**Background:** Camurati-Engelmann disease (CED) is a rare autosomal dominant disorder characterized by hyperostosis of long bones causing bone pain and muscle weakness, caused by missense mutations of the TGF-β1 gene leading to overactivation of TGF-β1. TGF-β1 is a multifunctional protein that plays roles in skeletal tissue differentiation and immune cell maturation, signaling, and immune tolerance in the gut. TGF-β1 signaling serves an antiinflammatory role, and its loss is associated with chronic inflammatory processes. However, TGF-β1 can also act as a proinflammatory cytokine in the presence of TNFα. The coincidence of CED and inflammatory bowel disease (IBD) is extremely rare, with only one prior report in the literature of a patient who improved on anti-TNFα therapy.
**Methods:** This is a single case report of a 13-year-old girl with CED who was referred for new onset hematochezia and diarrhea. Her medical history included severe growth failure attributed to bone disease, years of prednisone therapy, and caloric deficit. She was on methotrexate and losartan for CED-associated bone pain. Initial laboratory investigations showed hemoglobin 12.8 g/dL, erythrocyte sedimentation rate 16 mm/h, albumin 4.4 g/dL, and fecal calprotectin 224 µg/g. The family initially refused endoscopic investigation and PEG tube placement. Two years later, the patient returned with recurrent hematochezia. Ileocolonoscopy revealed mildly friable mucosa in the distal ileum and discontinuous ulcerated mucosa in the rectum and cecum. Biopsies showed focal active ileitis, chronic active inflammation of the left colon with mild-to-moderate active inflammation in the right colon, and chronic inactive proctitis. Fibrosis was not observed. Infliximab induction was given at 5 mg/kg/dose at 0, 2, and 6 weeks with planned every 8 week maintenance. After the third dose, infliximab level was 2.3 µg/mL (no antibodies), and the fourth dose was increased to 10 mg/kg/dose. Although gastrointestinal symptoms improved, bone pain worsened, and infliximab was discontinued after the fourth dose. Budesonide was started. Two months later, bone pain improved but hematochezia, diarrhea, and abdominal pain recurred. Vedolizumab was started at 300 mg at 0, 2, and 6 weeks, then every 8 weeks. Abdominal pain and hematochezia improved after the first dose without bone pain recurrence. Hematochezia recurred after the fourth dose, so the interval was shortened to every 4 weeks with addition of hydrocortisone enemas. After the seventh vedolizumab infusion, the patient developed severe pyoderma gangrenosum requiring hospitalization for debridement. Ustekinumab was added as a single loading dose of 260 mg IV followed by 45 mg subcutaneous injection every 28 days, based on the patient's weight of 20 kg.
**Key Results:** By 6 months of dual biologic therapy (vedolizumab and ustekinumab), clinical and biochemical remission were achieved. Pyoderma gangrenosum resolved completely. The patient experienced substantial weight gain, with body mass index increasing by 41% over the first year of dual biologic therapy. Inflammatory markers decreased, and hemoglobin and albumin levels increased. Bone pain remained well controlled.
**Clinical Implications:** This case demonstrates that dual biologic therapy with vedolizumab and ustekinumab may be an effective treatment option for patients with CED and CD who cannot tolerate anti-TNFα therapy. The heterogeneity in clinical response to infliximab—improving gastrointestinal symptoms but worsening bone pain—warrants further exploration of the underlying molecular mechanisms. The complex role of TGF-β1 signaling in both diseases, including its proinflammatory effects in the presence of TNFα and its interactions with IL-12/IL-23 pathways, may explain the differential responses to various biologic agents. The authors note that it is not yet clear if ustekinumab monotherapy would achieve a similar response, and discussion to remove vedolizumab has begun with the patient and family. This case provides insights into potential precision medicine approaches for patients with overlapping rare diseases involving TGF-β1 signaling pathways.