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Rheumatic and musculoskeletal diseases (RMDs) represent a multitude of degenerative, inflammatory and auto-immune conditions affecting millions of people worldwide. Persons with these diseases may potentially experience severe chronic pain, joint damage, increasing disability and even death. With an increasingly ageing population, the prevalence and burden of RMDs are predicted to increase, placing greater demands on the global practice of rheumatology and related healthcare budgets. Effective treatment of RMDs currently faces a number of challenges in both the developed and developing world, and individual countries may face more specific local challenges. However, limited understanding of the burden of RMDs amongst public health professionals and policy-makers means that these diseases are often not considered a public health priority. The objective of this review is to increase awareness of the RMDs and to identify opportunities to address RMD challenges on both a local and global scale. On 26 September 2014, rheumatology experts from five different continents met at the World Forum on Rheumatic and Musculoskeletal Diseases (WFRMD) to discuss and identify some key challenges for the RMDs community today. The outcomes are presented in this review, focusing on access to rheumatology services, diagnostics and therapies, rheumatology education and training and on clinical trials, as well as investigator-initiated and epidemiological research. The long-term vision of the WFRMD is to increase perception of the RMDs as a major burden to society and to explore potential opportunities to improve global and local RMD care.

Rheumatic and musculoskeletal diseases (RMDs) encompass a spectrum of degenerative, inflammatory conditions predominantly affecting the joints. They are a leading cause of disability worldwide and an enormous socioeconomic burden. However, worldwide deficiencies in adult and paediatric RMD knowledge among medical school graduates and primary care physicians (PCPs) persist. In October 2017, the World Forum on Rheumatic and Musculoskeletal Diseases (WFRMD), an international think tank of RMD and related experts, met to discuss key challenges and opportunities in undergraduate RMD education. Topics included needs analysis, curriculum content, interprofessional education, teaching and learning methods, implementation, assessment and course evaluation and professional formation/career development, which formed a framework for this white paper. We highlight a need for all medical graduates to attain a basic level of RMD knowledge and competency to enable them to confidently diagnose, treat/manage or refer patients. The importance of attracting more medical students to a career in rheumatology, and the indisputable value of integrated, multidisciplinary and multiprofessional care are also discussed. We conclude that RMD teaching for the future will need to address what is being taught, but also where, why and to whom, to ensure that healthcare providers deliver the best patient care possible in their local setting.

No clear consensus exists on whether methotrexate (MTX) should be continued or whether this therapy should be discontinued for a few weeks in patients with rheumatoid arthritis (RA) undergoing surgery. Continued MTX therapy may impair wound healing, but discontinuation of the therapy may increase the risk of flares. In this article we review published data on the perioperative management of MTX in patients with RA undergoing elective orthopedic surgery. Eight papers on this topic could be identified. These studies compare continued vs. discontinued MTX therapy or MTX therapy vs. therapies other than MTX. Summing up the published data, continued MTX therapy appears to be safe perioperatively and seems also to be associated with a reduced risk of flares. None of the examined papers addresses the issue of safety in connection with comorbidities, age or high doses of MTX.

Introduction Bone marrow edema (BME) is one of the main imaging characteristics of juvenile idiopathic arthritis (JIA) in children and rheumatoid arthritis (RA) in adult. Previous studies have shown that BME occurred in approximately 64% of adults with RA and was a key predictor of poor prognosis. But BME with JIA has not been of great concern. Therefore, we evaluated the prevalence, characteristics, and prognosis of knee joint BME in children with JIA. Methods In this retrospective study, we included children with JIA and knee joint involvement from January 2017 to December 2019. BME was evaluated according to the Juvenile Arthritis MRI Scoring system. Clinical characteristics were compared between the BME group and the non-BME group. The characteristics and prognosis of the BME were observed. Results A total of 128 children with 136 knee joint MRI data were identified, with 37 knee joints (27.2%) having BME. BME has positive correlation with synovial hypertrophy (Rs = 0.562, p = 0.019). There were significant differences in age (p = 0.010) and disease duration (p = 0.013) between the BME and non-BME groups. BME was found to be more common in older children and the patients with long duration of disease. Locations with BME were the lateral tibial plateau (17/37, 45.9%), the lateral weight-bearing femur (16/37, 43.2%), the medial tibial plateau and the medial femoral condyle (both with 15/37, 40.5%), and the medial weight-bearing femur (12/37, 32.4%). The lateral femoral condyle and both the lateral and medial sides of the patella were rarely involved. Of the 15 BME joints with the MRI follow-up data (interval 6.5 ± 3.0 months), the lesions disappeared or improved within 12 months after the treatments in 13 (86.7%) joints. Conclusions The prevalence of knee BME in JIA was 27.2%. There was positive correlation between BME and synovial hypertrophy. Older children and children with long disease duration had a higher risk for BME, which was commonly a late presentation and more likely involved the weight-bearing surfaces of the joint. The overall prognosis was satisfactory after the standard treatments. Key Points• To the best of our knowledge, this paper is the first one to investigate the MRI manifestation in JIA focus on knee BME sign.

Osteoarthritis (OA) is a common degenerative condition leading to significant pain, functional limitation, and economic loss. Generalized OA (GOA) is associated with greater morbidity and accounts for 5-25% of total OA cases depending on definition used. This paper aims to determine the frequency and pattern of GOA, compare clinical and laboratory parameters of GOA and non-GOA subjects, then identify independent associations of GOA among Nigerians with knee OA.A cross-sectional study of 180 knee OA patients with knee and generalized OA defined using ACR criteria. Questionnaire administration was followed by physical examination and appropriate radiographs. Data was summarized using tables and figures. Multivariate regression was done to identify independent GOA associations with statistical significance p0.05. Ethical approval was obtained for the study.There were 180 participants with mean age 59.7±9.1 years. Twenty-eight patients (15.6%) had GOA of which 26 were female. The hip/knee/spine pattern was the commonest while hand OA was rare. Comparisons showed that GOA patients were significantly older with longer pain duration, higher pain score, more Heberden's nodes, and greater fatigue. There were no significant differences between both groups in levels of inflammatory markers and other laboratory parameters. Further analysis identified joint stiffness as the only independent association of GOA (OR 3.34, p=0.01).A 15.6% frequency of GOA was identified among knee OA sufferers with the hip/knee/spine pattern most frequent. Nigerians with GOA are predominantly females with a large joint phenotype. Joint stiffness was the only independent association of GOA observed. Key Points • Generalized osteoarthritis occurs in 15.6% of Nigerian patients with knee osteoarthritis. • Females are predominantly affected with a large joint phenotype involving the hip/knee/spine. • Joint stiffness is an independent association of generalized osteoarthritis.

Objective This paper is aimed at investigating the clinical characteristics of primary Sjogren’s syndrome (pSS) with lymphocytic interstitial pneumonia (LIP). Methods The demographic data, clinical manifestations, laboratory and radiological findings, treatment, and prognosis from 15 cases of pSS-LIP patients were retrospectively analyzed. The data were compared with t test, χ2 test, and Pearson/Spearman correlation analysis. Results (1) Fifteen cases of patients with pSS-LIP are all females (100%). Compared with pSS with interstitial lung disease(pSS-ILD) patients, the incidence of dry cough, dental caries is higher in pSS-LIP patients. The incidence of shortness of breath, weight loss, and crackles is lower in pSS-LIP patients than that of pSS-ILD patients. (2) Compared with pSS-ILD patients, pSS-LIP patients had higher percentage of patients with ANA, anti-SSA52KD antibody, anti-SSA60KD antibody, and anti-SSB antibody, and the higher concentration of serum globulin. (3) Compared with pSS-ILD patients, the frequency of obstructive ventilation dysfunction is significantly higher and the frequency of diffusion dysfunction is significantly lower in pSS-LIP patients. (4) The most frequent HRCT findings in patients with pSS-LIP is cysts (100%), followed by ground-glass opacities (73.3%), nodular shadow (73.3%) among the pSS-LIP patients. Compared with PSS-ILD patients, the incidence of pulmonary nodule shadow is significantly higher in PSS-LIP patients, while that of grid shadow was significantly lower. (5) Compared with the baseline, the sum of the number, maximum diameter, and diameter of cysts in three levels of pSS-LIP patients showed an increasing trend after treatment. (6) Correlation analysis: The changes of ground-glass opacities were positively correlated with using GC or not, and those were negatively correlated with the dose of GC treatment. Besides, there is a positive correlation between the annual change rate of the maximum diameter of cysts (△Ømax1/t) and the use of CTX; there is a positive correlation between the annual change rate of the total diameter of cysts (△Øsum1/t) and the use of CTX. Conclusion To the patients of pSS-LIP, female were more common than male, and the onset of LIP was usually more insidious. Hyperglobulinemia and anti-SSA antibody were more prominent in patients with pSS-LIP. Pulmonary function showed the higher rate of obstructive ventilation dysfunction and the lower rate of diffusion dysfunction. The appearance of ground-glass opacities in pSS-LIP patients suggests that the infiltration of inflammatory cells increases, which may cause airway compression, the expansion of terminal bronchioles, and the formation of cysts. The more ground-glass opacities appear earlier, and the more appearance of new cysts later. Therapy with glucocorticoid may be effective on the ground-glass opacity during acute stage, and therapy with cyclophosphamide may be effective on the cysts during chronic stage. The heavier ground-glass opacity is at baseline, the more likely it will recur during maintenance treatment. So follow-up closely is needed.Key Points• It is the first clinical study with more cases of patients with pSS-LIP.• Female and hyperglobulinemia and anti-SSA antibody were more prominent in patients with pSS-LIP.• Pulmonary function showed the higher rate of obstructive ventilation dysfunction and the lower rate of diffusion dysfunction.• Therapy with glucocorticoid may be effective on the ground-glass opacity during acute stage, and therapy with cyclophosphamide may be effective on the cysts during chronic stage.

The purpose of this study was to compare and contrast the prevalence of rheumatoid arthritis in Northern Alberta estimated by health administrative data and data from a rheumatologist-based prescription database.The study was performed using administrative health data from the province of Alberta through the local health authority. The cases and population identified in the database were reported from the year 2016. Rheumatology prescribing data was accessed through the Physician Learning Program and based on Alberta health billing data of actively practicing rheumatologists between the years 2012 and 2016. Ethics was provided by the Conjoint Health Research Ethics Boards at the University of Calgary (REB 13-0459).The total population of the area examined was determined to be 2,086,181. The administrative health database identified 42,354 cases of RA based on their case definition with a prevalence of 2.08%. Based on rheumatologist diagnosis and prescribing data, the number of cases identified was 11,273 cases of RA with a prevalence of 0.542%. The average percentage of identified RA patients being seen by a rheumatologist was determined to be 26.7% with the range of 19.8 to 39.9%.In conclusion, this study compares and contrasts the prevalence of rheumatoid arthritis reported by administrative data versus identification by specialists. Our study again illustrates that accuracy of case definitions when studying chronic conditions such as rheumatoid arthritis is paramount. The results also suggest a lack of access to rheumatologist services in Northern Alberta and reiterate the need for ongoing recruitment of new rheumatologists as has been highlighted previously. Key Points • The main contribution of this paper is to compare and contrast the prevalence of rheumatoid arthritis as reported by administrative data versus identification by specialists. • Our study also shows the distribution of rheumatoid arthritis in a large geographical area and illustrates a lack of access to subspecialty care in certain regions.

To elicit and compare preferences of patients and first-degree relatives and rheumatologists for preventive treatments for rheumatoid arthritis, understand the influence of shared decision-making, and predict the probability of uptake of the preventive treatments currently being studied.An online discrete choice experiment was completed by patients and their first-degree relatives and rheumatologists. Results were analysed using mixed logit model to estimate preferences for the key features of treatments. Preferences for features of treatments were used to predict the probability of uptake of seven preventive treatment options.A total of 108 potential recipients (78 patients and 30 of their first-degree relatives) and 39 rheumatologists completed the survey. Preferences of patients/first-degree relatives and rheumatologists were similar (shared decision-making was most important, followed by the risk of side effects and potential benefit), but subtle differences existed; rheumatologists placed greater importance on certainty in evidence than patients/first-degree relatives, who felt that how a treatment was taken was more important. Predicted uptake suggested that 38% (95% CI 19%, 58%) of patients/first-degree relatives would not take a preventive treatment, compared with 12% (95% CI - 4%, 27%) of rheumatologists. A consistent finding across all groups was a preference for non-biologic disease-modifying anti-rheumatic drugs.Only relatively safe options for preventive treatment are likely to be acceptable to at-risk populations. This study of preventive treatments highlights that the preferences of physicians and recipients of treatment should take a central role in the design of clinical studies as well as in decisions to initiate treatments. Key Points • This paper is the first to compare preferences for preventive treatments between rheumatologists and patients and at-risk individuals. • The results of this study indicate that patients and at-risk individuals, as well as rheumatologists, are likely to prefer the safest options as preventive treatment, even if the potential benefit of these is lower. • Although preferences of patients and at-risk individuals are similar to those of rheumatologists, the choice of preventive treatment may differ between groups; this is important as shared decision-making was a critical factor in treatment decision-making. • Preferences of physicians and recipients of treatment should take a central role in the design of clinical studies as well as in decisions to initiate treatments.

Chronic fatigue syndrome (CFS) is a heterogeneous disease which presents with pronounced disabling fatigue, sleep disturbances, and cognitive impairment that negatively affects patients' functional capability. CFS remains a poorly defined entity and its etiology is still in question. CFS is neither a novel diagnosis nor a new medical condition. From as early as the eighteenth century, a constellation of perplexing symptoms was observed that resembled symptoms of CFS. Commencing with "febricula" and ending with CFS, many names for the disease were proposed including neurocirculatory asthenia, atypical poliomyelitis, Royal Free disease, effort syndrome, Akureyri disease, Tapanui disease, chronic Epstein-Barr virus syndrome, and myalgic encephalitis. To date, it remains unclear whether CFS has an autoimmune component or is a condition that precedes a full-blown autoimmune disease. Research suggests that CFS may overlap with other diseases including postural orthostatic tachycardia syndrome (POTS), autoimmune syndrome induced by adjuvants (ASIA), and Sjögren's syndrome. Additionally, it has been postulated that the earliest manifestations of some autoimmune diseases can present with vague non-specific symptoms similar to CFS. Sometimes only when exposed to a secondary stimulus (e.g., antigen) which could accelerate the natural course of the disease would an individual develop the classic autoimmune disease. Due to the similarity of symptoms, it has been postulated that CFS could simply be an early manifestation of an autoimmune disease. This paper will provide a historical background review of this disease and a discussion of CFS as an entity overlapping with multiple other conditions.

This paper is to examine the relationship between anti-cyclic citrullinated peptide (anti-CCP) antibody titers and the development of interstitial lung disease (ILD) in patients with and without rheumatoid arthritis (RA). A retrospective investigation was conducted on all adult patients tested for anti-CCP between January 1, 2007, and December 31, 2012, in a university healthcare system. Patients with specified exposures or conditions known to cause ILD were excluded. The prevalence of ILD was compared between those with and without a positive CCP. The study population was then divided into four titer groups based on anti-CCP titers: negative, low titer, moderate titer, high titer. Fisher’s exact tests compared the prevalence of ILD among the anti-CCP titer groups. Multivariate logistic regression examined the association between anti-CCP and ILD while controlling for confounders. These analyses were repeated in two subgroups: a “confirmed RA” subgroup and an “unconfirmed RA” subgroup. Two thousand and thirty patients met inclusion criteria and 453 of those had confirmed RA. Progressively higher anti-CCP titer groups developed an increasingly higher prevalence of ILD (p

This paper presents a case with refractory relapsing polychondritis (RPC), complicated with severe aortic involvement, which is successfully treated with tocilizumab. Previous treatments consisted of methotrexate, corticosteroids, cyclosporine, cyclophosphamide, infliximab, and etanercept. With these treatments, the patient had recurrent episodes of fever, polyarthritis, tenosynovitis, subcutaneous nodules, and progressive cardiac disease. One year after the start of treatment with tocilizumab, there is resolution of all symptoms, normalization of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and the dose of prednisolone is tapered down to 2 mg/day. We have reviewed the English literature for reports of patients with refractory RPC, successfully treated with tocilizumab. We found five additional case reports. In one case report, a patient with refractory RPC complicated with aortitis was successfully treated with tocilizumab. In three case reports, patients with refractory RPC complicated with laryngotracheal involvement were successfully treated with tocilizumab. All cases had, like our patient, failed conventional treatment. We also reviewed the literature for reports of the effect of biologicals on cardiac involvement in RPC. Current literature is presented and discussed.

Item does not contain fulltext This paper aims to examine the interchangeability of the disease activity score in 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) and DAS28-CRP scores in a diverse sample of rheumatoid arthritis (RA) patients and to evaluate generalizability over gender, age, and disease duration. A sample of 682 patients was drawn from the DREAM registry. Agreement between the two DAS28 scores was analyzed using the intraclass correlation coefficient (ICC), Bland Altman plots, and a matrix of classification agreement over DAS28 disease activity categories. Despite a strong linear correlation between the DAS28 scores and a high ICC value of 0.931, a considerable lack of individual agreement could be observed, with Bland-Altman 95 % limits of agreement ranging between -0.85 and +1.25 points. On average, DAS28-CRP scores were 0.20 points lower than DAS28-ESR scores, and data stratification on age and gender showed that this systematic bias was most severe in older women (0.39 points). The overall classification agreement across DAS28 categories was 76.69 %, with the agreement being lowest (35.37 %) in the low disease activity group. Patients were more easily classified as being in remission when using the DAS28-CRP measure. DAS28-ESR and DAS28-CRP scores are not interchangeable within individuals. The DAS28-CRP tends to yield lower values of disease activity than the DAS28-ESR, resulting in substantial classification differences.

Systemic sclerosis sine scleroderma is a rare form of limited cutaneous scleroderma. These patients manifest without cutaneous involvement, but do not differ in its clinical or laboratory features and prognosis from classical systemic sclerosis. In the absence of cutaneous signs/symptoms, its diagnosis is delayed leading to morbidity. The exact prevalence of dystrophic calcification in systemic sclerosis sine scleroderma, though a feature of systemic sclerosis, is not known. Development of dystrophic calcification further aggravates patient's woes. This paper describes systemic sclerosis sine scleroderma in a 17-year-old girl diagnosed initially as seronegative juvenile rheumatoid arthritis. She developed progressively increasing disk-like masses of calcinosis over the gluteal regions, knee, elbow, and ankle joints fixed to the overlying skin associated with malaise, anorexia, and weight loss. There was no Raynaud's phenomenon, dysphagia, dyspnoea, sclerodermatous skin, sclerodactyly, telangectasias, or muscle tenderness/weakness. Digital pitted scars, elevated anticentromere antibody values, esophageal hypomotility, and fluffy calcification in subdermal soft tissues in gluteal regions and around wrist, hip, knees, heels, and ankle joints (without affecting the underlying structures) were detected. Therapy with diltiazem and magnesium/aluminum antacids was useful in resolving calcinosis.

This paper aims to compare the results of single-joint knee vs hip hyaluronic acid (HA) injections in patients with osteoarthritis (OA) involving both the knee and hip joints. Thirty-eight patients who were diagnosed to have both hip and knee OA were enrolled. Patients were divided into two groups to receive HA injection three times at 1-week intervals either to the hip or knee joints. Pain level during activities and rest was measured by using visual analog scale (VAS). Western Ontario and McMaster University Osteoarthritis Index (WOMAC 5-point Likert 3.0) was also used prior to the injections and 1 month after the 3rd injection. In the knee injection group, the intragroup analysis revealed significant improvements in VAS activity pain, VAS rest pain, and WOMAC pain values following injection when compared with preinjection values, while no significant difference was detected in WOMAC stiffness, WOMAC physical function, and WOMAC total values. In the hip injection group, VAS activity pain, VAS rest pain, WOMAC pain, WOMAC stiffness, WOMAC physical function, and WOMAC total values showed significant improvement after the injection when compared with preinjection values. Although statistically not significant (p > 0.05), the comparison of the differences (preinjection-postinjection) between the groups demonstrated higher values in the hip injection group. We imply that intra-articular single-joint HA injections either to the knee or hip joints in OA patients with involvement of both of these joints are effective with regard to pain and functional status.

This is a preliminary report on a case-series of rheumatoid patients that underwent various kinds of elective surgery but did not withdraw etanercept therapy in spite of physician advise. Elective surgery consisted of right knee surgical prosthesis, bilateral cataract, bilateral hallux valgus, right hip prosthesis, bladder stone by cystoscopy and left inguinal hernia. All the patients had a regular healing rate. During follow-up (6-12 months) no one of these patients were suffering from infective complications after surgery. According to same recent literature results, our data suggest that it is the time to value rheumatoid patient preferences through a correct information about cost-benefit of this treatment to establish together with patients if etanercept therapy has to be discontinued before and after elective surgery. Finally, we think that adverse drug reaction surveillance has to be boosted, and editors of leading scientific journal should publish more papers on case-series about drug safety and tolerability in particular conditions.

Disease activity in rheumatoid arthritis (RA) is assessed by a combination of objective and subjective tests, combined to produce a disease activity score in 28 joints (DAS28). There is some evidence that RA disease activity, as assessed by DAS28, can be influenced by vitamin D levels. It is difficult to know whether this is due to a true immunomodulatory effect of vitamin D or a more subjective effect of low vitamin D on pain perception. We addressed this issue by comparing vitamin D levels with disease activity, analysing each component of the DAS28 score separately. We measured 25-hydroxy vitamin D levels in 176 outpatients with RA at two different centres and recorded a DAS28 score using an ESR checked at the same time. We calculated DAS28 both with and without the patient’s rating of their symptoms on the visual analogue score (VAS) to assess the effect of VAS on DAS28. The vitamin D results were expressed as nanomole per litre with 50 nmol/l taken as the lower limit of normal. We calculated mean levels of vitamin D and undertook a multivariate regression analysis to assess correlations between vitamin D levels and DAS28 (and its individual components), corrected for centre, age and gender. The overall mean DAS28 score was 3.66 (SE ± 0.11) using all four criteria and 3.43 (SE ± 0.10) using just three criteria (omitting VAS). The mean vitamin D level was 39.42 nmol/l (SE ± 1.55). There was no significant correlation between vitamin D and DAS28 scores with or without the inclusion of VAS. However, there was a significant inverse relationship between vitamin D and VAS itself (coefficient = 0.249, p = 0.013). The mean DAS28 score was greater in vitamin D-deficient patients and this was explained by their higher VAS scores. Our data confirms that vitamin D deficiency is common in RA. This paper provides evidence that the VAS component, assessing patient perception of symptoms, is inversely related to vitamin D, with lower levels producing higher VAS values. Although there was no overall correlation between vitamin D levels and DAS28, patients may perceive themselves or be perceived by assessors as having responded less well to disease modification in the presence of vitamin D deficiency. This could have major implications for subsequent management, and clinicians need to be aware of the potential confounding effect of vitamin D deficiency in assessing RA disease activity using the full DAS28 tool.

Systemic lupus erythematosus is an autoimmune and inflammatory disease with multiple clinical manifestations, including arthropathy. The clinical presentation of articular involvement is variable, ranging from arthralgia without erosions or deformity to an erosive arthropathy and severe functional disability. A subset of patients with this articular involvement have Jaccoud’s arthropathy, and others have an arthropathy with clinical findings similar to rheumatoid arthritis that has been called “rhupus.” In this paper we review the historical evolution of concepts of lupus arthropathy, from deforming arthritis to rhupus, and conclude that rhupus is not a combination of rheumatoid arthritis and lupus. Instead, rhupus arthropathy should be regarded as a variant of the arthropathy of systemic lupus erythematosus.

Raised serum alkaline phosphatase (ALP) activity in rheumatoid arthritis (RA) has been reported, although its aetiology is not clear. In this paper we investigate whether synovial tissue is a possible source of raised ALP activity in RA. The activities and isozymes of ALP were determined in sera and synovial fluids from 22 RA and seven osteoarthritis (OA) patients. The expression of both protein and ALP mRNA in synovial tissue was investigated immunohistochemically and by reverse transcription (RT) PCR. ALP activity was higher in serum and synovial fluid from RA patients than in those from OA patients. In addition, the ratio of levels of bone-type ALP to those of liver-type ALP was significantly higher in synovial fluid than in serum from RA patients. Bone-type ALP was positive around the perivascular area and the subepithelial cells in the synovial tissue from RA patients. In contrast, the synovial tissue from OA patients exhibited no staining. The mRNA of bone-type ALP was detected in RA synoviocytes. In conclusion, ALP levels were elevated in both serum and synovial fluid from RA patients. Bone-type ALP derived from the synovial tissue may contribute to the raised activities of ALP in RA patients.

The paper “Fear of movement and avoidance behaviour toward physical activity in chronic-fatigue syndrome and fibromyalgia: state of the art and implications for clinical practice” [1] is interesting but problematic. We agree that mild exercise is good but over exercise can cause relapse. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia patients suffer from relapse when is subjected to over exercise. We at the ME/CFS Center at Mount Sinai School of Medicine, New York are investigating the postexertional malaise seen in (ME/CFS). This is one of the criteria in the Canadian Consensus of diagnosis of ME/CFS. [2] The notion that ME/CFS is caused by poor conditioning is no longer widely accepted. It is thought that it is an immune system dysfunction, which after onset can be provoked by stress, over exercise or overwork [3]. Indeed, there can be depression, but this depression is secondary to the disease much like any other chronic disease. Cognitive behavioral therapy may be helpful to reverse the secondary depression but one must understand that this depression is indeed secondary and the initial disease entity is in the immune system and must be identified and treated.