|Year : 2022 | Volume
| Issue : 3 | Page : 431-434
A sinister call for the dermatologist from intensive care unit: Mucormycosis revisited
Vikas Pathania1, Rohit Kothari1, AW Kashif2, Kavita Bala Anand3, Prerna Guleria4, Ruby Venugopal1
1 Department of Dermatology, Command Hospital, Pune, Maharashtra, India
2 Department of Pathology, Armed Forces Medical College, Pune, Maharashtra, India
3 Department of Microbiology, Armed Forces Medical College, Pune, Maharashtra, India
4 Department of Pathology, Command Hospital, Pune, Maharashtra, India
|Date of Submission||13-Oct-2021|
|Date of Decision||04-Nov-2021|
|Date of Acceptance||09-Nov-2021|
|Date of Web Publication||22-Jan-2022|
Department of Dermatology, Command Hospital, Pune - 411 040, Maharashtra
Source of Support: None, Conflict of Interest: None
Mucormycosis is a rare angioinvasive fungal infection commonly found in immunocompromised individuals, especially in an intensive care setting. Rhino-orbito-cerebral (ROCM) form is the most common presentation in patients with diabetes mellitus in India. A high index of clinical suspicion in picking up early subtle clinical signs such as periorbital edema, sinusitis, and ophthalmoplegia coupled with an aggressive management plan including systemic antifungals and surgical debridement of invaded tissue can often avert an otherwise fatal outcome in susceptible patients. We report a case of ROCM in a 37-year-old male with diabetic ketoacidosis.
Keywords: Diabetic ketoacidosis, liposomal amphotericin B, mucormycosis, ROCM
|How to cite this article:|
Pathania V, Kothari R, Kashif A W, Anand KB, Guleria P, Venugopal R. A sinister call for the dermatologist from intensive care unit: Mucormycosis revisited. Med J DY Patil Vidyapeeth 2022;15:431-4
|How to cite this URL:|
Pathania V, Kothari R, Kashif A W, Anand KB, Guleria P, Venugopal R. A sinister call for the dermatologist from intensive care unit: Mucormycosis revisited. Med J DY Patil Vidyapeeth [serial online] 2022 [cited 2022 May 21];15:431-4. Available from: https://www.mjdrdypv.org/text.asp?2022/15/3/431/336315
| Introduction|| |
Mucormycosis is a rare fungal infection usually occurring in immunosuppressed individuals. It is caused by ubiquitous fungi belonging to the order Mucorales and associated with angioinvasion and high mortality rates ranging from 20% to 50% for localized and 70%–90% for disseminated disease. The incidence of mucormycosis has been increasing in recent decades, perhaps owing to the rise of immunocompromised patients. Its most common presentations include rhino-orbito-cerebral (ROCM) (34%), pulmonary (21%), cutaneous (20%), and disseminated (14%). ROCM is most often seen in patients with diabetes mellitus (DM). Pulmonary mucormycosis is seen frequently in patients with hematological malignancies and transplant recipients. Cutaneous mucormycosis is commonly seen following trauma in immunocompetent hosts. We report a case of ROCM in a 37-year-old male with diabetic ketoacidosis (DKA) with a fatal outcome.
| Case Report|| |
A 37-year-old male, a known case of Type-I DM presented to the emergency department with nausea, vomiting, and giddiness of 1-day duration. He was diagnosed and managed as a case of DKA in the intensive care unit (ICU). At admission, he was found to have a subtle erythematous swelling over the left cheek, which he gave a history of being present for 3 days and associated with mild pain [Figure 1]. Following admission, the swelling progressed rapidly over the next 2 days to involve the left cheek, adjoining regions of the nose, and area below the left eye, which was now associated with severe pain and developed grayish-blue discoloration with adherent eschar [Figure 2]. However, the lesion was nontender and firmly adherent to underlying structures. An ENT examination revealed trismus, bilateral nasal cavities congested and edematous, and multiple polyps arising from the middle meatus.
|Figure 2: Well-defined necrotic eschar over left cheek at day 3 of admission|
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On investigation, all hematological and biochemical parameters were normal except leukocytosis of 12,000/mm3 and microcytic hypochromic anemia (Hb: 9.4 g/dl). The radiography of paranasal sinuses was normal. A skin biopsy from the lesion revealed nonspecific mixed infiltrate in the dermis and necrosis of collagen fibers in the deeper part. No evidence of bacterial colonies, granuloma, or giant cells was seen [Figure 3]. Periodic Acid-Schiff (PAS) and Grocott methenamine silver (GMS) stain did not reveal any fungal element. An impression smear from the biopsy tissue was also negative for fungal elements on lactophenol cotton blue (LCB) mount. However, the same rapidly grew colonies at room temperature (25°C) in 1–2 days on sabouraud dextrose agar, which were initially white cottony and later turned grayish black. Growth was inhibited by cycloheximide [Figure 4]. The LCB mount from the growth showed broad nonseptate hyphae with long sporangiophores terminating in round sporangia [Figure 5]. A nasal swab revealed broad aseptate hyphae on GMS stain [Figure 6]. A head and neck magnetic resonance imaging (MRI) revealed soft tissue thickening of the left superior orbital fissure, left cavernous sinus, and along left maxillary nerve till foramen ovale. A computed tomography (CT) of paranasal sinuses showed radiolucency in the left maxillary sinus with acute on chronic maxillary sinusitis without osseous erosion.
|Figure 3: Rapidly growing colonies of mucormycosis on sabouraud dextrose agar which were initially white cottony and later turned grayish black|
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|Figure 4: Lactophenol cotton blue mount from the growth showing broad nonseptate hyphae with long sporangiophores terminating in round sporangia|
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|Figure 5: Grocott methenamine silver stain of nasal swab showing broad aseptate hyphae|
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|Figure 6: Section of skin biopsy showing focal areas of mixed infiltrat without granuloma formation in the dermis (a) (H and E, ×10) with necrosis of collagen fibers in deeper part (b) (H and E, ×40)|
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The patient was managed with injection liposomal amphotericin B 300 mg OD initially. Syrup posaconazole 200 mg BD was also added 1 week after amphotericin B. He underwent a surgical debridement on day 3 of admission which intraoperatively revealed necrotic mucosa of the left lateral wall of the nose including the inferior turbinate, middle turbinate, and middle meatus with multiple polyps arising from the left maxillary and ethmoid sinus and a histopathological picture consistent with mucormycosis with PAS stain positive for fungal hyphae within vessel walls [Figure 7]. The postoperative period was uneventful, and he was recovering, when the patient contracted COVID-19 infection and succumbed to severe pneumonia with acute respiratory distress syndrome on day 30 of surgery and day 33 of antifungal treatment.
|Figure 7: Section from maxillary sinus and bone showing broad aseptate fungal hyphae invading the fibroconnective tissue (a) (H and E, ×400). Periodic Acid Schiff stain of section from a blood vessel showing similar fungal hyphae within the lumen as well as invading the vessel wall (b) (Periodic Acid Schiff × 200)|
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| Discussion|| |
Mucormycosis is an opportunistic and invasive fungus belonging to the division Glomeromycota and subphylum mucormycotina. They are ubiquitously found in nature in decaying organic matter, soil, and animal excreta. In India, Rhizopus oryzae is the most common cause of the disease accounting for up to 70% of cases with Apophysomyces elegans, Apophysomyces variabilis, and Rhizopus homothallic being other emerging species. Mucorales are rapidly growing fungi releasing a large number of airborne spores which on intact skin and the immune system are not able to initiate infection but in an immunocompromised patient or a skin breach in an immunocompetent host (burns, soiled dressings, and trauma) can lead to rapidly invasive disease., ROCM is the most common presentation associated with DKA or uncontrolled DM with 88% of patients with ROCM having DM as per one Indian study., Our patient was a known diabetic with the onset of his symptoms appearing at the time of his admission for DKA. The presence of hyperglycemia and low pH in DKA renders phagocytes of the immune system ineffective by impairing chemotaxis and intracellular killing of the organism. Moreover, it has been demonstrated that patients with DKA have elevated levels of free iron in their serum, which supports the growth of R. oryzae at an acidic pH, thus explaining the unique susceptibility of these patients to mucormycosis. Finally, mucormycosis infections are characterized by early angioinvasion, and thus facilitating the rapid hematogenous spread of infection and simultaneously causing ischemic necrosis preventing the delivery of leucocytes and antifungals to the foci of infection.
Considering the rapidly progressive and fatal course of ROCM, a high index of clinical suspicion is warranted in patients with DKA/uncontrolled DM, especially in an ICU setting. Certain “red flag” signs of an evolving ROCM include cranial nerve palsy, diplopia, sinus involvement, periorbital swelling, proptosis, orbital apex syndrome, and ulcers on the palate. Our patient presented with painful swelling over the left cheek, which rapidly progressed over the next 3 days to form a necrotic eschar with left eyelid edema and ophthalmoplegia. A necrotic eschar over the maxillary, facial, or sino-orbital mucosal surface can be an early sentinel marker for invasive mucormycosis as in our case. Herein lies the importance of early investigations with prompt imaging, histology, and microbiology in a susceptible patient with suspicious early symptoms. Imaging in the form of CT and MRI can delineate the extent of the lesion before surgery in the form of mucosal thickening, osseous erosion, sinusitis, and orbital and/or cerebral extension. Microscopic examination and culture can help confirm mucormycosis and exclude other angioinvasive fungi with similar presentation such as aspergillus and Fusarium. On direct microscopy, hyphae of Mucorales are non or pauci-septate, ribbon-like, and show wide-angled branching. Tissue histopathology shows neutrophilic or granulomatous inflammation, but may be absent in severe immunosuppressed cases. Perineural and angioinvasion is the hallmark of the disease on histopathology. Fungal elements can be seen easily on hematoxylin-eosin, PAS, and GMS staining. Mucorales grow rapidly in potato dextrose agar and sebourauds agar at 25°C–30°C but may be positive in only 50% cases. Species identification is difficult and of value in the epidemiological investigation of outbreaks. Newer serology and molecular assays targeting 18S rRNA genes are under development.
Principles of the management of mucormycosis include timely initiation of antifungal agents, aggressive surgical debridement, and reversal of underlying immune suppression where possible. Liposomal amphotericin B and more recently isavuconazole is employed as first-line therapy, while posaconazole serves as salvage therapy. Other adjunctive agents studied include hyperbaric oxygen, granulocyte-macrophage colony-stimulating factor, interferon-γ, and investigational drug VT-1161, an inhibitor of fungal CYP51.,
| Conclusion|| |
This case is reported to highlight mucormycosis as a rapidly invasive infection that can prove fatal in susceptible individuals if not postsurgically disfiguring. A high index of clinical suspicion in picking up subtle early signs of spread and aggressive management is the key to a favorable outcome in most cases. Dermatologists and critical care specialists need to be alive to the fact that in the present era of the COVID-19 pandemic, these patients may be at a higher risk of contracting this sinister infection.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]