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ID PMID Title PublicationDate abstract
16571961 Atlantoaxial subluxation in different intraoperative head positions in patients with rheum 2006 Apr BACKGROUND: Disorders of the cervical spine are often observed in patients with rheumatoid arthritis (RA). However, the best head position for RA patients with atlantoaxial subluxation in the perioperative period is unknown. This study investigated head position during general anesthesia for the patients with RA and proven atlantoaxial subluxation. METHODS: During anesthesia of patients with RA and proven atlantoaxial subluxation, the authors used fluoroscopy to obtain a lateral view of the upper cervical spine in four different positions: the mask position, the intubation position, the flat pillow position, and the protrusion position. Copies of the still fluoroscopic images were used to determine the anterior atlantodental interval, the posterior atlantodental interval, and the angle of atlas and axis (C1-C2 angle). RESULTS: The anterior atlantodental interval was significantly smaller in the protrusion position (2.3 mm) than in the flat pillow position (5.1 mm) (P < 0.05). The posterior atlantodental interval was significantly greater in the protrusion position (18.9 mm) than in the flat pillow position (16.2 mm) (P < 0.05). The C1-C2 angle was, on average, 9.3 degrees greater in the protrusion position than in the flat pillow position (P < 0.05). CONCLUSION: This study showed that the protrusion position using a flat pillow and a donut-shaped pillow during general anesthesia reduced the anterior atlantodental interval and increased the posterior atlantodental interval in RA patients with atlantoaxial subluxation. This suggests that the protrusion position, which involves support of the upper cervical spine and extension at the craniocervical junction, might be advantageous for these patients.
17911417 Genetic background of anticyclic citrullinated peptide autoantibody production in Hungaria 2007 Sep Polymorphisms of the peptidylarginine deiminase 4 (PADI4) gene encoding for the isoenzyme that converts arginyl into citrullyl residues have been shown to contribute to susceptibility to rheumatoid arthritis (RA), depending on the population studied. We aimed at determining whether PADI4 single nucleotide polymorphisms (SNPs) are associated with RA in a Hungarian population. The relationship between anticyclic citrullinated peptide (anti-CCP) production and HLA-DRB1 alleles encoding the shared epitope (SE) was also investigated. DNA samples were obtained from RA (n = 261) patients and from control donors (n = 120). HLA-DRB1 genotyping was carried out by polymerase chain reaction (PCR) with sequence-specific priming. PAD4_92 G/C and PAD4_104 T/C SNPs were genotyped using real-time PCR allele discrimination. Autoantibodies against CCP were detected by ELISA. All healthy controls tested anti-CCP negative, whereas 171 (66%) RA patients were anti-CCP positive. No significant difference in allele or genotype frequencies were found between RA patients and controls for any of the PADI4 SNPs. Anti-CCP seropositivity was unrelated to these two SNPs. No association was found between any of the PADI4 SNPs and HLA-DRB1 subtypes. Presence of the HLA-RB1 SE alleles was significantly associated with anti-CCP seropositivity; HLA-DRB1*0401 and HLA-DRB1*1001 carriers showed the strongest association. In conclusion, our data suggest that polymorphisms of the PADI4 gene are not associated with rheumatoid arthritis and are unlikely to be responsible for the presence of anti-CCP autoantibodies in a white Hungarian population. HLA-DRB1 SE alleles, however, may significantly contribute to the genetic determination of anti-CCP production in Hungarian patients with RA.
18185909 Knee deformity in rheumatoid arthritis is closely correlated with generalized osteoporosis 2008 To examine the relationship between knee deformity and osteoporosis in women with rheumatoid arthritis (RA), bone mineral density (BMD) in the lumbar spine and distal radius was measured using dual X-ray absorptiometry, and knee deformity (valgus or varus deformity) was measured using plain radiograms in 55 women with RA. Associations between knee deformity and BMD, disease related variables, including RA stage, RA duration, age, cumulative doses of administered glucocorticosteroids, body mass index, or postmenopausal period were evaluated. Cut-off values of the BMD defining RA patients with knee deformity were very close to the BMD value corresponding to 70% of young adult mean in the lumbar spine and distal radius. The femorotibial alignment was significantly correlated with age and deformity of the proximal tibia. Deformity of the proximal tibia was negatively correlated with the radial BMD and lumbar BMD. Deformity of the proximal tibia showed a significant difference between the groups of less than 5 years after menopause and the group of 5-10 years after menopause. We concluded that knee deformity in RA derived from deformity of the proximal tibia, and it was closely correlated with generalized osteoporosis.
17273810 Atherosclerosis and inflammation: insights from rheumatoid arthritis. 2007 Aug Cardiovascular disease is a major health care problem and the most common cause of death among individuals from developed nations. Our understanding of atherosclerosis has evolved from a passive process resulting in narrowing of the lumen and consequent myocardial ischemia to a dynamic process that involves inflammation. The study of atherosclerosis in patients with chronic inflammation, such as rheumatoid arthritis (RA), will provide insights into the relationship between inflammation and atherosclerosis. We review the relationship between atherosclerosis and inflammation within the context of RA, providing evidence that patients with RA have increased cardiovascular morbidity and mortality and accelerated coronary and extra-coronary atherosclerosis. In addition, traditional and novel cardiovascular risk factors are discussed. Finally, actions that a rheumatologist can take to better control this cardiovascular morbidity are suggested. These can be summarized as follows: (1) careful assessment and treatment of cardiovascular risk, (2) better control of inflammation, and (3) individual risk-benefit evaluation of need for cyclo-oxygenase-2 inhibitors, nonsteroidal anti-inflammatory drugs, and high doses of corticosteroids.
17110315 Autoantibodies to citrullinated antigens in (early) rheumatoid arthritis. 2006 Nov Rheumatoid arthritis (RA) is a common, systemic autoimmune disease characterized by chronic inflammation of the synovium, that can lead to progressive joint destruction and in many cases results in severe disability and poor quality of life. With the availability of more sophisticated and effective therapies and with increasing evidence that the first few months of disease represent an unique therapeutic opportunity and that such early therapeutic intervention is crucial in preventing irreversible joint damage, it is widely accepted that early and accurate diagnosis of RA is critical in disease management. Within the last three years a growing number of publications have reported that the second generation anti-CCP (cyclic citrullinated peptide) test may become the marker of choice for diagnosing early RA as it appears to be highly specific for the disease with a sensitivity comparable to the widely used but less specific rheumatoid factor test. Additionally, anti-CCP2 positivity can predict future development of RA in both asymptomatic individuals and in patients with undifferentiated arthritis. Furthermore, antibody levels at presentation can correlate with progression to erosive disease.
16947383 Differential tissue expression and activation of p38 MAPK alpha, beta, gamma, and delta is 2006 Sep OBJECTIVE: Activation of p38 MAPK is a key signaling step in chronic inflammation. Inhibition of p38 MAPK is considered to be a promising future strategy to control inflammatory diseases, but studies of compounds to inhibit this kinase have so far been limited to investigation of their side effects. We undertook the present study to investigate which specific molecule, among 4 different isoforms of p38 MAPK (alpha, beta, gamma, and delta), is predominantly expressed and activated in inflammation. Such knowledge could allow more specific targeting of p38 MAPK in inflammatory disease. METHODS: Studies were performed on inflamed tissue from patients with rheumatoid arthritis, as a prototype of inflammatory disease. The expression and activation of the alpha, beta, gamma, and delta isoforms of p38 MAPK were examined by immunoblotting, immunoprecipitation, and immunohistochemistry. RESULTS: Immunoblot analysis revealed that alpha and gamma were the predominantly expressed p38 MAPK isoforms, whereas the other 2 isoforms were less frequently present. By immunohistochemistry, the expression of all p38 MAPK isoforms was localized to the synovial lining layer as well as to blood vessels. Colabeling with cell-specific markers revealed that macrophages expressed the alpha and gamma isoforms, synovial fibroblasts the beta and gamma isoforms, and granulocytes the delta isoform, whereas T lymphocytes were rarely positive for any p38 MAPK isoform. Double-labeling with isoform-specific antibody and pan-p38 antibody against the phosphorylated form of p38 MAPK showed activation of the alpha and gamma isoforms. Occasional activation of the beta isoform was also noted in the synovial lining and the endothelium, whereas the delta isoform, although expressed in pericytes around blood vessels, was not phosphorylated. This phosphorylation pattern was confirmed in immunoprecipitation studies in which activated p38 MAPK from synovial tissue extracts was identified as p38 MAPKalpha and -gamma but not p38 MAPKbeta or -delta. CONCLUSION: These data show that the alpha and gamma isoforms of p38 MAPK dominate in chronic inflammation. Effective strategies to inhibit p38 MAPK should therefore aim to specifically target either or both of these isoforms.
17328818 A new classification of HLA-DRB1 alleles differentiates predisposing and protective allele 2007 The HLA-DRB1 gene was reported to be associated with anticitrullinated protein/peptide autoantibody (ACPA) production in rheumatoid arthritis (RA) patients. A new classification of HLA-DRB1 alleles, reshaping the shared epitope (SE) hypothesis, was recently found relevant in terms of RA susceptibility and structural severity. We investigated the relevance of this new classification of HLA-DRB1 SE+ alleles in terms of rheumatoid factor (RF) and ACPA production in a sample of French RA patients. We studied 160 early RA patients included in a prospective longitudinal cohort of French Caucasian patients with recent-onset arthritis. RF, anticyclic citrullinated peptide 2 (anti-CCP2) and antideiminated human fibrinogen autoantibodies (AhFibA) were assessed in all patients at inclusion. The HLA-DRB1 gene was typed by PCR-sequence specific oligonucleotides probes (PCR-SSOP), and SE+ alleles were classified into four groups (S1, S2, S3P, S3D) according to the new classification. The new classification of HLA-DRB1 SE+ alleles distinguishes predisposing and protective alleles for RF, anti-CCP2 or AhFibA production. The presence of S2 or S3P alleles is associated with both RF, anti-CCP2 or AhFibA positivity, whereas the presence of S3D or S1 alleles appears to be protective for RF, anti-CCP2 or AhFibA positivity. The new classification of HLA-DRB1 SE+ alleles is relevant in terms of autoantibody production in early RA patients by differentiating predisposing and protective alleles for RF or ACPA production.
16724807 T cell activation as starter and motor of rheumatic inflammation. 2006 Rheumatic inflammation is driven by sustained specific immunity against self-antigens, resulting in local inflammation and cellular infiltration and, subsequently, in tissue damage. Although the specific autoantigen(s) eliciting the detrimental immune reactions in rheumatic diseases have rarely been defined, it has become clear that the mechanisms resulting in the destruction of tissue and the loss of organ function during the course of the diseases are essentially the same as in protective immunity against invasive microorganisms. Of fundamental importance in initiating, controlling, and driving these specific immune responses are CD4 T cells. Currently available data provide compelling evidence for a major role of CD4 T cells in the initiation and perpetuation of chronic rheumatic inflammation. Consequently, T cell-directed therapies have been employed with substantial clinical success in the treatment of rheumatic diseases. Here, we review current knowledge based on which CD4 T cells can be implicated as the motor of rheumatic inflammation.
18356170 Interleukin-7 in rheumatoid arthritis. 2008 Jun Recent data from several groups demonstrate high levels of IL-7 in the joints of RA patients, but much lower levels in OA. In contrast, circulating levels of IL-7 in RA remain a point of debate. IL-7 has many roles in T cell, dendritic cell and bone biology in humans. Reduced levels of circulating IL-7 probably underlie a number of the dysfunctions associated with circulating T cells in RA and may provide a mechanism for some of the unexplained systemic manifestations of the disease. However, IL-7 in the joint may have a more sinister role, contributing to a vicious cycle perpetuating inflammation. Typically, IL-1beta and TNF-alpha increase the stromal production of IL-7 and in turn, IL-7 up-regulates the production of TNF-alpha by macrophages. Most importantly, IL-7 induces the production of osteoclastogenic cytokines by T cells, leading to the maturation of osteoclasts and therefore bone destruction. By linking the stroma with innate and adaptive immunity in RA, IL-7 may be directing the cellular network, leading to chronic inflammation and joint destruction. Blocking IL-7 may well therefore be of therapeutic value.
18455683 Animal models for arthritis. 2008 Apr Animal models for rheumatic diseases complement human investigations to study in detail pathogenic hypotheses and therapeutic strategies. An overview of animal studies in the last years shows examples for ideas taken from bench to bedside and from bedside to bench. Depending on the disease studied, progress includes a refinement of physiological and pathogenic thinking and a better definition of promising cellular and molecular therapeutic targets.
18823645 Treatment with infliximab plus methotrexate improves anemia in patients with rheumatoid ar 2009 Oct OBJECTIVE: To evaluate the effect of antitumor necrosis factor-alpha monoclonal antibody infliximab treatment on anemia in patients with rheumatoid arthritis (RA). METHODS: Data from patients with RA who received infliximab or placebo in the multicenter, placebo-controlled, double-blind, randomized ATTRACT, ASPIRE, and START studies were included in this post-hoc, pooled analysis. Infliximab (3 to 10 mg/kg) was administered every 4 or 8 weeks, and all patients received stable doses of methotrexate (MTX). We determined the percentage of anemic patients (baseline hemoglobin level <12 g/dL) who had an increase from baseline in hemoglobin level greater than or equal to 1 or 2 g/dL or achieved normal hemoglobin level at week 22. The association of improvement in anemia with improvement in clinical parameters was also evaluated. RESULTS: Among patients with anemia at baseline, infliximab plus MTX treatment produced a significantly greater mean (standard deviation) increase in hemoglobin level from baseline to week 22 (0.74 [1.12], P < 0.0001) than placebo plus MTX (0.30 [0.92]). Significantly (P < 0.001) greater proportions of anemic patients treated with infliximab plus MTX had either at least a 1 g/dL (40%) or at least a 2 g/dL (12%) increase in hemoglobin level from baseline to week 22 or achieved normal hemoglobin level (43%) when compared with placebo plus MTX (19, 5, and 28%, respectively). Greater improvement in hemoglobin level among infliximab plus MTX-treated patients was consistently observed across subgroups and in patients without clinical response (American College of Rheumatology 20% response criteria) at week 22. Multiple regression analysis indicated that the effect of infliximab plus MTX on anemia was independent of improvement in disease activity. CONCLUSION: Treatment with infliximab plus MTX significantly improved hemoglobin level among anemic RA patients when compared with treatment with placebo plus MTX, even after adjusting for improvement in disease activity.
17928867 Expression of a pathogen-response program in peripheral blood cells defines a subgroup of 2008 Jan Rheumatoid arthritis (RA) is a heterogeneous disease with unknown etiology. Here we aimed to distinguish RA subtypes based on peripheral blood (PB) gene expression profiles in comparison with a pathogen-response transcriptional program. PB was obtained from 35 RA patients and 15 healthy individuals. For expression profiling we used DNA microarrays. A combined cluster analysis of RA and control samples together with samples from a viral infection model revealed that the gene expression profile of a subgroup of RA patients (RA(A)) was reminiscent to that of poxvirus-infected macaques. Statistical analysis, followed by Gene Ontology analysis of the RA(A) patients confirmed that these patients form a distinct group, with activation of several host defense mechanisms that resemble a common host-pathogen response. Analysis of the promoter region of genes that were overexpressed in the RA(A) patients, revealed an enrichment of transcription factor binding sites for NF kappaB and interferon-activated transcription factors. Moreover, this subgroup of RA patients expressed significantly increased titers of anti-cyclic citrullinated peptide antibodies. We conclude that activation of a host-pathogen response defines a subgroup of RA patients characterized by increased autoreactivity against citrullinated proteins.
16870102 An increased frequency of gallbladder stones in rheumatoid arthritis patients. Factors rel 2006 May OBJECTIVE: In this study, we determined the frequency of gallbladder stone (GBS) in rheumatoid arthritis (RA) patients and evaluated factors which could affect the formation of GBS--such as lipids and the GB motilities of the patients. METHODS: One hundred and thirteen RA patients (92F, 21M, mean disease duration: 8.9 years) and 117 healthy controls (94F, 23M) were included. In all RA patients, the clinical findings were recorded down; biochemical parameters and body mass index (BMI) were determined; and, abdominal ultrasonography was performed. In addition, 16 RA patients and 20 controls who were age-matched were randomly chosen for GB emptying monitored by ultrasound at 30-minute intervals for 2 hours after a mixed meal. Fasting volume (FV), residual volume (RV) and ejection fraction (EF) for all GBs were assessed. RESULTS: There was a tendency towards a higher frequency of GBS including cholecystectomy (11 GBS, 11 cholecystectomy, 19.5%) in RA patients when compared to controls (8 GBS, 5 cholecystectomy, 11.1%) (p = 0.08). The frequency of GBS plus cholecyctectomy in female RA patients (22.8%) was significantly higher than the control group (11.7%, p = 0.044). Logistic regression analysis showed that only older age was significantly associated with the presence of GBS in RA (OR:1.05, p = 0.048). There was no difference between the 2 groups in FV (p > 0.05). RV, PRV and EF were significantly higher in RA patients than in the control group (p < 0.05). CONCLUSION: We diagnosed a higher frequency of GBS in female RA patients when compared to controls. Impaired GB motility in RA patients might contribute to an increased incidence of GBS development.
18064397 Rare copresent rheumatoid arthritis and gout: comparison with pure rheumatoid arthritis an 2008 Feb Copresent rheumatoid arthritis (RA) and gout is seldom reported. This study summarizes the findings of eight cases of copresent RA and gout and compares them with 31 pure RA cases. Additional reported cases were retrieved from the current literature by Medline search. Patients with copresent RA and gout were older (p = 0.014) and predominantly male (p < 0.01). Synovial fluid, positive for urate crystals, was aspirated most frequently from the knee (five out of eight), followed by the first metatarsophalangeal joint (three out of eight). Serum creatinine and urate levels in the copresent group were significantly higher (p < 0.01, both), and serum hemoglobin was lower (p = 0.04) than those with pure RA. Copresent subjects had much lower percentage of positive rheumatoid factor (RF) tests than patients with pure RA (37.5 vs 80.6%). Only one copresent subject had both RF and anti-cyclic citrullinated peptide antibody. Of copresent subjects, 75% had gouty arthritis before diagnosis of RA, which is consistent with earlier reports. Seven copresent subjects had gout attacks under disease-modifying antirheumatic drug use. This study revealed that polyarthritis negative for RF in a previously gouty patient may be RA and vice versa. This combination occurs more frequently in males. Moreover, anti-CCP antibody examination is not helpful for this diagnosis. Therefore, physicians must obtain synovial fluid for analysis in joints with intense swelling, especially in old RA subjects with renal insufficiency or involvement of lower extremities. Conversely, RA must be considered in gouty patients with polyarticular involvement.
17131100 [Shoulder prostheses]. 2006 Dec The design of shoulder prostheses has been developed through four generations which mirror adaptation to our increasing knowledge of the biomechanics of the shoulder joint. Modern shoulder prostheses are adapted to the size, inclination, posterior offset, and retrotorsion of the shoulder. The main reasons for implantation of a shoulder prosthesis are primary osteoarthritis, posttraumatic and rheumatoid arthritis, avascular necrosis, instability arthritis and cuff defect arthropathy. Typical implants are cup prostheses for surface replacement, anatomical stem prostheses, and reverse prostheses. Total prostheses are functionally better as soon as the arthritis involves the glenoid, whereas hemiprostheses should be preferred as long as the glenoid is intact. The stem is mostly cemented, whereas in younger patients with good bone quality a cementless stem may be used. Cemented glenoids may be considered as standard.
17934091 Interpreting measurements of physical function in clinical trials. 2007 Nov Improving physical functioning is one of the major goals of anti-rheumatic treatment. However, functional limitations can have several different causes, which may differ in their capacity to respond to a given treatment. Functional limitations due to pain or other acute symptoms or signs may be readily reversible with efficacious treatment, while those due to chronic structural changes may be relatively irreversible in the short term. Because measures of physical function characterise the degree of limitation without regard to cause, patients with the same apparent degree of functional limitation may differ greatly in their ability to demonstrate response to treatment. Structural damage accumulates over the course of disease, so measures of functional limitations tend to be less responsive among patients with more longstanding disease. This decreased responsiveness leads to a decreased ability to discriminate between treatments in patients with more longstanding arthritis. In addition, the criteria for minimal clinically important improvement may be underestimated when patients with irreversible functional limitations are included as test subjects, because judgments of improvement may be associated with smaller measured changes in physical functioning. The interpretation of measurements of physical function in clinical trials should consider the composition of the study sample, with attention to the stage of disease and the heterogeneity in disease duration or structural damage among subjects.
18511237 Prevalence and significance of antibodies to citrullinated human papilloma virus-47 E2345- 2008 Sep It has been confirmed that antibodies to citrullinated profilaggrin306-324 may play important roles in RA. In this study, human papilloma virus (HPV)-47 E2345-362, homologous to profilaggrin306-324, was found using the NCBI BLAST program. Then, E2345-362 and citrullinated E2345-362, with arginine348 replaced by citrulline, were synthesized. The presence of antibodies against these peptides was examined by an enzyme-linked immunosorbent assay. Associations between these antibodies and the clinical and laboratory features of RA were evaluated. Although the prevalence and AU value of antibodies to the E2345-362 peptide were similar in RA and other rheumatic diseases, those of antibodies to the citrullinated E2345-362 peptide were significantly higher in RA than in other rheumatic diseases. Additionally, sera that were preincubated with cyclic citrullinated peptide (CCP) demonstrated lower AU values of anti-citrullinated E2345-362 peptide antibodies. Moreover, the prevalence of anti-CCP antibodies and that of anti-peptidylarginine deiminase (PADI4) antibodies in anti-citrullinated E2345-362-positive patients were all higher than those of anti-citrullinated E2345-362-negative patients. There were significant correlations between anti-citrullinated E2345-362 and anti-PADI4. RA patients with antibodies to citrullinated E2345-362 had higher DAS28 scores, erythrocyte sedimentation rates, and radiographic progression than those without the antibodies. These results suggest that HPV-47 E2 may act as an autoantigen in RA. The increase in PADI4 may make it easier to citrullinate the HPV-47 E2345-362 peptide, leading to the subsequent immune responses.
17414534 Successful etanercept use in an HIV-positive patient with rheumatoid arthritis. 2007 Apr Limited information exists on treatment of rheumatoid arthritis in a patient with coexisting human immunodeficiency virus (HIV) infection. We report a case of a patient with rheumatoid arthritis who then became HIV positive. His HIV viral load was controlled with antiretroviral therapy, but he continued to have active rheumatoid arthritis despite therapy with hydroxychloroquine, sulfasalazine, and corticosteroids. Because of unremitting rheumatoid disease, we are now treating him with a TNFalpha inhibitor, and his rheumatoid disease activity has decreased from 28 swollen and tender joint count to less than 5.
17717675 [Operative differential therapy of rheumatic wrists]. 2007 Sep The wrists are affected in the long-term in 90% of people with rheumatism and are often (42%) the first manifestation of a destructive disease. The functionality of the wrist and the whole hand is of great importance because in many cases loss of function of the wrists leads to severe limitations. Local and operative treatment of the wrist in rheumatoid arthritis (RA) is one of the main duties in rheuma-orthopaedics. For operative treatment there is a finely tuned differential therapeutic spectrum available. The diagnostic indications take the local and total pattern of affection, the current systemic therapy as well as patient wishes and patient compliance into consideration. In the early stages according to LDE (Larsen, Dale, Eek), soft tissues operations such as articulo-tenosynovectomy (ATS) are most commonly carried out. In further advanced stages osseus stabilisation must often be performed. At this point a smooth transition from partial arthrodesis to complete fixation is possible. After initial euphoria, arthroplasty of the wrist is being increasingly less used for operative treatment due to the unconvincing long-term results and high complication rate. With reference to the good long-term results of all operative procedures, in particular early ATS with respect to pain, function and protection of tendons, after failure of medicinal treatment and persistence of inflammatory activity in the wrist, patients should be transferred to an experienced rheuma-orthopaedic surgeon.
16855155 Revisiting the toxicity of low-dose glucocorticoids: risks and fears. 2006 Jun We have recently participated in a careful literature search and critical evaluation of glucocorticoids, and we have revised the side-effects data of four recent controlled trials of low-dose glucocorticoids (GCs) in rheumatoid arthritis. The toxicity profile stands out as remarkably more benign than expected from most textbook recommendations. Data regarding low-dose therapy are scarce and of low quality, as no controlled trials have been designed to specifically address toxicity. Common fears of GC toxicity seem to originate from an excessive weight on anecdotal data and observations with high doses, as in organ transplantation. There is now evidence that mechanisms of action of GCs vary considerably according to the dose, thus allowing the possibility of a different toxicity profile. Data from recent controlled trials are quite reassuring, overall. Certainly, risks and benefits of GCs need to be carefully weighed in every patient. But we need to make a clear distinction between established risks and unchecked fears while trying to get the best result for our patient. Clearly, there is a need for studies that are appropriately designed to address the toxicity of GCs and to avoid the risk of "throwing out the baby with the bath water."