Mohammad Ali Arif  ( Department of Medicine, Shaheed Zulfiqar Ali Bhutto Medical University/Pakistan Institute of Medical Sciences, Islamabad )
Fibhaa Syed  ( Department of Medicine, Shaheed Zulfiqar Ali Bhutto Medical University, Pakistan Institute of Medical Sciences, Islamabad )
Rauf Niazi  ( Shaheed Zulfiqar Ali Bhutto Medical University (SZABMU), Pakistan Institute of Medical Sciences, Islamabad, Pakistan )
Saba Ali Arif  ( Shaheed Zulfiqar Ali Bhutto Medical University (SZABMU), Pakistan Institute of Medical Sciences, Islamabad, Pakistan )
Umme e Laila Hashmi  ( Shaheed Zulfiqar Ali Bhutto Medical University (SZABMU), Pakistan Institute of Medical Sciences, Islamabad, Pakistan )
Zakir Shah  ( Shaheed Zulfiqar Ali Bhutto Medical University (SZABMU), Pakistan Institute of Medical Sciences, Islamabad, Pakistan )

Objective: To assess the prevalence and severity of fibromyalgia in hospital-visiting patients.

Methods: The cross-sectional study was conducted at the Pakistan Institute of Medical Sciences, Islamabad, Pakistan, from July, 2018, to January, 2019, and comprised patients aged 18-75 years of either gender. Demographic information, comorbidities and previous medications were recorded for each patient. The modified American College of Rheumatology preliminary diagnostic criteria 2010-11 for fibromyalgia diagnosis. If diagnosed, the fibromyalgia impact questionnaire was administered to assess its severity. Data was analysed using SPSS 25.

Results: Of the 750 hospital-visiting patients, fibromyalgia was diagnosed in 250(33.3%); 190(76%) of them being females (p<0.0001). Comorbidities, age and increased elevated body mass index were significantly associated with fibromyalgia. Severity was not influenced by comorbidities, marital status, education or economic status (p>0.05). Menarche at a later age and menstrual irregularity were associated with fibromyalgia severity (p<0.05).

Conclusion: The hospital-based prevalence of fibromyalgia was found to be high, especially among females.

Keywords: Fibromyalgia, Chronic widespread pain, Prevalence, Hospital setting, Pakistan. (JPMA 71: 1357; 2021)

DOI: https://doi.org/10.47391/JPMA.1000

 

Introduction

 

Fibromyalgia syndrome (FMS) has remained an enigma over the years. The first mention of the syndrome appeared in literature over a century ago, with the first official diagnostic guidelines being published by the American College of Rheumatology (ACR) in 1990.¹ The diagnosis has often been contested, with its acceptance in clinical literature becoming more gradually marked over the last three decades. It remains a diagnostic challenge due to the considerable overlap in clinical features and absence of specific laboratory investigations. The disease has been surrounded by controversy regarding both its diagnosis and management, and, despite the considerable impact on patients as a result of the condition, no medical specialty has yet laid claim to the syndrome. The ACR revisited the diagnosis, and published the revised ACR 2010 preliminary diagnostic criteria.² Further revisions were undertaken in 2016, the most significant of which was published by Wolfe et al.,³ stating that FM diagnosis is valid irrespective of other diagnoses, and an FM diagnosis does not exclude the presence of other clinically important diseases.

The hallmark of FM is chronic widespread pain, the origins of which have been proposed to be neurogenic in origin. It has been postulated that a central, amplified pain perception is linked with allodynia and hyperalgesia. Other components of the syndrome include fatigue, sleep disturbances, generalised tenderness and cognitive difficulties, the latter being referred to as ‘fibro fog’.⁴ Despite the diverse and wide-ranging nature of symptoms, FM may be considered a discrete diagnosis or a constellation of clinical features. The essential aspect that warrants mention is that effective treatment for FM, both pharmacological and non-pharmacological, is now possible.⁵

Population-based epidemiological studies in the United States have estimated an FM prevalence of 2-4%, with levels rising to 15% in patients presenting to rheumatology clinics.⁶ Epidemiological data is scarce in the Asian region. The current study was planned to assess FM prevalence in the hospital setting in a cross-section of Pakistani population, and to assess FM severity.

 

Patients and Methods

 

This cross-sectional study was conducted from July, 2018, to January, 2019, at the Pakistan Institute of Medical Sciences (PIMS), which is the largest tertiary care hospital in Islamabad, catering to patients from all over Pakistan. After approval from the institutional ethics review committee, the sample size was calculated using the World Health Organisation (WHO) calculator⁷ while setting the confidence level at 99%, margin of error at 5% and the reported hospital prevalence of FM up to 36%.⁸ The sample was raised using convenience sampling technique from among patients visiting different departments of the hospital. Those included were patients of either gender aged 18 years and above. Those excluded were patients on treatment for clinical depression and those who could not comprehend the questionnaire secondary to mental illness. Data was collected after taking written informed consent from each participant.

The administered questionnaire had three sections (Annexure).

 

 

The first part dealt with patients’ demographic data, including age, gender, marital status, education status, height, weight, body mass index (BMI), presence of comorbid illnesses, like diabetes, hypertension, ischaemic heart disease, arthritis, hypothyroidism and chronic kidney disease, and gender-specific details about menstrual cycles, like menarche, regularity, presence or absence of hyperandrogenism. Additionally, previous treatment, if any, for their symptoms was noted, and the extent of symptomatic improvement that they may have experienced.

The second segment consisted of the 2010-11 modified ACR preliminary diagnostic criteria for FM,² including the widespread pain index9 (WPI) comprising five body regions and 19 specific parts of the body overall, and the symptoms severity score (SSS), which measures the presence and severity of fatigue, cognitive symptoms, waking unrefreshed, headaches, abdominal pain/cramps and depression. The questionnaire was translated into Urdu and was validated in a subset of 40 bilingual patients (α=0.93). FM was diagnosed if a patient had WPI ≥7 with SSS ≥5, or WPI 4-6 and SSS ≥9, generalized pain, defined as involvement of 4 out of 5 regions, and persistence of symptoms for ≥3 months.

The third section measured FM severity using the Fibromyalgia Impact Questionnaire (FIQR) 2019 version,¹⁰ which is divided into three domains, measuring function, overall impact and symptom intensity. The physical functional domain has 9 questions, the overall impact domain has 2 questions, and the symptom severity domain has 10 items. Each of the 21 items is scored 1-10. Adjusted domain scores were calculated by adding half of the functional domain, the complete overall impact domain and one-third of the symptom intensity domain, thus giving a score out of 100. The adjusted individual domain scores were added and the severity of symptoms was graded according to the final score. The corresponding scores were considered as mild (score 0-42), moderate (43-59), severe (60-74) or extreme (75-100). The FIQR was translated into Urdu as well, and was validated before use in the study in a subset of 54 patients who were fluent in both English and Urdu (α=0.89).

Data was analysed using SPSS 25, and it was found to be normally distributed. Demographic and clinical parameters were measured using descriptive statistics and their statistical significance was measured by chi-square test. Differences in gender were further assessed by using binary logistic regression to calculate the odds ratio (OR). Continuous variables were analysed using analysis of variance (ANOVA). Multiple regression analysis was used to determine the factors affecting FM severity. The presence of correlation was determined with Pearson’s correlation coefficient. P<0.05 was taken as statistically significant.

 

Results

 

Of the 767 patients enrolled, 750(97.7%) completed the questionnaire 452(60.3%) females and 298(39.7%) males. The overall mean age was 42.2±16 years, with 537(71.6%) aged <50 years. The overall mean BMI was 24.6±5.5kg/m2 (Table-1).

 

 

FM was found in 250(33.3%) patients; 190(76%) females, 60(24%) males (p<0.0001). Diabetes, anxiety and rheumatoid arthritis, advancing age and increased BMI were significantly associated with FM presence (Table-2).

 

 

Further, 196(78.4%) patients reported pain as their most relevant problem, with fatigue/lethargy being reported by 49(19.6%). Unrefreshing sleep and was highlighted by 4(1.6%) patients and cognitive problems by 1(0.4%). Also, 180(70%) patients had musculoskeletal pain and had received multiple courses of non-steroidal anti-inflammatory drugs (NSAIDs), with 165(66%) being on long-term NSAID therapy exceeding 6 months.

The mean FIQR score was 37.17 (95% CI: 34.99-39.29) with 162(64.8%) having mild FM (Figure-1).

 

 

FM severity was not influenced by the presence of co-morbidities, marital status, level of education or economic status (p>0.05). The most relevant problem, as reported by the patient, also had no significant impact on FM severity (p>0.05). A unique finding was a small but significant correlation between the age of menarche (p=0.009) and irregularity of menstrual cycles (p=0.003) and FM intensity, with a later age of menarche and cyclical irregularity being associated with more severe FM symptoms (Figure-2).

 

 

No such correlation was observed when clinical features of androgen excess were analysed (p>0.05).

 

Discussion

 

The presence of FM has been extensively documented alongside other clinical illnesses and its recognition provides avenues for correct management.¹¹ These proposed mechanisms have been summarised¹² and involve abnormal sensitisation from a peripheral nerve stimulus that could originate from deep muscle or fascia, sensitising the central nervous system (CNS) as a final pathway for FM.^13-15 This phenomenon could in turn lead to allodynia or a more acute somatosensory perception, dysregulation of the autonomic nervous system, as well as alterations in CNS physiology.^16-18 Other abnormal physiological findings have been identified and include abnormal sleep electroencephalograms, neuroendocrine perturbations, a pro-excitatory state suggested by abnormal changes in the neurochemistry of cerebrospinal fluid (CSF), cortical hyper-activation in response to both noxious and non-noxious stimuli, central dopaminergic transmission disruption and an apparent acceleration in age-associated brain atrophy that correlates with illness duration.^19-22 The observation that FM tends to aggregate in families has led to the postulation that there may be a genetic predisposition, with the identification of several genes as possible candidates, predominantly those that involve neurotransmitter physiology.²³ The brainstem has also been implicated, with clinical studies having shown that there are alterations in excitatory and inhibitory brainstem inter-neuronal circuits signifying brainstem dysfunction.²⁴ It has also been hypothesised that there is maladaptive plasticity of the primary motor cortex in FM patients.²⁵ Recent studies have shown some evidence demonstrating that oxidative stress, mitochondrial dysfunction and inflammation may have a role in FM pathophysiology.²⁶

The current study found FM rate in hospital-visiting patients to be 33.3%. The rate is lower than the 31% reported in a study comprising Turkish geriatric population.²⁷ The current study also found a significant increase in FM prevalence with advancing age.

The association between an increased BMI and FM merits further understanding. Our observation regarding this significant correlation mirrors a study,²⁸ which confirmed that the prevalence of increased body weight and obesity was high in FM, and suggested that physicians treating FM should be aware of the bivariate linear correlations and discuss weight-loss with their FM patients. Even if increasing BMI is not intrinsic to FM, it contributes to poor mood and functional outcome and should be a treatment goal. The clinical implications of this association were further explored by a study²⁹ which found that C-reactive protein (CRP) and apolipoprotein B, biomarkers linked to cardiovascular events may be associated with FM-related dysfunction in normal- and over-weight women with FM and that their increased levels in these patients may indicate an increased risk of cardiovascular disease.

Researchers in Turkey concluded that FM patients had a better course of illness when their education and socio-economic status were in good condition, and the complications of pain and illness were further reduced. However, the current findings did not find any significance with regards to socio-economic status or education.³⁰

A unique observation of the current study is that there may be a hormonal basis to FM intensity, with menstrual irregularity and a later menarche age correlating with more severe FM symptoms in the female subset. A study³¹ found that day-to-day changes in progesterone as well as testosterone were significantly and inversely correlated with pain severity. It found no relationship between estradiol and pain or cortisol and pain. The results suggest that progesterone and testosterone play a protective role in FM pain severity and that gender and other hormones may serve to increase as well as decrease FM pain severity.³¹

A study³² using animals concluded that 17β-estradiol produced anti-hyperalgesic and antiallodynic effects 24h, but not 8h, after its administration, suggesting a genomic mechanism. It supports the FM model for searching alternatives of treatment, particularly during endocrine phases when pain is exacerbated, such as menopause, and that 17β-estradiol replacement might be useful.

Recent evidence has focussed on a possible immunological background in FM. Cytokines/ chemokines, lipid mediators, oxidative stress and several plasma-derived factors underlie the inflammatory state in FM, leading to potential new therapeutic options targeting inflammatory pathways in FM patients. There is evidence to support the inflammation-driven pathways in FM pathogenesis, but further research is required to fully understand the network of inflammation and its possible role in diagnosis and/or treatment.³³

The role of oxidative stress and the use of antioxidants also provides a window for new modalities of treatment in the future. There are several studies indicating oxidative stress in patients with FMS. Oxidant malondialdehyde and antioxidant superoxide dismutase balances were found to be changed in FMS patients. Furthermore, increased free radical levels may be responsible for the development of FMS, and free radical-mediated oxidative stress, including inflammatory cytokines, may also play important roles in its pathogenesis.³⁴

To the best of our knowledge, the current study is the first of its kind conducted in the Pakistani population. It has made significant observations that can be further explored in well-designed, longitudinal, multi-centre studies.

However, the current study has limitations, like having a cross-sectional design which limits the ability to identify a causal relationship between the factors analysed, and the fact that it was a single-centre study.

 

Conclusion

 

FM prevalence was noted in about one-third of the patients visiting a hospital. Adequate understanding of the diagnostic criteria, and the availability of treatment modalities could enable physicians from all disciplines to correctly manage the disorder. Incorrect management approaches, such as the indiscriminate use of NSAIDs, can only be corrected if the disorder is correctly diagnosed.

 

Disclaimer: None.

Conflict of Interest:  None.

Source of Funding: None.

 

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