Mandible / maxilla
Osteomyelitis
SAPHO syndrome



Topic Completed: 1 November 2014

Revised: 8 February 2019

Copyright: (c) 2004-2018, PathologyOutlines.com, Inc.

PubMed Search: SAPHO syndrome [title]


Annie S. Morrison, M.D.
Kelly Magliocca, D.D.S., M.P.H.
Page views in 2018: 233
Page views in 2019 to date: 191
Cite this page: Morrison A. Osteomyelitis: SAPHO syndrome. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/mandiblemaxillaSAPHO.html. Accessed October 21st, 2019.
Definition / general
  • Acronym for a complex clinical presentation that includes Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis
  • Unknown cause but may arise in genetically predisposed individuals who develop an autoimmune disturbance due to exposure to dermatologic bacteria
  • Increased prevalence of HLA-27 (10 - 15% cases of SAPHO)
  • SAPHO and Chronic recurrent multifocal osteomyelitis / CRMO are distinguished from other forms of osteitis / osteomyelitis as these two diseases may have extragnathic skeletal involvement
  • The precise relationship between primary chronic osteomyelitis, diffuse sclerosing osteomyelitis, CRMO and SAPHO is controversial - some consider CRMO and SAPHO as primary chronic osteomyelitis with additional extragnathic manifestations
Terminology
  • Acute suppurative osteomyelitis:
    • Early phase of osteomyelitis and usually a suppurative (pus forming) condition
    • Exists when an acute inflammatory process moves away from the site of initial infection and spreads through the medullary space of the bone and, in most cases, insufficient time has passed for the body to react to the presence of the inflammatory infiltrate
    • Acute phase may lead to the chronic phase which has been arbitrarily defined as an osseous infection lasting at least 1 month
  • Alveolar osteitis / fibrinolytic alveolitis:
    • After extraction of a tooth, a blood clot is formed at the extraction site with eventual organization of this clot by granulation tissue and gradual replacement by bone
    • Destruction of the initial clot is thought to delay the aforementioned additional series of steps required for uneventful extraction site healing and leads to clinical condition known as alveolar osteitis
    • Clot is lost secondary to transformation of plasminogen to plasmin with subsequent lysis of fibrin and formation of kinins which are potent pain mediators
  • Biofilm:
    • Collection of microorganisms often embedded in a self produced extracellular polymeric matrix which allows them to adhere to or coat the surface of a living or inanimate structure
  • Chronic osteomyelitis:
    • May be classified as primary or secondary and as suppurative or non-suppurative
      • Secondary chronic osteomyelitis (SCO)
      • Primary chronic osteomyelitis (PCO)
      • Chronic tendoperiostitis
        • Initially thought to be an obscure infectious process, the clinical presentation is similar to that of primary chronic osteomyelitis
        • May represent a reactive alteration of bone initiated and exacerbated by chronic overuse of the masticatory muscles, predominantly the masseter and digastric
        • Patients usually present with parafunctional complaints
        • Palpation of the temporal, masseter, medial pterygoid and the digastric muscles reveals tenderness
        • Radiographically, may be very similar to primary chronic osteomyelitis with diffuse sclerosing of the marrow and the cortical plate in the absence of pus formation or sequestration
  • Chronic sclerosing osteomyelitis / diffuse sclerosing osteomyelitis:
    • Although the term is usually used synonymously with primary chronic osteomyelitis, it represents a description of a strictly radiological appearance that can be caused by several similar processes, including:
      • Primary and secondary chronic osteomyelitis
      • Chronic tendoperiostitis
      • Ossifying periostitis or Garrè osteomyelitis
      • Medullary osseous infection, probably bacterial, which induces the complete sclerosis
        • Favors young women, is painful and appears radiographically as medullary sclerosis
        • Therapy includes antibiotics and surgical debridement and hyperbaric oxygen therapy in refractory cases
  • Condensing osteitis:
    • Localized areas of radiographic bone sclerosis associated with the apices of inflamed dead or dying teeth (pulpitis or pulpal necrosis) are termed condensing osteitis
    • The association with an area of inflammation, usually a neighboring tooth, is critical because these lesions can resemble several other intrabony processes that produce a somewhat similar pattern
    • Is not considered a true osteomyelitis in the classical sense
  • Cortical bone:
    • Cortical bone, synonymous with compact bone, is one of the two types of osseous tissue that forms bone
    • As its name implies, cortical bone forms the cortex, or outer shell, of most bones
    • Compact bone, as its name implies, is much denser than cancellous bone, which is the other type of osseous tissue
    • Furthermore, it is harder, stronger and stiffer than cancellous bone
  • Garrè sclerosing osteomyelitis:
    • In 1893, a Swiss physician, Carl Garrè, reported on patterns of acute osteomyelitis
    • Garrè did not have any pathologic specimens for microscopic examination nor radiographs to augment his descriptions
    • Nonetheless, his name is often associated with the condition in which periosteal duplication, or an "onion-skinning" pattern of periostitis, leads to enlargement of the jaw, usually mandible
  • Involucrum:
  • Medullary bone / medullary cavity / marrow cavity:
    • The medullary cavity (medulla, innermost part) of bone is the central cavity where red bone marrow or yellow bone marrow (adipose tissue) is stored; hence, the medullary cavity is also known as the marrow cavity
    • The medullary cavity has walls composed of spongy bone (cancellous bone) and is lined by endosteum, which are osteoprogenitor cells
  • Osteochemonecrosis of Jaws:
    • Synonyms: bisphosphonate related osteonecrosis of the jaws, bisphosphonate induced osteonecrosis of the jaw, osteonecrosis of jaw, bisphosphonate osteonecrosis, bis-phossy jaw
    • Necrosis of bone related to long term use of antiresorptive medications such as bisphosphonate medications and altered bone metabolism
    • Osteoclasts are thought to be qualitatively impaired, particularly with intravenous forms of bisphosphonate medication, which leads to inadequate remodeling of bone, necrosis
  • Osteoradionecrosis (ORN):
    • Clinically, a chronic non-healing wound of the affected jaw (most commonly mandible), typically with exposure of bone, in a patient with a history of radiation therapy to the head and neck region
    • Radiation injury to jaw that leads to ORN results from chronic hypovascularity, hypocellularity of marrow space and ultimately hypoxemia
    • Is more similar to avascular necrosis of bone than primary infection of bone, although infection or bacterial colonization can occur
  • Periapical granuloma:
    • Acute or chronic inflammation admixed with fibrous or granulation tissue locally at the apical or periapical region of a tooth
    • Is devoid of epithelium (i.e. no cyst lining) which distinguishes it from a periapical cyst
    • Periapical granuloma is located at the apex of a necrotic or partially necrotic tooth root
  • Periosteum:
    • Connective tissue membrane lining the outer / external surface bones, except at the joints of long bones
    • Is composed of an outer fibrous layer and an inner cambium / osteogenic layer (Wikipedia: Periosteum [Accessed 4 June 2018] )
  • Proliferative periostitis:
    • Represents a periosteal reaction to the presence of inflammation
    • The affected periosteum forms several rows of reactive vital bone that parallel each other and expand the surface of the altered bone
  • Sequestrum:
  • Zurich Classification of Osteomyelitis:
    • The Zurich classification system of osteomyelitis is primarily based on clinical course and features of imaging of the disease
    • Histopathology is considered a secondary classification criterion, taking into account that findings are mostly nonspecific and inconclusive by themselves; however, tissue examinations of biopsies are irreplaceable for confirmation of the diagnosis, if the clinical and radiological appearance is unclear or atypical, and to exclude possible differential diagnoses
    • The three major classifications are: (Baltensperger, Osteomyelitis of the Jaws: Definition and Classification (Figure 2.2))
      • Acute Osteomyelitis (AO)
      • Secondary Chronic Osteomyelitis (SCO)
      • Primary Chronic Osteomyelitis (PCO)
    • Further subclassification of these major osteomyelitis groups is based on presumed etiology and pathogenesis of disease
    • These criteria are therefore considered a tertiary classification criteria
    • These tertiary criteria help determine the necessary therapeutic strategies which may differ somewhat among the subgroups
Sites
  • Mainly affects the anterior chest wall, sacroiliac joints, vertebrae
  • When involves the jaws, predominantly involves the mandible
Pathophysiology
  • A number of causes have been proposed, such as altered immune response, but no single theory has received widespread acceptance
Clinical features
  • Synovitis commonly affects the anterior chest wall
    • Sternoclavicular joints are most commonly involved (63% of patients)
    • Symmetric or asymmetric joint involvement with one or many joints involved
  • Skin involvement usually precedes articular symptoms but may occur at any time
    • Skin manifestations include palmoplantar pustulosis (PPP), pustular psoriasis, psoriasis vulgaris (< 30% of cases)
    • Severe acne, specifically acne fulminans, acne conglobata and hidradenitis suppurativa, is seen in 20% of cases
  • Palmoplantar pustulosis is the most common skin manifestation (> 50% of cases), involves the palms and soles with pustular eruptions
  • Hyperostosis refers to excessive osteogenesis which radiographically is visualized as osteosclerosis
    • Often involves the sternoclavicular joints and seems to be a continuum of osteitis, a low grade inflammation of the bone
    • The most common target site for bone lesions in adults is anterior chest wall, clavicles, sternum, and sternoclavicular joints and spine
  • Osteitis refers to inflammation of bone which may involve the cortex, the medullary cavity, or both; clinically, the patient complains of bone pain and tenderness
  • 8% of SAPHO patients have inflammatory bowel disease
Diagnosis
  • Any one of the following is sufficient for diagnosis:
    1. Multifocal osteitis with / without skin symptoms
    2. Sterile acute / chronic joint inflammation with either pustules / psoriasis of palms / soles, or acne or hidradenitis
    3. Sterile osteitis in the presence of one of the skin manifestations
  • Clinical diagnosis may be challenging because the clinical picture and course of the disease may vary significantly
  • Mean time from disease onset to diagnosis is 3.8 ± 5.3 years (Semin Arthritis Rheum 2014;43:745)
  • Diagnosis can be difficult in the absence of skin lesions with only one bone site involved
  • Results of routine blood tests are not specific for SAPHO but may reveal elevated acute phase reactants such as C-reactive protein and erythrocytic sedimentation rate, and mild anemia
Radiology description
  • Inflammatory bone lesions may be detected in plain radiographs presenting as radiolucent, osteolytic or sclerotic lesions, depending on the disease stage
  • See Chronic recurrent multifocal osteomyelitis / CRMO for discussion of radiographic findings
Case reports
Treatment
  • Since SAPHO syndrome affects multiple systems, treatment is influenced by stage, extent and symptoms of disease
    • May include NSAIDs, glucocorticoids, TNF-inhibitors, bisphosphonates
  • See Table 1: Inflamm Allergy Drug Targets 2004;13:199
Clinical images

Images hosted on other servers:
Missing Image

Bilateral psoriasis

Gross description
  • Biopsies to confirm osteomyelitis and rule out neoplasia are often minute
Micro description of bone lesions
  • Bone biopsy is usually performed in atypical cases of SAPHO syndrome to rule out malignancy or infection, although it is nonspecific
  • Culture (see Diagnosis section) and PCR are useful to rule out acute and secondary chronic osteomyelitis due to infection
  • In acute osteomyelitis, bone is edematous with preponderance of polymorphonuclear leukocytes, plasma cells and prominent periostitis
  • In chronic osteomyelitis, there is a paucity of inflammation with predominant sclerosis and fibrosis
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