical and epidemiological study of 24 cases

From March 1994 to November 1995 24 cases of human parvovirus B19 infection were seen at the Infectious Diseases Department of the Hospital Universitário Antônio Pedro, Niterói - RJ. Serum samples for IgM detection (capture enzyme immunoassay) were positive from the 1st to the 27th day after the onset of the exathema. The classical features of erythema infectiosum (slapped cheecked syndrome) were observed in 8 (33.3%) cases all of them children. Eight patients (6 adults and 2 children) presented a symmetrical polyartropathy, seen more frequently in women. These results show that B19 infection diagnosis is difficult when the disease does not present the classical features and because of the frequent involvement of the joints this infection should be considered in the differential diagnosis of early rheumatoid arthritis.

Acute gouty arthritis as a manifestation of immune reconstitution inflammatory syndrome after initiation of antiretroviral therapy

Immune reconstitution inflammatory syndrome (IRIS) in HIV-infected subjects initiating antiretroviral therapy most commonly involves new or worsening manifestations of previously subclinical or overt infectious diseases. Reports of non-infectious IRIS are much less common but represent important diagnostic and treatment challenges. We report on a 34-year-old HIV-infected male patient with no history of gout who developed acute gouty arthritis in a single joint one month after initiating highly active antiretroviral therapy.

DOSE RESPONSE EFFECT OF Paracoccidioides brasiliensis IN AN EXPERIMENTAL MODEL OF ARTHRITIS

Paracoccidioidomycosis (PCM) is caused by the dimorphic fungus Paracoccidioides brasiliensis (Pb) and corresponds to prevalent systemic mycosis in Latin America. The aim of the present work was to evaluate the dose response effect of the fungal yeast phase for the standardization of an experimental model of septic arthritis. The experiments were performed with groups of 14 rats that received doses of 103, 104 or 105 P. brasiliensis (Pb18) cells. The fungi were injected in 50 µL of phosphate-buffered saline (PBS) directly into the knee joints of the animals. The following parameters were analyzed in this work: the formation of swelling in knees infused with yeast cells and the radiological and anatomopathological alterations, besides antibody titer by ELISA. After 15 days of infection, signs of inflammation were evident. At 45 days, some features of damage and necrosis were observed in the articular cartilage. The systemic dissemination of the fungus was observed in 11% of the inoculated animals, and it was concluded that the experimental model is able to mimic articular PCM in humans and that the dose of 105 yeast cells can be used as standard in this model.

Pyoderma gangrenosum and ulcerative colitis in the tropics

Pyoderma gangrenosum is a rare inflammatory skin condition, characterized by progressive and recurrent skin ulceration. There may be rapidly enlarging, painful ulcers with undermined edges and a necrotic, hemorrhagic base. Disorders classically associated with pyoderma gangrenosum include rheumatoid arthritis, inflammatory bowel disease, paraproteinemia and myeloproliferative disorders. There have been some reports of the occurrence of pyoderma gangrenosum in Africa, and in Nigeria, but only one specifically reported pyoderma gangrenosum in association with ulcerative colitis. We report on a 45-year-old man who presented with pyoderma gangrenosum associated with ulcerative colitis; the second report in Nigeria. The skin lesions were managed with daily honey wound dressings. Oral dapsone and prednisolone were started. The frequency of the bloody diarrhea decreased, and was completely resolved by the second week after admission. The ulcers also showed accelerated healing. The goal of therapy is directed towards the associated systemic disorder, if present.

Rheumatic fever: a multicenter study in the State of São Paulo

Rheumatic fever is still the most commonly seen rheumatic disease in Brazilian pediatric rheumatology clinics. It remains a significant health problem since subsequent cardiac sequelae represent one of the most important causes of chronic heart disease in children. We reviewed the clinical manifestations of rheumatic fever in 786 patients, followed at seven pediatric rheumatology clinics in the state of São Paulo, Brazil. All patients were diagnosed according to revised Jones' criteria. Regarding major criteria, 396 (50.4%) children exhibited carditis, 453 (57.6%) polyarthritis, 274 (34.8%) chorea, 13 (1.6%) erythema marginatum, and 12 (1.5%) subcutaneous nodules. Valvular lesions documented by echocardiography in the absence of accompanying auscultatory findings were found in 144 (18.3%) patients. Migratory polyarthritis was observed in 290 (64.0%) patients with articular involvement. Documented previous streptococcal infection assessed by serum antistreptolysin (ASO) titers occurred in 531 (67.5%) patients. Even though prophylaxis with benzathine penicillin was recommended to all patients, recurrent attacks were observed in 147 (18.7%). We emphasize the high frequency of chorea, silent carditis and recurrences in our series as well as the variable clinical presentation of arthritis in rheumatic fever. Multicenter studies should be encouraged to improve our understanding of the clinical features of rheumatic diseases in children and adolescents.

Correlation between osteochondral changes depicted by magnetic resonance imaging and disease progression

PURPOSE: To determine the consequences of the chronic use of systemic corticosteroids in children with juvenile rheumatoid arthritis by means of evaluating osteochondral effects depicted by magnetic resonance imaging. PATIENTS AND METHODS: We reviewed clinical and magnetic resonance imaging findings in 69 children (72 knees) with juvenile rheumatoid arthritis. Two groups were studied. Group I: 34 (49.3%) children had previous or current use of systemic corticotherapy (22 girls; 12 boys; mean age: 11.3 years; mean disease duration: 5.9 years; mean corticotherapy duration: 2.9 years; mean cumulative dose of previous corticosteroids: 5000 mg); Group II: 35 (50.7%) children had no previous use of corticosteroids (27 girls; 8 boys; mean age: 11.7 years; mean disease duration: 5.3 years). The groups were compared statistically. RESULTS: In the group that had received corticotherapy (Group I), osteochondral abnormalities were significantly correlated to long-standing disease (>3.5 years; p<0.001). This correlation was not found in the group that had no previous history of corticotherapy (Group II). No correlations were established between median dose of corticosteroids and magnetic resonance imaging findings. CONCLUSION: It is important to further investigate the long-term intra-articular effects of systemic corticotherapy to ensure that the side effects of the aggressive therapy will not be more harmful for the joints than the symptoms suffered over the natural course of the disease.

Antioxidant, cytotoxic and UVB-absorbing activity of Maytenus guyanensis Klotzch. (Celastraceae) bark extracts

Maytenus guyanensis Klotzch. is an Amazonian medicinal tree species known in Brazil by the common name chichuá and in Peru and Colombia by the name chuchuhuasi. It is used in traditional medicine as stimulant, tonic, and muscle relaxant, for the relief of arthritis, rheumatism, hemorrhoids, swollen kidney, skin eruptions, and skin cancer prevention, among others. Initially, different extraction solvents and methods were applied to dried, ground bark which made possible the preparation of extracts having both significant lethality to brine shrimp larvae (Artemia franciscana Leach) as well as antioxidant activity in vitro based on tests involving reactions with 2,2,-diphenyl-1-picrylhydrazyl (DPPH). Analysis of fractions from serial extractions with solvents of increasing polarity supports the notion that antioxidant activity is associated with compounds of intermediate polarity and cytotoxicity is associated with compounds of low to intermediate polarity. Variation of extraction time and conditions revealed that hot, continuous ethanol extraction provided good yields of bark extract in several hours. Hot extraction also provided ethanol extracts having greater lethality to brine shrimp and antioxidant activity (compared to the flavonoid rutin in semi-quantitative methods based on DPPH) than extracts obtained from maceration at room temperature. Freeze-dried ethanol extracts were prepared by: 1) maceration at room temperature and 2) hot extraction (eight hours) on several hundred gram scales and the latter extract was shown to have partial screening effects on UVB light. In this work, cytotoxic, antioxidant and potential sun-screening activity are shown for the first time in M. guyanensis.

Cardiac Damage from Chronic Use of Chloroquine: A Case Report and Review of the Literature

Chloroquine has been widely used in rheumatological treatment, but potential severe side effects require careful follow-up. Cardiac damage is not a common consequence, but its clinical relevance has not yet been described. We report the case of a 58-year-old woman with rheumatoid arthritis, in whom chronic chloroquine use resulted in major irreversible cardiac damage. She presented with syncopal episodes due to complete atrioventricular block confirmed by electrophysiological study whose changes were concluded to be irreversible and a permanent pacemaker was indicated. Endomyocardial biopsy was also performed to search for histopathological and ultrastructural cardiac damage. We also reviewed the 22 cases of chloroquine-induced cardiopathy described to date as well as its pathophysiology.

Low occurrence of arthritic manifestations in patients with pulmonary tuberculosis: T cell subsets and humoral studies

Given the suspected role of mycobacteria in the establishment of disorders with an autoimmune background and joint damage, a study was conducted to analize whether rheumatic symptoms were likely to be present in tuberculosis (TB) patients. To this end, 330 patients with a bacteriologic confirmation of tuberculosis were investigated for the presence of arthritic complaints. The latter were recorded in five of them with rheumatic symptoms mostly involving interphalangeal and metacarpophalanged joints, and preceding the clinical manifestations of the TB illness. Three out of these five patients remained arthritic by the time of the bacteriologic conversion and fulfilled the criteria for the diagnosis of rheumatoid arthritis. In the two remaining patients sputum negativization was accompanied by a disappearance of rheumatic manifestations. These patients were also assessed for their peripheral levels of major T cell subsets as well as for the presence of autoantibodies. Comparisons with a series of non-arthritic TB cases, rheumatoid arthritis patients, and controls revealed that presence of rheumatic manifestations was associated with a different profile of autoantibody formation and T cell subset changes. Evidence recorded in the present study indicates that joint affectation in TB is a rare event, being rather the exception than the rule.

Apoptosis as a target for gene therapy in rheumatoid arthritis

Rheumatoid arthritis (RA) is characterized by chronic inflammation of the synovial joints resulting from hyperplasia of synovial fibroblasts and infiltration of lymphocytes, macrophages and plasma cells, all of which manifest signs of activation. All these cells proliferate abnormally, invade bone and cartilage, produce an elevated amount of pro-inflammatory cytokines, metalloproteinases and trigger osteoclast formation and activation. Some of the pathophysiological consequences of the disease may be explained by the inadequate apoptosis, which may promote the survival of autoreactive T cells, macrophages or synovial fibroblasts. Although RA does not result from single genetic mutations, elucidation of the molecular mechanisms implicated in joint destruction has revealed novel targets for gene therapy. Gene transfer strategies include inhibition of pro-inflammatory cytokines, blockade of cartilage-degrading metalloproteinases, inhibition of synovial cell activation and manipulation of the Th1-Th2 cytokine balance. Recent findings have iluminated the idea that induction of apoptosis in the rheumatoid joint can be also used to gain therapeutic advantage in the disease. In the present review we will discuss different strategies used for gene transfer in RA and chronic inflammation. Particularly, we will highlight the importance of programmed cell death as a novel target for gene therapy using endogenous biological mediators, such as galectin-1, a beta-galactoside-binding protein that induces apoptosis of activated T cells and immature thymocytes.

Profile of circulating levels of IL-1Ra, CXCL10/IP-10, CCL4/MIP-1β and CCL2/MCP-1 in dengue fever and parvovirosis

Dengue virus (DENV) and parvovirus B19 (B19V) infections are acute exanthematic febrile illnesses that are not easily differentiated on clinical grounds and affect the paediatric population. Patients with these acute exanthematic diseases were studied. Fever was more frequent in DENV than in B19V-infected patients. Arthritis/arthralgias with DENV infection were shown to be significantly more frequent in adults than in children. The circulating levels of interleukin (IL)-1 receptor antagonist (Ra), CXCL10/inducible protein-10 (IP-10), CCL4/macrophage inflammatory protein-1 beta and CCL2/monocyte chemotactic protein-1 (MCP-1) were determined by multiplex immunoassay in serum samples obtained from B19V (37) and DENV-infected (36) patients and from healthy individuals (7). Forward stepwise logistic regression analysis revealed that circulating CXCL10/IP-10 tends to be associated with DENV infection and that IL-1Ra was significantly associated with DENV infection. Similar analysis showed that circulating CCL2/MCP-1 tends to be associated with B19V infection. In dengue fever, increased circulating IL-1Ra may exert antipyretic actions in an effort to counteract the already increased concentrations of IL-1β, while CXCL10/IP-10 was confirmed as a strong pro-inflammatory marker. Recruitment of monocytes/macrophages and upregulation of the humoral immune response by CCL2/MCP-1 by B19V may be involved in the persistence of the infection. Children with B19V or DENV infections had levels of these cytokines similar to those of adult patients.

Influence of tail biting on weight gain, lesions and condemnations at slaughter of finishing pigs

The present study assessed the association of tail-biting lesions in finishing pigs with weight gain, occurrence of locomotion or respiratory disorders and abscesses during finishing period, and carcass condemnation at slaughter. The study was carried out on 4 different farms. For each animal with a tail biting lesion, two control pigs were selected. The total number of animals in the study was 312, with 104 of them being tail-bitten. Tail lesions were classified according to the degree of severity into four scores: score 0 -normal tail withou lesion; score 1-3 - increasing lesion severity, and score 4 - healed lesions. Overall, the occurrence of severe tail lesions (score 3) varied from 55 to 73% of tail-bitten pigs among farms. On all farms, healing of tail lesions was observed in 95% to 100% of the animals at the evaluation performed within 41-43 days after the commencement of the study. In two out of the four evaluated farms, pigs with score of 3 showed lower weight gain (P<0.05) compared with score 0 pigs. Before slaughter, the occurrence of locomotion problems and nodules/abscesses was associated (P<0.05) with the presence of tail-biting lesions. At slaughter, tail-biting lesions were associated (P<0.05) with the presence of abscesses, lung lesions (pleuritis and embolic pneumonia) or arthritis in carcasses. Carcass condemnation was associated with the presence of tail-biting lesions (P<0.05). Overall, carcass condemnation rate was 21.4%, of which animals with tail-biting lesions accounted for 66.7% of condemnations. Among the animals diagnosed with cannibalism at farm level, only two had not healed their lesions at slaughter. The fact that there were a lot of carcass condemnations, despite the fact that tail-bitten animals had no more active lesions, suggests that different situations may be observed between the field and slaughter, reinforcing the need to analyze pigs both at farm and slaughter to allow proper assessment of losses related to tail biting. Collectively, the observations of the present study show that complications associated with tail-biting found in slaughterhouses are probably underestimating field prevalence.

Cyclosporin inhibits hyperalgesia and edema in arthritic rats: role of the central nervous system

Since arthritis induced by Mycobacterium products (adjuvant) in rats is considered to be immunologically driven, the objective of the present study was to determine if the immunosuppressor drug cyclosporin could affect hindpaw edema and joint hyperalgesia simultaneously. Female Holtzman rats (140-170 g) presented hyperalgesia and edema on the 8th and 12th day following adjuvant injection. Daily systemic (oral or intramuscular) administration of cyclosporin (0.5-5.0 mg kg-1 day-1) or dexamethasone (0.01-0.1 mg kg-1 day-1) for 15 days starting on day zero dose-dependently inhibited the hindpaw edema and hyperalgesia in arthritic rats. However, hyperalgesia but not edema could be detected two days after cyclosporin withdrawal. We concluded that a) the continuous presence of cyclosporin is essential to reduce the development of joint hyperalgesia and that b) different mechanisms underlie the appearance of hyperalgesia and edema in this model. The intracerebroventricular (icv) administration of 5-50-fold smaller doses of cyclosporin (1.5-150 µg/day) or dexamethasone (15 µg/day) also reduced the arthritic hindpaw edema and hyperalgesia. Peripheral blood from animals injected with effective systemic cyclosporin doses showed detectable levels of the drug, whereas peripheral blood from those injected with icv cyclosporin did not, as measured by specific RIA. Our results indicate that cyclosporin administered by the central route is as effective as by the systemic route to reduce joint hyperalgesia and hindpaw edema in arthritic rats. The antiarthritic effect induced by low doses of cyclosporin in the central nervous system (CNS) could be explored to avoid its often associated systemic side effects during chronic therapy. However, the mechanism(s) involved in the antiarthritic response to cyclosporin in the CNS remain to be elucidated