Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
28032845 Physical fatigue characterises patient experience of primary Sjögren's syndrome. 2017 Mar OBJECTIVES: Besides ocular and oral dryness, fatigue is a major symptom in patients with primary Sjögren's syndrome (pSS). Our aim was to investigate the importance of fatigue in relation to other symptoms experienced as well as to evaluate the effect of rituximab treatment on fatigue in pSS patients with active disease. METHODS: This analysis was based on data from our open-label rituximab study in 28 pSS patients. Symptoms of dryness, physical fatigue, pain, and mental fatigue were scored on 0-10 scales (according to ESSPRI). Systemic disease activity was assessed with ESSDAI. RESULTS: At baseline, 24 (86%) patients rated physical fatigue as the complaint most eligible for improvement (median importance of 10), followed by pain, dryness, and mental fatigue. After rituximab treatment, physical fatigue showed maximum improvement of 2.5 points and 31% in median values at group level, and 10 (36%) patients reached physical fatigue score<5 representing patient-acceptable symptom state (PASS). In comparison, systemic disease activity improved 5.5 points and 73% at group level, and 22 (79%) patients reached ESSDAI<5 representing low disease activity. GEE analysis over time revealed that physical fatigue was significantly associated with absolute number of B cells, dryness and mental fatigue, but not with ESSDAI, IgG levels and IgM-RF. CONCLUSIONS: Physical fatigue characterises patient experience of pSS. Rituximab treatment resulted in significant improvement of patient-reported symptoms. However, the large majority of patients still experienced physical fatigue at an unsatisfactory level, above the cut-off value for PASS. Therefore, attention for optimal management of this prominent symptom is warranted.
27017389 Autonomic dysfunction in primary Sjogren's syndrome: a prospective cohort analysis of 154 2017 Jan BACKGROUND/AIMS: To determine the prevalence of autonomic dysfunction among Korean patients with primary Sjogren's syndrome (pSS) and its associations with the clinical features of pSS. METHODS: We analyzed 154 participants from the Korean Initiative of primary Sjogren's Syndrome (KISS) as a prospective pSS cohort and 154 age- and sex-matched healthy controls. A standardized 5-minute, supine, resting heart rate variability (HRV) test was performed, and autonomic dysfunction was defined as standard deviation of normal-to-normal RR intervals (SDNN) < 30 ms in patients < 50 years old and SDNN < 20 ms in patients ≥ 50 years old. The associations between autonomic dysfunction and various clinical features of pSS were analyzed. RESULTS: The overall autonomic activity in patients with pSS was significantly lower than that in controls. Autonomic dysfunction with the HRV test was observed in 35.7% of the KISS participants and was associated with a higher European League Against Rheumatism Sjogren's Syndrome Patient Reported Index fatigue score (p = 0.024). Raynaud's phenomenon was a more frequent clinical presentation in pSS patients with autonomic dysfunction than in those without autonomic dysfunction (29.4% and 14.4%, respectively; p = 0.048). Decreased parasympathetic activity was observed in 41.6% of pSS patients. No differences were found in the oral and ocular signs of pSS according to the decreased parasympathetic activity. CONCLUSIONS: In Korean patients with pSS, decreased and imbalanced autonomic activity is prevalent and is associated with fatigue. However, an association between autonomic dysfunction and glandular manifestations was not detected.
28755070 [Still's disease in children and adults]. 2017 Sep Systemic juvenile idiopathic arthritis (sJIA) is characterized by fever, arthritis, and other signs of systemic inflammation. Historically, sJIA was named Still's disease after George Frederic Still, who first reported patients. Individuals who manifest after the 16(th) birthday are diagnosed with adult onset Still's disease (AOSD). The pathophysiology of sJIA and AOSD are incompletely understood. Increased activation of inflammasomes and the expression of proinflammatory cytokines play a central role. S100 proteins, which can activate Toll-like receptors, thus, maintaining positive feedback loops, have also been detected at increased levels in sera from sJIA patients. Reduced expression of the immune-modulatory cytokine IL-10 may further contribute to immune cell activation and the production of proinflammatory molecules. Here, we discuss the clinical picture, differential diagnoses, the current pathophysiological understanding, and treatment options in sJIA and AOSD.
27925697 Prevalence of Sjögren's syndrome in Brazilian patients infected with human T-cell lymphot 2017 Aug BACKGROUND: Human T-lymphotropic virus type I (HTLV-I) is known to be associated with neoplastic and neurodegenerative changes, and it is believed to be associated with various systemic inflammatory diseases, including Sjögren's syndrome (SS). Although HTLV-I infection is endemic in Brazil, there is no information regarding the association between HTLV-I infection and SS in the Brazilian population. The objective of this study was to determine the prevalence of SS in HTLV-I-infected individuals and the prevalence of HTLV-I infection in individuals diagnosed with SS. METHODS: Serology for HTLV-I was performed in 50 patients presenting with complaints consistent with SS (the SS group). The HTLV-I group comprised 129 HTLV-I-infected patients who were screened for SS. RESULTS: None of the patients in the SS group tested positive for HTLV-I. Of the 129 patients in the HTLV-I group, 46 (35.7%) had xerostomia, 18 (13.95%) had xerophthalmia, eight (6.2%) had hyposalivation, two (1.55%) showed impaired tear secretion, and one (0.77%) was positive for autoantibodies (anti-SSB). In addition, six underwent minor salivary gland biopsy, and the histopathological findings were consistent with SS. Only two (1.55%) met the diagnostic criteria for SS. CONCLUSIONS: The prevalence of SS was found to be three times as high in HTLV-I-infected individuals as it was in those without HTLV-I infection. However, given the small number of HTLV-seropositive patients with SS, it is impossible to state that HTLV acts as an immune-activating pathogen for SS.
28359271 The 2016 classification criteria for primary Sjogren's syndrome: what's new? 2017 Mar 31 New 2016 ACR/EULAR classification criteria for primary Sjogren's syndrome (SS) have been developed and endorsed by the ACR. The newly proposed criteria include simple-to-perform items.Two important points of the new criteria should be considered. Firstly, they indicate that either salivary gland biopsy or anti-Ro must be positive in order to corroborate the inflammatory and autoimmune nature of the disease. Secondly, the criteria recognize the systemic nature of SS, namely that patients without salivary or ocular glandular symptoms, but with extraglandular manifestations and B cell activation markers were also included in the SS classification. Additionally, the new criteria modified some technical points. The ocular staining score threshold was increased to 5 due to the higher specificity. The immunological profile includes only anti-Ro antibodies, while positivity for antinuclear antibodies and rheumatoid factor or isolated anti-La was excluded due to a lack of specificity.The 2016 ACR/EULAR criteria are suitable for early identification of SS, providing patients with the opportunity of enrollment in clinical trials for new specific treatment. Although validation has been successful, the real life application of these criteria will test their performance.
29238225 Validity and completeness of rheumatoid arthritis diagnoses in the nationwide DANBIO clini 2017 OBJECTIVES: In Denmark, patients with rheumatoid arthritis (RA) are registered in the nationwide clinical DANBIO quality register and the Danish National Patient Registry (DNPR). The aim was to study the validity of the RA diagnosis and to estimate the completeness of relevant RA cases in each registry. STUDY DESIGN AND SETTING: Patients registered for the first time in 2011 with a diagnosis of RA were identified in DANBIO and DNPR in January 2013. For DNPR, filters were applied to reduce false-positive cases. The diagnosis was verified by a review of patient records. We calculated the positive predictive values (PPVs) of the RA diagnosis registrations in DANBIO and DNPR, and estimated the registry completeness of relevant RA cases for both DANBIO and DNPR. Updated data from 2011 to 2015 from DANBIO were retrieved to identify patients with delayed registration, and the registry completeness and PPV was recalculated. RESULTS: We identified 1,678 unique patients in DANBIO or in DNPR. The PPV (2013 dataset) was 92% in DANBIO and 79% in DNPR. PPV for DANBIO on the 2015 update was 96%. The registry completeness of relevant RA cases was 43% in DANBIO, increasing to 91% in the 2015 update and 90% in DNPR. CONCLUSION: DANBIO held a high proportion of true RA cases (96%) and was found to be superior to the DNPR (79%) with regard to the validity of the diagnosis. Both registries were estimated to have a high completeness of RA cases treated in hospital care (~90%).
28151539 Non-pharmacological and pharmacological interventions in patients with early arthritis: a 2017 OBJECTIVE: To perform a systematic literature review (SLR) on pharmacological and non-pharmacological treatments, in order to inform the European League Against Rheumatism (EULAR) recommendations for the management of early arthritis (EA). METHODS: The expert committee defined research questions concerning non-pharmacological interventions, patient information and education, non-steroidal anti-inflammatory drug, glucocorticoid (GC) and disease-modifying antirheumatic drugs (DMARDs) use, as well as on disease monitoring. The SLR included articles published after the last EULAR SLR until November 2015 found in the MEDLINE, EMBASE and Cochrane databases and abstracts from the 2014 and 2015 American College of Rheumatology and EULAR conferences. RESULTS: Exercise programmes may improve pain and physical function in patients with EA. Patients with EA treated within the first 3 months of symptoms have better clinical and radiological outcomes than those treated beyond 3 months. The clinical and radiological efficacy of GCs is confirmed, with similar efficacy of oral and parenteral administrations. Long-term data raise concerns regarding cardiovascular safety when using GCs. Step-up DMARD therapy is as effective as intensive DMARD therapy 'ab initio' for the long-term outcome of EA. Short-term superiority of intensive therapy with bDMARDs is not maintained on withdrawal of bDMARD. Patients with early psoriatic arthritis have better skin and joint outcomes when tight control is used compared to standard care. CONCLUSIONS: The findings confirm the beneficial effect of exercise programmes and the importance of early drug therapy and tight control. They support the use of methotrexate and GCs as first-line drugs, although the long-term use of GCs raises safety concerns.
29033678 Quantitative Metabolic Volumetric Product on (18)Fluorine-2fluoro-2-deoxy-D-glucose-positr 2017 Oct The purpose of this study was to assess the role of fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) in the evaluation of treatment response evaluation to disease-modifying antirheumatic drug (DMARD) therapy in patients of rheumatoid arthritis (RA). A total of ten patients with proven diagnosis of RA as per the 2010 American College of Rheumatology/European League against Rheumatism (EULAR) criteria were prospectively evaluated. All patients underwent clinical and biochemical evaluation and a baseline FDG-PET/CT with assessment of maximum standardized uptake value and metabolic volumetric product (MVP) values. DMARD therapy was started with a combination of hydroxychloroquine and sulfasalazine. On follow-up at 3 and 6 months, the response to treatment was assessed by clinical, biochemical, and FDG-PET/CT parameters. These parameters were analyzed in a combined manner, and the patients were grouped into 4 categories as per response to DMARD therapy - complete response, good response, mixed response, and no response. Evaluation of treatment response in ten patients at 3(rd) month and in nine patients at 6 months showed (a) agreement for MVP, biochemical parameters with clinical symptomatic assessment in all patients, (b) while agreement for EULAR score was noted in only three patients and disagreement in seven patients with clinical symptoms Response EULAR (rEULAR) (0.37) and at 6 months in only three patients and disagreement in six patients, rEULAR (0.52). The correlation factors at 3(rd) month and 6(th) months were, respectively, as follows: rMVP (0.67 and 0.75), response RA factor (0.54 and 0.74), response erythrocyte sedimentation rate (0.81 and 0.73), response C-reactive protein (0.78 and 0.51), and response anti-cyclic citrullinated peptide antibodies (0.33 and 0.54). The overall response to DMARD therapy at 3 months was assessed with results showing good response by four cases (40%), mixed response by 1 (10%), no response by 5 (50%), and complete response by none (0%). Step-up therapy at 3 months was initiated in four patients showing nonresponse/progression on clinical symptomatic assessment; of these, two patients showed a good response, one mixed response, and the remaining one continued to show nonresponse at 6 months follow-up. One patient who had a minimal response at 3 months on PET-CT (only 5.96% reduction of MVP) was continued on the same DMARD in view of clinical symptomatic good response (at 3 months) but ultimately had disease progression in all scales and worsening of symptom (at 6 months). FDG-PET/CT-based assessment of inflammatory activity noted in the joints of RA with quantitative parameters can be a promising approach for the whole body assessment of RA disease activity and treatment response assessment, especially in inconclusive cases and correlates well with other parameters. MVP can be used as a useful objective and adjunct parameter for assessing response to treatment.
27899373 Influence of geolocation and ethnicity on the phenotypic expression of primary Sjögren's 2017 Jun OBJECTIVES: To analyse the influence of geolocation and ethnicity on the clinical presentation of primary Sjögren's syndrome (SjS) at diagnosis. METHODS: The Big Data Sjögren Project Consortium is an international, multicentre registry designed in 2014. By January 2016, 20 centres from five continents were participating. Multivariable logistic regression analyses were performed. RESULTS: We included 7748 women (93%) and 562 men (7%), with a mean age at diagnosis of primary SjS of 53 years. Ethnicity data were available for 7884 patients (95%): 6174 patients (78%) were white, 1066 patients (14%) were Asian, 393 patients (5%) were Hispanic, 104 patients (1%) were black/African-American and 147 patients (2%) were of other ethnicities. SjS was diagnosed a mean of 7 years earlier in black/African-American compared with white patients; the female-to-male ratio was highest in Asian patients (27:1) and lowest in black/African-American patients (7:1); the prevalence of sicca symptoms was lowest in Asian patients; a higher frequency of positive salivary biopsy was found in Hispanic and white patients. A north-south gradient was found with respect to a lower frequency of ocular involvement in northern countries for dry eyes and abnormal ocular tests in Europe (OR 0.46 and 0.44, respectively) and Asia (OR 0.18 and 0.49, respectively) compared with southern countries. Higher frequencies of antinuclear antibodies (ANAs) were reported in northern countries in America (OR=1.48) and Asia (OR=3.80) while, in Europe, northern countries had lowest frequencies of ANAs (OR=0.67) and Ro/La (OR=0.69). CONCLUSIONS: This study provides the first evidence of a strong influence of geolocation and ethnicity on the phenotype of primary SjS at diagnosis.
28937084 Primary Sjögren's syndrome complicated by anti-neutrophil cytoplasmic antibody-mediated c 2017 Sep Ocular and oral dryness are the hallmark of Sjögren's syndrome (SS). However, SS can be associated with a variety of complications, affecting organs such as the liver, kidneys, lungs, muscle, and nervous system. Renal involvement has been usually in the form of tubulointerstitial nephritis. However, glomerulonephritis is rare in primary SS. We report three clinical cases of SS with anti-neutrophil cytoplasmic antibody-mediated crescentic glomerulo-nephritis treated with prednisone and cyclophosphamide, with favorable outcome.
27390310 Severe Health-Related Quality of Life Impairment in Active Primary Sjögren's Syndrome and 2017 Apr OBJECTIVE: To identify the principal determinants of health-related quality of life (HRQOL) impairment in patients with active primary Sjögren's syndrome (SS) participating in a large therapeutic trial, Tolerance and Efficacy of Rituximab in Primary Sjögren's Syndrome (TEARS). METHODS: At the inclusion visit for the TEARS trial, 120 patients with active primary SS completed the Short Form 36 health survey (SF-36), a validated HRQOL assessment tool. Univariate then multivariate linear regression analyses were used to assess associations linking SF-36 physical and mental components to demographic data, patient-reported outcomes (symptom intensity assessments for dryness, pain, and fatigue, including the European League Against Rheumatism [EULAR] Sjögren's Syndrome Patient Reported Index [ESSPRI]), objective measures of dryness and autoimmunity, and physician evaluation of systemic activity (using the EULAR Sjögren's Syndrome Disease Activity Index [ESSDAI]). RESULTS: SF-36 scores indicated marked HRQOL impairments in our population with active primary SS. Approximately one-third of the patients had low, moderate, and high systemic activity according to the ESSDAI. ESSPRI and ESSDAI scores were moderately but significantly correlated. The factors most strongly associated with HRQOL impairment were patient-reported symptoms, best assessed using the ESSPRI, with pain and ocular dryness intensity showing independent associations with HRQOL. Conversely, systemic activity level was not associated with HRQOL impairment in multivariate analyses, even in the patient subset with ESSDAI values indicating moderate-to-high systemic activity. CONCLUSION: The cardinal symptoms of primary SS (dryness, pain, and fatigue, best assessed using the ESSPRI) are stronger predictors of HRQOL impairment than systemic involvement (assessed by the ESSDAI) and should be used as end points in future therapeutic trials focusing on patients' well-being. New consensual and data-driven response criteria are needed for primary SS studies.
28032844 Zaocys type II collagen regulates the balance of Treg/Th17 cells in mice with collagen-ind 2017 May OBJECTIVES: Zaocys type II collagen is an active collagen extracted from Zaocys that has been used to treat rheumatoid arthritis in China for over 1000 years. However, the mechanism still remains unknown. Therefore, we set out to investigate the inhibitory effect and possible mechanism of action of zaocys type II collagen on collagen-induced arthritis. METHODS: Collagen-induced arthritis was induced in C57BL/6 mice by immunisation with type II collagen. After immunisation, the mice were treated with Zaocys type II collagen. Clinical and histological scores were assessed and the cytokine levels in the serum and lymphocytes supernatant from the spleen and mesenteric lymph node were determined by enzyme-linked immune sorbent assay. The T-helper 17 cell and regulatory-T cell frequencies were analysed by flow cytometry and the expression of interest markers was examined by direct immuno-fluorescence. RESULTS: The arthritis score and severity of histological inflammation and cartilage destruction were dose-dependently reduced after treatment. The analysis results indicated that Zaocys type II collagen significantly increased the proportion of regulatory-T cells and lowered the T-helper 17 cells, it also increased the number of regulatory-T cells and conversely decreased the T-helper 17 cells in synovial tissue compared with the model group. Treatment also caused a higher level of transforming growth factor-β and a decreased production of interleukin -17A. CONCLUSIONS: The oral administration of Zaocys type II collagen potently suppressed the severity of collagen-induced arthritis by repairing the imbalance between regulatory-T cells and T-helper 17 cells, suggesting that it might be a promising candidate for the treatment of rheumatoid arthritis.
30650270 [Efficacy and Safety Evaluation of Liujin Runzao Concentrated Decoction in Treating Primar 2017 Feb Objective To evaluate the efficacy and safety of Liujin Runzao Concentrated Decoction (LRCD) for the treatment of primary Sjögren's syndrome (pSS). Methods Forty pSS patients with fluid depletion and distribution obstacles syndrome (FDDOS) were randomly assigned to the experimen- tal group and the control group according to 1:1 proportion. All patients received standard therapy: Radix Paeoniae alba total glycosides 600 mg, twice per day. Patients in the experimental group additionally took LRCD, 30 mL each time, twice per day. The therapeutic course for all was 4 weeks, and two courses for all. The improvement of dry mouth and dry eyes were comprehensively evaluated. Each outcome of composite index constitutions (integrals of dry eyes and dry mouth, salivary flow rate, Schirmer test) was respectively reported. Schirmer test and salivary flow rate were determined as well. Score of TCM syndrome, blood sedimentation,'immunoglobulin, and adverse drug reactions were observed. Results The effective rate of comprehensive effect for dry eyes and dry mouth improvement at the end of 8 weeks was 80% in the experimental group and 35% in the control group, with statistical difference (X² =8. 286, P <0. 05). As for the composition of comprehensive effect for dry eyes and dry mouth improvement: The score for dry eyes and dry mouth decreased in the two groups more after treatment than before treatment. The difference in pre-post treatment score for dry eyes and dry mouth at week 8 was higher in the experimental group than in the control group. The difference in pre-post treatment score at week 8 was 1. 71 (95% Cl: -0. 37 -3. 78) between the two groups (P <0. 05). The difference in pre-post treatment Schirmer test and salivary flow rate at week 8 was higher in the experimental group than in the control group, but with on statistical difference (P >0. 05). The difference in pre-post treatment Schirmer test and salivary flow rate at week 8 was 2. 74 mL/15 min (95% Cl: 0. 49 -4.98) and 0. 13 mm/5 min (95% Cl: 0. 92 -1. 23) between the two groups (P <0. 05). The score of TCM syndrome decreased more in the two groups, as compared with before treatment. The difference in pre-post treatment score of TCM syn- drome at week 8 was 1. 71 (95% CI: -1. 40 -4. 81) between the two groups (P >0. 05). One case of uri- nary tract infections occurred in the control group, while no obvious adverse event occurred in the exper- imental group. Conclusion Standard treatment combined LRCD showed better comprehensive effect for dry eyes and dry mouth in pSS patients with FDDOS, and was more safe.
28720215 Autoimmune meningitis and encephalitis in adult-onset still disease - Case report. 2017 Sep INTRODUCTION: Adult-onset Still disease (AOSD) is a rare systemic inflammatory disease of unknown cause. Its symptoms usually include persistent fever, fugitive salmon-colored rash, arthritis, sore throat (not specific), but it may also lead to internal organs' involvement, which presents with enlargement of the liver and spleen, swollen lymph nodes, carditis or pleuritis - potentially life-threatening complications. In rare cases, AOSD can cause aseptic meningitis or/and encephalitis. CASE PRESENTATION: We report a case of 31-year-old male patient, who was referred to neurological department for extending diagnostics of frontal lobes lesions with involvement of adjacent meninges. Abnormalities have been revealed in brain MRI, which was performed due to persistent headaches, visual disturbances, fever, fatigue and cognitive decline. Wide differential diagnosis was performed including laboratory findings, contrast enhanced MRI, MR spectroscopy, flow cytometry and finally brain biopsy to exclude neoplastic or infectious origin. Final diagnosis of autoimmune meningoencephalitis in adult-onset Still disease has been made. CONCLUSION: Adult-onset Still disease is a rare cause of inflammatory changes in central nervous system, which if diagnosed, may be treated successfully with steroids (commonly available agent), intravenous immunoglobulins or more specific immunomodulating regiments.
28815578 IL-17 polarization of MAIT cells is derived from the activation of two different pathways. 2017 Nov MAIT cells are expanded in salivary glands of patients with Sjogren's syndrome and are IL-17 polarized. IL-7 and IL-23 induce IL-17 production activating two different pathways: IL-7 stimulation induces in fact a significant STAT3 and HIF1alpha upregulation, conversely, IL-23 stimulation significantly induces RORc overexpression in MAIT cells of patients with Sjogren's syndrome.
31643860 Adalimumab. 2012 Adalimumab is a monoclonal antibody to human tumor necrosis factor (TNF) alpha which has potent antiinflammatory activity and is used in the therapy of severe rheumatoid arthritis and inflammatory bowel disease. Adalimumab has been linked to rare instances of idiosyncratic acute liver injury and is a potential cause of reactivation of hepatitis B.
30489709 2017 May The objective of this report is to provide a systematic review of the beneficial and harmful effects of sarilumab for the treatment of adults with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to one or more biologic or non-biologic disease-modifying antirheumatic drugs (DMARDs). [Table: see text]
28253339 Correction: The Expression of LIGHT Was Increased and the Expression of HVEM and BTLA Were 2017 [This corrects the article DOI: 10.1371/journal.pone.0155345.].
29278672 The initiation of autoimmunity at epithelial surfaces: a focus on rheumatoid arthritis and 2017 Nov It is well established that the autoantibodies that characterize both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are present systemically years before patients develop disease. In both these autoimmune rheumatic diseases, evidence is growing that local autoimmune processes occur at epithelial surfaces potentially initiating localized autoimmunity. For RA, these are mucosal surfaces including the oral mucosa, lung, and gut. At the oral mucosa and lung, risk factors such as periodontal disease and smoking may contribute to autoimmunity by driving the local generation of citrullinated autoantigens. For SLE, the skin may be integral in pathogenesis. It is proposed that defective clearance of apoptotic debris leads to initial innate immune responses preceding autoimmunity. Many tissues may be implicated but the frequency of skin disease, even without autoantibodies, and the role of UV light as a trigger suggest that keratinocytes may be a key site of initiation. In both diseases, a local break in immune tolerance could lead to systemic autoimmunity, and, in the gut, bacterial organisms that colonize the intestine may influence the localized gut immune response through T-cells and promote the development of systemic autoimmunity. In this review, we discuss the evidence for localized epithelial autoimmunity in those at risk of RA and SLE and early disease. Localized autoimmunity at the oral mucosa, lung, gut, and skin will be considered as potential initiating sites of ARD-related autoimmunity.
31643532 Chlorambucil. 2012 Chlorambucil is an orally administered alkylating agent which is currently used in the therapy of chronic lymphocytic leukemia, Hodgkin and non-Hodgkin lymphomas, and rarely in severe autoimmune conditions including rheumatoid arthritis, uveitis and nephrotic syndrome. Chlorambucil therapy has been associated with low rates of serum enzyme elevations during therapy and to rare instances of acute, clinically apparent injury.