Juvenile Fibromyalgia: Diagnostic Challenges and Treatment Options
Juvenile fibromyalgia (JFM) is a chronic condition of widespread musculoskeletal pain, fatigue, and nonrestorative sleep. The prevalence of JFM among school-aged children is approximately 1% to 6%.1,2 As is the case with adults, JFM appears to occur more commonly in females. JFM typically affects adolescents, but it can occur even in younger children.
This condition can be frustrating and often difficult to recognize and manage for everyone involved—from patients and families to physicians. Patients with JFM often present with additional symptoms, such as chronic daily headaches, irritable bowel syndrome (IBS), recurrent abdominal pain, dysmenorrhea, and associated mood disorders of anxiety and/or depression. In fact, the average time to diagnosis is approximately two years.3,4 Evidence-based pharmacologic treatment for JFM has been limited, although clinical drug trials are ongoing. Current therapies are multidisciplinary. To date, outcomes of JFM remain uncertain.
Although the true cause of JFM is still unknown, there are multiple theories that seek to explain the potential pathophysiology of fibromyalgia (FM). These proposed explanations are centered on the common observation that patients suffering from FM have an overall heightened sensitivity to pain. In 1965, Melzack and Wall5 described the gate control theory of pain, in which a “gate” monitors pain signals to and from the brain.5 In susceptible individuals, such as those with FM, pain sensations are heightened because the gate remains wide open, even to minimal stimuli. The major theory at present is based on a phenomenon known as central sensitization, whereby patients have a lower threshold for pain because of an overall increased responsiveness to pain signals within the brain.6 It is believed that a defect of the descending inhibitory pathway prevents normal inhibitory responses, such that signals from even mildly noxious and non-noxious stimuli trigger excessive and persistent pain. Similarly, hyperalgesia and allodynia, at times features of JFM, are explained by this central pathway theory.
Many patients with chronic pain suffer from a type of “memory” for painful stimuli, in which recurrent pain is rapidly and increasingly interpreted as severe pain. This concept is known as temporal summation or wind-up7 and is felt to involve C-fiber–evoked responses of the dorsal horn. Other proposed theories include the possibility of hormonal imbalances of insulin-like growth factor 1 (IGF-1) and growth hormone,8,9 substance P,10 and neurotransmitters,11,12 particularly serotonin and norepinephrine receptors, which have been the target of many of the newer medications.
Other researchers propose that an infectious trigger causes FM. Viral illnesses like mononucleosis often have been identified at the onset of a patient’s symptoms—although no clear link has been discovered. It is much likelier that the virus was a trigger for altering one’s lifestyle and the subsequent vicious cycle, but is not necessarily the underlying cause. Recent reports in 2009 suggested that a retrovirus known as XMRV (myalgic encephalitis virus) was linked to patients with chronic fatigue syndrome (CFS)13; however, more recent studies do not support this link.14,15
It has been found that there is a strong familial clustering of FM symptoms among family members, especially female relatives. Arnold et al found that the odds of developing FM in an adult relative of a person with FM vs. the odds of FM in a relative with rheumatoid arthritis (RA) was 8.5 (95% confidence interval [CI], 2.8-26, P = 0.0002).16 These findings might indicate the real possibility that susceptibility to chronic pain or heightened pain sensitivity is an inherited trait, although specific genetic links have yet to be identified.
A thorough history and review of symptoms is used to guide the diagnosis of JFM and rule out other possible medical conditions with similar symptom presentation (see Table). According to the Yunus and Masi classification criteria, symptoms of widespread musculoskeletal pain must be present for at least three months, and patients must have five or more tender points on examination.17 Exclusion of other medical conditions and otherwise normal laboratory tests also are necessary to classify a patient as having JFM. Other associated symptoms include fatigue, IBS, headaches, poor sleep, anxiety, numbness, subjective soft tissue swelling, and modulation of symptoms due to anxiety or stress, weather changes, and/or physical activity. Often, symptoms are preceded by a history of physical injury or acute illness that leads to a disruption in daily life. Subsequently, symptoms of pain, poor sleep, and fatigue arise and continue on a vicious cycle, leaving patients with persistent pain, altered mood, and poor functioning.
Upon examination, one would not expect to find abnormalities other than pain at sites of tender point locations (see Figure 1). These sites have been suggested to have greater pain sensitivity in patients with FM,18 and among children, the presence of five of 18 tender points is suggestive of JFM.
Most pediatric rheumatologists use the Yunus and Masi criteria; however, the 1990 American College of Rheumatology (ACR) criteria for FM also have been used for classification purposes.19 The ACR criteria are more specific to musculoskeletal pain, requiring widespread pain in at least three different locations for at least three months along with a total of 11 of 18 tender points. The newer, recently endorsed 2010 ACR criteria for FM evaluate widespread pain and symptom severity without the need for a tender point exam by a trained clinician.20 They have yet to be validated in a pediatric population.
As noted, patients with JFM often suffer from associated conditions like chronic migraines or headaches, chronic abdominal pain, IBS, restless leg syndrome, sleep disorders like narcolepsy and sleep apnea, postural orthostatic tachycardia syndrome, CFS, and mood and anxiety disorders. Differential diagnosis involves ruling out other illnesses, including thyroid disease and autoimmune diseases like chronic juvenile idiopathic arthritis, systemic lupus erythematosus, and juvenile dermatomyositis, which should be considered if symptoms are highly suggestive or if there is a strong family history of thyroid disease or autoimmunity.
As mentioned previously, viral symptoms often precede or are present at onset of JFM, but typically patients readily recover from these illnesses while symptoms of JFM persist. Some viral illness, including Epstein-Barr virus, cytomegalovirus, and HIV, could mimic certain features of JFM, but the latter is likely to present with other worrisome findings of fever, lymphadenopathy, anorexia, and weight loss. Generalized anxiety and depression or other mood disorders should be screened for, and patients should be referred for psychiatric evaluation and treatment if indicated.