The Iceberg nature of fibromyalgia burden: The clinical and economic aspects

This review has focused on important but less visible aspects of fibromyalgia (FM) with respect to the high impact of this disorder on patients and societies. FM is a common but challengeable illness. It is characterized by chronic widespread pain, which can be accompanied by other symptoms including fatigue, sleep disturbances, cognitive dysfunction, anxiety and depressive episodes. While our understanding of this debilitating disorder is limited, diagnosis and treatment of this condition is very difficult, even in the hands of experts. Due to the nature of disease, where patients experience invalidation by medical services, their families and societies regarding the recognition and management of disease, direct, indirect and immeasurable costs are considerable. These clinical and economic costs are comparable with other common diseases, such as diabetes, hypertension and osteoarthritis, but the latter usually receives much more attention from healthcare and non-healthcare resources. Present alarming data shows the grave and "iceberg-like" burden of FM despite the benign appearance of this disorder and highlights the urgent need both for greater awareness of the disease among medical services and societies, as well as for more research focused on easily used diagnostic methods and target specific treatment. © The Korean Pain Society, 2015

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 β-endorphine (β-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 β-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 β-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 β-END in both basal and post-exercise status. Exercise increased serum the β-END level in both groups but the average increase in β-END in FM patients was significantly lower than in the control group. � The Korean Pain Society, 2016

Correlation of invalidation with symptom severity and health status in fibromyalgia

Objective. Invalidation is a new construct in health psychology, especially in diseases with inherently invisible symptoms such as FM. It can potentially affect both the quality of life and disease severity in patients with FM. This study aimed to investigate the correlation of illness invalidation with health status and symptom severity in FM. Methods. A total of 112 consecutive patients with FM referred to the rheumatology clinic were enrolled. Invalidation was measured by the Illness Invalidation Inventory (3*I). To measure patient status and progress of FM, the Revised Fibromyalgia Impact Questionnaire (FIQR) was used and patients' quality of life was assessed by the 12-item Short Form Health Survey (SF-12). Multiple linear regression analyses were performed and Spearman's correlations were calculated. Results. All the patients were female and aged between 18 and 61 years. No significant differences in discounting and lack of understanding between various sources of invalidation were found. The strongest correlation was observed between FIQR symptom score and discounting by work (r = 0.519, P < 0.05). Multiple linear regression analyses revealed that only discounting from the spouse significantly predicted FIQR total scores of FM patients P = 0.03 (CI 0.28, 10.64). Conclusion. Discounting correlated more strongly with SF-12 subscales and FIQR domains than did lack of understanding. The current study revealed that active negative social responses and the source of invalidation are important in predicting symptom severity and quality of life in FM. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved

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. © The Korean Pain Society, 2019

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. © 2019, Springer Nature Switzerland AG

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 Korean Pain Society, 2016

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. © 2020, International League of Associations for Rheumatology (ILAR)

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. © 2021 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Lt

Common MEFV mutation analysis in 36 Iranian patients with familial Mediterranean fever: Clinical and demographic significance

The aim of our study was to determine the spectrum of the 12 most common familial Mediterranean fever gene (MEFV) mutations in Iranian patients with heterogeneous ethnicity, using the familial Mediterranean fever (FMF) strip assay test. A total of 36 patients were diagnosed according to established clinical criteria. Genomic DNA from all patients was tested for 12 common mutations located in exon 2 (E148Q), 3 (P369S), 5 (F479L), 10 M680I (G>C), M680I (G>A), I692del, M694V, M694I, K695R, V726A, A744S, R761H, respectively, using the FMF strip assay test. Of the 35 patients with mutations, ten were homozygote, 20 were compound heterozygote, and five were heterozygote. The most frequent genotype was M680I/M680I (6 patients, 16.7%). The most frequent mutation was M680I, followed by M694V, and V726A. The FMF strip assay test for common these 12 mutations was positive in 90.6% of alleles in this study, indicating that it appears to be an effective method for FMF mutation screening in Iranian patients. © 2010 Japan College of Rheumatology

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