Voriconazole-Induced Periostitis: A Mimicker of Skeletal Coccidioidomycosis.

BACKGROUND Coccidioidomycosis is caused by the fungi Coccidioides immitis and Coccidioides posadasii, which are endemic to the southwestern United States and other countries of the Western Hemisphere. Pulmonary coccidioidomycosis is the most common form of coccidioidomycosis. Rarely, coccidioidal infection disseminates to meninges, bones, skin, and soft tissues. While fluconazole remains the first line of treatment and is used for most patients, voriconazole is used in selected refractory cases of coccidioidomycosis. Voriconazole has more fluorine molecules than other azoles, and over time the fluorine molecules in voriconazole can cause disorganized bone formation in the periosteal region (periostitis), causing generalized bony pain, and radiographically can mimic skeletal coccidioidomycosis. While voriconazole-induced periostitis has been noted in aspergillosis and other infections, it has not been reported commonly in patients with coccidioidomycosis. CASE REPORT We present a case of a 50-year-old female patient with a diagnosis coccidioidal meningitis who was refractory to fluconazole and was treated with voriconazole. She presented with bony pain, which was initially radiographically attributed to multifocal skeletal coccidioidal infection. Reflecting upon the patient's history and serum levels of fluoride and bone alkaline phosphatase, a diagnosis of voriconazole-induced periostitis was made. Discontinuation of the voriconazole resulted in resolution of the periostitis. CONCLUSIONS Voriconazole-induced periostitis should be considered in patients with musculoskeletal pain with a history of voriconazole treatment or with laboratory abnormalities, such as elevated fluoride levels and/or bone alkaline phosphatase. Discontinuation of voriconazole reverses the condition promptly.

Voriconazole-induced periostitis in a patient with HIV treated for coccidioidomycosis meningitis.

Voriconazole-induced periostitis is a rare adverse effect in patients on long-term therapy, characterised by periosteal inflammation and associated bony pain. The accompanying lab abnormalities (elevated serum alkaline phosphatase and fluoride) and characteristic imaging findings (uptake of radionuclide tracer on nuclear bone scan) are critical for diagnosis. The disease process is thought to be secondary to excess fluoride from voriconazole which stimulates bone formation and decreases osteoclast bone resorption. Management includes stopping voriconazole and switching to another agent.

Voriconazole-induced periostitis.

Voriconazole is a fluorinated drug from the triazole group that is widely used in the prophylaxis and treatment of fungal infections in immunosuppressed patients. Chronic use of this medication can generate, as an adverse effect, a multifocal, asymmetric, diffuse and nodular periosteal reaction, associated with severe and disabling skeletal pain and elevated alkaline phosphatase and serum fluoride. Radiography is the imaging technique of choice for periostitis diagnosis. In general, clinical manifestations and radiographic findings disappear, when the drug is discontinued. We report the clinical case of a 44 year-old woman diagnosed with acute myeloid leukemia, who developed an invasive fungal infection treated with voriconazole after a stem cell transplant. Nine months after starting antifungal treatment, she manifested symptoms and radiological signs compatible with periostitis. Due to clinical suspicion, we decided to suspend voriconazole, with consequent resolution of clinical manifestations and radiological findings.

Voriconazole-associated periostitis presenting as hypertrophic osteoarthropathy following lung transplantation report of two cases and review of the literature.

BACKGROUND: Hypertrophic osteoarthropathy (HOA) is a syndrome characterized by abnormal proliferation of skin and osseous tissue frequently associated with underlying pulmonary disorders. Cardinal features include digital clubbing, periostitis and significant joint and bone pain. A number of recent reports have emerged of HOA and periostitis occurring in association with the antifungal agent voriconazole. METHODS: We present two additional cases of voriconazole-induced HOA and periostitis in lung transplant recipients with a review the medical literature. RESULTS: In both cases, symptoms were painful and severe enough to require opioid medication. Rapid improvement occurred within days of voriconazole cessation. A review of existing literature revealed an additional 17 cases of voriconazole-induced HOA and periostitis in lung transplant patients. CONCLUSION: We highlight the importance of recognizing the association of voriconazole with painful HOA and periostitis in lung transplant patients receiving antifungal therapy. Management of this painful condition involves cessation of voriconazole therapy, which may necessitate alternative anti-fungal drug therapies as well as adjustment of immunosuppressive drug dosage since voriconazole is a strong drug-inducer.

[Voriconazole-induced periostitis].

In this case report, a 49-year-old man was diagnosed with influenza-associated invasive aspergillosis. Voriconazole therapy was initiated and adjusted to meet therapeutic range. After 16 weeks of treatment the patient was admitted with multifocal, skeletal pains. Alkaline phosphatase was 1,900 U/L and S-voriconazole 9.9 mg/l. A bone scintigraphy and SPECT-CT were performed, and the diagnostic images along with the clinical findings were consistent with voriconazole-induced periostitis. Voriconazole therapy was discontinued, and isavuconazole therapy was initiated, and the patient's symptoms resolved completely.

Spectrum of Voriconazole-Induced Periostitis With Review of the Differential Diagnosis.

OBJECTIVE: Voriconazole is an antifungal medication used primarily for the treatment of Candida and Aspergillus infections. A fairly newly described side effect of long-term voriconazole use is periostitis. The purpose of this article is to describe the main differential consideration-hypertrophic osteoarthropathy-and other differential diagnoses, including venous stasis, thyroid acropachy, and hypervitaminosis A. CONCLUSION: With knowledge of imaging appearance, clinical manifestations, and outcomes, radiologists can make an accurate diagnosis of voriconazole-induced periostitis, and clinical teams can initiate appropriate management.

Voriconazole-Induced Periostitis After Allogeneic Stem Cell Transplantation.

A 34-year-old man with history of Hodgkin lymphoma presented 7 months after allogeneic stem cell transplantation with an unexplained severe musculoskeletal pain syndrome. A Tc-MDP bone SPECTCT showed multiple foci with moderate to intense bone uptake across the axial and appendicular skeleton consistent with periostitis. The patient had been on voriconazole daily for 4 months to treat an Aspergillus pneumonia, and in the absence of other causes, a drug-induced periostitis was suspected. Voriconazole was changed to posaconazole with complete resolution of the musculoskeletal symptoms within 3 weeks.

A vexing case of bone pain in a renal transplant recipient: Voriconazole-induced periostitis.

Immunosuppression increases the risk of opportunistic infections including fungal infections in solid organ transplant recipients. Voriconazole is used to treat invasive aspergillus infections but prolonged usage may rarely lead to periostitis. Increased plasma fluoride concentration leading to osteoblastic upregulation is thought to be the catalyst, and symptom reversal occurs with discontinuation of the offending agent. A renal transplant recipient who was on voriconazole for invasive aspergillosis developed diffuse debilitating symmetrical bone pain. Having ruled out other neurological, metabolic, and drug etiologies, voriconazole-induced periostitis was diagnosed. Increased plasma fluoride level was documented, but bone scan was non-specific. A therapeutic discontinuation of voriconazole and switch to posaconazole provided rapid symptom resolution. The patient accidently restarted voriconazole as an outpatient resulting in the same symptomology, and thus provided further evidence that this was drug related. Voriconazole-induced periostitis is a described entity in immunosuppressed solid organ transplant patients who are treated with a prolonged course of voriconazole. This case study is novel in that it demonstrates drug induced periostitis in a renal transplant recipient who developed debilitating periostitis within a short time after starting voriconazole and equally rapid resolution once it was discontinued. We conclude that patients treated with voriconazole should be routinely monitored for periostitis.

Voriconazole-induced Severe Periostitis Deformans.

Periostitis deformans is an uncommon condition of the skeletal system, mainly manifested as bone pain with or without bony swellings. Voriconazole-induced periostitis is widely reported in the literature, mainly in the organ transplant patients on immunosuppressant therapy. The patient in this case report, was not on any immunosuppressant therapy, but developed widespread periostitis deformans secondary to voriconazole, who was being treated for the base of skull aspergillus osteomyelitis. This report demonstrates the severity of voriconazole adverse effects and the wider impact on patient. Radiological features of periostitis deformans are still a cause of concern and the diagnosis of this condition is not easy due to its radiological features like bone tumours. This case report is an attempt to promote more awareness about this rare condition among both the orthopaedic surgeons and the radiologists, which will help in streamlining investigation and prompt diagnosis.

Voriconazole-induced periostitis deformans: serial imaging in a patient with ANCA vasculitis.

OBJECTIVES: A 61-year-old with acute granulomatosis and polyangiitis developed Aspergillus fumigatus pneumonia after admission to the intensive care unit with a small bowel perforation. This occurred after immunosuppression (intravenous methylprednisolone, intravenous cyclophosphamide, and plasmapheresis) for his initial presentation with stage 3 acute kidney injury. MATERIALS AND METHODS: The mycologist recommended long-term treatment with voriconazole after initial recovery. RESULTS: After 7 months of treatment, the patient complained of joint pain and swelling in his hands. Radiographs, computed tomography, and single-photon emission computed tomography appearances were consistent with periostitis. A diagnosis of Voriconazole-induced periostitis deformans was made and the voriconazole was stopped. Plasma fluoride level was 278 µg/L (normal range < 50 µg/L). Discontinuation of voriconazole led to clinical improvement. CONCLUSIONS: Periostitis deformans due to fluorosis is a rare complication of voriconazole treatment. The imaging in our case is unusually dramatic. We were able to track the evolution of periosteal reactions over serial imaging.