A previously healthy 12-year-old girl presented with a 2-year history of chronic progressive bilateral knee pain, worsening in the preceding 6 months. Her symptoms were episodic and variable in duration and severity, with difficulty participating in sports. She had a 2.5 kg weight loss over 2 months and low BMI of 14 kg/m2. She denied any gastrointestinal symptoms, oral ulcers, skin changes, or ocular symptoms. She had not tried any specific treatments or interventions. She is of South Asian background and the product of a non-consanguineous relationship. There is no relevant family history of CRMO, autoinflammatory disease, or IBD. Examination showed fullness and tenderness in both medial femoral condyles. Her abdominal and perianal examinations were benign.
Initial investigations showed a normocytic anemia (Hb 112 g/L, MCV 79 fL), raised transaminases (ALT 84, AST 81, ALP 227, GGT 146 U/L), and raised inflammatory markers (ESR 94 mm/hr., CRP 15 mg/L). X-rays of the hips, femur, and knees showed distal femoral metaphyseal lytic lesions with surrounding sclerosis, and MRI of the lower limbs revealed multifocal distal femoral bone marrow abnormalities with regional edema pattern, cortical thickening, and periostitis (Fig. 1). A whole-body MRI revealed additional bone marrow edema pattern involving bilateral medial clavicular heads and right acromion.
The patient was treated with a single dose of intravenous zoledronic acid (0.0125 mg/kg) with significant clinical improvement and improved mobilization, but demonstrated persistently abnormal liver enzymes (AST 71, ALT 67, GGT 124 U/L), anemia (Hb 106 g/L), and raised inflammatory markers (ESR 82 mm/hr) and gamma globulins (IgG 30.1 g/L, IgM 3.3 g/L). Conjugated bilirubin was < 0.2umol/L, albumin was 42 g/L, and INR was 1.0. The patient remained asymptomatic without abdominal pain or bowel alterations, jaundice, or pale stools.
Further workup with pediatric gastroenterology was concerning for Type 1 Autoimmune Hepatitis (AIH) with Anti-Smooth muscle > 1:640, ANA negative, Anti-LKM negative, and ANCA negative. Abdominal ultrasound showed mildly heterogeneous liver echotexture but a normal biliary tree; magnetic resonance cholangiopancreatography was normal. Transient elastography showed increased liver stiffness (8.8 kPa, IQR/median of 7%). Liver biopsy showed features of both small-duct PSC and AIH, with interface hepatitis with plasma cells, concentric fibrosis of bile ducts, grade 3–4 hepatitis and stage 3–4 fibrosis. Other diagnoses including hepatitis B/C and tuberculosis, Wilson disease and celiac disease were excluded.
Although the patient was asymptomatic, given the strong association between PSC and IBD, the patient’s fecal calprotectin was measured. This was elevated at 615 μg/g, and so she underwent gastroscopy and colonoscopy. This showed chronic mildly active colitis (non-granulomatous) from cecum to rectum with normal terminal ileum, and normal upper endoscopy, leading to a diagnosis of ulcerative colitis.
The patient’s liver and gastrointestinal disease was treated with oral prednisone (35 mg oral daily), azathioprine (75 mg oral once daily), and ursodeoxycholic acid (250 mg oral daily) with sufficient adherence. No reported adverse effects were reported. There was normalization of liver biochemistry and liver stiffness (5.5 kPa with IQR/median 19%) within 6 months. The patient’s musculoskeletal symptoms remain inactive 11 months since initial therapy with zoledronic acid.