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Diabetic ketoacidosis and rhino-orbital mucormycosis
Diabetes Research and Clinical Practice 57 (2002) 139– 142 www.elsevier.com/locate/diabres
Short communication
Diabetic ketoacidosis and rhino-orbital mucormycosis Hatice Sebila Do¨kmetas¸ a,*, Ercan Canbay b, Sarper Yilmaz c, Nazif Elaldi d, Ays¸en Topalkara e, I: brahim O8 ztoprak f, Esin Yildiz g a
Department of Endocrinology, Cumhuriyet Uni6ersity, Medical School, 58140 Si6as, Turkey Department of Otolaryngology, Cumhuriyet Uni6ersity, Medical School, 58140 Si6as, Turkey c Department of Plastic Surgery, Cumhuriyet Uni6ersity, Medical School, 58140 Si6as, Turkey d Department of Infectious Disease, Cumhuriyet Uni6ersity, Medical School, 58140 Si6as, Turkey e Department of Ophthalmology, Cumhuriyet Uni6ersity, Medical School, 58140 Si6as, Turkey f Department of Radiology, Cumhuriyet Uni6ersity, Medical School, 58140 Si6as, Turkey g Department of Pathology, Cumhuriyet Uni6ersity, Medical School, 58140 Si6as, Turkey b
Received 19 February 2001; received in revised form 10 January 2002; accepted 25 January 2002
Abstract Mucormycosis often develops in immunocompromised patients, particularly in patients with diabetic ketoacidosis. Unless early diagnosis and treatment is established mucormycosis leads rapidly to death. A 38-year-old woman was admitted to the hospital with a severe diabetic ketoacidosis. Her clinical status improved in 4 days as a result of aggressive medical treatment. She has complained left cheek pain on the 10th day and had a swelling of her left cheek, facial edema, a black eschar on the palate and nasal cavity in association with visual disturbance and total ophthalmology in a short time. CT scan revealed left orbital cellulitis and pansinusitis. Excessive surgical treatment was performed and liposomal amphotericin-B, 4 mg/(kg day) was applied. Extensive fungal invasion of the orbit and the sinuses was demonstrated in the pathological species and Rhizomucor species were yielded with culture. Repeated superficial debridement was also performed. After 10 weeks, she was discharged with suggestion of insulin treatment and liposomal amphotericin-B with progressively decreasing doses. At the 13th month following the presentation, the patient was free of disease as confirmed by serial imaging and under good glycaemic control with insulin treatment. Although mucormycosis is a fatal infection, early diagnosis and aggressive treatment may decrease mortality. © 2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Mucormycosis; Diabetic ketoacidosis
Do¨kmetas¸ H.S., Canbay E., Yılmaz S., Elaldı N., Topalkara A., O8 ztoprak I: ., Yıldız E. Diabetic ketoacidosis and rhino-orbital mucormycosis. 23rd Congress of Endocrinology and Metabolic Disease of Turkey/Joint Meeting with the European Federation of Endocrine Societies. J. Endocrinol. Invest. 23 (Suppl. to No. 7) (2000) 45. * Corresponding author. E-mail address: [email protected] (H.S. Do¨kmetas¸).
0168-8227/02/$ - see front matter © 2002 Elsevier Science Ireland Ltd. All rights reserved. PII: S0168-8227(02)00021-9
140
H.S. Do¨kmetas¸ et al. / Diabetes Research and Clinical Practice 57 (2002) 139–142
1. Introduction Mucormycosis is caused by saprophytic fungi of the order Mucorales. Rhizopus, Rhizomucor and Absidia are the most common isolated organisms from the patients with mucormycosis [1]. In the majority of immunocompromised patients, infection occurs following inhalation of spores of Mucorales. Several clinical forms are described such as rhino-orbital-cerebral, pulmonary, disseminated, cutaneous, and gastrointestinal [2]. Rhino-orbital-cerebral is the most common form in diabetic patients. Even though mucormycosis is a rarely seen aggressive infection, it may lead to death in a few days that can be related to undiagnosed cases, especially in severe immunocompromised patients such as malignancies, AIDS, severe burns. Nowadays, mortality rate was decreased from 80–90 to 20– 40% in diabetic patients [2,3]. Early diagnosis, close follow-up, aggressive medical and surgical treatment may be associated with decreased mortality. We report a case of mucormycosis in a patient with diabetic ketoacidosis.
2. Case report A 38-year-old woman with diabetic ketoacidosis was admitted to the Department of Endocrinology. Her medical history revealed that she had diabetes mellitus for 4 years with a poor glycaemic control under oral antidiabetics treatment. It was learned that she had not taken her oral antidiabetics regularly and her blood glucose levels remained high during her clinical course. She had stopped her antidiabetic treatment during the previous 6 days before application to the hospital. The initial laboratory data was HbA1c: 12.8%, blood glucose: 457 (70– 110 mg/dl), BUN: 26 (7– 18 mg/dl), serum creatinine: 1.5 (0.6–1.1 mg/dl), potassium: 3.2 (3.5– 5 mg/dl), pH: 6.7, urine ketone: 100 (0– 4 g/dl), erythrocyte sedimentation rate (ESR): 37 mm/1 h, C-reactive protein: 53 (0– 6 mg/l). In order to treat diabetic ketoacidosis, intravenous hydration, 0.1 U/kg regular human insulin as a con-
tinuous infusion, replacement of potassium and bicarbonate for appropriate metabolic support were applied. Her consciousness, glycaemic control and metabolic status improved on the 4th day. She has complained of severe pain and swelling of the left cheek on the 10th day of admission. Leukocyte count (11000/mm3), ESR (139 mm/1 h), serum levels of BUN (46 mg/dl), serum creatinine (4.5 mg/dl) and urinary creatinine (625 mg/dl, normal range: 50–170 mg/dl) were found to be elevated in the laboratory examination. After 36 h, she was found to have fever (39 °C), swelling of her left cheek, facial oedema, a black eschar on the palate and the sinuses. Visual disturbance, total ophthalmology developed in a short time. CT scan revealed left orbital cellulitis and pansinusitis with thickening of the mucosa (Fig. 1). The patient was admitted to surgery for turbinectomy, ethmoidectomy, sphenoidectomy and the exenteration of involved orbit in order to remove all of the necrotic tissue. Liposomal amphothericin-B (LAT-B) at a dosage of 4 mg/(kg day)/iv was applied along with a strict control of her diabetic disease. We have achieved to isolate Rhizomucor species by culture. Extensive fungal invasion of the orbit and the sinuses was
Fig. 1. Left orbital cellulitis and pansinusitis with thickening of the mucosa on CT scan.
H.S. Do¨ kmetas¸ et al. / Diabetes Research and Clinical Practice 57 (2002) 139–142
demonstrated in the pathological species. Repeated superficial paranasal debridement was maintained along with the application of daily LAT-B (1 mg/ml) to the sinuses and the orbit. Elevated levels of serum and urinary creatinine rapidly decreased and normalised on the 15th day of admission. Following administration of LAT-B 4 mg/(kg day) for 7 weeks, the dosage of LAT-B was decreased from 4 to 2 mg/(kg day) along 3 weeks, since serial MR imaging detected no intracranial extension. She was discharged to receive with twice-daily insulin mixed NPH and regular insulin treatment and LAT-B, 1 mg/kg daily for 2 months, once every other day for 15 days and three times a week for 6 weeks. Following specific treatment of mucormycosis, the patient was free of disease as confirmed by serial MR imaging, pathological and microbiological examination in the 7th month, LAT-B therapy was terminated. Reconstructive surgery was performed in order to repair infection damages on her palate and eye. The patient is now still under good glycaemic control (HbA1c: 7%) with insulin treatment. She was resumed back to her normal activities.
3. Discussion Mucormycosis is a rapidly progressive infection, which may be fatal in a few days. It is known that mucormycosis is most often seen in diabetics or immunocompromised hosts [1]. The mortality rate of mucormycosis may be associated with delayed diagnosis and underlying medical disease. In these patients, mucormycosis may also be undiagnosed because of their poorly medical condition. In our case with diabetic ketoacidosis, rhino-orbital mucormycosis was diagnosed on the 11th day of admission. Rhino-orbital-cerebral mucormycosis often develops in diabetic patients, especially with ketoacidosis [1,4]. The predisposition of diabetics to acquire the mucormycosis infection may be related to acidosis and hyperglycaemia. Acidosis disrupts iron binding of transferrin, resulting in increased proportion of unbound iron, which may promote growth of the fungus. Susceptibility of
141
the patients with diabetic ketoacidosis to this infection may also be due to decreased neutrophil chemotaxis and phagocytosis [4]. The rhino-orbital-cerebral mucormycosis typically begins in the nasal or oral mucosa. The fungal hyphae invade blood vessels in tissue. Histologically, disease is identified as invasion along elastic lamina of blood vessels with haemorrhage, thrombosis, infarction and tissue necrosis. Invasive fungal infection results damages of all affected tissue planes, locally [1,2]. In our case, extensive tissue necroses were observed in rhino-orbital region and palate. Black necrotic eschar filling the sinuses, orbital cavity and intranasal area was removed. Because of renal toxicity associated with amphotericin-B therapy, it should be changed to new formulations of the drug which would be less nephrotoxic such as LAT-B, amphotericin-B colloidal dispersion or lipid complex [5]. For this reason, we preferred the LAT-B therapy initially. LAT-B tolerance is excellent and results only minor increase in the serum creatinine level during the period of therapy [6]. Surgical procedures have become an important adjunct to the superficial treatment regimens for rhino-orbital mucormycosis because it is difficult for the antifungal agent to reach and penetrate ischemic tissue [1]. Therefore, debridement has been recommended in frequent intervals [1–7]. And also, LAT-B irrigation and packing of the orbit and paranasal sinuses may be a reasonable modality for rhino-orbital mucormycosis [2]. We applied LAT-B via both systemically and locally in this case. The infection can be spread into cavernous sinus, causing cavernous sinus thrombosis, from the orbit. In the presence of active fungal invasion of the orbit, exenteration may be life-saving [3,7]. We performed the exenteration of orbit and its pathological evaluation demonstrated active fungal invasion in the orbit. The combination of strict metabolic control, systemically and locally LAT-B therapy, aggressive surgical intervention, repeated surgical debridement played an important factor in the outcome of this case. Although mucormycosis is a fatal infection, early diagnosis and aggressive treatment may decrease mortality.
142
H.S. Do¨ kmetas¸ et al. / Diabetes Research and Clinical Practice 57 (2002) 139–142
References [1] A.M. Sugar, Mucormycosis, Clin. Infect. Dis. 14 (Suppl. 1) (1992) 126 – 129. [2] R.A. Yohai, J.D. Bullock, A.A. Aziz, R.J. Markert, Survival factors in rhino-orbital-cerebral mucormycosis, Surv. Ophthalmol. 39 (1994) 3 –22. [3] B.E. Weprin, W.A. Hall, J. Goodman, G.L. Adams, Longterm survival in rhinocerebral mucormycosis, J. Neurosurg. 88 (1998) 570 – 575. [4] K.O. Smitherman, J.E. Peacock, Infectious emergencies in patients with diabetes mellitus, Med. Clin. North Am. 79
(1995) 53 – 77. [5] A.E. Moses, G. Rahav, Y. Barenholz, et al., Rhinocerebral mucormycosis treated with amphotericin B colloidal dispersion in three patient, Clin. Infect. Dis. 26 (1998) 1430 – 1433. [6] M. Ericsson, H. Gustafsson, C.A. Hjalt, R. Stenling, A. Tarnvik, A case of chronic progressive rhinocerebral mucormycosis treated with liposomal amphotericin B and surgery, Clin. Infect. Dis. 16 (1993) 585 – 586. [7] K.L. Peterson, M. Wang, R.F. Canalis, E. Abemayor, Rhinocerebral mucormycosis: evaluation of the disease and treatment options, Laryngoscope 107 (1997) 855 – 862.
Short communication
Diabetic ketoacidosis and rhino-orbital mucormycosis Hatice Sebila Do¨kmetas¸ a,*, Ercan Canbay b, Sarper Yilmaz c, Nazif Elaldi d, Ays¸en Topalkara e, I: brahim O8 ztoprak f, Esin Yildiz g a
Department of Endocrinology, Cumhuriyet Uni6ersity, Medical School, 58140 Si6as, Turkey Department of Otolaryngology, Cumhuriyet Uni6ersity, Medical School, 58140 Si6as, Turkey c Department of Plastic Surgery, Cumhuriyet Uni6ersity, Medical School, 58140 Si6as, Turkey d Department of Infectious Disease, Cumhuriyet Uni6ersity, Medical School, 58140 Si6as, Turkey e Department of Ophthalmology, Cumhuriyet Uni6ersity, Medical School, 58140 Si6as, Turkey f Department of Radiology, Cumhuriyet Uni6ersity, Medical School, 58140 Si6as, Turkey g Department of Pathology, Cumhuriyet Uni6ersity, Medical School, 58140 Si6as, Turkey b
Received 19 February 2001; received in revised form 10 January 2002; accepted 25 January 2002
Abstract Mucormycosis often develops in immunocompromised patients, particularly in patients with diabetic ketoacidosis. Unless early diagnosis and treatment is established mucormycosis leads rapidly to death. A 38-year-old woman was admitted to the hospital with a severe diabetic ketoacidosis. Her clinical status improved in 4 days as a result of aggressive medical treatment. She has complained left cheek pain on the 10th day and had a swelling of her left cheek, facial edema, a black eschar on the palate and nasal cavity in association with visual disturbance and total ophthalmology in a short time. CT scan revealed left orbital cellulitis and pansinusitis. Excessive surgical treatment was performed and liposomal amphotericin-B, 4 mg/(kg day) was applied. Extensive fungal invasion of the orbit and the sinuses was demonstrated in the pathological species and Rhizomucor species were yielded with culture. Repeated superficial debridement was also performed. After 10 weeks, she was discharged with suggestion of insulin treatment and liposomal amphotericin-B with progressively decreasing doses. At the 13th month following the presentation, the patient was free of disease as confirmed by serial imaging and under good glycaemic control with insulin treatment. Although mucormycosis is a fatal infection, early diagnosis and aggressive treatment may decrease mortality. © 2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Mucormycosis; Diabetic ketoacidosis
Do¨kmetas¸ H.S., Canbay E., Yılmaz S., Elaldı N., Topalkara A., O8 ztoprak I: ., Yıldız E. Diabetic ketoacidosis and rhino-orbital mucormycosis. 23rd Congress of Endocrinology and Metabolic Disease of Turkey/Joint Meeting with the European Federation of Endocrine Societies. J. Endocrinol. Invest. 23 (Suppl. to No. 7) (2000) 45. * Corresponding author. E-mail address: [email protected] (H.S. Do¨kmetas¸).
0168-8227/02/$ - see front matter © 2002 Elsevier Science Ireland Ltd. All rights reserved. PII: S0168-8227(02)00021-9
140
H.S. Do¨kmetas¸ et al. / Diabetes Research and Clinical Practice 57 (2002) 139–142
1. Introduction Mucormycosis is caused by saprophytic fungi of the order Mucorales. Rhizopus, Rhizomucor and Absidia are the most common isolated organisms from the patients with mucormycosis [1]. In the majority of immunocompromised patients, infection occurs following inhalation of spores of Mucorales. Several clinical forms are described such as rhino-orbital-cerebral, pulmonary, disseminated, cutaneous, and gastrointestinal [2]. Rhino-orbital-cerebral is the most common form in diabetic patients. Even though mucormycosis is a rarely seen aggressive infection, it may lead to death in a few days that can be related to undiagnosed cases, especially in severe immunocompromised patients such as malignancies, AIDS, severe burns. Nowadays, mortality rate was decreased from 80–90 to 20– 40% in diabetic patients [2,3]. Early diagnosis, close follow-up, aggressive medical and surgical treatment may be associated with decreased mortality. We report a case of mucormycosis in a patient with diabetic ketoacidosis.
2. Case report A 38-year-old woman with diabetic ketoacidosis was admitted to the Department of Endocrinology. Her medical history revealed that she had diabetes mellitus for 4 years with a poor glycaemic control under oral antidiabetics treatment. It was learned that she had not taken her oral antidiabetics regularly and her blood glucose levels remained high during her clinical course. She had stopped her antidiabetic treatment during the previous 6 days before application to the hospital. The initial laboratory data was HbA1c: 12.8%, blood glucose: 457 (70– 110 mg/dl), BUN: 26 (7– 18 mg/dl), serum creatinine: 1.5 (0.6–1.1 mg/dl), potassium: 3.2 (3.5– 5 mg/dl), pH: 6.7, urine ketone: 100 (0– 4 g/dl), erythrocyte sedimentation rate (ESR): 37 mm/1 h, C-reactive protein: 53 (0– 6 mg/l). In order to treat diabetic ketoacidosis, intravenous hydration, 0.1 U/kg regular human insulin as a con-
tinuous infusion, replacement of potassium and bicarbonate for appropriate metabolic support were applied. Her consciousness, glycaemic control and metabolic status improved on the 4th day. She has complained of severe pain and swelling of the left cheek on the 10th day of admission. Leukocyte count (11000/mm3), ESR (139 mm/1 h), serum levels of BUN (46 mg/dl), serum creatinine (4.5 mg/dl) and urinary creatinine (625 mg/dl, normal range: 50–170 mg/dl) were found to be elevated in the laboratory examination. After 36 h, she was found to have fever (39 °C), swelling of her left cheek, facial oedema, a black eschar on the palate and the sinuses. Visual disturbance, total ophthalmology developed in a short time. CT scan revealed left orbital cellulitis and pansinusitis with thickening of the mucosa (Fig. 1). The patient was admitted to surgery for turbinectomy, ethmoidectomy, sphenoidectomy and the exenteration of involved orbit in order to remove all of the necrotic tissue. Liposomal amphothericin-B (LAT-B) at a dosage of 4 mg/(kg day)/iv was applied along with a strict control of her diabetic disease. We have achieved to isolate Rhizomucor species by culture. Extensive fungal invasion of the orbit and the sinuses was
Fig. 1. Left orbital cellulitis and pansinusitis with thickening of the mucosa on CT scan.
H.S. Do¨ kmetas¸ et al. / Diabetes Research and Clinical Practice 57 (2002) 139–142
demonstrated in the pathological species. Repeated superficial paranasal debridement was maintained along with the application of daily LAT-B (1 mg/ml) to the sinuses and the orbit. Elevated levels of serum and urinary creatinine rapidly decreased and normalised on the 15th day of admission. Following administration of LAT-B 4 mg/(kg day) for 7 weeks, the dosage of LAT-B was decreased from 4 to 2 mg/(kg day) along 3 weeks, since serial MR imaging detected no intracranial extension. She was discharged to receive with twice-daily insulin mixed NPH and regular insulin treatment and LAT-B, 1 mg/kg daily for 2 months, once every other day for 15 days and three times a week for 6 weeks. Following specific treatment of mucormycosis, the patient was free of disease as confirmed by serial MR imaging, pathological and microbiological examination in the 7th month, LAT-B therapy was terminated. Reconstructive surgery was performed in order to repair infection damages on her palate and eye. The patient is now still under good glycaemic control (HbA1c: 7%) with insulin treatment. She was resumed back to her normal activities.
3. Discussion Mucormycosis is a rapidly progressive infection, which may be fatal in a few days. It is known that mucormycosis is most often seen in diabetics or immunocompromised hosts [1]. The mortality rate of mucormycosis may be associated with delayed diagnosis and underlying medical disease. In these patients, mucormycosis may also be undiagnosed because of their poorly medical condition. In our case with diabetic ketoacidosis, rhino-orbital mucormycosis was diagnosed on the 11th day of admission. Rhino-orbital-cerebral mucormycosis often develops in diabetic patients, especially with ketoacidosis [1,4]. The predisposition of diabetics to acquire the mucormycosis infection may be related to acidosis and hyperglycaemia. Acidosis disrupts iron binding of transferrin, resulting in increased proportion of unbound iron, which may promote growth of the fungus. Susceptibility of
141
the patients with diabetic ketoacidosis to this infection may also be due to decreased neutrophil chemotaxis and phagocytosis [4]. The rhino-orbital-cerebral mucormycosis typically begins in the nasal or oral mucosa. The fungal hyphae invade blood vessels in tissue. Histologically, disease is identified as invasion along elastic lamina of blood vessels with haemorrhage, thrombosis, infarction and tissue necrosis. Invasive fungal infection results damages of all affected tissue planes, locally [1,2]. In our case, extensive tissue necroses were observed in rhino-orbital region and palate. Black necrotic eschar filling the sinuses, orbital cavity and intranasal area was removed. Because of renal toxicity associated with amphotericin-B therapy, it should be changed to new formulations of the drug which would be less nephrotoxic such as LAT-B, amphotericin-B colloidal dispersion or lipid complex [5]. For this reason, we preferred the LAT-B therapy initially. LAT-B tolerance is excellent and results only minor increase in the serum creatinine level during the period of therapy [6]. Surgical procedures have become an important adjunct to the superficial treatment regimens for rhino-orbital mucormycosis because it is difficult for the antifungal agent to reach and penetrate ischemic tissue [1]. Therefore, debridement has been recommended in frequent intervals [1–7]. And also, LAT-B irrigation and packing of the orbit and paranasal sinuses may be a reasonable modality for rhino-orbital mucormycosis [2]. We applied LAT-B via both systemically and locally in this case. The infection can be spread into cavernous sinus, causing cavernous sinus thrombosis, from the orbit. In the presence of active fungal invasion of the orbit, exenteration may be life-saving [3,7]. We performed the exenteration of orbit and its pathological evaluation demonstrated active fungal invasion in the orbit. The combination of strict metabolic control, systemically and locally LAT-B therapy, aggressive surgical intervention, repeated surgical debridement played an important factor in the outcome of this case. Although mucormycosis is a fatal infection, early diagnosis and aggressive treatment may decrease mortality.
142
H.S. Do¨ kmetas¸ et al. / Diabetes Research and Clinical Practice 57 (2002) 139–142
References [1] A.M. Sugar, Mucormycosis, Clin. Infect. Dis. 14 (Suppl. 1) (1992) 126 – 129. [2] R.A. Yohai, J.D. Bullock, A.A. Aziz, R.J. Markert, Survival factors in rhino-orbital-cerebral mucormycosis, Surv. Ophthalmol. 39 (1994) 3 –22. [3] B.E. Weprin, W.A. Hall, J. Goodman, G.L. Adams, Longterm survival in rhinocerebral mucormycosis, J. Neurosurg. 88 (1998) 570 – 575. [4] K.O. Smitherman, J.E. Peacock, Infectious emergencies in patients with diabetes mellitus, Med. Clin. North Am. 79
(1995) 53 – 77. [5] A.E. Moses, G. Rahav, Y. Barenholz, et al., Rhinocerebral mucormycosis treated with amphotericin B colloidal dispersion in three patient, Clin. Infect. Dis. 26 (1998) 1430 – 1433. [6] M. Ericsson, H. Gustafsson, C.A. Hjalt, R. Stenling, A. Tarnvik, A case of chronic progressive rhinocerebral mucormycosis treated with liposomal amphotericin B and surgery, Clin. Infect. Dis. 16 (1993) 585 – 586. [7] K.L. Peterson, M. Wang, R.F. Canalis, E. Abemayor, Rhinocerebral mucormycosis: evaluation of the disease and treatment options, Laryngoscope 107 (1997) 855 – 862.