1648
A rare infection caused by molds belonging to this subphylum Mucormycontina in the order Mucorales.
An invasive fungal infection.
Estimated incidence of 1.7 cases per million, with regional differences.
These fungi are ubiquitous in nature.
Found particularly in soil, decaying wood, and other organic matter.
Mucomycosis is a rapidly progressive invasive fungalu infection affecting primarily individuals who are severely immunocompromised as well as patients with diabetes and persons with immunocompetence who have had major trauma.
The most frequently encountered risk factors are immunosuppression, such as seen with cancer and diabetes, hematologic malignancies, hematopoietic stem cell transplant, solid organ transplantation, graft vs host disease, iron overload, prolong use of high dose glucocorticoids, low birth rate, metabolic acidosis, injection drug use, severe malnutritionand traumatic wound injuries.
It carries significant risk of morbidity and mortality in the setting of rhinocerebral, pulmonary, gastrointestinal, cutaneous, and disseminated infections.
Causes necrotizing infections of traumatic wounds.
Differentiating it initially from bacterial sinusitis is difficult in rhinocerebral infections.
Virtually all organs can be affected, but the sinuses and lungs are the most commonly involved.
Manifests in several clinical forms, including: Sino-orbital, rhino-cerebral, sino-pulmonary, gastrointestinal, cutaneous, musculoskeletal, osteoarticular, disseminated and single organ disease involvement.
The various forms of mucormycosis have a predilection for host with specific characteristics: Sinoorbital and rhinocerebral disease are the most common in patients with diabetes, whereas Sinopulmonary and disseminated mucomycosis are more common in patients with severe immunosuppression.
Some patients have a prediction with a specific clinical manifestation where a certain species cause wound and storm associated cutaneous and muscularskeletal trauma.
Without early surgical management, rhino-cerebral disease disease is progressive and rapid, resulting in sinorbital symptoms and extension to the CNS, resulting in death.
Have an affinity for iron rich environments, acidic environments and in iron overload states.
Iron metabolism has a key role in the pathogenesis of mucormycosis and in host defenses and patience with diabetes.
Mucorales species are dependent on the acquisition of free ionic iron from infected hosts.
Metabolic acid doses and decreases the affinity of transferrin and ferritin, resulting in more free iron.
In patients with blast injuries, burns and other major trauma, mucormycosis may develop due to immune paralysis, causing local neutrophil dysfunction and immune dysregulation.
Classically associated with tissue necrosis due to vascular invasion and subsequent thrombosis.
Members of the order Mucorales have invasive characteristics related to secreted proteases, a ricinlike toxin, and affinity for endothelial cells, resulting in tissue infarction.
Mucorales species grow in nature as a mycelium producing sporangiospores that are inhaled into the respiratory tract, in which pulmonary alveolar macrophages are efficient in eliminating them by phagocytosis.
In patients who are immunocompromised and some sporangiospores are not cleared and adhere to and invade respiratory epithelial cells: hyphae forms emerge and invade vascular structures resulting in ischemia, necrosis, and hematogenous spread.
Angioinvasion, thrombosis, and tissue infarction are clinical hall marks of mucormycosis.
CotH spore coat proteins of rhizopus bind to host receptors glucose regulated protein 78 on nasal epithelial cells and integrin alpha 3 beta 1 alveolar epithelial cells, allowing for an invasion and thrombosis.
Metabolic acidosis in poorly control diabetes may account for inducing a higher risk of mucormycosis.
In patients who are immunocompromised, mucormycosis develops as a result of qualitative and quantitative defects in phagocytic activity with functional defects in macrophages, neutrophils and lymphocytes, including natural killer cells.
Glucocorticoids impair neutrophil and macrophage host responses against mucorales species.
Hyperglycemia and metabolic acidosis in patients with diabetes permit proliferation of hyphae and impair phagocytic oxidative and non-oxidative host responses.
Hypoalbuminemia contributes to the progression of mucormycosis.
Necrotic lesions occur because the fungus targets the vasculature.
Predominately affects immunocompromised patients.
The estimated disease burden in India is approximately seven times higher than the global average with more than 200,000 cases per year.
Among the invasive mycoses, mucormycosis is widely considered to be the most rapidly invasive and destructive.
Characterized by hyphae growing in and around vessels.
Fungal infection affects patients undergoing immunosuppressive therapy, have diabetes and hematologic malignancies.
Most common clinical presentation is rhinocerebral infection in diabetes.
Can manifest as superficial or deep infections.
Can appear as pustules, blisters, nodules, necrotic ulcerations, necrotic ulcerations echythema gangrenosum like lesions, or necrotizing cellulitis.
Intravascular thrombosis is a hallmark histological feature of cutaneous mucormycosis.
Platelet aggregation is induced by the interaction of fungal spores with plasma, IgG leading to immune complex formation.
Pulmonary infections are associated with cough, pleurodynia, hemoptysis, and shortness of breath.
Chest imaging may show annular consolidation central ground glass in opacity.
Diagnosis:
Early diagnosis, initiation of anti-full therapy significantly reduces mortality from approximately 80 to 40%.
Biopsy is required for diagnosis, as cultures and fungal stains are not sensitive for diagnosis.
Periorbital cellulitis, diplopia, focal pallatal necrosis, and any necrotic wounds are suggestive of the diagnosis.
Cutaneous mucormycosis can occur in immunocompetent persons following trauma.
Occasionally cutaneous forms can disseminate to pulmonary involvement.
The leading cause of cancer related death worldwide.
Affected persons may present with perorbital infection, external ophthalmoplegia, visual loss as a result of vascular tissue structure destruction.
Mucormycosis originates in the nose or paranasal sinuses, but patients may have minimal sinus changes on x-ray studies.
When diagnosis is suspected patient should undergo immediate endoscopy of the nose and sinuses for necrotic tissue.
For suspected sino-orbital disease staging includes CT of the paranasal sinuses and chest, as well as endoscopy of the nasal terminates with brush biopsy of lesions.
If diagnosis is suspected biopsy and culture should be performed and antifungal therapy started before test results return.
Definitive diagnosis depends on direct examination of clinical specimens, culture of tissue or bronchioalveolar lavage,fluid, and histopathologic evaluation.
Patient often fail antibiotic therapy before correct the pathological diagnosis is made.
Nosocomial and home environmental sources of mucorales species increase the risk of disease with contaminated air handling systems, arm boards, plants, construction sites, all implicated source of nosocomial mucomycosis as have bed linens contaminated with sporangiospores.
In immunocompromise patients G.I. mucomycosis develops after ingestion of sporangiospores in herbal remedies, homeopathic medicines, food, and substances consumed in the context of pica.
G.I. mucormoses can occur in low birthweight infants and is associated with high mortality as a result of G.I. perforation and intraabdominal dissemination.
Diagnoses usually relies on direct microscopic observation or isolation of the fungus by culture from infected tissues.
There is no clinically useful biomarker to identify the disease and conventional diagnostic methods lack sensitivities.
New PCR techniques are promising for diagnosis.
Resection of local lesions and intravenous amphotericin B can prevent dissemination of cutaneous disease.
Management requires, usually, aggressive surgical debridement of the infected tissues.
The degree of infection, occurrence of dissemination, timeliness of diagnosis, and reversibility of underlying immunodeficiencies are important factors in determining outcome and in the assessment of treatment strategies.
Successfulness of treatment is based on: early detection and staging of the disease, timely initiation of antifungal treatment, surgical resection of infected tissue, reversal of immunodeficiencies, and correction of metabolic abnormalities.
Timeline surgical treatment and proper antifungal therapy are required to reduce the risk of mortality.
First line antifungal treatment of mucormycosis consists of intravenous liposomal or a lipid complex amphotericin B formulation.
Liposomal amphotericin B is preferred over amphotericin B deoxcholate because of liposomal amphotericin B has less nephrotoxicity.
Posaconazole therapy is an effective salvage therapy.
Isavuconaxole is a day alternative to liposomal amphotericin B, especially for extended treatment, and for the treatment of patients whom amphotericin is not an option because of dose limiting nephrotoxicity.