Ansel Mucormycosis Staging and Outcome Evaluation Score: Our Experience in Soaring Stage of Mucormycosis

Abstract

To propose Mucormycosis staging and Outcome evaluation score. (i) To provide method of conveying clinical experience to others without ambiguity. (ii) To facilitate an estimation of prognosis. (iii) To provide useful information for treatment decision. Retrospective observational study. Tertiary care center, Rajkot. 556 confirmed operated case of mucormycosis. It was a single center observational study of 556 confirmed cases of mucormycosis. In suspected cases of fungal infection, clinical symptoms were noted along with covid history and comorbid condition. Clinical findings were noted after nasal endoscopy. Rest neurological examination was done to rule out CNS involvement. Representative sample from nasal mucosa sent for microbiological examination. MRI PNS with Brain and Orbit was advised. After surgery, specimen was sent for histopathological confirmation. We reported most common age group was 51–60 years. 52% cases presented early with only nasal involvement and 1.8% cases with late cerebral involvement presentation. From recorded all above findings we have described this diseases progression in 4 components limited to nasal, orbital, palate and/or skull base, cerebral involvement. It is bases on anatomical progression on clinical and radiological findings. Considering all four components, staging system is designed that includes stage I to stage Vb. Outcome evaluation score designed to consider factors like patient’s age, comorbidity, stage of disease while presentation, IV antifungal coverage and patient’s psychological condition. Our clinical and radiological diagnostic staging and outcome evaluation score may helpful for others for early and better management of mucormycosis.

Introduction

Mucormycosis was rare diaease but now it is roaring after second wave of COVID 19 infectioon. It is serious angio-invasive infection caused by a group of fungi called mucormycetes. Mucormycosis is an aggressive, life-threatening infection. A hallmark of mucormycosis infection is the presence of extensive angioinvasion with resultant vessel thrombosis and tissue necrosis [1]. Treatment usually consists of antifungal medications and surgery. India has reported a recent surge in mucormycosis cases. The incidence rate of mucormycosis globally varies from 0.005 to 1.7 per million population. In India, prevalence of mucormycosis is estimated as 140 per million population, which is about 80 times higher than the prevalence in developed countries. In a systemic review and meta-analysis of 851 cases reports published in 2018, death was reported in 46% patients. Case fatality was observed to be highest among patients with disseminated mucormycosis 68% and lowest in those with cutaneous diseases 31% [2]. Considering sudden rise of mucormycosis cases, government of India has declared epidemic disease.

In our institute, we have noticed sudden rise in cases of fungal infection after second wave of COVID 19 pandemic. We have recorded data of clinical and radiological involvement of disease. Based on that, we have designed one staging system considering sino-nasal, orbital, palatal, cerebral involvement.

Methodology

It was a single center observational study of 556 confirmed cases of mucormycosis. In all suspected cases of fungal infection, clinical symptoms were noted along with covid history and comorbid condition. Clinical findings were noted after nasal endoscopy. Rest neurological examination was done to rule out CNS involvement. Representative sample from nasal mucosa sent for microbiological examination. MRI PNS with Brain and Orbit was advised. Ophthalmogical and cardio-respiratory assessment done in each cases before taking for operative procedure. In case of cerebral involvement neurosurgeon opinion taken. With patient and relative positive consent, patient was taken for surgical debridement of involved area. After surgery, specimen was sent for histopathological confirmation. We recorded multiple variant of fungal infection in histopathology reports. While designing staging system, we considered only confirmed cases of mucormycosis. All the patients were treated with IV anti-fungal coverage according to extend of disease post operatively. Oral antifungal treatment given on discharge for 3 months. Patients were followed regularly in OPD for nasal endoscopy for 3 months. Outcome of the disease evaluated at the end of 3 months.

Results

We reported most common age group was 51–60 years followed by 41–50 years and 61–70 years. 65.10% were males and 34.89% were females. In 84.50% cases, there was positive history of COVID 19 infection.

77.90% cases were having diabetes mellitus. Amongst them 27.60% were having uncontrolled diabetes mellitus (HBA1c > 8–9) and 11.7% cases were in diabetic ketoacidosis state. Other comorbidities like hypertension (16.9%), ischemic heart disease (7.3%), and morbid obesity (1.8%), hematological disorder (0.52%) were also noted.

52% cases presented early with only nasal involvement, 26.6% cases with rhino palatal involvement, 8.6% cases of rhino-orbital involvement, 6.1% cases of rhino-orbital-palatal involvement, 4.9% cases with rhino-orbital-cerebral involvement and 1.8% cases with all four components like rhino-orbital-palatal with cerebral involvement.

Amongst 556 patients, representative sample send for KOH was reported positive for fungal infection in 62.6% cases.

In histopathological examination report, 96.8% cases were confirmed for mucormycosis infection and 3.2% cases of mucormycosis associated with aspergilus fungal infection.

From recorded all above findings we have described this diseases progression in 4 components limited to nasal, orbital, palate and/or skull base, cerebral involvement. Considering all four components, staging system is designed that includes stage I to stage Vb. It is bases on anatomical progression on clinical and radiological findings. By considering staging system we found mortality of 6.66% in stage I though it is early stage. This led us to think about some other factors are having important role in disease progression. So Outcome evaluation score is designed by us to consider factors like patient’s age, comorbidity, stage of disease while presentation, IV antifungal coverage and patient’s psychological condition.

Ansel Mucormycosis Staging System

Introduction

• Staging is system designated to express the relative severity or progression of the disease.

• Staging is based on clinical and radiological findings.

Rules of Ansel Staging System

• For describing the anatomical progression of the disease.

• Based on four components:

  • N: Nose and para nasal sinuses
  • O: Absence or presence of Orbital involvement
  • P: Absence or presence of Palate and skull base involvement

• C: Absence or presence of Cranial involvement

Aim and Objectives of Ansel Staging System

• To provide method of conveying clinical experience to others without ambiguity.

• To facilitate an estimation of prognosis.

• To provide useful information for treatment decision.

Strength of Ansel Staging System

• Simplicity

• Lack of need of special technology

• Relative accuracy

Limitation of Ansel Staging System

• Based on limited number of patient’s findings.

Discussion

To deal with aggressive angio-invasive fungal disease, early diagnosis, multidisciplinary approach and adequate surgical debridement with medical management is must. For early diagnosis, one should know about disease from its roots like anatomical progression and pathophysiology. In our experience of treating large number of cases of mucormycosis, we got promising results in terms of good survival and less morbidity. From recorded data of clinical symptoms and radiological findings, we tried to describe disease progression in relation to its outcome. This might help others for early diagnosis of disease so one can get sound knowledge of disease progression and can get good results at the end of treatment. Already two types of staging are there for mucormycosis like “Code mucor” by Santosh G Honavar Editor, Indian Journal of Ophthalmology [3], and another one is by ‘King George's Medical University- Mucormycosis Treatment & Coordination Committee [4]. These both staging system describes progression of disease in single anatomical area. And in these both staging, stage of disease changed with involvement of nearer site, even though it is earliest involvement. These both can be very helpful to describe disease progression.

According to our experience, involvement of nearby site doesn’t mean change of staging of disease. There may be earliest changes in nearby local site. It doesn’t lead to change in overall prognosis of patients. So this controversies led us to stage the disease according to prognosis and outcome of patients we got. First we have describe disease progression in each local anatomical site (Tables 1, 2, 3, 4). Then made group of patients who were having similar prognosis in spite of involvement of different area. Each of stage group has different prognosis that becomes poorer from stage 1 to stage 5 (Table 5). But in particular stage, all subgroup patients have similar outcome in spite of different burden of disease.

Table 1.

Anatomical progression of disease in nose and para nasal sinuses

N-Limited to nasal and para nasal sinus mucosa (Nasal stuffiness, nasal discharge, epistaxis, foul smell, nasal blockage, altered smell sensation) (Paranasal sinus involvement: facial pain, facial edema, dental pain)

N1. Limited to unilateral nasal mucosal involvement and/or Ipsilateral single sinus mucosal involvement

N2. Unilateral nasal mucosal involvement and/or Ipsilateral two or more than two sinus mucosal involvement

N3. Bilateral nasal mucosal involvement with Unilateral or bilateral paranasal sinuses mucosal involvement

N4. Nasal septum involvement and/or bone marrow edema or rarefaction of para nasal sinus walls

Table 2.

Anatomical progression of disease in orbit

O-Orbital involvement (unilateral/bilateral) (pain in eye, ptosis, proptosis, chemosis, diplopia, loss of vision, infraorbital paresthesia, restricted ocular mobility, headache)

O0-No evidence of orbital involvement

O1-Eyelid edema, Vision normal, Movement normal in all direction

O2-Proptosis, Ptosis, Diplopia, Chemosis Edema of extra ocular muscle, optic nerve, fat bone marrow edema and/or rarefaction orbital rim Vision normal, Movement normal in all direction

O3-Diffuse orbital involvement, Reduced vision but not complete vision loss, Ophthalmoplegia

O4-Involvement of superior orbital fissure, inferior orbital fissure, orbital apex, optic canal with reduced vision and/or complete vision loss, Ophthalmoplegia

Table 3.

Anatomical progression of disease in palate and/or skull base

P-Palate and/or skull base involvement (Unilateral/Bilateral) (facial pain, facial edema,facial weakness, facial discoloration, dental pain, loosening of teeth, palate ulcer, palate swelling)

P0-No evidence of palatal or skull base involvement

P1-Pre-maxillary involvement

P2-Bone marrow edema or early osteomyelitic changes of hard palate with normal palatal mucosa

P3-Osteomyelitis of hard palate with palatal mucosal involvement and/or Edema of Retroantral space, Pterygopalatine fossa, Pterygoid plates and Pterygoid muscles, Infratemporal space, Masticator space, zygomatic arch

P4-Soft tissue thickening and/or osteomyelitis  Anterior extension-Zygomatic process, maxillary subcutaneous and cutaneous involvement  Posterior extension-Retroantral space extention, Pterygopalatine fossa, Pterygoid plates and Pterygoid muscles, Infratemporal space, Masticator space, Mandible bone

Table 4.

Anatomical progression of disease in the cranium

C-Intracranial involvement (severe headache, fever, altered sensorium, limb weakness, focal seizures)

C0-No evidence of cranial involvement

C1-Extradural involvement (Cribriform plate, Anterior clinoid process, Basisphenoid bone, Clivus, Cutaneous)

C2-Intradural involvement (Focal meningeal, Cavernous sinus involvement, Occlusion of ICA, Focal brain abscess)

C3-Diffuse cerebral involvement

Table 5.

©ANSEL Mucormycosis staging and outcome evaluation score

Stage	N	O	P	C
I	N 1–3	O 0	P 0	C 0
II	N 1–3	O 1	P 0	C 0
	N 1–4	O 0	P 1	C 0
III	N 1–4	O 2	P 0–2	C 0
	N 1–4	O 0–2	P 2	C 0
IV	N 2–4	O 3	P 0–3	C 0–1
	N 2–4	O 0–3	P 3	C 0–1
Va	N 2–4	O 4	P 0–3	C 1–2
	N 2–4	O 0–4	P 4	C 1–2
Vb	Any N	Any O	Any P	C3

By considering only staging system, we got mortality rate of 6.66% (Table 6) in stage 1 also even though it is early disease. This led us to think about various factors responsible for outcome along with burden of disease. That’s why we have designed outcome evaluation score (Tables 7, 8). In this we consider patients age, comorbidity, stage of disease, adequacy of IV antifungal coverage and patients psychological condition whether patient is self-motivated or not for treatment of disease. Still this is based on limited number of patients. This might get some up gradation with our experience in future as this disease is still dull roaring now a days.

Table 6.

Mortality rate by considering only stage of disease

Stage	Mortality (%)
I	6.66
II	9.75
III	9.48
IV	19.04
Va	38.88
Vb	71.42

Table 7.

Ansel’s outcome evaluation score

Outcome evaluation (©ANSEL Mucormycosis staging and outcome evaluation score)	Score
Age
< 30 years	1
30–50 years	2
> 50 years	3
Comorbidity
Absent	0
Present	1
Uncontrolled diabetes	+ 2
Stage of disease
I	1
II	2
III	3
IV	4
V	5
Injectable antifungal course
Completed	0
Incompleted	3
Not taken at all	6
Self motivation
Present	0
Absent	3

Table 8.

Ansel’s outcome evaluation score

Score (1–20)	Outcome
1–3	Very good
4–6	Good
7–10	Average
11–17	Poor
18–20	Very poor

Conclusion

Our clinical and radiological diagnostic staging and outcome evaluation score may helpful for others for early and better management of mucormycosis. So let’s catch up in portal, before it becomes mortal.

Funding

No any funding resources.

Declarations

Conflict of interest

Not applicable.