Radiographic changes of chronic recurrent multifocal osteomyelitis that persisted into adulthood

Background

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory disorder and the most severe form of chronic non-bacterial osteomyelitis that primarily affects women, occurring in less than 1 in 1 000 000.1 2 Autoinflammatory disorders have systemic involvement of serological markers such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin 6 and tumour necrosis factor (TNF) alpha without any autoantibodies, pathogens or antigen-specific T cells present.3 The age of onset of CRMO is between 4 and 14 years with a median of 10.4 The disorder has a variable presentation that can include local oedema, pain and warmth of the involved region with or without fever.4

This disease is now considered to be part of the same spectrum with SAPHO syndrome (an acronym for synovitis, acne, pustulosis, hyperostosis and osteitis).5 The most common location of involvement for SAPHO syndrome is the anterior chest such as the sternum, clavicles and sternocostoclavicular regions, whereas CRMO will most commonly involve in the metaphysis of long bones.1 5 CRMO itself is associated with other conditions such as sacroilitis, psoriasis and Crohn’s disease.2 Diagnosis is by exclusion since there are no specific biomarkers involved and usually requires a bone biopsy to rule out infectious or neoplastic processes.1–3 Bone scintigraphy, MRI, X-rays and bone biopsies may aid in the diagnosis.6

Radiographs will appear similar to bacterial osteomyelitis with osteolytic and sclerotic bone lesions; however, culture will result in sterility.7 Because this disease is not of an infectious nature but inflammatory one, antibiotics are ineffective for treatment.7 The case herein describes persistence of CRMO disease into adulthood and its destructive progression. We detail the case of a young teenager who presented initially at 13 years of age with right tibia pain, and three times more in the next decade because of worsening of his condition.

Case presentation

A 13-year-old Caucasian man presented to his family physician in May 2001, following a soccer injury. The patient was subsequently referred to the department of orthopaedic surgery for further evaluation because of right tibia, knee pain and elevated ESR and abnormal X-rays. The symptoms included dull pain localised to the right knee and anterior tibia, the left clavicle and left proximal humerus. The patient denied associated symptoms such as fever and weight loss. His medical history was unremarkable and denied prior hospitalisations, surgeries and allergies to medications. Examination of the patient revealed a young teenager in mild distress but with full range of motion (ROM) of all extremities. Slight swelling was noted on the anterior proximal tibia with associated tenderness to palpation but without erythema or warmth.

The patient presented with left hip pain as well as right tibia/knee pain the following year. In addition, he reported fever for about a week. He denied having diarrhoea, weakness, nausea, vomiting, cough or weight loss, and his overall food intake had been normal. Examination revealed ROM of all extremities, but tenderness was noted to the left greater trochanter.

The patient was evaluated again in October 2007 for right proximal tibia and knee pain post injury from karate. The patient did not present systemic signs at this time but did felt as though he had a recent fever. He admitted naproxen alleviated pain and walked in without assistance. He had a healed incision from the previous bone biopsy on the right proximal tibia area with associated pain. He had full ROM of all extremities.

The patient returned in November 2011 with right knee and tibia pain. He stated that the pain had become persistent. He denied any associated symptoms such as fevers, chills, night sweats or weight loss. He admitted to taking NSAIDS (non-steriodal anti-inflammatory drugs) for pain relief. An examination showed that he was healthy, in mild distress, alert and oriented. Inspection of the right lower extremity showed gross swelling and deformity of the proximal tibia area with significant tenderness to palpation. The patient had full ROM in the bilateral lower extremities. He had no effusion of the right knee area and his neurovascular status was intact.

Investigations

In 2001, right lower extremity anterior–posterior X-ray showed sclerotic changes in the proximal tibia suggesting osteomyelitis. MRI showed inflammatory changes with an increased T2 activity in the proximal metaphysis of the tibia extending down to the tibia tuberosity. White blood cell (WBC) count was slightly elevated (9.5×10⁹/L), with an elevated ESR of 57 mm/hour and a normal CRP of 1.4 mg/dL. The bone scan showed increased tracer activity in the right anterior proximal tibia. A bone biopsy was performed that revealed no evidence of malignancy and cultures resulted without the presence of microbes. The working diagnosis was chronic bacterial osteomyelitis versus CRMO. Repeat radiographs showed only marginal sclerosis with some healing and no signs of periosteal reactions or boney expansions.

In 2002, laboratory results showed a non-elevated CRP of 0.2 mg/dL, ESR of 26 mm/hour and WBC of 6.2×10⁹/L. X-rays displayed slight thickening of the cortex of the diaphysis of the left femur with periosteal elevation consistent with an ‘onion skinning’ appearance. The findings prompted advanced imaging with a triple-phase bone scan. The fat-suppression MRI of the left femur (figure 1A) showed some cortical thickening of the proximal area to the mid-shaft of the left femur with periosteal reactions. Figure 1B indicated an increased tracer uptake in the left proximal hip to the mid femur. Differential diagnosis included Ewing’s sarcoma, CRMO or stress fracture of the left femur. MRI imaging did not suggest invasion of bone. CT revealed the presence of a small stress fracture of the left femur and some cortical thickening suggesting chronic osteomyelitis (figure 1C). A follow-up fat-suppression MRI (figure 1D) showed some improvement with cortical thickening and periosteal reactions lessened. This stress fracture and local reactivity of the left femur probably resulted from CRMO.

In 2007, X-ray imaging showed sclerotic changes, thickened cortex of the proximal right tibia and periosteal elevation of the lateral cortex, which had worsened from radiographs in 2001 (figure 2A and B). Bone scan of lower extremities with 3-hour delay showed increased activity of the right proximal tibia through the metaphysis into the proximal diaphysis (figure 3). The differential diagnosis included CRMO versus osteogenic sarcoma; however, there was not sufficient evidence to suggest malignancy.

In 2011, CRP and ESR were both elevated at 23.2 mg/L (normal 0.1–8.2 mg/L) and 47 mm/hour (normal 0–10 mm/hour), respectively. X-rays of the right lower extremity showed an osteolytic process of the proximal tibia, elevation of the lateral cortex and thickening of the anterior cortex (figure 4A and B). MRI of the right lower extremity showed anterior cortical thickening and destruction of the proximal right tibia with extension to the mid-shaft as well as periosteal inflammatory changes in the proximal tibia (figure 5A–C). The differential diagnosis included CRMO, chronic bacterial osteomyelitis or osteogenic sarcoma; however, there were inflammatory changes without signs of marrow replacement on imaging or any presence of joint invasion suggesting CRMO or chronic bacterial osteomyelitis as a more likely diagnosis.

Treatment

Treatment initially in 2001 was daily intravenous cefazolin (1.2 g) for 7 weeks at home through a subclavian central line for possible chronic bacterial osteomyelitis. The patient was advised to follow-up after intravenous antibiotics to obtain repeat imaging. In 2002 and 2007, treatment included NSAIDS for pain control and also to avoid contact sports. Treatment in 2011 included sulfamethoxazole/trimethoprim for 6 weeks for possible chronic bacterial osteomyelitis, NSAIDS for pain and to avoid contact sports indefinitely. Recommendations for possible debridement surgery were offered at the time of this last visit but patient refused due to financial constraints.

Outcome and follow-up

The patient was told to follow-up with infectious disease for more lab work, imaging and possible orthopaedic surgery after antibiotic therapy in 2011. However, he did not attend any more appointments. The patient outcome overall was good, and he has not sought any more treatment for his condition as of this time.