Diffuse sclerosing osteomyelitis (DSO) of the mandible in SAPHO syndrome: A novel approach with anti-TNF therapy. Systematic review

Abstract

Diffuse sclerosing osteomyelitis of the mandible is now considered a local manifestation of SAPHO syndrome. This rare condition is thought to be of auto-inflammatory origin. The myriad of treatments shown in the literature, are basically empirical and reflect its unknown origin. We present a clinical case of refractory DSO treated with an anti-TNF drug (etanercept) with complete clinical remission. We advise against radical surgery and an interdisciplinary approach is recommended. A systematic literature review was also conducted.

Introduction

DSO is the clinical entity characterized by a nonsuppurative, inflammatory process of the mandible associated with recurrent swelling, trismus and pain (Montonen and Lindqvist, 2003). It usually affects the mandible, in the region of the corpus and ramus and may include the condyle (Utumi et al., 2008; Müller-Richter et al., 2009); the primary location can also be the mandibular condyle (Kodama et al., 2013) or the temporal bone (Marsot-Dupuch et al., 1999). It is generally unilateral, affecting the basal and alveolar bone that appears expanded. There is also compromise of the adjacent soft tissues. Radiology shows areas of sclerosis, lysis and periosteal reaction (Suei et al., 1997a).

It is also quite clear that diffuse sclerosing osteomyelitis is a manifestation of SAPHO syndrome (Kahn et al., 1994, Suei et al., 1996, García-Marín et al., 1996, Eyrich et al., 1999). Kahn et al. (1994) speculated that DSO is a symptom of SAPHO syndrome, because the features of the mandibular lesions observed in SAPHO syndrome are similar to those seen in DSO.

The synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare and of unknown etiology. It was first described by Chamot et al. in 1987. In 1994, Kahn et al. (1994) reported three diagnostic criteria for SAPHO syndrome:

• Multifocal osteomyelitis with or without skin manifestations.

• Sterile acute or chronic joint inflammation associated with pustules or psoriasis on the palms and soles, acne, or hidradenitis.

• Sterile osteitis in the presence of one of the skin manifestations.

The most frequent osteoarticular manifestation is pain in the anterior costal wall normally involving the sternoclavicular articulations (Hayem et al., 1999, Sato et al., 2001, Colina et al., 2009, Magrey and Khan, 2009, Salles et al., 2011), and less frequently involving the vertebral column, long bones, iliac, mandible, and sacroiliac articulations and small joints. Reports of affected jaws are rare and the mandible is involved in about 10% of cases (Hayem et al., 1999). The posterior body and ascending ramus are the most common sites affected.

SAPHO syndrome can be classified with the inflammatory spondyloarthropathies, which typically affects the spine. The therapeutic strategy was inspired by that for spondyloarthropathies but it remains unclear. Most reports describe treatment responses from anecdotal cases and a small series of patients. Most cases respond to nonsteroidal antiinflammatory drugs (NSAIDs) for osteoarticular symptoms (Hayem et al., 1999) and topical treatment for skin lesions. But nearly one third are refractory. For those cases different treatment protocols were tried: antibiotic therapy, methotrexate and sulfasalazine (Hayem et al., 1999, Yoshii et al., 2001, Assmann et al., 2009), and bisphosphonates (Amital et al., 2004, Kuijpers et al., 2011, Zemann et al., 2011, Urade et al., 2012). With analogy to spondyloarthropathy therapy, tumor necrosis factor-α (TNF-α) blockers have been proposed as third-line therapy (Wagner et al., 2002).

TNF-α is a cytokine that performs important functions in immune system regulation. Their blockade by monoclonal antibodies (infliximab, adalimumab, and golimumab certolizumab) or soluble receptors (etanercept) has led to significant advances in the treatment of diseases of an immunological nature such as rheumatoid arthritis and spondyloarthropathies.

We present a report of SAPHO syndrome affecting the mandible of a patient who presented after protracted problems with pain and swelling. A systematic literature review is conducted for DSO and its treatment.