CRMO syndrome M86.9-

Giedion et al. 1972

CRMO syndrome (CRMO stands for "Chronic Recurrent Multifocal Osteomyelitis") also called "Chronic Non-Bacterial Osteomyelitis" is a chronic disease with recurrent inflammation of the bone at one or more sites in the body.

Chronic recurrent multifocal osteomyelitis (CRMO) is a (non-bacterial) inflammation of the bone with no previously known cause.

School age; young children can also become ill.

Sufferers complain of bone or joint pain. In most cases, swelling occurs over the affected areas. In particular, the pain increases after exertion. There is usually no strong feeling of illness, but patients often feel fatigued and slight increases in temperature may occur. High and persistent fever is atypical. In principle, CRMO can occur in all bones. The clavicles and pelvic bones are particularly frequently affected. Other typical sites are the upper and lower leg bones, including the foot, and the spine. Less commonly, the bones of the head, arms, or ribs are affected.

Associations:

• GI tract: CRMO may be associated with inflammatory bowel disease (Crohn's disease, ulcerative colitis).
• Skin lesions(pustular psoriasis palmoplantaris) are detected in 30% of sufferers.

The changes of the bone can be visible in the X-ray image. Especially on the long tubular bones of the arms and legs, changes are found that are very typical for CRMO.

A whole-body MRI is recommended, which provides an overview of the extent of osteomyelitis. Later MRIs are usually necessary during the course of the disease if pain recurs after symptom-free intervals or if a change in therapy is pending.

Signs of inflammation: The erythrocyte sedimentation rate (ESR) is almost always elevated, and C-reactive protein (CRP) is also elevated in cases of severe inflammation. The rest of the blood count is unremarkable. Bacteria can be detected neither in the blood nor in the inflamed bones.

The typical "rheumatism values" such as antinuclear antibodies (ANA), rheumatism factors or other antibodies are negative.

The therapy of CRMO depends on the individual affection of the bones. Symptomatic therapy with NSAIDs such as naproxen, ibuprofen, indometacin or diclofenac is often sufficient. These show a good effect in most patients. The duration of the medication depends on the individual course.

In acute severe symptoms, the short-term use of cortisone can also be useful, as cortisone is a strong anti-inflammatory drug. Long-term therapy with cortisone is not indicated due to the many adverse effects.

If treatment with pain and anti-inflammatory drugs is not sufficient, or if critical areas such as the spine or pelvic bones are affected, it is necessary to extend drug therapy. In recent years, treatment with bisphosphonates has become more popular.

In severe cases of CRMO, drug therapy with a TNFα blocker has also proven effective. In children, the drugs approved for JIA, etanercept(Enbrel) or adalimimab (Humira), are primarily used.

Alternative therapy: methotrexate and sulfasalazine.

Azithromycin: The antibiotic has an anti-inflammatory and probably immunologic effect in addition to its antibacterial effect. The recommended dose guideline was an introductory daily dose for one week and then a dose every 3 days for 3 months.

The disease progresses in relapses. An episode can last a few weeks or even months. The course is usually benign and the disease eventually comes to a halt. In most cases, spontaneous healing can be expected by the beginning of adulthood. Sometimes the disease occurs once without further relapses.

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2. Golla A et al. (2002) Chronic recurrent multifocal osteomyelitis (CRMO): evidence for a susceptibility gene located on chromosome 18q21.3-18q22. Eur J Hum Genet 10:217-221.
3. Hofmann SR et al (2017) Chronic Recurrent Multifocal Osteomyelitis (CRMO): Presentation, Pathogenesis, and Treatment. Curr Osteoporos Rep 15:542-554.
4. Koryllou A et al (2021) Chronic nonbacterial osteomyelitis in children. Children (Basel) 8: 551.
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6. Stern SM et al (2013) Autoinflammatory bone diseases. Rheum Dis Clin N Am 39:735-749.
7. Zhao DY et al (2021) Chronic nonbacterial osteomyelitis (CNO) and chronic recurrent multifocal osteomyelitis (CRMO). J Transl Autoimmune 4:100095.