Case Presentation: A 19-year-old male presented with three days of fevers, cough, and pleuritic chest pain. He had a history of cystic fibrosis (CF) with lung and pancreatic involvement and allergic bronchiopulmonary aspergillosis (ABPA). Home medications were albuterol, dornase alfa, 3% normal saline, inhaled tobramycin, voriconazole, and pancrelipase. He was febrile, tachycardic, and had diminished breath sounds in the left lower lung field. Abdominal exam was benign with no hepatomegaly. Joint exam was normal. CT scan showed consolidations in left upper and lower lobes, acute-on-chronic bronchial wall thickening, and bronchiectasis.
White blood cell count was 14,000. Creatinine was normal. Alkaline phosphatase (ALP) was elevated at >1,650 units/L (normal <100). Aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, and gamma-glutamyl transferase (GGT) were normal. Bone-specific AP was elevated at 365 mcg/L (normal: 10 – 29). Parathyroid hormone, calcium, and vitamin D were normal. Serum fluoride level was undetectable.

Right-upper quadrant ultrasound was normal without evidence of ductal dilatation. Whole body bone scan showed increased radiotracer uptake in the bilateral shoulders, elbows, wrists, metacarpals, knees, and ankles. Patient was diagnosed with voriconazole-induced periostitis. Voriconazole was discontinued, and ALP subsequently trended down. Patient was started on high dose prednisone taper for ABPA.

Discussion: Voriconazole is a second-generation azole antifungal agent. Periostitis is a rare side effect of chronic voriconazole therapy, previously described in transplant patients. This is the first reported case of voriconazole-induced periostitis in a cystic fibrosis patient with ABPA.

ALP is a group of enzymes of made by the liver, bone, intestines, placenta. ALP elevation is most often seen in hepatobiliary disorder and bone disorder where there is increased osteoblast activity. Our patient had elevated alkaline phosphatase due to periostitis, an inflammatory disorder involving periosteum involving several joints.

In the hospital setting, patients frequently have elevated levels of alkaline phosphatase. GGT can help identify hepatic source of ALP elevation. Most non-hepatic causes of elevated ALP are due to bony disorders. This case highlights the importance of looking at medications as possible causative agents for elevated ALP.

Conclusions: This is the first reported case of voriconazole-induced periostitis in a patient with CF and ABPA. Periostitis should be in the differential for a patient presenting with elevated ALP while taking voriconazole.