SAPHO syndrome occurs in approximately one in 10,000 individuals. Individuals from northern and western European or Japanese descent are more commonly affected.

The causal mechanism of SAPHO syndrome remains unknown but several hypotheses exist. One hypothesis suggests that SAPHO syndrome is associated with persistent infections with certain bacteria. The most commonly found bacteria is Propionibacterium acnes. P. acnes is a bacterium that is found on the skin of healthy individuals without causing an infection. However, it is believed that in some cases, P. acnes might cause disease or inflammation. Bacterial infection is not present in all affected individuals.

There is also evidence suggesting that a genetic association might be present. Human Leukocyte Antigen (HLA) genes encode proteins that play an important role in the immune system. An association between SAPHO syndrome and certain HLA genes has been suggested but not confirmed. Other genes that might play a role in SAPHO syndrome are LPIN2 and NOD2, both of which encode proteins that are involved in inflammatory processes. However, none of these genes have been shown to be directly or consistently involved. 

It has also been suggested that SAPHO syndrome is an autoimmune disorder. The immune system has developed mechanisms to recognize foreign molecules from self molecules and only attack unfamiliar particles. Autoimmunity refers to the process by which the body’s immune system abnormally detects self molecules as foreign and initiates an immune response against healthy cells. SAPHO syndrome might be an autoimmune disorder triggered by bacterial infections in individuals with a genetic predisposition. 

SAPHO syndrome primarily affects bones, joints, and skin. Symptoms typically present during adolescence and adulthood and most commonly between thirty to forty years of age. Bone and joint lesions lead to pain, stiffness, and swelling in the affected bones and joints. Redness, heat, and limited motions at joints may also be experienced due to inflammation. The joints might be particularly stiff in the morning. The anterior chest wall is most commonly affected, but the spine, hip bone, and long bones may also be affected in some cases. The onset of these symptoms is usually gradual but can eventually lead to severe pain.

Severe acne, mostly in the face, chest, and back, and palmoplantar pustulosis are the most common skin involvements in SAPHO syndrome. Palmoplantar pustulosis is characterized by the formation of blisters filled with pus, often on the soles of feet and the palms of hands. The skin involvement might appear before or after bone and joint lesions. In most cases, the skin becomes affected two years before the bones and the joints; however, in rare cases, skin lesions have developed more than twenty years after symptoms related to bone and joint involvement.

Diagnosis of SAPHO syndrome is primarily based on medical history and physical examination although radiologic imaging and laboratory testing might provide some useful information. Clinical diagnosis focuses on the presence of or a history of signs and symptoms of bone and joint involvement and skin conditions that are common in SAPHO syndrome. 

Laboratory tests can only look for general evidence of inflammation but are not specific to SAPHO syndrome. Radiographic imaging can identify bone and joint involvement and visualize asymptomatic lesions. In addition, the diagnosis of SAPHO syndrome requires the exclusion of other possible disorders which may require a bone biopsy.

The diagnosis of SAPHO syndrome is mostly clinical. Initial evaluations may include a number of blood tests to identify certain molecules that indicate active inflammation. X-ray imaging and magnetic resonance imaging (MRI) of affected areas can visualize evidence of bone and joint involvement typical of SAPHO syndrome. In some cases, bone biopsy might be required to exclude other disorders. Bone biopsy is a procedure in which a needle is used to take a sample of an affected bone for further testing.

Treatment of SAPHO syndrome involves symptom management. The primary initial treatment involves a class of drugs called nonsteroidal anti-inflammatory drugs (NSAID) that reduce inflammation. If NSAIDs are ineffective, disease-modifying anti-rheumatic drugs (DMARD) may be used. DMARDs also act to reduce pain and inflammation but through a different mechanism than NSAIDs. Tumor necrosis factor (TNF) inhibitors have also shown promising results. TNF is a protein that facilitates and coordinates the inflammatory process in the body. Thus, TNF inhibitors can reduce inflammation.

Antibiotics may also be helpful in some cases that are associated with a bacterial infection. Typically, severe acne is treated with antibiotics but bone and joint manifestations may also improve. However, not everyone benefits from antibiotics since bacterial associations are not always present. 

Individuals with skin involvement may also benefit from retinoids. Retinoids are a class of drugs that are related to vitamin A and are used to treat inflammatory skin disorders. Psoralen and ultraviolet A (PUVA) therapy is another technique that can be used to treat skin lesions in SAPHO syndrome. PUVA is a technique that uses ultraviolet light to treat certain skin conditions.

Physiotherapy can provide additional relief from bone and joint pain and stiffness. Surgery is usually not recommended unless there are significant functional limitations.

While in some cases, SAPHO syndrome resolves after some time, in most affected individuals, it presents as a chronic condition with a relapsing-remitting pattern. That means that symptoms periodically flare up, followed by periods when few symptoms are experienced. The affected individuals have variable outcomes but affected women and individuals with anterior chest wall involvement and skin lesions tend to experience a more chronic course. SAPHO syndrome might lead to complications that negatively affect the quality of life.

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