Rhino-orbital-cerebral-mucormycosis in COVID-19: A systematic review.

Since the onset of COVID-19 pandemic, parallel opportunistic infections have also been emerging as another disease spectrum. Among all these opportunistic infection, mucormycosis has become a matter of concern with its rapid increase of cases with rapid spread as compared to pre-COVID-19 era. Cases have been reported in post-COVID-19-related immune suppression along with the presence of comorbidity which adds on the deadly outcome. There is no systematic review addressing the issue of COVID-19-associated mucormycosis. This is the first systematic review of published studies of mucormycosis associated with COVID-19. The aim was to analyze the real scenario of the disease statement including all the published studies from first November 2019 to 30th June to analyze the contemporary epidemiology, clinical manifestations, risk factor, prognosis, and treatment outcome of COVID-19 associated rhino-orbito-cerebral-mucormycosis. A comprehensive literature search was done in following databases, namely, PubMed, Google Scholar, Scopus, and EMBASE using keywords mucormycosis, rhino orbital cerebral mucormycosis, COVID-19, and SARS-CoV-2 (from November 01, 2019 to June 30, 2021). Our study shows that, while corticosteroids have proved to be lifesaving in severe to critical COVID-19 patients, its indiscriminate use has come with its price of rhino-orbito-cerebral mucormycosis epidemic, especially in India especially in patients with preexisting diabetes mellitus with higher mortality. Corticosteroid use should be monitored and all COVID-19 patients should be closely evaluated/monitored for sequelae of immunosuppression following treatment.

Diabetic versus non-diabetic rhino-orbito-cerebral mucormycosis.

OBJECTIVE: To compare the characteristics and outcomes of rhino-orbito-cerebral mucormycosis (ROCM) in diabetic versus non-diabetic patients. METHOD: It is a retrospective comparative case series on consecutive patients with biopsy-proven ROCM. Systemic and ophthalmic manifestations, imaging, management and final outcomes were compared between diabetic versus non-diabetic ROCMs referred the eye clinic of a university-based hospital (2008-2016). RESULTS: Forty-three diabetics (55 eyes) with mean age of 54.6 (SD:12.5) years and 20 non-diabetics (24 eyes) with mean age of 57.5 (SD:13.8) years were enrolled. Patients' survival was observed in 51% of diabetics and 70% of non-diabetics (P = .1). The mortality rate was 7.4 times (CI95%: 1.85-29.96) higher in diabetic ROCM treated with non-liposomal amphotericin (P = .01). Exenteration did not significantly change the mortality rate in either group. Globe survival was 40% and 50% in diabetics and non-diabetics (P = 1), respectively. Vision survival was observed in 20% of diabetics and 37% of non-diabetics (P = .2). CONCLUSION: Patients', globe and vision survivals were not different between diabetic and non-diabetic patients with ROCM. They were 51%, 40% and 20% in diabetic and 70%, 50% and 37% in non-diabetic ROCM.

Anesthetic management of rhinoorbitocerebral mucormycosis; Focus on challenges.

Mucormycosis is a progressive, opportunistic fungal infection with a high risk of mortality. Also mucormycosis may attack any organ system and may be accompanied by hemodynamic instability and difficult airway management. This study aimed to evaluate the anesthetic management of patients undergoing surgical resection for rhino-orbito-cerebral mucormycosis (ROC). The study evaluated 12 patients that underwent surgical resection for ROC mucormycosis under general anesthesia. Demographic characteristics, hemodynamic parameters, invasive monitoring methods, surgical procedures, hospital records, and mortality rates were reviewed for each patient. The patients had a median age of 58 (range, 5-86) years. Two patients had an American Society of Anesthesiologists (ASA) score of II while the remaining 10 patients had a score of III. Eleven (91.7%) patients had a diagnosis of rhino-orbital mucormycosis and 1 (8.3%) patient was diagnosed with ROC mucormycosis. Most common comorbidity was DM (n=8), followed by hematological malignancy (n=4), solid organ malignancy (n=3), and kidney transplantation (n=2). Invasive arterial monitoring was performed in 7 and central venous cannulation was performed in 5 patients. Six patients were transferred to the intensive care unit (ICU) and the mortality rate was 25% with an average mortality time was 7 days in 3 cases. In cases of ROC mucormycosis, necessary precautions should be taken for the difficult airway caused by fungal debris in the oropharyngeal region and supraglottic edema. Postoperative ICU is important due to comorbidities and fungal infection with high mortality.

A meta-analysis of survival factors in rhino-orbital-cerebral mucormycosis-has anything changed in the past 20 years?

BACKGROUND: Rhino-orbital-cerebral mucormycosis (ROCM) is an uncommon yet potentially lethal fungal infection. Although most cases originate from developing countries, an ageing population and increased prevalence of chronic illness may mean some clinicians practicing in developed countries will encounter ROCM cases in their careers. Yohai et al published a systematic review of 145 case reports from 1970 to 1993 assessing prognostic factors for patients presenting with ROCM. We present an updated review of the literature and assess whether survival outcomes have changed in the two decades since that seminal paper. SEARCH STRATEGY: An extensive Medline literature search was performed for case reports published between 1994 and 2015. RESULTS: In total, 210 published cases were identified from the literature review, of which 175 patients from 140 papers were included in this review. Fifty-five were female, with an overall mean age of 43 years. Overall survival rate was 59.5%, which was not significantly better than the previous series reported (60%) reported by Yohai et al. Survival rates in patients with chronic renal disease had improved, from 19% to 52%, and in patients with leukaemia (from 13% to 50%). Facial necrosis and hemiplegia remained poor prognostic indicators (33% and 39% survival rates, respectively). Early commencement of medical treatment related to better survival outcomes (61% if commenced within first 12 days of presentation, compared to 33% if after 13 days). Timing of surgery had less of an effect on overall survival. However, in 28 cases that did not receive any surgical treatment, survival was only 21%. CONCLUSIONS: Although overall survival rates have not improved, survival in patients with renal disease were better, potentially due to the introduction of liposomal amphotericin B which is less nephrotoxic. Prompt recognition of ROCM, reversal of predisposing co-morbidities and aggressive medical treatment remain the cornerstone of managing this highly aggressive disease.

Asthma and orbital immunoglobulin G4-related disease.

BACKGROUND: An association has been suggested between asthma and orbital immunoglobulin G4-related disease (IgG4-RD). OBJECTIVE: To explore this association, including asthma characteristics and risk factors. METHODS: A retrospective, computer-assisted search identified patients with orbital IgG4-RD seen at Mayo Clinic in Rochester, Minnesota from 1997 to 2014. Asthma prevalence and its related clinical and radiologic characteristics were studied. RESULTS: Thirty-one patients (17 men) with biopsy-proven orbital IgG4-RD were identified. Mean age at diagnosis was 54.3 years (SD 11.0 years). Median duration from onset of orbital symptoms to IgG4-RD diagnosis was 1.96 years (range 0.1-31.8 years). Twenty-two patients (71%) were not smokers, 6 (19%) were former smokers, and 3 (10%) were current smokers. Sixteen patients (52%) had asthma. Three patients had childhood asthma onset, and median age at asthma onset in the 7 patients with data available was 56 years (range 15-62 years). In this cohort, the most common findings at chest computed tomography were mediastinal and hilar lymphadenopathy (44%), linear scarring (20%), and nodules and bronchial wall thickening (16%). Bronchial wall thickening correlated with presence of asthma. Chronic sinusitis (94%) was most commonly associated with asthma. Serum IgG4 was markedly increased in patients with asthma (median 195.0 mg/dL, range 31.8-1,790.0 mg/dL) vs patients without asthma (median 78.9 mg/dL, range 7.7-166.0 mg/dL; P = .02). Treatment was commonly prednisone and then rituximab; rituximab helped control asthma in most cases. Two deaths were reported (median follow-up 4.2 years). CONCLUSION: Asthma is commonly associated with orbital IgG4-RD and generally manifests as adult-onset bronchial wall thickening seen at computed tomography, increased serum IgG4 levels, and good rituximab response.

Invasive fungal disease of the sinus and orbit: a comparison between mucormycosis and Aspergillus.

BACKGROUND/AIMS: Invasive fungal infections of the head and neck are rare life-threatening infections where prompt diagnosis and intervention is critical for survival. The aim of this study is to determine the clinical characteristics and outcomes of invasive fungal disease of the sinus and orbit, and to compare mucormycosis and Aspergillus infection. METHODS: A retrospective review was conducted from a single tertiary care eye and ear hospital over 20 years (1994-2014). Twenty-four patients with a confirmed pathological diagnosis of invasive fungal disease of the sinus and/or orbit were identified and their medical records were reviewed. The main outcome measures were type of fungus, location of disease, mortality and visual outcome. RESULTS: Patients with orbital involvement had a higher mortality and higher likelihood of mucormycosis infection compared with those with sinus-only disease (78.6% vs 20%, p=0.01; 86% vs 30%, p=0.01, respectively). Patients with mucormycosis had a higher mortality (71%) than patients with Aspergillus (29%); however, this was not statistically significant (p=0.16). All patients with orbital involvement and/or mucormycosis infections were immunosuppressed or had inadequately controlled diabetes, and had a cranial neuropathy or ocular motility dysfunction. All five post-transplant patients with orbital infections died, while the two transplant patients with sinus infections survived. CONCLUSIONS: Patients with orbital fungal infections are more likely to be infected with mucormycosis compared with Aspergillus and have a higher mortality compared with infections sparing the orbit. History of transplant portends a dismal prognosis in orbital infections. Invasive fungal disease should be considered in any immunocompromised patient presenting with a new cranial neuropathy or ocular motility abnormality.

Local control of rhino-orbito-cerebral mucormycosis dramatically impacts survival.

Surgery and antifungals are the reference standard for rhino-orbito-cerebral mucormycosis (ROCM) treatment. The impact of local control on survival of 22 consecutive ROCM adults was studied on day 90: none vs. 75% died, respectively, with or without local control (p <0.0001). Hence, repeated surgical procedures are recommended to achieve local control of ROCM.

Management of radiation-induced severe anophthalmic socket contracture in patients with uveal melanoma.

PURPOSE: High-dose radiotherapy can cause contracture of the anophthalmic socket, but the incidence of this complication in patients with enucleation for uveal melanoma has not been reported previously. The authors reviewed the surgical management and outcomes in terms of successful prosthesis wear in patients with severe contracture of the anophthalmic socket treated with high-dose radiotherapy for high-risk uveal melanoma, and they estimated the relative risk of this complication. METHODS: The medical records of all consecutive patients enrolled in a prospective uveal-melanoma tissue-banking protocol at the authors' institution who underwent enucleation between January 2003 and December 2010 were reviewed. Patients who underwent adjuvant radiotherapy of the enucleated socket were further studied. RESULTS: Of the 68 patients enrolled in the prospective tissue-banking protocol, 12 had high-risk histologic features (e.g., extrascleral spread or vortex vein invasion) and were treated with 60 Gy of external beam radiotherapy after enucleation. Five of these patients (41.7%) experienced severe socket contracture precluding prosthesis wear. The median time to onset of contracture following completion of radiotherapy was 20 months. Three patients underwent surgery, which entailed scar tissue release, oral mucous membrane grafting, and socket reconstruction; 2 patients declined surgery. All 3 patients who had surgery experienced significant improvement of socket contracture that enabled patients to wear a prosthesis again. CONCLUSION: High-dose radiotherapy after enucleation in patients with uveal melanoma caused severe socket contracture and inability to wear a prosthesis in approximately 40% of patients. Surgical repair of the contracted socket using oral mucous membrane grafting can allow resumption of prosthesis wear.

Postgraduate institute management protocol for invasive Aspergillus flavus sinusitis: is it effective?

OBJECTIVE: To analyze the results of a postgraduate institute management protocol for invasive Aspergillus flavus sinusitis. METHODS: This was a prospective study wherein all patients with a final histopathological diagnosis of invasive sino-orbital aspergillosis were included for the period between January 1998 and December 2005. All the patients were negative for HIV, diabetes, and chronic granulomatous disease. All patients were evaluated clinically, biochemically, and radiologically for the condition, and were classified into four groups on the basis of clinical and radiological findings. All patients were subjected to endonasal endoscopic biopsy and were subjected as per the management protocol. These patients were then followed up clinically, endoscopically, and radiologically for a period ranging from 9 months to 7 years. RESULTS: A total of 74 patients were enrolled in the study, 52 males and 22 females, ranging in age from 26 to 53 years. The most common sign was proptosis. The patients in each group were subjected to the treatment protocol decided for the group. Overall, residual disease was seen in 14 patients (18.9%) and recurrence was seen in six patients (8.1%). Twenty-four (32.4%) patients died of the disease in our series. Residual disease and recurrent disease were seen more often in the advanced cases. CONCLUSION: Invasive sino-orbital aspergillosis is associated with significant mortality. By following our management protocol we were able to reduce the mortality to 32.4% in our series.

Rhinocerebral Mucormycosis: consideration of prognostic factors and treatment modality.

OBJECTIVES: Rhinocerebral mucormycosis is rare, rapidly progressive, potentially life-threatening disease, and it usually occurs in immunocompromised patients. We present our clinical experience with 12 cases and we attempt to identify the prognostic features and proper treatment protocols. PATIENTS AND METHODS: All the cases of mucormycosis were proven by histology or culture. The prognosis was analyzed according to the predisposing factors, including underlying disease, extent of disease and surgical intervention. RESULT: The overall mortality rate in our series was 33.3%. 7 of the 10 operated patients recovered, while 1 of the 2 non-operated patients expired. The associated conditions included diabetes mellitus (n=9) and hematological disease (n=3). A poor prognosis was primarily related with uncontrolled underlying disease. Other associated prognostic factors were the extent of disease including orbital or intracranial extension. Surgical debridement is essential for a good prognosis, but timely intervention and complete aggressive debridement are not always needed in all patients. The patient who had slowly progressive disease also survived after conventional medical management and limited surgical debridement, including orbital preservation. CONCLUSION: Control of the underlying predisposing illness along with prompt parenteral administration of amphotericin B and aggressive surgical debridement remain the essential treatments even today. Contrary to this, as described in this study, for the patients with slowly progressive disease, the aggressive surgical debridement is spared, and a successful result may be obtained with the conventional management, including medical treatment and timely limited surgical intervention.

Rhino-orbital-cerebral mucormycosis and aspergillosis: differential diagnosis and treatment.

In immunocompromised patients, symptoms and the pathogen spectrum of sinusitis are frequently atypical. If progressive loss of vision occurs, an infection of the anterior skull base or nasal sinuses should be considered. We report on four patients with orbit-associated symptoms. CT-imaging revealed bony defects in sinus borders to orbits or endocranium. In all the cases immediate surgical drainage was performed because complications following sinusitis were suspected. Histopathological diagnosis revealed two cases of aspergillosis and mucormycosis. The possibility of opportunistic infections by saprophytic fungi must be taken into account in immunocompromised patients, as they may endanger both vision and survival. Immediate diagnosis and therapy are essential. Nowadays, therapeutic success can be achieved due to advances in antimicrobial therapy, hyperbaric oxygen therapy and treatment of the underlying disease. Radical procedures like orbital exenteration must be considered in all cases. The current state of diagnostics, therapy and prognosis is discussed based on these case reports and the recent literature.

Mortality in an ophthalmic ward at a tertiary eye unit in Zimbabwe.

OBJECTIVE: To review and determine the attributed causes of deaths among patients who died in Sekuru Kaguvi Hospital (SKH) Eye Unit Wards between August 1984 and October 2008 STUDY DESIGN: Retrospective study of completed BD12 forms and case records of inpatients who died betweenAugust 1984 and October 2008. SETTING: Sekuru Kaguvi Hospital Eye Unit, Parirenyatwa Group ofHospitals, Harare, Zimbabwe. RESULTS: Eighty three deaths occurred in the unit during the 24 year period, 51% were females and 33.7% were children below 13 years of age. Ninety three percent of deaths among children were attributed to neoplasias, while 22% of deaths among adults were attributed to infections. Non-ophthalmic causes of deaths were seen among adults. CONCLUSION: Malignancies are the commonest attributable causes of mortality in the Ophthalmic Wards at Sekuru Kaguvi Hospital Eye Unit. Resource mobilization is essential to improve Eye Care Services.

Fatal strokes in patients with rhino-orbito-cerebral mucormycosis and associated vasculopathy.

Within a 10-y period, fatal strokes occurred during parenteral administration of amphotericin B and surgical debridement of paranasal sinuses in 6 pathologically verified cases of rhino-orbito-cerebral mucormycosis (ROCM). All patients had unnoticed type-2 diabetes mellitus without ketoacidosis. They presented with unilateral orbital cellulitis and cavernous sinus syndrome. Fatal malignant cerebral infarctions occurred in the carotid system in 5 patients, and in the basilar artery or its major branches in 2 patients. Accelerated thrombotic occlusion of the cavernous portion of the carotid artery or the basilar artery was likely to be due to mucormycosis associated-vasculopathy and diabetic vasculopathy. One patient died of massive subarachnoid hemorrhage following rupture of the mycotic aneurysm. Despite parenteral administration of amphotericin B, fatal outcome of ROCM in patients with unnoticed diabetes mellitus occurs due to mucormycosis-associated malignant strokes. To improve outcome, a combination of early radical debridement, ocular exenteration, parenteral and local administration of amphotericin B, and decompression craniotomy should be considered.

Zygomycosis in Qatar: a retrospective review of six cases.

Six cases of zygomycosis that were diagnosed at Hamad Medical Corporation over an eleven-year period are retrospectively reviewed. All patients had at least one predisposing condition. Renal transplant and diabetes mellitus were the most common predisposing conditions. Sites of involvement were pulmonary in two patients, rhinocerebral two, rhino-orbital, and cutaneous in one each. The clinical features in patients with rhinocerebral and rhino-orbital involvement were very suggestive of the diagnosis, while patients with pulmonary and cutaneous involvement, the disease was not suspected and was only made after the histopathology or culture results were available. Diagnosis was made premortum in all patients. Diagnosis was confirmed by histopathology in three patients and by culture in the other three. Five of the six patients died. Poor outcome correlated with rhinocerebral and pulmonary involvement, while cutaneous disease was associated with favorable outcome. Therapy with amphotericin B, surgical debridement, and correction of the underlying predisposing condition offers the best chance for survival.

Survival factors in rhino-orbital-cerebral mucormycosis.

Mucormycosis is a highly aggressive fungal infection affecting diabetic, immunocompromised, and, occasionally, healthy patients. This infection is associated with significant mortality. We have reviewed 208 cases in the literature since 1970, 139 of which were presented in sufficient detail to assess prognostic factors, and added data from six of our patients. The histories of these 145 patients were analyzed for the following variables: 1) underlying conditions associated with mucormycotic infections; 2) incidence of ocular and orbital signs and symptoms; 3) incidence of nonocular signs and symptoms; 4) interval from symptom onset to treatment; and 5) the pattern of sinus involvement seen on imaging studies and noted at the time of surgery. Factors related to a lower survival rate include: 1) delayed diagnosis and treatment; 2) hemiparesis or hemiplegia; 3) bilateral sinus involvement; 4) leukemia; 5) renal disease; and 6) treatment with deferoxamine. The association of facial necrosis with a poor prognosis fell just short of statistical significance, but appears clinically important. This is the first review that documents the heretofore intuitive claim that early diagnosis is necessary to cure this disease. Standard treatment with amphotericin B and aggressive surgery are reviewed and adjunctive therapeutic modalities are discussed, including local amphotericin B irrigation, hyperbaric oxygen, and optimizing the immunosuppressive regimen in transplant patients. Hyperbaric oxygen was found to have a favorable effect on prognosis. In addition, possible treatment options for patients with declining renal function are reviewed.