SAPHO syndrome

SAPHO syndrome
DiseasesDB	30718

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CEditor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Synonyms and keywords: Acquired hyperostosis syndrome

Overview

SAPHO syndrome is thought to comprise a spectrum of disorders that share some clinical, radiologic and pathologic characteristics. An entity known as chronic recurrent multifocal osteomyelitis (CRMO) was first described in 1972. Subsequently in 1978 several cases of CRMO were associated with clinical findings of palmoplantar pustulosis. Since then, a number of associations between skin conditions and osteoarticular disorders have been reported with a variety of different names including sternocostoclavicular hyperostosis, pustulotic arthro-osteitis, and acne-associated spondyloarthropathy. SAPHO was coined in 1987 and basically represents a spectrum of inflammatory osteitis which may or may not be associated with dermatologic pathology.

Definition

• Synovitis
• Acne -- commonly involving the face and upper back.
• Pustulosis -- usually involving the palms of the hands and/or soles of the feet (palmo-plantar pustulosis).
• Hyperostosis
• Osteitis

Etiology

• The etiology is still unknown [2]. The pathogenesis involves a combination of genetic and immunological components.
• HLA-B27 is more frequent in SAPHO.

Chromosome 18 plays a role in the SAPHO syndrome. LPIN2 and NOD2. LPIN2 encodes lipin 2, which is involved in modulating

apoptosis of polymorphonuclear cells, and mutations of the

NOD2 gene may lead to an abnormal immune response to

bacterial peptidoglycans via activation of the proinflammatory

transcription factor nuclear factor kappa B [19].

There are also hypotheses of infectious disease, suggesting

that bone lesions are caused by a low-virulence

pathogen [2, 13]. Different types of pathogens were isolated

from different bone sites and pustules in the skin,

including Staphylococcus aureus [20], Haemophilus parainfluenzae,

and Actinomyces, as well as Treponema

pallidum, Veillonella, and Eikenella [21]. The most

important is Propionibacterium acnes, which is identified

more often, but positive cultures can only be seen in a

small number of total bone biopsy specimens. The largest

number of P. acnes-positive biopsy specimens was proved

by Assmann and Simon [2] in their study of 21 SAPHO

patients, where 67 % of them were positive. This infectious

hypothesis is supported by increased levels of circulating

IgA in these patients and there is also evidence that intraarticular

injection of inactivated P. acnes in rats can cause

erosive joint lesions. On the other hand, according to some

of the latest considerations, since P. acnes is found in only

two-thirds of biopsies at most and the treatment with

antibiotics is effective only for as long as it is taken, it is

considered that SAPHO cannot be classified among

infections, even due to latent organisms [22–24].

There are various reports on immune system dysfunction

in SAPHO [25–29]. According to some of them,

humoral immune response is hyperactive and in others, it is

hypoactive. This is similar to the cell-mediated immune

response that has been reported as normal or hyperactive;

total immune system impairment has been reported as well

[28]. Hurtado-Nedelec et al. showed that SAPHO is characterized

by elevated IL-8 and IL-18 levels. They had not

detect any autoantibodies among their SAPHO patients,

including rheumatoid factor, anti-CCP2, or antinuclear

antibodies. IL-8 and TNFa production by purified polymorphonuclear

leukocytes (PMN) were elevated in these

patients compared to the controls, but the oxidative burst

and IL-18 production were normal. They also showed that,

after 28 days of etanercept therapy, PMN, IL-8, and TNFa

Differential diagnosis

SAPHO must be differentiated from other diseases that cause bone pain, edema, and erythema.

Disease	Findings
Soft tissue infection (Commonly cellulitis)	History of skin warmness, swelling and erythema. Bone probing is the definite way to differentiate them.
Osteonecrosis (Avascular necrosis of bone)	Previous history of trauma, radiation, use of steroids or biphosphonates are suggestive to differentiate osteonecrosis from ostemyelitis. MRI is diagnostic.
Charcot joint	Patients with Charcot joint commonly develop skin ulcerations that can in turn lead to secondary osteomyelitis. Contrast-enhanced MRI may be diagnostically useful if it shows a sinus tract, replacement of soft tissue fat, a fluid collection, or extensive marrow abnormalities. Bone biopsy is the definitive diagnostic modality.
Bone tumors	May present with local pain and radiographic changes consistent with osteomyelitis. Tumors most likely to mimic osteomyelitis are osteoid osteomas and chondroblastomas that produce small, round, radiolucent lesions on radiographs.
Gout	Gout presents with joint pain and swelling. Joint aspiration and crystals in synovial fluid is diagnostic for gout.
SAPHO syndrome (Synovitis, acne, pustulosis, hyperostosis, and osteitis)	SAPHO syndrome consists of a wide spectrum of neutrophilic dermatosis associated with aseptic osteoarticular lesions. It can mimic osteomyelitis in patients who lack the characteristic findings of pustulosis and synovitis. The diagnosis is established via clinical manifestations; bone culture is sterile in the setting of osteitis.
Sarcoidosis	It involves most frequently the pulmonary parenchyma and mediastinal lymph nodes, but any organ system can be affected. Bone involvement is often bilateral and bones commonly affected include the middle and distal phalanges (producing “sausage finger”), wrist, skull, vertebral column, and long bones.
Langerhans' cell histiocytosis	The disease usually manifests in the skeleton and solitary bone lesions are encountered twice as often as multiple bone lesions. The tumours can develop in any bone, but most commonly originate in the skull and jaw, followed by vertebral bodies, ribs, pelvis, and long bones.

Radiologic Findings

Anterior chest wall (most common site, 65-90% of pts): Hyperostosis, sclerosis and bone hypertrophy especially involving the sternoclavicular joint, often with a soft tissue component.

Above images demonstrate sclerosis and hyperostosis of the medial left clavicle (sternocostoclavicular hyperostosis), a very typical site of involvement in the SAPHO syndrome.

Spine (second most common site, 33% of pts): Segmental, usually involving the thoracic spine. 4 main presentations include spondylodiscitis, osteosclerosis, paravertebral ossifications, and sacroiliac joint involvement.

Long bones (30% of pts): usually metadiaphyseal and located in the distal femur and proximal tibia. It looks like chronic osteomyelitis but will not have a sequestrum or abscess.

Flat bones: mandible and ilium (10% of pts).

Peripheral arthritis has been reported in 92% of cases of SAPHO as well.

Children: There is a predilection for the metaphysis of long bones in the legs (tibia, femur, fibula), followed by clavicles and spine.

Treatment

Treatment of patients with SAPHO syndrome is based on clinical symptoms. Generally, treatment involves non-steroidal antiinflammatory drugs and corticosteroid medications (either in the form of topical creams, tablets, or by injection into the involved area). Topical cold applications may also help in affected areas. If unsuccessful, both sulfasalazine and methotrexate have been tried with mixed results.

References

• Skeletal Radiology. 2003 Jun;32(6):311-27.

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