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.

Florid reactive periostitis of the clavicle: A case report and literature review.

RATIONALE: Florid reactive periostitis (FRP), a rare reactive bone lesion, typically presents in the short tubular bones of the extremities, with infrequent occurrences in the long tubular bones. This report discusses a unique case of FRP in the clavicle, managed through comprehensive lesion debridement and bone grafting, yielding positive results over a 3-year duration. PATIENT CONCERN: A 25-year-old male presented with a discernible mass at the left sternal end of the clavicle, discovered incidentally 2 weeks prior. The patient exhibited no clinical signs of inflammation, pain, sinus tract, or suppuration. DIAGNOSIS: Initial pathological examination of the local excision suggested benign lesions, although malignancy could not be ruled out. A definitive diagnosis of clavicular FRP was reached post complete lesion resection, with supporting evidence from postoperative pathology, imaging, and clinical symptoms. INTERVENTION: The left clavicle was reconstructed through an open surgical procedure involving total mass removal and ipsilateral extraction of an iliac bone of suitable dimensions. This was implanted into the clavicular bone defect and internally fixed with a plate. OUTCOMES: Three years of consecutive follow-up revealed no recurrence of hyperplasia, absence of mass or tenderness at the left sternal end of the clavicle, and unimpaired function of adjacent joints. LESSONS: The primary clinical challenge with FRP is its diagnosis. While pathological diagnosis remains crucial, it is also important to incorporate imaging and clinical symptoms for a comprehensive assessment. Complete mass excision may offer specific benefits in distinguishing FRP from its malignant counterparts.

An Enigmatic Case of Skeletal Fluorosis: Inhalant-Induced Toxicity.

ABSTRACT: Skeletal fluorosis is more common in the developing world, but is occasionally seen in the United States. We present radiographic, scintigraphic, CT, and clinical images of a 26-year-old woman with rapidly progressive, debilitating, polyostotic periostitis, and diffuse osteosclerosis typical of skeletal fluorosis. Laboratory analyses supported this diagnosis. The source of excess fluoride intake was elusive until a concurrent mental health workup revealed the patient's proclivity for inhaling air-duster cans containing difluoroethane. Difluoroethane inhalant abuse is an increasingly reported cause of skeletal fluorosis that astute clinicians should recognize. Discontinuation and sobriety from this toxic agent are essential for recovery.

Using disproportionality analysis to explore the association between periostitis and triazole antifungals in the FDA Adverse Event Reporting System Database.

Though triazole antifungals are the first choice for preventing and treating invasive fungal infections, periostitis caused by voriconazole has been described in emerging case reports; however, no studies exist on this association in real-world clinical settings. Our study aimed to identify the association between periostitis and triazole antifungals by analyzing data from the FDA Adverse Event Reporting System (FAERS). We extracted and analyzed reports on the association between periostitis and triazole antifungals in FAERS from the first quarter of 2004 to the second quarter of 2022 using OpenVigil 2.1. Disproportionality analysis was performed to evaluate the association between periostitis and triazole antifungals, and chi-squared (χ2), relative reporting ratio (RRR), reporting odds ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural networks (BCPNN) of information components (IC) were reported. In total, 143 patients experienced periostitis while using voriconazole. Disproportionality analysis identified an association between periostitis and voriconazole (χ2 = 82,689.0, RRR = 583.6, 95%CI [472.4, 721.1], PRR = 1808.9, 95%CI [1356.0, 2412.9], ROR = 1831.7, 95%CI [1371.6, 2446.3], IC = 9.2, 95%CI [8.6, 9.8]). However, no safety signals were observed between periostitis and other triazole antifungals. When stratified by sex and age, disproportionality analysis identified positive signals between periostitis and voriconazole. The possible association between periostitis and voriconazole should attract sufficient attention in clinical practice. Alternative treatment with other triazole antifungals can be considered, and causality needs to be verified in further prospective studies.

Identification of Pathogenic Microflora and Its Sensitivity to Antibiotics in Cases of the Odontogenic Purulent Periostitis and Abscesses in the Oral Cavity.

Odontogenic infections are the most common infectious and inflammatory diseases of the maxillofacial area and problem of the causative pathogen identification is an actual task, part of a permanent process of updating and modernization of treatment and diagnostic protocols and standards. In presented study a purulent exudate from 13 patients with acute purulent odontogenic intraoral lesions was studied by bacteriological method with detection of sensitivity to antibacterial agents. Bacteriological studies showed that genus Streptococcus predominated in 69.23% cases. Pathogenic microorganisms in clinically significant concentrations (105 per 1 ml and above) (Streptococcus and Staphylococcus) were resistant to Tetracycline and Doxycycline, had moderate sensitivity to macrolides in 22.22% and resistance in 77.78%. Amoxicillin/clavulanate caused effective growth retardation in 22.22% cases and moderate delay - in 77.78% without cases of resistance. Sensitivity to cephalosporins was detected in 50.00% cases, moderate sensitivity - in 38.89%, resistance - in 11.11%. Fluoroquinolones were the most effective - sensitivity in 72.22% cases, moderate sensitivity - in 22.22%, resistance - in 5.56%. The most effective fluoroquinolones were Moxifloxacin and Ciprofloxacin. The highest resistance to antifungal agents was shown by genus Candida, antifungal susceptibility was observed only in 20.00% cases. The microbiota of purulent odontogenic inflammation in the oral cavity was identified in clinically significant concentrations in only 61.54% cases with predominance of Streptococcus. The most effective antibacterial agents for odontogenic purulent process may be considered among cephalosporins and fluoroquinolones. There is a need to repeat similar studies in other regions of Ukraine and at other times of the year.

Recurrent osteomyelitis with proliferative periostitis after segmental resection and reconstruction of the mandible: a case report.

A 50-year-old patient presented with a two-year history of chronic osteomyelitis of the left mandibular body. It was treated by wide segmental resection of the left hemimandible and reconstruction with a free vascularized fibular graft. Six months after surgery, the patient returned with pain, swelling, and moth-like lesions in the transplant in combination with appositional bone formation surrounding the ossified fibular bone. Radiographic and histological examination led to the diagnosis of a recurrent osteomyelitis with proliferative periostitis affecting the resected and reconstructed mandible. Application of ibandronate led to a significant symptom decrease.

[Bilateral periostitis and arthritis: about a case of hypertrophic osteoarthropathy]. / Périostite bilatérale et polyarthrite : à propos d'un cas d'ostéoarthropathie hypertrophique pneumique.

We report the case of a 67-year-old female patient presenting swelling of the hands and feet and pain in both legs. Clinical examination and bone scintigraphy identify the triad "digital clubbing - arthritis - bilateral periostitis of the long bones", leading to a diagnosis of hypertrophic osteoarthropathy, a syndrome usually associated with pulmonary neoplasia. The thoracic CT-scan, followed by a biopsy, effectively diagnosed a right upper lobe adenocarcinoma. Surgical treatment of the neoplasia allowed the resolution of the clinical complaints and the pathological scintigraphic findings.

Nous rapportons le cas d'une patiente de 67 ans présentant des gonflements des mains et des pieds ainsi que des douleurs des deux jambes. L'examen clinique et la scintigraphie osseuse identifient la triade «hippocratisme digital - arthrites - périostite bilatérale des os longs¼, permettant de poser un diagnostic d'ostéoarthropathie hypertrophique, un syndrome habituellement associé à une néoplasie pulmonaire. Le scanner thoracique, suivi d'une biopsie, ont en effet diagnostiqué un adénocarcinome localisé au niveau du lobe supérieur droit. La prise en charge chirurgicale de la néoplasie a permis la résolution des plaintes cliniques et de l'aspect scintigraphique pathologique.

Bisphosphonate therapy in chronic diffuse sclerosing osteomyelitis/tendoperiostitis of the mandible: Retrospective case series.

This study aims to evaluate short-term and long-term results of bisphosphonate therapy in patients with diffuse sclerosing osteomyelitis/tendoperiostitis (DSO/TP) of the mandible. Eighteen patients (12 female, 6 male) aged 34.8 ± 22.2 years with DSO/TP of the mandible that were treated with bisphosphonates were included. In 16 patients, the bisphosphonate treatment led to remission with decrease of symptoms (pain, swelling of the cheek, trismus, tenderness of masticatory muscles) with a follow-up period of 4.5 (0.8-11.9) years between start of bisphosphonate treatment and latest follow-up consult. Of these, three patients were still in need of regular bisphosphonate therapy. Two patients were lost to follow-up. Bisphosphonate therapy is a treatment option for DSO/TP of the mandible that is associated with a high chance of remission of symptoms. Within the limitations of the study it seems that this treatment might be an effective second step in DSO/TP refractory to conservative treatment.

Spectrum of voriconazole-associated periostitis in clinical characteristics, diagnosis and management.

PURPOSE: Previous knowledge about the relationship between voriconazole exposure and periostitis was mainly based on limited case reports and few retrospective studies. The purpose of this study was to assess the clinical characteristics, diagnosis and management of voriconazole-associated periostitis. METHODS: Case reports and case series from 1998 to November 30, 2021 on periostitis induced by voriconazole were collected for retrospective analysis. RESULTS: Forty four patients (18 male and 26 female) from 34 studies were included in total. The median age was 58 years (29-74). The majority of patients had undergone organ transplantation (50.0%) or suffered from hematologic malignancy (31.81%). The median onset time of symptoms was 6 months after the start of voriconazole. The most common initial symptom was diffuse skeletal pain (68.28%) which can be severe and even disabling (66.7%). Ribs (37.21%), femurs (32.56%), scapulae (25.58%), humerus (23.26%), and clavicle (23.26%) were the common involved locations. Most cases were accompanied by different degrees of elevated serum alkaline phosphatase and fluoride level, while some presented with elevated bone-specific alkaline phosphatase. The main radiological features included periosteal reaction and multifocal high radiotracer uptake on bone scintigraphy. The formation of new bone was characterized with bilateral, irregular, nodular, as well as high density. The resolution of symptoms was observed with discontinuation of voriconazole in all patients, of whom 18 patients (52.94%) were relieved within a week. Itraconazole, posaconazole or isavuconazole were safe alternatives to voriconazole in voriconazole-induced periostitis. CONCLUSION: Voriconazole-induced periostitis is an infrequent complication characterized by bone inflammation involving one or multiple skeletal areas. Bony pain, elevated serum alkaline phosphatase as well as fluoride level are suspicious signs during voriconazole treatment.

Recurrent Tibial Periostitis Due to Blunt Trauma.

Periostitis is characterized by periosteal inflammation surrounding tubular bones. The pathophysiology is now considered to be multifactorial and a spectrum of disorders, recently being redefined as medial tibial stress syndrome (MTSS). Current treatment modalities include preventative and conservative measures, such as activity modification and footwear alterations. There is a paucity of literature for more invasive treatments, such as steroid injections. In conflict with the currently available limited literature, this study reports a case of recurrent tibial periostitis due to blunt trauma treated with steroid injections resulting in symptom resolution and no adverse events. While this case may suggest a therapeutic role for steroids in the treatment of MTSS from blunt trauma, it also highlights the need for additional studies to elucidate the safety profile and therapeutic efficacy of steroid injections.

Chronic Osteomyelitis With Proliferative Periostitis of the Mandible in a Child: Report of a Case Managed by Immunosuppressive Treatment.

BACKGROUND: Osteomyelitis with proliferative periostitis is a relatively uncommon inflammatory condition of the jaws, mainly characterized by periosteal formation of reactive bone. It primarily affects children and adolescences, also referred to as Garre's osteomyelitis, more frequently involving the molar region of the mandible. Cases lacking an obvious source of infection may have an immunologically mediated etiopathogenesis, falling under the spectrum of primary chronic osteomyelitis or chronic recurrent multifocal osteomyelitis (CRMO). CASE REPORT: Herein, we present a case of chronic osteomyelitis in a 6.5-year-old girl, who suffered from recurrent painful episodes of swelling of the mandible for the last 2 years, previously requiring hospitalization and administration of intravenous (IV) antibiotics and NSAIDs with limited responsiveness. The biopsy showed features consistent with osteomyelitis with proliferative periostitis. The patient was initially managed with an IV combination antibiotic regimen with only partial improvement. The possibility of an autoimmune mechanism in the context of primary chronic osteomyelitis or CRMO was considered, and immunosuppressive therapy (TNF inhibitor etanercept along with corticosteroids and methotrexate) was administered, resulting in clinical resolution. CONCLUSIONS: Osteomyelitis and its childhood variants are relatively rare and their management presents several challenges. Although typically treated with administration of antibiotics, possibly along with surgical intervention, other treatment modalities may be necessary for resilient and persistent cases. In a subset of cases, especially in the absence of local infectious factors, immunologically mediated mechanisms may play an important role and appropriate immunosuppressive therapy may be effective.

Some Reactive Lesions of Bone Are Probably Neoplasms.

CONTEXT.­: A number of fibro-osseous and osteocartilaginous lesions, especially common in the small bones of the hand and feet, pose a diagnostic challenge and have historically been thought to be reactive lesions. However, modern molecular techniques when supplementing clinical, radiographic, and histologic evaluation suggest they may, in fact, be neoplasms. OBJECTIVE.­: To review the clinical presentation and histopathologic, molecular, and radiologic features of selective bone lesions, focusing most specifically on subungual exostosis, florid reactive periostitis, and bizarre periosteal osteochondromatous proliferation. DATA SOURCES.­: Literature review and personal experience are the sources of this review. CONCLUSIONS.­: Some lesions previously thought to be reactive are locally aggressive and demonstrate reproducible molecular abnormalities, and thus may be neoplasms. Although most common in the bones of the fingers and toes, these lesions also occur in long and other bones. The clinical presentations, radiologic appearances, and histopathologic features often overlap, making the diagnosis challenging, and these lesions may require molecular evaluation to maximize accurate prognostication.