CRMO / SAPHO
Chronic Recurrent Multifocal Osteomyelitis (CRMO)
Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis (SAPHO)
Chronic Recurrent Multifocal Osteomyelitis (CRMO) and Synovitis, Acne, Pustulosis,
Hyperostosis and Osteitis (SAPHO) are both forms of Chronic Nonbacterial Osteomyelitis (CNO) In children and adolescents, CNO primarily affects the ends (“metaphyses”) of the long bones and the collarbone, but inflammatory lesions can occur in any part of the skeleton. Symptoms usually include bone pain, but there may also be asymptomatic lesions. The cause is unknown, but likely autoinflammatory. Treatment options are NSAIDs, Bisphosphonates and anti-TNF
Explanation of terms
Chronic: for a longer period of time
Recurrent: always coming back
Multifocal: in multiple places
Osteomyelitis: inflammation of the bone and marrow
Synovitis: inflammation of the joint
Acne: condition of the sebaceous glands
Pustulosis: presence of larger numbers of pustules on the skin
Hyperostosis: excessive growth of the bone
Ostitis: inflammation of the bone
Most patients suffer from bone and/or joint pain. Because of the pain, patients are often unable to use the affected body part well. This can result in limping. On physical examination, there is often localized bone swelling and bone pain and sometimes inflammation of the joints. There may also be areas of inflammation in the bone that do not affect the patient. These are called silent asymptomatic lesions. The type of bone that is affected, the severity and the duration of the symptoms vary between patients and even between attacks in the same patient.
Other organs, such as the eyes, gastrointestinal tract and lungs, may also be affected.
Common skin abnormalities associated with SAPHO are pustules on the palms of the hands and on the feet. The disease may have a chronic course, or there may be episodes of recovery and recurrence. CRMO is more common in children and SAPHO is more common in adults.
The frequency of occurrence is not precisely known. Based on records of the disease in several European countries, approximately 1-5 persons per 10000 residents appear to have the disease. Men and women are equally affected.
The cause is unknown. It is believed that the disease is the result of a disturbed regulation of the innate
immune system (see also section on the immune system). There is possibly a defect of the bone metabolism, because rare innate disorders of bone metabolism can give similar abnormalities.
There is no evidence for this, but it is possible that genetic factors play a role. There are rare
cases in which CRMO/SAPHO occurred in several members of the same family.
CNO is a diagnosis of exclusion. Laboratory testing is not specific or sensitive
to the condition. X-rays of early lesions often appear normal. If the
abnormalities have existed longer, an elevation in bone density and bone formation, consistent with CNO/CRMO,
may be seen on X-rays of the long bones or collar bones.
If the patient has had the disease for a longer period of time, collapsed vertebrae may occur, but these are not specific to CNO. Collapsed vertebrae can also be caused by osteoporosis and cancer. To be able to make a diagnosis it is therefore very important to combine the symptoms, the findings of the physical examination and the results of the X-rays.
Because x-rays are often nonspecific and only show abnormalities at a late stage, an MRI can be made using a contrast agent (administered via an IV). With an MRI, bones and the surrounding muscles can be imaged more accurately. By administering a contrast agent, inflammations can be seen more clearly. To detect silent asymptomatic lesions, an MRI of the entire body can be made, the so-called whole body MRI. Because an MRI is a long and expensive procedure, a bone scintigraphy with radionuclides technetium or a PET scan are sometimes used as alternatives. Both techniques show the entire body but are less sensitive than an MRI.
Often a biopsy is needed to rule out other causes (such as an infection or cancer) of bone pain and swelling. During a biopsy, a small piece of bone is removed, usually while the patient is under general anaesthesia. The bone sample is examined under a microscope and part of the sample is often analysed via culture to rule out infection.
A diagnosis of CNO is very probable if the bone abnormalities have been present for a longer period of time, are in multiple locations, and if the patient also has typical skin abnormalities consistent with SAPHO. If that is the case, a biopsy is not always needed.
The first step of treatment is usually an NSAID, with preference given to Naproxen. This treatment is successful in controlling the inflammation in about half of the patients. However, a significant number of patients require heavier
medications, such as corticosteroids (prednisolone), MTX or sulfasalazine. Recently, favourable
results have been reported for treatment with bisphosphonates (pamidronate, alendronate), and some patients respond well to anti-TNF (humira, infliximab, enbrel).
With the right treatment, the prognosis is usually good: recovery with little or no
residual symptoms. Unfortunately, there are also patients with a chronic course of the disease who do not respond to medication.