Ollier Disease

Ollier disease (enchondromatosis) is a rare, non-hereditary skeletal disorder with multiple enchondromas that are often unilateral, cause deformity and shortening, and carry a high risk of malignant change. Its prevalence is about 1 in 100 000.

It is caused by mosaic somatic variants of IDH1 (R132, in about 80%) or IDH2 in cartilage cells, so it is not passed on to children in most families. Lesions appear in early childhood (often by age 5), and are mainly in the metaphyses and diaphyses of the hands, feet, femur, tibia and humerus, and in the pelvis. They tend to predominate on one side of the body. Males and females are equally affected.

Complications are limb length difference and bowing, short stature, pathological fracture, pain, restricted joint motion (hands), and malignant transformation to chondrosarcoma in about 25 to 50% of patients by middle age. Other tumours occur: brain gliomas, juvenile granulosa cell tumours of the ovary, acute myeloid leukaemia, and pancreatic and other cancers. Maffucci syndrome is the variant with haemangiomas.

Pathophysiology.

IDH1 and IDH2 mutations cause the cells to make 2-hydroxyglutarate, which inhibits histone and DNA demethylases, blocks cartilage cell differentiation, and leaves growth plate cartilage in the shaft. The proportion of affected cells, the mosaic extent, and the age at which the variant arose decide how many lesions develop and how severe they are. Further genetic events (TP53, CDKN2A, COL2A1) lead to chondrosarcoma.

Swelling and deformity of the fingers, wrists or limbs, found in childhood. Hand lesions cause expanded bony fingers, shortening and limited grip. Long bone lesions cause bowing, valgus or varus, limb length difference (up to several centimetres), and short stature. Pain is uncommon, and suggests a fracture or malignant change. Fracture after minor injury is frequent.

Examine all limbs for length, alignment, joint range and hand function, the spine, the skin for haemangiomas (to separate Maffucci syndrome), and neurological signs.

• Radiographs: multiple lucent medullary lesions with a linear or columnar pattern extending from the physis into the metaphysis and diaphysis, with fine stippled calcification (chondroid matrix), thin cortex and bone expansion.
• Whole body MRI at diagnosis maps all lesions and identifies those with a thick cartilage matrix, soft tissue mass or bone marrow oedema.
• Signs of malignant change: new pain, rapid growth, cortical destruction, a soft tissue mass, endosteal scalloping over two thirds of cortical thickness, loss of mineralisation, and lesions over 5 to 6 cm.
• Genetic testing of lesional tissue for IDH1 or IDH2; blood testing is often negative because of mosaicism.
• Brain MRI when neurological symptoms occur.

Differential diagnosis.

• Maffucci syndrome and metachondromatosis.
• Multiple hereditary exostoses and fibrous dysplasia.
• Solitary enchondroma and atypical cartilaginous tumour.
• Langerhans cell histiocytosis and metaphyseal dysplasia.

No drug has proven benefit. Treatment is surgical correction of deformity and fracture, and lifelong surveillance. Inhibitors of IDH1 are under investigation for chondrosarcoma and are not part of routine care.

Surveillance. Clinical review every 6 to 12 months, and whole body MRI every 1 to 2 years (more often with new symptoms), and imaging of any growing or painful lesion. Review of pelvic, scapular and long bone lesions, which carry the highest risk.

Surgery.

• Fracture: treat by cast or fixation, and curettage with bone graft once healed when symptomatic.
• Deformity and length difference: growth modulation with a tension band plate (hemiepiphysiodesis), corrective osteotomy, and lengthening by external fixation or an intramedullary lengthening nail, usually in late childhood and adolescence. Healing after lengthening may be slow.
• Hands: curettage and graft for deformity or fracture, and corrective osteotomy.
• Atypical cartilaginous tumour: extended curettage with adjuvant or wide resection; grade 2 or 3 chondrosarcoma needs wide excision with reconstruction suited to a growing limb.

Operative antibiotic prophylaxis. Cefazolin 2 g intravenously (3 g when weight is 120 kg or over; 30 mg/kg to a maximum of 2 g in children) within 60 minutes before incision as a single dose (repeat after 4 hours or blood loss over 1500 mL); with severe penicillin allergy, vancomycin 15 mg/kg intravenously starting 90 to 120 minutes before incision as a single dose, with levels and creatinine checked in prolonged cases.

Analgesia.

• Paracetamol 1 g orally every 6 hours as needed for up to 5 to 7 days (maximum 4 g daily; 3 g daily when weight is under 50 kg, with chronic alcohol use or hepatic impairment).
• Ibuprofen 400 mg orally every 8 hours with food for up to 5 days (maximum 1200 mg daily); avoid with eGFR under 30 mL/min/1.73 m2, peptic ulcer, heart failure or anticoagulant use.
• Children: paracetamol 15 mg/kg orally every 4 to 6 hours (maximum 75 mg/kg daily and not exceeding 4 g daily) and ibuprofen 10 mg/kg orally every 6 to 8 hours with food (maximum 40 mg/kg daily and not exceeding 2400 mg daily), for up to 5 days.

Monitoring. Alignment, limb length and function at 6-month visits during growth. Radiographs of treated limbs at 6 weeks, 3 months and 12 months. Whole body MRI every 1 to 2 years, with earlier imaging for pain. Neurological review and, in adults, symptom directed brain imaging.

Referral and escalation. Refer every patient to a bone tumour service and to paediatric orthopaedics for children. Urgent referral for a growing or painful lesion, cortical destruction, a soft tissue mass, neurological symptoms, or a pathological fracture of a large lesion.

Special groups.

• Children: correct deformity during growth; avoid unnecessary resection of benign lesions.
• Adults: the risk of chondrosarcoma and other cancers is high; life long surveillance is needed.
• Pregnancy: avoid NSAIDs in the third trimester; follow lesions in pregnancy only by symptoms and ultrasound.
• Families: recurrence in a relative is unusual because the disease is mosaic; genetic counselling is advised.