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ID PMID Title PublicationDate abstract
16680757 Use of breath carbon monoxide measurements to assess erythrocyte survival in subjects with 2006 Jun Anemia is very common in patients with chronic diseases. To determine the role of increased red blood cell (RBC) turnover in such subjects, we estimated RBC survival in three groups of chronically ill patients using a simple technique in which RBC life span is estimated via measurements of breath carbon monoxide concentration. The study groups consisted of subjects with: (1) osteoarthritis, (2) rheumatoid arthritis, and (3) anemia who were hospitalized for treatment of a variety of chronic illnesses. None of the anemic subjects had evidence of hemorrhage, a deficiency state, or a marrow abnormality to account for their reduced hemoglobin concentration. Subjects with osteoarthritis had a mean RBC life span (127 +/- 25 days) that did not differ significantly from normal (122 +/- 23 days). In contrast, RBC life span was significantly reduced (P < 0.001) in both the rheumatoid arthritis subjects (90 +/- 15 days) and the anemic, hospitalized patients (87 +/- 33 days). The hemoglobin concentration of the rheumatoid patients was near normal (13.5 +/- 1.5 g/dl), indicating that the marrow was compensating for the reduced RBC life span, whereas no such compensation was apparent in the anemic, chronically ill subjects. We conclude that a modest (approximately 25%) reduction in RBC life span commonly occurs in patients with chronic disease, and this reduction becomes clinically relevant in subjects whose marrow cannot respond with increased RBC output.
18708894 Identification of patients with arthritis and arthritis-related functional limitation usin 2008 Sep OBJECTIVE: To develop algorithms on the basis of administrative data to identify patients with arthritis and arthritis-related functional limitation (AFL). STUDY DESIGN AND SETTING: In this retrospective study, 361 enrollees of a health plan underwent a clinical examination to confirm arthritis and assessment of functional limitation on the basis of responses to the health assessment questionnaire. Administrative data were obtained on these subjects and included arthritis drugs dispensed, as well as outpatient and emergency department diagnoses and procedures (including radiographic studies, arthritis procedures, and laboratory tests). Composite risk scores for arthritis and AFL were created on the basis of the association of arthritis-related healthcare utilization with confirmed arthritis and AFL. Algorithms were then developed on the basis of the composite risk scores using logistic regression models. RESULTS: The algorithm using the arthritis composite score to identify arthritis patients had an area under the ROC curve (AUC) of 0.74, sensitivity of 75 percent and specificity of 57 percent. Similarly, the algorithm using the AFL composite score to identify patients with AFL had an AUC of 0.73, sensitivity of 62 percent, and specificity of 75 percent. CONCLUSION: The developed algorithms will enable health plans to screen their enrollees for persons with arthritis and AFL. This will facilitate enrollment of patients with arthritis and AFL in disease management programs and/or targeted interventions.
15941839 Low circulating soluble interleukin 2 receptor level predicts rapid response in patients w 2006 Jan BACKGROUND: Treatment with infliximab induces a rapid therapeutic response in most patients with active rheumatoid arthritis. Factors predicting good response are not well known. OBJECTIVE: To study the predictive value of baseline level of soluble interleukin 2 receptor (sIL2R), a marker of lymphocyte activation, on the treatment response. METHODS: 24 patients with active rheumatoid arthritis received intravenous infusions of infliximab at study entry, at two weeks, at six weeks, and at eight week intervals thereafter. Outcome was evaluated at six weeks and 22 weeks. Clinical assessment and standard laboratory tests were made and the DAS28 disease activity score was calculated. Serum sIL2R level at entry was measured by automated immunoassay analyser (Immulite). The mean change in DAS28 score from entry to six weeks and 22 weeks was calculated and related to sIL2R level using baseline adjusted robust regression analysis. RESULTS: Baseline level of serum sIL2R (mean (SD), 621 (325) U/ml) did not correlate with baseline DAS28 score (r = 0.24 (95% confidence interval, -0.18 to 0.58)). At six weeks DAS28 scores improved, with a mean change of -2.53 (-3.08 to -1.98) (p<0.001). This change was predicted by low baseline sIL2R level (regression coefficient per 100 U/ml: 0.205 (0.003 to 0.407) (p = 0.047)). At 22 weeks the DAS28 scores improved, with a mean change of -2.26 (-2.75 to -1.77) (p<0.001). The change was not predicted by baseline sIL2R level. CONCLUSIONS: Low baseline sIL2R level may predict a rapid clinical response in patients with refractory rheumatoid arthritis treated with infliximab.
17330301 Effectiveness of the introduction of an International Classification of Functioning, Disab 2007 Mar 15 OBJECTIVE: To investigate whether the use of an International Classification of Functioning, Disability and Health (ICF)-based instrument to structure multidisciplinary care improves clinical effectiveness and satisfaction in patients with rheumatoid arthritis (RA) admitted for multidisciplinary team care. METHODS: Consecutive patients with RA admitted to an inpatient or day patient multidisciplinary team care ward were included during a 12-month period before (period I) and after (period II) the introduction of an ICF-based rehabilitation tool (Rehabilitation Activities Profile [RAP]). Patients were assessed at admission, discharge, and 6 weeks thereafter. The primary outcome measure was a patient-oriented measure of functional ability (McMaster Toronto Arthritis Patient Preference Disability Questionnaire [MACTAR]), whereas secondary outcome measures included measures of physical and mental functioning, quality of life, disease activity, and patient satisfaction. Change scores between periods were compared using analysis of covariance. RESULTS: A total of 80 and 85 patients were included in periods I and II, respectively. Concerning the improvement of the MACTAR score and all other secondary clinical outcome measures, there was no significant difference between the 2 periods. Patient satisfaction with care was slightly higher in period II than in period I, with the differences regarding the total score of a multidimensional satisfaction questionnaire and the domains focusing on individual problems and empathy reaching statistical significance. CONCLUSION: The introduction of the RAP did not change clinical effectiveness but had a modest beneficial impact on patient satisfaction with care in patients with RA admitted for multidisciplinary team care.
18363473 Invasive mucormycosis of the maxillary sinus: extensive destruction with an indolent prese 2008 Feb BACKGROUND: Mucormycosis (zygomycosis) is a rare, aggressive, invasive fungal infection that usually afflicts immunosuppressed patients. Indolent presentations are rare, especially in the setting of immune suppression. METHODS: Case report and review of the pertinent English-language literature. CASE REPORT: A 64-year-old male patient with diabetes mellitus and rheumatoid arthritis, treated chronically with infliximab, presented with toothache, headache, and right facial numbness. Therapy with intravenous glucocorticoids and antibiotics resulted in transitory improvement before his referral to a tertiary-care center, where imaging studies and biopsy revealed rhinocerebral mucormycosis. Four weeks after initial presentation, a radical right maxillectomy, followed by long-term therapy with amphotericin B lipid complex, resulted in clinical improvement. Five reconstructive procedures were required to obliterate the facial defect and restore contour. Although biopsies during the reconstructive procedures revealed persistent fungal colonization, there was no clinical recurrence during nearly five years of followup. CONCLUSIONS: Indolent rhinocerebral mucormycosis is rare and is seldom survived by immunosuppressed patients. Multimodal therapy with surgical debridement and antifungal chemotherapy is required for an optimal outcome. Discontinuance of immunosuppressive therapy, if possible, is a cornerstone of management.
17406855 [Indications and alternatives for arthroplasty in young patients]. 2007 Apr Due to the significant risk of aseptic implant loosening, the indications for endoprosthetic treatment of young adults must be assessed critically. All conservative and surgical therapy options must always be considered cautiously. Even advanced osteoarthritis of the upper extremities (shoulder, elbow and wrist joints) can often be treated with joint sparing, non-endoprosthetic therapy that leads to good clinical results and sufficient joint function. Total joint replacement is often inevitable for regaining an acceptable gait and adequate mobility in cases of advanced joint destruction of the lower extremities (hip and knee joints). Arthrodesis of the upper ankle joint in cases of isolated osteoarthritis remains a valid therapeutic option. Replacement of the upper ankle joint should be considered in cases of bilateral affliction as well as in the event of additional osteoarthritis of the adjacent joints of the lower ankle and the tarsus.
16450150 [T-large granular lymphocyte leukaemia. An important differential diagnosis to Felty's syn 2006 Sep T-Large Granular Lymphocyte (T-LGL) leukaemia is a rare clonal disease characterized by neutropenia and/or anaemia. Because of its strong association with rheumatoid arthritis (RA), T-LGL leukaemia is an important differential diagnosis to Felty's syndrome. This differentiation might be especially difficult since, in severe RA with extraarticular manifestations, there is often an expanded memory effector T-cell population which can hardly be separated from T-LGL leukaemia cells by means of immunophenotyping. The main criterion for T-LGL leukaemia is the detection of a clonal T-cell-receptor rearrangement by PCR. First-line therapy consists of weekly low-dose methotrexate. Alternatively, other immunosuppressives or cytotoxic agents can be useful. There are very limited data from therapy studies. The German CLL study group has initiated a protocol using parenteral low-dose methotrexate as first-line therapy and fludarabine as second-line medication.
17678829 A three-page Standard Protocol to Evaluate Rheumatoid Arthritis (SPERA) for efficient capt 2007 Aug A Standard Protocol to Evaluate Rheumatoid Arthritis (SPERA) has been developed to collect essential data from patients and health professionals to assess, monitor, and document change in standard clinical care and clinical research. Three one-page forms are completed by a health professional assessor, which can be completed at baseline for use at all future visits: (1) clinical features of rheumatoid arthritis (RA); (2) medications taken; and (3) a 42-joint count. The patient also completes a patient questionnaire, and a radiographic scoring sheet can also be included for a comprehensive database. The 15-20 minutes involved in completing the SPERA generally add efficiency to subsequent visits in standard clinical care. Collection of additional information for clinical care and/or clinical research is also possible. The SPERA is presented not as an optimal format but rather as an example of a possible approach to develop a common format for core clinical data to be collected in standard clinical care.
15912568 Effect of Semecarpus anacardium Linn. nut milk extract on rat neutrophil functions in adju 2006 Jul Neutrophils play an important role in the pathogenesis of rheumatoid arthritis (RA) and various inflammatory conditions, by accumulation and liberation of active proteolytic enzymes. The effect of milk extract of Semecarpus anacardium Linn. nuts (SA) at a dosage of 150 mg kg(-1) body weight day(-1) for 14 days on adjuvant arthritis was studied to gain some insight into this intriguing disease in relation to neutrophil functions. The decreased phagocytic function of neutrophils (phagocytic index and avidity index) found in adjuvant arthritis was significantly increased by the administration of the drug SA. Increased levels of reactive oxygen species (superoxide radical, hydroxyl radical, H2O2 and myeloperoxidase), lysosomal enzymes (acid phosphatase and cathepsin D) and increased accumulation of neutrophils in the joints observed in adjuvant arthritic animals were reverted back to near normal levels by treatment with SA. The results of this study indicate that SA can be considered to be a good therapeutic agent for inflammation and arthritis.
18385279 The tumour necrosis factor receptor superfamily member 1b 676T>G polymorphism in relation 2008 Aug OBJECTIVE: To assess the effect of a functional polymorphism (676T>G, M196R) in the tumour necrosis factor receptor super family 1b (TNFSF1b) gene on disease activity, radiological joint damage and response to infliximab and adalimumab treatment in patients with rheumatoid arthritis (RA). METHODS: Two cohorts of patients with RA were genotyped for the 676T>G polymorphism (rs1061622) in exon 6 of the TNFSF1b gene by restriction fragment length polymorphism analysis. One cohort (n = 234) included patients from the Dutch Rheumatoid Arthritis Monitoring register with detailed information on their response to anti-TNF therapy (infliximab and adalimumab), the other cohort comprised patients from a long-term observational early inception cohort at our centre (n = 248). RESULTS: The 676T>G polymorphism was not associated with anti-TNF response after 3 or 6 months of treatment. Linear regression analysis showed no significant difference in the progression of radiological joint damage during the first 3 and 6 years of disease between the three genotype groups (TT, TG and GG). Additionally, no difference in mean disease activity between genotypes was seen after 3 and 6 years of disease. CONCLUSION: Despite its demonstrated functionality, the 676T>G polymorphism in the TNFSF1b gene does not have a major role in either the response to anti-TNF therapy or in the disease severity or radiological progression in RA.
17113236 Rembrandt's Maria Bockenolle has a butterfly rash and digital deformities: overlapping syn 2007 Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are the most common autoimmune disorders, although they each have very different pathophysiology. In general, RA is considered to be a Th1-mediated disease, while SLE is a Th2-mediated disease. Thus, their overlapping, in so called "rhupus", is a rare condition. In Rembrandt van Rijn's (1606-1669) portrait of the middle-aged Maria Bockenolle, we have what may be the earliest depiction of a case of rhupus syndrome: the coexistence of a butterfly rash and digital deformities. This suggests the possible historical importance of an RA epidemic which took place in the early 17th century.
18975324 HMOX1 promoter polymorphism modulates the relationship between disease activity and joint 2008 Nov OBJECTIVE: The guanine-thymidine (GT)n repeat in the HMOX1 promoter determines the level of induction of the heme-degrading enzyme heme oxygenase 1 (HO-1), which protects against inflammatory and oxidative stress. In individuals with short (GT)n repeats (where n < 25; SS genotype), higher levels of HO-1 activity are induced more rapidly than in those with long (GT)n repeats (where n > or = 25; LL genotype). Recently, it was demonstrated that HO-1 activity protects against the onset of rheumatoid arthritis (RA). The aim of this study was to determine whether the (GT)n-repeat length within the HMOX1 promoter region is associated with RA disease severity and radiographic joint damage. METHODS: A cohort of 325 well-characterized RA patients and 273 controls was investigated by DNA fragment-length analysis for the association of (GT)n repeats in the HMOX1 promoter region with RA disease susceptibility and severity. RESULTS: Although no significant differences in genotype or allele frequency were found between controls and RA patients, the odds ratios corresponded well to those in the previously described cohort. Among patients, those carrying the SS genotype had a more favorable radiographic outcome over 9 years than those carrying the LL genotype. This was unexpected since no differences in disease activity were found between the genotypes or alleles. CONCLUSION: Patients with the SS genotype have a better long-term radiographic outcome despite poor prognostic markers at baseline and despite disease activity at followup similar to that of patients with the LL genotype. This suggests that the HMOX1/HO-1 system is involved in the uncoupling of disease activity and joint damage and may provide a novel target for the treatment of RA.
16414968 Do patients with older-onset rheumatoid arthritis receive less aggressive treatment? 2006 Sep Rheumatoid arthritis among elderly people is an increasingly important health concern. Despite several cross-sectional studies, it has not been clearly established whether there are important clinical differences between elderly-onset rheumatoid arthritis (EORA) and younger-onset rheumatoid arthritis (YORA). The aim of this study was to compare disease activity and treatment in EORA and YORA, using the Consortium of Rheumatology Researchers of North America (CORRONA) registry, a database generated by rheumatologist investigators across the USA. From the CORRONA registry database of 9381 patients with rheumatoid arthritis, 2101 patients with disease onset after the age of 60 years (EORA) were matched, on the basis of disease duration, with 2101 patients with disease onset between the ages of 40 and 60 years (YORA). The primary outcome measures were the proportion of patients on methotrexate, multiple disease-modifying antirheumatic drugs (DMARD) and biological agents (etanercept, infliximab, adalimumab and kineret) in each group. Disease activity and severity differed slightly between the EORA and YORA groups: Disability Index of the Health Assessment Questionnaire: 0.30 v 0.35; tender joint count: 3.7 v 4.7; swollen joint count: 5.3 v 5.2; Disease Activity Score 28: 3.8 v 3.6; patient global assessment: 29.1 v 30.9; physician global assessment: 24.9 v 26.3; patient pain assessment: 31.4 v 34.9. Regarding treatment, the use of methotrexate use was slightly more common among patients with EORA (63.9%) than among those with YORA (59.6%), although the mean methotrexate dose among the YORA group was higher than that in the EORA group. The percentage of patients with EORA who were on multiple DMARD treatment (30.9%) or on biological agents (25%) was considerably lower than that of patients with YORA (40.5% and 33.1%, respectively; p<0.0001). Toxicity related to treatment was very minimal in both groups, whereas toxicities related to methotrexate were more common in the YORA group. Patients with EORA receive biological treatment and combination DMARD treatment less frequently than those with YORA, despite identical disease duration and comparable disease severity and activity.
17509138 Pro-apoptotic Bid is required for the resolution of the effector phase of inflammatory art 2007 Rheumatoid arthritis is an autoimmune disease characterized by hyperplasia of the synovial lining and destruction of cartilage and bone. Recent studies have suggested that a lack of apoptosis contributes to the hyperplasia of the synovial lining and to the failure in eliminating autoreactive cells. Mice lacking Fas or Bim, two pro-apoptotic proteins that mediate the extrinsic and intrinsic death cascades, respectively, develop enhanced K/BxN serum transfer-induced arthritis. Since the pro-apoptotic protein Bid functions as an intermediate between the extrinsic and intrinsic apoptotic pathways, we examined the role that it plays in inflammatory arthritis. Mice deficient in Bid (Bid-/-) show a delay in the resolution of K/BxN serum transfer-induced arthritis. Bid-/- mice display increased inflammation, bone destruction, and pannus formation compared to wild-type mice. Furthermore, Bid-/- mice have elevated levels of CXC chemokine and IL-1beta in serum, which are associated with more inflammatory cells throughout the arthritic joint. In addition, there are fewer apoptotic cells in the synovium of Bid-/- compared to Wt mice. These data suggest that extrinsic and intrinsic apoptotic pathways cooperate through Bid to limit development of inflammatory arthritis.
17927821 Differential responsiveness to immunoablative therapy in refractory rheumatoid arthritis i 2007 In order to identify pathogenic correlates of refractory rheumatoid arthritis (RA), antibodies against anti-cyclic citrullinated protein (ACPAs) were investigated in RA patients in whom the dysregulated immune system had been ablated by high-dose chemotherapy (HDC) and autologous haematopoietic stem cell transplantation (HSCT). Six patients with refractory RA were extensively characterized in terms of levels of total immunoglobulins, RA-specific autoantibodies (ACPAs and rheumatoid factor) and antibodies against rubella, tetanus toxoid (TT) and phosphorylcholine before and after HDC plus HSCT. Additionally, the avidity of ACPAs was measured before and after treatment and compared with the avidity of TT antibodies following repeated immunizations. Synovial biopsies were obtained by arthroscopy before HDC plus HSCT, and analyzed by immunohistochemistry. In the three patients with clinically long-lasting responses to HDC plus HSCT (median 423 days), significant reductions in ACPA-IgG levels after therapy were observed (median level dropped from 215 to 34 arbitrary units/ml; P = 0.05). In contrast, stable ACPA-IgG levels were observed in three patients who relapsed shortly after HDC plus HSCT (median of 67 days). Clinical responders had ACPA-IgG of lower avidity (r = 0.75; P = 0.08) and higher degree of inflammation histologically (r = 0.73; P = 0.09). Relapse (after 38 to 530 days) in all patients was preceded by rising levels of low avidity ACPA-IgG (after 30 to 388 days), in contrast to the stable titres of high avidity TT antibodies. In conclusion, humoral autoimmune responses were differentially modulated by immunoablative therapy in patients with synovial inflammation and low avidity ACPA-IgG autoantibodies as compared with patients with high levels of high avidity ACPA-IgG. The distinct clinical disease course after immunoablative therapy based on levels and avidity of ACPA-IgG indicates that refractory RA is not a single disease entity.
17234650 Calprotectin (a major leucocyte protein) is strongly and independently correlated with joi 2007 Aug OBJECTIVE: Calprotectin is a major leucocyte protein, shown to correlate well with laboratory and clinical assessments in several inflammatory rheumatic diseases, and large concentrations of calprotectin have been found in synovial fluid from patients with rheumatoid arthritis (RA). The objective of the present study was to examine correlations between calprotectin and joint damage. METHODS: 145 patients with RA were analysed cross sectionally with laboratory (calprotectin, C reactive protein (CRP), and erythrocyte sedimentation rate (ESR)), clinical (28 joint counts (tender, swollen), physician global VAS, DAS28 and RA Articular Damage score (RAAD)), and radiographic (plain hand radiographs; modified Sharp's method) measurements, on the same day. RESULTS: Calprotectin showed a highly significant correlation with measures of joint damage; modified Sharp score r = 0.43 (p<0.001) and RAAD r = 0.40 (p<0.001). The association with modified Sharp score and RAAD score was maintained after adjustment for CRP, ESR, rheumatoid factor, DAS28, sex, and age in a multiple regression analysis (p = 0.018 and p = 0.04, respectively), while neither CRP nor ESR showed any independent associations. Highly significant correlations (p<0.001) were also found between calprotectin and both laboratory and clinical markers of inflammation. CONCLUSION: Calprotectin was found to significantly and independently explain the variation in the radiological and clinical assessments of joint damage. Longitudinal studies are required to examine whether calprotectin may predict the progression of joint damage in RA.
17340045 Development of sarcoidosis in etanercept-treated rheumatoid arthritis patients. 2007 Nov We report two rheumatoid arthritis patients developing sarcoidosis possibly induced by etanercept. Both women, aged 46 and 53, had erosive, rheumatoid-factor-positive rheumatoid arthritis (RA) for 7 and 6 years, respectively. The eldest had received infliximab for over a year with good response, which was stopped because of a perfusion reaction. She developed a cough and dyspnea after 6 months of etanercept treatment. The other developed erythema nodosum and a plaque lesion on the right arm after 1 year of etanercept. Imaging showed, in both cases, mediastinal adenopathies. Biopsies were compatible with sarcoidosis. Etanercept withdrawal led to a complete remission. Recently, there have been reports of noninfectious granulomatous syndromes in patients receiving etanercept for a variety of diseases. In our cases, the temporal association with etanercept therapy and the complete remission after suspension of etanercept suggest a triggering role of this agent. Possible mechanisms of action and supporting evidence are discussed.
16612613 Genome-wide meta-analysis for rheumatoid arthritis. 2006 Jul Meta-analysis is being increasingly used as a tool for integrating data from different studies of complex phenotypes, because the power of any one study to identify causal loci is limited. We applied a novel meta-analytical approach (Loesgen et al. in Genet Epidemiol 21(Suppl 1):S142-S147, 2001) in compiling results from four studies of rheumatoid arthritis in Caucasians including two studies from NARAC (Jawaheer et al. in Am J Hum Genet 68:927-936, 2001; Jawaheer et al. in Arthritis Rheum 48:906-916, 2003), one study from the UK (MacKay et al. in Arthritis Rheum 46:632-639, 2001) and one from France (Cornelis et al. in Proc Natl Acad Sci USA 95:10746-10750, 1998). For each study, we obtained NPL scores by performing interval mapping (2 cM intervals) using GeneHunter2 (Kruglyak et al. in Am J Hum Genet 58:1347-1363, 1996; Markianos et al. in Am J Hum Genet 68:963-977, 2001). The marker maps differed among the three consortium groups, therefore, the marker maps were aligned after the interval mapping was completed and the NPL scores that were within 1 cM of each other were combined using the method of Loesgen et al. (Genet Epidemiol 21(Suppl 1):S142-S147, 2001) by calculating the weighted average of the NPL score. This approach avoids some problems in analysis encountered by using GeneHunter2 when some markers in the sample are not genotyped. This procedure provided marginal evidence (P<0.05) of linkage on chromosome 1, 2, 5 and 18, strong evidence (P<0.01) on chromosomes 8 and 16, and overwhelming evidence in the HLA region of chromosome 6.
17482423 Identification of a two-loci epistatic interaction associated with susceptibility to rheum 2007 Jul Altered synovial fibroblast (SF) transcriptional activity is a key factor in the disease progression of rheumatoid arthritis (RA). To determine the transcriptional regulatory network associated with SF response to an RA proinflammatory stimulus we applied a CARRIE reverse engineering approach to microarray gene expression data from SFs treated with RA synovial fluid. The association of the inferred gene network with RA susceptibility was further analyzed by a case-control study of promoter single-nucleotide polymorphisms, and the presence of epistatic interactions was determined using the multifactor dimensionality reduction methodology. Our findings suggest that a specific NF-kappaB transcriptional regulatory network of 13 genes is associated with SF response to RA proinflammatory stimulus and identify a significant epistatic association of two of its genes, IL6 and IL4I1, with RA susceptibility.
17141365 Methotrexate-associated lymphoproliferative disorder in a patient with rheumatoid arthriti 2007 Apr A 91-year-old woman who had been taking methotrexate for approximately 5 years for rheumatoid arthritis developed papules and nodules on her face that enlarged during 6 months. A series of biopsy specimens demonstrated a lymphoplasmacytic infiltrate with increasingly atypical histopathologic features that resembled diffuse large B-cell lymphoma. Epstein-Barr virus was not identified. Withdrawal of methotrexate resulted in complete resolution of all lesions within 8 weeks. This case illustrates the rare occurrence of methotrexate-associated lymphoproliferative disorder with primary presentation in the skin and documents clinical and histopathologic progression from early changes to fully developed lesions.