Long-term Voriconazole Therapy Research Articles

Successful treatment of large hemoptysis and pseudoaneurysm of the pulmonary artery associated to oesophagomediastinal fistula with amphotericin B cholesterol sulfate complex: A case report.

Oesophagomediastinal fistula is uncommon. Oesophageal fistulas, may manifest as recurrent pneumonias. While pulmonary infections can lead to pulmonary artery pseudoaneurysms (PAPs), particularly in fungal infections. PAPs pose a rupture risk, potentially causing life-threatening hemoptysis. We report a unique case of a 45-year-old male who presented with sudden cough, dyspnea, and hemoptysis. Bronchoscopy triggered massive hemoptysis, necessitating emergency embolization. Persistent hemoptysis prompted further imaging, revealing an aneurysmal dilation located next to the spine and infectious lesions, suggesting an oesophagomediastinal fistula. After initiating therapy with Amphotericin B Cholesterol Sulfate Complex and fistula closure, the patient's hemoptysis resolved, with imaging resolution of the PAP. Long-term Voriconazole therapy ensured continued improvement. This case highlights the rarity and severity of such fistulas may be associated with fungal infections and PAPs, emphasizing the importance of prompt recognition, aggressive treatment for favourable outcomes.

Unraveling the Dual Role of Voriconazole as an Antifungal Agent and Precursor to Squamous Cell Carcinoma

Voriconazole, a potent triazole antifungal medication, is extensively used to treat serious fungal infections in immunocompromised patients. Despite its efficacy, recent findings suggest a potential link between long-term voriconazole therapy and the development of squamous cell carcinoma (SCC). This review examines the dual role of voriconazole, emphasizing both its therapeutic benefits and carcinogenic risks. The pharmacodynamics of voriconazole involve the inhibition of ergosterol synthesis, crucial to fungal cell integrity. However, its metabolites, such as voriconazole-N-oxide, have been implicated in phototoxic reactions that lead to DNA damage and tumor formation. This is particularly significant in patients with prolonged drug exposure, such as organ transplant recipients, where increased SCC incidence has been observed. Clinical evidence and molecular studies suggest that voriconazole may disrupt key cellular pathways like the Hedgehog pathway, affecting epidermal differentiation and increasing cancer risk. Given these concerns, the necessity for careful therapeutic monitoring and patient education about potential risks is discussed. Alternative antifungal therapies and protective measures against phototoxic effects are also recommended as strategies to mitigate SCC risk. Future research should focus on understanding the mechanisms of voriconazole-induced carcinogenesis and refining patient management protocols. This review highlights the need for a balanced approach to voriconazole therapy, weighing its antifungal benefits against the risks of adverse dermatological outcomes.

A rare case of voriconazole-induced vertebral periostitis in a patient with invasive aspergillus spondylodiscitis

The author illustrates the first ever reported case of voriconazole-induced periostitis of vertebral body. A 66-year-old immunocompetent male patient was diagnosed with multilevel invasive aspergillus spondylodiscitis of dorsal spine and was put on long-term voriconazole therapy for the same. Initially, the patient showed a good response to treatment but later on paradoxically the patient started to deteriorate symptomatically as well as radiologically. Differential diagnosis of misdiagnosis or co-in­fection with an another mold, inadequate voriconazole blood levels, voriconazole-induced periostitis were thought. After a detailed radiological and serological investigation, the patient was diagnosed with voriconazole-induced vertebral periostitis. Based on thorough literature review, discontinuation of voriconazole therapy was opted as treatment. Clinically, the patient started improving within four weeks of cessation of therapy and was symptom-free by the end of four months. Hence, to conclude, clinicians and spine surgeons should be aware of the fact that long-term voriconazole treatment of invasive aspergillosis can be complicated by skeletal fluorosis and painful periostitis. Once the symptoms of periostitis develop, investigations such as skeletal imaging and measurement of serum fluoride levels should be performed and if periostitis deformans is confirmed, reducing the dose or ceasing voriconazole should be considered.

Voriconazole-Associated Periostitis: New Insights into Pathophysiology and Management.

ABSTRACTVoriconazole‐associated periostitis (VAP) is an underrecognized and unpredictable side effect of long‐term voriconazole therapy. We report two cases of VAP occurring in the post‐transplant setting: a 68‐year‐old lung transplant recipient who required ongoing voriconazole therapy, in whom urinary alkalinization was used to promote fluoride excretion and minimize voriconazole‐related skeletal toxicity, and a 68‐year‐old stem‐cell transplant recipient with a high voriconazole dose requirement, identified on pharmacogenomic testing to be a CYP2C19 ultrarapid metabolizer, the dominant enzyme in voriconazole metabolism. This is the first reported case of pharmacogenomic profiling in VAP and may explain the variability in individual susceptibility to this uncommon adverse effect. Our findings provide new insights into both the management and underlying pathophysiology of VAP. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

North by Northeast - a case of CNS Aspergilloma mistaken for pituitary tumour

Background Fungal pituitary sellar infection is a rare condition and can resemble a pituitary tumour. Our patient required two debridements across two continents. Case A 47-year-old diabetic man presented with history of headaches and sudden visual loss, on neuroimaging found to have an infiltrative sella lesion compressing the optic nerves. He had an incomplete transsphenoidal resection in Nigeria, with a histological diagnosis of chordoma. Ten months prior he suffered a gunshot wound destroying his femur, initially managed with an intramedullary nail, subsequently requiring implant removal, multiple debridements antibiotic spacer, ultimately leading to a Girdlestone’s. Endoscopic redo-transphenoidal-resection at Newcastle-Upon-Tyne, for cystic/solid inflammatory changes in the pituitary fossa/sphenoid-sinus/suprasellar-cisterns suggestive of residual tumour, however did not show any neoplasm. Instead, histology yielded a chronic necrotising fungal infection, morphologically suggestive of Aspergillus on Grocott/PAS-stains, with septate branching hyphae and fruiting bodies. Culture and 18s PCR of sphenoid tissue was negative. Good therapeutic response to longterm voriconazole therapy with TDM confirming adequate levels >2 mg/L, and hormone substitution for pan-hypopituitarism. He underwent further 2-stage-arthroplasty of the hip due to polymicrobial bacterial osteomyelitis but negative fungal cultures/histology. Discussion Aspergillus infection of the pituitary fossa is rare and a recognised mimic of macroadenoma/tumour. The original lesion is likely to have been aspergillus, with diabetes as a well-established risk factor for primary paranasal fungal infection, rather than iatrogenic inoculation during surgery. Radiological/microbiological features from Girdlestones’ pointed against haematogenous spread from the osteomyelitic hip.

Invasive aspergillosis of tympanomastoid cavity

Invasive aspergillosis of the tympanomastoid cavity is an extremely rare clinical incidence in comparison to the invasive fungal infections of the paranasal sinus and other parts of the body. Delay in the diagnosis and treatment of this rare clinical entity often leads to fatal complications such as skull base osteomyelitis and progressive multiple cranial nerve palsies. The invasive aspergillosis of the tympanomastoid region should be considered as a differential diagnosis for atypical mastoiditis in immunocompromised patients. Here, we report a case of invasive aspergillosis of the tympanomastoid region in a 60-year-old diabetic patient with facial nerve palsy. The diagnosis was done by the demonstration of fungi in the tissue with Gomori methenamine silver staining and confirmed with molecular diagnosis. Surgical debridement of the tympanomastoid region was done along with long-term voriconazole therapy.

ボリコナゾール（ブイフェンド®）内服中に発症した急速進行性多発性有棘細胞癌の２例

ボリコナゾール（ブイフェンド®）内服中に発症した急速進行性多発性有棘細胞癌の２例

Metformin-induced hepatitis; paliperidone-related peripheral edema; vasospastic angina induced by oral capecitabine; skin hyperpigmentation due to long-term voriconazole therapy; vaccine-associated measles.

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA's MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner.

Plasma fluoride level as a predictor of voriconazole-induced periostitis in patients with skeletal pain.

Voriconazole is a triazole antifungal medication used for prophylaxis or to treat invasive fungal infections. Inflammation of the periosteum resulting in skeletal pain, known as periostitis, is a reported side effect of long-term voriconazole therapy. The trifluorinated molecular structure of voriconazole suggests a possible link between excess fluoride and periostitis, as elevated blood fluoride has been reported among patients with periostitis who received voriconazole. Two hundred sixty-four patients from Michigan were impacted by the multistate outbreak of fungal infections as a result of contaminated methylprednisolone injections. A retrospective study was conducted among 195 patients who received voriconazole therapy at St Joseph Mercy Hospital during this outbreak. Twenty-eight patients who received both bone scan and plasma fluoride measurements for skeletal pain were included in the statistical analyses. Increased tracer uptake on bone scan was considered positive for periostitis. The primary outcome measure was the correlation between plasma fluoride and bone scan results. Blood fluoride (P < .001), alkaline phosphatase (P = .020), daily voriconazole dose (P < .001), and cumulative voriconazole dose (P = .027) were significantly elevated in patients who had periostitis compared with those who did not. Discontinuation or dose reduction of voriconazole resulted in improvement of pain in 89% of patients. High plasma fluoride levels coupled with skeletal pain among patients who are on long-term voriconazole therapy is highly suggestive of periostitis. Initial measurement of fluoride may be considered when bone scan is not readily available. Early detection should be sought, as discontinuation of voriconazole is effective at reversing the disease.

Atypical Lentigines in a Man With Mixed African American and White Race/Ethnicity Receiving Long-term Voriconazole Therapy

Atypical Lentigines in a Man With Mixed African American and White Race/Ethnicity Receiving Long-term Voriconazole Therapy

Post‐traumatic Pseudallescheria apiosperma osteomyelitis: positive outcome of a young immunocompetent male patient due to surgical intervention and voriconazole therapy

The present case describes thesuccessful treatment of an immunocompetent youngmale patient suffering from a severe, post-traumaticPseudallescheria apiosperma osteomyelitis of the tibia.Cure of the patient was achieved by long-termvoriconazole administration and surgical debridementof infected soft tissue and bone.

A Case of Periostitis Secondary to Voriconazole Therapy in a Heart Transplant Recipient

A 66-year-old man with a history of heart transplant for idiopathic dilated cardiomyopathy presented with progressive bone pain and myalgias. He has been on voriconazole for a pulmonary Aspergillus infection for 9 months. He had an elevated alkaline phosphatase of 280. There is no history of rheumatologic disease. Drug-induced periostitis has recently been reported in patients on long-term voriconazole therapy after lung transplantation for prophylaxis and treatment of Aspergillus infection. This case demonstrates the same phenomenon in a heart transplant patient. This patient's symptoms improved after discontinuation of voriconazole.

Multifocal Nodular Periostitis Associated With Prolonged Voriconazole Therapy in a Lung Transplant Recipient

We report a case of painful, nodular periostitis in a lung transplant recipient on long-term voriconazole therapy. Symptoms, signs, and laboratory abnormalities resolved quickly after drug withdrawal. The presentation more closely resembles periostitis deformans than hypertrophic osteoarthropathy, suggesting that the fluoride moiety of voriconazole may be pathogenic for this condition. Clinicians should be aware of this association.

Fluoride Excess and Periostitis in Transplant Patients Receiving Long-Term Voriconazole Therapy

We describe a heart transplant patient with painful periostitis and exostoses who was receiving long-term therapy with voriconazole, which is a fluoride-containing medication. Elevated plasma and bone fluoride levels were identified. Discontinuation of voriconazole therapy led to improvement in pain and reduced fluoride and alkaline phosphatase levels. To determine whether voriconazole is a cause of fluoride excess, we measured plasma fluoride levels in 10 adult post-transplant patients who had received voriconazole for at least 6 months and 10 post-transplant patients who did not receive voriconazole. To assess the effect of renal insufficiency on fluoride levels in subjects receiving voriconazole, half were recruited on the basis of a serum creatinine level of ≥1.4 mg/dL on their most recent measurement, whereas the other 5 subjects receiving voriconazole had serum creatinine levels <1.4 mg/dL. All control subjects had serum creatinine levels of ≥1.4 mg/dL. Patients were excluded from the study if they received a fluorinated pharmaceutical other than voriconazole. All subjects who received voriconazole had elevated plasma fluoride levels, and no subjects in the control group had elevated levels (14.32 μmol/L ± 6.41 vs 2.54 ± 0.67 μmol/L; P<.001). Renal function was not predictive of fluoride levels. Plasma fluoride levels remained significantly higher in the voriconazole group after adjusting for calcineurin inhibitor levels and doses. Half of the voriconazole group subjects had evidence of periostitis, including exostoses in 2 patients. Discontinuation of voriconazole therapy in patients with periostitis resulted in improvement of pain and a reduction in alkaline phosphatase and fluoride levels. Voriconazole is associated with painful periostitis, exostoses, and fluoride excess in post-transplant patients with long-term voriconazole use.

Voriconazole, Chronic Photosensitivity, and Melanoma

The antifungal agent voriconazole is indicated for the treatment of serious fungal infections. One of its complications is chronic photosensitivity. We recently covered a report describing the development of aggressive squamous cell carcinomas (SCCs) in immunosuppressed recipients of long-term voriconazole therapy. The same researchers now describe the occurrence of five melanomas in two patients treated with voriconazole for fungal infections. The first patient was a 39-year-old woman with Fitzpatrick skin type III who was …

Multifocal squamous cell carcinomas in an HIV-infected patient with a long-term voriconazole therapy

Multifocal squamous cell carcinomas in an HIV-infected patient with a long-term voriconazole therapy

Severe Photosensitivity Causing Multifocal Squamous Cell Carcinomas Secondary to Prolonged Voriconazole Therapy

A 32-year-old woman was treated with long-term voriconazole therapy for recurrent aspergillosis associated with chronic granulomatous disease. A short time after commencement of voriconazole therapy, a severe photosensitivity reaction developed. Continued voriconazole exposure led to the development of multifocal facial squamous cell carcinomas. The photosensitivity reaction resolved after the patient changed therapy to posaconazole.