SAPHO Syndrome

SAPHO syndrome is a rare condition that combines bone and joint inflammation with skin problems, creating a unique challenge for both patients and doctors trying to understand and manage this complex disorder.

Synovitis-acne-pustulosis-hyperostosis-osteitis syndrome, pphs, synovitis acne pustulosis hyperostosis osteomyelitis syndrome

M86.3; L70.1; M40.3; M85.8; D89
4A61
D020083
10051316

Table of contents

• What is SAPHO syndrome?
• What causes SAPHO syndrome?
• Signs and symptoms
• Who gets SAPHO syndrome?
• How is it diagnosed?
• Treatment options
• Living with SAPHO syndrome

What is SAPHO syndrome?

SAPHO syndrome is a rare condition that affects both the skin and the bones and joints of the body. The name SAPHO is an acronym that describes the main features of the condition^[1]. Each letter stands for a different aspect: Synovitis (inflammation of the joints), Acne, Pustulosis (thick yellow blisters containing pus), Hyperostosis (increase in bone substance), and Osteitis (inflammation of the bones)^[1][6].

People with SAPHO syndrome can have any combination of these features, not necessarily all of them at once^[1][6]. The condition is considered a rare disorder, and its exact prevalence is probably underestimated^[2]. SAPHO syndrome is classified as an autoinflammatory disease, meaning the body’s immune system causes inflammation without a clear external trigger^[2].

What causes SAPHO syndrome?

The exact cause of SAPHO syndrome remains unknown^[1][6]. However, researchers believe the condition has a complex origin involving multiple factors^[2].

SAPHO syndrome appears to have a multifactorial origin with genetic, environmental, immunologic, and infectious components^[2]. Some studies suggest that certain genetic factors may play a part, including mutations in genes called copy number variations^[6].

Slow-growing bacteria, particularly Propionibacterium acnes (a bacterium known for its role in acne), could act as a triggering factor^[2]. This bacterium has been isolated from bone biopsies of SAPHO patients, which has led some doctors to try antibiotic treatments^[3]. However, this does not mean SAPHO syndrome is an infection in the traditional sense.

Signs and symptoms

SAPHO syndrome affects different parts of the body, primarily the bones, joints, and skin. The symptoms can vary widely among people with this condition^[2].

Bone and joint symptoms

The onset of bone and joint pain, stiffness, and swelling is most often gradual^[2]. In adults, inflammation occurs mainly in the anterior chest wall, especially affecting the breastbone (sternum) and collar bones (clavicles), but also in the spine, and less frequently in the jaw and hip bones^[2][3]. The sternum is affected in 65 to 90 percent of patients, resulting in decreased mobility due to pain, tenderness, and swelling^[3][4].

When synovitis (inflammation of the joint lining) occurs, it most often affects the sacroiliac joints (at the base of the spine), hips, knees, or the joints where the collarbone meets the breastbone^[2]. Depending on the severity of symptoms, a limited range of motion may be observed^[2].

In children, the pattern of bone involvement is similar to a condition called chronic nonbacterial osteomyelitis, affecting long bones (such as the tibia and femur), clavicle, and spine^[2][3].

Skin symptoms

The skin problems in SAPHO syndrome include severe acne, palmoplantar pustulosis (pustules on the palms and soles), and pustular psoriasis^[2]. The pustules are thick yellow blisters containing pus, often appearing on the palms of the hands and soles of the feet^[1][4].

Skin manifestations often begin one to two years before the bone changes appear, but they may appear simultaneously or even more than 20 years later^[2]. Other skin conditions seen in SAPHO syndrome include hidradenitis suppurativa (painful lumps under the skin) and dissecting cellulitis of the scalp^[4].

Other symptoms

Some patients may also experience abdominal pain, diarrhea, anal fissures, or abscesses, suggesting a possible association with inflammatory bowel disease^[2]. Fatigue and weight loss can also occur in severe cases^[5].

Who gets SAPHO syndrome?

SAPHO syndrome can begin at various ages, though the age of onset most commonly ranges from adolescence to late adulthood, with a median age between 30 and 40 years^[2]. The condition can affect both children and adults, though it presents somewhat differently in these age groups^[2].

Many doctors regard chronic nonbacterial osteomyelitis in children as the pediatric form of SAPHO syndrome, as both conditions share similar features^[2].

How is it diagnosed?

Diagnosing SAPHO syndrome can be challenging because the condition is often confused with infectious osteomyelitis (bone infection), which has similar clinical and pathologic findings^[5]. The diagnosis becomes even more difficult when unusual sites are involved and there are no skin lesions^[5].

Clinical examination

SAPHO syndrome is suspected when a patient presents with a pustular skin disease in association with bone or joint pain^[4]. A thorough clinical history and high clinical suspicion are essential^[5].

Imaging tests

Diagnosis must be confirmed with imaging procedures^[2]. X-rays, CT scans, and MRI scans can show a combination of bone breakdown (osteolysis) and abnormal bone density (osteosclerosis) with secondary hyperostosis, bone marrow swelling, inflammation of the bone lining, inflammation of surrounding muscles, and nearby arthritis^[2].

Magnetic resonance imaging shows inflammation of the bone marrow or joints at characteristic sites such as the collar bone, breast bone, pelvis, heel, and lower jaw^[4]. On bone scans using radioactive tracers, a characteristic pattern called the “bull’s head sign” can be seen in the chest area^[3].

Laboratory tests and biopsies

There are no specific blood tests for SAPHO syndrome. Bone biopsy often reveals an infiltrate of certain white blood cells (neutrophils) in early stages, which are progressively replaced by other immune cells and associated with scarring in later stages^[2]. A study looking for bacteria sometimes finds Propionibacterium acnes, though synovial fluid culture (from the joint) is usually negative^[2].

Conditions to rule out

Doctors must rule out other conditions that look similar, including infectious osteomyelitis or arthritis, Langerhans cell histiocytosis, and bone tumors such as Ewing sarcoma and osteoblastoma^[2].

Treatment options

SAPHO syndrome has no specific cure, but various treatments can help manage symptoms^[4]. The condition can be chronic but eventually may resolve on its own^[4].

Anti-inflammatory medications

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to manage joint symptoms^[3][4]. Treatment with antibiotics, particularly clindamycin, combined with NSAIDs has been remarkably effective in some patients, with symptom relief lasting for years after a three to eight month course of treatment^[5][7].

Disease-modifying drugs

Other drugs that may be used include sulfasalazine, methotrexate, colchicine, cyclosporin, and leflunomide^[3][4]. These medications are also used in related conditions like psoriatic arthritis^[3].

Bisphosphonates

Bisphosphonate therapy has been suggested as a first-line treatment option in many case reports^[3][4]. These medications help regulate bone metabolism and can reduce bone pain.

Biologic therapies

Treatment with tumor necrosis factor (TNF) blockers, such as infliximab and etanercept, has been tried with limited success in some patients^[3][4]. Newer biologic treatments targeting specific inflammatory pathways, including interleukin (IL)-1 inhibitors, IL-17 inhibitors, and JAK inhibitors like baricitinib, have shown promise^[8][11].

Treatments for skin symptoms

A dermatologist may use vitamin A derivatives (oral retinoids) to treat the acne (isotretinoin) and the pustulosis on palms and soles (acitretin)^[4]. Topical and systemic corticosteroids may also be used^[4].

Individual treatment approach

Different treatments may work better for bone and joint symptoms versus skin symptoms, possibly because different inflammatory pathways are involved^[8]. Patients with bone and joint symptoms might consider TNF blockers, JAK inhibitors, IL-1 inhibitors, and IL-17 inhibitors, while those with skin symptoms should consider IL-17 inhibitors and JAK inhibitors^[8].

Living with SAPHO syndrome

Living with SAPHO syndrome presents unique challenges in daily life. The chronic pain, stiffness, and fatigue can significantly affect a person’s ability to work, exercise, and participate in social activities^[14].

Opening up about the condition can be difficult. Some people worry about how sharing information about their pain and limitations might affect loved ones^[14]. However, talking with family and friends who understand can be comforting and help them provide appropriate support^[14].

It’s important to be honest about how you’re feeling, especially when you need to decline activities or ask for help. Living honestly, rather than trying to hide symptoms, can reduce stress and improve relationships^[14].

Connecting with others who have SAPHO syndrome or similar conditions can be particularly helpful. Sharing experiences and ways of coping can have a huge positive impact^[14]. Support networks and patient stories can help you feel less alone and provide practical strategies for managing the condition.

One important piece of advice from people living with SAPHO syndrome is to give yourself the same empathy you would give others^[14]. Living with a chronic condition is challenging, and it’s important to acknowledge that while finding ways to thrive.