Chronic recurrent multifocal osteomyelitis

Giedion et al (1972) were the first to describe a syndrome known as chronic recurrent multifocal osteomyelitis (CRMO).

Chronic recurrent multifocal osteomyelitis-3 (CRMO) is an autosomal dominant autoinflammatory bone disease characterized by early childhood bone pain and arthritis due to sterile osteomyelitis. The disease results from constitutive activation of the IL1-mediated inflammatory pathway due to loss of sensitivity of the IL1 receptor to its antagonist IL-1RN. Wang et al. (2023) proposed the term "Loss of IL1R1 Sensitivity to IL1RA (IL1RN)" or "LIRSA" to describe this disease.

Although the exact molecular pathophysiology of CRMO is not yet fully understood, it seems likely that variable defects in the TLR4/MAPK/inflammasome signaling cascade lead to an imbalance between pro- and anti-inflammatory cytokine expression in monocytes of CRMO patients. This imbalance leads to sterile autoinflammation of bone and other organs (especially skin).

The inflammation exhibits both subacute and chronic features. The lesions predominantly affect the metaphyses of the long bones, including the spine (Chun CS 2004). However, localized osteomyelitis (jaws) has also been described, also in connection with pustulosis palmo-plantaris (Brand CU et al. (1996). No pathogens are isolated from the affected areas!

Associations are given with:

• SAPHO (Greenwood S et al 2017)
• Pyoderma gangraenosum (Schaen L et al. 1998)
• Pustulosis palmo-plantaris (Epple A et al. 2018)
• Pustular psoriasis (Prose NS et al. 1994)

Wang et al. (2023) reported on a 13-year-old girl with CRMO3 who had a mutation in the IL1R1 gene. She presented at the age of 15 months with left knee swelling and arthralgia. During childhood, she developed arthritis in her shoulders, elbows, wrists, hips, knees and ankles. She suffered from chronic pain, gait disturbances and poor overall growth. A skin rash and recurrent fever were not observed.

Radiographs showed heterotopic ossification, osteolytic lesions and multifocal metaphyseal lesions. Laboratory tests revealed an increase in serum amyloid A, C-reactive protein (CRP; 123260) and erythrocyte sedimentation rate (ESR), indicating an inflammatory process. Serum concentrations of inflammatory cytokines, including IL-1B, IL-6 and IL-8, were elevated. Antinuclear antibodies (ANA) were positive (1:100), IgA was elevated. Therapy: Treatment with TNF inhibitors generally did not lead to significant clinical improvement and treatment with a monoclonal antibody against IL1B (canakinumab) generally led to a rapid and significant clinical improvement and a reduction in inflammatory marker values (case report from: Wang Y et al. 2023).

A 12-year-old girl presented with recurrent erythematous palmoplantar plaques and pustules. She also complained of left ankle pain that had started 7 months earlier. Previous magnetic resonance imaging (MRI) scans had consistently shown multifocal bone edema of the left foot. Symptoms such as weakness, fever and morning stiffness were not present. The family history was unremarkable. Active range of motion of the left upper ankle was painfully limited by 50%. Laboratory results showed a slight increase in inflammatory parameters, including c-reactive protein and erythrocyte sedimentation rate. The tests for antinuclear antibodies, rheumatoid factor, HLA-B27 and Lyme disease were negative (case report from: Epple A et al. 2018).

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