Chronic recurrent multifocal osteomyelitis

Chronic recurrent multifocal osteomyelitis is a rare disorder of unknown etiology, characterized by multiple bone lesions and a variable clinical course. We present a 10 year old boy with chronic recurrent multifocal osteomyelitis who improved after treatment with naproxen.     

Chronic recurrent multifocal osteomyelitis – report of eight patients

The authors undertook a retrospective review of the clinical records and radiologic findings of eight children with chronic, recurrent multifocal osteomyelitis (CRMO). This disease is a recognized clinicopathologic entity with typical radiographic findings, mostly in the metaphyses of the long bones. The diagnosis is one of exclusion without pathognomonic findings. The patients were treated with non-steroidal anti-inflammatory drugs. There was no evidence of altered bone growth or abnormal joint development. It is concluded that CRMO is a distinct clinical entity that is different from acute or subacute bacterial osteomyelitis. Recognition of this condition is important to avoid treatment with antibiotics and repeated operations. Accepted: 8 April 1998     

Bacterial bone and joint infections in childhood--a review. 4. Subacute and primary-chronic osteomyelitis, rare forms of osteomyelitis

This is an overview of the most important aspects of pathogenesis, etiology, diagnostics, therapy and differential diagnostics of the subacute and primary chronic osteomyelitis in children. This group of disease includes Brodie's abscess, plasma cellular osteomyelitis, sclerosing osteomyelitis (Garré) and the chronic recurrent multifocal osteomyelitis. The treatment of children with these not completely understood diseases requires a close cooperation between pediatricians, pediatric surgeons and radiologists.     

Chronic recurrent multifocal osteomyelitis: a noninfectious inflammatory process

We report seven patients with chronic recurrent multifocal osteomyelitis, an uncommon childhood disease of unknown etiology. These patients presented with insidious onset of bone pain at one or more sites associated with erythema, swelling and tenderness. Scintigraphy and radiography were consistent with osteomyelitis at multiple sites. Bone biopsies confirmed osteomyelitis but no organisms were consistently isolated. During a 1- to 3-year follow-up, most patients developed new symptomatic lesions. The disease was unaffected by antimicrobial therapy. Two of our patients had psoriasis and all were rheumatoid factor-, antinuclear factor- and HLA-B27-negative. We speculate that chronic recurrent osteomyelitis is a noninfectious inflammatory condition, a seronegative spondyloarthropathy. Chronic recurrent osteomyelitis is a clinical entity that should be recognized so that invasive diagnostic procedures and antimicrobial therapy are appropriately used. The patient may be reassured that this is not a malignant condition although there may be exacerbations over many years.     

Chronic recurrent multifocal osteomyelitis in children: report of 17 cases]

Chronic recurrent multifocal osteitis (OCRM) is a rare condition in children, of unknown aetiology, which may be misdiagnosed as osteomyelitis, arthritis or tumour. PATIENTS AND METHODS: We present a retrospective multicentric study of 17 patients (five boys and 12 girls) with an average follow-up of 7.5 years (six months-25 years). RESULTS: A spectrum of presenting features is possible, ranging from bone lesions alone to lesions combined with arthritis, palmoplantar pustulosis or psoriasis. The diagnosis was delayed from two weeks to five years. Roentgenographic evaluation was often normal at the beginning of the disease or showed nonspecific bone reactions. Radioisotope bone scans assisted in establishing the diagnosis and in identifying lesions that were initially clinically silent. Bone biopsies were performed in seven cases. Histopathological examination showed only mild inflammatory nonspecific changes. Microbiological cultures were always negative. Treatments were different according to the evolution of the disease and the hospital. There was no response to antibiotics in seven patients. The response to nonsteroidal anti-inflammatory agents and steroids was moderate and often transient. Salazopyrine and pamidronate treatment used in two patients allowed a durable remission. We lost sight of four patients, pain persisted in three in spite of treatment, it disappeared in two with treatment, mild pain persisted in five without treatment and remission occurred in three without treatment. CONCLUSION: This study clarifies the clinical and radiologic features of chronic recurrent multifocal osteomyelitis. The recognition of this rare entity is often delayed and difficulties in patient management sometimes emerge from its usual protracted course.     

Successful management of chronic multifocal Q fever Osteomyelitis with adjuvant interferon-gamma therapy

We present a 3-year-old girl who had chronic recurrent multifocal osteomyelitis caused by Coxiella burnetii despite long-term dual antibiotic therapy. Excellent clinical response was achieved and sustained when immunomodulatory therapy with interferon-γ was initiated. This is the case of a first child who was successfully treated with interferon-γ as adjuvant therapy for chronic multifocal Q fever osteomyelitis.     

The syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia. Report of a new family and a review

A new autosomal recessive syndrome of chronic recurrent multifocal osteomyelitis (CRMO) and congenital dyserythropoietic anaemia (CDA) with microcytosis has recently been described in four children (two sibships) of one consangineous Arab family. In this report, we describe the clinical features and course of the syndrome of CRMO and CDA in two additional patients (one sibship) from another consanguineous Arab family and review the literature. The two patients (brother and sister), the products of a consanguineous marriage, developed the syndrome at an early age of 3 weeks and 2 months respectively. The diagnosis of CRMO was confirmed by radiological and technetium isotope bone scans. Bone marrow studies confirmed the diagnosis of CDA. Peripheral blood films showed hypochromia and microcytosis. The sites involved by CRMO were periarticular, mainly around the elbow, knee, wrist and small joints of the hand. The brother is now 21 years old and the sister 3.5 years old and CRMO is still active with frequent relapses. The brother developed flexion deformities at the age of 13 years. Both patients failed to thrive; weight and height were below the 5th percentile. CONCLUSION: This is the second report of the syndrome of chronic recurrent multifocal osteomyelitis and microcytic congenital dyserythropoietic anaemia, confirming it as a clinical entity, inherited as an autosomal recessive trait. The disease is characterised by an early onset, long clinical course of remissions and relapses, and seems to be different from the sporadic form of chronic recurrent multifocal osteomyelitis.     

Rare forms of chronic osteomyelitis in children (author's transl)

4 cases of chronic osteomyelitis in children and adolescents are described. The first one concerns a girl with severe plasmacellular osteomyelitis of the right upperarm. As the treatment with antibiotics failed a partial resection of the right humerus, followed by plastic covering of the resulting defect was successful. Two further cases of chronic metatarsal osteomyelitis of both feet could be classified as a kind of "sclerosing osteomyelitis Garré", mostly corresponding to the clinical feature of the "chronic recurrent multifocal osteomyelitis" (Bj?rkstén et al., 1978). Furthermore, a case of chronic ostitis localized in the symphyseal area is described, the clinical symptoms of which were resembling to the cortical osteoid, a special kind of sclerosing osteomyelitis. It is suggested that these different forms of chronic osteomyelitis in children are caused by bacterial infections. Nevertheless, this hypothesis remains to be proved. The problems of the differential diagnosis are discussed. Generally, the only therapy with antibotics is not successful, whereas the combination of removing of the inflammatory process with plastic covering of the bone-defect usually results in recovery.     

Chronic recurrent multifocal osteomyelitis of the spine and mandible: case report and review of the literature

At initial presentation, chronic recurrent multifocal osteomyelitis may mimic acute hematogenous osteomyelitis; however, cultures of affected bone are sterile. Nuclear scintigraphy identifies additional foci of involvement that present concurrently or sequentially. Unlike acute bacterial osteomyelitis, chronic recurrent multifocal osteomyelitis seems unaffected by antibiotic therapy and typically responds to treatment with antiinflammatory drugs. Surgical decortication has been reported for refractory cases. The case presented here illustrates the rare involvement of the mandible after initial presentation in the spine of a 4-year-old girl and the refractory nature of the disease over 6 years despite treatment with various medical and surgical therapies.     

Pyoderma gangrenosum in a six-month-old boy

Pyoderma gangrenosum (PG) is an uncommon, chronic ulcerative condition of the skin that was first described in 1930. It can occur in any age group, but only 4% of the patients are infants or children. An underlying systemic disease is present in approximately 50% of the patients with PG. The most common associations include inflammatory bowel disease, arthritis, lymphoproliferative disorders and chronic recurrent multifocal osteomyelitis (CRMO). PG has been reported in association with CRMO in only a few children whose ages were between 18 months and 12 years. We report a six-month-old boy who was diagnosed as CRMO based on his clinical examination and histological findings. This is the youngest case reported in the literature (under 12 months of age) with PG associated with CRMO.     

Chronic recurrent multifocal osteomyelitis with unusual features

We describe two children with chronic recurrent multifocal osteomyelitis who showed unusual extraskeletal manifestations. The first patient developed an asymptomatic pulmonary consolidation; the second had an atypic localization of the associated pustulosis, which involved the trunk, groin, thighs and buttocks, but spared the palms and soles. We conclude that this disease is clinically more heterogeneous than previously thought.     

Dramatic pain relief and resolution of bone inflammation following pamidronate in 9 pediatric patients with persistent chronic recurrent multifocal osteomyelitis (CRMO)

Background  

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.     

Locations of osteomyelitis in children with sickle-cell disease at Tokoin teaching hospital (Togo)

Background  The sickle-cell children are particularly affected by osteomyelitis in specific locations. This study was done in order to point out the locations of osteomyelitis in children with sickle-cell disease. This direct clinical examination for a quick diagnosis. Materials and methods  This is a retrospective study done by examining files of 43 children (15 girls and 28 boys), aged from 0 to 15 years, treated for osteomyelitis between January 1998 and December 2006. Their phenotypes included 18 SS, 14 SC and 11 AS. Osteomyelitis was acute in 20 cases and chronic in 23 cases. The different localisations are classified according to the type of osteomyelitis and the kind of bones concerned. Results  The 43 children presented 63 locations: 57 on long bones and 6 on short bones. The osteomyelitis was unifocal in 32 cases, and multifocal in 11 cases. The locations on long bones were humeral (18 cases), tibial (12 cases), femoral (9 cases), fibular (7 cases), radial (7 cases) and ulnar (4 cases). The 6 short bones included 3 metacarpus and 3 phalanxes. The 11 multifocal locations concerned 8 SS, 2 AS and 1 SC. In chronic osteomyelitis, 7 patients had sequestrum and 2 had pathological fracture. Conclusion  During examination of sickle-cell children with fever, particular attention must be shown, respectively to the arm, the leg and the thigh, in order to track down quickly, an acute osteomyelitis. Early diagnosis and quick treatment permit to avoid complications and heavy sequela in these children.     

Primary multifocal osseous lymphoma in a child

We report a case of primary multifocal osseous lymphoma in a 6-year-old girl presenting with multifocal osteolytic lesions without systemic symptoms or identifiable non-osseous primary tumor. The differential diagnoses for such a presentation include histiocytosis X, chronic recurrent multifocal osteomyelitis, acute lymphoblastic leukemia, metastatic disease, and primary bone lymphoma. Although non-Hodgkin lymphoma is common in the pediatric population, its presentation as a primary bone tumor, especially with multifocal disease, is extremely rare and is frequently misdiagnosed. We hope that awareness of this entity will help radiologists achieve timely diagnosis and intervention.     

儿童慢性骨髓炎应用抗感染活性骨Ⅰ期植骨治疗的疗效评价

目的 验证抗感染活性骨(anti-infective reconstituted bone xenograft,ARBX)Ⅰ期植骨治疗儿童慢性骨髓炎的疗效.方法 自2001年9月对21例慢性骨髓炎患儿进行病灶清除,应用抗感染活性异种骨(anti-infective reconstituted bone xenograft,ARBX)Ⅰ期植骨治疗,其中获得12个月以上随访的儿童慢性骨髓炎患儿共16例.包括血源性慢性骨髓炎8例,原发性慢性骨髓炎3例,创伤性慢性骨髓炎5例.结果 16例中除1例骨髓炎复发,1例骨髓炎合并大段骨缺损在术后发生骨不连外,其余14例感染均获得控制无复发,病变部位均获得确实骨修复.本组感染治愈率(感染控制且无复发)为93.8%,完全治愈率(感染控制既无复发又完成骨修复)为87.5%.结论 ARBX具有高效诱导成骨活性和强效抗感染能力,是Ⅰ期植骨治疗儿童慢性骨髓炎的有效方法.     

Chronic recurrent osteomyelitis with clavicular involvement in children: diagnostic value of different imaging techniques and therapy with non-steroidal anti-inflammatory drugs

Chronic recurrent, uni- or multifocal osteomyelitis (CRMO), an inflammatory disorder of unknown origin, involves mk:/night/arul/4310946m.3dultiple osseous sites and may affect the clavicle. We report on 6 children with clavicular involvement out of 11 children suffering from CRMO. The major clinical symptoms were local swelling and pain. Five children had hyperostosis of the clavicle and synovitis of adjacent joints. Histology showed chronic osteomyelitis with a predominance of lymphocytes in the inflammatory infiltrates. Cultures of biopsy tissue specimens were sterile. The patients were followed for at least 3.5 years. Three patients had up to six relapses. The most effective diagnostic tools to define CRMO were standard X-ray and bone scan in combination with biopsy and cultures. In our patients CT and MRI were misleading as they suggested the presence of malignancy. However, the sensitivity of MRI to detect involvement of bone, adjacent joints and soft tissues were better in comparison to X-ray or bone scan. Non-steroidal anti-inflammatory drugs were effective in reducing pain, swelling and limitation of motion. Reconstructive surgery was not indicated in any case. The long-term outcome of growth and function of affected bones was excellent. Conclusion Diagnosis of chronic osteomyelitis of the clavicle should be made by history and physical examination and be confirmed by standard X-ray, bone scan and open biopsy. In contrast MRI and CT can provide data on the involvement of adjacent joints, soft tissue and muscles especially in the early process of disease, but do not add information relevant to the patient's management. Treatment with non-steroidal anti-inflammatory drugs is rapidly beneficial in most patients. Received: 24 January 1997 / Accepted: 26 May 1997     

Systematic review of systemic antibiotic treatment for children with chronic and sub‐acute pyogenic osteomyelitis

Background: There is a lack of consensus on the most appropriate antibiotics to treat children with chronic or sub‐acute pyogenic bacterial osteomyelitis and on the optimal duration of antibiotic therapy. Aim: To review the published evidence on the duration of antibiotic therapy and outcomes in children with chronic and sub‐acute pyogenic bacterial osteomyelitis. Methods: Systematic review of the literature. Results: We found no randomised controlled trials comparing different antibiotic regimens or comparing duration of antibiotic treatment for chronic or sub‐acute osteomyelitis in children. We found 14 observational case series published between 1973 and 2008. Most children with chronic osteomyelitis received 4–6 weeks of parenteral antibiotics followed by oral antibiotics to a total duration of 3–6 months. Small observational studies suggest that a shorter duration of parenteral and oral antibiotics may be equally effective. Conclusion: There is no high level evidence on the optimal duration of parenteral and oral antibiotics for children with chronic or sub‐acute osteomyelitis. A large randomised controlled trial is needed comparing short course parenteral and oral antibiotics with longer antibiotic duration.     

Oral alendronate in pediatric chronic recurrent multifocal osteomyelitis

Chronic recurrent multifocal osteomyelitis (CRMO) primarily affects children and adolescents, and is characterized by episodic sterile osteomyelitis over several years. No definitive treatment is available. Non‐steroidal anti‐inflammatory drugs (NSAID) are common first‐line agents, but provide limited improvement in bone pain and do not affect disease duration. Several agents are utilized in the case of non‐response to NSAID, including corticosteroids, methotrexate, and tumor necrosis factor‐blocking agents. Bisphosphonates are increasingly being used. Most case series involve cyclic i.v. pamidronate, but this restricts the social lives of children and their families. Although oral medication has advantages over cyclic i.v. infusion because it does not require repeated hospital admissions, there have been no reports on treatment with oral bisphosphonates, such as alendronate, in pediatric CRMO patients. This case report describes the use of oral bisphosphonate as an alternative treatment in CRMO patients in whom standard therapy has failed.     

Acute multilocular osteomyelitis in infancy and childhood

38 cases of acute multilocular osteomyelitis out of a total of 165 osteomyelitis patients were treated between 1974 and 1986 at the Department of Paediatric Surgery and Paediatric Diseases at the University of Mainz. Osteomyelitis in infants was separated from juvenile osteomyelitis because of the different problems inherent to this disease depending upon the age; likewise, multilocular remote involvement was separated from regional multiple involvement. It was found that distant involvement is of special importance in infancy. 6 of the 8 cases in this group presented with symmetrical involvement. This interesting phenomenon is described in this article for the first time in acute multilocular osteomyelitis; so far, it was known to occur only in chronic recurrent multifocal osteomyelitis (CRMO). The infants in this group were predominantly newborn who were particularly severely handicapped by predisposing factors such as necessary intensive-care measures or surgical interventions. Our findings showed that in this age group most of the problems occurred, namely: 3 deaths and 2 healing defects in 8 children. For this reason it is imperative to effect particularly close monitoring of multilocular acute osteomyelitis in infancy. This must be considered as a paediatric and paediatric-surgical emergency requiring not only accurate diagnostic measures but also early internistic and surgical treatment to improve the prognosis of this specific disease pattern.     

Chronic recurrent multifocal osteomyelitis: clinical outcomes after more than five years of follow-up

OBJECTIVE: To determine the clinical outcomes of children with chronic recurrent multifocal osteomyelitis (CRMO). STUDY DESIGN: Inception cohorts of children with CRMO were established at two tertiary pediatric centers. Outcome data were obtained through review of hospital charts, interview and examination of patients, and completion of questionnaires by patients. RESULTS: Of 45 eligible subjects, 23 (51%) were assessed. Median time since diagnosis was 13 years (range, 6-25). At evaluation, 6 (26%) had active disease; 18 (78%) had Health Assessment Questionnaire scores of 0 (no/minimal physical disability), and 5 had scores >0. Some impairment was seen in all domains of measurement of quality-of-life test, especially those concerning nonphysical aspects of health. Six (26%) subjects continued to have pain as a result of CRMO. Associated medical problems included arthritis in 6, sacroiliitis in 3, psoriasis in 5, recurrent pustular rashes in 2, and inflammatory bowel disease in 3. CONCLUSIONS: Long-term clinical outcomes for children with CRMO appear to be generally good, with most subjects having no evidence of disease activity or sequelae. However, a number of subjects had persistent disease and, therefore, remain at risk of physical and psychologic complications. Further research is required to identify patients at risk for persistent disease, and to determine therapies that may prevent morbidity.