Encephalopathy with acute fulminant mucormycosis caused by skin fungal infection

Acute invasive fungal rhinosinusitis (AIFR) is characterized by invasion of the nasal cavity and paranasal sinuses, which also has a high potential of infiltrating palate, orbital, and intracranial [1]. Finally, this disease might cause vasculitis with thrombosis, tissue infarction, and central nervous system involvement. In this case report, we present a AIFR patient from the time who was admitted, she was given emergency treatment for several days, but eventually died of multiple organ dysfunction syndromes (MODs).

A 49-year-old lady, who had suffered from diabetes mellitus for 5 years, was referred to the dentistry emergency department complaining of high fever with toothache and pain from swelling in the left side of the face for 3 days without impairment of consciousness. The doctor highly suspected invasive fungal sinusitis and immediately consulted the otolaryngologist, ophthalmologist, endocrinology, immunology neurology and dermatologist considering the patient's condition. The relevant departments recommended that pathological examinations and imaging examinations be completed as soon as possible, while paying attention to the patient's vital signs and general condition.

Physical examination showed that the left eyelid and the left cheek were swollen, and there were 3 rashes on the back skin, each about 5 cm × 5 cm in size (Figure 1). Laboratory tests showed neutrophilic, leukocytosis and blood glucose concentration of 24.44 mmol/L. Sinus CT indicated left maxillary sinusitis. Insulin and ceftriaxone sodium were administered. However, the patient began to suffer from gradual impairment of consciousness.

Immediately, we administered systemic antifungal treatment (amphotericin B) and local antifungal irrigation, and waited for the pathological culture results to adjust the subsequent medication plan according to the strain.

Twenty-four hours later, the skin from the left inner iliac along the nose began to turn dark purple in color, with a relatively low temperature (Figure 2). A fungal infection was suspected as the cause of this condition, and thus biopsies samples were taken from the nasal mucosa in the left nostril. Staining of sections showed hypha mucor invading blood vessels (Figure 3). A check of the patient's recent history indicated that the patient had been suffering from rashes on the back skin for several months, and that this was continuously neglected. A subsequent biopsy from the skin patch also showed hypha mucor (Aspergillus), and MRI showed a massive cerebral infarction throughout the left hemisphere (Figure 4). The above departments continued to work hard to rescue the patient for several days. After 4-days of treatment, the patient developed MODs and passed away.

To date, several fungal species have been identified in patients with AIFRS, in which most frequently belonging to Aspergillus [2]. Normally, AIFR is a kind of life-threatening disease affects who have diabetes or hematologic malignancy patients due to the bone marrow transplantation with an incidence ranging from 1.7% to 2.6% [2, 3]. Despite several methods have been developed for the treatment of AIFR, the average mortality of it remains range from 47% to 80% [4, 5]. Meanwhile, mortality appears to be highly associated with the extent of disease [2] and the prognosis is related to whether the appropriate treatment was given in time.

For doctors, the diagnosis AIFR in time is also a challenge because some patients only present with vague or unspecific symptoms during the initial period of disease onset, such as fever, facial pain, toothache, headache [6]. Firstly, the endoscopic examination sometimes showed negative in the nasal cavity or only mucosal swelling. Secondly, radiological findings sometimes are completely normal or only show nonspecific feature (only mucosal thickening). Thirdly, the pathologic examination is with poor sensitive sometimes. Therefore, it can easily be misdiagnosed and underestimated. Upon the high-risk patient arrive, the doctor should obtain the clinical information and finish the endoscopic examination, computed tomography (CT) scan and routine blood examination as soon as possible. The most important is that, no matter the positive or negative results of the examinations above, biopsy and serum galactomannan assay should be performed simultaneously.

For this patient, she suffered from rashes on the skin for up to 1 month asymptomatically, which was ignored and misdiagnosed. Therefore, this was a case of an AIFR with encephalopathy originating from skin due to poor glycemic control, which lead to embolism of internal and external carotid artery branches and eventually encephalopathy. The early stage of AIFR might be asymptomatic. However, this can range from local infection to general severely infection or even bacteremia rapidly. Therefore, early diagnosis and immediate treatment are most important factors for better prognosis of AIFR [7]. A study showed that the time for AIFR diagnosis was directly associated with mortality (p = 0.002) [2]. Another study suggested that during the first 4 weeks of the entity, timely antifungal and surgical intervention were important for preventing several complications and, ultimately, survival [5]. Meanwhile, Early identification of it gives the multidisciplinary team, such as emergency, otolaryngology, and neurology, enough time to decide medical treatments timely based on the patient condition which might be achieve a better outcome. Another study demonstrated that early diagnosis and aggressive surgical debridement within different departments have been identified as positive prognostic factors [7, 8]. This case suggested that for diabetic patients with skin rashes, biopsy should be performed as early as possible to exclude the possibility of AIFR. Pathologically, direct examination, fungal culture and antifungal susceptibility testing are recommended in AIFS sample and can detect cases missed by other assays [1]. Normally, A single sample is sufficient for multiple assays [1]. Hematoxylin-eosin (HE) and Gomori methenamine-silver (GMS) staining are the most reliable tests to confirm fungi invasion into the tissue [6].

Although AIFR is a very urgent disease and sometimes it is not time-enough for surgical treatment, surgical intervention has been still reported as the most important factor in the treatment of AIFR [9]. Because the endoscopic surgery can reduce the fungal burden and allows for better penetration of antifungals into local involved areas in nasal cavity or nasal sinuses [9]. Meanwhile, antifungal therapy with amphotericin B should be initiated as soon as AIFR is suspected, because it is considered be the mainstay of pharmacologic treatment of AIFR [9]. Even though this patient missed the best time for surgery due to delayed treatment, surgery combined with antifungal therapy was demonstrated to be the gold standard of AIFR [2]. Diabetes or hematologic malignancy are high risk factors for AIFR, so the corresponding hypoglycemic and anti-infective treatment should also be given in time.

Yifan Meng: Writing—original draft (lead); writing—review and editing (supporting). Kuiji Wang: Resources (equal).

The authors declare no conflicts of interest.

This study was carried out according to the Declaration of Helsinki. This study protocol was reviewed and approved by the medical ethics committee of Beijing Tongren Hospital (version 1.0, 15-12-2023).

Informed consent to participate and publication was obtained from the patient prior to submission.