Multifocal Osteomyelitis Research Articles

Adult-onset chronic recurrent multifocal osteomyelitis: a case report.

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone disease predominantly affecting the metaphyses of long bones and is usually seen in children. Although CRMO is generally a pediatric disease, it may also occur in adults. This may result in a delay in the diagnosis of adult-onset CRMO. This report presents an adult-onset female patient who presented with left leg pain followed by swelling in the right knee. The patient was initially started on colchicine treatment, but, due to unresponsiveness in the follow-up the patient, the treatment was switched to a combination of methotrexate and prednisolone. A satisfactory clinical recovery was achieved with these drugs. CRMO could be considered in the differential diagnosis of patients presenting with bone pain and joint complaints. Considering that the disease progresses with clinical flare-ups and remission periods, it should be kept in mind that patients should be followed closely and treatment can be changed.

Chronic Recurrent Multifocal Osteomyelitis Presenting With Fever of Unknown Origin

Chronic Recurrent Multifocal Osteomyelitis Presenting With Fever of Unknown Origin

A rare mutation causing autosomal dominant STAT1 deficiency in a South African multiplex kindred with disseminated BCG infection

BackgroundAutosomal dominant signal transducer and activator of transcription 1 (STAT1) deficiency, part of the Mendelian susceptibility to mycobacterial disease (MSMD) group, frequently causes disseminated Bacillus Calmette-Guérin (BCG) infections, but has not been reported from Sub-Saharan Africa (SSA) where routine birth BCG vaccination is practiced.Case presentationTwo half-siblings presented five years apart, with multifocal osteomyelitis as the dominant feature of disseminated BCG, which was successfully treated with antimycobacterial therapy. Whole exome sequencing demonstrated a novel heterozygous substitution in the splice site between intron 13 and exon 14 of the STAT1 gene, NM_007315: c.1128-1G>A, in the proband and his mother and was later confirmed in his half-brother.ConclusionsChildren with BCG vaccine complications in SSA should be referred for further investigation and particular consideration of MSMD.

Multifocal osteomyelitis in a child with sickle cell disease and review of the literature regarding best diagnostic approach

Key Clinical MessageIn patients with sickle cell disease, we must be more cognizant of the possibility of multifocal osteomyelitis. Diagnosis can be challenging in this patient population as the symptoms mimic vaso‐occlusive crisis. There is no gold standard in imaging.AbstractOsteomyelitis occurs more frequently in children with sickle cell disease. Diagnosis is challenging as it mimics vaso‐occlusive crises, a common manifestation of sickle cell disease. We present a case of a 22‐month‐old girl with sickle cell disease and multifocal osteomyelitis. We review the literature on the utility of diagnostic imaging.

Identification of an IL-1 receptor mutation driving autoinflammation directs IL-1-targeted drug design

The interleukin 1 (IL-1) pathway signals through IL-1 receptor type1 (IL-1R1) and emerges as a central mediator for systemic inflammation. Aberrant IL-1 signaling leads to a range of autoinflammatory diseases. Here, we identified a de novo missense variant in IL-1R1 (p.Lys131Glu) in a patient with chronic recurrent multifocal osteomyelitis (CRMO). Patient PBMCs showed strong inflammatory signatures, particularly in monocytes and neutrophils. The p.Lys131Glu substitution affected a critical positively charged amino acid, which disrupted the binding of the antagonist ligand, IL-1Ra, but not IL-1α or IL-1β. This resulted in unopposed IL-1 signaling. Mice with a homologous mutation exhibited similar hyperinflammation and greater susceptibility to collagen antibody-induced arthritis, accompanied with pathological osteoclastogenesis. Leveraging the biology of the mutation, we designed an IL-1 therapeutic, which traps IL-1β and IL-1α, but not IL-1Ra. Collectively, this work provides molecular insights and a potential drug for improved potency and specificity in treating IL-1-driven diseases.

Pyoderma gangrenosum following anti-TNF therapy in chronic recurrent multifocal osteomyelitis: drug reaction or cutaneous manifestation of the disease? A critical review on the topic with an emblematic case report.

Chronic recurrent multifocal osteomyelitis (CRMO) is a rare autoinflammatory disease, clinically characterized by chronic and recurrent episodes of osteoarticular inflammation, that generally presents in children and adolescents. From a dermatological point-of-view, CMRO can be associated with skin rashes mainly including psoriasis, palmoplantar pustulosis and acne. Pyoderma gangrenosum (PG) is a rare immune-mediated inflammatory skin disease classified within the spectrum of neutrophilic dermatoses that, in some cases, has been reported as cutaneous manifestation in CMRO patients. This paper presents a 16-year female patient diagnosed with CMRO, who presented PG lesions located on the lower leg, that arose after the administration of the tumour necrosis factor (TNF)-α inhibitor adalimumab. Cases of PG have been reported in patients being treated with certain medications, including TNF-α antagonists, leading to classified them in a setting aptly termed "drug-induced PG." In this paper, we discuss the co-occurrence of PG and CRMO, in the light of recent evidence on the pathogenesis of both diseases and giving ample space to a literature review on drug induced PG. In our case, it is plausible that PG could be considered a cutaneous manifestation of CRMO, although the mechanisms underlying this intriguingly relationship remain to be fully unraveled.

Septic Arthritis and Multifocal Osteomyelitis Caused by Capnocytophaga canimorsus: A Case Report

Microbiological diagnosis of chronic osteoarticular infections remains a major challenge, particularly when the clinical presentation is atypical and the pathogen is uncommon. In this unique case, Capnocytophaga canimorsus, a microorganism belonging to the oral microbiota of some domestic animals, caused septic arthritis and multifocal osteomyelitis in the long bone of a 43-year-old immunocompetent man. The patient was treated with two-stage surgery and local and systemic antibiotic therapy, and had a successful recovery. C. canimorsus should be considered as a possible etiological agent in patients with osteoarticular pathology and a history of exposure to domestic animals.

Whole-body MRI in Pediatric Patients with Chronic Recurrent Multifocal Osteomyelitis

Whole-body MRI in Pediatric Patients with Chronic Recurrent Multifocal Osteomyelitis

Scurvy, abnormal MRI, and gelatinous bone marrow in an adolescent with avoidant restrictive food intake disorder

BackgroundAlthough medical literature describes pediatric scurvy as “rare”, a growing number of case reports suggests otherwise. Patients often undergo costly and unnecessary workup due to unfamiliarity with the presentation of scurvy. This case report further supports the small yet growing literature documenting scurvy and its manifestations in patients with eating disorders.Case presentationA 15-year-old female presented to the emergency department with bilateral knee and ankle swelling and pain in the setting of chronic lower limb rash and BMI of 16.3. For years, she had restricted her diet to carbohydrates. Exam showed perifollicular petechial hemorrhagic rash with corkscrew hairs, knee edema, ankle edema with restricted range of motion, and antalgic gait. She was admitted for severe malnutrition from avoidant restrictive food intake disorder. Her hospital course was complicated by recurrent normocytic anemia and fever. Hematology workup revealed anemia from iron deficiency, vitamin K deficiency, and anemia of chronic disease. Rheumatology workup was negative. MRI findings showed dark T1 and bright T2 signals and were read as consistent with leukemia/lymphoma, chronic multifocal osteomyelitis, or Langerhans cell histiocytosis. However, bone marrow biopsy showed gelatinous transformation secondary to malnutrition. She was treated with vitamin C and a nutrition plan and her symptoms improved.ConclusionsAlthough this patient had common manifestations of scurvy, including perifollicular petechial hemorrhagic rash, joint effusions, anemia, and recurrent fevers, she still underwent an extensive workup. Clinicians should be aware that scurvy can present with multiple symptoms that mimic infectious, rheumatic, oncologic and hematological disease. Clinicians should have a high index of suspicion for scurvy in patients with malnutrition and eating disorders.

CHRONIC RECURRENT MULTIFOCAL OSTEOMYELITIS IN CHILDREN: A NATIONAL EXPERIENCE AT A TERTIARY REFERRAL CENTRE OVER 20 YEARS

IntroductionChronic recurrent multifocal osteomyelitis (CRMO) is a rare condition characterised by bony pain and swelling which may be initially mistaken for bacterial osteomyelitis. The episodic course of the disease may confound the diagnosis and potentially be mistaken for a partial response to antimicrobial therapy. It is an orphan disease and consequently results in many unclear aspects of diagnosis, treatment and follow up for patients. The aim of this study is to evaluate a national tertiary centre's experience with the clinical condition and present one of the largest cohorts to date, emphasizing the vast array of clinical spectrum, course and response to treatment.MethodsWe retrospectively evaluated all children identified with CRMO from the period 2000–2022 within Wales. Demographic data and clinical parameters were selectively identified through the utilisation of a national clinical platform (Welsh Clinical Portal). The diagnosis was based on clinical findings, radiological images, histopathological and microbiological studiesResultsA total of 21 patients were identified as suitable for inclusion. The mean age of diagnosis was 9.4 ±2 years. The age range of children being diagnosed was 6–14 years. Of the 21 patients, only 2 reported feeling unwell prior to their first presentation with generalized coryzal illness reported. The most common presenting site for CRMO was knee (33%) followed by back pain (28%). 19% of the included cases at initial presentation had localised warmth and had nocturnal pain. 4 of the patients went on to have dermatological conditions of which psoriasis was the most common (14%). Bilateral symptoms developed in 38% of the included patients. Biochemical investigations revealed only 19% of patients had a raised C-reactive protein level and erythrocyte sedimentation rate whilst 9/21 patients went on to have a bone biopsy to aid diagnosis. 100% of patients had MRI whilst whole body MRI was utilised in 8/21 patients. NSAID's were utilised for 81%, Pamidronate for 33% and methotrexate for 14%. Biologics were utilised for a further 24% of the total population in failed medical therapy. Surgical intervention was utilised for a single individual in this cohort of patients in the form of posterior spinal stabilisation. The most common referring speciality for these patients was Rheumatology (71%) followed by Orthopaedics (33%).DiscussionCRMO represents a challenging diagnosis to make with such varied clinical and biochemical presentations for this condition. The absence of diagnostic Radiological features on X-ray could argue over early MRI imaging. The utilisation of whole body-MRI can now identify multifocal disease burden which may facilitate a timely diagnosis and ensure that effective medical treatment is started promptly without delay. This study is the largest cohort of CRMO patients conducted in this country. Future work will serve to build upon a framework and national referral pathway so that these patients can be seen by the appropriate specialist in a timely manner.

A Successful Bisphosphonates Monotherapy in Spinal Form of Paediatric Chronic Recurrent Multifocal Osteomyelitis (CRMO)—Case Report

Chronic recurrent multifocal osteomyelitis (CRMO) is a non-infectious inflammatory disorder resulting from the multifocal bone and bone marrow lesions with periodic relapses and remissions and with an uncertain prognosis. Treatment options in CRMO are based on expert opinion and relatively small groups of patients. A nine-year-old female patient with no significant past medical history presented with compression fractures and multifocal bone lesions in the thoracic and lumbar spine, as shown in imaging (CT, MRI). Densitometry revealed a diffuse decrease in bone density. Based on the patient's clinical image and above examinations, the other possible aetiologies-infectious (including tuberculosis), neoplasms, Langerhans cell histiocytosis-were ruled out, which led to eventual final diagnosis-CRMO. The patient was successfully treated with pamidronate infusion initiated in cycles over three consecutive days every 3 months. In addition to clinical improvement, there was a significant remission of inflammation and bone structure healing assessed by MRI after four treatment cycles. Intravenous bisphosphonates usage seems to be a good therapeutic option in CRMO paediatric patients with spinal localization of the lesions complicated by compressive fractures. However, more data, based on larger patient populations, are needed to provide a detailed paediatric CRMO treatment algorithm.

Correlation between the Clinical Course of CRMO Lesions and the Imaging Characteristics on Follow-up MRIs

Objective: To evaluate the correlation between the clinical course of chronic recurrent multifocal osteomyelitis (CRMO) lesions and their imaging characteristics on follow-up MRIs. Material and Methods: Two musculoskeletal fellowship-trained radiologists retrospectively reviewed the initial and follow-up MRI images of 9 CRMO patients who were treated in our institution from 2008 to 2018. Evaluation of clinical course was based on symptomatology, lab results and physical examination and was compared to MRI findings, on follow-up MRIs. Results: Thirty-five CRMO lesions in 9 patients were identified. Patient’s ages ranged from 4 to 15 years with a mean age of 10 years (S.D.±3.22). Six of the 9 patients were female. Only 21 of 35 lesions had been longitudinally followed by MRI. Of the 39 follow-up MRI exams, there was clinical improvement 15 times, and 24 times there was no clinical improvement confirmed by the clinician. Three MRI features: 1) bone marrow edema (BME) size, 2) BME signal intensity and 3) periosteal edema, significantly correlated with the clinical course (p-value<0.001). When there was the improvement of all these three findings, the correlation with clinical improvement was high with 80% sensitivity and 100% specificity. The area under the receiver operator characteristic curve was 0.90 (95% confidence interval 0.795-1.005). Fourteen silent clinical lesions were also identified. Conclusion: Bone marrow edema and periosteal edema correlated best with the clinical course of CRMO patients on follow-up MRIs.

Axial Skeleton Bone Marrow Changes in Inflammatory Rheumatologic Disorders.

Magnetic resonance imaging (MRI) of the axial skeleton, spine, and sacroiliac (SI) joints is critical for the early detection and follow-up of inflammatory rheumatologic disorders such as axial spondyloarthritis, rheumatoid arthritis, and SAPHO/CRMO (synovitis, acne, pustulosis, hyperostosis, and osteitis/chronic recurrent multifocal osteomyelitis). To offer a valuable report to the referring physician, disease-specific knowledge is essential. Certain MRI parameters can help the radiologist provide an early diagnosis and lead to effective treatment. Awareness of these hallmarks may help avoid misdiagnosis and unnecessary biopsies. A bone marrow edema-like signal plays an important role in reports but is not disease specific. Age, sex, and history should be considered in interpreting MRI to prevent overdiagnosis of rheumatologic disease. Differential diagnoses-degenerative disk disease, infection, and crystal arthropathy-are addressed here. Whole-body MRI may be helpful in diagnosing SAPHO/CRMO.

Retrospective Review of 80 Patients with Chronic Recurrent Multifocal Osteomyelitis Evaluated by Pediatric Orthopaedic Surgeons

Background: Chronic Recurrent Multifocal Osteomyelitis (CRMO) is a rare aseptic autoinflammatory disease with a wide and vague clinical presentation that often mimics infection, malignancy, or benign conditions, leading to a delayed diagnosis. We aimed to evaluate the clinical characteristics, differential diagnoses from evaluating pediatric orthopaedic surgeons, and compared the number of patients that could have avoided a biopsy in 80 patients with CRMO.Methods: Children diagnosed with CRMO at a single tertiary pediatric hospital in the United States between 2012 and 2022 who were evaluated by a pediatric orthopaedic surgeon were retrospectively reviewed. The differential diagnoses from the surgeons were recorded from their initial presentation. The Jansson criteria and Bristol Criteria were retrospectively applied to evaluate patients who could have been spared a biopsy.Results: 80 children (65% female) with CRMO were identified. The mean age at diagnosis was 10.28 ± 3.52 years, follow-up of 37.13 ± 27.67 months, and delay in diagnosis of 6.21 ± 9.75 months. Common presenting symptoms were antalgic gait (45%), local inflammation (30%), and fever/fatigue (26.25%). 58% presented clinically with unifocal symptoms, but 81% had multifocal disease on imaging. Radiographs were unremarkable in 35%, had periosteal reaction/sclerosis (23%), or a lytic lesion (22%). On MRI, 72% of patients had marrow edema, periosteal reaction (23%), and/or osteitis (19%). 69% of patients received a whole-body MRI, and 75% received a bone biopsy. The femur, tibia, pelvis, and spine were involved in >30% of patients. The most common initial differential diagnoses were related to infection (34%) and neoplasm (21%). The Jansson criteria was found to be more sensitive than the Bristol criteria for diagnosing CRMO (OR 3.94, P < 0.001) and identified 80% that could have been spared biopsy.Conclusions: This cohort of 80 patients with CRMO in the U.S. displayed an ambiguous presentation. Whole-body MRI was useful for identifying multifocal lesions. In conjunction with clinical reasoning, the Jansson criteria may be useful in the diagnosis of CRMO and perhaps avoid an unnecessary bone biopsy.Levels of Evidence: Level IVKey Concepts•Chronic Recurrent Multifocal Osteomyelitis is a rare condition in children with a delay in definitive diagnosis of approximately 6 months after initial presentation.•Chronic Recurrent Multifocal Osteomyelitis often has unremarkable radiographs and MRI findings similar to a neoplasm or infectious osteomyelitis.•The most common lesions were found in the femur, tibia, pelvis, and spine.•Pediatric orthopaedic surgeons evaluating these patients placed neoplasm/malignancy and infection on their differential most frequently.•The Jansson criteria may be used in some patients to possibly prevent unnecessary bone biopsies.

Neurosurgical management of vertebral lesions in pediatric chronic recurrent multifocal osteomyelitis: patient series.

Chronic recurrent multifocal osteomyelitis (CRMO) is a rare pediatric autoinflammatory disorder involving 2 or more inflammatory bone lesions separated in time and space associated with pathological vertebral fractures. There are no current guidelines for the role of pediatric spine surgeons in the management of this condition. The authors demonstrate the importance of close and early involvement of neurosurgeons in caring for patients with CRMO with vertebral involvement. Fifty-six pediatric patients with clinical and radiographic evidence of CRMO were identified and clinical, radiographic, laboratory, and histopathological data were reviewed. All were evaluated via Jansson and Bristol CRMO diagnostic criteria. Ten had radiographic evidence of vertebral involvement (17.9%). Nine of these had multifocal disease. Five patients had multiple vertebrae affected. Six patients were evaluated for possible surgical intervention and one required intervention due to vertebra plana leading to a progressive kyphotic deformity and significant spinal canal stenosis. In conjunction with management by the primary pediatric rheumatology team using nonsteroidal anti-inflammatory drugs, disease-modifying anti-rheumatic drugs, immunotherapies, and bisphosphonates, given the risk of pathological fractures and potential resulting long-term neurological deficits, the authors recommend close monitoring and management by pediatric spine surgeons for any patient with CRMO with vertebral lesions.

Chronic Recurrent Multifocal Osteomyelitis (CRMO) and Juvenile Spondyloarthritis (JSpA): To What Extent Are They Related?

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory disease occurring mainly in the pediatric age group (before 16 years) and generally presents as a separate entity. Synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome combines osteoarticular and cutaneous involvement, similar to CRMO, and falls into the spectrum of spondyloarthritis (SpA). The fact that a patient can progress from one disease to another raises the question of whether CRMO, like SAPHO, could fall within the spectrum of SpA, ranging from a predominantly osteoarticular form to an enthesitic form with more or less marked skin involvement. In this review, we set out to discuss this hypothesis by highlighting the differences and similarities between CRMO and juvenile SpA in clinical, radiological and pathophysiological aspects. A common hypothesis could potentially consider intestinal dysbiosis as the origin of these different inflammatory diseases. Interindividual factors such as gender, environment, genetics and/or epigenetic background could act as combined disease modifiers. This is why we suggest that pathophysiology, rather than clinical phenotype, be used to reclassify these diseases.

Chronic recurrent multifocal osteomyelitis on magnetic resonance imaging

Chronic recurrent multifocal osteomyelitis on magnetic resonance imaging

Childhood Leukemia Presenting as Clinical Arthritis and Chronic Recurrent Multifocal Osteomyelitis (CRMO): Case Report

Childhood Leukemia Presenting as Clinical Arthritis and Chronic Recurrent Multifocal Osteomyelitis (CRMO): Case Report

Pioderma gangrenoso

.Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis, characterized by unknown aetiology and sterile neutrophilic infiltrate on histological examination, clinically showing recurrent skin ulcers and mostly affecting lower limbs areas. In 2/3 of the cases, PG is secondary to another disorder such as inflammatory bowel and lymphoproliferative diseases, infections, rheumatic diseases and auto-inflammatory syndromes. The paper describes the cases of three paediatric patients showing the association of PG with rheumatic conditions such as Behçet’s disease, chronic recurrent multifocal osteomyelitis (CRMO) and PAPA (Pyogenic Arthritis, Pyoderma gangrenosum and Acne) syndrome and proposes a diagnostic flow-chart to help paediatricians recognize PG and associated conditions.

Imaging features of chronic recurrent multifocal osteomyelitis (CRMO) involving the vertebral column of a lemur with subsequent paraplegia due to pathological fractures

A seven-year-old, female ring-tailed lemur was referred for progressive non-ambulatory paraplegia. A computed tomographic (CT) scan of the whole body revealed multifocal lytic lesions involving multiple vertebrae and several pathological vertebral fractures. Necropsy and histopathology identified pyogranulomatous osteomyelitis. The imaging and histopathological findings resemble chronic recurrent multifocal osteomyelitis described in human medicine.