Abstract

Fibromyalgia is a very common diagnosis in the primary care practice, characterized by diffuse muscoloskeletal pain and cognitive and psychiatric symptoms. It may be the exclusive diagnosis or affect patients with other chronic diseases; the role of the rheumatologist may be very useful in perfecting the diagnosis, lowering the cost for unuseful exams and alleviate anxiety of the patients. In this work we present the results of the collaboration between general practitioner and rheumatologist in diagnosing fibromyalgia, based on one month of real life activity.

Introduction:

Fibromyalgia [FM] is a complex disorder characterized by chronic musculoskeletal pain, weakness, sleep disorders, cognitive and psychiatric symptoms that negatively affect the quality of life [ 1 , 2 ]. The patients usually present chronic and diffuse muscle pain and stiffness and achiness on specific sites, the so-called trigger points, in the absence of local signs of inflammation and anatomical joint abnormalities [ 3 , 4 ]. Symptoms may be so serious to significantly and negatively affect all the daily activities, at home, at work and in the free time, resembling the poor quality of life find in rheumatoid arthritis [ 5 ].

The total direct and indirect costs to treat FM may be very high, as described in previous studies [ 6 , 7 , 8 ]. It is estimated that symptoms related to fibromyalgia are responsible of up to 7% of the general practitioner [GP]’s visits and from 10 to 20% of the rheumatologist’s ones [ 9 ].

The worldwide prevalence of the disease, diagnosed using the 20 10 American College of Rheumatology [ACR] criteria, is from 2 to 8% [ 10 ]. In Italy it is estimated that about 2% of the total population is affected by FM [ 11 ].

Women are more frequently affected [F:M 9:1] and mostly in the fifth-sixth decade.

The diagnosis of FM is based on specific criteria. Particularly, in 2010 and 2011 the American College of Rheumatology [ACR] proposed two sets of criteria, revised in 2016 [ 12 , 13 ], when sleep and attention disturbance, neuropsychiatric symptoms and their severity, in addition to widespread and localized pain, were included.

However, in the real life, the diagnosis of FM is usually a long and difficult process because it is necessary to exclude other diseases [ 14 , 15 , 16 ] and rheumatologist’s consult is usually required.

Using clinical data from patients who were referred by their GP to our Rheumatology Unit over a period of one month [from September 17th to October 17th 2018] because of muscoloskeletal pain, the aims of the present study were [i] to assess the prevalence of FM in our population, [ii] to describe the different clinical subsets and the presence of extraskeletal symptoms, [iii] to evaluate the effectiveness of our diagnostic and care model.

Materials and Methods:

Study design, setting and participants

We retrospectively collected clinical data from patients who were referred by their GP to our Rheumatology Unit, visited by a clinician between September 17th and October 17th 2018. Each participant of the study provided informed consent.

Diagnosis of Fibromyalgia

The diagnosis of FM was based on the 2016 American College of Rheumatology [ACR] criteria.

Variables

Variables included

  • demographics [age, sex],

  • the GP suspected diagnosis,

  • patient’s self-reported musculoskeletal symptoms, type of pain, presence of sleep or cognitive disorders, headache,

  • musculoskeletal signs assessed during the clinical evaluation,

  • final diagnosis.

Statistical analysis

Characteristics of the population are presented as mean±standard deviation [ SD ]. Analyses and figures were performed using Excel Microsoft Office.

Results:

In one month a total of 121 patients underwent to a visit at our Rheumatology Unit. Of these, 26 patients [21%] were finally discharged with the diagnosis of FM. Most of them [ 25 ] were women. Average age [±SD] was 56,3±15,6 years.

Most of patients who received a final diagnosis of FM [ 24 ] have been referred to the rheumatologist without any urgency, while for 2 of them the consult was required with "B priority", that in our health care system means that it needs to be performed within 7 days.

Two patients were referred without any diagnostic suspect, while FM was suspected by GP in 8 patients. For the remnants, an alternative diagnosis was suspected.

For 21 in 26 patients, some preliminary diagnostic investigations have been performed prior to the rheumatologist’s consultant.

Concerning the self-reported symptoms, it was central neuropathic in 13/26 [50%], inflammatory or mechanic in 6 patients [26%] respectively and neuropathic/mechanic only in 1 patient [3.8%] [fig.1]. Among non musculoskeletal symptoms, 5 patients [19.2%] complained headache, 14 sleep disturbance [ 53.8% ], 6 [ 23 % ] cognitive and neuropsichiatric symptoms, [anxiety and/or depression]; 1 patient had restless leg syndrome [fig. 2]. In 18 patients [ 69.3% ] FM was considered secondary to other disease like osteoarthritis [ 10 patients, 55.5% ] and connective tissue diseases [ 8 patients, 44.4% ]; in the other 8 patients [ 30.7% ] FM was the only disease diagnosed: the so-called primary FM.

Figure 1 Distribution of pain characters

Figure 2 Percentage distribution of symptoms

Discussion:

Using data from 121 patients who underwent to a rheumatologic visit at our Unit between September 17th and October 17th, 2018, we described the prevalence [21%] and different clinical subsets of FM in our population.

In the present study, the prevalence of FM is similar to what has been reported in previous literature about US population, while is slightly higher than what was previously described about Italian population [ 10 , 11 ]. The difference may be related to selection bias due to the fact the patients visited in our Unit had been already screened by the GP. Another possible explanation may be the different diagnostic criteria used to perform the diagnosis being the 20 16 ACR criteria more sensitive and specific than the previous ones. Our findings confirm a higher prevalence of the disease in women compared to men and in the fifth and sixth decades compared to other ages. The etiology of FM is unknown [ 17 ]. It has been described a relationship between FM and psycho-emotional stress, physical traumatism or viral infections [ 18 ]. Other studies showed that patients could have genetic predisposition to the disease [ 19 ], having the first grade relatives of patients with FM a 8.5 fold higher risk of getting the same the disease during their life [ 20 ]. Unfortunately, we did not register sociodemographic data like familiarity, education, job, civil status, cigarette smoke, possible predisposing or etiologic factors.

Regarding the clinical manifestations of the disease, all our patients complained for pain, mostly central-neuropathic reported in more than double of cases compared to the pure mechanical or inflammatory pain. As the drug treatment should be personalized on each patient on the basis of the characteristics of pain, its correct interpretation and classification plays a key role in the management of the patient with FM [ 21 , 11 ]. Similarly, a careful evaluation of the presence of any other non musculoskeletal symptoms, in addition to pain, is strongly recommended because it can affect treatment choice. For example, sleep disturbance, headache, cognitive and psychiatric symptoms [mostly anxiety and depression] may be the reason to involve other specialists [such as neurologist or psychologist] in the best care of the patient.

Moreover, primary and secondary FM need to be distinguished when targeting the therapy. In fact, in the presence of a primary organic disease, especially a connective tissue disease like in our experience [ fig. 3 ], it is required to analyze each new sign or symptom to understand if it derives from the primary disease or be expression of the FM itself, to make the right therapeutic choice.

Finally, in most cases , the GP referred the patient with musculoskeletal pain to the rheumatologist with a diagnostic hypothesis and a minimum set of blood test performed prior to the visit consistently with what the international guidelines suggest [ 10 , 11 ]. In fact some blood tests[C-reactive Protein, total blood cells count] may be useful are necessary to exclude the presence of an inflammatory disease, while others [such as TSH, CK, ANA test and RA test] are not useful for the diagnosis of FM. We believe that if FM is strongly suspected, standard diagnostic criteria and few exams are sufficient to confirm the diagnosis. In some selected cases, additional exams may be useful to exclude other systemic organic diseases, like connective tissue diseases, hypotiroidism, neurologic diseases

Figure 3 Distribution of primary vs secondary Fibromyalgia

Clinical suspect Recommended exams
Early arthritis [a] Total blood cell count, C-reactive protein,creatinine,ALT, plasma urate, RA test, APCA
Connective tissue disease or vasculitis at onset [b] Total blood cells count, C-reactive protein, Creatinine, ANA test, CreatinKinase, C4, urine exam
Temporal arteritis [c] C-reactive protein or ESR

Distribution of primary vs secondary Fibromyalgia

a] Pain or swelling of ≥ hand/foot joints or 1 large joint for at least 2-4 weeks. RA test [Rheumatoid Factor]; APCA: anticiclic citrullinated peptide. b] Raynaud’s phenomenon, digital ulcers; purpura, mostly in the presence of ulcers, arthralgias, peripheral parestesias; proximal symmetrical debilitating muscle weakness; fever or mild fever lasting for 3 weeks, with arthralgia, photosensitivity, malar rash. c] New onset temporal pain, age >50 years, expecially with girdle pain

Tab: Criteria to request a rheumatologic consult in B priority in AUSL Romagna

Conclusions:

Data from real life showed that about 1 in 5 patients referred to a rheumatologist by GP because of musculoskeletal pain was diagnosed with fibromyalgia. Most of them suffered of central neuropathic pain. Additional non musculoskeletal symptoms, mainly sleep disorders, were also reported. Also, in most cases FM was secondary to other conditions such as autoimmune arthritis and connective tissue diseases. Because symptoms of FM may often be confounding and blood tests are only partially useful, a strong collaboration between the rheumatologist and the GP is necessary to reach an accurate diagnosis of FM and to provide the best care to the patients.

References:

[1.]Wolfe F, Clauw DJ, Fitzcharles M-A, Goldenberg DL, Katz RS, Mease P, et al: The American College of Rheumatology Preliminary Diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res 2010; 62: pp. 600-610

[2.] Belt NK, Kronholm E, and Kauppi MJ: Sleep problems in fibromyalgia and rheumatoid arthritis compared with the general population. Clin Exp Rheumatol 2009; 27: pp. 35-41

[3.] Bellato E, Marini E, Castoldi F, Barbasetti N, Mattei L, Bonasia DE, et al: Fibromyalgia syndrome: etiology, pathogenesis, diagnosis, and treatment. Pain Res Treat 2012; 2012:

[4.] Schmidt-Wilcke T, and Clauw DJ: Fibromyalgia: from pathophysiology to therapy. Nat Rev Rheumatol 2011; 7: pp. 518-527

[5.] Birtane M, Uzunca K, Tatekin N, Tuna H. The evaluation of quality of life in fibromyalgia syndrome: a comparison with rheumatoid arthritis by using SF-36 Health Survey. Clin Rheumatol. 2007 .

[6.] Robinson RL, Birnbaum HG, Morley MA, Sisitsky T, Greenberg PE, Claxton AJ. Economic cost and epidemiological characteristics of patients with fibromyalgiaclaims. J Rheumatol. 2003 Jun;30[6]:1318-25

[7.] Boonen A 1 , van den Heuvel R, van Tubergen A, Goossens M, Severens JL, van der Heijde D, van der Linden S. Large differences in cost of illness and wellbeing between patients with fibromyalgia, chronic low back pain, or ankylosing spondylitis. Ann Rheum Dis. 2005 Mar;64[3]:396-402. Epub 2004 Jul 22.

[8.]Berger A, Dukes E, Martin S, Edelsberg J, Oster G Characteristics and healthcare costs of patients with fibromyalgia syndrome. Int J Clin Pract. 2007

[9.] Gwenda Hughes,Carlos Martinez,Eric Myon,Charles Taeb,Simon Wessely. The impact of a diagnosis of fibromyalgia on health care resource use by primary care patients in the UK: An observational study based on clinical practice. Arthr and Rheum Vol. 54, No. 1, January 2006, pp 177.183 doi 10.1002/art.21545.

[10.] Weir P, Harlan G, Nkoy F, et al. The incidence of fibromyalgia and its associated comorbidities: a population-based retrospective cohort study based on International Classification of Diseases, 9th Revision codes. J Clin Rheumatol, 2006; 12: 124.8.

[11.] Parere reso dal Consiglio Superiore di Sanit al Ministero della Salute, in data 14 settembre 2015, a seguito della interrogazione di Paola Boldrini [5-07313] rispetto allinserimento della fibromialgia nei livelli essenziali di assistenza.

[12.] Wolfe F, Clauw DJ, Fitzcharles MA, et al. The American College of Rheumatology Preliminary Diagnostic Criteria for Fibromyalgia and Measurement of Symptom Severity. Arthritis Care and Research, 2010; 62 [5]: 600.610 .

[13.] Wolfe F, Clauw DJ, Fitzcharles MA, et al. Fibromyalgia criteria and severity scales for clinical and epidemiological studies: a modification of the ACR Preliminary Diagnostic Criteria for Fibromyalgia. J Rheumatol, 2011; 38[6]: 1113-22

[14.]Goldenberg DL, Schur PH, Romain PL. Clinical manifestations and diagnosis of fibromyalgia in adults. Literature review. UpToDate, aggiornamento al 14 settembre 2016.

[15.]Goldenberg DL, Schur PH, Romain PL. Differential diagnosis of fibromyalgia. Literature review. UpToDate, aggiornamento al 12 settembre 2016.

[16.]Arnold LM, Clauw DJ, McCarberg BH. Improving the recognition and diagnosis of fibromyalgia. Concise review for clinicians. Mayo Clin Proc 2011; 86 [5]: 457.64 .

[17.]Don L Goldenberg, Peter H Schur and Paul Romain Pathogenesis of fibromyalgia Up to Date Ultimo aggiornamento Ottobre 2018.

[18.]Buskila D, Sarzi-Puttini P. Biology and therapy of fibromyalgia. Genetic aspects of fibromyalgia syndrome. Arthritis Res Ther 2006; 8:218.

[19.]Arnold LM, Hudson JI, Hess EV, et al. Family study of fibromyalgia. Arthritis Rheum 2004; 50:944.

[20.] Smith SB, Maixner DW, Fillingim RB, et al. Large candidate gene association study reveals genetic risk factors and therapeutic targets for fibromyalgia. Arthritis Rheum 2012; 64:584.

[21.] Jensen KB, Kosek E, Petzke F, et al. Evidence of dysfunctional pain inhibition in Fibromyalgia reflected in rACC during provoked pain. Pain 2009; 144:95.