<Brief
History>
A 51-year-old woman has been diagnosed
as having diabetes mellitus with insulin control and end stage
renal disease (ESRD) with regular hemodialysis for 12 and 10
years respectively. She was found to have iron overload by
routine monthly blood check. The iron overload was suspected
to be resulted from frequent blood transfusion and she was
treated with deferoxamine (DFO). During the treatment of DFO,
she had suffered from progressive left frontal headache and
low-grade fever. Besides, progressive left orbital swelling
with exophthalmos and erythematous change in skin color
developed one week after the onset of headache. Sinusitis was
diagnosed initially by LMD. However, a few nodules were noted
on her nose, and they enlarged and coalesced gradually,
associated with yellowish, mucus-like discharge. She visited
another hospital and chronic paranasal sinusitis was
impressed, too. Functional Endoscopic Sinus Surgery (FESS) was
performed immediately, but was complicated with high fever and
dyspnea. She was transferred to medical ward for further care.
Physically, her conscious ness was clear. The temperature was
38.1¢XC, the pulse was 100 per minute, and the respiration rate
was 28 per minute. The blood pressure was 141/76mmHg. The
conjunctiva was pink and the pupils were isocoric. The neck
was supple without jugular venous engorgement or
lymphadenopathy. The chest wall was symmetrically expanded.
The breath sounds were coarse with diffuse wheezes. The heart
sounds were regular without murmur. The abdomen was flat and
soft with normoactive bowel sound. No pitting edema was noted
in both arms and legs. Marked swelling and erythematous skin
lesions on the left forehead and periorbital areas were noted.
Besides, two nodules measuring 3 x 1cm and 2 x 1cm were found
in the left eye and on the nasal ridge, respectively,
associated with local tenderness, local heat and fragile bony
structure on palpation. (Fig.
1
)
<Laboratory and Image
Study>
1.CBC/DC:
|
WBC (/£gl) |
RBC (M/£gl) |
Hb (g/dl) |
Hct (%) |
MCV (fl) |
PLT (k/£gl) |
CRP (mg/d) |
921028 |
11340 |
2.22 |
6.9 |
19.8 |
89.2 |
98 |
10.32 |
921104 |
10090 |
3.36 |
10.5 |
28.7 |
85.4 |
76 |
13.29 |
921116 |
30470 |
2.69 |
8.5 |
25.5 |
94.8 |
116 |
|
|
Blast(%) |
Band(%) |
Seg(%) |
Eos(%) |
Baso(%) |
Mono(%) |
Lym(%) |
921028 |
0 |
0 |
92.9 |
0.2 |
0.1 |
3.4 |
3.4 | 2.Biochemistry
|
UN |
Cr |
T-bili |
D-bili |
Alb |
AST |
ALT |
ALP |
r-GT |
HbA1c |
Glucose |
|
mg/dL |
mg/dL |
mg/dL |
mg/dL |
g/dL |
U/L |
U/L |
U/L |
U/L |
% |
mg/dL |
921028 |
59 |
5.7 |
0.9 |
0.84 |
3.5 |
110 |
56 |
587 |
562 |
6.6 |
287 |
921104 |
53.6 |
4.9 |
2.6 |
2.05 |
2.8 |
|
|
|
|
|
|
921116 |
58.2 |
5.0 |
3.8 |
3.6 |
|
462 |
247 |
|
|
|
|
|
Na |
K |
Ca |
Mg |
Cl |
P |
CK/MB |
TG |
CHO |
|
mmol/L |
Mmol/L |
mmol/L |
mmol/L |
mmol/L |
mg/dL |
U/L |
mg/dL |
mg/dL |
921028 |
130 |
2.8 |
2.36 |
1.06 |
|
4.4 |
117/9.5 |
344 |
110 |
921104 |
133 |
4.3 |
2.42 |
1.3 |
93 |
4.0 |
<20/<1 |
|
| ABG:
nasal cannula 3L/min: pH 7.42, pCO2 27.5, pO2 69, HCO3
17.6
3. Urine analysis:
|
Sp.Gr |
pH |
Protein |
Glu. |
Ketone |
O.B |
Urobil |
Bil |
Nitrite |
RBC |
WBC |
Epith |
Cast |
921103 |
1.025 |
7.5 |
>300 |
- |
+/- |
3+ |
1.0 |
1+ |
+ |
25-30 |
>100 |
15-20 |
- |
<Course and
Treatment>
The biopsy revealed mucormycosis and
MRI disclosed mucormycosis with invasion into paranasal sinus,
and penetration of nasal cartilage, nasal floor and hard
palate (Fig
2A &Fig 2B&Fig 3
). During admission, she was treated with
amphotericin B (100mg/day) and Tazocin. Because of the
patient¡¦s impending respiratory failure, intubation was
performed. Otolaryngeal specialist was consulted but only
palliative debridement was performed due to the severe
bleeding tendency. She was transferred to ICU and tracheostomy
was performed due to difficulty in weaning. A second
debridement was scheduled but was postponed due to frequent
ventricular tachycardia refractory to DC shocks. Her family
refused further aggressive treatment, and she passed away on
November 16, 2004, 19 days after admission.
<Analysis>
Mucormycosis is an aggressive, opportunistic infection
caused by fungi in the class of Phycomycetes. The genera most
commonly responsible for mucormycosis usually are Mucor or
Rhizopus. Orbitorhinocerebral mucormycosis, the most common
type, generally occurs in conjunction with sinus or nasal
involvement. Mucormycosis also may affect other parts of the
body, including the lungs, GI tract, or skin. Most cases of
mucormycosis are acute surgical emergencies. The fungus gains
entry into the body through the nasopharynx and can be inhaled
into the lungs, or it can extend to the sinuses, orbit, and
brain. The occurrence of mucormycosis depends on host
immunity. The overall mortality rate in adults is 50%.
Survival rates are largely determined by early diagnosis and
resolution of the underlying condition.
The most common symptoms of rhinocerebral mucormycosis
include altered mental status, fever, and pain over the
involved site. Most characteristic feature of mucormycosis is
hyphal invasion of blood vessels, leading to hemorrhage,
thrombosis, infarction & necrosis. It may lead to
cavernous sinus and internal carotid artery thrombosis.
Diagnosis based on direct morphologic identification of broad,
irregular, perpendicular angle branching, nonseptate hyphae or
tissue culture, CT/MRI etc.
The predisposing factors for mucormycosis are including:
-Immunosuppression: neutropenia, corticosteroid therapy,
transplantation, HIV infection. -Metabolic: DKA, uncontrolled
DM, chronic metabolic acidosis, deferoxamine therapy. -Skin or
soft tissue breakdown: burn, traumatic or surgical wounds.
-Iron overload: phagocytic, chemotatic, bactericidal
dysfunction. -Others: IVDU, prematurity, malnutrition, malt
and lumber workers. Mucoraceae synthesizes siderophore
(rhizoferrin), and Deferoxamine behaves like siderophore,
uptake by Mucoraceae and then stimulates its growth.
Treatments includeƒÞantifungal therapy with Amphotericin B
(1-1.5mg/kg/d), hyperbaric oxygen, surgical therapy or frozen
section-guided debridement. The best outcomes are achievable
with combined surgical and medical approaches. The lipid-based
Amphotericin B appears to be the best medical option
considering length of therapy and need for very high doses.
But Deferoxamine-related mucormycosis still has very high
mortality which had been reported to be around 89% in dialysis
patients from international registry. Immunocompromised status
plus prolonged half-life of DFO are all possible mechanism of
high mortality in dialysis patients.
<Reference>
- Clin Microbiol Infect. 2004 Mar;10
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- Orbit. 1998 Dec;17(4):237-245.
- Neth J Med. 1992 Dec;41(5-6):275-9.
- Laryngoscope. 1992
Jun;102(6):656-62.
- Am J Kidney Dis. 2003
Sep;42(3):E14-7.
- J Clin Invest. 1993
May;91(5):1979-86.
- Clin Infect Dis. 1992 Mar;14 Suppl 1:S126-9.
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