The crosstalk of the pathophysiologic models in fibromyalgia.

Fibromyalgia (FM) is a heterogeneous condition with various mechanisms (endotype) and manifestations (phenotypes). Many worthy endeavors have been dedicated to exploring the main trajectories of FM pathogenesis, depicted as the models of FM development. The Imbalance of Threat and Soothing Systems (FITSS) model, which is an advancing psychosocial form of the "central sensitization" model, and autonomic nervous system (ANS) model, besides new discoveries of potential pathways for FM development such as autoimmunity, small fiber pathology, and gut-brain axis currently comprise all our knowledge assets about FM pathogenesis. The pathophysiology of fibromyalgia is too complex to justify with one model, one main loop of pathogenesis, and one terminator. It appears that the variable FM models could justify some phenotypes of FM. Currently, our knowledge about FM pathogenesis and trying to match the different pathways and links mimic solving a puzzle in the hands of beginners. Until unraveling many missed interconnections and formulas between numerous scrambled pieces of the FM puzzle, proposing an integrated model seems not possible. This review focuses on the main trajectories of FM pathogenesis proposed thus far and tries to illuminate the crosstalking between them. We also propose the subgrouping FM into more homogenous categories based on the endotype-phenotype characteristics. It could provide a more pragmatic approach toward understanding of the diverse network of FM pathogenesis as well as the personalized stratification of FM. Key Points • The disentangled nature of FM pathogenesis escapes from embracing under one integrated model. • There appears to be no way for formulizing FM pathogenesis except the acknowledgment of the different pathways and their crosstalk explored as yet. • Acknowledging the different endotypes/phenotypes of FM spectrum and classifying them into more homogenous groups can help to the pragmatic approach to FM.

Immune thrombocytopenic purpura secondary to COVID-19 vaccination: A systematic review.

INTRODUCTION: This systematic review aimed to retrieve patients diagnosed with de novo immune thrombocytopenic purpura (ITP) after COVID-19 immunization to determine their epidemiological characteristics, clinical course, therapeutic strategies, and outcome. MATERIALS AND METHODS: We conducted the review using four major databases, comprising PubMed, Scopus, Web of Science, and the Cochrane library, until April 2022. A systematic search was performed in duplicate to access eligible articles in English. Furthermore, a manual search was applied to the chosen papers' references to enhance the search sensitivity. Data were extracted and analyzed with the SPSS 20.1 software. RESULTS: A total of 77 patients with de novo COVID-19 vaccine-associated ITP were identified from 41 studies, including 31 case reports and 10 case series. The median age of patients who developed COVID-19 vaccine-associated ITP was 54 years (IQR 36-72 years). The mRNA-based COVID-19 vaccines, including BNT16B2b2 and mRNA-1273, were most implicated (75.4%). Those were followed by the adenovirus vector-based vaccines, inclusive of ChAdOx1 nCoV-19 and vAd26.COV2.S. No report was found relating ITP to other COVID-19 vaccines. Most cases (79.2%) developed ITP after the first dose of COVID-19 vaccination. 75% of the patients developed ITP within 12 days of vaccination, indicating a shorter lag time compared to ITP after routine childhood vaccinations. Sixty-seven patients (87%) patients were hospitalized. The management pattern was similar to primary ITP, and systemic glucocorticoids, IVIg, or both were the basis of the treatment in most patients. Most patients achieved therapeutic goals; only two individuals required a secondary admission, and one patient who presented with intracranial hemorrhage died of the complication. CONCLUSIONS: De novo ITP is a rare complication of COVID-19 vaccination, and corresponding reports belong to mRNA-based and adenovirus vector-based vaccines, in order of frequency. This frequency pattern may be related to the scale of administration of individual vaccines and their potency in inducing autoimmunity. The more the COVID-19 vaccine is potent to induce antigenic challenge, the shorter the lag time would be. Most patients had a benign course and responded to typical treatments of primary ITP.

Effect of vitamin B12 on the symptom severity and psychological profile of fibromyalgia patients; a prospective pre-post study.

BACKGROUND: Fibromyalgia (FM) as a prototypical nociplastic pain condition displays a difficult therapeutic situation in many cases. Given the promising data on the effect of vitamin B12 in improving pain and cognitive functions in various nociplastic pain conditions, we aimed to determine the efficacy of 1000 mcg daily dose of oral vitamin B12 on the symptom severity and psychological profile of FM patients. METHODS: This open-label, pre-post study was performed on FM patients whose diagnoses were confirmed by a rheumatologist based on the 2016 American College of Rheumatology (ACR). Patients were instructed to take a daily dose of 1000mcg vitamin B12 for fifty days. Outcome measures including the Revised Fibromyalgia Impact Questionnaire (FIQR), Hospital Anxiety and Depression Scale (HADS), 12-item Short-Form health survey (SF-12), and pain Visual Analog Scale (pain-VAS) were fulfilled by patients before and after the treatment. RESULTS: Of 30 eligible patients, 28 patients completed the study protocol. Patients were female with a mean age of 47.50 ± 8.47 years. FIQR scores in all domains improved significantly after treatment (total FIQR: 49.8 ± 21.86 vs 40.00 ± 18.36, p value < 0.01; function: 13.17 ± 7.33 vs 10.30 ± 5.84, p value: 0.01; overall: 10.32 ± 6.22 vs 8.25 ± 6.22, p value: 0.03; symptoms: 26.30 ± 10.39 vs 21.44 ± 8.58, p value < 0.01). Vitamin B12 also improved anxiety scores from 9.33 ± 4.30 to 7.70 ± 3.60, p value: 0.01. Depression, pain-VAS, and SF-12 didn't improve following the treatment. The Generalized estimating equations (GEE) analysis showed the improvement in total FIQR score is not cofounded by the improvement of anxiety and patients' baseline characteristics. CONCLUSIONS: This study showed a short course of sublingual vitamin B12, 1000 mcg daily, significantly improves the severity of FM and anxiety score. We postulate that vitamin B12 has a strong potential to consider, at least, as adjunctive therapy of FM. TRIAL REGISTRATION: The study protocol was approved by the ethics committee of Guilan University of Medical Sciences (IR.GUMS.REC.1400.197) in accordance with the World Medical Association's code of ethics (Declaration of Helsinki, revised in Brazil 2013), and registered at an ICMJE and WHO recognized registry of clinical trials ( www.irct.ir ) on 28/08/2021 (registration number: IRCT20200920048782N1).

Nociplastic pain concept, a mechanistic basis for pragmatic approach to fibromyalgia.

Nociplastic pain (NP), as a mechanistic term, denotes pain arising from altered nociception without clear evidence of tissue or somatosensory damage. Fibromyalgia (FM), a prototypical NP condition, incorporates a broad continuum of phenotypes with a distinct neurobiological signature and shared NP attributes. The nociplastic concept may provide a new opportunity for early diagnosis of FM by identifying the characteristic NP features before a state of pain generalization and symptoms clustering. In this approach, even individual symptoms associated with NP features are worthy of attention to denote FM. It may provide a timely diagnosis of FM before clinical progression to a severe and hard-to-manage condition. Furthermore, collecting all various FM phenotypes under the nociplastic concept and not delimiting FM to the only typical presentation allows investigators to identify FM subgroups reflecting potentially distinct pathophysiologic mechanisms and biomarkers. This viewpoint can be served in future studies to develop individualized management. In this review, we postulate a novel approach to early FM diagnosis and management based on NP conceptualization and phenotype recognition. Key Points • FM as a NP condition represents overlapping clinical phenotypes and incomplete presentations especially in early stage of illness. • The mechanistic approach based on the NP features of FM can be implicated in the timely diagnosis and management of FM. • The NP-based approach to FM provides a broader viewpoint beyond FM delimitation to pain generalization and polysymptomatic complaints.

Comparison of the serum brain-derived neurotrophic factor (BDNF) between fibromyalgia and nociceptive pain groups; and effect of duloxetine on the BDNF level.

BACKGROUND: The primary objective was to compare the serum brain-derived neurotrophic factor (BDNF) level in the patients with two types of pain: fibromyalgia (FM) and non-FM nociceptive pain (non-FM NP). The secondary objective was to investigate the effect of duloxetine on serum BDNF in FM patients and assess the direction of BDNF changes' relation to clinical parameters' alterations. METHODS: This is a study on 73 patients (50 FM and 23 non-FM chronic non-inflammatory pain patients). Serum BDNF was first compared between both groups. Patients with FM, then prospectively, underwent standardized FM treatment with duloxetine maximized to 60 mg/day. The Revised Fibromyalgia Impact Questionnaire (FIQR), Short-Form Health Survey (SF-12), pain visualized analog scale (pain VAS), Beck Depression Inventory-II (BDI-II), polysymptomatic distress scale (PSD) and serum BDNF were measured and compared at baseline and 4 weeks after treatment in FM group. RESULTS: The mean of adjusted BDNF level in the FM group had no significant difference than the non-FM NP group ((5293.5 ± 2676.3 vs. 6136.3 ± 4037.6; P value = 0.77). Using linear mixed model, we showed that duloxetine reduced BDNF level significantly in FM patients, even after adjusting for depression, pain and severity of the disease (P < 0.01). The FIQR, BDI-II, PSD, and pain VAS improved significantly after duloxetine treatment. CONCLUSIONS: Non-significant BDNF level difference between FM and non-FM nociceptive pain suggested that peripheral BDNF is not a pathophysiological feature of FM. The decreased BDNF level parallel with improvement of PSD/pain scores after duloxetine treatment indicates BDNF alteration in the pain modulation process, regardless of cause and effect.

Validity and reliability of the Persian version of illness invalidation inventory (3*I) among patients with non-inflammatory rheumatic painful disorders.

BACKGROUND: The Invalidation Illness Inventory (3*I) is an instrument that assesses invalidation (including discounting and lack of understanding dimensions) experienced by patients with rheumatic disorders. This study aimed to translate and validate the 3*I in Iran. METHODS: Following translation of the 3*I into the Iranian language (Persian), a cross-sectional study was conducted. A consecutive sample of females with chronic non-inflammatory rheumatic painful diseases completed the questionnaire. Patients also completed the Revised Symptom Impact Questionnaire (SIQR) and the Short Form Health Survey-12 (SF-12). To examine convergent validity, the correlation between the 3*I, the SIQR, and the SF-12 was assessed. The reliability of the 3*I was examined by internal consistency (the Cronbach's alpha coefficient) and intraclass correlation coefficient (ICC). RESULTS: In all 196 patients participated in the study. The mean (SD) age of patients was 45.62 ± 10.70 years. Several significant correlations between the Invalidation Illness Inventory (discounting/lack of understanding) with the symptom impact (SIQR) and the short form health survey (SF-12) were observed lending support to the convergent validity of the 3*I. The Cronbach's alpha coefficients were acceptable for most dimensions and sources, ranging from 0.52 to 0.88. Most ICC values for the dimensions of 3*I were above 0.75. CONCLUSIONS: The findings indicated that the Persian version of Illness Invalidation Inventory (3*I) is a valid instrument for invalidation assessment in patients with chronic pain. Given the high frequency of perceived invalidation among patients with rheumatic painful disorders, serious attention is needed to the issue in clinical and research settings.

No effect of approved fibromyalgia drugs on the social pain (invalidation) contrary to physical pain: an open-label short-term randomized clinical trial.

OBJECTIVES: The social pain or invalidation denoting painful feeling following social conflicts or misunderstanding about illness legitimacy has been proposed as a salient disabling symptom besides physical pain or non-pain symptoms in fibromyalgia (FM). We sought to evaluate the effect of 1-month administration of duloxetine or pregabalin on the invalidation dimensions in FM patients with respect to the comparison of these two drugs on this issue. METHOD: This open-label randomized clinical trial study was performed on FM patients whose diagnoses were confirmed by a rheumatologist based on the 2016 American College of Rheumatology (ACR). Primary outcome measure (Illness Invalidation Inventory (3*I)) and secondary outcome measures (Beck Depression Inventory-II (BDI-II), widespread pain index (WPI), and polysymptomatic distress scale (PSD)) were compared before and after treatment, using paired t test or Wilcoxon signed test. RESULTS: Of 81 eligible FM patients, 44 patients in the duloxetine arm and 27 patients in the pregabalin arm completed the study protocol. Overall, no significant improvement was seen in 3*I scores after treatment with either duloxetine or pregabalin, except in the lack of understanding of medical professionals which improved after treatment with pregabalin (2.43 ± 1.38 to 1.79 ± 0.94, p value: 0.01). There were no intragroup and intergroup differences in the effects of duloxetine and pregabalin on 3*I scores when adjusted with the cofounders. Both duloxetine and pregabalin improved WPI, BDI-II, and PSD scores significantly. CONCLUSIONS: Short-term FM pharmacological treatment had no effect on social pain. This finding was regardless of drug type, improvement of physical pain, and depression.

Implication of the Nociplastic Features for Clinical Diagnosis of Fibromyalgia: Development of the Preliminary Nociplastic-Based Fibromyalgia Features (NFF) Tool.

OBJECTIVE: Nociplastic concept incorporates a broad continuum of pain phenotypes shared with clinical peculiarity. This study aimed to develop and validate a diagnostic tool, the preliminary Nociplastic-based Fibromyalgia Features (NFF), to detect fibromyalgia (FM) in patients with chronic pain. METHODS: Items requiring yes or no responses and relating to the most relevant clinical nociplastic pain (NP) features of FM were compiled by a group of expert rheumatologists. The provisional list was tested in a prospective study on 185 consecutive patients with chronic pain (126 patients with FM and 59 patients with non-FM non-inflammatory chronic pain) diagnosed based on expert decision. Identification of the most discriminant combinations of items for FM and the calculation of their sensitivity and specificity were based on both univariate and multivariate (stepwise logistic regression) analyses. All participants were investigated through the final NFF, the 2011 American College of Rheumatology (ACR) criteria, and the 2016 ACR criteria. NFF performance was assessed with receiver operating characteristic curve analysis. RESULTS: Based on multivariate analyses, we retained only seven items in the final version of the NFF. A cut-off score of 4 (corresponding to the number of positive items) gave the highest rate of correct identification of patients (85%), with a sensitivity of 82% and a specificity of 91%. The NFF showed the highest concordance rate with expert diagnosis (85%) and the lowest value (77%) with the ACR 2016 criteria. CONCLUSION: The preliminary NFF with respect to the various aspects of NP showed good performance for detection of the FM in the clinical setting. This tool may provide a more pragmatic approach to the timely diagnosis of FM.

High cost of illness in fibromyalgia patients in Iran, irrespective of disease severity: A prospective cost study.

AIMS: This study aimed to estimate the economic burden of fibromyalgia (FM) in 6 months, using a cost-diary, and to evaluate its relationship with the disease severity. METHODS: This is a prospective cost-of-illness study on 62 participants with an FM diagnosis within a 6 month period. Patients completed the questionnaires, including FIQR (Revised Fibromyalgia Impact Questionnaire) and SF-12 (12-item short-form survey). The cost-diary method was used to track the cost of the disease. The participants received six cost-diary booklets during the study period to report their FM-related costs, hours, and days of productivity loss. The final costs are reported in US dollars. RESULTS: Most of the participants were women (90.3%) with a mean (±SD) age of 40.80 (±5.50) years and a mean (±SD) FIQR score of 54.38 (±14.13). Moreover, 45.2% of patients fulfilled all six booklets, whereas 24.2% returned only one booklet. The participants showed a mean (±SD) direct healthcare, non-healthcare, and indirect cost of $ 2817.08 (±$ 1860.04), $ 1497.98(±$ 1358.21), and $ 1449.05(±$ 3637.41) per patient for 6 months, respectively. CONCLUSION: Fibromyalgia is associated with high health-related and non-health-related costs in our country, irrespective of its severity. This study warrants urgent consideration in managing the disease burden on both patients and society.

Implication of invalidation concept in fibromyalgia diagnosis.

OBJECTIVES: The invalidation or social pain is an important but neglected issue in polysymptomatology of fibromyalgia (FM). This study sought whether tracing-perceived invalidation could be effective to discriminate between the presence and absence of FM in chronic pain patients with respect to five different sources, including spouses, family, colleagues, health professionals, and social services. METHODS: A total of 207 consecutive chronic pain patients were evaluated for the presence of FM by rheumatologic assessment. Invalidation was measured by the Illness Invalidation Inventory (3*I). Receiver operator characteristic (ROC) analyses were used to evaluate the ability of 3*I dimensions and sources to discriminate having FM among chronic pain patients. Binary logistic regression analyses were performed. RESULTS: The perceived discounting and lack of understanding from spouse and family sources were higher in FM rather than non-FM patients. ROC analyses demonstrated that invalidation dimensions stemming from spouse and family could appropriately discriminate between the presence and absence of FM. The area under the curve (AUC) for other sources showed non-significant values. Adjusted logistic regression analysis by age, education level, and work status showed that discounting by family and lack of understanding by the spouse could be significant predictors of FM (OR 2.30; 95% CI 1.29-4.11, P = 0.005; OR 1.72; 95% CI 1.08-2.74, P = 0.022, respectively). CONCLUSIONS: This study elucidated the discriminatory power of invalidation in identification of FM from non-FM patients, especially when originated from spouse and family. Our results provide a basis to propose the invalidation as a salient component in the FM dictionary parallel to other famous FM symptoms. Key Points • The incorporation of newly highlighted social definition of pain seems warranted in the pain practice. • Despite proposing invalidation in painful conditions, its diagnostic role in FM remains unexplored. • Acknowledging of invalidation or social pain in polysymptomatology of FM could shift the paradigm of diagnosis of FM.

Two sides on the fibromyalgia coin: physical pain and social pain (invalidation).

Although fibromyalgia (FM) has been traditionally defined by the extent of physical pain sites alongside other non-pain symptoms, recent evidence has highlighted the importance of social dimension in definition of pain perception. Social pain or invalidation, which denotes painful feeling following social conflicts or misunderstanding about illness legitimacy, is an important but ignored issue in the FM lexicon. While physical and social pain seem to be different and separate entities, we hypothesize that they are completely intertwined with indistinct borders in FM. Accumulating emergent neuroscience and behavioral evidence highlights the overlapping of physical and social pain in different painful conditions. However, this overlapping seems to reach its maximum in FM. This review sheds more light on the tight interconnectivity between physical and social pain in FM from the perspective of intuitional commonalities, clinical aspects, and shared neural pathways. The conceptualization of FM as an integrative physical-social pain paradigm will move us closer to necessitating the incorporation of social pain in future models of FM diagnosis and management. Key Points • Considering of social pain as one key concept is relatively mute in FM literature. • Overlapping of physical and social pain seems to be unique in FM due to its nature. • Acknowledging social pain in the FM lexicon could shift the paradigm of diagnosis and management of FM patients.

Fibromyalgia diagnostic model derived from combination of American College of Rheumatology 1990 and 2011 criteria.

BACKGROUND: We aimed to explore the American College of Rheumatology (ACR) 1990 and 2011 fibromyalgia (FM) classification criteria's items and the components of Fibromyalgia Impact Questionnaire (FIQ) to identify features best discriminating FM features. Finally, we developed a combined FM diagnostic (C-FM) model using the FM's key features. METHODS: The means and frequency on tender points (TPs), ACR 2011 components and FIQ items were calculated in the FM and non-FM (osteoarthritis [OA] and non-OA) patients. Then, two-step multiple logistic regression analysis was performed to order these variables according to their maximal statistical contribution in predicting group membership. Partial correlations assessed their unique contribution, and two-group discriminant analysis provided a classification table. Using receiver operator characteristic analyses, we determined the sensitivity and specificity of the final model. RESULTS: A total of 172 patients with FM, 75 with OA and 21 with periarthritis or regional pain syndromes were enrolled. Two steps multiple logistic regression analysis identified 8 key features of FM which accounted for 64.8% of variance associated with FM group membership: lateral epicondyle TP with variance percentages (36.9%), neck pain (14.5%), fatigue (4.7%), insomnia (3%), upper back pain (2.2%), shoulder pain (1.5%), gluteal TP (1.2%), and FIQ fatigue (0.9%). The C-FM model demonstrated a 91.4% correct classification rate, 91.9% for sensitivity and 91.7% for specificity. CONCLUSIONS: The C-FM model can accurately detect FM patients among other pain disorders. Re-inclusion of TPs along with saving of FM main symptoms in the C-FM model is a unique feature of this model.

Comparing duloxetine and pregabalin for treatment of pain and depression in women with fibromyalgia: an open-label randomized clinical trial.

BACKGROUND: Duloxetine and pregabalin are among the most widely used medications in the treatment of patients with fibromyalgia syndrome (FM). OBJECTIVES: To add to the very few lines of evidence that exist on the comparative safety and efficacy of these two medications. METHODS: In this open-label randomized clinical trial, outpatient women, who were diagnosed with FM based on American College of Rheumatology 2010 criteria, and had an age range of 18-65 years old were assigned to either duloxetine 30-60 mg or pregabalin 75-150 mg per day for 4 weeks. Patients were excluded in cases of having used duloxetine, pregabalin, gabapentin, or antidepressants within 12 weeks prior to the study, having had a history of comorbid medical conditions that could provoke chronic pain, or having had comorbid neuropsychiatric disorders, except for major depressive/anxiety disorders. Primary outcomes were between-group differences in mean score changes from baseline to end point for Widespread Pain Index (WPI) and Beck Depression Inventory-II. Secondary outcomes were the same statistical estimates, but for Fibromyalgia Impact Questionnaire-Revised and 12-Item Short Form Survey. Descriptive statistics and independent samples t-test were the main methods of analysis. ( www.irct.ir ; IRCT2016030626935N1). RESULTS: Among all the scales, only WPI scores improved with a statistically significant difference between the two treatment arms, favoring duloxetine (Mean difference in score change - 2.32, 95% CI, -4.46 to - 0.18; p = 0.034; Cohen's d 0.53 95% CI, 0.04 to 1.02). Drop out rate and cumulative incidence of nausea was significantly higher in the duloxetine arm compared to the pregabalin arm. CONCLUSION: This study provides further evidence on higher efficacy of duloxetine compared to pregabalin for the treatment of pain in patients with fibromyalgia. Future comprehensive pragmatic clinical trials are warranted.

Challenges in fibromyalgia diagnosis: from meaning of symptoms to fibromyalgia labeling.

Fibromyalgia (FM) is a contested illness with ill-defined boundaries. There is no clearly defined cut-point that separates FM from non-FM. Diagnosis of FM has been faced with several challenges that occur, including patients' health care-seeking behavior, symptoms recognition, and FM labeling by physicians. This review focuses on important but less visible factors that have a profound influence on under- or over-diagnosis of FM. FM shows different phenotypes and disease expression in patients and even in one patient over time. Psychosocial and cultural factors seem to be a contemporary ferment in FM which play a major role in physician diagnosis even more than having severe symptom levels in FM patients. Although the FM criteria are the only current methods which can be used for classification of FM patients in surveys, research, and clinical settings, there are several key pieces missing in the fibromyalgia diagnostic puzzle, such as invalidation, psychosocial factors, and heterogeneous disease expression. Regarding the complex nature of FM, as well as the arbitrary and illusory constructs of the existing FM criteria, FM diagnosis frequently fails to provide a clinical diagnosis fit to reality. A physicians' judgment, obtained in real communicative environments with patients, beyond the existing constructional scores, seems the only reliable way for more valid diagnoses. It plays a pivotal role in the meaning and conceptualization of symptoms and psychosocial factors, making diagnoses and labeling of FM. It is better to see FM as a whole, not as a medical specialty or constructional scores.

Are general practitioners well informed about fibromyalgia?

AIM: Fibromyalgia syndrome (FMS) is a common rheumatologic disorder characterized by easy fatigability, widespread musculoskeletal pain and sleep disorder. In spite of its high prevalence, general practitioners, as primary care providers, seem to have inadequate knowledge about FMS. This study aimed to assess Iranian general practitioners' knowledge about FMS and its treatment. METHOD: A detailed questionnaire (including items on signs and symptoms, diagnostic criteria and treatment) was completed by 190 general practitioners (54.7% male; mean age: 41 years). Data analysis was performed with SPSS for Windows 15.0 and awareness about all aspects of FMS was reported as percentages. RESULTS: About one-third (30%) of the participants had seen at least one case of FMS during their practice. Most subjects (62.7%) claimed to know 1-6 tender points. Only 3.2% knew 16-18 points. The common proposed symptoms of FMS were widespread pain (72.6%), excessive fatigue (72.6%), weakness (60.5%), sleep disorder (36.3%), anxiety (34.7%) and depression (34.2%). Wrong symptoms including elevated erythrocyte sedimentation rate and C-reactive protein, arthritis, joint swelling, weight loss and abnormal radiologic findings were selected by 27.9%, 18.9%, 14.7%, 12.6% and 2.1% of the physicians, respectively. Moreover, selective serotonin reuptake inhibitors, tricyclic antidepressant and pregabalin were identified as treatment options for FMS by, respectively, 45.8%, 22.1% and 15.3% of the participants. Finally, 52.1% and 23.7% of the subjects incorrectly considered nonsteroidal anti-inflammatory drugs and corticosteroids as treatment modalities for FMS. CONCLUSION: Iranian general practitioners are not well informed about FMS. Therefore, FMS should be specifically integrated in continuing medical education programs and undergraduate medical training curriculum.

The acute effect of maximal exercise on plasma beta-endorphin levels in fibromyalgia patients.

BACKGROUND: This study aimed to investigate the effect of strenuous exercise on ß-endorphine (ß-END) level in fibromyalgia (FM) patients compared to healthy subjects. METHODS: We enrolled 30 FM patients and 15 healthy individuals. All study participants underwent a treadmill exercise test using modified Bruce protocol (M.Bruce). The goal of the test was achieving at least 70% of the predicted maximal heart rate (HRMax). The serum levels of ß-END were measured before and after the exercise program. Measurements were done while heart rate was at least 70% of its predicted maximum. RESULTS: The mean ± the standard deviation (SD) of exercise duration in the FM and control groups were 24.26 ± 5.29 and 29.06 ± 3.26 minutes, respectively, indicating a shorter time to achieve the goal heart rate in FM patients (P < 0.003). Most FM patients attained 70% HRMax at lower stages (stage 2 and 3) of M.Bruce compared to the control group (70% versus 6.6%, respectively; P < 0.0001). Compared to healthy subjects, FM patients had lower serum ß-END levels both in baseline and post-exercise status (Mean ± SD: 122.07 ± 28.56 µg/ml and 246.55 ± 29.57 µg/ml in the control group versus 90.12 ± 20.91 µg/ml and 179.80 ± 28.57 µg/ml in FM patients, respectively; P < 0.001). CONCLUSIONS: We found that FM patients had lower levels of ß-END in both basal and post-exercise status. Exercise increased serum the ß-END level in both groups but the average increase in ß-END in FM patients was significantly lower than in the control group.

Serum Vitamin D Status in Iranian Fibromyalgia Patients: according to the Symptom Severity and Illness Invalidation.

BACKGROUND: This study was designed to assess serum vitamin D status (25-OHD) in the fibromyalgia (FM) patients and to compare it with a healthy control group. It also aimed to investigate the correlation of serum vitamin D level with FM symptom severity and invalidation experiences. METHODS: A total of 74 consecutive patients with FM and 68 healthy control participants were enrolled. The eligible FM patients completed the Illness Invalidation Inventory (3(*)I), the Revised Fibromyalgia Impact Questionnaire (FIQR) and a short-form health survey (SF-12). Venous blood samples were drawn from all participants to evaluate serum 25-OHD levels. Mann-Whitney tests and multiple logistic regression analyses were performed and Spearman's correlations were calculated. RESULTS: 88.4% of FM patients had low levels of serum 25-OHD. FM patients had significantly higher level of serum 25-OHD than the control group (17.24 ± 13.50 and 9.91 ± 6.47 respectively, P = 0.0001). There were no significant correlations between serum 25-OHD levels and the clinical measures of disease impact, invalidation dimensions, and health status. Multiple logistic regression analyses revealed that an increased discounting of the disease by the patient's spouse was associated with a 4-fold increased risk for vitamin D deficiency (OR = 4.36; 95% CI, 0.95-19.87, P = 0.05). CONCLUSIONS: This study showed that although high rates of vitamin D insufficiency or deficiency were seen among FM patients and healthy non-FM participants, but it seems there was no intrinsic association between FM and vitamin D deficiency. Addressing of invalidation experience especially by the patient's spouse is important in management of FM.

The impact of fibromyalgia on health status according to the types, demographic background and pain index.

OBJECTIVES: To compare fibromyalgia (FM) core symptoms, FM impact severity and health status between the recently defined type A and type B of fibromyalgia. To compare disease impact and health status between FM patients and non-FM chronic pain control group. Finally, to compare health related quality of life and disease symptom severity by demographic background and widespread pain index (WPI). METHODS: A total of 284 consecutive FM patients and 96 non-FM control patients were enrolled. The information of four questionnaires including the Fibromyalgia Survey Questionnaire (FSQ), the Fibromyalgia Impact Questionnaire (FIQ), the 12-item Short Form Health Survey (SF-12) and questionnaires regarding demographic features were collected from a local FM registry. RESULTS: Of all FM patients, 102 (94%) and 7 (6%) were type A and B, respectively. We found statistically significant differences in symptomatology, the FIQ scores and the SF-12 subscales across two type and control groups (p<0.001). However, when we compared these scores pairwise, except WPI there were no significant differences in other scores between type A and B. Also, there were no significant differences in FIQ and SF-12 scores across different age or educational status groups. Interestingly, patients with higher WPI had significantly higher FIQ (overall, symptom, and total) scores, worse PCS-12 and MCS-12 scores, and vice versa. CONCLUSIONS: Type B constitutes a minor but important component of FM that probably has a marked impact on the patient's perceived illness severity and quality of life. Further, WPI probably is the most important single indicator of disease severity and quality of life in FM.

Validation of fibromyalgia survey questionnaire and polysymptomatic distress scale in a Persian population.

The aim of this study was to assess validity of the fibromyalgia survey questionnaire (FSQ) and polysymptomatic distress scale (PSD) in an Iranian population. We also sought to classify the severity levels of fibromyalgia (FM) symptoms according to the PSD scale. Participants were divided into FM and non-FM chronic pain disorder groups according to expert physician diagnosis. Patients in both groups answered to Persian-translated version of FSQ, fibromyalgia impact questionnaire (FIQ) and Short-Form-12 (SF-12). Both 1990 ACR criteria and FSDC were assessed in participates of two groups. Internal consistency and construct validity were evaluated. There was good internal consistency measured by Cronbach's alpha (0.814 for FSQ). FSQ and its subscales correlated significantly with FIQ scores and SF-12 subscales, indicating acceptable construct validity. The concordance rates of FSQ with 1990 ACR criteria and expert diagnosis were 61.2 and 75.7, respectively (convergence validity). The mean score of PSD and its components in FM group were significantly more than in control groups (discriminative validity). Using lower PSD score cutoff (≥8.5) for the diagnosis of fibromyalgia appeared to be the most effective approach in our population. ROC analysis of the PSD scores revealed 8.5-11.5, 11.5-15 and more than 15, respectively, as a mild, moderate and severe FM. Persian version of FSQ was a valid instrument for application in survey research among Iranian patients with chronic pain disorders. The current study revealed that PSD could be used as a valid tool for assessment of symptoms intensity regardless of fibromyalgia diagnosis.