Chronic Multifocal Osteomyelitis – Is Mycobacterium avium Complex Really the Culprit? A Case Report in an Adult Female

Introduction:There are reports which describe multiple lytic lesions seen on X-ray resulting from a non-tuberculous Mycobacterium skeletal infection in immunocompetent adults and children. AdditionallyIn addition, similar multifocal lesions have also been described in chronic recurrent multifocal osteomyelitis (CRMO) which is more common in children but has have rarely been reported in adults. We present a case of a 47-year-old female who presented with multiple osteolytic lesions and discuss how her diagnosis overlaps with CRMO and multifocal non-tuberculous osteomyelitis associated with Mycobacterium avium complex (MAC). Case Report:A 47-year-old female presented with a mass at her left sternoclavicular joint. Biopsy of the lesion showed acute and chronic inflammation suggesting osteomyelitis. The patient was on intravenousIV antibiotics with some improvement. After three 3 ½ and a half months, she was having knee pain and imaging showed another lesion and a bone scan found a third. Delayed cultures grew Mycobacterium avium complexMAC but ultimately the patient improved when she was taking naproxen for multifocal osteomyelitis. Conclusion:Multifocal lytic lesions on imaging in an adult can be multifocal osteomyelitis that, like in pediatric patients, may be treated best with nonsteroidal anti-inflammatory medications as with the patient in this case. Keywords:Multifocal Osteomyelitis, Mycobacterium Avium Complex, Osteitis Multifocal Osteomyelitis, Mycobacterium avium complex, osteitis.

Regulation of neutrophil NADPH oxidase by PSTPIP2 affects bone damage in murine autoinflammatory osteomyelitis

Autoinflammatory diseases are characterized by dysregulation of the innate immune system leading to spontaneous inflammation. Pstpip2cmo mouse strain is a well-characterized model of this class of disorders. Due to the mutation leading to the lack of adaptor protein PSTPIP2, these animals suffer from autoinflammatory chronic multifocal osteomyelitis similar to several human syndromes. Current evidence suggests that it is driven by hyperproduction of IL-1β by neutrophil granulocytes. Here we show that in addition to IL-1β, PSTPIP2 also negatively regulates ROS generation by neutrophil NADPH oxidase. Pstpip2cmo neutrophils display highly elevated ROS production in response to a range of stimuli. Inactivation of NADPH oxidase in Pstpip2cmo mice did not affect IL-1β levels and the autoinflammatory process was initiated with similar kinetics. However, the bone destruction was almost completely alleviated, suggesting that dysregulated NADPH oxidase activity is a key factor promoting autoinflammatory bone damage in Pstpip2cmo mice.

Unusual Manifestation of Ulcerative Colitis

The relationship of inflammatory bowel disease (IBD) and chronic recurrent multifocal osteomyelitis (CRMO) is understood as extraintestinal rheumatic manifestations. CRMO is a chronic, relapsing, inflammatory, noninfectious disorder of the skeletal system of unknown origin. The disease course is not always recurrent. The association of CRMO and ulcerative colitis (UC) is very rarely reported. We report a case of a 10-year-old Saudi female who was diagnosed with CRMO, when she developed fever in association with left foot pain, and ulcerative colitis was confirmed endoscopically and histologically based on a previous settled diarrheal illness and severe iron deficiency anemia which required blood. Both conditions responded well to IBD therapy. To the best of our knowledge, this is the first reported case of chronic, multifocal osteomyelitis associated with pediatric UC in Saudi Arabia. This report supports the use of IBD therapy in treating CRMO.

NLRP3 inflammasome plays a redundant role with caspase 8 to promote IL-1β–mediated osteomyelitis

Missense mutation in the proline-serine-threonine phosphatase-interacting protein 2 (Pstpip2) gene results in the development of spontaneous chronic bone disease characterized by bone deformity and inflammation that is reminiscent of patients with chronic multifocal osteomyelitis (cmo). Interestingly, this disease is specifically mediated by IL-1β but not IL-1α. The precise molecular pathways that promote pathogenic IL-1β production inPstpip2cmomice remain unidentified. Furthermore, how IL-1β provokes inflammatory bone disease inPstpip2cmomice is not known. Here, we demonstrate that double deficiency of Nod like receptor family, pyrin domain containing 3 (NLRP3) and caspase 8 inPstpip2cmomice provides similar protection as observed in caspase-1 and caspase-8–deficientPstpip2cmomice, demonstrating redundant roles for the NLRP3 inflammasome and caspase 8 in provoking osteomyelitic disease inPstpip2cmomice. Consistently, immunofluorescence studies exhibited distinct caspase-1 and caspase-8 puncta in diseasedPtpn6spinneutrophils. Data from our chimera studies demonstrated that IL-1β produced by hematopoietic cells is sensed by the radioresistant compartment to promote bone disease. Furthermore, our results showed that the IL-1β signaling is unidirectional and feedback signaling of IL-1β onto the hematopoietic compartment is not important for disease induction. In conclusion, our studies have uncovered the combined actions of the NLRP3 inflammasome and caspase 8 leading to IL-1β maturation and the directionality of IL-1β in driving disease inPstpip2cmomice.