SAPHO syndrome is a chronic disease of unclear etiology, combining bone and joint (arthritis, synovitis, hyperostosis, osteitis) and skin changes (pustulosis, acne, psoriasis, hydradenitis). Clinically manifested by psoriatic and pustular rashes on the skin of the palms and feet, conglobate acne, pain in the chest, joints, spine, sacroiliac joint. Diagnosis is based on detectable laboratory and X-ray abnormalities. NSAIDs, glucocorticoids, antimetabolites, bisphosphonates, TNF inhibitors, retinoids are used in treatment courses.
ICD 10
M07.3 Other psoriatic arthropathies
Meaning
As an independent nosological unit, SAPHO syndrome (pustular arthroosteitis, sternoclavicular hyperostosis) has existed since 1987, although the first clinical observations were described two decades earlier. The abbreviation SAPHO consists of the first letters of the five main clinical signs: synovitis (synovitis), acne (acne), pustulosis (pustulosis), hyperostosis (hyperostosis), osteitis (osteitis). To date, about 300 cases of pathology are presented in the literature, but its real prevalence is probably much higher: the frequency of pustulosis in European countries is 0.5%, while bone and joint changes on its background are diagnosed in 15% of patients. Young people are more likely to suffer from the disease (the average age is 30-40 years).
Causes
The etiology of SAPHO syndrome continues to be studied. Different researchers associate the disease with genetic, autoimmune, infectious causes. It is assumed that the genetic factor is of decisive importance: in 30-40% of patients with this disease, the carrier of HLA-B27, the leading marker of ankylosing spondylitis, is detected. The association of SAPHO syndrome with haplotypes B35+, Cw4+ has also been established. However, most cases of the disease are sporadic, not hereditary.
Associations of SAPHO syndrome with other immuno-mediated diseases are described: Crohn’s disease, NYC, seronegative spondyloarthritis, psoriasis. Triggers that trigger the manifestation of clinical symptoms of the disease can be:
- viral infections;
- chronic bacterial infection (staphyloderma, streptoderma, acne, tonsillitis, chronic sinusitis, odontogenic infection);
- intracellular infections: mycoplasmosis, chlamydia;
- hypothermia;
- injury;
- taking certain medications.
However, it is not always possible to identify the trigger factor when studying anamnesis.
Pathogenesis
SAPHO syndrome is considered as an autoinflammatory disorder occurring with osteoarticular syndrome and variable dermatological changes. The main pathomorphological link of pathology is aseptic osteitis combined with hyperostosis. The bone structures of the chest are always involved in the inflammatory process: clavicles, sternum, ribs and their joints. There may also be an interest in the spine, pelvic bones, and limb joints.
Osteitis in its clinical course is close to bacterial osteomyelitis, however, in most cases with SAPHO syndrome, microorganisms are not sown from the bone tissue. At the same time, destructive changes occur early in the lesions. Late pathohistological changes detected during biopsy include thickening of bone trabeculae and periosteum, osteosclerosis, sclerotic changes in the bone marrow.
The most typical dermatological manifestations of pathology are pustular dermatosis and acne, which indicates the defeat of sweat and sebaceous glands (hyperplasia, inflammation, violation of secretion). A skin biopsy reveals parakeratosis, pronounced neutrophil infiltration. A local increase in the level of IL-17 and IL-6 in the epidermis, as well as pro-inflammatory interleukins in the blood (TNF-α, IL-17, IL-22 IFN-γ) is determined.
Classification
Based on clinical, radiological, morphological and immunopathological characteristics in modern rheumatology, SAPHO syndrome is classified as a group of seronegative spondyloarthritis. In some literary sources there is a division of pathology into 2 forms:
- primary (idiopathic) – occurs as an independent disease;
- secondary – develops against the background of another disease (psoriatic arthritis, Behcet’s disease, NYAK).
Also, a number of researchers consider chronic recurrent multifocal osteomyelitis as a juvenile form of SAPHO syndrome.
Symptoms
In most cases, SAPHO syndrome manifests itself with dermatological symptoms. Less often, skin changes develop a second time against the background of osteoarticular manifestations. On average, 1-2 years pass between the development of cutaneous and rheumatic syndromes, but there are cases when this interval was extended to 10-20 years or lesions occurred synchronously. In 16% of cases (more often in children and adolescents), SAPHO syndrome occurs without skin damage.
Skin syndrome
Dermatological changes include palmar-plantar pustulosis (in 50% of patients), pustular psoriasis (25%), acne (19%). Pustulosis is characterized by the appearance of pustules (pustules) on the skin of the palms and feet. Also, erythema, peeling, cracks are found in the lesions. In place of the resolved pustules, yellowish-brown crusts, crater-shaped depressions, scales are formed. Palmoplantar pustulosis is a variant of pustular psoriasis, occasionally SAPHO syndrome is preceded by symptoms of vulgar psoriasis.
Acne rashes are usually represented by spherical acne. These are painful subcutaneous nodes, prone to abscessing. When opened, a creamy purulent exudate is released from them. The healing process is long, with the formation of fistulas and scars after acne. Infiltrates, opened and scarring elements can be located on one area of the skin at the same time. Bacterial damage to the apocrine sweat glands leads to the development of recurrent hydradenitis in the armpits, groin area.
Bone-joint syndrome
Aseptic osteitis is clinically expressed by soreness and swelling in the sternum, sternocostal and sternoclavicular joints, collarbones. Often there is oligo-/ polyarthritis of the metacarpal and metatarsophalangeal joints, arthritis and synovitis of the hip, knee, elbow, wrist joints. At the same time, depending on the severity of symptoms, arthralgias, joint deformities, limitation of the amplitude of movements, lameness when walking can be observed.
Spinal column lesions in the syndrome are presented in pairs by spondylitis and spondylodiscites. They are accompanied by stiffness of the spine in the cervical-thoracic and lumbar regions, dorsalgias, most pronounced in the morning. In 10% of cases, unilateral sacroiliitis develops, which is manifested by pain in the pelvis and buttocks. The same number of patients develop sclerosing osteomyelitis of the lower jaw.
Other syndromes
In some cases, the development of sialadenitis, chronic tonsillitis, and soft tissue abscesses was noted in patients with SAPHO syndrome. There are cases of a combination of pustular arthroosteitis with inflammatory bowel diseases – then abdominal pain, diarrhea, anal fissures, perianal abscesses are added to typical complaints.
Complications
SAPHO syndrome refers to diseases that dramatically reduce the quality of life, interaction with society, psychological comfort. The persistent course of conglobate acne can turn into fulminant acne with the development of a severe general hyperergic reaction of the body (multiple painful infiltrates, fever). A prognostically unfavorable sign is the addition of gangrenous pyoderma associated with the development of sclerodactyly, Raynaud’s syndrome, systemic vasculitis.
Hyperostosis is accompanied by a decrease in the mobility of the chest, spine, pain syndrome, limiting motor activity. In rare cases, fusion of the vertebrae can lead to compression of nerves, blood vessels, compression myelopathy. Spontaneous fractures are also among the complications of SAPHO syndrome.
Diagnostics
The diagnosis of SAPHO syndrome is verified taking into account clinical and anamnestic data, laboratory parameters, and radiological changes. There are no clear diagnostic criteria, however, similar pathological findings are found in most patients:
- Laboratory tests. Markers of inflammation are detected in blood tests: acceleration of ESR, leukocytosis, an increase in the level of CRP, alpha2-globulins, and the activity of alkaline phosphatase. When typing histocompatibility genes, HLA-B27 is often detected.
- X-ray of the skeleton. Chest X-ray show thickening and osteosclerosis of flat bones, ankylosis of the joints of the sternum with collarbones and ribs, spinal images reveal sclerosis of vertebral bodies, syndesmophytes, signs of discitis, sacroiliitis. Other findings include destructive symphysitis, sclerotic changes in the pelvic bones, periostitis of tubular bones, mandible. If typical radiological signs of SAPHO disease are detected, it is advisable to additionally perform a CT scan/MRI of bones and spine.
- Skeleton scintigraphy. According to the results of radionuclide diagnostics, the accumulation of radiopharmaceuticals in the foci of bone tissue damage is revealed intensively: in the body and the handle of the sternum, the sternal ends of the collarbones and ribs, ileosacral joints.
Differential diagnosis
The defeat of the bone and articular apparatus in SAPHO syndrome requires the exclusion of the following nosologies:
- bone tumors: osteoid osteoma, Ewing’s sarcoma, bone metastases;
- infectious diseases of bones: hematogenous osteomyelitis, tuberculosis of bones;
- arthritis: reactive, psoriatic;
- other skeletal lesions: Titze syndrome, Paget’s disease, Forestier’s disease, marble disease, etc.
Cutaneous manifestations of SAPHO syndrome differentiate with those in the following pathologies:
- isolated pustules;
- vulgar psoriasis;
- OK-plantar keratodermia;
- furunculosis;
- juvenile acne.
Treatment
Etiological therapy of pustular arthroosteitis has not been developed. Treatment, as a rule, is symptomatic. Anti-inflammatory and immunosuppressive therapy is prescribed for SAPHO syndrome.
Usually, treatment begins with nonsteroidal anti-inflammatory drugs. In severe cases, glucocorticoids are used orally, intravenously (pulse therapy), in the form of intraarticular and periarticular injections (for arthritis, enteritis). Resistant forms of the disease are treated with antimetabolites.
Antibacterial agents (azalides, tetracyclines), retinoids, antiandrogens are used to relieve acne. Pustulosis responds well to treatment with topical GCS, PUVA therapy. With persistent inflammatory and pain syndrome, X-ray therapy, resection of the clavicle and ribs are resorted to.
Experimental therapy
There are publications reporting effective relief of the main manifestations of SAPHO syndrome when bisphosphonates are prescribed as monotherapy, as well as in combination with calcitonin and azalides. In recent years, TNF-a inhibitors have been successfully used as targeted therapy. A number of studies have noted a positive result from the use of interleukin blockers-1, 12, 17, 23.
Prognosis and prevention
SAPHO syndrome is a rare and little–studied disease in the practice of rheumatologists, which leads to difficulties in making a diagnosis. The disease has a chronic course, often with a tendency to progression. However, in most cases, when prescribing rational therapy, the course of SAPHO syndrome can be controlled. Even in severe cases, it is possible to achieve long-term remissions. Sometimes the pathological process resolves spontaneously. In the prevention of the disease, a significant role is played by the rehabilitation of chronic infection: foci of caries, tonsillitis, pyoderma.