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207]

Case Report

Mucormycosis in a Diabetic Patient: A Case Report with an Insight into

Its Pathophysiology

Abstract Syeda Neelam

Mucormycosis is one of the most rapidly progressing and fulminant forms of fungal infection which Afroze,
usually begins in the nose and paranasal sinuses following inhalation of fungal spores. It is caused by Rajani Korlepara,
organisms of the subphylum Mucormycotina, including genera as Absidia, Mucor, Rhizomucor, and
Rhizopus. The incidence of mucormycosis is approximately 1.7  cases per 1,000,000 inhabitants per Guttikonda
year. Mucormycosis affecting the maxilla is rare because of rich blood vessel supply of maxillofacial Venkateswara Rao,
areas although more virulent fungi such as Mucor can overcome this difficulty. The common form Jayakiran Madala
of this infection is seen in the rhinomaxillary region and in patients with immunocompromised Department of Oral Pathology
state such as diabetes. Hence, early diagnosis of this potentially life‑threatening disease and prompt and Microbiology, Mamata
treatment is of prime importance in reducing the mortality rate. Dental College, Khammam,
Telangana, India
Keywords: Diabetes, maxilla, mucormycosis, necrosis

Introduction may generate inadequate response.

The fungus may then spread to the
Mucormycosis (phycomycosis, zygomycosis)
paranasal sinuses and consequently to
is a rare opportunistic fungal infection caused
the orbit, meninges, and brain by direct
by fungi belonging to the Mucorales order extension. However, some patients with
and the Mucoraceae family. It was first mucormycosis have no identifiable risk
described by Paultauf in 1885.[1] It represents factors.[6] Successful management of this
the third most common angioinvasive fatal infection requires early identification
fungal infection following candidiasis of the disease and aggressive and prompt
and aspergillosis.[2] It usually affects medical and surgical interventions to
the immunocompromised individuals prevent the high morbidity and mortality
and is rarely seen in apparently healthy associated with this disease process.[7] We
individuals.[3] In the compromised host, report here with a case of mucormycosis of
mucormycosis infection results from altered the maxilla in a diabetic patient.
immunity in which rapid proliferation and
invasion of fungal organisms ensue in deeper Case Report
tissues.[4] A 50‑year‑old female patient came to
The various predisposing factors the outpatient department with a chief
for mucormycosis are uncontrolled complaint of pain and swelling on her right
diabetes  (particularly in patients having side of the face for 4  months. The patient Address for correspondence:
ketoacidosis), malignancies such as was apparently asymptomatic 4  months Dr. Syeda Neelam Afroze,
lymphomas and leukemias, renal failure, back and subsequently developed pain in Department of Oral
the upper right posterior tooth region. The Pathology and Microbiology,
organ transplant, long‑term corticosteroid Mamata Dental College,
and immunosuppressive therapy, cirrhosis, patient gave a history of dental extraction Khammam, Telangana, India.
burns, protein‑energy malnutrition, of the upper posterior tooth  (both 15 E‑mail: neelamsyeda@
and acquired immune deficiency and 16) previously, due to swelling and gmail.com

syndrome  (AIDS).[5] Pathophysiology mobility 4  months back. Following the

involves inhalation of spores through the extraction, the socket had not healed, and
Access this article online
nose or mouth or even through a skin then, she noticed denuded bone over the
Website:
laceration. Individuals with compromised same area associated with nasal twang www.contempclindent.org
cellular and humoral defense mechanisms of voice. Her medical history revealed
DOI: 10.4103/ccd.ccd_558_17
that she had uncontrolled diabetes for Quick Response Code:
4  months with fasting blood sugar level,
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License, which allows others to remix, tweak, and build upon the
work non-commercially, as long as the author is credited and the How to cite this article: Afroze SN, Korlepara R,
new creations are licensed under the identical terms. Rao GV, Madala J. Mucormycosis in a diabetic patient:
A case report with an insight into its pathophysiology.
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Afroze, et al.: Mucormycosis in a diabetic patient

154  mg/dl  (normal 70–110  mg/dl) and postlunch sugar mucormycosis of the maxilla was given. The patient was
level, 197  mg/dl  (normal 70–140  mg/dl) and asthmatic for referred to physician for increased blood sugar levels and
5 years, and she was on medication for the same. decreased hemoglobin. Oral hypoglycemic medications
were changed  (Metformin 400  mg BD was changed to
On extraoral examination, there was a mild diffuse swelling
Gluconorm 500  mg BD). Two‑unit blood transfusion was
over the right middle third of the face which was extending
done and iron supplements were given  (Venofer 800  mg
mediolaterally from the lateral aspect of nose to the outer
which is iron sucrose solution, the drug has a pH of
canthus of the eye and superoinferiorly from the infraorbital
10.5–11.5 which makes the alkaline environment, so the
region to 1 cm above the corner of the mouth, respectively.
Rhizopus cannot multiply as they require acidic medium
The skin over the swelling was normal with blackish for their growth). Subsequently, surgical excision of the
pigmentation near infraorbital region. On palpation, the maxilla was done, and an acrylic plate was given as a
swelling was soft in consistency, tender with no local rise splint. Oroantral communication was treated with primary
of temperature  [Figure  1a]. The lymph nodes were not closure and healing was normal. The excisional biopsy
palpable. A  small swelling of size 1  cm in diameter is also revealed similar histopathological findings as that of
seen in relation to the medial aspect of bridge of the nose. incisional biopsy. No recurrence was noticed after 1 year
Nasal twang of voice is also noted. Eye movements were of patient follow-up [Figure 6].
normal, and pupils were reactive. Paraesthesia over right
side infraorbital region with circumorbital edema over the Discussion
right eye was noted. The facial expressions were normal.
Mucormycosis incorporates a range of infections caused
Intraoral examination revealed missing tooth in relation to by Zygomycetes, a class of fungi that produce branching
15, 16. Denuded mucosa with exposed necrotic gray‑colored ribbon‑like hyphae and reproduce sexually by formation of
bone was seen from mesial aspect of 13 to distal aspect of zygospores. Pathogen can be found ubiquitously in fruits,
17 extending buccally and palatally involving the alveolar soil, and feces and can also be cultured from the oral
ridge in region of 15 and 16. The surrounding mucosa cavity, nasal passages, and throat of healthy disease‑free
was normal with an oroantral communication in the mid individuals. Mucorales is a subtype of Zygomycetes, which
palatine region was seen  [Figure  1b]. On palpation, the produces a distinct pattern of clinical infection. The fungi
affected area was rough in texture with mild tenderness. are usually avirulent; they become pathogenic only when
the host resistance is exceptionally low. Ulceration in the
Based on the history and clinical findings, a provisional
mucosa or an extraction wound in the mouth can be a harbor
diagnosis of mucormycosis of the maxilla was made and
of entry for mucormycosis in the maxillofacial region,
differentials include osteomyelitis, chronic granulomatous
particularly when the host is immunocompromised.[8]
infection, and deep fungal infections. Orthopantomogram
was taken, but no significant changes were noted [Figure 2] Infection by mucormycosis is caused by asexual spore
whereas a paranasal sinus view (PNS) radiograph showed formation. The tiny spores become airborne and settle
haziness of the right maxillary sinus with destruction on the oral and nasal mucosa of humans. In majority
of the sinus walls [Figure 3a]. A computed tomography of immunologically competent hosts, these spores will
(CT) scan revealed hyperdensity of the maxillary antrum be limited by a phagocytic response. If this response
with destruction of all the boundaries of sinus including fails, germination will follow and hyphae will develop.
nasal wall and floor of the orbit [Figures 3b and 4]. On As polymorphonuclear leukocytes are less effective in
biochemical investigation, an elevated fasting blood removing hyphae, in immunocompromised individuals,
sugar level and decreased hemoglobin%  (7  g %) was the infection becomes established in these cases. It further
noticed and HbA1c level was 8.3%. Further, cytological progresses as the hyphae begin to invade arteries, wherein
smear was taken from alveolar and palatal region, and they propagate within the vessel walls and lumens causing
Papanicolaou staining revealed numerous aseptate fungal thrombosis, ischemia, and infarction with dry gangrene
hyphae within a background of epithelial cells and mixed of the affected tissues. Hematogenous spread to other
inflammatory cells [Figure 5a]. Incisional biopsy was done organs can occur  (lung, brain, and so on) and results in
from alveolar region, and microscopic examination under sepsis[9] [Chart 1].
H&E revealed necrotic bone interspersed with fungal Mucormycosis of the oral cavity can be of two different
hyphae [Figure 5b]. These fungal hyphae were broad origins. One is from disseminated infection where the
aseptate and showed branching at right angles. Further, gateway of entry is inhalation  (through the nose) and
hemorrhagic areas and chronic inflammatory cell infiltrate the other is through direct wound contamination with
were also seen  [Figure  5c]. Special staining with periodic dissemination to other viscera as a common complication.
acid–Schiff was done which showed numerous magenta When it arises from nose and PNS, the infection may cause
pink‑colored fungal hyphae which are nonseptate showing palatal ulceration leading to necrosis and the affected area
branching at 90°  [Figure  5d]. Based on radiological appears black in preponderance of the cases. When the
and histopathological findings, a final diagnosis of infection spreads from direct wound contamination, the

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Afroze, et al.: Mucormycosis in a diabetic patient

a b
Figure 1: (a) Extraoral photograph showing diffuse swelling on the right
middle third of the face (red circle). (b) Intraoral photograph showing necrotic
bone (black arrow) and oroantral communication in the palate (red circle) Figure 2: Orthopantomogram

a b
Figure  3: (a) Paranasal sinus radiograph showing haziness of the right
maxillary sinus with destruction of sinus walls. (b) Three-dimensional
computed tomography scan showing hyperdensity of maxillary antrum
with destruction of all boundaries

Figure 4: Computed tomography images

a b

c d
Figure 5: (a) Papanicolaou-stained section showing aseptate fungal hyphae
(black arrow) within background of epithelial cells and inflammatory cells.
(b) H and E-stained tissue section showing necrotic bone (black arrow) and
hemorrhagic areas. (c) H and E-stained tissue section showing aseptate
fungal hyphae branching at right angles (black arrow). (d) Periodic
acid–Schiff-stained section showing magenta pink-colored aseptate fungal
hyphae (black arrow) Figure 6: One-year follow-up total resolution of the lesion

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Afroze, et al.: Mucormycosis in a diabetic patient

such as tuberculosis, tertiary syphilis, midline lethal

granuloma, and other deep fungal infections.[15]
Radiographically, opacification of sinuses may be noticed
in conjunction with patchy effacement of bony walls of
sinuses.[5] CT with contrast or magnetic resonance image
scan can demonstrate erosion or destruction of bone and
helps to know the extent of disease.[15]
Histopathologically, the lesion demonstrates broad
aseptate fungal hyphae that show branching at right
angles.[5] In the present case, the same histopathology
was revealed. The histopathological differential diagnosis
includes aspergillosis where the hyphae of Aspergillus
species are septate, smaller in width and branch at more
acute angles.
When diagnosed early, mucormycosis may be cured by a
Chart  1: Pathophysiology of mucormycosis
combination of surgical debridement of the infected area and
clinical findings may appear anywhere in the oral cavity, systemic administration of amphotericin B for 3  months.
including the mandible. A  significant difference between Proper management of the underlying condition is also an
infection involving the maxilla and mandible is cavernous essential aspect affecting the outcome of the treatment.[16]
sinus thrombosis, a serious complication of maxillary Conclusion
infections.[10]
Mucormycosis is an aggressive fulminant invasive fungal
Diabetes mellitus tends to change the normal immunological
infection that can occur in patients with diverse precipitating
response of body to any infection in several ways.
factors such as uncontrolled diabetes, renal failure, organ
Hyperglycemia stimulates fungal proliferation and also
transplant, long‑term corticosteroid and immunosuppressive
causes decrease in chemotaxis and phagocytic efficiency
therapy, cirrhosis, burns, and AIDS malignancies such as
which permits the otherwise innocuous organisms to thrive
lymphomas and leukemias. In a diabetic patient, it can be
in acid‑rich environment. In the diabetic ketoacidosis
triggered even by minor dental procedures such as tooth
patient, there is an increased risk of mucormycosis caused
extraction. Further attempts should be made for the early
by Rhizopus oryzae as these organisms produce the enzyme
diagnosis of this disease and prompt management of the
ketoreductase, which allows them to utilize the patient’s
patient.
ketone bodies.[8] It has been established that diabetic
ketoacidosis temporarily disrupts the ability of transferrin Declaration of patient consent
to bind iron, and this alteration eliminates a significant host
The authors certify that they have obtained all appropriate
defense mechanism and permits the growth of Rhizopus
patient consent forms. In the form the patient(s) has/have
oryzae.[11] In the present case, the patient presented with
given his/her/their consent for his/her/their images and
diabetes mellitus.
other clinical information to be reported in the journal. The
Frequent clinical presentations include rhinocerebral, patients understand that their names and initials will not
pulmonary, and cutaneous forms  (superficial) and less be published and due efforts will be made to conceal their
frequently, gastrointestinal, disseminated, and miscellaneous identity, but anonymity cannot be guaranteed.
forms.[12] The rhinocerebral  (rhinomaxillary) form is the most
common form of infection commonly seen in patients with Financial support and sponsorship
uncontrolled diabetes mellitus.[13] Patients with rhinocerebral Nil.
mucormycosis clinically present with malaise, headache, facial
pain, and swelling and with low‑grade fever. The disease Conflicts of interest
usually initiates in the nasal mucosa or palate and extends There are no conflicts of interest.
to the paranasal sinuses spreading through the surrounding
vessels such as angular, lacrimal, and ethmoidal vessels. In References
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