Chronic widespread pain in spondyloarthritis.

The pain associated with spondyloarthritis (SpA) can be intense, persistent and disabling. It frequently has a multifactorial, simultaneously central and peripheral origin, and may be due to currently active inflammation, or joint damage and tissue destruction arising from a previous inflammatory condition. Inflammatory pain symptoms can be reduced by non-steroidal anti-inflammatory drugs, but many patients continue to experience moderate pain due to alterations in the mechanisms that regulate central pain, as in the case of the chronic widespread pain (CWP) that characterises fibromyalgia (FM). The importance of distinguishing SpA and FM is underlined by the fact that SpA is currently treated with costly drugs such as tumour necrosis factor (TNF) inhibitors, and direct costs are higher in patients with concomitant CWP or FM than in those with FM or SpA alone. Optimal treatment needs to take into account symptoms such as fatigue, mood, sleep, and the overall quality of life, and is based on the use of tricyclic antidepressants or selective serotonin reuptake inhibitors such as fluoxetine, rather than adjustments in the dose of anti-TNF agents or disease-modifying drugs.

Somatoform disorders and rheumatic diseases: from DSM-IV to DSM-V.

Medically unexplained symptoms are considered 'somatoform disorders' in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). The introduction of this nosographic category has been helpful in drawing attention to a previously neglected area, but has not been successful in promoting an understanding of the disorders' biological basis and treatment implications, probably because of a series of diagnostic shortcomings. The newly proposed DSM-V diagnostic criteria try to overcome the limitations of the DSM-IV definition, which was organised centrally around the concept of medically unexplained symptoms, by emphasising the extent to which a patient's thoughts, feelings and behaviours concerning their somatic symptoms are disproportionate or excessive. This change is supported by a growing body of evidence showing that psychological and behavioural features play a major role in causing patient disability and maintaining high level of health care use. Pain disorders is the sub-category of DSM-IV somatoform disorders that most closely resembles fibromyalgia. Regardless of the diagnostic changes recently brought about by DSM-V, neuroimaging studies have identified important components of the mental processes associated with a DSM- IV diagnosis of pain disorder.

Psychiatric problems in fibromyalgia: clinical and neurobiological links between mood disorders and fibromyalgia.

OBJECTIVES: To review the literature addressing the relationship between mood disorders and fibromyalgia/chronic pain and our current understanding of overlapping pathophysiological processes and pain and depression circuitry. METHODS: We selectively reviewed articles on the co-occurrence of mood disorders and fibromyalgia/chronic pain published between 1990 and July 2012 in PubMed. Bibliographies and cross references were considered and included when appropriate. RESULTS: Forty-nine out of 138 publications were retained for review. The vast majority of the studies found an association between depression and fibromyalgia. There is evidence that depression is often accompanied by symptoms of opposite polarity characterised by heights of mood, thinking and behaviour that have a considerable impact on pharmacological treatment. Recent developments support the view that the high rates of fibromyalgia and mood disorder comorbidity is generated by largely overlapping pathophysiological processes in the brain, that provide a neurobiological basis for the bidirectional, mutually exacerbating and disabling relationship between pain and depression. CONCLUSIONS: The finding of comparable pathophysiological characteristics of pain and depression provides a framework for understanding the relationship between the two conditions and sheds some light on neurobiological and therapeutic aspects.

Fibromyalgia and arthritides.

Fibromyalgia (FM) is a chronic pain syndrome that affects at least 2% of the adult population. It is characterised by widespread pain, fatigue, sleep alterations and distress, and emerging evidence suggests a central nervous system (CNS) malfunction that increases pain transmission and perception. FM is often associated with other diseases that act as confounding and aggravating factors, such as rheumatoid arthritis (RA), spondyloarthritides (SpA), osteoarthritis (OA) and thyroid disease. Mechanism-based FM management should consider both peripheral and central pain, including effects due to cerebral input and that come from the descending inhibitory pathways. Rheumatologists should be able to distinguish primary and secondary FM, and need new guidelines and instruments to avoid making mistakes, bearing in mind that the diffuse pain of arthritides compromises the patients' quality of life.

Fibromyalgia syndrome: preventive, social and economic aspects.

There many open questions concerning the concept of primary prevention in FM. Diagnostic or classification criteria are not universally accepted, and this leads to difficulties in establishing the onset and duration of the disease. In the case of FM, primary prevention may consist of the immediate care of acute pain or treatment for affective disturbances as we do not have any specific laboratory or instrumental tests to determine risk factors of the disease. The goal of secondary prevention is early detection of the disease when patients are largely asymptomatic and intervention improves outcome. Screening allows for identification of an unrecognized disease or risk factor, which, for potential FM patients, includes analysis of tender points, Fibromyalgia Impact Questionnaire (FIQ), pain location and intensity, and fatigue and sleep complaints. Tertiary prevention inhibits further deterioration or reduces complications after the disease has developed. In FM the aim of treatment is to decrease pain and increase function via multimodal therapeutic strategies, which, in most cases, includes pharmacological and non-pharmacological interventions. Patients with FM are high consumers of health care services, and FM is associated with significant productivity-related costs. The degree of disability and the number of comorbidities are strongly associated with costs. An earlier diagnosis of FM can reduce referral costs and investigations, thus, leading to a net savings for the health care sector. However, every social assessment is closely related to the socio-economic level of the general population and to the legislation of the country in which the FM patient resides.

Fibromyalgia syndrome: definition and diagnostic aspects.

Ever since it was first defined, fibromyalgia (FM) has been considered one of the most controversial diagnoses in the field of rheumatology, to the point that not everybody accepts its existence as an independent entity. The sensitivity and specificity of the proposed diagnostic criteria are still debated by various specialists (not only rheumatologists), whose main criticism of the 1990 American College of Rheumatology criteria is that they identify subsets of particular patients that do not reflect everyday clinical reality. Furthermore, the symptoms characterising FM overlap with those of many other conditions classified in a different manner. Over the last few years, this has led to FM being considered less as a clinical entity and more as a possible manifestation of alterations in the psychoneuroendocrine system (the spectrum of affective disorders) or the stress reaction system (dysfunctional symptoms). More recently, doubts have been raised about even these classifications; and it now seems more appropriate to include FM among the central sensitisation syndromes, which identify the main pathogenetic mechanism as the cause of skeletal and extra-skeletal symptoms of FM and other previously defined "dysfunctional" syndromes.

Etiopathogenetic mechanisms of fibromyalgia syndrome.

Fibromyalgia syndrome (FMS) is a common chronic condition of widespread pain with causal mechanisms that are largely unknown. It is characterized by moderate to severe musculoskeletal pain and allodynia, but its pathogenesis appears confined to the nociceptive structures of the central nervous system. FMS is often triggered by negative environmental influences, especially if they occur in childhood. In a fetus, these environmental triggers may influence the development of the autonomic nervous system (ANS) and the hypothalamic-pituitary-adrenal axis (HPA). Increasing evidence supports the comorbidity of psychological conditions including depression, panic disorders, anxiety, and post-traumatic stress disorder (PTSD). Recent evidence suggests that genetic factors may play a role in the pathogenesis of FMS. Central sensitization has long been associated with FMS pain. It describes enhanced excitability of dorsal horn neurons, which leads to transmission of altered nociceptive information to the brain. Understanding of pathogenetic pathways in FMS has advanced beyond observing patient responses to neurophysiologically targeted therapies and basic research.

Non pharmacological treatments in fibromyalgia.

Fibromyalgia is a complex syndrome associated with significant impairment in quality of life and function and with substantial financial costs. Once the diagnosis is made, providers should aim to increase patients' function and minimize pain. Fibromyalgia patients frequently use alternative therapies, strongly indicating both their dissatisfaction with and the substantial ineffectiveness of traditional medical therapy, especially pharmacological treatments. At present, pharmacological treatments for fibromyalgia have a rather discouraging cost/benefit ratio in terms of poor symptom control and high incidence of side effects. The interdisciplinary treatment programs have been shown to improve subjective pain with greater success than monotherapy. Physical therapies, rehabilitation and alternative therapies are generally perceived to be more "natural," to have fewer adverse effects, and in some way, to be more effective. In this review, physical exercise and multimodal cognitive behavioural therapy are presented as the more accepted and beneficial forms of nonpharmacological therapy.

Symptoms and signs in fibromyalgia syndrome.

Fibromyalgia syndrome (FM) is a common chronic pain condition that affects at least 2% of the adult population. Chronic widespread pain is the defining feature of FM, but patients may also exhibit a range of other symptoms, including sleep disturbance, fatigue, irritable bowel syndrome, headaches, and mood disorders. The etiology of FM is not completely understood and the syndrome is influenced by factors such as stress, medical illness, and a variety of pain conditions. Establishing diagnosis may be difficult because of the multifaceted nature of the syndrome and overlap with other chronically painful conditions. A unifying hypothesis is that FM results from sensitization of the central nervous system; this new concept could justify the variety of characteristics of the syndrome. FM symptoms can be musculoskeletal, non-musculoskeletal, or a combination of both; and many patients will also experience a host of associated symptoms or conditions. The ACR classification criteria focus only on pain and disregard other important symptoms; but three key features, pain, fatigue and sleep disturbance, are present in virtually every patient with FM. Several other associated syndromes, including circulatory, nervous, digestive, urinary and reproductive systems are probably a part of the so called central sensitivity or sensitization syndrome. A minority subgroup of patients (30-40%) has a significant psychological disturbance. Psychological factors are an important determinant of any type of pain, and psychological comorbidity is frequent in FM. Psychiatric disorders most commonly described are mood disorders, but psychiatric illness is not a necessary factor in the etiopathogenesis of FM.

Fibromyalgia syndrome: the pharmacological treatment options.

Pharmacological treatment has been gradually enriched by a variety of compounds; however, no single drug is capable of fully managing the constellation of fibromyalgia (FM) symptoms. Currently, it is not possible to draw definite conclusions concerning the best pharmacological approach to managing FM because results of randomized clinical trials present methodological limitations and therapeutic programs are too heterogeneous for adequate comparison. However, a variety of pharmacological treatments including antidepressants, nonsteroidal anti-inflammatory drugs (NSAIDS), opioids, sedatives, muscle relaxants and antiepileptics have been used to treat FM with varying results. In this review, we will evaluate those pharmacological therapies that have produced the most significant clinical results in treating FM patients. The nature of FM suggests that an individualized, multimodal approach that includes both pharmacologic and nonpharmacologic therapies seems to be the most appropriate treatment strategy to date.

The evaluation of the fibromyalgia patients.

Fibromyalgia (FM) is a rheumatic disease characterized by musculoskeletal pain, chronic diffuse tension and/or stiffness in joints and muscles, easy fatigue, sleep and emotional disturbances, and pressure pain sensitivity in at least 11 of 18 tender points. At present, there are no instrumental tests or specific diagnostic markers for FM; in fact, many of the existing indicators are significant for research purposes only. Many differential diagnoses may be excluded by an extensive clinical examination and patient history. Considering overlap of FM with other medical conditions, the treating physicians should be vigilant: chest-X-rays and abdominal ultrasonography are the first steps of general evaluation for all the patients with suspected FM. Functional neuroimaging methods have revealed a large number of supraspinal effects in FM, a disorder mediated by mechanisms that are essentially unknown. Many treatments are used in FM patients, but evaluating their therapeutic effects in FM is difficult because the syndrome is so multifaceted. To address the identification of core outcome domains, the Initiative on IMMPACT and OMERACT workshop convened a meeting to develop consensus recommendations for chronic pain clinical trials.

Treatment of morbid obesity by intraparietogastric administration of botulinum toxin: a randomized, double-blind, controlled study.

OBJECTIVE: The stomach is the main target organ for bariatric surgery, but no medical treatment has been developed to increase satiety and decrease food intake via gastric pathways. The aim of our study was to investigate whether or not the intraparietogastric administration of botulinum toxin A (BTX), able to modify the motility patterns of the stomach, could be useful for treatment of obesity. DESIGN: Double blind controlled study. SUBJECTS: Twenty-four morbidly obese patients (mean weight (s.e.m.) 116.1+/-4.89 kg, mean body mass index (BMI) 43.6+/-1.09 kg/m(2)) were blindly randomized to receive 200 IU BTX or placebo into the antrum and fundus of the stomach by intraparietal endoscopic administration. MEASUREMENTS: We evaluated weight loss, BMI changes, satiety score, the maximal gastric capacity for liquids and the gastric emptying time (octanoic acid breath test). RESULTS: The two groups were homogeneous for anthropometric characteristics. Eight weeks after treatment, BTX patients had significantly higher weight loss (11+/-1.09 vs 5.7+/-1.1 kg, P<0.001) and BMI reduction (4+/-0.36 vs 2+/-0.58 kg/m(2), P<0.001) and a higher satiety score on a visual analogic scale (7.63+/-0.38 vs 4.72+/-0.44, P<0.001) than controls. Furthermore, BTX patients showed a significantly greater reduction in maximal gastric capacity for liquids (266.6+/-48 vs 139+/-31, P<0.001) and a greater prolongation in gastric emptying time (+18.93+/-8 vs -2.2+/-6.9 min, P<0.05). No significant side effects or neurophysiologic changes were found. CONCLUSIONS: Topical intragastric BTX was effective in reducing food intake and body weight in morbidly obese patients.

New-onset delusions and hallucinations in patients infected with HIV.

OBJECTIVE: To assess the relationship between HIV-associated psychotic symptoms (i.e., delusions, hallucinations) and demographic, psychopathological and medical variables by comparing patients with and without cerebral opportunistic infections or metabolic encephalopathy. DESIGN: Cross-sectional study. PATIENTS: 26 patients admitted to hospital with HIV and new-onset psychotic symptoms, defined according to DSM-III-R criteria. OUTCOME MEASURES: A semistructured psychiatric interview using the Psychopathology Assessment Scale (AMDP-4) of the Association for Methodology and Documentation in Psychiatry system. Comprehensive medical assessments, including laboratory tests and computed tomographic scans, were also performed. RESULTS: Patients with cerebral opportunistic infections or metabolic encephalopathy (i.e., "secondary" psychosis, n = 13) were more likely to show disorders of consciousness, disorders of orientation and disturbances of attention and memory than those with no evidence of HIV-related cerebral disease (i.e., "primary" psychosis, n = 13); 10 patients (77%) with cerebral opportunistic infections or metabolic encephalopathy and only 1 (8%) patient without (p < 0.001) were diagnosed with delirium. These associations were stronger for the "secondary" patients with no focal brain lesions than for those with lesions. CONCLUSIONS: These findings suggest that "organic" symptoms of psychosis in those infected with HIV are related to the systemic and cerebral complications of HIV infection rather than to the psychotic process itself.

Changes in lymphocyte subsets in depressed HIV-infected patients without antiretroviral therapy.

The authors studied the effects of major depression on lymphocyte subsets by comparing depressed and matched control subjects in a population of HIV-seropositive outpatients not treated with antiretroviral therapy. Twelve patients with major depression, as determined by the Structured Clinical Interview for DSM-III-R, were assessed in comparison with 15 matched nondepressed control subjects. Flow cytometric analysis of peripheral blood lymphocyte subsets together with immunological parameters were performed. In HIV-infected patients, major depression was significantly (P=0.001) associated with a reduction in natural killer cell absolute count and percentage. This report suggests that depression may alter the natural killer cell population that provides a cytotoxic defense against HIV infection.

Has there been a decrease in the prevalence of mood disorders in HIV-seropositive individuals since the introduction of combination therapy?

PURPOSE: The aim of this study was to assess the prevalence of current mood disorders in HIV-seropositive patients treated with combined antiretroviral drug therapy including or not protease inhibitors. SUBJECTS AND METHODS: A random sample of 90 subjects consecutively attending, between February 1 and July 31, 1998, the outpatient unit of the Second Department of Infectious Diseases of the 'L. Sacco' Hospital in Milan was assessed by means of the Structured Clinical Interview for DSMIII-R (SCID) and the Zung Self-Rating Depression Scale (ZSDS). RESULTS: Twenty-three-point-three percent of the subjects were classified in CDC stage A, 32.3% in CDC stage B and 44.4% in CDC stage C. A DSMIII-R psychiatric diagnosis of current mood disorder was found in 4.4% of the recruited sample (dysthymia: 2.2%; adjustment disorder with depressed mood: 2.2%). CONCLUSIONS: Direct and indirect effect of new combination therapies, epidemiological changes in social groups affected by HIV and possible modifications in social perception of people with HIV infection may explain, at least in part, the decreased prevalence of current mood disorders observed in our study as compared to prevalence rates reported in the pre-HAART era.

Three cases of delirium after "ecstasy" ingestion.

Three cases of delirium experienced by three young friends after recreational use of "ecstasy" are reported--a syndrome which, to the best of the authors' knowledge, has not been previously observed in MDMA abusers. Special attention is given to the etiological factors and clinical features of the adverse reaction.

Heterogeneity of major affective disorders. Biological and clinical evidence.

In this paper we summarize the results of our recent and present research focused on analyzing the correlations between neurochemical, pharmacological and clinical parameters in patients with Major Depression. There is evidence that: a) pretreatment urinary MHPG is a useful predictor for clinical response to tricyclic antidepressants and to long-term lithium treatment; b) urinary MHPG is positively correlated to the age at onset of the disease; c) previous responses to tricyclics and age at onset of affective illness are supplementary tools for predicting the effectiveness of lithium and antidepressant drugs; d) platelet alpha-2-adrenoceptor density is inversely correlated with both urinary MHPG and age at onset; e) cerebral ventricular size is positively correlated with urinary MHPG and age at onset and may discriminate between patients with different outcomes on lithium prophylaxis; f) low MHPG excretors are more likely to have suffered from stressful life events in early childhood than normal-to-high excretors. Taken together, these results lend strong support to the hypothesis that Major Affective Disorder is a heterogeneous illness and that inherently different subgroups of affective patients can be recognized.

Platelet alpha 2-adrenoceptors in major depression: relationship with urinary 4-hydroxy-3-methoxyphenylglycol and age at onset.

Platelet alpha 2-adrenoceptor number and affinity were measured in 31 drug-free patients with major depressive illness utilizing 3H-clonidine as ligand. A significant negative correlation was found between number of alpha 2-adrenoceptors, baseline urinary 4-hydroxy-3-methoxyphenylglycol (MHPG) excretion, present age and age at onset of the disease. Kd did not correlate with any of these variables not with the Bmax of platelet alpha 2-adrenergic binding. Multiple regression analysis, with MHPG and age at onset as independent variables, explained variance for alpha 2-adrenoceptor density better than single regression (from 19% for MHPG and 30% for age at onset to 40%), with the addition of both these variables being significant.