A Surgical Approach in the Management of Mucormycosis in Trauma Patients.

Introduction: Fungal infections are rare occurrence in the oral cavity. They are most often seen in other medical conditions such as the immunocompromised states, diabetes, on immunosuppressants, and more recently, among the COVID patients. There are various ways that are employed to manage these infections. The most usual of fungal infection in these conditions is mucormycosis, also called as zygomycosis. Hence, in our study, we aim to evaluate the management of the fungal infection mucormycosis in trauma patients by the surgical approach. Materials and
Methods: We piloted a retrospective observational study among 50 subjects who were admitted to the department with oral fungal infections with mucormycosis. We analyzed various clinical and demographic parameters among the subjects. The data thus obtained were analyzed with proper statistical tools deliberating P < 0.05 as significant.
Results: We observed that among the 50 subjects, the mean age was 41 ± 1.7 years. There was no significant difference between the genders and the age groups. The most common reason for the oral involvement was uncontrolled diabetes. This was followed by malignancy, specifically leukemia, AIDS, and COVID. The most common site of the involvement was the palate, followed by the mandibular region. All the subjects tested positive for the fungal hyphae of Rhizopus arrhizus which was the most common of the species. The surgical debridement along with the medical management showed satisfactory results, while one death was noted in our study.
Conclusion: Although rare, oral involvement in the fungal infection with the mucormycosis is often easily managed when diagnosed early. The proper surgical debridement is the best method of treatment along with the appropriate medications. The management of the underlying medical conditions is the primary key for the success of the treatments. Copyright:

INTRODUCTION

The fungal infections of the oral cavity have been on a raise in recent times. The common fungal infection that is usually seen is oral candidiasis. However, the other fungal infection that has been increasingly reported is oral mucormycosis. This is an opportunistic, aggressive, and rare mycotic infection. This has been associated with a raised morbidity.[123] The organism that is causative of this disease is Rhizopus arrhizus which belongs to the Mucorales family.[34] The most common of the sites that are attacked by this microbe is the “Rhinocerebral” region. It has been seen in more than 80% of the cases who are with an underlying disease. The most common medical conditions and diseases that are involved in the etiology of this mycosis are uncontrolled diabetes, malignancy, specifically leukemia, AIDS, and post-COVID surgeries. The incidence of these diseases vary among the different regions of the world such as the most common disease in developing nations is diabetes, while for developed nations is malignancies.[56]

The region of the infections for this mycosis in over half of the cases is the oral cavity. In the oral cavity, the most common site is the palate and the mandibular region.[7] These lesions show a rapid rate of progress, where in some cases may even perforate the palate even before the patient visits the doctor. The previous studies have suggested a combination of pharmacological and surgical treatments along with the regulation of the underlying medical condition.[78] However, there has been a paucity of data on the surgical approaches of oral mucormycosis after the trauma.[910] Hence, in our study, we aim to evaluate the management of the fungal infection mucormycosis in trauma patients by the surgical approach.

MATERIALS AND METHODS

We piloted a retrospective observational study among the patients who had been positively diagnosed for oral mucormycosis, at the department of oral surgery, at our tertiary care hospital and college. The ethical clearance was obtained for the study and the patients were contacted by phone and the consent was obtained for the study after the details were explained. We included the patients admitted from 2010 to 2020 for the trauma who had developed the oral mucormycosis. All the patients who had other infections were excluded. We finalized 50 subjects for the study. The incisional biopsies were collected from the included subjects during their period of stay. The subjects were included who had the direct examination for the fungi with 20% potassium hydroxide, positive culture, and a confirmatory DNA analysis specific for the mucormycosis. All the details of the subjects along with the clinical and the treatment data were recorded. The data thus collected were noted and compared. The analysis of the obtained observations was made using SPSS- Statistical Package for social service version 26.IBMCORB. which was compared using the Chi-square tests deliberating P < 0.05 as significant.

RESULTS

We observed that among the 50 subjects included in the study, majority were men. The male:female ratio was 29:21. There was no significant difference observed between the genders. The mean age of the subjects was 41 ± 1.7 years. The mean age in the females was 36 ± 1.8 years and the mean age among was 42 ± 0.39 years. There was no significant difference between the age groups of the genders. The most common site was the palate, followed by the mandibular region in almost 76% of the subjects. The other sites were tongue and gingiva. There was a significant difference observed for the site of the infections. The first symptom was reported after 11.1 ± 2.12 days during the disease evolution.

The underlying medical condition in majority was diabetes mellitus type II, followed by acute lymphocytic leukemia, hematological diseases, acute myeloid leukemia, COVID, and AIDS/HIV. There was no significant difference observed for underlying medical conditions. Direct microscopy and the culture were done in all the subjects. In majority of the subjects, the pathogen identified was Candida and R. arrhizus. There was no significant difference observed for the pathogens identified among the subjects [Table 1].

Table 1

Comparison of the various demographic and clinical parameters in the study

Parameters	Observations (n)	P
Gender
Male	29	0.258
Female	21
Age	41±1.7
Male	42±0.39	0.548
Female	36±1.8
Associated medical conditions
HIV/AIDS disease	2	0.065
COVID	5
AML	4
ALL	10
Hematologic disease	5
Diabetes mellitus	24
Type II diabetes mellitus	21
Type I diabetes mellitus	3
Presentation of the first symptom (days)	11.1±2.12
Site
Tongue	4	0.05
Gingiva	8
Palate	25
Mandible	13
Diagnosis
Histology	28
Direct microscopy	50
Culture	50
Pathogens identified
Rhizopus arrhizus	36	5.12 (significance)
Lichtheimia corymbifera	2
Candida albicans	45
Others	2

AML: Acute myeloid leukemia, ALL: Acute lymphocytic leukemia

The combination treatment with the pharmacological agents and the surgical debridement was done in 96% of the subjects, and in 4% of the subjects, only medication was prescribed. In 98% of the cases, the successful outcome was seen, while death occurred in 1 (2%) subject. There was a significant variation in the treatment and the outcome among the subjects [Table 2].

Table 2

Comparison of the treatment and outcome given among the subjects

	n	P
Type of the treatment
Pharmacological	2	0.05
Surgical + pharmacological	48
Outcome
Success	49	0.001
Death	1

DISCUSSION

Fungal infections have been reported increasingly in the last 10 years. The infection with mucormycosis is the most common among the reported cases only after candidiasis.[1112131415] The most common site of this fungal infection is the oral cavity along with the nose and the brain. The disease of mucormycosis is notorious for its fast spread and mortality and morbidity.[15]

In our study, we noted that majority were men. Our observation is similar to the study of Corzo-León et al.,[6] and Bonifaz et al.[7] In their study, they also observed that male patients had a higher incidence of mucormycosis than females. This could be due to the increased incidence of comorbidities among men than women. In our study, the most common site was the palate, followed by the mandible. This observation is in unison with the previous studies.[15] The most common underlying medical conditions in our study were diabetes mellitus-Type II and ALL. Similar observations were made in the study of Prakash et al.,[2] Patel et al.,[4] and Skiada et al.[12] The unique observation made in our study was the recent recovery from COVID among 10% of the subjects.

The common site of infection in mucormycosis was palate with the presentation of the lesion as ulcer. After the maxillary involvement, the infection progressed to nose and when untreated may enter the brain causing various manifestations. The valve less vessels and the rich blood supply in the head region are attributed to this quick and uncontrolled spread of the mucormycosis.[78910]

The site of infection becomes black due to the tissue necrosis and if untreated may rapidly perforate. This progress is aggravated by the comorbidities such as diabetes and the lack of immunity due to lower white blood cells or due to severe anemia. Some immunosuppressive conditions such as HIV/AIDS and in transplant cases, may also be associated where infection with mucormycosis is seen.

The lesions of this fungal infection closely resemble the lesions of the oral squamous cell carcinoma, lymphomas, and other fungal infections such as Aspergillosis.[710]

The involvement of the palate for mucormycosis is associated with a poor prognosis.[7810] The other sites that are seen in our study were mandible, tongue, and the gingiva. Very few studies have reported the involvement of the tongue.[1415]

The success of the treatment depends on the early diagnosis. In our study, the direct microscopy and the culture were done among all the subjects. This ensured the identification of the organism and the initiation of the treatment, and hence, a greater success rate was seen in our study. The fungal hyphae are thick, with nondichotomous branches at right angles, which differentiate them from other mycological species.[7810] The lesional biopsies are very significant when the direct fungal examinations are inconclusive. The lesional tissue shows PMNL cells, inferring the inflammation, and the necrotic cells are also seen. The special stain with the “Gomori-Grocott stain” that has the silver methamine helps in the identification of the mycotic hyphae.[714] The results from the culture are usually obtained after 3–5 days that may delay the initiation of the treatment. Similar to the previous studies of Rapidis et al.[14] and Zahoor et al.[15] In our study, the main organism for the mucormycosis was identified as R. arrhizus. Along with this, the other species identified in our study were Candida seen in 45 subjects. Candida is the most common pathogen identified in the oral cavity. It is also the most common pathogen in diabetics which is similar to mucormycosis. These two organisms compete for growth, and hence, in many patients, the mucormycosis may be wrongly diagnosed as candidiasis. This may cause a delay in the start of the treatment.[78910]

In our study, surgical debridement was done for 98% of the subjects in combination with pharmacological management. The surgical management was only by the thorough debridement. The drugs that are used are liposomal amphotericin B. This drug has been showing promising results for mucormycosis. Other antifungal drugs like Isavuconazole and Posaconazole were also used in singular or also in combinations with Amphotericin B. These drugs are easily available and are economical that abet in the wide application in the countries such as India. The management of the comorbidities has been recommended by the global guidelines for the management of the mucormycosis.[131415]

The limitations of the study were the limited size of the sample. The study is retrospective and hence inherent to the bias as there are no controls to compare.

Further prospective studies are suggested with larger samples to corroborate our findings.

CONCLUSION

Within the limitations of our study, the oral involvement may be the first presentation in the fungal infection with the mucormycosis. The underlying medical conditions influence the severity of the disease. When identified at an early stage, the mucormycosis has a satisfactory prognosis. The surgical intervention by thorough debridement along with the pharmacological management will lead to a successful outcome.

Financial support and sponsorship

This study was financially supported by the Department of Oral and Maxillofacial Surgery, Government Dental College and Hospital, Afzalgunj, Hyderabad, Telangana.

Conflicts of interest

There are no conflicts of interest.