CRMO (Chronic Recurrent Multifocal Osteomyelitis)

Key Points:

  • Culture negative inflammatory process of bones
  • Affects long bones, pelvis and spine (produces vertebra plana)
  • Inflammatory markers are elevated 
  • Treatment is symptomatic based on pain and disability with nonsteroidial anti-inflammatory drugs (NSAIDs), corticosteroids, or disease-modifying antirheumatic drugs (DMARDs)
  • Remission occurs

Description:

Chronic Recurrent Multifocal Osteomyelitis (CRMO) is thought to be an auto-inflammatory process and possibly the pediatric form of SAPHO (Synovitis Acne Pustulosis Hyperostosis Osteitis) syndrome. It is a noninfectious/culture negative inflammation of involved bones which leads to pain and bony destruction. When present in the spine it can result in vertebra plana.

Epidemiology:

An Australian study demonstrated an occurrence of 1/100,000 new cases/year (Walsh, 2015). CRMO is more common in girls than boys (Voit, 2015; Walsh, 2015; Johnsson, 2015; Catalano-Pons, 2008). Not all patients have multiple lesions at presentation with some recurring and other lesions presenting at a different location later (Walsh, 2015; Johnsson, 2015). Due to similarity in presentation with bacterial acute osteomyelitis, the delay in diagnosis may be up to 1-2 years. 
Personal or family history of psoriasis or inflammatory bowel disease may be present in patients with CRMO, suggesting a genetic component to disease susceptibility (Ferguson, 2012).

Clinical Findings:

Pain is the most common presenting symptom, followed by swelling and then fever, which may occur in 21% of patients (Walsh, 2015; Johnsson, 2015). It may present in long bones, the pelvis, calcaneus, sternum, clavicle, or spine. There may be multiple symptomatic lesions per episode or different areas may appear at a later interval. Pain and inflammation may resolve and then recur (Walsh, 2015; Johnsson, 2015; Catalano-Pons, 2008; Huber, 2002). It is similar in presentation and in clinical appearance to bacterial osteomyelitis, which can lead to the delay in diagnosis due to initial treatment for bacterial osteomyelitis.

Imaging Studies:

X-rays of the involved body part may show sclerosis or lysis with new bone formation. Spinal involvement results in vertebra plana (Voit, 2015; Ferguson, 2012).  MRI is considered the most sensitive imaging study (Ferguson, 2012) and is effective in the diagnosis of painful and asymptomatic lesions with greater success than plain radiographs (Johnsson, 2015). Recent studies have utilized whole body MRI to document and follow multiple lesions (Voit, 2015). Bone scans were used previously with lesions showing increased uptake (Ferguson, 2012; Abril, 2007).
C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are routinely elevated, but leukocytosis is less common (Walsh, 2015; Ferguson, 2012; Catalano-Pons, 2008; Manson, 1989). By definition, all cultures of blood and tissue specimens are negative. Biopsies of bone will be consistent with chronic inflammation (Walsh, 2015; Abril, 2007; El-Shanti, 2007; Manson, 1989).

Etiology:

CRMO is thought to be an auto-inflammatory process and possibly the pediatric form of SAPHO syndrome.  It is estimated that up to 25% of CRMO patients have an associated inflammatory disorder such as pustulosis, psoriasis or inflammatory bowel disease (Ferguson, 2012; Huber, 2002).

Treatment:

Treatment is routinely managed by rheumatologists and is aimed at relieving symptoms. NSAIDs are the first line of treatment but may not be successful. If nonsteroidial anti-inflammatory drugs (NSAIDs) fail to relieve symptoms, other treatments such as corticosterioids or disease-modifying antirheumatic drugs (DMARDs), such as methotrexate or tumor necrosis factor (TNF) inhibitors are used (Walsh, 2015; Johnsson, 2015; Voit, 2015; Ferguson, 2012). 
CRMO is thought to be a self-limited disorder that resolves with time, although the time to resolution of symptoms appears longer than previously thought. In a French study, 50% of patients still had active disease after 3.5 years (Calatlo-Pons, 2008).  In a Norwegian study of 28 patients with CRMO diagnosed before 16 years of age, only 50% were in clinical remission after mean disease duration of 4 years. Most patients in remission were still on medication (Johnsson, 2015).  
An international study demonstrated 26% of patients had active disease 6-25 years after the initial diagnosis (Huber, 2002). In a German study, 50% of patients had ongoing clinical symptoms 10+ years after onset, also longer than previously reported. Patients may be in clinical remission yet still have positive radiographic findings or MRI changes (Voit, 2015).

Complications:

Leg length discrepancy (Walsh, 2015; Catalano-Pons, 2008; Manson, 1989), angular deformity, premature physeal closure (Manson, 1989) and chronic pain (Johnsson, 2015; Huber, 2002) have been documented. With prolonged disease symptoms, there is concern for local joint contracture and muscle atrophy/deconditioning from chronic pain.  
Complications due to steroid treatment can also occur such as decreased height potential and vertebral body compression fractures (Catalano-Pons, 2008).
Sulko published a case report and review of the literature documenting 3 cases of adolescents diagnosed with CRMO who later developed lymphoma, raising the question of an association between these two diseases (Sulko, 2013).

References:

  1. Abril JC, Ramirez A. Successful treatment of chronic recurrent multifocal osteomyelitis with indomethacin. J Pediatr Orthop. 2007;27(5):587-591.
  2. Catalano-Pons C, Comte A, Wipff J et al. Clinical outcome in children with chronic recurrent multifocal osteomyelitis. Rheum. 2008;47:1397-1399.
  3. El-Shanti HI, Ferguson PJ. Chronic recurrent multifocal osteomyelitis: a concise review and genetic update. Clin Orthop Relat Res. 2007.;462:11-19.
  4. Ferguson PJ, Sandu M. Current understanding of the pathogenesis and management of chronic recurrent multifocal osteomyelitis. Curr Rheumatol Rep. 2012;14:130-141.
  5. Huber AM, Lam PY, Duffy CM, et al. Chronic recurrent multifocal osteomyelitis: clinical outcomes after more than five years of follow-up. J Pediatr. 2002;141(2):198-203.
  6. Johnsson A, Flate B, Knudsen PK et al. Clinical outcome in a Norwegian cohort of patients with chronic recurrent multifocal osteomyelitis. Scan J Rheumatol. 2015;44(6):513-514.
  7. Manson D, Wilmot DM, King S, Laxer RM. Physeal involvement in chronic recurrent multifocal osteomyelitis. Pediatr Radiol. 1989;20:76-79.
  8. Sulko J. Diagnosit difficulties: chronic recurrent multifocal osteomyelitis and ymphoma. One or two diseases? J Pediatr Ortho B. 2013;22:170-174.
  9. Walsh P, Manners PJ, Vercoe J, et al. Chronic recurrent multifocal osteomyelitis in children: nine years’ experience at a statewide tertiary paediatric rheumatology referral centre. Rheumatol. 2015;54:1688-1691.
  10. Voit AM, Arnoldi AP, Douis H, et al. Whole-body magnetic resonance imaging in chronic recurrent multifocal osteomyelitis: clinical longterm assessment may underestimate activity. J Rheumatol. 2015;42(8):1455-1462.

Top Contributors:

Teresa Cappello MD