Case Discussion <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 Suppl 1:31-47. 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. Ä~Äò±Ð¨|¦ÒÃD 1. (C) The most common mucormycosis? A Gastrointestinal mucormycosis B  Pulmonary mucormycosis C Orbitorhinocerebral mucormycosis D Cardiac mucormycosis 2. (A) The entry site of fungus in orbitorhinocerebral mucormycosis? A Nasopharynx B Eye C Oral cavity D  Ear 3. (D) The predisposing factor for mucormycosis? A Diabetes Mellitus B AIDS C Deferoxamine D All of above 4. (D) The most common symptoms of rhinocerebral mucormycosis? A Altered mental status B Fever C  Pain over the involved site D All of above 5. (E) Most characteristic feature of mucormycosis? A Hyphal invasion of blood vessels B  Hemorrhage C Thrombosis D Infarction & necrosis E All of above 6. (E) The most effective treatment in mucormycosis? A Local debridement B Sugar control C Hyperbaric oxygentherapy D Anti-fungal treatment E Anti-fungal treatment with surgical debridement 7. (C) Which is the most effective anti-fungal therapy in mucormycosis? A Fluconazole B Itraconazole C Amphotericin B D Ketoconazole 8. (B) The possible mechanism for high mortality in dialysis patient treated with Deferoxamine does not include? A Immunocompromised B Deferoxamine induces leukopenia C  Deferoxamine stimulates fungal growth D Prolonged Deferoxamine half-life 9. (D) Diagnosis of mucormycosis can be made by? A Direct microscopy observation B Tissue culture C  Imaging study D All of above 10. (D) The possible differential diangnosis of orbitorhinocerebral mucormycosis? A Orbital cellulitis B Pre-septal cellulitis C Hypercoagulable state D All of above

µª®×¸Ñ»¡ (C ) Orbitorhinocerebral mucormycosis is the most common form of mucormycosis (A) 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. (D) Immunocomprised status including neutropenia, corticosteroid therapy, transplantation, HIV infection are the predisposing factors for mucormycosis (D ) The most common symptoms of rhinocerebral mucormycosis include altered mental status, fever, and pain over the involved site. (E ) Most characteristic feature of mucormycosis is hyphal invasion of blood vessels, leading to hemorrhage, thrombosis, infarction & necrosis. (E ) The best outcomes are achievable with combined surgical and medical approaches. (C ) The lipid-based Amphotericin B appears to be the best medical option considering length of therapy and need for very high doses. (B ) Immunocompromised status plus prolonged half-life of DFO are all possible mechanism of high mortality in dialysis patients. (D ) Diagnosis is based on direct morphologic identification of broad, irregular, perpendicular angle branching, nonseptate hyphae or tissue culture, CT/MRI etc. (D)Cellulitis may mimic the initial presentation, and hypercoagulable state may mimic the venous thrombosis with subsequent hemorrhage or necrosis of orbito rhinocerebral mucormycosis.