Pediatric Amplified Musculoskeletal Pain
Syndrome Complicated by a Fever of
Justin Hovey1*, MD, Jennifer H. Ra1, BA and Nola Ernest2, MD, PhD
1Alabama College of Osteopathic Medicine, Dothan, Alabama, USA
2Dothan Pediatric Clinic, Dothan, AL, USA
Submission: September 20, 2022; Published: October 13, 2022
*Corresponding author: Justin Hovey, M.D, Alabama College of Osteopathic Medicine, Dothan, Alabama, 445 Health Sciences Blvd. Dothan, AL 36303, USA
How to cite this article:Justin Hovey, Jennifer H. Ra, BA, Nola Ernest, M. Pediatric Amplified Musculoskeletal Pain Syndrome Complicated by a Fever of Unknown Origin. Acad J Ped Neonatol 2022; 12(2): 555886. 10.19080/AJPN.2022.12.555886
Amplified musculoskeletal pain syndrome (AMPS) is a rare diagnosis that is part of a broad spectrum of chronic pediatric musculoskeletal pain. Typically, females are more affected than males with an average age of onset of 9-15 years. The lower extremity is most often the primary site of injury and subsequent chronic pain. Labs and imaging studies are usually unrevealing. The various clinical presentations and psychosocial complexities of each patient commonly leads to delayed diagnosis. In this article, we present a nine-year-old female with no significant medical history who sustained a Salter-Harris type I fracture to her left ankle. After removal of her cast, she subsequently developed swelling and pain along with a fever of unknown origin. The fever persisted for 115 days and led to a comprehensive work-up. Following consultation with pediatric rheumatology, a diagnosis of AMPS was made. After the diagnosis was made, the patient underwent intense physical therapy, and her symptoms resolved. This case highlights the complications that arise with diagnosing AMPS when affected by an autonomic component leading to fevers. The prolonged nature of diagnosing AMPS stems from the complicated spectrum of clinical presentations and pathophysiological etiologies. The unique autonomic component of AMPS in this patient complicated and delayed the diagnosis. Future studies should focus on exploring the possible manifestations of AMPS when affected by seemingly unassociated symptoms, like fevers.
Increased knowledge and understanding of various clinical manifestations of AMPS can help physicians more quickly diagnose and treat the disease.
Article Summary: AMPS can present with a broad spectrum of clinical manifestations. This case highlights a unique presentation of AMPS complicated by FUO that lasted 115 days
Amplified musculoskeletal pain syndrome (AMPS) is a relatively rare diagnosis in children that encompasses a spectrum of pain syndromes. Children who are diagnosed with this condition describe musculoskeletal pain that is intense, can be localized or diffuse, and associated with functional disability despite the lack of extensive tissue damage . Females are affected more often than males in a 3 to 1 ratio, and the typical age of onset is 9-15 years . Affected children are typically of higher socioeconomic status, more mature than their counterparts, are accomplished in school and extracurricular activities, and are usually described as perfectionists. Major life stressors are frequently discovered with the presentation .
During childhood, the lower limb is most often the primary site of AMPS related disability . Although most patients report continuous pain in an affected limb and can often recall exactly when it began, some children may have a more nebulous onset, and it may be difficult to localize the pain . Approximately 14% of children affected by AMPS will have autonomic signs associated with more localized pain. When autonomic signs are present, the pain is more likely to be limited . On the other hand, children without autonomic involvement are more likely to have pain involving multiple sites or joints [1,3].
Frequently, families make multiple visits to emergency departments and outpatient clinics before a diagnosis is made, leading to numerous and often duplicate tests being performed
on symptomatic patients resulting in substantial costs to both
the health care system and families . Labs and imaging studies
performed on patients with AMPS are typically unrevealing .
These factors, along with the various clinical presentations and
psychosocial complexities of each patient, often lead to a delayed
diagnosis . Though AMPS is rare, the overall cost burden of this
syndrome is nearly equivocal to the high cost of ADHD .
Given the peculiar spectrum of AMPS, the understanding
of the pathophysiology is ever evolving. Currently, a number of
pathophysiological processes are theorized to be responsible
for the development of the condition. Genetic predisposition,
central sensitization, blood flow, abnormal cytokine production,
and psychosocial factors all likely play a role in the development
of AMPS. Central sensitization with dorsal horn activity is the
primary abnormality driving the exaggerated pain responses seen
in the disease process. Glutamate and Substance P are the two
neurotransmitters that are in involved in this central sensitization
and the amplified pain. Cytokine dysregulation produced
peripherally may play a role in sensitization of the central nervous
system as well. Furthermore, sympathetically maintained pain
may cause regional ischemia that results in significant localized
or widespread pain. Alterations in developing brains due to
environmental influences probably play a role as well. Trauma
and toxic stress can impact the developing brains of children and
adolescents; particularly the networks concerned with reward,
motivation/learning, and descending modulatory control for pain
Despite the intense pain symptoms and loss of function
associated with the syndrome, patients diagnosed with AMPS
generally have good outcomes with exercise therapy alone.
Psychotherapy may be added to physical therapy but is rarely
needed. Re-establishing normal use of the affected limbs and
returning to normal daily function with multidisciplinary therapy
(physical therapy, occupational therapy, and cognitive behavioral
therapy when needed) are the mainstays of AMPS treatment
[2,5,6]. Typically, greater than 80-90% of children who are
diagnosed regain full function and are without pain in one month.
Around 5% of children will not improve and have to be referred
for significant psychotherapy. Although the long-term prognosis
is generally favorable, 15-30% of all children diagnosed will have
a significant relapse within the first six months, most of which
resolve with self-initiated exercise programs [2,3].
Here, we report on a 9-year-old female with fever of
unknown origin and significant ankle pain following a left ankle
fracture that lasted over a three-month period. The patient was
diagnosed with Amplified Musculoskeletal Pain Syndrome with
an autonomic component leading to her fevers. Fortunately, the
patient responded well to intensive physical therapy and is now
fever and pain free.
A 9-year-old female gymnast presented to the Emergency
Department (ED) with a left ankle injury after getting her foot
trapped on a caged pedal resulting in forced hyper-dorsiflexion
of her foot while on a stationary bike. Upon arrival to the ED,
x-rays of the left ankle were taken. Findings revealed widening of
the distal left fibular physis consistent with a Salter-Harris type I
injury with lateral soft tissue swelling. No major acute fractures
or dislocations were noted at the time. Orthopedics assessed and
casted the injured ankle with no complications. Patient and family
were sent home with directions to follow-up with orthopedics.
The cast was removed one month later.
Following removal, the patient began to experience arthralgia
and edema to the left ankle. She also developed a fever at the
moment of cast removal (100.4 F). Her symptoms persisted for
two weeks. A CBC, CRP, ESR, UA, and monospot were ordered
and all labs were unrevealing (Tables 1 and 2). The fevers
continued to persist a week following the initial presentation to
her pediatrician. On the second visit, a murmur was found on
exam, thus an echocardiogram was ordered. ECHO findings were
negative for endocarditis and other cardiac abnormalities. The
patient started naproxen following the negative work-up, which
only provided transient relief for fever and pain.
After visiting her pediatrician, the patient was no longer able
to bear weight on left ankle and her fever persisted. She was seen
in consultation by orthopedics, where she received a magnetic
resonance imaging (MRI) without IV contrast of her left ankle. MRI
findings revealed edema at the lateral malleolus at the epiphysis
and physis with an associated fracture of the epiphysis, which were consistent with a Salter-Harris type I fracture and a tear to the anterior talofibular ligament. With written parental consent,
the patient also received fluoroscopic-guided joint aspiration,
which revealed no fluid, major infections, or abnormalities. Repeat
CBC, CRP, ESR showed no abnormalities. She was re-casted about
one week later following consultation with a pediatric orthopedic
During the four-week casting period, the patient did not
experience any ankle pain nor fever. Shortly after the 2nd cast
was removed, she again was unable to bear weight and began
experiencing the same symptoms of arthralgia and fever (100.9
F). Around the time of cast removal, she began to complain of
right lower quadrant pain. The patient again returned to her
primary pediatrician, and an abdominal ultrasound was ordered.
The ultrasound findings revealed no fluid collection, mass,
appendix abnormalities, or other abnormalities. Repeat labs were
unrevealing. At this point, the patient’s family sought consultation
with pediatric infectious disease and hematology/oncology.
Repeated labs and imaging ordered by those consultants found no
abnormalities (Tables 1 and 3).
A few weeks after consulting infectious disease and
hematology/oncology, the patient was referred to pediatric
rheumatology. She started intensive physical therapy (PT) for
her left ankle, which included therapeutic exercises & activities,
gait training, neuromuscular rehabilitation, manual therapy,
patient education, and self-care. Over 17 PT sessions, the patient’s
symptoms began to improve. At the end of PT, the patient had
successfully met goals of walking on ground level, squatting,
tumbling, and bar work. She is pain and fever free as well.
Amplified musculoskeletal pain syndrome (AMPS) is a
relatively rare diagnosis in children that encompasses a spectrum
of pain syndromes. Typically, females are more affected than
males with an average age of onset of 9-15 years. In most cases,
the lower extremity is the primary site of injury and subsequent
chronic pain .
About 14% of children with AMPS will have autonomic
signs associated with more localized pain, while those without
autonomic signs tend to have pain at multiple sites or joints
[1,3]. The prolonged nature of diagnosing AMPS stems from
this complicated spectrum of clinical presentations and
pathophysiological etiologies. The inability to diagnose AMPS
more efficiently often results in families making multiple visits to
the ED or outpatient clinics, which leads to numerous and often
duplicate tests being performed on symptomatic patients and substantial costs to both the healthcare system and families . In addition, the deterioration of quality of life in patients cannot
In this case, a 9-year-old female presented significant ankle
pain and swelling with fever of unknown origin of 115 days. The
unique autonomic component of AMPS in this patient complicated
and prolonged her diagnosis. Like most patients affected by
AMPS, she was subjected to numerous repeat blood tests, imaging
studies, and multi-specialty consults. For 115 days, patient was in
pain and unable to enjoy her favorite activities like gymnastics.
Eventually, intense physical therapy improved her symptoms to
the point where she was fever and pain free.
As past studies and this case reveal that intense physical
therapy is a highly effective treatment for AMPS, the issue remains
identifying AMPS in a timely fashion. The ability to diagnose AMPS
efficiently can potentially prevent prolonged disease in patients
and allow them to return to normal daily life more quickly.
Therefore, future studies should focus on further exploring the
possible manifestations of AMPS, especially when affected by
seemingly unassociated symptoms, like fevers, so that AMPS can
be better diagnosed and treated.
Here, we report a patient with AMPS complicated by fevers.
AMPS is a rare and difficult condition to diagnose because of the
broad spectrum of clinical presentations and pathophysiology.
Increased knowledge and understanding of various clinical
manifestations of AMPS can help physicians more quickly diagnose
and treat the disease.
Gmuca S, Weiss PF, McGill M, Xiao R, Ward M, et al. (2022) The Feasibility and Acceptability of Resilience Coaching for Adolescent Chronic Musculoskeletal Pain: A Single-Arm Pilot Trial. Children 9: 1432.