SAPHO Syndrome

The adult classic — present in roughly two-thirds of adult SAPHO.

• History: insidious deep anterior chest ache, worse at night and in the early morning, better with movement and NSAIDs; weeks to years of relapsing episodes; often labelled "costochondritis" or "cardiac" and investigated as such.
• Distribution: sternoclavicular joints (often bilateral, may be asymmetric), manubriosternal joint, medial clavicle, first costochondral junctions.

Examination sequence

1. Inspection — patient sitting, shoulders exposed to the nipple line, arms relaxed. Look for asymmetric fullness over the medial clavicle and the sternoclavicular region; overlying erythema and shininess in active flares; venous distension over the anterior chest wall or arm swelling suggests subclavian vein compression or thrombosis.
2. Palpation — examiner stands in front, thumbs on the medial ends of both clavicles simultaneously to compare. Positive finding: a firm, bony, non-fluctuant enlargement that is warm and exquisitely tender. Bony hardness distinguishes hyperostosis from a fluctuant septic sternoclavicular abscess.
3. Provocation — cross-body adduction and forced shoulder protraction load the sternoclavicular joint and reproduce pain.
4. Vascular — assess for arm swelling, collateral veins, and compare radial pulses; document if thoracic outlet symptoms are present.
5. False positives — sternoclavicular osteoarthritis in older women, condensing osteitis of the clavicle (usually unilateral, medial clavicle, in young women, no skin disease), post-traumatic and post-catheter septic arthritis.

• Inflammatory back pain pattern: night pain, morning stiffness greater than 30 minutes, improvement with exercise, response to NSAIDs.
• Thoracic spine is disproportionately affected compared with ankylosing spondylitis.
• Lesions: vertebral corner erosions, dense sclerosis of the vertebral body, discitis-like endplate change (a classic infection mimic), non-marginal, bulky paravertebral bony bridges (differ from the thin marginal syndesmophytes of ankylosing spondylitis), and occasional vertebral collapse in children.
• Sacroiliitis: often unilateral or markedly asymmetric, with striking iliac-side sclerosis and hyperostosis.
• Examination: Schober test for lumbar flexion (position patient standing, mark 5 cm below and 10 cm above the lumbosacral junction, less than 5 cm increase on full flexion is abnormal); chest expansion; sacroiliac provocation with FABER and posterior shear. These tests localise but do not distinguish SAPHO from axial spondyloarthritis.

• CRMO/CNO in children: metaphyseal lesions of distal femur, proximal and distal tibia, and the clavicle — clavicular involvement in a child is highly suggestive of CNO rather than pyogenic osteomyelitis.
• Presentation: limp, focal bone pain, localised swelling, low or absent fever, symptoms often multifocal and symmetrical, waxing and waning over months.
• Mandible involvement (diffuse sclerosing osteomyelitis of the mandible) belongs to the same spectrum.
• Peripheral synovitis: sternoclavicular, hip, knee, ankle; usually mild and non-erosive.

• Palmoplantar pustulosis — sterile pustules on palms and soles, most tightly associated with anterior chest wall osteitis. Ask the patient to show both palms and soles; the pustules evolve into brown macules and scaling.
• Severe acne — acne conglobata and acne fulminans, typically face, back and chest; may have healed years earlier leaving scarring.
• Hidradenitis suppurativa and pyoderma gangrenosum are recognised associations.
• Timing: skin disease may precede bone disease by years, follow it by years, or never occur. Documented skin disease is supportive, not required.

• Anterior chest wall: sclerosis and expansion of the medial clavicle and manubrium, joint space narrowing and erosion of the sternoclavicular joint, ossification of the costoclavicular ligament. Plain films underestimate disease — request CT.
• Spine: vertebral corner erosion with reactive sclerosis, endplate irregularity, bulky non-marginal paravertebral ossification, occasional vertebra plana in children.
• Long bones: metaphyseal lucency with a sclerotic rim, periosteal new bone, cortical thickening.

• The best modality for hyperostosis, cortical thickening, erosion and ligamentous ossification — it defines the bony architecture and quantifies overgrowth.
• Chest CT with contrast additionally assesses subclavian vein patency where arm swelling or collateral veins are present.
• CT is also the modality that most often triggers a cancer referral: dense sclerosis with cortical expansion is easily reported as sclerotic metastasis or osteosarcoma. Correlate with distribution and skin history before booking a biopsy.

• Sequences: STIR or T2 fat-saturated for bone marrow oedema (the marker of active disease); T1 for marrow replacement and to assess a mass; post-gadolinium T1 fat-sat where infection or tumour remains in the differential.
• Active SAPHO: confluent marrow oedema in medullary bone, periosteal and soft-tissue oedema, synovitis; no drainable abscess and no sequestrum.
• Chronic SAPHO: T1 and T2 low signal (fibrosis and sclerosis) with cortical thickening — a "burnt-out" appearance with little oedema.
• Whole-body MRI (STIR) is now the preferred whole-body tool, especially in children, revealing clinically silent symmetrical metaphyseal lesions and avoiding ionising radiation.

• Technetium-99m bone scintigraphy shows intense tracer uptake in the manubrium and both sternoclavicular regions — the "bull's head" sign (sternum as the skull, sternoclavicular joints and medial clavicles as the horns).
• The sign is highly characteristic but not universal or pathognomonic; a negative or atypical scan does not exclude SAPHO.
• Value: demonstrates multifocality, identifies clinically silent lesions, and directs biopsy to the most accessible active site if biopsy is needed.
• FDG-PET/CT shows uptake but cannot reliably separate SAPHO from infection or malignancy — it does not replace biopsy where malignancy is a real concern.

When biopsy is genuinely indicated

• A solitary lesion, particularly in a child or adolescent (Ewing sarcoma, osteosarcoma, lymphoma, Langerhans cell histiocytosis, pyogenic osteomyelitis).
• Atypical features: rapid growth, a soft-tissue mass, permeative destruction, systemic toxicity, weight loss, night sweats.
• Adults with a sclerotic lesion and a cancer history or an abnormal screening panel.
• Failure to respond to an adequate medical trial where diagnostic doubt persists.

When biopsy can be avoided: a typical multifocal distribution with characteristic imaging plus a supporting skin phenotype in a well patient.

How to biopsy — image-guided or open, along a line resectable at any subsequent oncological surgery; take multiple cores, both microbiology and histology, and send extended cultures (14 days, anaerobic) to capture Cutibacterium acnes. Warn the pathologist that SAPHO is in the differential, otherwise early neutrophil-rich lesions are reported as acute osteomyelitis and chronic lesions as chronic sclerosing osteomyelitis or a low-grade tumour.

Histology: early — neutrophilic infiltrate with marrow oedema; intermediate — lymphocytes, plasma cells, histiocytes; late — marrow fibrosis, reactive woven bone and sclerosis. No organisms, no granulomas, no malignant cells.