Low-dose Methotrexate Research Articles

MTHFR Gene Polymorphism Association With Psoriatic Arthritis Risk and the Efficacy and Hepatotoxicity of Methotrexate in Psoriasis

AimsTo assess whether MTHFR rs1801131 and rs1801133 SNPs are associated with concomitant psoriatic arthritis (PsA) and investigate the efficacy and hepatotoxicity of MTX in patients with psoriasis in the Han Chinese population.MethodsThis prospective, single-arm, interventional study recruited a total of 309 patients with psoriasis, 163 with psoriatic arthritis and 146 without psoriatic arthritis, who completed a 12-week MTX treatment and 1,031 healthy controls. Patients' characteristics including age, gender, disease duration, height, weight, smoking status, alcohol consumption, medical history, disease severity and liver function test results were accessed and recorded. Single nucleotide polymorphism (SNP) genotyping of rs1801131 and rs1801133 in the MTHFR gene was performed.ResultsThe rs1801133 CC genotype was more frequent in patients with PsA than those with PsO and healthy controls (42.3% vs. 28.8% vs. 33.1%, p < 0.05). The 90% reduction from baseline PASI score (PASI 90) response rates to MTX were significantly higher in patients with the rs1801133 TT genotype than those with the CT and CC genotype (33.96% vs. 19.31% vs. 14.41%, OR = 2.76, p = 0.006). The rs1801133 CT+TT genotype was more frequent in PsA patients with abnormal liver function than in those with normal liver function (p < 0.05). In addition, patients with the rs1801131 CT genotype had lower PASI 75 response rates to MTX (OR = 0.49, p = 0.01), and lower risk of ALT elevation (OR = 0.46, p = 0.04).ConclusionsThis study provided some evidence for MTHFR polymorphism association with the risk of PsA and the efficacy and hepatotoxicity of the low-dose MTX in the Chinese population. Given the relatively small sample size and potentially missed diagnosis of PsA, the results from this study warrant further investigation.

Extracorporeal Treatment for Methotrexate Poisoning: Systematic Review and Recommendations from the EXTRIP Workgroup.

Methotrexate is used in the treatment of many malignancies, rheumatological diseases, and inflammatory bowel disease. Toxicity from use is associated with severe morbidity and mortality. Rescue treatments include intravenous hydration, folinic acid, and, in some centers, glucarpidase. We conducted systematic reviews of the literature following published EXtracorporeal TReatments In Poisoning (EXTRIP) methods to determine the utility of extracorporeal treatments in the management of methotrexate toxicity. The quality of the evidence and the strength of recommendations (either "strong" or "weak/conditional") were graded according to the GRADE approach. A formal voting process using a modified Delphi method assessed the level of agreement between panelists on the final recommendations. A total of 92 articles met inclusion criteria. Toxicokinetic data were available on 90 patients (89 with impaired kidney function). Methotrexate was considered to be moderately dialyzable by intermittent hemodialysis. Data were available for clinical analysis on 109 patients (high-dose methotrexate [>0.5 g/m2]: 91 patients; low-dose [≤0.5 g/m2]: 18). Overall mortality in these publications was 19.5% and 26.7% in those with high-dose and low-dose methotrexate-related toxicity, respectively. Although one observational study reported lower mortality in patients treated with glucarpidase compared with those treated with hemodialysis, there were important limitations in the study. For patients with severe methotrexate toxicity receiving standard care, the EXTRIP workgroup: (1) suggested against extracorporeal treatments when glucarpidase is not administered; (2) recommended against extracorporeal treatments when glucarpidase is administered; and (3) recommended against extracorporeal treatments instead of administering glucarpidase. The quality of evidence for these recommendations was very low. Rationales for these recommendations included: (1) extracorporeal treatments mainly remove drugs in the intravascular compartment, whereas methotrexate rapidly distributes into cells; (2) extracorporeal treatments remove folinic acid; (3) in rare cases where fast removal of methotrexate is required, glucarpidase will outperform any extracorporeal treatment; and (4) extracorporeal treatments do not appear to reduce the incidence and magnitude of methotrexate toxicity.

Using FibroScan to Assess for the Development of Liver Fibrosis in Patients With Arthritis on Methotrexate: A Single-center Experience.

Methotrexate (MTX) is often the primary medication to treat various rheumatic diseases (RDs) because of its low cost and its demonstrated efficacy in controlling disease activity. However, a concern has been the potential for hepatic fibrosis associated with long-term MTX usage. This study investigated the association between cumulative MTX intake and development of liver fibrosis by utilizing noninvasive transient elastography (FibroScan). All patients with inflammatory arthritis treated with MTX were offered screening with FibroScan. A certified technician measured liver stiffness after patients adhered to a fast. Relevant clinical information was obtained by patient survey and medical records review. The population was divided into quartiles based on participants' cumulative dosage of MTX. Five hundred twenty patients with RD were included in this study. The prevalence of stages F3 or F4 liver fibrosis was 13.3% in the control group and 12.7% in the entire sample. Compared with subgroup 1 (control with cumulative MTX exposure of ≤ 499 mg), MTX subgroups 2 to 4 were not significantly correlated with higher FibroScan scores (P = 0.82, 0.59, and 0.18, respectively). In multivariable linear regression analysis, statistically significant factors for liver stiffness were BMI, waist circumference, male sex, and age. No significant correlation between the cumulative MTX dosage and liver stiffness, even at high MTX doses, was observed. The analyses showed significant correlations between the FibroScan score and BMI. These findings were reassuring in that current rheumatology practice appears to be safe and effective in screening for liver fibrosis in patients on long-term low-dose MTX therapy.

Neuropsychiatric adverse drug reactions associated with low dose methotrexate in rheumatoid arthritis patients

Background: Neuropsychiatric adverse drug reactions (NPADRs) are not commonly associated with low dose methotrexate (LDMTX) in patients with rheumatoid arthritis (RA). Research design and methods: In this case series assessment, we described the nature and frequency of NPADRs with LDMTX in the Dutch DREAM-RA registry, including causality of NPADRs, the impact on further LDMTX treatment and the impact on patient reported Health Related Quality of Life (HRQoL). Results: A total of 71 NPADRs (frequency 6.8%) associated with LDMTX were captured in the DREAM-RA registry. NPADRs were registered for 62 (5.9%) out of 1048 patients with 10.9 NPADRs per 1000 patient years. Headache, dizziness and depression were most frequently reported. The causality was considered probable for 67 NPADRs (94.4%) and definite for 1 NPADR (1.4%). NPADRs led to LDMTX withdrawal in 34 cases (47.9%) and was not restarted in 16 cases (47.1%). Median mental HRQoL was significantly decreased around the occurrence of the NPADR and remained significantly lower after the event. Median physical HRQoL was not significantly affected. Conclusions: Knowledge on the nature, frequency and impact of the demonstrated NPADRs during LDMTX therapy will enhance attention towards these potential ADRs allowing better risk assessment and communication to patients.

Factors influencing methotrexate and methotrexate polyglutamate in patients with rheumatoid arthritis: a systematic review of population pharmacokinetics.

Low dose methotrexate (MTX) is commonly used in the treatment of rheumatoid arthritis. The clinical effect is mediated by its metabolite, methotrexate polyglutamate (MTX-PGn). The drug exhibits high interindividual pharmacokinetic variability and the optimal MTX dose is different among individuals. Thus, several MTX population pharmacokinetic (PopPK) models were developed to characterize factors affecting MTX pharmacokinetic variability. This review summarizes significant predictors for MTX pharmacokinetics and identifies knowledge gaps to be further examined. A total of 359 articles were identified from a systematic search of four databases: PubMed, Science Direct, and CINAHL Complete. Of these eight studies were included. Most studies investigated influential factors on MTX pharmacokinetics, but information on MTX-PGn is limited, with only one study performing a parent-metabolite (MTX-PG3) model. MTX pharmacokinetics was described using a two-compartment model with first-order elimination in most studies, with the MTX clearance ranging from 6.94 to 12.39L/h. Significant predictors influencing MTX clearance included weight, creatinine clearance, sex, OATP1B3 polymorphism, and MTX multiple dosing. While body mass index and red blood cell counts were significant predictors for MTX-PG3 clearance. Providing that MTX-PGn plays a crucial role in clinical effect, further studies should determine other factors affecting MTX-PGn as well as its relationship with clinical response.

Primary Cutaneous Anaplastic Large Cell Lymphoma: A Rare Case Report in a Young Soldier

Primary cutaneous anaplastic large cell lymphoma (C-ALCL) usually presents with scaly patches or plaques and nodular skin lesion. Most people with C-ALCL have indolent (i.e., chronic, slow growing) lymphomas which are treatable and curable. Histologically cutaneous anaplastic large cell lymphoma is diffuse, non-epidermotropic with anaplastic large lymphoid cells. Immunohistochemically most of the tumor cells express CD30 antigen and prognosis is good. Excision of the lesion followed by radiotherapy and/or low dose methotrexate are the treatment of choice. The present study reports a rare case of 30-year-old-man presenting with multifocal papulonodular lesions in the right forearm and biopsy confirmed that the case is cutaneous anaplastic large-cell lymphoma. He was treated with low dose of methotrexate and patient became completely cured without any residual disease. JAFMC Bangladesh. Vol 17, No 1 (June) 2021: 46-48

Medication Dosing Error Leading to Potentially Lethal Methotrexate Toxicity

Pancytopenia is a rare consequence of rheumatoid arthritis treatment with low-dose methotrexate. Several literature reviews discovered earlier examples of severe pancytopenia caused by low- dose or dosage error of methotrexate. We discuss the case of a 67-year-old ACPA (Anti- citrullinated protein/peptide antibody) positive rheumatoid arthritis patient who had severe pancytopenia and oral mucositis as a result of methotrexate toxicity. To reduce medication dosing errors, we highlight its uncommon dose schedule.

Medication Dosing Error Leading to Potentially Lethal Methotrexate Toxicity

Pancytopenia is a rare consequence of rheumatoid arthritis treatment with low-dose methotrexate. Several literature reviews discovered earlier examples of severe pancytopenia caused by low- dose or dosage error of methotrexate. We discuss the case of a 67-year-old ACPA (Anti- citrullinated protein/peptide antibody) positive rheumatoid arthritis patient who had severe pancytopenia and oral mucositis as a result of methotrexate toxicity. To reduce medication dosing errors, we highlight its uncommon dose schedule.

Methotrexate-loaded nanoparticles ameliorate experimental model of autoimmune arthritis by regulating the balance of interleukin-17-producing T cells and regulatory T cells

BackgroundRheumatoid arthritis (RA) is a progressive systemic autoimmune disease that is characterized by infiltration of inflammatory cells into the hyperplastic synovial tissue, resulting in subsequent destruction of adjacent articular cartilage and bone. Methotrexate (MTX), the first conventional disease-modifying antirheumatic drug (DMARD), could alleviate articular damage in RA and is implicated in humoral and cellular immune responses. However, MTX has several side effects, so efficient delivery of low-dose MTX is important.MethodsTo investigate the efficacy of MTX-loaded nanoparticles (MTX-NPs) against experimental model of RA, free MTX or MTX-NPs were administered as subcutaneous route to mice with collagen-induced arthritis (CIA) at 3 weeks after CII immunization. The levels of inflammatory factors in tissues were determined by immunohistochemistry, confocal microscopy, real-time PCR, and flow cytometry.ResultsMTX-NPs ameliorated arthritic severity and joint destruction in collagen-induced arthritis (CIA) mice compared to free MTX-treated CIA mice. The levels of inflammatory cytokines, including interleukin (IL)-1β, tumor necrosis factor-α, and vascular endothelial growth factor, were reduced in MTX-NPs-treated mice. Number of CD4 + IL-17 + cells decreased whereas the number of CD4 + CD25 + Foxp3 + cells increased in spleens from MTX- NPs-treated CIA mice compared to MTX-treated CIA mice. The frequency of CD19 + CD25 + Foxp3 + regulatory B cells increased in ex vivo splenocytes from MTX-loaded NPs-treated CIA mice compared to MTX-treated CIA mice.ConclusionThe results suggest that MTX-loaded NPs have therapeutic potential for RA.

Low-dose methotrexate use in skin diseases: An old drug with new purposes

Low-dose methotrexate use in skin diseases: An old drug with new purposes

Clinical Characteristics and Efficacy of Adalimumab and Low-Dose Methotrexate Combination Therapy in Patients With Vogt-Koyanagi-Harada Disease.

This retrospective study investigated the clinical characteristics and efficacy of adalimumab and low-dose methotrexate combination therapy in patients with Vogt–Koyanagi–Harada disease who were treated at Hiroshima University from February 2012 to May 2021. The patients' demographics, clinical features at administration of immunosuppressive therapy, steroid-sparing immunosuppressive therapy, side effects, and relapses were recorded. The efficacies of steroid-sparing immunosuppressive therapy (methotrexate, cyclosporine A, adalimumab, and adalimumab and methotrexate combination therapy) were analyzed. Among 62 patients, the median age at diagnosis was 47 years and the median duration of uveitis was 51 months. Systemic corticosteroid therapy was administered to 93.5% of patients (n = 58). Thirty-four patients (54.8%) were treated with steroid-sparing immunosuppressive therapy. Methotrexate and cyclosporine A were administered to 12 and 22 patients, respectively; relapse occurred in 50.0% and 22.7% of the patients, respectively. Discontinuation of cyclosporine A was required in 63.6% of patients because of side effects. Adalimumab was administered to 14 patients. Recurrence occurred in 11 patients, requiring methotrexate concomitantly. The mean dose of methotrexate at inflammatory quiescence after side effect-related dose decrease was 8.0 mg/week (0.13 mg/kg). The median duration of combination therapy without recurrence was 20 months. There were no serious adverse events during adalimumab therapy. A high relapse rate was observed in patients receiving methotrexate; a high rate of side effects requiring discontinuation was observed in patients receiving Cyclosporine A. Patients with late-stage Vogt–Koyanagi–Harada disease may achieve better control with adalimumab and methotrexate combination therapy.

A Gastrointestinal Toxicity during Low-Dose Methotrexate Treatment in Two Pediatric Patients with Acute Lymphoblastic Leukemia

Low-dose Methotrexate (LD-MTX) and 6-mercaptopurine (6-MP) are used in the maintenance phase of treatment of childhood acute lymphoblastic leukaemia. It was reported that individuals with reduced activity of two of the enzymes involved in the pathway of purine metabolism, thiopurine S-methyltransferase (TPMT) and nudix hydrolase 15 (NUDT15), will be exposed to higher levels of active metabolites and will be at higher risk of side effects, such as myelosupression. Therefore, dosing recommendations for 6-MP based on TPMT and NUDT15 genotype have been approved by FDA and have been published by the Clinical Pharmacogenetics Implementation Consortium and the Ditch Working Group. Though several studies were conducted on the toxicity of LD and HD-MTX in childhood ALL patients, none of the genetic markers so far have been used in MTX therapy protocols due to the lack of a clear association with the response and/or toxicity. We describe two pediatric patients who suffered from gastrointestinal toxicity following peroral administration of LD-MTX during maintenance therapy of ALL that diminished after switching to parenteral administration of the drug.

Is there still a place for methotrexate in severe psoriatic arthritis?

The management of psoriatic arthritis (PsA) has long been equated with that of rheumatoid arthritis (RA), particularly because methotrexate (MTX) was found efficient in RA in the 1990s. However, results of collective evidence-based medicine, included and argued in this narrative review, do not currently support the use of MTX as first-line therapy in severe PsA. A recent Cochrane systematic review examining the efficacy of MTX in PsA concluded that low-dose MTX was only slightly more effective than placebo. Questions about a structural effect of MTX in PsA remains non-elucidated. Even if tolerance data on MTX are more consensual and adverse events generally non-severe, subjective side effects such as fatigue might lead to MTX withdrawal based on the patient’s decision. PsA patients with axial disease, radiographic lesions, and extensive and disabling skin or joint involvement should receive early treatment with targeted therapy and no longer with MTX. Finally, the usefulness of MTX combined with targeted therapies is limited. MTX does not affect efficacy but only seems to increase the therapeutic maintenance of monoclonal TNF inhibitors. This narrative review may help clarify the place of MTX in PsA management. It allows for reflection on the evolution of current concepts and practices.

Patient-reported adverse effects when switching from oral to subcutaneous administration of methotrexate: A prospective, multicenter, paired cohort study

To the Editor: Many inflammatory skin disorders can be treated with weekly low-dose oral methotrexate (oMTX). However, nausea (25%) and asthenia (15%) are common adverse effects (AEs) that reduce drug survival. Changing from oral to subcutaneous methotrexate (scMTX) may reduce the AEs, but the results of a few prior studies are inconsistent.1,2

New developments in osteoarthritis pharmacological therapies.

OA is an increasingly common, painful condition with complex aetiology and limited therapies. Approaches to expanding our therapeutic armamentarium have included repurposing existing therapies used for other rheumatological conditions, modifying existing OA preparations to enhance their benefits, and identifying new therapeutics. HCQ and low-dose MTX have been unsuccessful in improving hand OA pain or reducing structural progression. Anti-IL-6 and anti-GM-CSF also did not improve symptoms in hand OA trials, but IL-1 remains an intriguing target for large-joint OA, based on reduced joint replacements in a post hoc analysis from a large cardiovascular disease trial. The peripheral nociceptive pathway appears an attractive target, with mAbs to nerve growth factor and IA capsaicin demonstrating efficacy; tropomyosin receptor kinase A inhibitors are at an earlier stage of development. Limited evidence suggests pharmacological therapies can modify cartilage and bone structural progression, though evidence of synchronous symptom benefits are lacking.

Drug Therapy and Literature Review of Low dose Methotrexate in the Treatment of Bone Marrow Suppression due to Ectopic Pregnancy

Drug Therapy and Literature Review of Low dose Methotrexate in the Treatment of Bone Marrow Suppression due to Ectopic Pregnancy

Pharmacomicrobiology of Methotrexate in Rheumatoid Arthritis: Gut Microbiome as Predictor of Therapeutic Response.

Rheumatoid arthritis (RA) is a disabling autoimmune disease with invasive arthritis as the main manifestation and synovitis as the basic pathological change, which can cause progressive destruction of articular cartilage and bone, ultimately leading to joint deformity and loss of function. Since its introduction in the 1980s and its widespread use in the treatment of RA, low-dose methotrexate (MTX) therapy has dramatically changed the course and outcome of RA treatment. The clinical use of this drug will be more rational with a better understanding of the pharmacology, anti-inflammatory mechanisms of action and adverse reaction about it. At present, the current clinical status of newly diagnosed RA is that MTX is initiated first regardless of the patients’ suitability. But up to 50% of patients could not reach adequate clinical efficacy or have severe adverse events. Prior to drug initiation, a prognostic tool for treatment response is lacking, which is thought to be the most important cause of the situation. A growing body of studies have shown that differences in microbial metagenomes (including bacterial strains, genes, enzymes, proteins and/or metabolites) in the gastrointestinal tract of RA patients may at least partially determine their bioavailability and/or subsequent response to MTX. Based on this, some researchers established a random forest model to predict whether different RA patients (with different gut microbiome) would respond to MTX. Of course, MTX, in turn, alters the gut microbiome in a dose-dependent manner. The interaction between drugs and microorganisms is called pharmacomicrobiology. Then, the concept of precision medicine has been raised. In this view, we summarize the characteristics and anti-inflammatory mechanisms of MTX and highlight the interaction between gut microbiome and MTX aiming to find the optimal treatment for patients according to individual differences and discuss the application and prospect of precision medicine.

ML-13 Primary central nervous system malignant lymphoma in a patient with rheumatoid arthritis receiving tocilizumab

Background: Although the risk of developing malignant lymphoma is higher in patients with rheumatoid arthritis (RA) than in the general population, the occurrence of primary central nervous system lymphoma (PCNSL) in patients with RA is extremely rare. In recent years, there has been concern that biological disease-modifying antirheumatic drugs (DMRADs), which are widely administered to patients with RA, may increase the risk of developing cancer. We report the first case of PCNSL in a patient with RA who was treated with the biological DMRADs, tocilizumab. Case description: A 70-year-old man, who was diagnosed with RA in 2010 was treated with low-dose methotrexate from 2010 to 2015. He was started on tocilizumab in 2012. In 2018, he suffered from gait disturbance and was diagnosed with lumbar spinal stenosis. He underwent L2/3 posterior fusion surgery, but his paraplegia gradually deteriorated. Two months after the surgery, a head Gd-MRI showed multiple contrast-enhanced lesions in the basal ganglia and brain stem. A stereotactic brain biopsy was performed and DLBCL was diagnosed, and finally PCNSL was diagnosed because of no neoplastic lesions in other organs. He was treated with 5 courses of MTX 3.5g/m2 with rituximab and has been in remission for 23 months. He has maintained an independent life with residual paraplegia, but his ADLs gradually worsened. He was restarted on tocilizumab with a diagnosis of worsening RA. Conclusion: Low-dose methotrexate and biological DMRADs including tocilizumab, have been concerned to increase the risk of cancer in patients with RA, but there is no solid evidence. Since it has been a short time since the use of biological DMRADs, further accumulation of cases and careful follow-up are necessary.

O08 A case of juvenile systemic lupus erythematosus with pyrexia of unknown origin

Case report - IntroductionAn 18-year-old young man with diagnosis of Juvenile SLE with lupus nephritis maintained in remission on Mycophenolate Mofetil (MMF), presented with high-grade fever without focus close to his 18th birthday. History or examination did not point to any focus of infection, but blood tests showed systemic inflammation. Extensive investigations, including extended infection screen and bone marrow aspiration, were negative. His blood tests were suggestive of macrophage activation syndrome with no clinical or laboratory evidence of flare of lupus. MRI scan revealed extensive para-aortic lymphadenopathy and a diagnosis of classical Hodgkin's lymphoma confirmed on lymph node biopsy.Case report - Case descriptionInterestingly he first presented with fever and cervical lymphadenopathy at 13 years of age to local hospital, when a biopsy had revealed lymphoma but the diagnosis was changed to SLE following review at tertiary hospital. He was started on steroids and low-dose methotrexate. He later developed facial swelling, abdominal distension and groin swelling, following which he was referred to tertiary renal centre. His examination revealed scarring malar rash, anaemia, ankle and scrotal oedema, ascites and pleural effusion. His investigations showed anaemia, thrombocytopaenia, ESR over 100mm/hour, hypoalbuminaemia, low complement levels, positive ANA and double-stranded DNA. He had nephrotic range proteinuria and renal biopsy showed Class V lupus nephritis. He was treated with intravenous and later weaning dose of oral steroids and started on MMF. He remained in remission on a stable dose of MMF, except for brief flare of proteinuria, which settled with short course of oral steroids.A few months before his eighteenth birthday, he presented to local hospital with recurrent episodes of high-grade fever with no clear focus. He was twice managed with broad spectrum antibiotics, despite negative septic screen and an extended infection screen including viral PCRs and IGRA for tuberculosis. He had no focal symptoms or symptoms to suggest flare of underlying lupus, but had loss of appetite and loss of weight. He developed splenomegaly with increasing inflammatory markers and fall in all cell lines of full blood count with deranged coagulation. He satisfied the clinical and laboratory criteria of the preliminary Diagnostic Guidelines for Macrophage Activation Syndrome in JSLE (2009), following which he was commenced on three days of IV methylprednisolone following normal bone marrow aspirate. However, fever recurred after initial response and MRI scan revealed mediastinal and para-aortic lymphadenopathy, and a diagnosis of classical Hodgkin's lymphoma was confirmed on lymph node biopsy.Case report - DiscussionThis young man initially presented with fever and cervical lymphadenopathy, when a diagnosis of lymphoma was made. Yet, following review of the biopsy at the local tertiary centre and the abnormal immunological profile, a diagnosis of lupus was made. He then developed nephrotic syndrome, when a diagnosis of lupus nephritis was confirmed on biopsy. Other clinical and laboratory profile (raised ESR, hypocomplementeamia, serositis and haematological parameters) corroborated the diagnosis. He responded well to steroids and immunosuppression, when he presented with fever again. He had no evidence of flare of underlying lupus or any infection, but blood tests and splenomegaly pointed to macrophage activation syndrome (MAS). A negative bone marrow examination suggested that pancytopaenia was unlikely to be due to bone marrow infiltration, which is why he was treated with steroids. Yet, when fever recurred, MRI was arranged to investigate further, which eventually led to revelation of lymphadenopathy and biopsy, which eventually led to the right diagnosis. Another dilemma was if his MAS was to respond to steroids, whether we should change his baseline immunosuppression which had worked well so far for him and if we chose to, what would be the best agent.Case report - Key learning points1. Although extremely uncommon, children and young people with rheumatic diseases can develop malignancy, which may be unrelated to the primary condition or the therapeutic agents used. Unexplained symptoms in the absence of flare of underlying condition and with infections ruled out, warrant extension of investigations to rule out an underlying malignancy.2. Diagnosis of secondary MAS in a rheumatological condition without any evidence of flare of the underlying condition should be viewed as suspicious and warrants more investigations to rule out other causes.3. In patients who develop MAS, there are very few agents which work for both lupus and MAS, choosing an agent which treats both conditions is challenging.

O04 Orbital lymphoma in a 72-year-old lady with rheumatoid arthritis: an argument for rituximab

O04 Orbital lymphoma in a 72-year-old lady with rheumatoid arthritis: an argument for rituximab