2000-2020 yılları arasında Bursa Uludağ Üniversitesi Tıp Fakültesinde izlenen mukormikoz olgularının retrospektif irdelenmesi
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Date
2022
Authors
Belik, Hazel Öztürk
Journal Title
Journal ISSN
Volume Title
Publisher
Bursa Uludağ Üniversitesi
Abstract
Mukormikoz son yıllarda artış gösteren, Mucorales takımı mantarların neden olduğu anjioinvazif bir enfeksiyondur. İnvazif mikozlar arasında Kandidiyaz ve Aspergilloz’dan sonra 3. sırada gelmektedir, mortalitesi yüksektir. Anatomik lokalizasyona göre farklı klinik formları mevcuttur. Paranazal sinüs, akciğer, deri, böbrek, gastrointestinal sistemden kaynaklanabilir, dissemine olarak tüm organlara yayılabilir. Yıllar içinde immünsüpresif olgu artışına bağlı olarak mukormikoz olgu sayısında artış görülmüştür. Gelişmekte olan ülkelerde en sık görülen predispozan faktör hala kontrolsüz diyabetes mellitus (DM) iken, gelişmiş ülkelerde en sık immünsüpresif durumlar karşımıza çıkmaktadır. Altta yatan hastalıklar ve klinik bulgular birlikte değerlendirilerek mukormikozdan şüphelenildiğinde en kısa zamanda uygun örnekleme ve radyolojik bulgular ile tanı desteklenmelidir. Tedavide geniş debridman yapılması, lipozomal amfoterisin B (L-AmB) 5 – 10 mg/kg/gün başlanması, periyodik değerlendirmeler ile tekrarlayan cerrahi ve antifungal modifikasyonu gerekliliği açısından değerlendirilmesi önerilmektedir. Mortalite oranları altta yatan hastalık ve klinik forma göre değişmekle beraber %40 – %80 arasında bildirilmiştir. Bu çalışmada merkezimizdeki lokal epidemiyolojik veriler, predispozan faktörler, tanı ve tedavi seçenekleri, sağkalımın incelenmesi amaçlanmıştır. Çalışmada 2000 – 2020 yılları arasında Bursa Uludağ Üniversitesi Tıp Fakültesinde Mukormikoz tanısı ile takip edilen 86 erişkin hasta retrospektif olarak incelendi. Olguların 39’u (%45,35) erkek, 47’si (%54,65) kadındı. Yaşları 20 – 86 aralığında, ortalama yaş 51 ± 15 idi. En sık 77 (%89,53) olgu ile sinüs tutulumu görüldü. 38’i (%44,19) sinonazal, 5’i (%5,81) sinoorbital, 9’u (%10,47) rinoserebral, 25’i (%29,07) rinoorbitoserebral mukormikozdu. Geriye kalan 9 (%10,47) olgu pulmoner mukormikozdu. Olguların tümünde en az bir adet predispozan faktör mevcuttu, 51 (%55,30) olguda hematolojik hastalık, 33 (%38,37) olguda DM, 7 (%8,14) olguda vii solid organ transplantasyonu (SOT), 7 (%8,14) olguda solid organ malignitesi olduğu görüldü. En sık saptanan semptomlar ateş (%70,93), göz çevresinde ve yüzde şişlik (%51,16), ağrı (%40,7), kızarıklık (%34,88), burun akıntısı (%30,23) ve baş ağrısı (%25,58) idi. Fizik muayenede en sık ağız ve sinüslerde nekrotik lezyonlar (%87,21), oftalmopleji (%29,07), pitozis (%26,74), görme kaybı (%25,58) ve proptozis (%22,09) saptandı. Olguların hepsinde başlangıç tedavisinde amfoterisin B formları (amfoterisin B deoksikolat (AmB-D), amfoterisin b lipid kompleks (ABLC), L-AmB) tercih edilmişti. L-AmB ile kombinasyon yapılan 14 olgudan 13’üne posakonazol (POS), 1’ine itrakonazol (ITC) eklendiği; idame tedavisi alan 14 olguda POS kullanıldığı görüldü. Amfoterisin B tedavi süresi ortalama 59,27 ± 58,41 (1 – 318) gün, toplam antifungal tedavi süresi ortalama 88,99 ± 126,98 (1 – 632) gün saptandı. Tüm amfoterisin B formlarında en sık istenmeyen etki olarak hipokalemi görüldü (L-AmB %68,75, AmB-D %54,84, ABLC %50). POS alan hastalarda en sık görülen istenmeyen etki %12,5 oranında üre – kreatinin yüksekliği idi. Olguların %74,42’sinde en az bir kez cerrahi girişim uygulandığı görüldü. Mortalite oranı %61,63 saptandı. DM varlığı, kavernöz sinüs tutulumu ve yoğun bakım ihtiyacı kötü prognoz ile ilişkili bulundu (sırasıyla p=0,016, p=0,039, p=0,001). Antifungal tedavi ile cerrahi tedavinin kombine edilmesinin -sadece antifungal tedavi kullananlara kıyasla- sağkalımı artırdığı gösterildi (p=0,045).
Mucormycosis is an angioinvasive infection caused by fungi of the order Mucorales, which has increased in recent years. Among invasive mycoses, it is the most common fungal infection after Candidiasis and Aspergillosis, and its mortality is high. It has different clinical forms according to it’s anatomical localization. It may originate from the paranasal sinus, lung, skin, kidney, gastrointestinal tract, and disseminate to all organs. Over the years, there has been an increase in the number of mycormycosis cases due to the increase in immunosuppressive cases. While the most common predisposing factor in developing countries is still uncontrolled diabetes mellitus (DM), immunosuppressive conditions are the most common predisposing factor in developed countries. When the diagnosis of mucormycosis is suspected due to the underlying diseases and clinical findings combined, the diagnosis should be supported with proper sampling and radiological findings as soon as possible. In treatment, it is recommended to perform extensive debridement, to start liposomal amphotericin B (L-AmB) 5-10 mg/kg/day, and to follow up the patient in terms of repetitive surgery and antifungal modification with periodic evaluations. Although mortality rates vary according to the underlying disease and clinical form, it has been reported to be between 40% and 80%. In this study, it was aimed to examine local epidemiological data, predisposing factors, diagnosis and treatment options, and survival in our center. In our study, 86 adult patients who were followed up with the diagnosis of mucormycosis at Bursa Uludağ University Faculty of Medicine between 2000 and 2020 were retrospectively analyzed. 39 (45.35%) of the cases were male and 47 (54.65%) were female. Their ages ranged from 20 to 86 years, with a mean age of 51 ± 15. Sinus involvement was most common involvement with 77 (89.53%) cases: 38 (44.19%) sinonasal, 5 (5.81%) sinoorbital, 9 (10.47%) rhinocerebral ix and 25 (29.07%) rhinoorbitocerebral mucormycosis. The remaining 9 (10.47%) cases were pulmonary mucormycosis. There was at least one predisposing factor in all cases: hematological disease in 51 (55.30%), DM in 33 (38.37%), solid organ transplantation in 7 (8.14%), and solid organ malignancy in 7 (8.14%) cases was observed. The most common symptoms were fever (70.93%), swelling around the eyes and face (51.16%), pain (40.7%), redness (34.88%), runny nose (30.23%) and headache (25.58%). In the physical examination, necrotic lesions in the mouth and sinuses (87.21%), ophthalmoplegia (29.07%), ptosis (26.74%), vision loss (25.58% and proptosis (22.09%) were found most frequently. In the initial treatment in all cases, amphotericin B forms (amphotericin B deoxycholate (AmB-D), amphotericin b lipid complex (ABLC), L-AmB) were preferred. Posaconazole (POS) was added to 13 of 14 cases and itraconazole (ITC) was added to 1 of 14 patients who were combined with L-AmB. POS was used in 14 patients who received maintenance therapy. The mean duration of amphotericin B treatment was 59.27 ± 58.41 (1 – 318) days, and the mean total antifungal treatment duration was 88.99 ± 126.98 (1 – 632 days). Hypokalemia was the most common side effect in all amphotericin B forms (L-AmB 68.75%, AmB-D 54.84%, ABLC 50%). The most common side effect in patients receiving POS was urea-creatinine elevation at a rate of 12.5%. Surgical intervention was performed at least once in 74.42% of the cases. Mortality rate was 61.63%. Presence of DM, cavernous sinus involvement and need for intensive care were found to be associated with poor prognosis (p=0,016, p=0,039, p=0,001 respectively). Survival was found to be higher in patients who recieved both surgical and medical treatment than those who recieved medical treatment only (p=0,045).
Mucormycosis is an angioinvasive infection caused by fungi of the order Mucorales, which has increased in recent years. Among invasive mycoses, it is the most common fungal infection after Candidiasis and Aspergillosis, and its mortality is high. It has different clinical forms according to it’s anatomical localization. It may originate from the paranasal sinus, lung, skin, kidney, gastrointestinal tract, and disseminate to all organs. Over the years, there has been an increase in the number of mycormycosis cases due to the increase in immunosuppressive cases. While the most common predisposing factor in developing countries is still uncontrolled diabetes mellitus (DM), immunosuppressive conditions are the most common predisposing factor in developed countries. When the diagnosis of mucormycosis is suspected due to the underlying diseases and clinical findings combined, the diagnosis should be supported with proper sampling and radiological findings as soon as possible. In treatment, it is recommended to perform extensive debridement, to start liposomal amphotericin B (L-AmB) 5-10 mg/kg/day, and to follow up the patient in terms of repetitive surgery and antifungal modification with periodic evaluations. Although mortality rates vary according to the underlying disease and clinical form, it has been reported to be between 40% and 80%. In this study, it was aimed to examine local epidemiological data, predisposing factors, diagnosis and treatment options, and survival in our center. In our study, 86 adult patients who were followed up with the diagnosis of mucormycosis at Bursa Uludağ University Faculty of Medicine between 2000 and 2020 were retrospectively analyzed. 39 (45.35%) of the cases were male and 47 (54.65%) were female. Their ages ranged from 20 to 86 years, with a mean age of 51 ± 15. Sinus involvement was most common involvement with 77 (89.53%) cases: 38 (44.19%) sinonasal, 5 (5.81%) sinoorbital, 9 (10.47%) rhinocerebral ix and 25 (29.07%) rhinoorbitocerebral mucormycosis. The remaining 9 (10.47%) cases were pulmonary mucormycosis. There was at least one predisposing factor in all cases: hematological disease in 51 (55.30%), DM in 33 (38.37%), solid organ transplantation in 7 (8.14%), and solid organ malignancy in 7 (8.14%) cases was observed. The most common symptoms were fever (70.93%), swelling around the eyes and face (51.16%), pain (40.7%), redness (34.88%), runny nose (30.23%) and headache (25.58%). In the physical examination, necrotic lesions in the mouth and sinuses (87.21%), ophthalmoplegia (29.07%), ptosis (26.74%), vision loss (25.58% and proptosis (22.09%) were found most frequently. In the initial treatment in all cases, amphotericin B forms (amphotericin B deoxycholate (AmB-D), amphotericin b lipid complex (ABLC), L-AmB) were preferred. Posaconazole (POS) was added to 13 of 14 cases and itraconazole (ITC) was added to 1 of 14 patients who were combined with L-AmB. POS was used in 14 patients who received maintenance therapy. The mean duration of amphotericin B treatment was 59.27 ± 58.41 (1 – 318) days, and the mean total antifungal treatment duration was 88.99 ± 126.98 (1 – 632 days). Hypokalemia was the most common side effect in all amphotericin B forms (L-AmB 68.75%, AmB-D 54.84%, ABLC 50%). The most common side effect in patients receiving POS was urea-creatinine elevation at a rate of 12.5%. Surgical intervention was performed at least once in 74.42% of the cases. Mortality rate was 61.63%. Presence of DM, cavernous sinus involvement and need for intensive care were found to be associated with poor prognosis (p=0,016, p=0,039, p=0,001 respectively). Survival was found to be higher in patients who recieved both surgical and medical treatment than those who recieved medical treatment only (p=0,045).
Description
Keywords
Mukormikoz, İnvazif fungal enfeksiyon, Amfoterisin b, Posakonazo, Mucormycosis, Invasive fungal infection, Amphotericin b, Posaconazole
Citation
Belik, H. Ö. (2022). 2000-2020 yılları arasında Bursa Uludağ Üniversitesi Tıp Fakültesinde izlenen mukormikoz olgularının retrospektif irdelenmesi. Yayınlanmamış tıpta uzmanlık tezi. Bursa Uludağ Üniversitesi Tıp Fakültesi.