Chronic Recurrent Multifocal Osteomyelitis With Dermatologic Involvement

Introduction

Chronic recurrent multifocal osteomyelitis (CRMO), also called chronic nonbacterial osteomyelitis (CNO), is a bone disease mainly affecting kids and teens, but it is not widely known. It was first described in 1972 as a condition with bone lesions resembling osteomyelitis.

The main symptom of CRMO is gradually appearing pain along with swelling and tenderness in certain bones, usually the clavicle, but also in other places like the thigh or upper arm bones. It can happen in any bone, even the spine.

Recently, CRMO has been labeled as an autoinflammatory disorder, which means it is a condition where the body's immune system causes inflammation without any specific trigger like an infection or autoimmune response.

What Is CRMO With Dermatologic Involvement?

Chronic recurrent multifocal osteomyelitis with dermatologic involvement is a rare autoinflammatory bone disorder characterized by recurrent episodes of bone inflammation and dermatologic manifestations. CRMO was once considered a pediatric condition, but it is now recognized that it can affect individuals of any age. In recent studies, a connection has been found between certain skin conditions and chronic, recurrent multifocal osteomyelitis in children.

What Causes CRMO?

The cause of CRMO is still unknown, but it is thought to involve immune system dysfunction, causing too much inflammation in the bones. Genetic factors may be involved, as shown by families having the condition and certain genetic variations in immune system genes. Environmental factors could also affect the disease, but the exact triggers are unknown.

What Are the Symptoms of CRMO?

CRMO's symptoms can mimic those of other bone disorders or infections. However, symptoms can differ greatly in severity and frequency from person to person. Some individuals may have times when symptoms worsen or go away for a while. Patients with CRMO usually show symptoms associated with bone inflammation. CRMO often appears in places like the clavicle, metaphyseal area of long bones, and the shoulder area. Sometimes, it can also affect the spine, ankle, and foot.

Common symptoms are:

• CRMO often causes persistent or recurring bone pain, which is the main symptom.

• The pain can be felt in one or multiple bones and can vary in intensity.

• Swelling may also occur over the affected bones or joints, which may be tender to touch.

• Inflammation in the bones or nearby joints can result in stiffness and reduced flexibility, making moving difficult.

• Some people with CRMO may have a low-grade fever, especially with active inflammation.

• Chronic pain and inflammation can lead to fatigue and a general feeling of being unwell.

What Are the Skin Manifestations of CRMO?

Not every person with CRMO will have skin problems; if they do, the symptoms can differ for each individual. These skin symptoms may not be specific and can look like other skin conditions, which makes them difficult to diagnose.

The following are the dermatological manifestations and involvement seen in people affected by CMRO:

• Psoriasis - In CRMO, psoriasis often presents as well-defined, red, scaly skin patches known as plaques. These plaques can appear on the elbows, lower back, knees, and scalp. Psoriatic lesions may exacerbate flare-ups of bone inflammation.

• Palmoplantar Pustulosis - This is seen as sterile pustules on the palms of the hands and/or the soles of the feet, often accompanied by erythema (redness) and scaling. The pustules can be painful and may lead to discomfort while walking or using the hands.

• Acne - CRMO-related acne presents as inflammatory lesions such as papules, pustules, and nodules on the face, chest, and back.

• Sweet's Syndrome - This is characterized by the abrupt onset of fever, painful erythematous (red) nodules or plaques, and an elevated neutrophil count in the blood.

• Pyoderma Gangrenosum - In CRMO patients, pyoderma gangrenosum manifests as rapidly evolving, painful ulcers with violaceous (purplish) borders and necrotic (dead) tissue at the center. These ulcers can occur at sites of trauma or surgical incisions and may be associated with underlying bone inflammation.

• Erythema Nodosum - It presents as tender, erythematous nodules on the shins, although they can also appear on the thighs, arms, or trunk. These nodules may be accompanied by systemic symptoms such as fever, malaise, and joint pain.

• Dermatitis - In CRMO patients, dermatitis may manifest as redness, itching, swelling, and blistering. The exact presentation can vary widely, ranging from mild irritation to severe eczematous or vesicular eruptions.

How Is It Diagnosed?

Because it is not commonly recognized, doctors often mistake CRMO for bacterial osteomyelitis, leading to delays in getting the right diagnosis. This can result in unnecessary treatments like long courses of antibiotics, repeated X-rays or bone scans, and multiple biopsies before the right diagnosis is made. To diagnose CRMO, doctors must rule out other diseases first, which often requires a bone biopsy to ensure it is not an infection, cancer, or another bone disorder.

Diagnosing CRMO can be challenging due to its rarity and variable presentation. It often requires clinical assessment, radiographic imaging (such as X-rays, MRI, or bone scintigraphy), and histopathological examination of bone biopsy specimens. Laboratory tests may reveal nonspecific markers of inflammation, such as elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels.

How Is It Treated?

• NSAIDs (nonsteroidal anti-inflammatory drugs) are commonly used as the initial treatment to relieve pain and inflammation during sudden episodes.

• If NSAIDs do not work well or the disease is severe, corticosteroids, DMARDs (disease-modifying antirheumatic drugs), and biologic agents may be options.

• Bisphosphonates have shown potential in certain patients by targeting bone resorption and promoting bone healing.

• Dermatological issues may need specialized treatment like topical corticosteroids or systemic therapies for psoriasis.

What Is the Link Between CRMO and SAPHO Syndrome?

Many researchers have proposed that CRMO and synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome are related conditions. Some even suggest that CRMO could be the pediatric version of SAPHO. These syndromes share similar features, such as bone inflammation, occurring in one or multiple areas, and hyperostosis and skin pustules, typically affecting otherwise healthy individuals. One study involving seven patients found that five of them had CRMO and two had SAPHO syndrome.

Conclusion

Although less common, skin manifestations highlight CRMO's systemic nature and potential to affect multiple organ systems beyond the bones. Skin symptoms alone may not always be sufficient for diagnosing CRMO, as they overlap with other dermatological conditions. Despite the progress made in understanding CRMO, significant obstacles still need to be overcome to diagnose and manage the condition. Further research is needed to investigate long-term outcomes, such as the risk of chronic disability and skeletal deformities.