Geoffrey Owen Littlejohn

A multi‐center, observational study shows high proportion of Australian rheumatoid arthritis patients have inadequate disease control

To evaluate the disease activity and current pharmacological interventions used to achieve remission in rheumatoid arthritis (RA) patients in Australia.

Altered heat pain thresholds and cerebral event-related potentials following painful CO2 laser stimulation in subjects with fibromyalgia syndrome

&NA; A decrease in mechanical pressure pain thresholds, particularly over pre‐designated tender points, is one of the defining characteristics of fibromyalgia syndrome (FS); however, changes in thermal pain sensitivity have not been investigated. The present study examined heat pain thresholds and cerebral event‐related potentials following CO2 laser stimulation in 10 subjects with FS and 10 age‐matched control volunteers. The results indicate that patients with FS exhibit a significant reduction in heat pain threshold when tested on the dorsal surface of the hand. In accordance with previous research, we also found a decrease in mechanical pain threshold over pre‐designated tender points and at control sites as well as a significantly larger mechanically induced neurogenic flare response. These measures were highly correlated with thermal pain threshold even though different anatomical sites were stimulated. Hence, it seems likely that FS patients display a multimodal change in pain sensitivity which is generalized rather than anatomically restricted. Patients with FS also displayed a significant increase in the peak‐to‐peak amplitude of the cerebral potential evoked by CO2 laser stimulation at pain threshold intensity and 1.5 times pain threshold intensity. These findings suggest a greater activation of central nervous system (CNS) pathways following noxious input. Putative explanations for the increased CNS response are discussed, including mechanisms of peripheral nociceptor sensitization, altered CNS function and the role of psychological factors.

Incidence of melanoma and other malignancies among rheumatoid arthritis patients treated with methotrexate

OBJECTIVE To determine cancer risk in a cohort of 459 rheumatoid arthritis (RA) patients treated with methotrexate in community practice. METHODS All RA patients who started methotrexate prior to June 1986 and were attending 1 of 6 rheumatologists were studied. Demographic data were matched to the State Cancer Registry to identify all malignancies (except nonmelanoma skin cancer) for 1983-1998, and to the National Death Index to identify all deaths to the end of 1999. Followup started on the date when methotrexate was started and ended either on the last confirmed date on which the patient was seen by the rheumatologist or at death. Standardized incidence ratios (SIRs) were calculated using state population cancer rates stratified by sex, age (in 5-year groups), and calendar year. RESULTS There were 4,145 person-years of followup (average 9.3 years). Eighty-seven malignancies were identified (14 before, 64 during, and 9 after the followup period). There was an estimated 50% excess risk of malignancy among methotrexate-exposed RA patients relative to the general population (SIR 1.5, 95% confidence interval [95% CI] 1.2-1.9), with a 3-fold increase in melanoma (SIR 3.0, 95% CI 1.2-6.2), a 5-fold increase in non-Hodgkins lymphoma (SIR 5.1, 95% CI 2.2-10.0), and an almost 3-fold increase in lung cancer (SIR 2.9, 95% CI 1.6-4.8). CONCLUSION Compared with the general population, methotrexate-treated RA patients have an increased incidence of melanoma, non-Hodgkins lymphoma, and lung cancer. There may be a role for regular skin cancer screening for all RA patients, particularly those receiving immunosuppressive therapy.

Continuation of long term treatment with hydroxychloroquine in systemic lupus erythematosus and rheumatoid arthritis.

BACKGROUND: Hydroxychloroquine is used for the treatment of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Long term studies have shown a high rate of termination of hydroxychloroquine treatment in patients with RA. Although it has been shown that discontinuation of treatment with hydroxychloroquine is associated with exacerbation of SLE, long term maintenance rates of treatment with hydroxychloroquine in patients with SLE have not been investigated. METHODS: Hydroxychloroquine use in patients with RA and SLE in a group of patients in a single community rheumatology practice was studied. Information was drawn from a computer drug use database containing details of the beginning and end of treatment. Data were analysed using life table methods. RESULTS: Four hundred and three treatment episodes (366 patients with RA, 37 patients with SLE) were observed over eight years. In patients with RA, the cumulative probability of discontinuing treatment was 37% at 12 months and 54% at 24 months. In contrast, hydroxychloroquine treatment of patients with SLE continued over significantly longer periods of time (p < 0.001); the discontinuation probabilities at 12 and 24 months were 8 and 24% respectively. Treatment terminations were predominantly for inefficacy; terminations for toxicity were limited to the first 19 months of treatment. No ocular toxicity was observed. CONCLUSIONS: Treatment of patients with RA in a community rheumatology practice with hydroxychloroquine has a low probability of long term continuation, mostly because of inadequate control of disease manifestations rather than toxicity. In patients with SLE, treatment with hydroxychloroquine has a significantly higher probability of long term continuation.

The use of opioids in fibromyalgia

Fibromyalgia syndrome (FMS) is a chronic disorder of widespread pain with high personal and societal burdens. Although targeted pharmacotherapies have become available in recent years, it remains a challenging condition to treat. Despite no randomized controlled trials addressing the short‐ or long‐term use of opioids in FMS, their use remains prevalent. In this article we discuss the role of opioids and other analgesics in the management of FMS, with particular focus on problems associated with their use. We review aspects of the pathophysiology of FMS and consider how specific factors may contribute to the lack of efficacy of opioids in this condition. Finally, we discuss drugs with combined opioid and anti‐opioid action and their roles in FMS. There is insufficient evidence to recommend the routine use of opioids in FMS. As well as having a significant adverse effect profile, their inefficacy may be due to their inability to target the pathophysiologic processes involved in this central sensitization syndrome.

Measuring quality of life in rheumatic conditions.

Musculoskeletal disorders often have associated pain, functional impairment and work disability, and, not surprisingly, are the most common reasons for utilizing healthcare resources. Rheumatoid arthritis (RA) and fibromyalgia (FM) are causes of musculoskeletal pain and disability. Research indicates that there is a widespread impact of RA and FM on physical, psychological and social factors in affected individuals, and thus, outcome measures that encompass multiple aspects of quality of life are needed. Generic measures of quality of life identify associations between physical conditions and mental health and highlight the need to address psychological functioning to ultimately improve the individuals’ quality of life.

Neurogenic neuroinflammation in fibromyalgia and complex regional pain syndrome

Although fibromyalgia and complex regional pain syndrome (CRPS) have distinct clinical phenotypes, they do share many other features. Pain, allodynia and dysaesthesia occur in each condition and seem to exist on a similar spectrum. Fibromyalgia and CRPS can both be triggered by specific traumatic events, although fibromyalgia is most commonly associated with psychological trauma and CRPS is most often associated with physical trauma, which is frequently deemed routine or minor by the patient. Fibromyalgia and CRPS also seem to share many pathophysiological mechanisms, among which the most important are those involving central effects. Nonetheless, peripheral effects, such as neurogenic neuroinflammation, are also important contributors to the clinical features of each of these disorders. This Review highlights the differing degrees to which neurogenic neuroinflammation might contribute to the multifactorial pathogenesis of both fibromyalgia and CRPS, and discusses the evidence suggesting that this mechanism is an important link between the two disorders, and could offer novel therapeutic targets.

Barriers to optimal disease control for rheumatoid arthritis patients with moderate and high disease activity

To evaluate barriers that prevent rheumatoid arthritis (RA) patients from achieving Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28‐ESR) scores within the current recommended levels for low disease activity (LDA) or clinical remission (DAS28‐ESR score <3.2).

Personality and Fibromyalgia Syndrome

Objectives: We aimed to review how personality characteristics contribute to the onset, maintenance or modulation of fibromyalgia. Method: The databases Medline and PsychINFO were examined from 1967 to 2012 to identify studies that investigated associations between fibromyalgia and personality. Search terms included fibromyalgia and personality, trait psychology, characteristics and individual differences. Results: Numerous studies indicate that patients with fibromyalgia experience psychological distress. Various instruments have been used to evaluate distress and related psychological domains, such as anxiety or depression, in fibromyalgia. In many cases, these same instruments have been used to study personality characteristics in fibromyalgia with a subsequent blurring of cause and effect between personality and psychological distress. In addition, the symptoms of fibromyalgia may change pre-illness personality characteristics themselves. These issues make it difficult to identify specific personality characteristics that might influence the fibromyalgia process. Despite this inherent problem with the methodologies used in the studies that make up this literature review, or perhaps because of it, we found no defined personality profile specific to fibromyalgia. However, many patients with fibromyalgia do show personality characteristics that facilitate psychological responses to stressful situations, such as catastrophising or poor coping techniques, and these in turn associate with mechanisms contributing to fibromyalgia. Conclusion: No specific fibromyalgia personality is defined but it is proposed that personality is an important filter that modulates a person’s response to psychological stressors. Certain personalities may facilitate translation of these stressors to physiological responses driving the fibromyalgia mechanism.

Fibromyalgia Syndrome: Which Antidepressant Drug Should We Choose

Fibromyalgia syndrome [FM] has core clinical features of widespread pain and widespread abnormal tenderness. The specific cause of the altered neurophysiology that underpins these clinical manifestations remains unclear. However, increased sensitisation of neural networks that relates to pain, as well as interacting mechanoreceptors, appear important targets for modulation by pharmacological agents. Further, many FM patients have emotional distress and some are depressed. Antidepressant agents have therapeutic benefits in FM. If depression is present antidepressant drugs will provide typical benefits to mood but not always to other key outcome measures, such as pain or tenderness. Selective serotonin receptor reuptake blockers are not as effective for overall FM improvement as drugs that block both serotonin and norepinephrine in a relatively balanced way. Thus tricyclic antidepressants will improve many important FM outcomes but are effective in only about 40 percent of individuals. Newer agents of this class, such as duloxetine and milnacipran, show improvement in key FM outcomes in about 60 percent of patients. Longer term studies will indicate the durability of these responses and the overall tolerance of the drugs. Any drug therapy will need to be integrated with appropriate education, exercise and attention to psychological modulatory factors to achieve best results.