A 59-year-old man with a 1-month history of headache was examined in an otolaryngological clinic of a general hospital. The patient’s anterior nasal septum was swollen, and he was diagnosed with nasal septal abscess and admitted to the hospital the same day. Enhanced computed tomography (CT) revealed a swollen, ring-enhanced lesion in the anterior nasal septum (Fig. ). He was treated with incisional drainage of the abscess and antibiotic drip for 1 month (fosfomycin, ampicillin/sulbactam, ceftriaxone, and meropenem). In addition, insulin-based therapy was started because the patient had uncontrolled diabetes and hemoglobin A1c of 13.3%. His symptoms persisted despite 1 month of antibiotic drip. Pus from the nasal septum was cultured three times. Culture tests detected low concentrations of Capnocytophaga spp. and Serratia marcescens, which were sensitive to the antibiotic drip. No fungi were detected. The septal lesion was biopsied twice and showed granulation-like tissue with infiltrated inflammatory cells (nothing indicating malignancy or fungus). Despite the antibiotic drip for >1 month, diplopia developed due to bilateral abducens nerve palsy, with subsequent impairment of right eye movement and eventual visual loss. The patient was then referred to our department.\nThe patient’s initial visit revealed a saddle nose. Nasal fiberscope revealed bulging of the nasal septum and granulation-like tissue on the right side of the nasal septum. The patient’s left eye fixed at the central position and the supraduction and adduction of the right eye were limited. His visual acuities were light perception in the right eye and “count fingers” in the left eye. The functions of the 5th, 7th, and 8–12th cranial nerves were intact.\nThe patient’s hemoglobin A1c was 9.2%. Plain CT showed a poorly marginated lesion with soft tissue density at the superior nasal septum, which was invading the anterior cranial fossa. Another mass with soft tissue density appeared in the left maxillary sinus (Fig. ). A spinal tap and cerebrospinal fluid culture were immediately performed, and the results revealed elevated glucose levels (130 mg/dL) and cell counts (mononucleosis 19/m3, polynucleosis 1/m3). No pathogen was detected by microscopic examination or culture methods. Owing to the possibility of a fungal and/or bacterial infection, we prescribed an antibiotic (ampicillin/sulbactam) and antifungal (amphotericin B) drip. Subsequently, we performed diagnostic endoscopic sinus surgery under general anesthesia. Histopathological examination revealed that the ball-like lesion in the left maxillary sinus harbored fungi, with filaments slightly thinner than those of Aspergillus spp. (Fig. ). A commercially available fungal DNA detection kit (Robust HotStart ReadyMix PCR Kit; KAPA biosystems, Inc., U.S.A.) was used to detect pathogens in tissues from the nasal septal lesion and ball-like fungal lesion in the left maxillary sinus. A broad-range polymerase chain reaction (PCR) was performed targeting the highly conserved sequence of the ribosomal RNA genes in fungal DNA shared by most fungi. Internal transcribed spacer (ITS) regions in ribosomal DNA were then amplified by PCR using primers ITS1F (5′-TCCGTAGGTGAACCTGCGG-3′) and ITS4R (5′-TCCTCCGCTTATTGATATGC-3′). PCR products of 150–500 bp were obtained and sequenced to match a known DNA sequence from a reference database (BLAST: Basic Local Alignment Search Tool). The organism detected by PCR and tissue cultures was S. apiospermum. Subsequent enhanced magnetic resonance imaging (MRI) revealed strongly enhanced lesions of the nasal septum, ethmoid sinuses, bilateral orbital apexes, and cavernous sinus. The dura along the anterior and bilateral middle cranial fossa was thickened and well-enhanced. (Fig. ). The diagnosis was orbital apex syndrome and hypertrophic pachymeningitis secondary to fungal nasal septal abscess caused by S. apiospermum.\nDrug susceptibility testing (Table ) led us to change the antifungal drip to voriconazole (500 mg/day). Since voriconazole had no apparent effect on the patient’s symptoms after four days, we surgically resected the lesion under general anesthesia.\nUsing endoscopy-assisted open skull base surgery, we removed the fungal ball-like lesion and the mucosa of the left maxillary sinus. We then incised the anterior border of the nasal septum and removed the mucosa of the bilateral ethmoid and sphenoid sinuses. After anterior craniotomy, we resected the anterior skull base between both sides of the ethmoid tegmen, from the frontal table anteriorly to the optic chiasm posteriorly. We avoided the extirpation of the eye ball or removal of the orbital content, because the medial bony wall of the orbit was intact.\nThe resected nasal septum was thickened and necrotic, strongly suggesting infectious inflammation and necrosis of the tissue. Mild mucosal edema was observed in the bilateral ethmoid and sphenoid sinuses. No fungal invasion or pus was observed. The dura was thinned just above the affected part of the cranial fossa, suggesting that the infection and inflammation had spread to the dura; however, there was no apparent dural deficit, and the dura was preserved. Following resection, we reconstructed the affected anterior cranial fossa with pericranium.\nThe patient’s headache decreased and almost disappeared 3 weeks postoperatively. His preoperative mild fever and inflammation normalized, and he was discharged on postoperative day 29. The patient continued oral voriconazole (400 mg/day) until 12 months post-surgery, when bilateral ocular movements completely improved; however, loss of visual acuity persisted. At 22 months post-surgery, a follow-up MRI demonstrated that the enhanced lesion in the orbital apex diminished. Thirty months has passed without any evidence of recurrence until now. The timeline of the patient’s illness is illustrated in Fig. .
A 69-year-old Japanese woman had a macular oedema in her right eye, which occurred secondary to BRVO and was unresponsive to intravitreal injection of anti-vascular endothelial growth factor aflibercept. She was subsequently treated by STTA injection at the referral hospital twice. During the treatments, her eye was anaesthetized with 4% topical lidocaine. A sterilized eyelid speculum was used, and the superior-temporal conjunctiva was incised using sterilized scissors to inject 20 mg of triamcinolone acetonide into the posterior subtenon space. After the injection, the conjunctiva was not sutured because this step is usually unnecessary. These procedures were performed in an outpatient treatment room with wearing sterilized gloves. A 1.5% topical levofloxacin ophthalmic solution was administered four times daily for 3 days post-injection. Four months after the second injection, the patient noted a conjunctival mass that became progressively larger with a little pain and redness. She was then referred to Kindai University with a clinical diagnosis of orbital fat herniation.\nDuring her first visit, best-corrected visual acuity (BCVA) was 6/30 in the right eye and 6/6 in the left eye. Intraocular pressure was normal in both eyes. Slit-lamp microscopic examination revealed no inflammation in both the anterior chamber and vitreous. A soft, well-demarcated mass mimicking herniated orbital fat was observed in the super-temporal quadrant, which corresponded to the posterior STTA site (Fig. a). Magnetic resonance imaging (MRI) of the orbits revealed a hypo-intensity lesion on T2-weighted imaging at the super-temporal peribulbar area (Fig. b). Her white cell count and C reactive protein levels were normal.\nTo excise the conjunctival mass, first, we made an incision in the conjunctiva, and found that yellowish pus was discharged. The local administration of antibiotics was performed empirically based on the presumed diagnosis of bacterial infection. Although a strain of dematiaceous fungi was isolated from the pus 1 month later, the antifungal drug susceptibility of the strain was not determined at that time. We did not immediately administer antifungal drugs because there were no significant changes in clinical findings initially. The abscess was debrided again 2 months after the surgery through a superior forniceal incision because the orbital abscess at the same lesion had developed gradually. During the second surgery, the wound was irrigated with 0.1% amphotericin B after three large abscesses were removed. Postoperatively, she was treated with 400 mg/day of oral voriconazole because of Fungiflora Y staining of the pus (Fig. a) and the presence of a large amount of fungi by pathological examination of the abscess by Grocott’s staining (Fig. b).\nWe obtained the pathogenic strain from the abscess during the second surgery and observed it macroscopically and microscopically. The colony on potato dextrose agar medium (PDA; Difco, Becton, Dickinson and Company, Sparks, USA) had a diameter of 10 mm 14 days after inoculation and with incubation at 25 °C. The colony appeared as a moist-form pigmented yeast-like colony (Fig. a). The slide culture using lactophenol cotton blue staining revealed cylindrical conidogenous cells producing ellipsoidal conidia (Fig. b). From the Basic Local Alignment Search Tool search using the sequence of the ribosomal RNA gene internal transcribed spacer domain base, the sequence (the accession number LC566592 in the DDBJ) of this strain showed 100% similarity to those of some strains of E. dermatitidis. The isolate was thus identified as E. dermatitidis on the basis of morphology and phylogeny. The pathogenic strain in the current case was deposited at the Medical Mycology Center, Chiba University in Japan, as IFM 65961.\nMinimum inhibitory concentrations (MICs) of several antifungal drugs and the minimal effective concentration of micafungin against the strain were determined using of the broth dilution method according to M38-A2 of the Clinical and Laboratory Standard Institute (Table ). The inhibitory concentrations of amphotericin B, itraconazole, voriconazole, and miconazole against the pathogenic strain were found to be low. Based on these results, topical and systemic voriconazole were administered for 3 months. The patient’s serum beta-D-glucan levels were normal during the follow-up periods since the first surgery, and no recurrence was observed after the second drainage.