scispace - formally typeset
Search or ask a question

Chronic recurrent multifocal osteomyelitis in children

01 Jan 2002-
TL;DR: It has been shown that histological examination alone does not allow the distinction of CRMO from acute or subacute bacterial osteomyelitis, therefore an extensive microbial workup of the tissue biopsy, including PCRtechniques, is essential in order to establish the diagnosis and decide as to the treatment.
Abstract: Chronic recurrent multifocal osteomyelitis (CRMO) in children is an inflammatory disorder. It affects mainly the metaphyses of the long bones, in addition to the spine, the pelvis and the shoulder girdle. However, bone lesions can occur at any site of the skeleton. Even though this disease has been recognized as a clinical entity for almost three decades now, its origin and pathogenesis are not entirely clear. No apparent infectious agents are detectable at the site of the bone lesion. No epidemiological data on incidence and prevalence have been published so far. However, incidence might be something around 1:1,000,000, thus reflecting the number of patients followed-up. Clinical diagnosis in an affected child can be difficult because the clinical picture and course of disease may vary significantly. It has been shown that histological examination alone does not allow the distinction of CRMO from acute or subacute bacterial osteomyelitis. Therefore an extensive microbial workup of the tissue biopsy, including PCRtechniques, is essential in order to establish the diagnosis and decide as to the treatment. Non steroid anti-inflammatory drugs (NSAID) are the treatment of choice. In case of frequent relapses oral steroid treatment, bisphosphonates and azulfidine have been used and are reported to be beneficial.
Citations
More filters
Journal ArticleDOI
TL;DR: CNO is a spectrum of inflammatory conditions, with CRMO being the most severe, but most children with CNO have a favourable outcome of the disease.
Abstract: Background: Chronic recurrent multifocal osteomyelitis (CRMO) in children is a chronic non-suppurative inflammation involving multiple sites. Some children affected by chronic non-bacterial osteomyelitis (CNO) do not have multiple lesions or a recurrent course. Objective: To characterise the long term outcome of children with the full spectrum of CNO. Methods: 30 children diagnosed with CNO were followed up for a mean of 5.6 years and their disease assessed using a clinical score, multiple imaging, and a diagnostic biopsy, including extensive microbial analysis. Results: 9 patients had unifocal non-relapsing disease, 3 unifocal lesions with relapses, 9 multifocal lesions without relapses, and 9 multifocal lesions with relapses (CRMO). Granulocytes were present significantly more often in CRMO than in unifocal and non-recurrent lesions. Pustulosis was more common in multifocal cases regardless of recurrence. Mean duration of treatment in 15 children with a single occurrence was 9.2 months. Naproxen treatment was generally effective. Naproxen treatment in 12 patients with relapses lasted 25 months. However, 7 of these were not effectively treated with naproxen alone. Five were treated with oral glucocorticoids for 27 days in addition to naproxen, which induced remission in four, lasting for at least 1.5 years. Longitudinal growth of affected bones was not altered, except for the development of hyperostosis. Conclusion: CNO is a spectrum of inflammatory conditions, with CRMO being the most severe. Most children with CNO have a favourable outcome of the disease. Oral glucocorticoids may be necessary in severe recurrent cases.

228 citations

Journal ArticleDOI
TL;DR: Pamidronate resulted in resolution of pain and MRI documented inflammation in all patients and it is proposed that pamidronsate is an effective second-line therapy in persistent CRMO.
Abstract: Chronic recurrent multifocal osteomyelitis (CRMO) is an inflammatory, non-infectious osteopathy that affects predominantly patients ≤ 18 years of age. There is no uniformly effective treatment. Our objective is to describe clinical, magnetic resonance imaging (MRI), and bone resorption response to intravenous pamidronate in pediatric CRMO. We report our prospectively documented experience with all CRMO patients treated with pamidronate between 2003 and 2008 at a tertiary pediatric centre. Pamidronate was administered as intravenous cycles. The dose of pamidronate varied among subjects but was given as monthly to every 3 monthly cycles depending on the distance the patient lived from the infusion center. Maximum cumulative dose was ≤ 11.5 mg/kg/year. Pamidronate treatment was continued until resolution of MRI documented bone inflammation. Visual analog scale for pain (VAS) and bone resorption marker urine N-telopeptide/urine creatinine (uNTX/uCr) were measured at baseline, preceding each subsequent pamidronate treatment, at final follow-up, and/or at time of MRI confirmed CRMO flare. MRI of the affected site(s) was obtained at baseline, preceding every 2nd treatment, and with suspected CRMO recurrence. Nine patients (5 F: 4 M) were treated, with a median (range) age at treatment of 12.9 (4.5–16.3) years, and median (range) duration of symptoms of 18 (6–36) months. VAS decreased from 10/10 to 0–3/10 by the end of first 3–day treatment for all patients. The mean (range) time to complete MRI resolution of bone inflammation was 6.0 (2–12) months. The mean (confidence interval (CI)) baseline uNTX/uCr was 738.83 (CI 464.25, 1013.42)nmol/mmol/creatinine and the mean (CI) decrease from baseline to pamidronate discontinuation was 522.17 (CI 299.77, 744.56)nmol/mmol/creatinine. Median (range) of follow-up was 31.4 (24–54) months. Four patients had MRI confirmed CRMO recurrence, which responded to one pamidronate re-treatment. The mean (range) uNTX/uCr change as a monthly rate from the time of pamidronate discontinuation to flare was 9.41 (1.38–19.85)nmol/mmol/creatinine compared to -29.88 (-96.83–2.01)nmol/mmol/creatinine for patients who did not flare by the time of final follow-up. Pamidronate resulted in resolution of pain and MRI documented inflammation in all patients. No patient flared while his/her uNTX/uCr remained suppressed. We propose that pamidronate is an effective second-line therapy in persistent CRMO.

158 citations

Journal ArticleDOI
TL;DR: The synovitis, acne, pustulosis, hyperostosis, osteitis syndrome is pertinent even in paediatrics since skin involvement is frequent, and in adults, chronic recurrent multifocal osteomyelitis is now a classical manifestation of SAPHO syndrome.
Abstract: Chronic recurrent multifocal osteomyelitis is a rare chronic inflammatory musculoskeletal process observed in children and young adults. Recently, the acronym SAPHO syndrome (for synovitis, acne, pustulosis, hyperostosis, osteitis) was coined to emphasise the association between osteo-articular inflammations and different skin abnormalities which are aseptic and filled with neutrophils. In adults, chronic recurrent multifocal osteomyelitis is now a classical manifestation of SAPHO syndrome. Chronic skin disorders were seen in eight of ten children on follow-up at the University Children's Hospitals in Bern and Zurich and in 61 of 260 paediatric cases reported in the literature. The different skin lesions were palmoplantar pustulosis (n=40), non-palmoplantar pustulosis (n=6), psoriasis vulgaris (n=16) or severe acne (n=4). More rarely Sweet syndrome (n=2) or pyoderma gangrenosum (n=1) were reported. Conclusion The synovitis, acne, pustulosis, hyperostosis, osteitis syndrome is pertinent even in paediatrics since skin involvement is frequent.

155 citations

Journal ArticleDOI
TL;DR: There is a strong association with inflammatory disorders of the skin and intestinal tract in affected individuals and their close relatives, suggesting a shared pathophysiology and supporting a genetic component to disease susceptibility.
Abstract: Chronic recurrent multifocal osteomyelitis (CRMO) is an inflammatory disorder that primarily affects children. Its hallmark is recurring episodes of sterile osteomyelitis. The clinical presentation is insidious onset of bone pain with or without fever. Laboratory studies typically reveal nonspecific evidence of inflammation. Radiologic imaging and histologic appearance resemble those of infectious osteomyelitis. There is a strong association with inflammatory disorders of the skin and intestinal tract in affected individuals and their close relatives, suggesting a shared pathophysiology and supporting a genetic component to disease susceptibility. Two genetic syndromes have CRMO as a prominent phenotype—Majeed syndrome and deficiency of the interleukin-1 receptor antagonist—and suggest that interleukin-1 may be a key cytokine in disease pathogenesis. This review briefly summarizes the main clinical and radiologic aspects of the disease and then focuses on genetics and pathophysiology and provides an update on treatment.

154 citations


Cites background from "Chronic recurrent multifocal osteom..."

  • ...Other less-frequent associations include acne [1, 4], generalized pustulosis [23, 24••, 25••], Sweet syndrome [26–30], dyserythropoietic anemia [27, 31], pyoderma gangrenosum [5, 32, 33], sclerosing cholangitis [5, 20], inflammatory arthritis [1, 2, 5, 34], sacroiliac joint involvement [35], Still disease [36], Takayasu arteritis [37–39], antineutrophil cytoplasmic antibody–positive vasculitis [5, 40], Ollier disease (multiple enchondromatosis) [5], parenchymal lung disease [41, 42], dermatomyositis (Ferguson, unpublished data), and tumoral calcinosis [43–45]....

    [...]

  • ...Laboratory investigations often reveal mild elevations in white blood cell count and erythrocyte sedimentation rate (ESR), but both of these may be normal [1, 3, 4]....

    [...]

Journal ArticleDOI
TL;DR: Non-steroidal anti-inflammatory drugs cause relief of symptoms in the majority of cases and Bisphosphonates and TNF-α blockers are alternatives for patients who do not respond or who have spinal involvement.
Abstract: Chronic recurrent multifocal osteomyelitis is a rare auto-inflammatory condition that primarily affects children and adolescents. It presents with recurrent episodes of pain related to the presence of foci of sterile bone inflammation. The long bones of the lower extremities are more frequently affected and the spine can also be involved. Imaging studies, including whole-body magnetic resonance, are important for diagnosis and detection of asymptomatic lesions. Bone biopsies may be necessary to exclude other diseases, including malignancy and infections. Non-steroidal anti-inflammatory drugs cause relief of symptoms in the majority of cases. Bisphosphonates and TNF-α blockers are alternatives for patients who do not respond or who have spinal involvement.

148 citations


Cites background from "Chronic recurrent multifocal osteom..."

  • ...Usually NSAIDs are the first therapeutic choice, and they are effective in approximately 80% of patients [7, 41]....

    [...]

  • ...An infectious cause for CRMO seems, therefore, rather unlikely and the previously described isolation of organisms, such as Staphylococcus epidermidis, has been attributed to sample contamination [7]....

    [...]

References
More filters
Journal Article

353 citations


"Chronic recurrent multifocal osteom..." refers background in this paper

  • ...Even though this disease has been recognized as a clinical entity for almost three decades now (1), its origin and pathogenesis are not entirely clear....

    [...]

Journal Article
TL;DR: From this investigation, it appears that dermatological and osseous pictures described under various denominations, present common characteristics and transition forms justifying their common study under the acronym SAPHO (Syndrome Acne-Pustulosis-Hyperostosis-Osteitis).
Abstract: The authors report the data collected by a national investigation organized by the French Society of Rheumatology, concerning the osteo-articular manifestations of severe acne, palmo-plantar pustulosis and primary thoracic and peripheral hyperostosis. This investigation collected 85 case-reports including 13 severe acne, 44 PPP and 28 hyperostosis without the dermatitis mentioned above. From this investigation, it appears that dermatological and osseous pictures described under various denominations, present common characteristics and transition forms justifying their common study under the acronym SAPHO (Syndrome Acne-Pustulosis-Hyperostosis-Osteitis). The bony involvement, especially anterior thoracic, but also vertebral and even peripheral seems to be the common denominator between these diseases. It realizes a true rheumatoid inflammatory osteitis, osseous counterpart of synovial and cartilagenous affections in inflammatory rheumatoid diseases. This group has rather loose connections with common psoriasis and slightly more definite relationships with primary ankylosing spondylarthritis. These clinical and immunogenetic connections occur also through bony involvement.

324 citations


"Chronic recurrent multifocal osteom..." refers background in this paper

  • ...In adults a similar disease has been named "SAPHO-syndrome" (Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis) (19, 20)....

    [...]

  • ...CRMO has been regarded by Kahn et al. as the pediatric subset of the SAPHO-syndrome (21,22)....

    [...]

  • ...as the pediatric subset of the SAPHO-syndrome (21,22)....

    [...]

Journal ArticleDOI
TL;DR: The association of sterile inflammatory bone lesions and neutrophilic skin eruptions is the cornerstone of this new syndrome, which also has links with spondyloarthropathies and plain psoriasis.
Abstract: The occurrence of musculoskeletal manifestations (including synovitis, chest wall arthro-osteitis and multifocal aseptic osteomyelitis) in association with severe acne, palmoplantar pustulosis and perhaps with some presentations of psoriasis, have been described by many authors in the past 30 years. These different multifaceted descriptions have been designated by a variety of terms. More recently, a possible link between these conditions and spondarthritides has also been underlined by a slightly increased prevalence of HLA-B27 and occasional occurrences of sacroiliitis, chronic inflammatory bowel disease and possibly psoriasis. An acronym, the SAPHO syndrome (which stands for Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis) is proposed for this group of diseases because of the similarity of musculoskeletal manifestations in patients with severe acne and pustulosis. The clinical, epidemiological, pathophysiological, immunogenetic and diagnostic aspects, as well as the management of this syndrome, are reviewed.

282 citations


Additional excerpts

  • ...In adults a similar disease has been named "SAPHO-syndrome" (Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis) (19, 20)....

    [...]

  • ..."SAPHO-syndrome" (Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis) (19, 20)....

    [...]

Journal ArticleDOI
TL;DR: Morphologically CRMO begins as an acute inflammatory process with a predominance of polymorphonuclear leucocytes, which occasionally form an abscess and osteoclastic bone resorption, but at a later stage the predominant features are lymphocytes in the inflammatory infiltrates and occasional granulomatous foci and sigans of bone formation.
Abstract: Chronic recurrent multifocal osteomyelitis (CRMO) is characterised by an insidious onset of fever, local swelling and pain in affected bones, and radiological abnormalities suggestive of osteomyelitis. The histopathological features in 14 patients are described. Morphologically CRMO begins as an acute inflammatory process with a predominance of polymorphonuclear leucocytes, which occasionally form an abscess and osteoclastic bone resorption. At a later stage the predominant features are lymphocytes in the inflammatory infiltrates and occasional granulomatous foci and sigans of bone formation. The clinical course may be prolonged for many years.

216 citations


"Chronic recurrent multifocal osteom..." refers background in this paper

  • ...Histologically, bone lesions in uni- and multifocal CRMO, as well as SAPHO show similar features (6, 13, 23-26)....

    [...]