SAPHO syndrome

Overview

SAPHO syndrome is a rare and chronic autoinflammatory disorder that affects the bones, joints, and skin. The term "SAPHO" is an acronym that stands for Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis—the key features of the condition. It most commonly manifests in adults between the ages of 30 and 50 but can also occur in children and adolescents. Due to its overlapping symptoms with other rheumatologic and dermatologic diseases, SAPHO syndrome is frequently underdiagnosed or misdiagnosed.

The syndrome presents with a combination of musculoskeletal symptoms (such as joint pain and bone inflammation) and skin conditions like severe acne or palmoplantar pustulosis (pus-filled blisters on the hands and feet). The most frequently affected bones include the anterior chest wall (especially the sternoclavicular joints), spine, and long bones. SAPHO syndrome is generally considered a benign condition, but it can cause significant discomfort and impair quality of life if left untreated.

Causes

The exact cause of SAPHO syndrome remains unknown, but it is believed to be multifactorial, involving a combination of genetic, immunological, and possibly infectious triggers. The syndrome is categorized under autoinflammatory diseases, where the immune system is inappropriately activated, leading to chronic inflammation without an infectious cause.

Potential contributing factors include:

• Genetic predisposition: Although no single gene mutation has been definitively linked, some cases show familial clustering, suggesting a hereditary component.

• Immune system dysregulation: Abnormal activation of neutrophils and other immune cells may contribute to chronic bone and skin inflammation.

• Bacterial involvement: Some studies suggest a role for Propionibacterium acnes (now Cutibacterium acnes) in initiating or exacerbating symptoms, particularly in bone lesions.

While SAPHO syndrome is not considered an autoimmune disease, it shares characteristics with other spondyloarthropathies and inflammatory skin disorders.

Symptoms

The clinical presentation of SAPHO syndrome varies widely, but the most common symptoms involve the musculoskeletal and dermatologic systems. Key symptoms include:

Musculoskeletal Symptoms

• Osteitis: Inflammation of the bone, often causing deep, localized pain

• Hyperostosis: Excessive bone growth leading to swelling and deformity, especially in the anterior chest wall

• Synovitis: Joint inflammation, most commonly affecting the sternoclavicular, sacroiliac, and spinal joints

• Spinal involvement: Back pain and stiffness, sometimes with limited mobility

Skin Symptoms

• Palmoplantar pustulosis: Recurrent pustules and scaling on the palms of the hands and soles of the feet

• Severe acne: Often nodulocystic or conglobate, typically on the face, chest, and back

• Pustular psoriasis: In some cases, SAPHO may resemble or co-exist with pustular psoriasis

Symptoms may appear simultaneously or sequentially. The disease course is typically chronic and relapsing, with periods of flare-ups and remissions.

Diagnosis

Diagnosing SAPHO syndrome can be challenging due to its rarity and similarity to other conditions like infections, malignancies, or autoimmune diseases. There is no single test for SAPHO; diagnosis is clinical and based on a combination of history, imaging, and exclusion of other diseases.

Diagnostic Criteria

While formal criteria vary, common diagnostic features include:

• Osteoarticular involvement (especially in the anterior chest wall)

• Dermatologic findings such as acne or pustulosis

• Chronic or recurrent sterile bone inflammation

• Exclusion of infectious, neoplastic, or autoimmune causes

Diagnostic Tests

• X-rays: May reveal hyperostosis or bone lesions

• CT or MRI: Provides detailed imaging of bone and joint inflammation

• Bone scintigraphy: Often shows increased uptake in the sternoclavicular joints (bull’s head sign)

• Biopsy: Occasionally performed to rule out malignancy or infection; may show sterile inflammation

• Laboratory tests: Inflammatory markers like ESR and CRP may be elevated; autoimmune markers (e.g., ANA, RF) are typically negative

Treatment

Treatment of SAPHO syndrome focuses on reducing inflammation, relieving pain, and managing skin lesions. Since the condition is chronic, long-term management is often necessary. Treatment approaches may include:

Medications

• NSAIDs: First-line therapy to relieve pain and reduce inflammation

• Corticosteroids: Used short-term for acute flares, either systemically or via local injections

• Bisphosphonates: Such as pamidronate or alendronate; shown to reduce bone pain and inflammation

• Antibiotics: Long-term courses of antibiotics like doxycycline or azithromycin may be beneficial, especially in cases with suspected C. acnes involvement

• DMARDs: Methotrexate or sulfasalazine may be considered for refractory joint symptoms

• Biologics: TNF inhibitors (e.g., infliximab, adalimumab) or IL-1/IL-17 blockers may be used in severe or treatment-resistant cases

Skin Treatment

• Topical therapies (e.g., corticosteroids, salicylic acid)

• Systemic retinoids or isotretinoin for severe acne

Supportive Care

• Physical therapy to maintain joint mobility and function

• Psychosocial support to address chronic pain and quality-of-life issues

Prognosis

The long-term prognosis of SAPHO syndrome is generally favorable, although the condition tends to be chronic and relapsing. Most patients experience persistent but manageable symptoms. With appropriate treatment, many individuals achieve significant symptom control and maintain a good quality of life.

However, untreated or poorly managed cases can lead to chronic pain, joint damage, and reduced mobility. Early recognition, regular monitoring, and individualized therapy are essential to minimize complications and improve outcomes. Ongoing research into the pathophysiology of SAPHO may lead to more targeted treatments in the future.