Some characteristics of this case are striking and deserve to be analyzed in the light of current knowledge; one of the characteristics that make it unique is the therapeutic response to zoledronic acid; also, it presented multifocal without skin changes and persistence of refractory symptoms longer than 5 years, and imaging was required to establish the diagnosis. On the other hand, some of its usual characteristics included that it was a woman older than 40 years, with osteitis in the anterior thoracic wall and without initial response to NSAID. All of the above shows us that we cannot always expect typical findings in this entity and that we must have a high index of clinical suspicion.
The term SAPHO was introduced by Chamot et al. in the late 1980s to describe a syndrome characterized by the combination of chronic inflammatory osteoarticular lesions and neutrophilic skin eruptions [7, 8], but similar associations had been reported in the literature going back to the 1960s . Synovitis and osteitis in SAPHO predominantly affect the anterior chest wall (68–83%), spine (19–66%), and sacroiliac joints (13–40%) . The symphysis pubis, long bones, and temporomandibular joints are less frequently involved. Peripheral arthritis may occur in up to one third of patients, typically affecting the knees or wrists . Joint and bone inflammation in SAPHO manifest clinically as pain, swelling, and stiffness. The osteitis in SAPHO is sterile and may involve the cortex and the medulla, often adjacent to involved joints. Bone inflammation may result in the development of lytic lesions as well as formation of new bone causing bony prominence (hyperostosis) and joint ankylosis. Palmoplantar pustulosis (46–60%) and severe acne (5–39%) are the most common skin manifestations in SAPHO . Psoriasis vulgaris, hidradenitis suppurativa, pyoderma gangrenosum, and sweet syndrome are less frequently found. The skin disease in SAPHO may develop before, concomitantly with or after the osteoarticular disease features in roughly equal proportions . Importantly, patients with SAPHO do not always present with all of the features defining the syndrome. In two large case series, 19/120 (15.5%) and 14/71 (19.7%) SAPHO patients had no skin lesions at all [11, 12].
Incomplete presentations of the SAPHO syndrome, in particular when typical skin findings are absent, may be confused with other entities such as costochondritis resulting in delayed or missed diagnosis. Costochondritis is characterized by anterior chest wall pain without local swelling that is reproduced by palpation of the involved costosternal joints. In 90% of patients, more than one joint is affected, typically at the level of the second through fifth rib. Involvement of the second or third costochondral junction with local swelling is called Tietze syndrome. Costochondritis may result from chest wall trauma, chronic cough, or sports-related overuse injury, but most commonly is idiopathic. Women older than 40 are frequently affected. The majority of costochondritis cases will resolve over the course of 1 year. Long-term persistence of symptoms (7 years in our patient) should be considered a red flag suggesting an alternative diagnosis . Sternoclavicular swelling is also atypical for simple costochondritis.
Imaging studies are important in making a diagnosis of SAPHO. Radiographs are typically normal early on but can show osteolytic lesions with or without sclerotic margins, joint erosions, or ankylosis at later stages. Whole-body 99mTc scintigraphy is particularly useful. The bullhead sign is a characteristic pattern of high tracer uptake in the sternocostoclavicular region, with the manubrium sterni representing the skull and the sternoclavicular joints and adjacent clavicles forming the horns . This configuration is virtually pathognomonic for SAPHO. While sensitivity is not 100%, a bullhead may be present in SAPHO patients who do not have anterior chest wall symptoms, and whole-body bone scintigraphy may reveal clinically silent lesions elsewhere. CT scanning may demonstrate bone erosions, joint space narrowing, ligament ossifications, subchondral sclerosis, and periosteal new bone formation at affected sites.
NSAID are typically used as first-line drugs in SAPHO patients but do not sufficiently control pain in half of the patients. Other treatment options include colchicine, corticosteroids, DMARD such as methotrexate and sulfasalazine, and bisphosphonates . Randomized controlled drug trials have not been performed in SAPHO. However, efficacy of bisphosphonate therapy has been documented by multiple case reports. Most of these patients were treated with pamidronate, but other bisphosphonates including zoledronic acid, as in our patient, may work equally well . TNF (tumor necrosis factor) inhibitors have been used in refractory cases but may exacerbate cutaneous manifestations .