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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 25  |  Issue : 3  |  Page : 99-103

Fibromyalgia, a disease or a subclinical presentation? A different perspective


1 Department of Physical Medicine, Rheumatology and Rehabilitation, Faculty of Medicine, Tanta University, Tanta, Egypt
2 Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Tanta University, Tanta, Egypt

Date of Submission16-Nov-2019
Date of Decision03-Dec-2019
Date of Acceptance18-Dec-2019
Date of Web Publication08-Aug-2020

Correspondence Address:
MD Shyma A Hablas
Department of Rheumatology and Rehabilitation, Faculty of Medicine, Tanta University, Tanta, 31 111
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/kamj.kamj_29_19

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  Abstract 


Context Fibromyalgia is a disease of exclusion. There is a huge overlap between symptoms of fibromyalgia and a lot of rheumatic, endocrinal, and metabolic diseases. Confirming the diagnosis of fibromyalgia might mask the diagnosis of a lot of conditions especially with the lack of periodic reevaluation to fibromyalgia patients.
Objective The aim was to evaluate the diagnosis of fibromyalgia in unresponsive patients after more than a year of diagnosis.
Patients and methods This is a cross-sectional observational study performed on 100 patients diagnosed with primary fibromyalgia for more than 1 year and that showed no response to two or three lines of treatments. Patients were investigated for erythrocyte sedimentation rate, rheumatoid factor, antinuclear antibody, in addition to serum vitamin D levels, total serum calcium, serum phosphorus, thyroid-stimulating hormone, parathormone hormone, and Dual energy Xray Absorptiometry (DEXA) scan. Patients were regrouped after laboratory investigations into two groups. Group I are patients who showed no abnormalities in their laboratory investigations. Group II are patients who showed abnormalities in their laboratory investigations. Functional assessment was performed for all patients by the fatigue assessment scale, insomnia severity index, and the visual analog scale for pain for patients in the beginning of the study and after 6 months.
Results Less than 20% of the patients remained with no abnormality in their laboratory investigations, while about 80% showed laboratory abnormalities for other associated conditions.
Conclusion Fibromyalgia patients showing response to treatment should be investigated on a regular basis even for markers that were shown to be normal. Treatment of any associated condition can improve symptoms of fibromyalgia dramatically.

Keywords: chronic fatigue syndrome, irritable bowel disease, subclinical hypothyroidism, vitamin D deficiency, widespread pain


How to cite this article:
Hablas SA, Darwish NF, Gaber RA. Fibromyalgia, a disease or a subclinical presentation? A different perspective. Kasr Al Ainy Med J 2019;25:99-103

How to cite this URL:
Hablas SA, Darwish NF, Gaber RA. Fibromyalgia, a disease or a subclinical presentation? A different perspective. Kasr Al Ainy Med J [serial online] 2019 [cited 2020 Sep 30];25:99-103. Available from: http://www.kamj.eg.net/text.asp?2019/25/3/99/291757




  Introduction Top


Fibromyalgia is a systemic disorder characterized by widespread musculoskeletal pain accompanied by fatigue, sleep, and mood disturbances. Fibromyalgia often coexists with other painful conditions, such as: irritable bowel syndrome, migraine, interstitial cystitis, and temporomandibular joint disorders [1],[2],[3],[4].

The American College of Rheumatology (ACR) classification criteria require a specialized examination to quantify tender point distribution and number, which is not the case for the 2010 ACR diagnostic criteria that depend mainly on history [5],[6].

Fibromyalgia is a diagnosis of exclusion so any disorder that mimics the manifestation of fibromyalgia must be excluded first. These disorders have nearly the same musculoskeletal and psychological manifestations of fibromyalgia, for example, thyroid dysfunctions, vitamin D deficiency, and rheumatic and metabolic diseases [7].

Treatment of fibromyalgia includes lifestyle modifications, behavioral and psychological therapy, aerobic exercise, and pharmacological therapy to alleviate symptoms of anxiety, depression, sleep disturbance, musculoskeletal pain, and fatigue [8].


  Patients and methods Top


Patients

This is a cross-sectional, observational study, performed on 100 patients diagnosed with primary fibromyalgia for more than 1 year according to the 2010 ACR diagnostic criteria for fibromyalgia [6] and showed no response to two or three lines of treatments.

Ethics, consent, and permission

The patients were collected from the outpatient clinic of Physical Medicine, Rheumatology and Rehabilitation Department, Faculty of Medicine, Tanta University. All the investigations were conducted at the Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Tanta University.

The study was approved by the Local Research Ethics Committee of Faculty of Medicine, Tanta University, approval code 31082/07. Written consents for publication were obtained from all patients.

An exclusion criterion was fibromyalgia secondary to any known chronic systemic disease.

Methods

All patients were investigated for erythrocyte sedimentation rate, rheumatoid factor, antinuclear antibody, in addition to serum vitamin D level, total serum calcium, serum phosphorus, thyroid-stimulating hormone, parathormone hormone, and Dual energy Xray Absorptiometry (DEXA) scan. After investigations patients were regrouped into two groups.

Group I included patients who showed no abnormalities in their laboratory investigations. Group II included patients who showed abnormalities in their laboratory investigations. Functional assessment for all patients was by
  1. Fatigue assessment scale [9].
  2. Insomnia severity index [10].
  3. Visual analog scale for pain [11].


Which were conducted at the beginning of the study and after 6 months of receiving treatment of any associated conditions that were detected.

Statistical analysis

All statistical calculations and analysis were done using the computer program SPSS version 16 (SPSS 16 Inc., Chicago, IL). Frequency distribution, Student’s t-test were used in analysis. A difference was considered to be statistically significant when the probability values or P values were less than 0.05. P values less than 0.01 were considered highly significant. P values greater than 0.05 were considered statistically nonsignificant.


  Results Top


This study examined 100 adult patients (14 men and 86 women) with primary fibromyalgia. The mean age of our patients was 43.5±9.1 years with mean disease duration of 4.2±1.1 years. Symptom frequency among our patients is illustrated in [Table 1]. Laboratory investigations are illustrated in [Table 2]. Classification of patients according to the presence or absence of associated conditions are given in [Table 3]. Symptom frequency among patients after 6 months of treatment of the associated conditions is given in [Table 4]. Comparison between functional assessment of patients without any associated conditions and patients with associated conditions after 6 months of treatment is given in [Table 5].
Table 1 Frequency of symptoms among all patients

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Table 2 The distribution of mean values of ESR, RF, ANA, serum calcium, serum phosphorus, sreum vitamin D, TSH, T3, T4, parathormone hormone, bone mineral denisty of hip and lumber spine

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Table 3 Classification of patients according to the presence or absence of associated conditions

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Table 4 Symptoms frequency among patients after 6 months of receiving treatment to the associated conditions

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Table 5 Functional assessment of fibromyalgia patients without associated conditions and fibromyalgia patients with associated conditions after 6 months of receiving treatment for the associated conditions

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  Discussion Top


Fibromyalgia has been proven to have neurophysiological abnormalities that result in abnormal pain processing and abnormal levels of chemical transmitters that are responsible for central sensitization and whole-body hypersensitivity to pain also, a neuroendocrinal abnormalities and abnormal hypothalamic-pituitary adrenocortical axis were detected in fibromyalgia patients [12],[13]. These changes resemble exactly what happens to the body in stressful conditions or any other chronic diseases and these changes are responsible for the symptoms in fibromyalgia patients. Unfortunately, these changes are undetectable by ordinary laboratory workup or clinical assessments [14],[15],[16].

The highly frequent symptoms in our patients were fatigue, widespread pain, and sleep disturbance ([Table 1]), which was also reported in a German study by Häuser et al. [17] These are the same vague symptoms that patients with vitamin D deficiency, endocrinal abnormalities especially hyperthyroidism or hypothyroidism or osteoporosis complain of. These diseases are slowly progressive and sometimes their abnormalities are on the level of receptors, which make it more difficult to detect by ordinary laboratory workup.

The laboratory assessment of erythrocyte sedimentation rate, rheumatoid factor, and antinuclear antibody showed normal parameters while serum 25(OH) vitamin D showed deficiency in 55 patients with a mean±SD of 11.27±7.12 ([Table 2] and [Table 3]). The same results were obtained from Matthana [18] and Abokrysha [19] while Tandeter et al. [20] found no relation between vitamin D and fibromyalgia. Actually, we are not talking here about fibromyalgia patients being at risk of developing other conditions, rather we want to clarify that a lot of conditions among them, vit. D deficiency, are having the exact same symptoms we rely on to diagnose fibromyalgia. Vitamin D might be the primary cause for the symptoms and having the highest frequency among our patients might be related to other epidemiological factors.{Table 3}

Subclinical hypothyroidism with a thyroid-stimulating hormone of more than 5.5 was found in 12 patients with a mean±SD of 6.14±1.4 ([Table 2] and [Table 3]). The same was reported in a study of Suk et al. [21] John [22] et al. studied the effectiveness of eltroxin therapy in the treatment of euthyroid fibromyalgia and suggested in his results that patients with fibromyalgia might have resistance to thyroid hormones and needs a higher level of eltroxin therapy. So, having resistance to thyroid hormones might be the cause for musculoskeletal symptoms.

We found 10 osteoporotic patients with a mean of −2.93±0.23 in the lumbar region by DEXA scan ([Table 2] and [Table 3]). Upala [23] reported that fibromyalgia patients are at risk for osteoporosis. Though fibromyalgia is a disease that has a lot of co-morbidities that might be higher than the general population, treatment of these associated conditions resulted in nearly full improvement of fibromyalgia symptoms which raises our question: Can fibromyalgia be a clinical presentation rather than be a separate entity in these patients?We also found four patients with primary hyperparathyroidism. Among our patients the diagnosis was based on the level of their parathyroid hormone 153.75±52.81 and confirmed with the parathyroid scan ([Table 2] and [Table 3]). The results of Freitas [24] were compatible with ours. Our patients reported full improvement pain and myalgia from the following day after parathyroidectomy operation.

After comparison of the functional assessment of the 19 fibromyalgia patients without associated conditions and the 81 fibromyalgia patients with associated conditions after 6 months of their treatment each according to their condition ([Table 4] and [Table 5]), we found that the most frequent symptoms showed significant improvement in fibromyalgia patients with associated conditions after treatment regardless of their different conditions and methods of treatment in comparison to fibromyalgia without association. In our study we did not analyze the use of pain medications because of their diversity with different mechanism of action but of our patients some remained on their regular medications, others became nonadherent to therapy and some stopped treatment except for NSAIDS when required.{Table 4}{Table 5}

In our opinion, stress conditions that arise from undiagnosed and untreated medical conditions can cause the same impact and same symptoms of fibromyalgia which might be misdiagnosed as fibromyalgia.

The wide range of hormonal assays and vitamin deficiencies takes long time before reaching the detectable laboratory levels and their clinical manifestations are vague enough to lead physicians to early diagnosis of fibromyalgia.

Our study and the many studies mentioned here found a great number of patients that are misdiagnosed or at least suffered from a treatable disease masked by the diagnosis of fibromyalgia. This raises our question: can fibromyalgia be a clinical presentation of these associated conditions rather than be a diagnosis of its own. We cannot generalize our results to all fibromyalgia patients because we performed our study on a subgroup of patients that were not responding to treatment.


  Conclusion Top


This study proves that fibromyalgia is a disease of exclusion even after the diagnosis has been made. Periodic evaluation of unresponsive fibromyalgia patients is mandatory even for markers that were shown to be normal.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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National Institute of Arthritis and Musculoskeletal and Skin Diseases. Fibromyalgia. Accessed. Available at: http://www.niams.nih.gov/Health_Info/Fibromyalgia/default.asp [Accessed January 28, 2018].  Back to cited text no. 1
    
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4.
Goldenberg DL. Clinical manifestations and diagnosis of fibromyalgia in adults. Available at: http://www.uptodate.com/home [Accessed January 28, 2018].  Back to cited text no. 4
    
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Wolfe F, Smythe HA, Yunus MB. The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum 1990; 33:160–172.  Back to cited text no. 5
    
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Wolfe F, Clauw DJ, Fitzcharles MA. The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res (Hoboken) 2010; 62:600–610.  Back to cited text no. 6
    
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MacReady N. Test excludes fibromyalgia in patients with rheumatic disease. Medscape Medical News. Available at: http://www.medscape.com/viewarticle/865753 [Accessed January 28, 2018].  Back to cited text no. 7
    
8.
Fitzcharles MA, Ste-Marie PA, Goldenberg DL, Pereira JX, Abbey S, Choinière M et al. 2012 Canadian Guidelines for the diagnosis and management of fibromyalgia syndrome: executive summary. Pain Res Manag 2013; 18:119–126.  Back to cited text no. 8
    
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Shahid A, Wilkinson K, Marcu S, Shapiro CM. Fatigue Assessment Scale (FAS). In: Shahid A, Wilkinson K, Marcu S, Shapiro C, (editors) STOP, THAT and One Hundred Other Sleep Scales. New York, NY: Springer 2011.  Back to cited text no. 9
    
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Sawaddiruk P, Paiboonworachat S, Chattipakorn N, Chattipakorn SC. Alterations of brain activity in fibromyalgia patients. J Clin Neurosci 2017; 38:13–22.  Back to cited text no. 12
    
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Griep EN, Boersma JW, de Kloet ER. Altered reactivity of the hypothalamic-pituitary-adrenal axis in the primary fibromyalgia syndrome. J Rheumatol 1993; 20:469–474.  Back to cited text no. 13
    
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Crofford LJ. The hypothalamic-pituitary- adrenal stress axis in fibromyalgia and chronic fatigue syndrome. Z Rheumatol 1998; 57: 67–71.  Back to cited text no. 14
    
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Martinez-Lavin M. Biology and therapy of fibromyalgia. Stress, the stress response system, and fibromyalgia. Arthritis Res Ther 2007; 9:216.  Back to cited text no. 15
    
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Tanriverdi F, Karaca Z, Unluhizarci K. The hypothalamo-pituitary-adrenal axis in chronic fatigue syndrome and fibromyalgia syndrome. Stress 2007; 10:13–25.  Back to cited text no. 16
    
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Häuser W, Zimmer C, Felde E, Köllner V. What are the key symptoms of fibromyalgia? Results of a survey of the German Fibromyalgia Association. Schmerz (Berlin, Germany) 2008; 22:176–183.  Back to cited text no. 17
    
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Matthana MH. The relation between vitamin D deficiency and fibromyalgia syndrome in women. Saudi Med J 2011; 32:925–929.  Back to cited text no. 18
    
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Abokrysha NT. Vitamin D deficiency in women with fibromyalgia in Saudi Arabia. Pain Med 2012; 13:452–458.  Back to cited text no. 19
    
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Tandeter H, Grynbaum M, Zuili I, Shany S, Shvartzman P. Serum 25-OH vitamin D levels in patients with fibromyalgia. Isr Med Assoc J 2009; 11:339–342.  Back to cited text no. 20
    
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Suk JH, Lee JH, Kim JM. Association between thyroid autoimmunity and fibromyalgia. Exp Clin Endocrinol Diabetes 2012; 120:401–404.  Back to cited text no. 21
    
22.
John CL, Richard LG, Alan JR, Jackie Y, Mervianna T, Daniel K. Effectiveness and safety of T3 (Triiodothyronine) therapy for euthyroid fibromyalgia clinical bulletin of myofascial therapy. Clin Bull Myofasc Ther J 1996; 2:2–3.  Back to cited text no. 22
    
23.
Upala S, Yong WC, Sanguankeo A. Bone mineral density is decreased in fibromyalgia syndrome: a systematic review and meta-analysis. Rheumatol Int 2017; 37:617.  Back to cited text no. 23
    
24.
Freitas JM, Costa T, Ranzolin A, Costa Neto CA, LopesMarques CD, Branco PintoDuarte AL. High frequency of asymptomatic hyperparathyroidism in patients with fibromyalgia: random association or misdiagnosis? Rev Bras Reumatol Engl Ed 2016; 56:391–397.  Back to cited text no. 24
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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