Mucormycosis is most often an acute surgical emergency, however, some cases display chronic symptoms that gradually develop over time (weeks or months). Symptoms depend heavily on which form of the disease patients have.

Symptoms of rhino-orbito-cerebral mucormycosis include acute sinusitis, fever, eye swelling and protrusion, dark nasal scabbing, cellulitis, facial pain, retinal artery thrombosis, redness of skin around sinuses and nasal congestion with black discharge. Diplopia and blindness may be observed in later stages of the disease, which indicates the infection has spread to the orbital nerves and vessels, and prognosis for these patients is poor.

Symptoms of pulmonary mucormycosis are nonspecific and may include fever, cough, rales, shortness of breath and possibly hemoptysis if tissue necrosis is present. Symptoms of GI mucormycosis include abdominal pain and distension, nausea, vomiting blood, tenderness upon palpation and hematochezia [5]. Presentation of cutaneous mucormycosis is marked by a single area of skin that is painful, hardened and may have a necrotic (blackened) central area [11]. If the mucormycosis infection has disseminated to the central nervous system patients will present with decreased consciousness and focal neurological symptoms, such as cranial nerve deficits.

• Fever

  […] include: Cough Coughing blood (occasionally) Fever Shortness of breath Symptoms of gastrointestinal mucormycosis include: Abdominal pain Blood in the stools Diarrhea Vomiting blood Symptoms of kidney (renal) mucormycosis include: Fever Pain in the upper [nlm.nih.gov]

  However, the patient then developed fever, dyspnea, and subsequent right hemiparesis. [ncbi.nlm.nih.gov]

  M CGN DDRT 2 months Fever RF graft tend Induction- baxiliximab and ART CSA, Pred OKT3 no response (ACR 2) Enlarged graft resistive index Nx. specimen Graft Nx Ampho-B 6 weeks dose 2 g Survived 19 [ 16 ] 62 M DM LURT- Pakistan 3 weeks Fever, RF PRED CSA [academic.oup.com]

• Pain

  […] include: Cough Coughing blood (occasionally) Fever Shortness of breath Symptoms of gastrointestinal mucormycosis include: Abdominal pain Blood in the stools Diarrhea Vomiting blood Symptoms of kidney (renal) mucormycosis include: Fever Pain in the upper [nlm.nih.gov]

  Also, in the case of facial pain, the low mortality rate may indicate the importance of early diagnosis. [ncbi.nlm.nih.gov]

• Malaise

  […] drug use, history of transplant, and history of multiple blood transfusions.[1] [3] Initial symptoms of sinus-involving mucormycosis are consistent with acute or chronic sinusitis; congestion, blood-tinged secretions, rhinorrhea, headaches, fever, and malaise [eyewiki.aao.org]

  Presentation The onset of sinus mucormycosis may be associated with nonspecific symptoms such as nasal congestion, postnasal drip, dark blood-tinged or purulent rhinorrhea, sinus tenderness, headache, fever, and malaise. [aao.org]

  The timeliness of definitive surgical and medical treatment is directly related to the prevention of morbidity and mortality in affected patients. 1 Case Reports Case 1 A 66-year-old man with diabetes presented to the emergency department with malaise [ajnr.org]

  […] incidence of rhinocerebral mucormycosis, is expected.[ 1 5 7 ] It is essential for the clinician to maintain a high index of suspicion in populations at risk, as early diagnosis can be life-saving.[ 4 ] Clinical symptoms usually begin as nonspecific malaise [surgicalneurologyint.com]

• Fatigue

  J, a 74-year-old man from Costa Rica with diabetes, was admitted to the geriatric inpatient service with a 2-week history of fatigue, weakness, and confusion, and 1 day of vomiting. [consultant360.com]

  Author: Brit Long, MD (@long_brit; EM Resident at SAUSHEC; USAF) // Editor: Alex Koyfman, MD (@EMHighAK) & Justin Bright, MD (@JBright2021) A 42 year-old female with poorly controlled type II diabetes presents with several days of fatigue, headache, fever [emdocs.net]

  […] with diabetes mellitus type I, hypertension, hyperlipidemia, history of myocardial infarction, chronic myelogenous leukemia (CML), and recurrent methicillin sensitive S. aureus (MSSA) right arm cellulitis presented to a local community hospital with fatigue [clinmedjournals.org]

  58 (22.4) Elevated liver laboratory tests 44 (17.1) 63 (24.3) Dyspnea 44 (17.1) 35 (13.5) Abdominal pain 43 (16.7) 59 (22.8) Headache 43 (16.7) 38 (14.7) Peripheral edema 39 (15.2) 47 (17.8) Constipation 36 (14) 54 (20.8) Insomnia 27 (10.5) 25 (9.7) Fatigue [fda.gov]

  In May 2016, the patient was admitted to Affiliated Hangzhou First People's hospital again due to disease progression with fatigue and dizziness. Bone marrow pathology and chromosome karyotyping revealed MM progression and secondary MDS. [spandidos-publications.com]

• Cough

  Coughing blood (occasionally) Fever Shortness of breath Symptoms of gastrointestinal mucormycosis include: Abdominal pain Blood in the stools Diarrhea Vomiting blood Symptoms of kidney (renal) mucormycosis include: Fever Pain in the upper abdomen or [nlm.nih.gov]

  Associatedsymptoms included chronic cough and fatigue.Bilateral lung opacities with hilar lymphadenopathywere noted on chest computed tomographyscan. [ncbi.nlm.nih.gov]

• Dyspnea

  However, the patient then developed fever, dyspnea, and subsequent right hemiparesis. [ncbi.nlm.nih.gov]

• Nasal Discharge

  Manifestations may include pain, fever, orbital cellulitis, proptosis, ophthalmoplegia, loss of vision, purulent nasal discharge, and mucosal necrosis. [msdmanuals.com]

  Facts : Fungal infection of the sinuses, brains, lungs MCC is Rhizopus History / PE : Low grade fever Bloody nasal discharge Necrotic turbinates Diagnosis : CT / MRI imaging Treatment : Surgical debridement plus IV amphotercin B Complications : Death [medlibes.com]

  Diagnosis is difficult as the symptoms can be subtle at first, but when they proceed to serious conditions such as nasal discharge and necrosis, these are usually blamed on other conditions. [house.wikia.com]

  Rhinocerebral mucormycosis is severe sinusitis with caused by a non- Aspergillus mold, most commonly Rhizopus arrhizus CLINICAL FEATURES Rhinocerebral mucormycosis headache facial pain confusion fever purulent nasal discharge (black) Other manifestations [lifeinthefastlane.com]

• Hemoptysis

  Overall in-hospital mortality was 52.5%, with hemoptysis (P   .017), dyspnea at presentation (P   .022) and angioinvasion (P   .03) as independent risk prognostic factors. [ncbi.nlm.nih.gov]

  The presence of hemoptysis should bring mucormycosis to mind because it is one of the angioinvasive fungi. [doi.org]

• Nasal Congestion

  Mucormycosis Pathology Type Fungus Cause(s) Exposure to fungal spores Symptoms Clots, necrosis, headache on one side, facial pain, fever, black discharge after nasal congestion, acute sinusitis, swelling of eyes, reddening of skin, edema, difficulty breathing [house.wikia.com]

  Signs of a related sinus or respiratory infection may include: cough fever headache nasal congestion sinus pain With a skin infection, mucormycosis can develop within any part of your body. [healthline.com]

• Vomiting

  We report a case of 19 year old female, with no pre-existing co-morbidities, presented with fever, dysentery, vomiting, and melena for 4 days. [ncbi.nlm.nih.gov]

  Symptoms of gastrointestinal mucormycosis include: Abdominal pain Nausea and vomiting Gastrointestinal bleeding Disseminated mucormycosis typically occurs in people who are already sick from other medical conditions, so it can be difficult to know which [cdc.gov]

  […] skin above sinuses Sinus pain or congestion Symptoms of lung (pulmonary) mucormycosis include: Cough Coughing blood (occasionally) Fever Shortness of breath Symptoms of gastrointestinal mucormycosis include: Abdominal pain Blood in the stools Diarrhea Vomiting [nlm.nih.gov]

  Exposure to fungal spores Symptoms Clots, necrosis, headache on one side, facial pain, fever, black discharge after nasal congestion, acute sinusitis, swelling of eyes, reddening of skin, edema, difficulty breathing, coughing, coughing up blood, nausea, vomiting [house.wikia.com]

• Abdominal Pain

  A 14-year-old boy presented to our clinic with fever and left upper quadrant abdominal pain, and on evaluation was found to have pancytopaenia, and imaging revealed ill-defined splenic collection with thrombus in the splenic vein. [ncbi.nlm.nih.gov]

  Symptoms of gastrointestinal mucormycosis include: Abdominal pain Nausea and vomiting Gastrointestinal bleeding Disseminated mucormycosis typically occurs in people who are already sick from other medical conditions, so it can be difficult to know which [cdc.gov]

  pain Blood in the stools Diarrhea Vomiting blood Symptoms of kidney (renal) mucormycosis include: Fever Pain in the upper abdomen or back Symptoms of skin (cutaneous) mucormycosis include a single, painful, hardened area of skin that may have a blackened [nlm.nih.gov]

  Presentation is nonspecific, with abdominal pain, abdominal distension, nausea, and vomiting. [patient.info]

• Nausea

  The most commonly reported TEAEs among isavuconazole recipients were gastrointestinal disorders such as nausea, vomiting and diarrhoea. [ncbi.nlm.nih.gov]

  Symptoms of gastrointestinal mucormycosis include: Abdominal pain Nausea and vomiting Gastrointestinal bleeding Disseminated mucormycosis typically occurs in people who are already sick from other medical conditions, so it can be difficult to know which [cdc.gov]

  (s) Exposure to fungal spores Symptoms Clots, necrosis, headache on one side, facial pain, fever, black discharge after nasal congestion, acute sinusitis, swelling of eyes, reddening of skin, edema, difficulty breathing, coughing, coughing up blood, nausea [house.wikia.com]

  Presentation is nonspecific, with abdominal pain, abdominal distension, nausea, and vomiting. [patient.info]

   ABDOMINAL PAIN,NAUSEA VOMITING, ,,,MAY PRESNT AS INTRAABDOMINAL ABSCESS,OR PERFORATION OF THE VISCUS.NEEDS BIOPSY. PROGNOSIS VERY POOR 19. [slideshare.net]

• Abdominal Distension

  Abdominal distension and peritonitis were secondary complications. [ncbi.nlm.nih.gov]

  Presentation is nonspecific, with abdominal pain, abdominal distension, nausea, and vomiting. [patient.info]

  distension, flank pain, an ulcer with a dark center and sharply defined edges, and mental-status changes may occur. [medicinenet.com]

• Hematochezia

  Una enfermedad que también existe Juan Carlos Pozo Laderas,Antonio Pontes Moreno,Carmen Pozo Salido,Juan Carlos Robles Arista,María José Linares Sicilia Revista Iberoamericana de Micología. 2014; 3 Gastrointestinal Mucormycosis Initially Manifest as Hematochezia [jpgmonline.com]

  Hematochezia [24] or obstruction [25] may occur. Some patients have tenderness to palpation or a mass. Rupture may lead to signs of peritonitis. [emedicine.medscape.com]

  Symptoms of GI mucormycosis include abdominal pain and distension, nausea, vomiting blood, tenderness upon palpation and hematochezia. [symptoma.com]

  A Rare Cause of Hematochezia: Colon Mucormycosis. Clin Gastroenterol Hepatol. 2012 Aug 28. [Medline]. Chawla N, Reddy SJ, Agrawal M. Ileocolic mucormycosis causing intestinal obstruction. Indian J Med Microbiol. 2012 Jul-Sep. 30(3):373-4. [Medline]. [emedicine.com]

• Refractory Shock

  The patient finally succumbed to his illness as he developed peritonitis and refractory shock. To date, only two cases of isolated splenic mucormycosis have been reported. [ncbi.nlm.nih.gov]

• Skin Lesion

  The identification of pathogen based on the fungus morphology and DNA sequencing revealed M. irregularis as the responsible fungus for skin lesion. [ncbi.nlm.nih.gov]

  Affected platypuses can develop ugly skin lesions or ulcers on various parts of the body including their backs, tails and legs. [dpipwe.tas.gov.au]

• Diplopia

  Late symptoms from invasion of the orbital nerves and vessels include diplopia and visual field loss. These are late symptoms with a poor prognosis and usually are followed by reduced consciousness. [patient.info]

  However, 60% to 89% of mucoceles arise from the frontal sinuses, an unusual site for mucor involvement, according to investigators. 25 Thyroid eye disease can also present with pain, diplopia, chemosis, and pressure sensation behind the eyes. [reviewofoptometry.com]

  Involvement of the superior orbital fissure and its contents, such as cranial nerves III, IV, and VI, and branches of V1 and V2, may cause diplopia, ophthalmoplegia, and sensory loss to the corresponding areas of the cornea and face. [aao.org]

• Eye Swelling

  swelling Any of the other symptoms listed above Because the fungi that cause mucormycosis are widespread, the best way to prevent this infection is to improve control of the illnesses associated with mucormycosis. [nlm.nih.gov]

  swelling.[10] Affected skin may appear relatively normal during the earliest stages of infection. [en.wikipedia.org]

• Visual Impairment

  The clinical syndromes were classified as rhino-orbital, rhinocerebral or rhino-orbito-cerebral based on the presenting features such as unilateral periorbital facial pain, numbness, visual impairment/loss, eyelid edema, chemosis, proptosis, opthalmoplegia [neurologyindia.com]

• Visual Impairment

  The clinical syndromes were classified as rhino-orbital, rhinocerebral or rhino-orbito-cerebral based on the presenting features such as unilateral periorbital facial pain, numbness, visual impairment/loss, eyelid edema, chemosis, proptosis, opthalmoplegia [neurologyindia.com]

• Facial Pain

  Also, in the case of facial pain, the low mortality rate may indicate the importance of early diagnosis. [ncbi.nlm.nih.gov]

  Critical Essential Core Tested Community Questions (1) (M2.ID.4766) A 54-year-old male presents to the emergency department with facial pain. He reports feeling well until yesterday, when he developed a headache that has gotten progressively worse. [medbullets.com]

  Mucormycosis Pathology Type Fungus Cause(s) Exposure to fungal spores Symptoms Clots, necrosis, headache on one side, facial pain, fever, black discharge after nasal congestion, acute sinusitis, swelling of eyes, reddening of skin, edema, difficulty breathing [house.wikia.com]

  Rhinocerebral mucormycosis is severe sinusitis with caused by a non- Aspergillus mold, most commonly Rhizopus arrhizus CLINICAL FEATURES Rhinocerebral mucormycosis headache facial pain confusion fever purulent nasal discharge (black) Other manifestations [lifeinthefastlane.com]

  pain sinus pressure Physical exam fevers may be only presenting symptom in immunocompromised patients with pulmonary infections soft tissue swelling black necrotic eschar on face, particularly nares or palate may affect cranial nerves blurry vision loss [step2.medbullets.com]

• Headache

  Symptoms of rhinocerebral mucormycosis include: Eyes that swell and stick out (protrude) Dark scabbing in nasal cavities Fever Headache Mental status changes Redness of skin above sinuses Sinus pain or congestion Symptoms of lung (pulmonary) mucormycosis [nlm.nih.gov]

  A 75-year-old man with type 2 diabetes mellitus presented with complete loss of vision in his right eye and severe headaches for the past 24 hours. [ncbi.nlm.nih.gov]

• Reduced Consciousness

  These are late symptoms with a poor prognosis and usually are followed by reduced consciousness. Pulmonary mucormycosis presents nonspecifically with fever, dyspneoa, and cough. [patient.info]

  These late symptoms indicate a poor prognosis and are usually followed by reduced consciousness. [webmedcentral.com]

• Akinesia

  The myocardial abscess diffusely infiltrated the left ventricular wall and was associated with akinesia, which led to sudden cardiac arrest. [ncbi.nlm.nih.gov]

Diagnosis is achieved through a variety of factors including patient’s history, risk factors and physical exam, however, a definitive diagnosis is hard to reach. The extent of infection or necrosis may be assessed through magnetic resonance imaging (MRI) or computerized tomography (CT) scan but these findings are nonspecific [12]. Biopsies can be stained with Grocott methenamine-silver stain or periodic acid-Schiff (PAS) stain and others to identify the fungus, but the specific fungal species is hard to determine [13]. More complicated cultivation and imaging techniques must be performed to identify structures unique to mucormycosis and distinguish this from other fungal infections like candidiasis and histoplasmosis. Therefore, the diagnosis of mucormycosis may be used without definitive evidence since the supportive care and treatment for many fungal infections are similar.

• Cavitary Lesion

  Gross specimen from the left upper lobectomy shows a 7 cm cavitary lesion surrounded by congestive and necrotic lung tissue. Fig. 5. [rc.rcjournal.com]

  Imaging features in pulmonary mucormycosis are nonspecific, it can present as a solitary nodule, lobular consolidation as in pneumonia, cavitary lesion or in disseminated form 2. CT On CT, ground-glass opacities may be encountered 3. [radiopaedia.org]

  Cavitary lesions with the “air crescent sign” have been described, but are rare. [omicsonline.org]

  So computed tomographic (CT) scan chest was done which showed a consolidation with cavitary lesion in right middle lobe ( Figure 1B ). [jtd.amegroups.com]

Mucormycosis is treated with antifungal medications (conventional or lipid formulations of amphotericin B) administered orally or IV [14] [15]. Infected areas of skin may require surgical resection to remove infected and dead tissues [15]. Patient survival relies on proper debridement of necrotic tissue when applicable. Surgical care of rhino-orbito-cerebral infection may include repeated surgeries to excise orbital contents and infected brain tissue along with drainage of sinuses.

There are a number of potential adjunct therapies to treat mucormycosis. Hyperbaric oxygen after surgery is thought to improve neutrophil function and wound healing and inhibit fungal growth. However, the effectiveness of hyperbaric oxygen for mucormycosis has not been studies extensively and this is not a currently approved use of hyperbaric oxygen. Administration of colony stimulating factor (CSF) or interferon-gamma (IFNγ) may be done to enhance immune response in neutropenic patients and white blood cell transfusions, respectively. However, the effectiveness of these treatments is unclear. Case reports on the use of iron chelators without xenosiderophore activity, such as deferasirox, indicated that adjunct use of deferasirox leads to increased mortality rates although only a small patient sample was investigated [16].

The mortality rate for mucormycosis is extremely high (at least 50%). Due to the late diagnosis associated with pulmonary and GI mucormycosis infections, the mortality rate in these forms is relatively higher. Transplant patients that contract mucormycosis may experience mortality rates of 80%. An Italian study indicated that 65% of diagnoses were made postmortem [10]. The lifesaving surgery associated with rhino-orbito-cerebral mucormycosis often leaves survivors with severe facial disfigurements.

The primary risk factor for murcormycosis is a compromised immune system. Patients with particularly high risk include those with uncontrolled diabetes mellitus, especially with ketoacidosis. Cancer patients receiving broad-spectrum antibiotics that display neutropenia, hematologic cancer patients with herpetic infection (eg. Cytomegalovirus) and graft versus host disease and individuals on immunosuppressive drugs, such as steroids and tumor necrosis factor (TNF) blockers are also at high risk for contracting murcormycosis infection.

The GI form of murcormycosis infection is linked to extreme malnutrition. The cutaneous form of murcormycosis is associated with trauma, the use of contaminated medical supplies, burns and intravenous (IV) drug use. Not all patients that develop murcormycosis will exhibit risk factors [2] [4].

Chemicals that increase chances of developing murcormycosis include iron, which is a growth stimulant for Mucorales, and deforoxamine, which is a siderophore that delivers iron to Mucorales [2] [3].

Compared to other fungal infections, Mucorales infections occur much less frequently (10 to 15 fold less) [5]. Annually in the United States (US) there are an estimated 1.7 cases per million people which equates to about 500 cases per year [5].

Mucormycosis is commonly observed in immunosuppressed individuals but certain strains, such as those in the order Entomophthorales, have occurred in immunocompetent hosts. Individuals with the highest risk include those with diabetic ketoacidosis, hematologic malignancies, organ transplant recipients, chronic corticosteroid use and graft-versus-host-disease [5].

The most common form of mucormycosis is rhino-orbito-cerebral (44-49%) [7]. Cutaneous mucormycosis accounts for 10-16% of cases followed by pulmonary (10-11%), disseminated (6-11.6%) and GI (2-11%). Diabetic patients are more likely to present rhino-orbito-cerebral mucormycosis, while patients with hematological malignancies or transplants commonly present with pulmonary mucormycosis.

Outbreaks of mucormycosis have been reported including a nosocomial outbreak of GI mucormycosis that occurred in a hospital in Spain. This outbreak was linked to the use of wooden tongue depressors that were contaminated with Rhizopus and the mortality rate in this case was 40% [6].

The most common mode of entry of Mucorales is inhalation of fungal spores. Once spores enter a host they may germinate to produce hyphae that can enter blood vessels and cause thrombosis which may results in tissue necrosis. Experimentally, germinated fungal spores can adhere to the sub-endothelial matrix and cause damage to endothelial cells after phagocytosis [9]. This outcome occurs regardless of viability indicating that cidal antifungals will not be effective for the treatment of established disease [9]. Mucorales may be disseminated to other organs through the blood stream. An efficient host immune response to Mucorales infection requires normal mononuclear and polymorphonuclear phagocytes that can produce oxidative metabolites and definsins to kill fungi along with macrophages and neutrophils to inhibit spore germination and damage hyphae, respectively [8].

Factors that decrease the abundance or functioning of neutrophils, such as chemotherapy (induces neutropenia), corticosteroids, acidosis and hyperglycemia, increase the risk of developing mucormycosis [5]. Other conditions and factors that hamper the immune response to fungi include acidosis and hyperglycemia which hinder the ability of phagocytes to kill fungi and corticosteroids which prevent the ability of macrophages to stop germination [9]. Actions that result in better outcomes include early recognition and appropriate treatment along with reversal of acidosis (if it applies).

To prevent risk of mucormycosis infection, immunosuppressants, such as corticosteroids, should be used sparingly and patients should control their diabetes. Physicians and hospitals should use appropriate rooms equipped with high-efficiency particulate air (HEPA) filters and patients with immunosuppressive conditions should use masks [5].

Several different fungal species in the order Mucorales may cause murcormycosis infections. The organisms most commonly associated with murcormycosis infection are Rhizopus. Other disease causing genera include Mucor, Cunninghamella, Apophysomyces, Absidia, Saksenaea and Rhizomucor [1] [2]. Mucormycosis infections are serious and in most cases life-threatening with disorders such as diabetic ketoacidosis and neutropenia present in most cases. Patients commonly present with severe infection of the facial sinuses which may extend to the brain (rhino-orbito-cerebral). Other infections, including pulmonary, cutaneous, gastrointestinal (GI) and disseminated, are also observed. Effective treatment of murcormycosis requires rapid correction of underlying risk factors, administration of antifungals (liposomal amphotericin B) and aggressive surgery.

Mucormycosis is a serious and sometimes life-threatening fungal infection that may affect the sinuses, brain, lungs and skin. The fungi that cause mucormycosis are often found in soil, decaying plants and compost and can enter the body through cuts or inhalation. Once the fungus enters the body it can spread quickly. Individuals with healthy immune systems often destroy and eliminate the fungus, however, if the immune system is weak the fungus may go on to cause a severe infection. Symptoms of mucormycosis infection include fever, facial pain, swollen eyes, redness of skin over sinuses, bloody cough, shortness of breath, abdominal pain, vomiting blood, pain on side of the body between upper abdomen and back and a skin infection that starts with blisters and later becomes tender, red, swollen and black in the center.

Patients with a compromised immune system that display the symptoms above are often diagnosed with mucormycosis. Analysis of tissue biopsies (tissue removed using small needle) is required to obtain a definitive diagnosis. Doctors may also perform CT scan or MRI to determine the extent of infection within the body and whether surgery is needed. If the central nervous system is thought to be infected patients may receive a lumbar puncture (spinal tap), if it is safe, to assess protein levels in the cerebrospinal fluid (CSF). Aggressive treatment is required if mucormycosis is suspected and early treatment is associated with better outcomes. Oral or IV antifungal medication will be administered as soon as possible and surgery may be required to remove infected and dead tissue.

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