Successful treatment of SAPHO syndrome with apremilast

Psoriasis and psoriatic arthritis are common clinical conditions that negatively impact health-related quality of life and are linked to serious medical comorbidities. Disease mechanisms involve local and systemic chronic inflammatory processes. Available biologic therapies specifically target single inflammatory mediators, such as tumor necrosis factor-α (TNF-α), in the context of a larger inflammatory signaling cascade. To interrupt this pathological cascade earlier in the response or further upstream, and return pro-inflammatory and anti-inflammatory signaling to a homeostatic balance, the use of a phosphodiesterase4 (PDE4) inhibitor has been explored. PDE4 is the major enzyme class responsible for the hydrolysis of cyclic adenosine monophosphate (cAMP), an intracellular second messenger that controls a network of pro-inflammatory and anti-inflammatory mediators. With PDE4 inhibition, and the resulting increases in cAMP levels in immune and non-immune cell types, expression of a network of pro-inflammatory and anti-inflammatory mediators can be modulated. Apremilast is an orally available targeted PDE4 inhibitor that modulates a wide array of inflammatory mediators involved in psoriasis and psoriatic arthritis, including decreases in the expression of inducible nitric oxide synthase, TNF-α, and interleukin (IL)-23 and increases IL-10. In phase II studies of subjects with psoriasis and psoriatic arthritis, apremilast reversed features of the inflammatory pathophysiology in skin and joints and significantly reduces clinical symptoms. The use of an oral targeted PDE4 inhibitor for chronic inflammatory diseases, like psoriasis and psoriatic arthritis, represents a novel treatment approach that does not target any single mediator, but rather focuses on restoring a balance of pro-inflammatory and anti-inflammatory signals. Copyright © 2012 Elsevier Inc. All rights reserved.

To review the epidemiology, presentation, diagnosis, treatment, pathogenesis, and genetics of the syndrome known under the acronym of SAPHO for Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis to heighten awareness of this entity. We conducted a Medline search using SAPHO syndrome, chronic recurrent multifocal osteitis/osteomyelitis, and related terms as keywords and extracted further relevant articles from the retrieved references. The SAHPO acronym identifies a syndrome encompassing a variety of osteoarticular disorders that are frequently accompanied by dermatoses characterized by neutrophilic pseudoabscesses, but can also occur in isolation. SAPHO syndrome is rare, although probably underrecognized because its diagnosis may be challenging because of the wide variability in its musculoskeletal and cutaneous manifestations. This is especially true when atypical sites are involved and when specific skin lesions are absent. There are no standardized treatment protocols available. Current treatments are empirical and have the objective of providing relief from the at times debilitating pain associated with SAPHO syndrome. They include nonsteroidal anti-inflammatory drugs and analgesics as first-line agents. Systemic corticosteroids, disease-modifying anti-rheumatic drugs, biologicals targeting tumor necrosis factor alpha and interleukin-1, and bisphosphonates have all been beneficial in some patients, but ineffective in others. This suggests that the pathogenesis of SAPHO syndrome is multifactorial, but this aspect remains poorly explored, although bacteria and immunological dysfunction are hypothesized to play a role. The early recognition, diagnosis, and prompt treatment of SAPHO syndrome can prevent the unnecessary use of long-term antibiotics or invasive procedures, while rapidly alleviating pain in a majority of affected patients. Copyright © 2012 Elsevier Inc. All rights reserved.

Introduction Synovitis–acne–pustulosis–hyperostosis–osteitis (SAPHO) is an acronym for various osteoarticular and dermatological manifestations that can appear in the same patient. It is a rare syndrome, but since its awareness has increased, there have been more and more such reports in the literature. Aims The objectives of this review are to summarize the current state of knowledge on pediatric and adult-onset SAPHO syndrome, and to discuss treatment strategies that should be considered. Results The SAPHO syndrome can affect patients of any age, and its etiology is still not known. The syndrome has its cognizable radiological characteristics that are most important in making the diagnosis. There are several diagnostic criteria as well, but they need further validation. No standard treatment protocols are available and current treatment options are not evidenced-based due to the rarity of the syndrome. Therapy is empirical and aimed at easing pain and modifying the inflammatory process. It includes nonsteroidal anti-inflammatory drugs (NSAIDs) as the first-line agents. Antibiotics, corticosteroids, disease-modifying anti-rheumatic drugs, biologicals targeting tumor necrosis factor alpha or interleukin-1, and bisphosphonates have all been used with variable success. Surgery is reserved to treat complications. Even though it is a disease with good long-term prognosis, its treatment remains a challenge and the results are known to be disappointing, especially with the skin component of the disease. Conclusion It is expected that these patients present at the time of diagnosis and the treatment should be as early, effective, and safe as possible in order to prevent osteoarticular progression and to limit the adverse events associated with pharmacological drugs.