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Year : 2023  |  Volume : 11  |  Issue : 1  |  Page : 89-92

Mucormycosis and cryptococcosis with gastrointestinal involvement in a patient with poorly managed diabetes

1 Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
2 Department of Medicine, King Abdulaziz Medical City, National Guard Health Affairs, Riyadh, Saudi Arabia
3 Department of Anatomic Pathology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

Date of Submission29-Apr-2022
Date of Decision07-Aug-2022
Date of Acceptance20-Nov-2022
Date of Web Publication04-Jan-2023

Correspondence Address:
Fahad I Alsohaibani
Department of Medicine, King Faisal Specialist Hospital and Research Centre, P. O. Box 3354, Riyadh 11211
Saudi Arabia
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/sjmms.sjmms_201_22

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Mucormycosis and cryptococcosis are invasive fungal infections that mostly infect immunocompromised patients and are associated with high mortality rates. Here, we report a case of a 54-year-old male with poorly controlled diabetes mellitus who was initially admitted with a complaint of right frontal headache and vomiting for 5 days. The patient was found to have paranasal sinuses mucormycosis, and later developed gastrointestinal cryptococcosis. A multidisciplinary approach and early management are important to avoid any delay in managing these life-threatening infections. To the best of the authors' knowledge, this is the first case reporting concurrent invasive fungal infections in a patient.

Keywords: Cryptococcosis, diabetes, gastric mucosa, gastrointestinal, headache, invasive fungal infection, paranasal sinus, mucormycosis, mycoses

How to cite this article:
Aldahash BA, Alnemer MA, Alsaad KO, Alsohaibani FI. Mucormycosis and cryptococcosis with gastrointestinal involvement in a patient with poorly managed diabetes. Saudi J Med Med Sci 2023;11:89-92

How to cite this URL:
Aldahash BA, Alnemer MA, Alsaad KO, Alsohaibani FI. Mucormycosis and cryptococcosis with gastrointestinal involvement in a patient with poorly managed diabetes. Saudi J Med Med Sci [serial online] 2023 [cited 2023 Mar 26];11:89-92. Available from: https://www.sjmms.net/text.asp?2023/11/1/89/367038

  Introduction Top

Multifocal fungal infections in highly immunocompromised patients are likely to include two or more pathogens, especially if the effects of antifungal agents are insufficient on the lesions. Invasive fungal diseases (IFDs) are associated with high morbidity and mortality and are more common among patients with immune deficiency and neutropenia. In non-neutropenic patients, IFDs especially occur in those with fungal colonization, total parenteral nutrition, renal replacement therapy, mechanical ventilation, and diabetes mellitus.[1] The prevalence of IFDs in diabetic patients requiring intensive care unit (ICU) admission was reported to be as high as 41.9%.[2] ICU admission due to organ failure is another important risk factor for IFDs. A multinational study that included patients from 1265 ICUs found that 19% of the infected patients had fungal infection, with Candida being the most common pathogen followed by Aspergillus.[3]

During the coronavirus disease-2019 (COVID-19) pandemic, numerous IFDs, such as invasive candidiasis, pulmonary aspergillosis and mucormycosis, were increasingly reported in patients. This was attributed to the combination of hyperglycemia, the use of steroid therapy along, and an inflammatory state of COVID-19, creating a dysfunctional immune response that allowed secondary infections.[4],[5]

Cryptococcosis, primarily caused by Cryptococcus neoformans and Cryptococcus gattii, is a common and lethal disease, especially among HIV-positive patients. While effective antiretroviral therapies have reduced Cryptococcal infections among HIV-positive patients, the wide use of chemotherapy and immunosuppressive agents has contributed to an overall increase in its incidence.[6] Cryptococcal infection commonly causes meningoencephalitis and pneumonia; gastrointestinal (GI) tract involvement was first reported about 50 years ago, but in general, is rarely reported.[7]

Mucormycosis, a rare but life-threatening infection caused by fungi of the order Mucorales, has an increasing incidence, particularly among patients with diabetes mellitus, hematologic malignancies, and those who have undergone bone marrow transplantation.[8] The mortality rate with mucormycosis is high (>40%), and it is even higher among patients with hematological malignancies and bone marrow transplantation.[9] Mucormycosis is categorized as rhino-cerebral (the most common type), pulmonary, gastrointestinal, cutaneous, renal, and disseminated diseases.[10]

Here, we present the case of a middle-aged male patient with uncontrolled diabetes who was initially diagnosed with rhino-cerebral mucormycosis, and during the same hospital course, was diagnosed with GI cryptococcosis.

  Case Report Top

A 54-year-old male with a longstanding history of uncontrolled diabetes mellitus (HbA1c of 13%) was admitted to our hospital with a complaint of right frontal headache and vomiting for 5 days. The initial laboratory investigations showed normal complete blood count, renal, and hepatic profiles but elevated glucose level (24.4 mmol/L). His blood culture and HIV serology were negative and the CD4 count was normal. The initial brain CT scan showed circumferential mucosal thickening in the sphenoid sinuses, which was more on the right side, and mild scattered mucosal thickening in the other paranasal sinuses. In addition, there was fluid opacification of the mastoid air cells and middle ear cavities. The patient was started on insulin and Augmentin intravenously.

Five days later, the patient complained of sudden loss of vision in the right eye and jaw pain. The brain CT scan was repeated, and it showed progression of the inflammatory changes in the paranasal sinuses without acute brain insult. Giant cell arteritis was suspected and treatment with pulse intravenous methylprednisolone 1 gm daily was initiated. Temporal artery biopsy was performed 2 days later and found to be normal, and corticosteroids were discontinued. However, the patient's symptoms worsened, and thus a third CT scan brain was obtained, which showed progression of the sinusitis to the retropharyngeal abscess. A sinonasal biopsy was obtained, and its histopathological examination showed positive GMS stain for fungus, suggestive of mucormycosis [Figure 1]. The patient was then treated with amphotericin B. A week later, the patient developed sepsis, and thus was started on broad-spectrum antibiotics including vancomycin and meropenem. The chest and abdominal CT scan showed mild bilateral pleural effusions and mucosal edema involving the ascending colon without obstruction or significant lymphadenopathy.
Figure 1: Sinonasal biopsy showing non-pigmented, pauciseptate ribbon-like hyphae with right angle branching. The morphological features are most consistent with mucorales genera. Periodic acid Schiff (left image) and Grocott methenamine silver (right image) special stains × 600

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Two weeks after his admission, he developed melena mixed with streaks of blood and his hemoglobin dropped from 83 to 75 g/L. Subsequently, the patient underwent an upper GI endoscopy and sigmoidoscopy. The upper GI endoscopy revealed severe erythematous gastritis and a huge gastric ulcer covered by necrotic-looking tissues with non-bleeding visible vessel, which was clipped [Figure 2]. Multiple biopsies were obtained from the edges of the ulcer. Sigmoidoscopy revealed pale mucosa, with ischemic changes 18–25 cm from the anal verge [Figure 3], following which biopsies were obtained.
Figure 2: Huge gastric corpus ulcer with stigmata of recent bleeding covered by necrotic-looking tissue over the greater curvature with abnormal mucosa underneath and nonbleeding visible vessel seen, a hemoclip was placed

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Figure 3: Severe pale mucosa with ischemic changes noted in the rectosigmoid area

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Microscopic examination of the gastric mucosa demonstrated severe acute chronic inflammation, fibrinous exudate, and extensive ulceration. In the rectal mucosa, numerous fibrin microthrombi were also identified. Periodic acid Schiff (PAS) and Grocott methenamine silver (GMS) special stains demonstrated numerous fungal microorganisms in the form of single and clustered small (2–10 μm) narrow-based budding yeasts in ulcerated gastric and rectal mucosa, suggestive of cryptococcus species [Figure 4]a and [Figure 4]b. Specific stains such as Fontana-Masson or mucicarmine stain were not available, and the tissues were not sent for microbiological cultures. The immunohistochemical staining for cytomegalovirus was negative. Despite the early diagnosis and appropriate treatment with broad-spectrum antibiotics and an antifungal agent, the patients' condition deteriorated with refractory septic shock and multiorgan failure, and unfortunately, he passed away.
Figure 4: (a and b) Numerous fungal microorganisms in the form of single and clustered, small (1–10μ) narrow-based budding yeasts admixed with a fibrinous exudate in the ulcerated gastric (a) and rectal (b) mucosae with morphological features most consistent with cryptococcus species. (a) Periodic acid Shciff (PAS) stain, ×600, (b) Grocott methenamine silver (GMS) stain, ×600

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  Discussion Top

Hematological malignancies, poorly controlled diabetes mellitus, immunosuppressive therapy, AIDS, and/or long-term corticosteroids use are risk factors for opportunistic infections, especially IFDs such as cryptococcosis and mucormycosis. In our case, the patient had a history of uncontrolled diabetes mellitus who presented with severe headache, and later, was found to have rhino-cerebral mucormycosis. Therefore, clinicians should have a high index of suspicion when dealing with patients with uncontrolled diabetes mellitus presenting with headache or nasal congestion, as a misdiagnosis can cause delay in the proper treatment or inappropriate administration of corticosteroids, which may lead to deleterious outcome.[11]

Gastrointestinal mucormycosis is relatively uncommon (5–13% of all mucormycosis), but has a high mortality rate of about 50%. Gastric and colonic involvement are the most frequently affected portions of the GI tract. Giant ulcers are the most common gross manifestation, with rolled, irregular edges that may mimic malignancy. Mucormycosis superinfection can also occur in previously ulcerated tissues, and can lead to a disseminated disease.[9],[10] A combined approach of surgical debridement and medical treatment using amphotericin derivative, isavuconazole, or posaconazole is strongly recommended for patients with mucormycosis including gastrointestinal mucormycosis because the infection is associated with a high risk of perforation.[12]

Cryptococcosis is one of the most common opportunistic invasive fungal pathogens that can cause fatal infection in immunocompromised patients. Clinical presentation varies from being asymptomatic to life-threatening central nervous system (CNS) involvement such as meningoencephalitis in HIV-positive patients with low CD4 counts (<200 cells/mm3). Globally, approximately 957,900 cases of cryptococcal meningitis occur each year, resulting in 624,700 deaths within 3 months of infection in HIV-positive patients.[13] GI involvement in cryptococcosis is very rare but mostly affects immunocompromised patients: between 1951 and 2008, 30 cases of GI cryptococcosis were identified in the literature, of which 26 (86.7%) were in immunocompromised patients.[14] A review of 24 autopsy cases of disseminated or pulmonary cryptococcal infection showed that 33% has GI involvement.[15] GI involvement can develop at any level of the GI tract, but colon is the most frequently affected site. Management of cryptococcal infection varies, depending on the localization and evidence of dissemination. Non-CNS, non-severe pulmonary, and localized cryptococcal infection can be treated with fluconazole alone. Intravenous amphotericin B is considered as the first line of treatment for disseminated cryptococcus.

In this case, the patient had uncontrolled diabetes mellitus and received high-dose corticosteroid and broad-spectrum antibiotics that put him at a risk of invasive fungal infections. The diagnosis of mucormycosis and cryptococcosis was based on histopathological examination using PAS and GMS stains by an expert pathologist of tissues obtained from nasal turbinate and gastric and rectal mucosae, respectively. Although the patient was managed appropriately, given that his overall condition was poor and the invasiveness of the fungal infections in general, it led to his mortality.

  Conclusion Top

Gastrointestinal fungal infections including cryptococcosis are extremely rare. The current case explored the different clinical presentations of two different fungal infections and the risk factors, diagnosis, treatment, and prognosis of such invasive infections. Given the highly lethal aspect of IFDs, vigilance of its risk factors and clinical presentation will lead to early diagnosis and treatment to improve the prognosis.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient's kin gave consent for the patient's images and other clinical information to be reported in the Journal. They understand that the patient's name and initials will not be published, and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Peer review

This article was peer-reviewed by one independent and anonymous reviewer.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

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Vincent JL, Rello J, Marshall J, Silva E, Anzueto A, Martin CD, et al. International study of the prevalence and outcomes of infection in intensive care units. JAMA 2009;302:2323-9.  Back to cited text no. 3
Singh AK, Singh R, Joshi SR, Misra A. Mucormycosis in COVID-19: A systematic review of cases reported worldwide and in India. Diabetes Metab Syndr 2021;15:102146.  Back to cited text no. 4
Hoenigl M, Seidel D, Carvalho A, Rudramurthy SM, Arastehfar A, Gangneux JP, et al. The emergence of COVID-19 associated mucormycosis: A review of cases from 18 countries. Lancet Microbe 2022;3:e543-52.  Back to cited text no. 5
Kwon-Chung KJ, Fraser JA, Doering TL, Wang Z, Janbon G, Idnurm A, et al. Cryptococcus neoformans and Cryptococcus gattii, the etiologic agents of cryptococcosis. Cold Spring Harb Perspect Med 2014;4:a019760.  Back to cited text no. 6
Chaitowitz M, Shaw ML, Mokoena TR. Gastrointestinal cryptococcosis presenting as spontaneous jejunal perforation in a nonimmunocompromised host. Dig Dis Sci 2003;48:1196-9.  Back to cited text no. 7
Cornely OA, Alastruey-Izquierdo A, Arenz D, Chen SC, Dannaoui E, Hochhegger B, et al. Global guideline for the diagnosis and management of mucormycosis: An initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium. Lancet Infect Dis 2019;19:e405-21.1.  Back to cited text no. 8
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Kaur H, Ghosh A, Rudramurthy SM, Chakrabarti A. Gastrointestinal mucormycosis in apparently immunocompetent hosts-a review. Mycoses 2018;61:898-908.  Back to cited text no. 10
Trief D, Gray ST, Jakobiec FA, Durand ML, Fay A, Freitag SK, et al. Invasive fungal disease of the sinus and orbit: A comparison between mucormycosis and Aspergillus. Br J Ophthalmol 2016;100:184-8.  Back to cited text no. 11
Alghamdi A, Lutynski A, Minden M, Rotstein C. Successful treatment of gastrointestinal mucormycosis in an adult with acute leukemia: Case report and literature review. Curr Oncol 2017;24:e61-4.  Back to cited text no. 12
Park BJ, Wannemuehler KA, Marston BJ, Govender N, Pappas PG, Chiller TM. Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS 2009;23:525-30.  Back to cited text no. 13
Osawa R, Singh N. Colitis as a manifestation of infliximab-associated disseminated cryptococcosis. Int J Infect Dis 2010;14:e436-40.  Back to cited text no. 14
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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


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