We described a case of CRMO whose final diagnosis and treatment was delayed for over 18 months due to uncommon presentation of his disease. The patient had received several courses of different antibiotics and had two vertebroplasty surgeries prior to his CRMO diagnosis.
First described in 1972 by Giedion et. al.(6), CRMO is an autoinflammatory disease that typically involves children. It affects girls 2-3 times more frequently (7), and its classic presentation is involving the lower extremities (metaphysis of the long bones), spine, pelvis, and clavicle (8). The disease typically affects more than one site; however, at the initial workup the number of lesions might be underestimated due to some of them not having any symptoms (1).
Having described the typical from of CRMO involvement, the disease can manifest a variety of presentations (9). There have been many case reports and case series of patients with atypical involvement (4, 10, 11). For instance, patients with acute vertebral deformities (12), chronic painful scoliosis (13), and chronic mandible involvement as their only presentation (9). This variety has been considerable, to the point that some studies have proposed classification of CRMO cases into subgroups based on their presented phenotypes, such as spinal or axial versus peripheral form (14, 15).
Spine involvement can be seen in almost 26% of CRMO patients (16). Since presenting only with chronic osteomyelitis of the vertebrae is not a common presentation of this rare disease (1), and there can be other serious conditions causing the symptoms, CRMO was not among the probable differentials for our patient at first. However, after finding clavicle involvement alongside spine osteomyelitis through imaging, CRMO diagnosis became most likely, since the clavicle can be considered a classical involvement site in CRMO (1). Thus, it can be suggested that in similar cases, whole-body imaging can be considered beside other workups. A great example of such imaging modalities is Whole-Body MRI, which has recently been considered the gold standard for CRMO diagnosis, as it is not invasive and does not expose the patient to radiation (1, 9).
According to the studies that report long-term follow-up of the patients, CRMO is generally well-prognosed (1). In a multicenter study following 131 CRMO patients, 82% of them were in remission a few years after treatment and had no relapse (7). Nonetheless, there are some concerns regarding this disease. Definite diagnosis of CRMO is only achievable by ruling out other critical diseases, namely infectious osteomyelitis and malignancies (2). This matter, in addition to its vast range of presentations (explained before) might result in delayed diagnosis of the disease. A study have reported the median time to CRMO diagnosis to be 15 months, with up to 92 months delay for one case (17). Moreover, another study reported a 6-year-old boy in whom symptoms started when he was 2, and it took 4 years to be diagnosed and properly treated (18). A delay in the diagnosis, similar to our case, can lead to the following issues:
First, the patient might receive several prolonged and unnecessary courses of treatment, such as antibiotics (13). In our case, the patient had received various antibiotics, and was on the treatment with Linezolid, which is mostly used for resistant, complicated and hospital-acquired infections (19). Second, the patients might develop deformities during this long period of disease activity without proper treatment (20). In the present case, our patient had developed spinal deformities and had undergone two spine surgeries. Earlier diagnosis can prevent the future cases from experiencing multiple invasive diagnostics (such as biopsies) and treatments, that will most probably have financial and emotional burden on the patients and their family. Another disadvantage of delayed diagnoses is that chronic pain and the impression of having a chronic disease might have psychological impact on the affected children, especially when the disease gives rise to physical deformities (21, 22). This might lead to their depression, anxiety, and consequently, less favorable educational and social function in the school and in future (5, 23). One study reported that even after the remission of their disease, children affected by CRMO had lower health-related quality of life than their healthy peers (24).
CRMO is considered as a rare disease, with estimated incidence of 4 per million children (1). However, as awareness about the disease increased through years, it can be stated that CRMO’s incidence has not been much far behind the incidence of bacterial osteomyelitis (3, 25). Thus, the low incidence rate can be due to underestimation and underdiagnosis of the disease. Nevertheless, the awareness about this disease is still suboptimal, leading to prolonged times to diagnoses (26, 27).
CRMO patients may initially approach or be referred to varying specialists. A case like ours is likely to be seen by an orthopedic surgeon at first because of his kyphosis. Hence, having different specialists, such as orthopedic and general surgeons, radiologists (considering various radiological patterns of the disease mimicking other diagnoses (9, 28)), and rheumatologists, as well as family physicians and general practitioners (as the frontline doctors that visit and refer these patients in the first place) in a close collaboration network is called for. Such interdisciplinary collaboration can possibly establish opportunities to discuss similar cases, and might lead to a timelier diagnosis by increasing the knowledge and awareness about the vast and varied presentations of CRMO.