Chronic recurrent multifocal osteomyelitis in a patient with selective immunoglobulin M deficiency

Chronic recurrent multifocal osteomyelitis is an unusual inflammatory process of unknown origin involving multiple osseous sites, often recurrently. Selective immunoglobulin M (IgM) deficiency is a rare primary immunodeficiency disease, which can be associated with autoimmune diseases such as systemic lupus erythematosus, Hashimoto’s disease, or hemolytic anemia. Here we report a case of a chronic recurrent multifocal osteomyelitis coexisting with selective IgM deficiency.     

持续负压引流治疗慢性骨髓炎23例疗效观察

目的探讨持续负压引流(VSD)对慢性骨髓炎的治疗效果。方法收治的慢性骨髓炎合并有慢性溃疡的患者共23例,均采用溃疡清创后,使用VSD治疗,待创面清洁、肉芽组织生长良好后,12例直接缝合,8例植皮封闭创面,3例经邻位皮瓣转移封闭创面。结果 VSD平均吸引15 d,平均更换VSD 2.5次。创面渗液均明显减少,且创面面积均有不同程度的缩小。经二期手术后治愈,随访6～29个月,无复发。结论 VSD治疗对慢性骨髓炎具有引流充分、缩小创面、促进肉芽组织生长、降低复发率等优点,疗效确切。     

How can calcium pyrophosphate crystals induce inflammation in hypophosphatasia or chronic inflammatory joint diseases?

Hypophosphatasia (HP) is a rare inborn error of bone and mineral metabolism characterized by a defect in the tissue non-specific alkaline phosphatase (TNSALP) gene. Calcium pyrophosphate dihydrate (CPPD) crystals are known to accumulate as substrates of TNSALP in tissues and joints of patients with HP. In CPPD-induced arthritis these crystals are known to induce an inflammatory response. HP patients do suffer from pain in their lower extremities. However, it is not clear whether CPPD crystals contribute to these musculoskeletal complaints in HP. As long as there is no curative treatment of HP, symptomatic treatment in order to improve clinical features, especially with regard to pain and physical activity, is of major interest to the patients. Knowledge of the mechanisms underlying crystal-induced cell activation, however, is limited. Here we describe recent advances in elucidating the signal transduction pathways activated by CPPD crystals as endogenous "danger signals". Recent investigations provided evidence that Toll/interleukin-1 receptor (TIR) domain containing receptors including Toll-like receptors (TLRs) and interleukin-1 receptor (IL-1R), as well as the triggering receptor expressed on myeloid cells 1 (TREM-1) and the NACHT-leucin rich repeat and pyrin-domain-containing protein (NALP3) containing inflammasome are essentially involved in acute CPPD crystal-induced inflammation. These receptors are considered in part as components of the innate immune system. Further studies are needed to improve our understanding of the pathophysiological mechanisms leading to inflammation and tissue destruction associated with deposition of microcrystals. They might support the development of new therapeutic strategies for crystal-induced inflammation. Eventually, patients with HP might as well profit from such strategies addressing these metabolic disorders secondary to the gene defect.     

An unusual presentation of chronic recurrent multifocal osteomyelitis involving bones of the skull

Chronic recurrent multifocal osteomyelitis is a rare, multisystemic inflammatory disease that affects children and adolescents. We present the case of an African-American adolescent male who presented with recurrent swelling of the temporal region with skull involvement on head imaging, which is atypical for chronic recurrent multifocal osteomyelitis. He had clinical and laboratory improvement after initiation of indomethacin and pamidronate.     

Acute osteomyelitis of the patella in a child

An 8-year-old boy presented with acute osteomyelitis in his right patella. Radiographs demonstrated an osteolytic lesion in the superior pole. Curettage was performed, followed by the administration of antibiotics. Four months later, the patient’s symptoms completely disappeared. Our case suggests that acute osteomyelitis of the patella is caused by hematogenous spread from surface, paralleling unique intraosseous arterial patterns.     

Acute osteomyelitis of the patella in a child

Abstract

An 8-year-old boy presented with acute osteomyelitis in his right patella. Radiographs demonstrated an osteolytic lesion in the superior pole. Curettage was performed, followed by the administration of antibiotics. Four months later, the patient’s symptoms completely disappeared. Our case suggests that acute osteomyelitis of the patella is caused by hematogenous spread from surface, paralleling unique intraosseous arterial patterns.     

Long-term follow-up of jaw osteomyelitis associated with bisphosphonate use in a tertiary-care center

Objectives

This study reviews our experience in bisphosphonate-associated jaw osteomyelitis (BJOM), focusing on the incidence, etiology, treatment, and long-term outcome.

Methods

Retrospective review of the clinical histories adult patients diagnosed with BJOM (1995–2008) in a tertiary hospital.

Results

BJOM was found in 30 of 132 (22.7%) consecutive patients with jaw osteomyelitis. The percentage of BJOM cases increased from 8.7% (4/46) in 1995–2005 to 30.2% (26/86) in 2005–2008. Symptoms appeared in a median of 2.5 years after intravenous use, and 4.5 years after oral exposure. Viridans group streptococci were isolated in 83.3% of cases. Actinomyces spp. was found in 16 (39.0%) of 41 bone histologies. All included patients received a median of 6 months of appropiate antibiotic therapy and a surgical procedure (debridament and/or sequestrectomy). Thirteen of 27 cases (48.1%) with long-term follow-up (median 22 months, IQR _25–75 17–28) failed. Clinical failure defined as, persistent infection or relapse, was more frequent in patients receiving intravenous than oral bisphosphonates (11/16 [68.8%] vs. 2/11 [18.2%]; P < .05) and in cases with Actinomyces spp. (7/10 [70.0%] vs6/17 [35.3%]; P = .08).

Conclusions

Bisphosphonate therapy is now a frequent cause of JO. BJOM is difficult to cure and relapses are common, particularly in patients exposed to intravenous bisphosphonates.     

Spontaneous pyogenic vertebral osteomyelitis and endocarditis: incidence, risk factors, and outcome

Purpose

The relationship between pyogenic vertebral osteomyelitis and infectious endocarditis is uncertain. This study investigates the incidence and risk factors of infectious endocarditis in patients with pyogenic vertebral osteomyelitis, and the outcome of pyogenic vertebral osteomyelitis with and without associated infectious endocarditis.

Methods

A retrospective record review was conducted of all cases of vertebral osteomyelitis from January 1986 to June 2002, occurring in a tertiary referral hospital. Patients were followed for at least 6 months with careful attention to detection of infectious endocarditis and relapses.

Results

Among 606 patients with infectious endocarditis, 28 (4.6%) had pyogenic vertebral osteomyelitis. Among 91 cases of pyogenic vertebral osteomyelitis, 28 (30.8%) had infectious endocarditis. In 6 patients with no clinical signs of infectious endocarditis, the disease was established by routine echocardiography. Infectious endocarditis was more common in patients with predisposing heart conditions and streptococcal pyogenic vertebral osteomyelitis infection. Overall, pyogenic vertebral osteomyelitis in-hospital mortality was 11% (7.1% with infectious endocarditis). Twelve of 25 patients with infectious endocarditis with uncomplicated pyogenic vertebral osteomyelitis were treated for 4 to 6 weeks (endocarditis protocol), with no pyogenic vertebral osteomyelitis relapses.

Conclusions

When specifically sought, the incidence of infectious endocarditis is high in patients with pyogenic vertebral osteomyelitis. Oral therapy may be an option for uncomplicated pyogenic vertebral osteomyelitis; nevertheless, in gram-positive infections, this approach should only be considered after excluding infectious endocarditis. Favorable outcome with shorter treatment in uncomplicated pyogenic vertebral osteomyelitis associated with infectious endocarditis suggests that prolonged therapy may not be needed in this subgroup except for those infected by difficult to treat microorganisms, such as methicillin-resistant Staphylococcus aureus or Candida spp.     

Inflammasome-independent IL-1β mediates autoinflammatory disease in Pstpip2-deficient mice

Chronic recurrent multifocal osteomyelitis (CRMO) is a human autoinflammatory disorder that primarily affects bone. Missense mutation (L98P) of proline-serine-threonine phosphatase-interacting protein 2 (Pstpip2) in mice leads to a disease that is phenotypically similar to CRMO called chronic multifocal osteomyelitis (cmo). Here we show that deficiency of IL-1RI in cmo mice resulted in a significant reduction in the time to onset of disease as well as the degree of bone pathology. Additionally, the proinflammatory cytokine IL-1β, but not IL-1α, played a critical role in the pathology observed in cmo mice. In contrast, disease in cmo mice was found to be independent of the nucleotide-binding domain, leucine-rich repeat-containing family, pyrin domain-containing 3 (NLRP3) inflammasome as well as caspase-1. Neutrophils, but not bone marrow-derived macrophages, from cmo mice secreted increased IL-1β in response to ATP, silica, and Pseudomonas aeruginosa compared with neutrophils from WT mice. This aberrant neutrophil response was sensitive to inhibition by serine protease inhibitors. These results demonstrate an inflammasome-independent role for IL-1β in disease progression of cmo and implicate neutrophils and neutrophil serine proteases in disease pathogenesis. These data provide a rationale for directly targeting IL-1RI or IL-1β as a therapeutic strategy in CRMO.Chronic recurrent multifocal osteomyelitis (CRMO) is a sterile inflammatory disorder that affects children and presents with bone pain due to sterile osteomyelitis (1). The etiology of the disease is unknown, but it is associated with Crohn disease, inflammatory arthritis, and psoriasis in affected individuals and their close relatives, suggesting a shared pathophysiology and supporting a genetic contribution to disease (2). There are two autosomal recessive disorders that present with neonatal- or infant-onset sterile osteitis that are histologically similar to the bone disease in CRMO and clinically improve with IL-1 blockade (3, 4). Majeed syndrome, caused by mutations in LPIN2, presents with CRMO, congenital dyserythropoietic anemia, and sterile neutrophilic dermatosis (5). Deficiency of the IL-1 receptor antagonist (DIRA) is caused by mutations in IL1RN, which encodes the IL-1 receptor antagonist (3), resulting in dysregulation of the IL-1 pathway. Affected individuals present with neonatal-onset cutaneous pustulosis, marked elevation of inflammatory markers, sterile multifocal osteitis, and periostitis (3).There are two autosomal recessive murine models of CRMO both due to mutations in proline-serine-threonine interacting protein 2 (Pstpip2) (6–8). The mutation (L98P) present in the chronic multifocal osteomyelitis (cmo) model results in no detectable expression of Pstpip2, a protein expressed predominantly in the cells of the myeloid lineage, and leads to disease that resembles human CRMO (6, 9). The development of osteomyelitis in the cmo mouse is hematopoietically driven and develops in the absence of lymphocytes, consistent with an autoinflammatory mechanism of disease (9). Although it is known that cmo mice have a dysregulated innate immune system, it is not clear what inflammatory pathway is critical for disease.Mutations within NLRP3 (also known as NALP3 or cryopyrin) are associated with the autoinflammatory Muckle-Wells syndrome, familial cold autoinflammatory syndrome, and neonatal-onset multisystem inflammatory disease, collectively known as cryopyrin-associated periodic syndrome (10). These NLRP3 mutations result in a constitutively active form of NLRP3 that leads to increased inflammasome activation with a resultant increase in secretion of IL-1β (10). A diverse array of agonists has been identified that are capable of activating NLRP3, which results in the assembly of the NLRP3 inflammasome composed of NLRP3, the adaptor molecule apoptosis-associated speck-like protein containing a CARD (ASC), and caspase-1 (11). The activation of the inflammasome leads to the activation of caspase-1, with the resultant processing of pro-IL-1β and pro-IL-18 to their mature and secreted forms (12). However, the role of the NLRP3 inflammasome in the pathogenesis of cmo remains unknown.Given the evidence that IL-1 is important in the pathogenesis of sterile bone inflammation in humans (3, 4), we investigated the role of IL-1 in the pathogenesis of sterile osteomyelitis in the cmo mouse. Here we demonstrate that deficiency of IL-1RI (interleukin-1 receptor type I) or IL-1β in cmo mice resulted in delayed onset of disease and an attenuation of disease severity. In contrast, disease progression in cmo mice was found to be independent of the NLRP3 inflammasome, and in vitro findings support a role for neutrophil serine proteases in the abnormally increased secretion of IL-1β. Taken together these data demonstrate an inflammasome-independent role for the IL-1 pathway in the disease pathogenesis of cmo.     

Complications following oat head aspiration

We report 5 cases of oat head aspiration in children that resulted in serious complications due to the unidirectional migration of the oat head to the periphery of the lung. The complications included pneumothorax, pneumomediastinum, recurrent hemoptysis, chronic lung disease, bronchiectasis, lobectomy, bronchopleural and bronchocutaneous fistulae, pleural effusion, empyema cavity, and, one not described before, osteomylitis of the rib. Physicians should be aware of the dangers with this particular foreign body aspiration. © 1993 Wiley-Liss, Inc.     

Agranulocytosis associated with chronic oral administration of cloxacillin for suppression of staphylococcal osteomyelitis

Oral cloxacillin was used for chronic suppression of a 59-year-old woman with staphylococcal osteomyelitis. She received 380.5 gm of cloxacillin over 263 consecutive days. Severe agranulocytosis followed, reverting rapidly to normal with cessation of drug. The absence of signs of an allergic reaction such as rash, fever, or eosinophilia suggests that cloxacillin, like other semisynthetic penicillins, may exert a direct bone marrow toxicity.     

Aspergillus vertebral osteomyelitis and ureteral obstruction after liver transplantation

L.‐P. Zhu, X.‐S. Chen, J.‐Q. Wu, F.‐F. Yang, X.‐H. Weng. Aspergillus vertebral osteomyelitis and ureteral obstruction after liver transplantation.
Transpl Infect Dis 2011: 13 : 192–199. All rights reserved Abstract: Aspergillus osteomyelitis has been reported as a result of dissemination in solid organ transplant recipients. Vertebral osteomyelitis is one of the most common forms of Aspergillus osteomyelitis. An Aspergillus fungal ball is a rare cause of ureteral obstruction. We describe an unusual case of simultaneous vertebral osteomyelitis and ureteral obstruction caused by A. flavus in a hepatic transplant recipient, who was successfully treated with sequential intravenous and oral itraconazole solution.     

Carbapenem‐resistant Klebsiella pneumoniae vertebral osteomyelitis in a renal transplant recipient treated with ceftazidime‐avibactam

Ceftazidime‐avibactam (CAZ‐AVI) is a novel cephalosporin beta lactamase inhibitor combination that has shown activity against carbapenem‐resistant Enterobactericeae. Data are limited on its utilization in the treatment of carbapenem‐resistant Klebsiella pneumoniae osteomyelitis in solid organ transplant patients. We describe a case report on the use of CAZ‐AVI in the treatment of vertebral osteomyelitis in a renal transplant recipient.     

The diagnosis of osteomyelitis of the foot in diabetes: microbiological examination vs. magnetic resonance imaging and labelled leucocyte scanning.

AIMS: Foot infections and their sequelae are among the most common and severe complications of diabetes mellitus. As diabetic patients with foot infections develop osteomyelitis and may progress to amputation, early diagnosis of osteomyelitis is critical. METHODS: We compared the diagnostic values of labelled leucocyte scanning with Tc(99)m, magnetic resonance imaging (MRI) and microbiological examination of bone tissue specimens with histopathology, the definitive diagnostic procedure. Thirty-one diabetic patients with foot lesions were enrolled in the study and histopathological examination was performed in all. Patients had clinically suspected foot lesions of > or = grade 3 according to the classification of Wagner. RESULTS: Bone specimens were obtained for histopathological examination. Microbiology had a sensitivity of 92% and specificity of 60%. Labelled leucocyte scanning had a sensitivity of 91%, specificity of 67%, and MRI a sensitivity of 78%, specificity of 60%. CONCLUSIONS: Microbiological examination may be as useful as and less costly than other diagnostic procedures and is the only method which can guide the choice of antibiotic therapy.     

'Sausage toe': a reliable sign of underlying osteomyelitis.

AIMS: To follow-up patients with a 'sausage' deformity of the toe associated with local neuropathic ulceration to confirm the diagnosis of underlying osteomyelitis. This was based on our observation that some diabetic patients with suspected pedal osteomyelitis with a local neuropathic ulcer have a 'sausage' deformity of a toe. METHODS: Over a period of 2 years, 14 patients with foot ulcers, who were observed to have the 'sausage' deformity of a toe in the diabetic foot clinic were followed up and investigated. RESULTS: Underlying osteomyelitis was confirmed in six on the very first X-ray examination. A further seven had osteomyelitis diagnosed on bone scanning. Both the X-ray and the bone scan were equivocal in one patient, whose ulcer only healed after an 8-week course of antibiotics. Antibiotic therapy was successful in 11 patients and three patients required amputation of the affected toe. Following successful treatment, there was full resolution of the 'sausage toe' in the majority. CONCLUSIONS: The appearance of a 'sausage toe' should alert the physician of the possibility of underlying osteomyelitis in diabetic foot, so that prompt treatment can be commenced with antibiotics.     

Non-contiguous multifocal vertebral osteomyelitis caused by Serratia marcescens

Abstract

Serratia marcescens is a common nosocomial infection but a rare cause of osteomyelitis and more so of vertebral osteomyelitis. Vertebral osteomyelitis caused by this organism has been reported in few studies. We report a case of S. marcescens vertebral discitis and osteomyelitis affecting multiple non-contiguous vertebras. Although Staphylococcus aureus is the most common cause of vertebral osteomyelitis, rare causes, such as S. marcescens, need to be considered, especially when risk factors such as intravenous heroin use, post-spinal surgery and immunosuppression are present. Therefore, blood culture and where necessary biopsy of the infected region should be undertaken to establish the causative organism and determine appropriate antibiotic susceptibility. Prompt diagnosis of S. marcescens vertebral osteomyelitis followed by the appropriate treatment can achieve successful outcomes.