Noninflammatory Musculoskeletal Pain

Patients are often referred to Rheumatology clinic for joint pain. The majority of these cases ultimately fall into the category of noninflammatory musculoskeletal pain as opposed to inflammatory arthritis. Recognizing common causes of noninflammatory musculoskeletal pain and knowing initial steps in diagnosis and management are important. In this section, we provide a framework to guide your approach to the patient presenting with noninflammatory joint pain. Although not an exhaustive list of etiologies, we review the following:

• Joint Hypermobility

• Overuse Injuries

• Developmental Conditions

• Amplified Musculoskeletal Pain Syndrome

Joint Hypermobility

Diagnosis and Classification

Joint hypermobility is most often benign and asymptomatic. In some cases, joint hypermobility is associated with musculoskeletal complaints and extra-articular symptoms, leading to a diagnosis of hypermobility spectrum disorder or hypermobile Ehlers-Danlos syndrome (hEDS, described below). Additionally, joint hypermobility is a clinical feature of a number of heritable disorders of connective tissue. The Beighton scale is used most often to diagnose hypermobility on exam (see table).

Hypermobility spectrum disorder (HSD):

• Symptoms include hypermobility and at least one additional symptomatic musculoskeletal complaint including trauma, pain, degenerative joint and bone disease, neurodevelopmental manifestations, or orthopedic traits.

• Features do not fulfill either the criteria for hEDS or criteria for another heritable disorder of connective tissue (e.g., Marfan syndrome, Stickler syndrome, EDS)

Hypermobile Ehlers-Danlos syndrome (hEDS):

• hEDS presentation is characterized by generalized joint hypermobility and mild skin hyperextensibility but less skin fragility and severe scarring than classic EDS.

• A genetic etiology has not been identified (unlike other subtypes of EDS) but often is found in multiple family members, suggesting genetic predisposition.

• The distinction between HSD and hEDS is subtle, and the two conditions are often considered to be on the same spectrum of joint hypermobility. The clinical manifestations described below apply to both HSD and hEDS.

• More-stringent international diagnostic criteria for hEDS in adults were developed in 2017.

• International diagnostic criteria for pediatric joint hypermobility was published in 2023 by the International Consortium on Ehlers-Danolos Syndromes and Hypermobility Spectrum Disorders to help differentiate HES and hEDS and defines 8 new subtypes of hypermobility.

Heritable disorders of connective tissue: Marfan syndrome, Stickler syndrome, homocystinuria, EDS, osteogenesis imperfecta, Williams syndrome, and trisomy 21 are important to consider in the differential for joint hypermobility. See the Pediatric Genetic and Metabolic Disorders rotation guide for more information on some of these disorders.

Clinical Features of HSD and hEDS

• The incidence of chronic widespread pain and pain localized to specific joints is higher in patients with hypermobility.

• The cause of pain is not entirely clear and may be related to joint instability, impaired proprioception and related microtrauma, and/or a central sensitization and disturbance in the autonomic nervous system.

• Additional musculoskeletal manifestations:

  • temporomandibular joint dysfunction with disc displacement

  • patellofemoral pain syndrome (PFPS)

  • frequent ankle sprains

  • flexible flat feet (Note: rigid flat feet are always pathologic and warrant further orthopedic evaluation)

  • genu recurvatum

  • joint dislocations

• Significant associations with specific extra-articular disorders:

  • anxiety disorders

  • functional GI disorders

  • pelvic and bladder dysfunction

  • postural orthostatic tachycardia syndrome (POTS) and other dysautonomia

Treatment of HSD and hEDS

• primarily reassurance about the absence of underlying arthritis or joint damage

• Supportive footwear; possible role for orthotics in some cases, especially for pes planus

• may benefit from post-activity or evening dose of acetaminophen or NSAID

• formal physical therapy for more severely affected children, focused on periarticular muscle strengthening

• cognitive behavioral therapy for more widespread pain or disability

Overuse Injuries

The following tables summarize the key demographic characteristics, signs and symptoms, and management of common overuse injuries.

Developmental Conditions

Legg-Calvé-Perthes Disease

• idiopathic avascular necrosis (AVN)/osteonecrosis of the femoral epiphysis

• disruption of blood supply to femoral head (possibly due to mechanical overloading in genetically susceptible individual) leads to necrosis of femoral head and weakened mechanical strength, resulting in deformity of femoral head

• femoral AVN also associated with systemic disease (leukemia, lymphoma, systemic lupus erythema [SLE]), hemoglobinopathies, coagulopathies, and chronic glucocorticoid use

• affects children age 4-10 years (peak age, 5-7 years)

• affects boys more often than girls

• more common in white children and children of low socioeconomic status

• can be bilateral, but is usually asynchronous

Clinical features:

• limp and pain in hip, thigh, or knee

• pain with internal rotation and abduction of hip

Diagnosis:

• initial screen with x-ray, but MRI has greater sensitivity for early changes

• radiographic stages: AVN stage, fragmentation stage, reossification or healing stage, residual stage (femoral head healed but deformed)

Treatment:

• focused on maintaining the femoral head within the acetabulum to minimize the deformity of the head

  • rest

  • exercises to preserve hip range of motion

  • bracing only in patients with deformed femoral heads before complete reossification

  • better outcomes with surgical intervention in more-severe cases and older patients (age >6 years)

Slipped Capital Femoral Epiphysis

• displacement of the proximal femoral epiphysis on the femoral neck

• etiology unknown; growth plate failure thought due to mechanical, endocrine, and metabolic changes at puberty

• affects boys more often than girls

• more common in obese children

• bilateral in 20%-40% of cases

• peak age at 11-14 years

Clinical features:

• limp with hip, groin, thigh, or knee pain

• Trendelenburg test may be positive due to gluteus medius and gluteus minimus weakness

Diagnosis:

• anteroposterior and frog-leg lateral radiographs

• widening and irregularity of the physis with posterior inferior displacement of femoral head (like a scoop of ice cream falling off a cone)

Treatment:

• non-weight-bearing, traction, and surgery with epiphyseal fixation and osteotomy

• can lead to AVN and chondrolysis if not diagnosed early and treated promptly with surgical fixation

Benign Idiopathic Nocturnal Pains of Childhood (“Growing Pains”)

• peak age of 3-12 years not coincident with adolescent growth spurt

• cause unknown

• familial occurrence

Clinical features:

• episodic nonarticular leg pain in the thigh, calf, or shin at night; often bilateral

• often improved with massage and over-the-counter pain relievers

• normal physical exam

Diagnosis of exclusion:

• atypical features include articular or focal bony pain, daytime and/or persistent pain, systemic symptoms, or abnormal physical exam

Amplified Musculoskeletal Pain Syndrome (AMPS)

• AMPS features acute and chronic pain for which an overt primary cause for the pain cannot be found and the pain seems disproportional or amplified.

• The etiology is unknown, but AMPS often seems to be triggered by injury, illness, and/or psychological stress.

• Pain is caused by inappropriate firing of nerves, which sense pain and control vascular tone, and is not responsive to pharmacotherapy such as NSAIDs.

• The terminology is confusing, with many different terms and overlapping features among subsets of amplified musculoskeletal pain. Presentation, evaluation, and treatment among subsets is similar and grouped together in this review.

  • AMPS subtypes:

    • diffuse amplified musculoskeletal pain syndrome: more than two sites of amplified pain

      • fibromyalgia: included as a specific subtype of diffuse AMPS with defined diagnostic criteria; diagnosis often reserved for adults; juvenile fibromyalgia is occasionally used to discuss adolescents with AMPS, but this terminology is controversial (beyond the scope of this review)

    • localized amplified musculoskeletal pain syndrome: one or two sites of amplified pain

      • complex regional pain syndrome (CRPS): a specific subtype in which AMP is localized with defined diagnostic criteria (including swelling, temperature change, and color change)

• Peak incidence is in late childhood and adolescence.

• AMPS affects girls more often than boys.

Clinical Features

Features across AMPS subtypes:

• insufficient inciting event to cause the degree of pain and disability (e.g., minor trauma or illness)

• increasing pain and dysfunction over time (e.g., missing school due to pain, dropping out of activities)

• associated conversion symptoms (numbness, paralysis, pseudoseizures, blindness, bizarre [histrionic] gait)

• incongruent affect; la belle indifférence

• commonly associated personality traits include mature, perfectionistic, pleaser, driven

• multiple life changes or psychological stressors present

Features of CRPS:

• Subtype of localized AMPS

• Often preceded by minor trauma not clearly recalled, pain often worsened by cast or splint (especially once removed)

• Autonomic signs present: edema, cyanosis, coolness, increased perspiration (can be transient or persistent)

• allodynia (pain caused by normally nonpainful stimuli): border usually varies on repeat testing

Features of diffuse AMPS:

• gradual onset, less often with autonomic changes

• more often associated with poor sleep and depression

• counting painful points (“tender points”) can be helpful and is part of fibromyalgia criteria

Diagnosis

Often, patients have been through extensive diagnostic testing and “overmedicalization” by the time of referral to Rheumatology or pain clinic, which leads to worsening of the amplified pain pathway.

Laboratory tests

• normal complete blood count (CBC), comprehensive metabolic panel (CMP), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), 25-hydroxy vitamin D, thyroid studies

• atypical features should prompt further diagnostic workup:

  • abnormal systemic symptoms (fevers, weight loss, night sweats)

  • abnormal blood counts

  • increased inflammatory markers

Imaging

• often not indicated except for specific circumstances such as to rule out a specific diagnosis (e.g., trauma, spinal cord lesion, tumor)

• x-ray can show diffuse osteoporosis in AMPS depending on duration and degree of disability

• MRI in localized AMPS can show regional bone-marrow edema, but it can be difficult to distinguish between AMPS and trauma (e.g., subtle fracture)

Diagnosis

Differential diagnosis is extensive but can often be quickly narrowed based on history and physical exam.

• Fabry disease: episodic; excruciating burning pain in distal extremities; blue, maculopapular, hyperkeratotic skin lesions

• neoplasia: episodic or migratory pain or arthritis, malaise, anorexia, bone pain

• erythromelalgia: pain with erythematous, warm, swollen hands or feet eased by cold

• hypermobility: intermittent pains at night, especially after activities

• chronic recurrent multifocal osteomyelitis: specific point tenderness

• chronic compartment syndrome: severe muscle pain (usually calf) after exercising

• post-traumatic peripheral mononeuropathy

• vitamin D deficiency

• thyroid disease

Treatment

• Start at the onset of first clinic visit by developing a rapport with patient/family; validating pain is critical

• The two goals of treatment are restoration of function and relief of pain

  • function returns before pain diminishes

• The best evidence is for intense physical and occupational therapy and psychotherapy:

  • cognitive behavioral therapy (CBT) is the preferred mental health treatment modality

  • explore school issues and family dynamics

  • intensive physical and occupational therapy

    • up to 5-6 hours of daily therapy depending on severity of illness

    • aerobic exercise, especially for diffuse amplified musculoskeletal pain

    • desensitization of areas of allodynia

• Medications have not been adequately studied in pediatric amplified musculoskeletal pain syndrome and are not recommended. Comorbid conditions, such as depression or anxiety, should be managed according to treatment guidelines.