Because to the variety of clinical presentations, the treatment of SAPHO syndrome remains a challenge and outcomes are known to be disappointing, especially with the skin component of the disease. There have been no randomized controlled trials on the effectiveness of various therapies, but nonsteroidal anti-inflammatory drugs (NSAIDs) are generally considered as the first-line treatment option [
4]. Antimicrobial therapy is useful in patients with positive biopsy cultures, but it has little or no effect in others. Successful treatment has been reported for doxycycline, azithromycin, sulfamethoxazole/trimethoprim, and clindamycin [
20,
55]. Azithromycin acts not only as an antimicrobial, but also as an anti-inflammatory and immunomodulatory drug, and Schilling and Wagner suggest the simultaneous usage of azithromycin together with calcitonin (osteotropic drug) [
56]. Other treatment options include colchicine, corticosteroids, bisphosphonates, and disease-modifying agents, such as methotrexate, sulfasalazine, and anti-TNFα therapy. Bisphosphonates act by inhibiting bone resorption and turnover, and by possible anti-inflammatory activity that suppresses the production of IL-1, IL-6, and TNFα [
57]. They have no effect on skin lesions. Local corticosteroid injections have also been tried, but this treatment modality has a significant effect only on osteitis lesions [
53]. Some authors used corticosteroids orally and, in that case, they will act on both skeletal and skin manifestations. Dermatologists use topical corticosteroids, psoralen plus ultraviolet A (PUVA) photochemotherapy, and retinoids [
58]. Disease-modifying agents are only indicated when symptoms persist for at least 4 weeks, despite adequate NSAID therapy. There is increasing evidence of anti-TNFα usage in the treatment of such patients. Case reports and case series on TNFα blockade often demonstrate a marked improvement in the clinical picture, regardless of whether or not this treatment is permanently effective. The most often published cases in the literature are about the use of infliximab in these patients. Usually, 5 mg/kg at weeks 0, 2, and 6 followed by a 6–8-week interval has been used, just like that used in spondyloarthropathies. Lower doses of infliximab and reduction in the duration of intervals have been tested, but it has been noted that decreased infusion intervals like in spondyloarthropathies and lower dosages cannot maintain the remission of disease [
58]. Both skeletal and cutaneous lesions responded well in most of the described cases, with exception of PPP, which sometimes failed to respond. In some cases, infliximab induced exacerbation of skin manifestation. Arias-Santiago et al. [
59] suggested adalimumab as a possible alternative therapy in such cases, and there are also reports on the successful treatment of SAPHO with etanercept and the IL-1 receptor antagonist anakinra. Anakinra appeared to be helpful in five out of six SAPHO patients, two of which previously failed to respond to TNF blockers [
60]. Autologous bone transplantation using microvascular flaps is applied as an experimental treatment procedure [
15].
Physiotherapy can always be used as an additional treatment for osteoarticular manifestations. Surgery is considered for patients whose condition has failed to respond to all other therapeutic interventions [
61]. Wide resections are reserved to treat complications when patients develop deformity or loss of function with pain [
15]. There are several reports in the literature about the surgical treatment of such patients; for example, resection of the medial clavicle or the sternoclavicular joint, which seemed to provide variable improvement in pain, although some authors report no improvement with this intervention [
54]. Furthermore, mandibular involvement has been treated with minor surgical procedures, such as decortications and curettage, but extensive extirpation of the cortical jaw was done as well [
62].