In this case, the patient had an acute onset and a short course of illness, and died after 3 days of admission without rescue, and the cause of death was septic shock and multiple organ dysfunction syndrome caused by AIFRS. The patient's condition progressed rapidly and critically after admission to the hospital, and after transfer to the ICU, although timely emergency surgery was performed to completely debride the necrotic tissues of the nasal septum and turbinate, but due to the complication of septic shock resulting in multiple organ failure, and the death of resuscitation was ineffective.AIFRS belongs to the invasive fungal rhinosinusitis. AIFRS is a form of invasive fungal sinusitis, which is characterized by intravascular inflammation of the local mucosa, thrombosis, mucosal granulation, ulcerative necrosis, and even necrosis of the bone tissue, and mycelium can be found in the mucosa or bone on pathologic sections.AIFRS is extremely rare, and is commonly seen in immunosuppressed patients with poorly controlled diabetes mellitus, and is extremely lethal, with a mortality rate of up to 50%-80% [3, 4]. The diagnosis of AIFRS has not yet been standardized and includes the following: (1) radiographic evidence of sinusitis; (2) nasal endoscopy to confirm the presence of sinusitis; (3) histopathological confirmation of invasion of fungal hyphae into the nasal mucosa, submucosal layer, blood vessels, or bone tissues; (4) pathogenic microbiology; and (5) medical history as well as clinical manifestations[2].
According to previous literature [5, 6], AIFRS in diabetes mellitus, especially in patients with ketoacidosis, is mostly caused by fungi of the phylum Spliceomycetes, which can be up to 80%, such as Rhizoctonia solani, Rhizopus rhizopus, Trichoderma reesei, and Ploughshares, etc., which is in line with the characteristics of the disease as well as the pathology of the present case. The final pathological diagnosis of the patient's left turbinate resection in this case was Trichoderma, cerebrospinal fluid, serum and urine glucose and urine ketone indexes were significantly higher than normal values, and glycosylated hemoglobin measured 12.2%, although the patient denied a history of diabetes mellitus, the test results showed that the patient was not a short-term glucose increase, and accordingly, it was considered that the patient had type 2 diabetes mellitus. Blitzer et al [7] analysis, diabetic patients are susceptible to infection of the physiological basis of trichothecene mycoses: one is diabetic ketoacidosis environment is favorable for the survival of this type of fungi; the second is the phagocytosis of polymorphonuclear leukocytes in diabetic patients is weakened. Trichoderma often invades the vascular wall and lumen, and after invading the tissues, it first resides in the elastic lamina of the arteries or in the veins and lymphatics, inducing an inflammatory reaction and the formation of fungal emboli, leading to embolism, ischemia, and necrosis of the adjacent tissues. Mycelial invasion of blood vessels can cause progressive tissue necrosis of the nasal septum, palate, and orbital or perisinus bones.Patients with AIFRS present clinically with painless, necrotizing nasal septal ulcers (crusts), and sinusitis can lead to death with rapid orbital and intracranial invasion. The course of the disease is acute, about days to weeks, and the fungus invades the mucous membranes, submucosa, blood vessels, and bone walls of the nasal cavity and sinuses. Hematogenous spread is common. Symptoms include fever, facial pain or numbness, nasal congestion, bloody clear mucus, and rhinorrhea. It often extends to invade the orbital, intracranial, and maxillofacial regions, resulting in protruding eyes, visual disturbances, headache, altered mental status, seizures, neurologic deficits, and coma, and swelling of the soft tissues of the maxillofacial region [8].
The symptoms of the patient in this case were consistent with most of the clinical manifestations reported in the literature.The patient was initially admitted to the hospital with headache.After admission, there was a sharp decrease in vision in the left eye, left eyelid ptosis covering the pupil, loss of light reflex, paralysis of the left eye eye muscles and inability to rotate, accompanied by redness and swelling of the left side of the face and nose, decreased sensation, increased skin temperature, and ischemic changes of the skin swelling of the nasofacial region, which progressively aggravated, prior to the transfer to the ICU. Before transferring to ICU, although the patient was conscious, the patient's mental state was getting worse and worse, and the patient fell into coma again in a short time after transferring to ICU, and after successful resuscitation, emergency surgery was performed to remove the fungal infection and necrotic lesions in the nose, but the patient fell into coma again in the night of the same day, and then died after failing to be resuscitated. This is consistent with the clinical presentation of AIFRS, and septic shock due to intracranial infection may have been the primary cause of death in this patient. Previous studies have shown possible routes of spread of fungal infection into the skull: 1. direct erosion penetrating the sieve plate and the bone wall of the frontal and pterygoid sinuses into the skull; 2. intracranial spread of the fungus via the veins of the nasal cavity and sinuses into the large internal jugular vein; 3. intraorbital spread of the fungus via penetration of the bony plates of the maxillary sinus and sieve sinus into the orbit, and then via the orbital vessels or the optic foramen into the skull. Orbital complications of fungal sinusitis mainly include anterior chamber cellulitis, orbital cellulitis, subperiosteal abscess, orbital abscess, and cavernous sinus syndrome.
Invasive fungal sinusitis with orbital complications is a life-threatening disease with a mortality rate of up to 80%. In the present case, the patient had ocular muscle paralysis in the left eye, fixation of the eyeball and ptosis of the eyelid, which was considered to be the result of fungal infection involving the cranial nerves and presenting like orbital aponeurotic syndrome or cavernous sinus syndrome. Orbital aponeurotic syndrome is a clinical syndrome resulting from a series of etiologic factors involving cranial nerves II, III, IV, V, VI, and V1. The clinical symptoms of it and cavernous sinus syndrome are mainly orbital pain, decreased vision, ocular muscle paralysis, and ptosis. Our patient had a dramatic loss of vision to No Light Perception in the left eye 1 day after admission and was finally diagnosed with CRAO in the left eye, which may be associated with an inflammatory thrombus or a fungal thrombus blocking the ophthalmic artery in the left eye. Case reports of Trichophyton rubrum infection leading to AIFRS complicating monocular CRAO are rare. Yang Yongqi et al [9] reported a case of AIFRS complicated by cavernous sinus syndrome caused by Trichophyton rubrum infection in a 22-year-old young woman with type 1 diabetes mellitus, who complained of "recurrent fever, facial swelling, and loss of visual acuity for 15 days", and her ocular symptoms included gradual loss of visual acuity in the right eye to the point where there was no sense of light, a drooping of the right eyelid, a complete fixation of the eye, and an increase in intraocular pressure in the right eye. The ophthalmologist of the hospital considered that the ocular symptoms were related to the spread of sinus fungal infection to the cavernous sinus and the complication of cavernous sinus syndrome after consultation, but no further ophthalmologic imaging examination was performed and no ophthalmologic treatment was done, so he did not find out whether the loss of vision in the right eye was related to CRAO. The patient was discharged from the hospital with improvement after aggressive antifungal treatment and surgical debridement, but the vision and ocular muscle paralysis of the right eye failed to recover. Xie Jun et al [10] reported a case of AIFRS complicated with cerebral infarction caused by Rhizopus infection. On the second day after the onset of the disease, the vision of the right eye suddenly decreased to no light sensation, accompanied by obvious swelling of the right eyelid, and then gradually appeared to be unable to open the eye, and the left eye did not have any abnormality, and the ophthalmology department of the local hospital diagnosed the right eye as CRAO, and then the patient was given a puncture of the right anterior chamber of the eye to improve the microcirculation, mannitol to lower the pressure of the skull and other symptomatic supportive treatment, but the right eye vision did not improve. After the patient was treated with symptomatic supportive therapy such as right anterior chamber puncture, microcirculation improvement, mannitol cranial pressure reduction, etc., the vision of the right eye did not improve, and the patient developed optic nerve atrophy of the left eye, and the vision was reduced to photopic sensation after three months of "nasal sinus exploration + lesion enlargement excision" and antifungal and other symptomatic treatments under general anesthesia and rhinosonasal endoscopy in an emergency clinic.
In the China Clinical Case Outcomes Database [11], a case of AIFRS mixed infection with Trichoderma and Aspergillus complicated by orbital apical syndrome was reported in a 53-year-old middle-aged female diabetic patient, who was admitted to the hospital with a headache of 2 weeks' duration, which was aggravated by a swelling of the left side of the nose and face for 5 days. On the day of admission, the patient's ocular symptoms were left eyelid muscle weakness, accompanied by impaired eye movement and fixation of the eyeball, and the hospital diagnosed orbital aponeurotic syndrome on the basis of the involvement of the motor and abducens nerves, probably because the patient fell into a coma the next day after admission, so the case did not mention the loss of visual acuity, and did not ask ophthalmologists to consult with the patient to do relevant specialized examinations, so the patient did not find out whether the CRAO occurred or not., and finally the patient died in the ICU without resuscitation. It has also been reported in the literature [12]that orbital cellulitis secondary to paranasal sinusitis resulted in monocular CRAO, and after aggressive rescue treatment, vision was not restored, and the prognosis was extremely poor, but not life-threatening. Due to the rarity of AIFRS and its critical condition, ocular symptoms and signs are easily overlooked by non-ophthalmology clinicians. Previous reports in the literature of concurrent ocular disorders of AIFRS were mainly orbital aponeurotic syndrome and cavernous sinus syndrome, because the signs of ocular muscle paralysis, impaired ocular motility, pupil dilatation, and loss of light reflex are more easily detected and recognized and both of them are characterized by decreased visual acuity, whereas the CRAO The diagnosis of CRAO relies on fundus imaging, such as fundus color photography, autofluorescence, and FFA, but patients with ocular muscle paralysis, ptosis, coma, and those in urgent need of resuscitation are often unable to cooperate with further fundus examination; therefore, many case reports on AIFRS are prone to miss the diagnosis of CRAO, and in the reported cases with concomitant CRAO, the vision in the affected eyes was aphakia, and the vision of those who survived remained unrecoverable. .
Treatment: At present, there is no uniform expert consensus and guidelines on the treatment of AIFRS, early nasal endoscopy and do secretion or necrotic tissue culture and pathology section, find the causative fungus, timely to give systemic antifungal treatment and local infected necrotic tissue thorough debridement surgical treatment is necessary. The final pathologic diagnosis of this case was Trichophyton infections, and according to the latest global guidelines for the diagnosis and treatment of trichophyton diseases, it is recommended that: in immunocompromised patients suspected of having trichophyton, liposomal amphotericin B 5–10 mg/kg/d is preferentially recommended as first-line treatment in all systemic infections; if severe nephrotoxicity occurs, it can be reduced in due time, but there is insufficient evidence for the recommendation of a dose of less than 5 mg/kg/d. Exaconazole is moderately recommended for the first-line treatment of trichotillomania [13]. According to the recommendations of the Chinese guidelines for the treatment of severe sepsis/septic shock (2014) [14], empiric antifungal therapy is recommended for adult patients with sepsis or septic shock who are at high risk of fungal infection, with empiric anti-G- bacillus, G + cocci, and fungal therapy at the early stage of the disease and timely addition of liposomal amphotericin B 60 mg per day for anti-infective therapy based on pathologic and culture results. In this case, the patient was admitted to the hospital without finding the infected foci in the sinus area, and imaging such as CT and MRI of the cranium was atypical for the foci in the sinus area, so empirical antifungal treatment was not carried out in a timely manner and a small amount of hormone was used in the first department, which might aggravate the fungal infection, and the fungal infection necrosis in the sinus area was only detected after the transfer to the ICU on the second day of admission at night, and an emergency consultation with the department of otorhinolaryngology and rhinolaryngology was carried out to detect the necrotic foci in the sinus area. foci, and promptly empirically added Caspofungin acetate for broad-spectrum antifungal treatment. Caspofungin inhibits the synthesis of a basic component of the cell wall of many filamentous fungi and yeasts, i.e., β(1,3)-D-glucan, thus exerting an antifungal effect, which is more effective in controlling invasive Pseudomona aeruginosa and Candida infections [15, 16], and a study [17]confirmed that for the treatment of invasive Candida infections, Caspofungin is as effective as amphotericin B. However, this case was an invasive Trichophyton mentagrophytes infection, so the patient's inflammatory indexes kept rising after admission, with persistent fever, tachycardia, and ineffective control of the infection.
CRAO is an acute ischemic disease of the retina due to obstruction of the central retinal artery and is an acute condition leading to severe impairment of the patient's visual function or even complete loss of vision. The most common cause is embolization of the retinal artery by an embolus. The nature of the obstructing emboli can be categorized as follows: thrombotic emboli, originating from the internal carotid artery or originating from the heart, account for 15.5% of cases. Calcified emboli, usually originating from heart valve disease, 10.5%. Cholesterol emboli, 74.5%; when the possible origin of the embolus cannot be confirmed by primary screening, arterial inflammatory CRAO should be considered, especially in patients with hypercoagulable states as well as giant cell arteritis [18]. In this case, the patient was admitted to the hospital with a fibrinogen of 6.176 G/L (reference value of 2–4) and a D-dimer of 4.65 mg/L (reference value of 0-0.5), and after transfer to the ICU, the D-dimer increased dramatically from 5.76 mg/L to 15.66 mg/L, and the last value was 18.27 mg/L. The above results indicated that the patient's blood was hypercoagulable, and the patient's The white blood cell count fluctuated around 19.35-22.9210^9/L (reference value 3.5–9.5), C-reactive protein 235.14 mg/L (reference value ≤ 6), and calcitoninogen fluctuated from 1.11 ng/mL to 2.59 ng/mL (reference value 0-0.05), so the formation of thrombus was probably closely related to the fungal infection and the increasing level of systemic inflammatory factors.There have also been studies that suggest that thrombophilia plays a vital role in the pathogenesis of CRAO. Thus, proper laboratory screening should be considered in the primary and secondary prevention of those episodes, with implementing appropriate therapy as needed [19].The combination of these findings suggests that this case is a case of atherosclerotic CRAO, which is currently being treated with conservative treatments such as vasodilatation and intraocular pressure lowering, as well as aggressive treatments such as thrombolysis and Nd:YAG laser. Although there are no high-quality studies demonstrating that the visual prognosis of conservative treatment is better than that of the natural course of the disease [20], it has been observed clinically that patients who present to the clinic within 4–6 hours of onset of the disease and who are treated promptly with conservative emergency care usually do not have blindness, and typically retain light-sensitive vision and beyond. Intravenous or microcatheter intraocular arterial injection of tissue-type plasminogen activator (tPA) for the treatment of acute CRAO has been controversial because of its possible efficacy and concomitant complications. Whereas the pathogenesis of CRAO is similar to that of acute stroke, thrombolytic therapy is theoretically effective for CRAO. There have been previous case reports [21, 22] that early thrombolytic therapy is effective for CRAO, but there has been a lack of high-quality randomized controlled trials to validate this.
Previous case reports of patients with AIFRS who had been diagnosed with CRAO were treated with a conservative regimen, and like the patient in this case, the affected eye was blinded. Because similar cases of acute fungal infections are more specific, the treatment plan prioritizes systemic antifungal and anti-infection and rescue to maintain stable vital signs, and the treatment of ocular diseases such as CRAO is easy to be delayed or even ignored. If absolute contraindications such as coagulation dysfunctions are excluded, early and aggressive intravenous or intra-arterial injections of tPA may promptly release the thrombus from the blockage, and even help to alleviate the orbital aponeurotic syndrome or the cavernous sinus syndrome caused by the orbital aponeurosis. cavernous sinus syndrome leading to ocular muscle paralysis, and an aggressive treatment program is significant for the improvement of visual function in successful salvage, especially in young patients.