Is there a role for prevention or early diagnosis in fibromyalgia?

Piercarlo Sarzi-Puttini, Alberto Batticciotto, Daniela Marotto, Fabiola Atzeni
ASST Fatenebefratelli-Sacco University Hospital, Milan; Rheumatology Unit, Ospedale del Circolo Varese; Rheumatology, Department of Medical Sciences and Public Health Assl Olbia, Olbia; Rheumatology Unit , University of Messina, Messina, Italy

It is well known that fibromyalgia is prevalent, difficult to manage, and associated with high costs, in health care and society in general. The current diagnostic and treatment pathway for patients with fibromyalgia (FM) is complex, and  early and effective identification and appropriate treatment of FM remain a challenge in current clinical practice (1). Ideally, FM management involves a multidisciplinary approach with the preferable patient pathway originating in primary care but supported by a range of health care providers, including referral to specialist care when necessary (2). Recently published guidelines recommend the adoption of a symptom-based approach to guide pharmacologic treatment. Emerging treatment options for FM may be best differentiated on the basis of their effect on comorbid symptoms that are often associated with pain (e.g. sleep disturbance, mood, fatigue) (3). 

Acute pain is of sudden onset and expected to last less than 3 months. Chronic pain is defined as ongoing or recurrent pain, lasting beyond the usual course of injury healing or more than 3 to 6 months. The development of chronic pain results from complex interactions between biological, psychological, and social factors. There is increasing evidence that the transition from acute to chronic pain (particularly FM)  is associated with permanent neurophysiological transformations (i.e., central sensitization, gliopathy, and an emotional shift in the brain circuitry involved in nociception) and genetic and epigenetic factors (4,5).  A variety of different conditions can play a role in the transition from acute to chronic pain:  demographic aspects (e.g., female gender and low socio- economic status), injury-related (e.g., lower limb injury and compensable injury), autoimmune or neoplastic diseases, small fiber neuropathies, surgery (e.g., mastectomy, thoracotomy, and amputation), psychological risk factors such as anxiety, depression, pain catastrophizing and pain-related fear. Because of the link between FM and exposure to stress, and because both the neuroendocrine and autonomic nervous systems could cause many of the symptoms of FM, these factors have been fairly extensively studied; however, these factors are now generally thought to play a role in some individuals, but not to be central pathogenic factors in all individuals with these conditions (6,7).

The prevalence of FM varies from 2 to 5%, depending on the population sampled and the method of evaluation (8). The incidence of FM was determined in a population-based sample of Norwegian women between the ages of 20 and 49 years who were followed for 5.5 years. The incidence of FM among women who began the observation period without any complaints of musculoskeletal pain was 3.2%, corresponding to an average annual incidence of 583 cases/100,000 women between 20 and 49 years of age. For those with any self-reported pain at the beginning of the study, the incidence was 25% and risk factors for the development of FM included pain for 6 years or more, self-assessed depression, lack of professional education, and the presence of 4 or more associated symptoms, such as disturbed bowel function, unrefreshing sleep, paresthesia, and subjective swelling (9). In another cohort of 1,198 early arthritis patients followed by rheumatologists, the incidence of FM was 6.77/100 person-years in the first year after diagnosis of arthritis, and declined to 3.58/100 person-years in the second year. Pain severity and poor mental health predicted FM risk  (10).

Why prevention is so difficult in potential FM patients? This is a list of  some potential topics: 1) there is no biomarker; 2) we should treat any type of acute pain to prevent cronicity; 3) we do not know why central sensatization occurs in some patients and not in others; 4) can we improve resilience or is it only genetically and/or enviromentally determined?  5) what is the role of psycoaffective and/or personality problems in these patients? 

We do not have an answer to these questions and we can only treat patients early both with non pharmacological or /and pharmacological armamentarium. We can teach the patient how to handle fibromyalgia ( perceived self-efficacy in pain management and pain acceptance) but not how to get rid of it or even better how not to develop the syndrome in presence of risk factors.

Long-term outcome data for FM are limited. Although available studies indicate that symptoms of FM often persist, many patients are able to identify strategies over time that can moderate symptoms (7).

1. Sarzi-Puttini P, Atzeni F. Fibromyalgia: a never-ending story of central and peripheral pain mechanisms. Arthritis Rheumatol. 2014 ;66:1687-8
2. Sarzi-Puttini P, Atzeni F, Salaffi F, Cazzola M, Benucci M, Mease PJ. Multidisciplinary approach to fibromyalgia: what is the teaching? Best Pract Res  Clin Rheumatol. 2011 ;25:311-9.
3. Macfarlane GJ, Kronisch C, Dean LE, Atzeni F, Häuser W, Fluß E, Choy E, Kosek  E, Amris K, Branco J, Dincer F, Leino-Arjas P, Longley K, McCarthy GM, Makri S, Perrot S, Sarzi-Puttini P, Taylor A, Jones GT. EULAR revised recommendations for  the management of fibromyalgia. Ann Rheum Dis. 2017 ;76 :318-328.
4. Alciati A, Atzeni F, Grassi M, Caldirola D, Riva A, Sarzi-Puttini P, Perna G.  Childhood adversities in patients with fibromyalgia: are they related to comorbid lifetime major depression? Clin Exp Rheumatol. 2017 May-Jun;35 Suppl 105:112-118.
5. Alciati A, Caldirola D, Sarzi-Puttini P, Atzeni F, Grassi M, Perna G. Is panic disorder associated with clinical severity of fibromyalgia? A preliminary study in a tertiary-care centre. Clin Exp Rheumatol. 2016 Mar-Apr;34(2 Suppl 96):S99-105.
6. Buskila D, Sarzi-Puttini P, Ablin JN. The genetics of fibromyalgia syndrome.Pharmacogenomics. 2007; 8: 67-74.
7. Arnold LM, Bennett RM, Crofford LJ, Dean LE, Clauw DJ, Goldenberg DL, Fitzcharles MA, Paiva ES, Staud R, Sarzi-Puttini P, Buskila D, Macfarlane GJ. AAPT Diagnostic Criteria for Fibromyalgia. J Pain. 2018 Nov 16. pii: S1526-5900(18)30832-0.
8. Jones GT, Atzeni F, Beasley M, Flüß E, Sarzi-Puttini P, Macfarlane GJ. The prevalence of fibromyalgia in the general population: a comparison of the American College of Rheumatology 1990, 2010, and modified 2010 classification criteria. Arthritis Rheumatol. 2015;67:568-75.
9. Forseth KO, Gran JT, Husby G. A population study of the incidence of fibromyalgia among women aged 26-55 yr. Br J Rheumatol, 1997; 36 :1318-1323
10. Lee YC, Lu B, Boire G, Haraoui BP, Hitchon CA, Pope JE, Thorne JC, Keystone. EC, Solomo DH,  Bykerk VP. Incidence and predictors of secondary fibromyalgia in an early arthritis cohort Ann Rheum Dis, 2013; 72, 949-954.