Group 14 presented on mucormycosis, a fungal infection caused by mold in the soil. It primarily affects immunocompromised patients like those with diabetes or undergoing chemotherapy. Symptoms vary depending on the infected site but commonly include nasal congestion, vision changes, and skin lesions. Diagnosis involves imaging, biopsy of infected tissues, and identifying characteristic fungal hyphae. Treatment requires controlling underlying conditions, surgical debridement of infected areas, and high-dose antifungal medications like amphotericin B. Even with aggressive treatment, outcomes are often poor if the patient's immunity cannot be improved.
4. OVERVIEW
• Mucormycosis results from a variety of fungi that may be typically
innocuous environmental fungi and primarily affects
immunocompromised patients. For this reason, the clinician must
have a high index of suspicion to diagnose this disease in any of its
forms when it presents in a patient with these risk factors.
• Starting with the features of the host and the tropism of the fungus
once it invades the host, this activity discusses the manifestations of
this disease, appropriate evaluation/management of mucormycosis,
and highlights the role of the interprofessional team in evaluating and
treating patients with this condition.
5. INTRODUCTION
• Mucormycosis is an opportunistic fungal infection of the zygomycete
family that can cause various types of infections. In most cases, there
exist underlying conditions that predispose the hosts to the infection.
As the fungi responsible are typical environmental organisms, they
are usually non-pathologic in immunocompetent individuals. In
immunosuppressed patients, however, these otherwise innocuous
organisms can become a devastating and difficult-to-treat
opportunistic infection.
6. CONT’N…
• There are several clinical forms of infection: pulmonary,
gastrointestinal, cutaneous, encephalic, and rhinocerebral. The latter
must be differentiated from allergic fungal sinusitis, which is a non-
invasive, local overgrowth in immunocompetent patients.
Mucormycosis is characterized by tissue necrosis due to an invasion
of blood vessels and subsequent thrombosis, which usually follows a
rapid progression. The key to treatment is early and aggressive
surgical debridement, along with high doses of intravenous antifungal
therapy
7. ETIOLOGY
• Mucormycosis is an infectious disease caused by a fungus of the class
of Zygomycetes and the order of Mucorales.
• The species most frequently isolated from patients are
Apophysomyces (A. variabilis), Cunninghamella (C. bertholletiae),
Lichtheimia [Absidia] (L. corymbifera L. raosa), Mucor (M.
circinelloides), Rhizopus (R. arrhizus (oryzae) R. microsporus),
Rhizomucor (R. pusillus), and Saksenaea (S. vasiformis). These are
common environmental organisms that are not harmful to humans
who are immunocompetent.
8. CONT’N…
• In patients with overt immunocompromise (i.e., transplant patients,
HIV, patients of chronic steroids or disease-modifying anti-rheumatic
medications, leukemia or other cancer patients), they can present
with rapidly progressive necrotizing infection. Similarly, uncontrolled
diabetics (particularly those with a history of diabetic ketoacidosis)
are also at risk.
9. EPIDEMIOLOGY
• Mucorales are thermotolerant fungi found in soil and decaying matter
and rarely cause disease because of low virulence. Rhizopus is
considered the most frequent fungal infection in
immunocompromised populations, though various Aspergillus species
are also commonly encountered.
• Mucormycosis has increased its frequency because of the increased
prevalence of immunosuppression states in the general population
owing to improved lifespan in cancer and transplant patients, as well
as expanding indications for immunosuppressive medications for
various autoimmune diseases.
10. CONT’N…
• The primary route of infection is via air spore inhalation, which
deposits in the paranasal sinuses and the lung. Other routes less
frequently encountered result from ingestion or direct skin
inoculation.
11. RISK FACTORS
• Risk factors include diabetes mellitus, malnutrition, malignancies
(lymphomas and leukemias), renal failure, organ transplant, burns,
immunosuppressive therapy, cirrhosis, and AIDS. Patients with
diabetic ketoacidosis and patients on dialysis who receive treatment
with iron chelator deferoxamine are also more susceptible to
mucormycosis.
• The most commonly encountered clinical form is rhinocerebral
mucormycosis, and the resultant mortality, even with
pharmacological and/or surgical treatment is high unless the immune
system status can be restored.
12. PATHOPHYSIOLOGY
• Mucorales are present in soil and decaying matter, in
immunocompetent people, the spores of Mucorales that reach the
respiratory tract adhere to the nasal mucus and are eliminated either
by swallowing or sneezing, if there is any wound in the mucous
membranes, the polymorphonuclear neutrophils phagocytose and
destroy the fungal structures.
• Neutrophils are the host defense against these infections; therefore,
individuals with neutropenia or neutrophil dysfunction are at the
highest risk. This is seen clinically in leukemia patients and bone
marrow transplant patients, who are at the highest risk.
13. CONT’N…
• Rhizopus arrhizus studies have demonstrated that the ketone bodies
present in these patients are metabolized by a ketone reductase,
which allows them to survive in conditions with an acid medium;
thus, the fungi become hyphal forms in host tissues and then invade
blood vessels. This extensive angioinvasion results in vessel
thrombosis and tissue necrosis.
• Diabetes patients usually present with clinically uncontrolled diabetes
and the increased amounts of circulating glucose, providing excellent
conditions for the rapid development of filamentous structures that
first bind to blood vessels and then penetrate them, completely
clogging them in a few days and causing extensive areas of ischemic
necrosis.
14. CONT’N…
• Also, metabolic acidosis prevents chemotaxis of polymorphonuclear
leukocytes, causes decreased phagocytic activity, and reduces local
inflammatory response in a patient whose immune system is already
compromised from one or more additional diseases.
15. CLINICAL PRESENTATION
• Mucormycosis can invade different body systems. Sites of infection
include the lung, central nervous system, paranasal sinuses,
gastrointestinal system, and the skin. Its clinical manifestations are
varied but characteristically demonstrate rapid progression. The
clinical manifestations largely depend on the route of entry of the
fungus and the predisposing disease.
16. Rhinocerebral Mucormycosis
• Rhinocerebral mucormycosis is initiated with inhalation of spores into
the paranasal sinuses and the invasion of blood vessels in the tissue.
The infection starts with nasal congestion or discharge, though it may
progress to facial numbness, blurry vision, nasal discharge,
nasofrontal headache, ocular pain, fever, diplopia, and chemosis.
Intranasal lesions characteristically have painless ulcerations with
exudate and necrotic tissue, and usually progress rapidly over days.
• In an immunocompromised patient with prolonged nasal symptoms,
one should maintain a low threshold to obtain a biopsy to rule out
mucormycosis (often termed “invasive fungal sinusitis – IFS).
17. Pulmonary Mucormycosis
• Pulmonary mucormycosis consists of the development of bilateral
pneumonia, which is rapidly progressive and the result of the
inhalation of infectious material. The most common clinical features
are fever, hemoptysis, dyspnea, and cough. This clinical form is seen
more frequently in patients with hematological diseases. This
pulmonary condition can present as bronchitis, bronchopneumonia,
and even pulmonary embolism.
• The infection can spread to contiguous tissues, such the mediastinum
and heart, though it may also lead to cavitary lesions that can mimic
tuberculosis or more benign allergic fungal disease.
18. Cutaneous Mucormycosis
• Cutaneous mucormycosis presents in both primary and secondary
disease. In primary disease, the skin infection results from direct
inoculation and in secondary form, by dissemination from other
locations.
• The primary form often occurs in patients with burns and traumatic
skin wounds, usually appears as a single and indurated area of
cellulitis that progresses a necrotic lesion, other forms of manifesting
are abscesses, skin swelling, and necrosis.
19. Gastrointestinal Mucormycosis
• Gastrointestinal form occurs via the ingestion of contaminated food,
though the use of contaminated herbal medicines has been linked to
gastrointestinal disease development.
• There may be nausea, vomiting, ulceration, and thrombosis of the gastric,
esophageal and intestinal mucosa, manifested by diarrhea, hematemesis,
and melena.
• Perforation and peritonitis can result from necrotic ulcers. Also, the
presence of bowel infarctions and hemorrhagic shock lead to poor
prognosis.
• Gastrointestinal symptoms are rare in all but the most severely
immunocompromised (leukemia patients, intestinal transplant patients,
etc.), owing to a large amount of immune tissue in the GI tract.
20. Disseminated form of Mucormycosis
• Disseminated form of mucormycosis may originate from any primary
sites of infection, manifestations are nonspecific, which makes
diagnosis even harder, but a metastatic skin lesion is undoubtedly a
sign to suspect disseminated mucormycosis and portends a dismal
prognosis.
21. DIAGNOSIS
• Routine blood work is rarely diagnostic but can find the presence of
neutropenia as a correlating risk factor.
• Imaging can be valuable in evaluating the extent of the disease.
Radiological imaging studies are required to investigate areas with
suspected mucormycosis, specifically in the brain, paranasal sinuses,
lungs, and abdomen, always guided by the clinic.
22. CONT’N…
• The first intervention in the suspicion of rhinocerebral mucormycosis
is with the endoscopic evaluation and biopsy of the sinuses to
examine for tissue necrosis and to obtain examples of tissue, the
presence of characteristic hyphae provides a presumptive diagnosis.
The area of highest-yield, and greatest accuracy, is to biopsy the
middle turbinate.
• A computed tomography (CT) scan can help evaluate contiguous
structures such as the eyes and brain, findings in CT scan included
soft tissue edema of cavity mucosa, sinus mucoperiosteal thickening,
bone erosions, and orbital invasions.
23. CONT’N…
• Patients with immunosuppression and respiratory symptoms should
have a CT chest for possible pulmonary mucormycosis. The
presentation of the infection does not differ from pneumonia;
therefore, the diagnosis is difficult.
• Chest radiologic findings are pleural effusion, nodules, consolidation,
and ground-glass infiltrates. Bronchoalveolar lavage can show broad
nonseptate hyphae.
24. CONT’N…
• If there is a concern for gastrointestinal mucormycosis (abdominal
pain, gastrointestinal bleeding), a CT scan to evaluate for colitis is
necessary.
• Once confirmed, colitis should be further investigated by endoscopy
with biopsy. The presence of characteristic hyphae in the biopsy
provides a presumptive diagnosis.
25. TREATMENT AND MANAGEMENT
• The standard management of mucormycosis requires early diagnosis,
a reversal of risk factors and underlying illness, surgical debridement,
and prompt administration of intravenous antifungals – usually
amphotericin B. This entails the prompt management of
hyperglycemia, acidosis, and cessation of immunosuppressive agents
when possible.
• Amphotericin B is considered first-line therapy for mucormycosis. The
lipid formulation of amphotericin B is administered in high doses
intravenously once a day as initial therapy. The initial starting dose is
5 mg/kg IV daily, with a maximum dose of 10 mg/kg IV. Treatment
duration depends upon the patient’s clinical picture.
26. CONT’N…
• Surgical debridement of infected tissue should be urgently performed
to limit the further spread of infection. Aggressive surgical
debridement of necrotic tissue should take place immediately. This
may involve radical facial resections, partial pneumonectomy,
colectomy, etc., in accordance with the site of disease.
• Similar to necrotizing fasciitis, this requires very aggressive surgical
management and often carried dramatic morbidity. Unless the
immune status can be restored, the outcomes are unfortunately very
poor even with the most aggressive therapies and drastic surgical
intervention.
27. CONT’N…
• Posaconazole or isavuconazole has some evidence as second-line
therapy in mucormycosis. For salvage treatment, posaconazole 200
mg IV four times daily is recommended. The guidelines do not
support the combination of amphotericin and posaconazole.
• Other adjuncts include hyperbaric oxygen. The increased oxygen
pressure improves the ability of neutrophils to kill the organism and
facilitates wound healing.
28. DIFFERENTIAL DIAGNOSIS
• In a case of mucormycosis in its rhinocerebral form, one must
consider different pathologies such as orbital cellulitis and cavernous
sinus thrombosis.
• When we consider the diagnosis of pulmonary mucormycosis, we
should think about aspergillosis, nocardiosis, and Wegener’s
granulomatosis.
29. PROGNOSIS
• The prognosis is dependent upon the timing of therapeutic
intervention, as well as the degree of the underlying
immunodeficiency of the patient with mortality ranging from 25% to
87% depending on the site of infection.
• Severity and poor prognostic indicators include disseminated
infection, renal injury, central nervous system disease, and
inadequate response to medical treatment.
• The most important prognostic factor is the ability to restore a
normal immune status. If this is not possible, the prognosis is
uniformly dismal. If immunocompetence can be restored, even
temporarily, then prognosis does improve.
30. COMPLICATIONS
• Complications of mucormycosis subdivide into those that result from
the disease itself and those that are caused by the antifungal
treatment. Complications associated with the disease are cavernous
sinus thrombosis, disseminated infection, periorbital destruction,
palatine ulcers, osteomyelitis, and death.
• Complications due to treatment are nephrotoxicity, hypokalemia,
prolonged hospitalization (specifically with the use of deoxycholate
amphotericin B).
31. PEARLS AND OTHER ISSUES
• The key to the diagnosis is the identification of key risk factors and
hallmark symptoms. The “classic” presentation is the immunocompromised
patient, with rhinosinusal involvement, demonstrating a very rapid
progression of infection, and the presence of tissue necrosis. If there is any
suspicion, early endoscopic biopsy is warranted to avoid disaster
potentially.
• Depending on the degree of immunosuppression and predisposing
conditions, the progression of the disease can be acute, fulminant, or
chronic.
• The identification of the exact species that cause mucormycosis is not
straightforward due to the difficulty of isolating the fungus in culture
media. However, regardless of the causative species and clinical
presentation, therapeutic management is the same.
32. ENHANCING HEALTHCARE TEAM OUTCOMES
• Mucormycosis is a life-threatening fungal infection, with very high
mortality. Interprofessional management typically consists of
infectious disease, otolaryngology, hematology/oncology,
endocrinology, microbiology, specialty-trained nursing, and
pharmacist assistance of therapeutic drug administration and
monitoring, all collaborating across disciplines to achieve optimal
patient results.
• Coordination of care among nurses and clinicians will lead to the best
outcomes. [Level 5] However, even with prompt, adequate evaluation
and treatment by the interprofessional team, the prognosis remains
poor.