Background
Invasive fungal rhinosinusitis is a rare but life threatening infection, typically affecting immunocompromised hosts. Despite the sharp rise in the incidence of Invasive fungal rhinosinusitis in patients on immunosuppressive therapies, the most common risk factor for this infection continues to be diabetes. The literature on diabetes and invasive fungal rhinosinusitis is scarce and most of data is regarding patients with hematological malignancies and solid organ transplant. However, poorly controlled diabetes in developing countries continues to predispose patients to invasive fungal rhinosinusitis. In view of the paucity of literature, there is difficulty in planning and monitoring treatment of these patients. 

Aim
We report a case series of 22 cases of invasive fungal rhinosinusitis from a tertiary care center in North India with an emphasis on the radiological changes seen in response to treatment.

Method
All patients admitted with a diagnosis of invasive fungal rhinosinusitis with pre-existing or newly diagnosed diabetes from 1st January 2008 to 31st December 2015 were included in this study. Hospital records were used to identify clinical features, biochemical investigations and treatment modalities used. The imaging findings were reported at baseline, 30, 60, 90 and 120 days of admission (the day 30 represents imaging findings of any radiological study done between 3-6 weeks of admission. Day 60 represents study done between 6-9 weeks, day 90 represents study done at 9-12 weeks and day 120 represents after 12 weeks). Disease was staged at these intervals as sinonasal, orbital or intracranial. The progression of disease was also studied at day 30, 60 and 90 and reported as static, worse or improved. ‘Static’ was defined as disease which is similar to the previous imaging (for example, baseline imaging for the day 30 imaging report). ‘Worse’ was defined as evidence of increase in the disease with respect to the previous imaging. ‘Improved’ was defined as reduction of disease as compared to the previous imaging. The criteria used to assess progression were extent of disease, involvement of new areas, abscess formation and contrast enhancement. The outcome of the study was assessed as visual loss or death at end of hospital stay and as death at last follow up. 

Results
Twenty two patients of invasive fungal sinusitis and diabetes were identified. At presentation, five patients had ketoacidosis. Facial pain and swelling were the most common presenting features. Loss of vision in one eye as seen in 68% at presentation.
Radiologically, sinonasal disease was present in 31.8% (7/22), orbital disease in around 50%(11/22) and 18.2%(4/22) had intracranial extension. Of the 11 patients with orbital disease, six developed intracranial extension during the hospital stay. None of  the patients showed radiological improvement  at day 30 imaging.
The microbiological diagnosis was aspergillosis in one case and mucormycosis in  all the other cases.
Surgical debridements( including orbital exenteration in nine cases) were performed in 86.3% while liposomal amphotericin B was used in 40.9%.
At the end of hospital stay, 72.7% survived and loss of vision in one eye was seen in 70% cases. The six deaths included all the four cases with diabetic ketoacidosis. 

Diabetic ketoacidosis, baseline intracranial disease and lower hemoglobin were associated with death.Use of  liposomal amphotericin B was not associated with a better survival compared to  conventional amphotericin B. 

Table 1. Baseline characteristics of the patients (n=22)

Age (yrs) a	44.1± 13.9
Maleb	12 (54.5%)
Femaleb	10 (45.5%)
Type 2 DMb	19(86.4%)
Type 1 DMb	3 (13.6%)
Duration of diabetes (yrs) a	4.40± 5.06
Diabetic Retinopathyb	4 (18.1%)
Diabetic Nephropathyb	4 (18.1%)
Diabetic Neuropathyb	2 (9.0%)
BMI (kg/m2)a	25.86±3.40
Diabetic ketoacidosisb	5 (22.7%)
Diabetic ketosisb	4 (18.1%)
HbA1c(%)a	10.9 ± (1.7)
Hemoglobin (gm/dl)a	10.8± 1.5
Serum creatinine (mg/dl)a	1.2± 1.2
Serum albumin (gm/dl)a	3.2± 0.3
a= mean±SD, b= n(%)

Discussion
The mortality in invasive fungal sinusitis with diabetes is high and ketoacidosis is a strong predictor of mortality. Radiological improvement is usually not apparent before two months of therapy although  intracranial extension may be picked up during this period.

Invasive fungal rhinosinusitis in patients with diabetes: a case series