Long-Term Outcomes and New Developments in Juvenile Fibromyalgia

Recent findings indicate that symptoms persist throughout adolescence and young adulthood for the majority of fibromyalgia patients.

Recommended treatments continue to be interdisciplinary and may involve parental guidance and family support for lifestyle changes.

By Susan T. Tran, PhD, Tracy V. Ting, MD, MSc and Susmita Kashikar-Zuck, PhD

Juvenile fibromyalgia (JFM) is a chronic rheumatologic condition characterized by persistent widespread musculoskeletal pain, fatigue, and sleep disturbances. Additional symptoms are common and include chronic headaches, gastrointestinal problems, anxiety and stress, mood problems, muscle stiffness, cognitive symptoms, and dysautonomia. JFM, which affects between 2% to 6% of school-age children, is more prevalent in girls compared to boys.

Although JFM is one of the most understudied pain syndromes in children, in recent years more has come to light about the clinical characteristics, long-term outcomes, and effective treatments for managing the many symptoms of JFM. Recent findings indicate that symptoms of JFM persist throughout adolescence and young adulthood for the majority of JFM patients. There is little evidence to support pure pharmacological management of JFM, particularly as a long-term solution. Recommended treatments continue to be interdisciplinary and may involve parental guidance and family support for lifestyle changes. With this in mind, more effective and long-lasting new treatments need to be developed to treat chronic symptoms.

What Causes JFM?
It is now thought that patients with fibromyalgia (FM) have a ramping up of their pain perception. Research on the neurobiology of FM supports the prevailing theory that heightened sensitivity to pain signals in the brain and disturbances in descending inhibition of pain, also known as central sensitization, are a primary underlying mechanism for the pain symptoms in FM. In other words, patients with FM may be unable to modulate pain signals, which results in excessive and persistent pain. The fact that chronic pain disorders, particularly FM, tend to co-occur in families lends credence to theories that there may be a genetic predisposition to pain sensitivity in such conditions. Other potential explanations for heightened pain sensitivity include increased physiologic “memory” for pain, hormonal imbalances, or an infectious trigger.

Recently, there has been some skepticism about the role of central sensitization as the primary underlying pathology in FM, particularly due to mixed findings for central nervous system dysfunction as well as overlap found between symptoms of FM and those of newly identified peripheral anomalies, such as small-fiber polyneuropathy. Small-fiber polyneuropathy is caused by the dysfunction and degeneration of the small-diameter unmyelinated C-fibers and thinly myelinated A-δ peripheral nerves that initiate pain perception. Recent findings indicate that adults with FM have increased evidence of small-fiber neuropathy compared with healthy control subjects. One study that examined children, adolescents, and young adults with juvenile-onset chronic widespread pain also found evidence of definite small-fiber neuropathy in 59% of the sample, and probable or possible neuropathy in an additional 39%. Further, markers of immune dysfunction were found in many of the patients with FM and chronic widespread pain with small-fiber neuropathy, suggesting a possible mediating process.

There are several biological causes of small-fiber neuropathy (eg, diabetes); therefore, it is possible that a subset of patients with FM may have a potentially treatable underlying cause for neuropathy. Anecdotally, treatment with corticosteroids or immunoglobulin therapy was reported to be effective in patients with chronic widespread pain, as well as in patients with FM and chronic polyneuropathy. The findings of these studies should be interpreted with caution because small-fiber neuropathy has been identified in only a subset of FM patients, and no research has been done thus far in JFM. Additionally, the underlying cause of neuropathy in adults and children with FM is unknown, as is the effectiveness of treating neuropathy to manage FM pain.

Long-Term Outcomes in JFM

New studies are beginning to document the longitudinal outcomes of youth diagnosed with JFM, thereby shedding more light on the prognosis for JFM patients. Using longitudinal data from the national Childhood Arthritis and Rheumatology Research Alliance dataset, Connelly et al examined outcomes in children with JFM, comparing findings at the patients’ initial clinic visits and at follow-up visits 0.25 to 2.5 years later. They found that pain intensity, well-being, and functioning worsened during the follow-up period. Widespread pain was less frequent, but associated symptoms (eg, headache, disrupted sleep, irritable bowel symptoms, paresthesias) did not change over time, regardless of treatment modality or adherence to treatment. These findings suggest that JFM symptoms are persistent even at early stages of the condition, and that currently offered treatments are not very effective in reducing symptoms or their impact on functioning.

In fact, it appears that symptoms of JFM continue into adulthood for the majority of patients. In a 6-year follow-up study of young adults diagnosed with JFM during adolescence, patients with JFM had significantly higher pain scores, poorer physical functioning, and a greater number of medical visits compared with healthy control subjects. The majority of JFM patients (80%) continued to experience FM symptoms into early adulthood, and half (51.1%) met American College of Rheumatology criteria for adult FM.

In addition to physical symptoms, mood difficulties also seem to persist in many patients with JFM. Symptoms of anxiety and depression are higher in youth with JFM compared with healthy controls. These symptoms tend to remain comorbid with FM into young adulthood. The young adult years seem to be a particularly vulnerable time for increasing anxiety and mood difficulties this is true for young adults in general but is, perhaps, even more so for youth with JFM as they struggle with increasing social and vocational demands and expectations for greater independence from family. The literature on psychiatric comorbidity in FM indicates that rates of current major depression are lower in young adults with JFM than in older adults with FM, whereas rates of lifetime major depression and dysthymia are higher for those who have FM starting in their childhood. Additionally, rates of anxiety disorders have been shown to be high across the lifespan in FM patients. Considered together, these findings highlight the crucial importance of targeting mood symptoms early in the course of treatment, with particular emphasis placed on the management of anxiety and assessment of risk for depression.