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Acute fulminant fungal sinusitis: clinical presentation, radiological findings and treatment
Acta Tropica 80 (2001) 177– 185 www.parasitology-online.com
Acute fulminant fungal sinusitis: clinical presentation, radiological findings and treatment M.A. Sohail, Mazin Al Khabori *, Jamil Hyder, Ashok Verma ENT Department, Al Nahdha Hospital, P.O. Box 937, Postal Code 112, Sultanate of Oman, Oman Received 29 May 2000; received in revised form 30 November 2000; accepted 16 February 2001
Abstract Acute fulminant fungal sinusitis is characterized by acute symptoms and rapid progress with a mortality rate of 60–80%. A large number of survivors have permanent neurological, visual and cosmetic disabilities. This clearly underscores the need of early recognition of this disease in at risk population in order to start urgent treatment. The at-risk population of diabetics, AIDS and other immunosupressed is likely to increase, as will the incidence of acute fulminant fungal sinusitis. In the present study we have reviewed nine cases of acute fulminant fungal sinusitis to determine clinical presentation, related radiological picture and optimum treatment. Most common presenting features were fever, headache, facial swelling and proptosis. Many patients presented with blindness, facial paralysis and meningitis. Predisposing causes were uncontrolled diabetes with ketoacidosis in four out of six cases, post renal transplant immunosuppression and leukemia. All patients were treated with of amphotrecin B or liposomal amphotericin B (AmBisome). Diagnosis was confirmed by biopsy and culture of sinus mucosa, soft tissues of cheek, or orbit. Mucor (Zygomycetes) was identified on culture or histopathology in all cases. Surgical debridement was performed in seven cases. Six out of nine patients survived but morbidity was high: only two patients survived without any permanent disability. © 2001 Elsevier Science B.V. All rights reserved. Keywords: Fungal sinusitis; Mycoses
1. Introduction It is estimated that as many as 8 – 10% of patients undergoing surgery for sinusitis or polyposis have fungal sinusitis (Stammberger, 1991), either extramucosal non-invasive or invasive.
* Corresponding author. Tel.: + 968-7733998; fax: + 9687737522. E-mail address: [email protected] (M. Al Khabori).
DeShazo et al. (1997) have described diagnostic criteria for invasive fungal sinusitis: (1) mucosal thickening or air fluid levels compatible with sinusitis on radiological imaging; and (2) histopathological evidence of hyphae within sinus mucosa, submucosa, blood vessels or bone. They also described three forms of invasive fungal sinusitis: (1) granulomatous; (2) acute fulminant; and (3) chronic invasive. Acute fulminant fungal sinusitis though comparatively infrequent, has an invasive and destructive nature. It progresses rapidly with a very high mortality rate. Ochi et al.
0001-706X/01/$ - see front matter © 2001 Elsevier Science B.V. All rights reserved. PII: S 0 0 0 1 - 7 0 6 X ( 0 1 ) 0 0 1 7 4 - 7
178
Table 1 Age, sex, side of disease, underlying medical problem, sites involved other than sinuses and other organ involvement or disease Age in year
Sex
Side
Underlying medical problem/risk group
Sites involved other than sinuses
Other organ/disease
1
28
Female
Left
Diabetes
and
Blindness, ophthalmoplegia, facial paralysis
2
40
Male
Left
of
Meningitis
3
48
Male
Left
of
Meningitis
4
60
Female
Left
Renal failure/renal transplant Renal failure/renal transplant Diabetes
of
Facial paralysis
5
63
Male
Right
Diabetes
6
18
Male
Right
Leukemia
7
45
Female
Left
8
55
Female
Right
Renal failure/renal transplant Diabetes
9
38
Male
Left
Diabetes
Orbit, soft tissue skin of cheek Orbit, soft tissue cheek Orbit, soft tissue cheek Orbit, soft tissue cheek Orbit, soft tissue cheek Orbit, soft tissue skin of cheek Orbit, soft tissue cheek Orbit, soft tissue skin of cheek Orbit, soft tissue cheek
of and
Blindness, ophthalmoplegia
of and
Facial paralysis
of
Blindness, ophthalmoplegia, facial paralysis , cavernous sinus involvement
M.A. Sohail et al. / Acta Tropica 80 (2001) 177–185
Case
M.A. Sohail et al. / Acta Tropica 80 (2001) 177–185
(1988) and Denning (1996) report mortality rates of 82% and 66% repsectively. These patients often present with visual and neurologic features: survivors may have permanent disability. A better understanding of presenting clinical features in high-risk individuals will prompt early relevant investigations, early diagnosis and appropriate surgical and medical intervention This study reviews cases of acute fulminant fungal sinusitis, identifies early clinical features, and evaluates diagnostic methods.
2. Material and methods Retrospective review of case records, CT and MRI scans, operation notes and follow-up records of cases of acute fulminant fungal sinusitis seen in ENT Department, treated at Al Nahdha Hospital over a period of 8 years. Criteria for inclusion in study were as follows: 1. Symptoms suggestive of acute sinusitis or orbital cellulitis. 2. Clinical and radiological evidence of sinusitis. 3. Histological evidence of fungal hyphae in nasal or sinus mucosa or soft tissues of cheek or orbit.
3. Results Nine cases were identified from our records: all had undergone clinical examination, nasal endoscopy and CT scanning: a MRI scan was performed in Case 9. Endoscopic or combined
179
endoscopic external surgery was performed in seven cases. In two cases (2 and 3) surgery was limited to endoscopic examination and biopsy from nose. Both patients died before definitive surgery could be done. Mucor spp (Zygomycetes) was identified on culture or histopathology in all cases. Age, sex, risk factor, sites involved other than sinuses and other organ/disease are presented in Table 1. Disease was unilateral in all cases. The symptoms and signs are presented in Table 2. Fever, nasal obstruction, headache, facial induration, and proptosis were found in all cases (Fig. 1). Neurological involvement included ophthalmoplegia and blindness in three cases, facial paralysis in four cases, and meningitis leading to coma in two cases. Except in Case 8 neurological deficits were irreversible. Necrosis of skin was seen in three cases (Fig. 2).
3.1. Endoscopic findings All patients had swelling of the lateral wall of the nose on endoscopic examination. This was due to soft tissue swelling of the cheek and nasal vestibule. Necrosis and discoloration of the middle turbinate was seen in three cases. Cases also had necrosis of facial skin. Biopsies were taken endoscopically in two cases: (A) from the middle turbinate; and (B) from soft tissues of nasal vestibule and cheek. Biopsies from the middle turbinate were negative for hyphae whereas biopsies from soft tissues of cheek were positive. Swabs taken from the middle meatus during endoscopic examination were negative for fungus.
Table 2 Symptoms and clinical signs Symptoms
No of patients
Signs
No. of patients
Nasal obstruction Facial swelling Headache Fever Nasal discharge Loss of vision Loss of consciousness
9 9 9 9 4 3 2
Facial induration Proptosis Ophthalmoplegia, blindness Facial paralysis Skin necrosis Comatose
9 9 3 4 3 2
180
M.A. Sohail et al. / Acta Tropica 80 (2001) 177–185
3.3. Surgical findings In seven cases affected sinuses were cleaned and ventilated endoscopically. In all cases necrotic bone was found in ethmoids. Necrotic tissue was also found in maxillary sinus in five cases. In one case, the orbital apex was exposed endoscopically, orbital periostium was incised and fungus was curetted out from around the medial rectus muscle. ‘Fungal mucin’ as commonly seen in AFS was not seen in any of these cases. Endoscopic surgery was combined with external debridement in three cases to remove the fungus from soft tissues of cheek. In one case it was needed to debride necrosed skin.
3.4. Medical treatment and follow up Table 3 presents details of medical treatment. This includes drug used, dose regime and duration
Fig. 1. Photograph showing facial swelling and induration, proptosis and facial paralysis.
3.2. Radiological findings CT scan of paranasal sinuses with 4 mm cuts showed varying degree of mucosal edema in ethmoid and maxillary sinus in all cases. The frontal sinus was not involved in any case. Sphenoid opacification was found in one case. Bony destruction either in the region of the lamina paprycea or floor of orbit was seen in all cases. Soft tissue swelling of orbit and cheek was seen in all cases. Hyperdense shadow (double density sign) was seen in the soft tissue swelling in five cases (Fig. 3). Such high attenuation areas were not seen in the sinus cavities. In one case a hyper dense shadow was seen near the orbital apex (Fig. 4). Although CT scan failed to show the involvement of cavernous sinus it was demonstrated on MRI scan in one case (Fig. 5).
Fig. 2. Photograph showing necrosis of facial skin.
M.A. Sohail et al. / Acta Tropica 80 (2001) 177–185
181
with facial palsy recovered facial nerve function: neither of the two blind patients receovered facial nerve function (Table 1). None of the patients showed any sign of recurrence at the end of followup.
4. Discussion
Fig. 3. CT scan showing edema of orbit and hyperdense shadow in the edematous tissue of check.
of treatment for each case. It also shows surgical treatment, follow-up period, and outcome. Four patients received amphotrecin B (Case 1, 2, 3, 4): AmBisome was not available at that time. AmBisome which is less toxic than amphoteracin was used in four cases (Case 5– 8). In Case 9, AmBisome was not tolerated and therapy was switched to amphotericin B after 4 days. In Case 4, therapy had to be stopped after 30 days (1 g of total amphotericin B) due to liver impairment. In three cases, patients died within 10 days of starting therapy: the cause of death was meningitis in Cases 2 and 3. In Case 6 death was due to uncontrollable hemorrhage from multiple sites in a leukaemic patient. Surprisingly the bleeding was minimal from the operated site. Surviving patients were followed for an average range of 4– 12 months. Only one of 4 patients
Fig. 4. CT scan showing hyperdense shadow at orbital apex.
Fungi incriminated in acute fulminant fungal sinusitis include Actinonycete eg. Aspergillus (Talbot et al., 1991) or Zygomycetes eg. Rhizopus and Mucor (Baker, 1957). These saprophytic fungi reproduce and grow in soil, decaying food, grain, and plants. They thrive in any environment with an acidic pH and an abundance of glucose. After becoming airborne, Mucor spores may settle onto the mucosa of a susceptible host. They penetrate into the tissue, allowing angioinvasion to occur. Mucor has a predilection for the internal elastic lamina of the arteries. The invasion produces thrombosis, with secondary ischemic infarction and hemorrhagic necrosis. The fungus thrives in this environment and spreads along injured vessels. Acute fulminant fungal sinusitis is characterized by its acute symptoms, rapid progress and high mortality. Patients at highest risk for acute fulminating fungal sinusitis are poorly controlled diabetics and those with conditions that predispose to metabolic acidosis such as chronic renal failure or diarrhea. Immunosuppressive states secondary to chemotherapy, hematologic disorders, transplantation, and AIDS also place their hosts at risk for opportunistic infection. Blitzer et al. (1980) found the prevalence of diabetes as high as 70% in his series of 179 cases. Gillespie et al. (1998) has also cited increased incidence in those patients who are using heavy dose of prednisolone or multiple IV antibiotics for long time. Patients in the present study either had uncontrolled diabetes (five cases) or were immunocompromised due medications received after a renal transplant (three cases). One of our patients had leukemia (Table 1). Most common clinical symptoms in our patients were facial swelling, nasal obstruction, fever, headache and proptosis. Similar findings were reported by Blitzer and Lawson (1993),
182
Table 3 Drug used, dosage, duration of treatment, surgical treatment, follow up period and final outcome Case no.
Medical treatment
Dose (mg/kg)
Duration (days)
1
Amphotericin B
0.1–1
43
2 3 4
Amphotericin B Amphotericin B Amphotericin B
0.1 0.1 0.1–1
3 5 30
5
AmBisome
1–3
26
6
AmBisome
3
A7
AmBisome
1–3
25
8
AmBisome
1–3
25
9
AmBisome
1–2
4
0.1–0.7
40
Amphotericin B
9
Follow-up (month)
Outcome
External and endoscopic debridement Endoscopic biopsy Endoscopic biopsy External and endoscopic debridement Endoscopic debridement Endoscopic debridement External and endoscopic debridement Endoscopic debridement Endoscopic debridement
8
Recovered with permanent disability
0 0 4
Died Died Medicine stopped due to poor liver function. Recovered with permanent disability
6
Fully recovered
0
Died
12
Fully recovered
12
Fully recovered
5
Chills, rigor and vomiting AmBisome stopped. Recovered with permanent disability
Permanent disability: (1) blindness in two surviving cases (Case 1 and 9); (2) facial paralysis in three cases (Case 1, 4, 9); (3) facial nerve functions recovered in Case 8.
M.A. Sohail et al. / Acta Tropica 80 (2001) 177–185
Drug used
Surgery
M.A. Sohail et al. / Acta Tropica 80 (2001) 177–185
183
Fig. 5. MRI scan showing infiltration of left cavernous sinus and narrowing of internal carotid artery.
Blitzer and Lawson (1993), Schwartz and Thiel (1997), Schwartz and Thiel (1997) and Gillespie et al. (1998). However, with the exception of Blitzer and Lawson (1993) they less commonly noted ophthalmologic complaints. In comparison this we found proptosis in all our cases (Table 2). Either the disease was more aggressive in our cases or the treating physician failed to recognize early acute fulminant fungal sinusitis. Five of our 9 cases were initially referred to an ophthalmologist as cases of suspected bacterial orbital cellulitis. Unlike Gillespie et al. (1998), we did not find nasal endoscopic examination helpful in early diagnosis. The most common finding was swelling of the lateral wall, which was due to soft tissue swelling of cheek; necrosis of middle turbinate was found in three cases but necrosis of skin was also present. Hence endoscopy did not add any information. However, in order to reach an early diagnosis we advocate early endoscopic examination in all cases and biopsies should be taken from
suspicious areas, middle turbinate and from soft tissue of cheek in case of swelling. The tissues should be subjected for histopathological examination and fungal culture. Wiatrak et al. (1991) found that CT scans of invasive fungal rhinosinusitis are non-specific and do not correlate well with surgical and pathological findings. In the present series, areas of high attenuation within the sinus cavities, so commonly found in allergic fungal sinusitis, were singularly absent. However, there was some amount of opacification of sinuses, bony destruction and soft tissue edema in all cases. This may not be specific to invasive fungal sinusitis but indicates severe inflammatory process in sinuses. We also found areas of high density within the soft tissue in five cases (Fig. 3) and within the orbit in one case (Fig. 4). Presence of fungus in these areas was confirmed during surgery. (Fig. 6). We feel that such areas of high density shadow in soft tissues strongly indicate invasive fungus. Silverman and Mancuso (1998) state: ‘‘Infiltration of
184
M.A. Sohail et al. / Acta Tropica 80 (2001) 177–185
the periantral fat planes may represent the earliest imaging evidence of invasive fungal disease. When encountered as the sole radiologic finding, periantral soft-tissue infiltration should suggest the possibility of invasive fungal sinusitis in the appropriate clinical setting’’. MRI scan may provide new information about intracranial extention. We found evidence of involvement of the cavernous sinus and the internal carotid artery on MRI scan in one case (Fig. 5). CT scan alone cannot obtain this information. Most authors feel that a combination of surgical debridement and high dose amphotrecin B gives the best chance of survival (Talbot et al., 1991; Gillespie et al., 1998; Goering et al., 1988). Surgical debridement should be tailored according to the extent of disease. It may involve an external approach to clear disease form soft tissue of cheek or to debride skin. Extent of disease also influences final outcome. Of three deaths in our cases two patients died due to meningitis. Similar findings were noted by Gillespie et al. (1998). In their study eight of nine patients who died had disease that extended to the base of skull and out of 10 patients who survived, nine had disease limited to the nasal cavity or sinuses. Even when patients survived, neurological deficits (blindness, opthalmoplegia: two cases facial paralysis: three cases) were not reversible in the majority. The underlying medical problem needs to be addressed because it confers important prognostic implications. According to Blitzer et al. (1980),
Fig. 6. Endoscopic surgical finding of fungal debris at the orbital apex as seen in Fig. 4.
diabetic patients have an overall survival rate of 60%, compared with 70% in patients with no underlying disease and 20% in patients with other systemic disorders. All diabetic patients in our series survived whereas only one out of three renal transplant patients survived.
4.1. Conclusion Acute fulminant fungal sinusitis is associated with high mortality and morbidity. Fever, nasal obstruction, headache and facial swelling in an immunocompromised patient may be the earliest indication of this problem. Nasal endoscopy with biopsies and CT scan may contribute to confirmation of diagnosis. Treatment involves surgical debridement, high dosage amphoteracin B, and management of underlying medical problems.
References Baker, R.D., 1957. Mucormycosis: a new disease? J. Am. Med. Assoc. 163, 805 – 808. Blitzer, A., Lawson, W., Meyers, B.R., Biller, H.F., 1980. Patient survival factors in paranasal sinus mucormycosis. Laryngoscope 90, 635 – 648. Blitzer, A., Lawson, W., 1993. Fungal infections of the nose and paranasal sinuses. In: Otolaryngology Clinics of North America: Fungal Infections of the Head and Neck, vol. 26, pp. 1007 – 1035. Denning, D.W., 1996. Therapeutic outcome in invasive aspergillosis. Clin. Infect. Dis. 23, 608 – 615. DeShazo, R.D., O’Brien, M., Chapin, K., Soto-Aguilar, M., Gardner, L., Swain, R., 1997. A new classification and diagnostic criteria for invasive fungal sinusitis. Arch. Otolaryngol. Head Neck Surg. 123, 1181 – 1188 November. Gillespie, M.B., O’Malley, B.W., Francis, H.W., 1998. An approach to fulminant invasive fungal rhinosinusitis in the immunocompromised host. Arch. Otolaryngol. Head Neck Surg. 124, 520 – 526. Goering, P., Berlinger, N.T., Weisdorf, D.J., 1988. Aggressive combined modality treatment of progressive sinonasal fungal infections in immunocompromised patients. Am. J. Med. 85 (5), 619 – 623. Ochi, J.W., Harris, J.P., Feldman, J.I., Press, G.A., 1988. Rhinocerebral mucormycosis: results of aggressive surgical debridement and amphotericin B. Laryngoscope 98, 1339 – 1342. Schwartz, S., Thiel, E., 1997. Clinical presentation of invasive aspergillosis. Mycoses 40 (Suppl. 2), 21 – 24. Silverman, C.S., Mancuso, A.A., 1998. Periantral soft-tissue infiltration and its relevance to the early detection of
M.A. Sohail et al. / Acta Tropica 80 (2001) 177–185 invasive fungal sinusitis: CT and MR findings. AJNR Am. J. Neuroradiol. 19 (2), 321 –325. Stammberger, H., 1991. Mycoses. In: Hawke, M. (Ed.), Functional Endoscopic Sinus Surgery. Decker, BC, Philadelphia, p. 399. Talbot, G.H., Huang, A., Provencher, M., 1991. Invasive
185
aspergillus rhinosinusitis in patients with acute leukemia. Rev. Infect. Dis. 13, 219 – 232. Wiatrak, B.J., Wilging, P., Myer, C.M., Cotton, R.T., 1991. Functional endoscopic sinus surgery in immunocompromised child. Otolaryngol. Head Neck Surg. 105, 818 – 825.
Acute fulminant fungal sinusitis: clinical presentation, radiological findings and treatment M.A. Sohail, Mazin Al Khabori *, Jamil Hyder, Ashok Verma ENT Department, Al Nahdha Hospital, P.O. Box 937, Postal Code 112, Sultanate of Oman, Oman Received 29 May 2000; received in revised form 30 November 2000; accepted 16 February 2001
Abstract Acute fulminant fungal sinusitis is characterized by acute symptoms and rapid progress with a mortality rate of 60–80%. A large number of survivors have permanent neurological, visual and cosmetic disabilities. This clearly underscores the need of early recognition of this disease in at risk population in order to start urgent treatment. The at-risk population of diabetics, AIDS and other immunosupressed is likely to increase, as will the incidence of acute fulminant fungal sinusitis. In the present study we have reviewed nine cases of acute fulminant fungal sinusitis to determine clinical presentation, related radiological picture and optimum treatment. Most common presenting features were fever, headache, facial swelling and proptosis. Many patients presented with blindness, facial paralysis and meningitis. Predisposing causes were uncontrolled diabetes with ketoacidosis in four out of six cases, post renal transplant immunosuppression and leukemia. All patients were treated with of amphotrecin B or liposomal amphotericin B (AmBisome). Diagnosis was confirmed by biopsy and culture of sinus mucosa, soft tissues of cheek, or orbit. Mucor (Zygomycetes) was identified on culture or histopathology in all cases. Surgical debridement was performed in seven cases. Six out of nine patients survived but morbidity was high: only two patients survived without any permanent disability. © 2001 Elsevier Science B.V. All rights reserved. Keywords: Fungal sinusitis; Mycoses
1. Introduction It is estimated that as many as 8 – 10% of patients undergoing surgery for sinusitis or polyposis have fungal sinusitis (Stammberger, 1991), either extramucosal non-invasive or invasive.
* Corresponding author. Tel.: + 968-7733998; fax: + 9687737522. E-mail address: [email protected] (M. Al Khabori).
DeShazo et al. (1997) have described diagnostic criteria for invasive fungal sinusitis: (1) mucosal thickening or air fluid levels compatible with sinusitis on radiological imaging; and (2) histopathological evidence of hyphae within sinus mucosa, submucosa, blood vessels or bone. They also described three forms of invasive fungal sinusitis: (1) granulomatous; (2) acute fulminant; and (3) chronic invasive. Acute fulminant fungal sinusitis though comparatively infrequent, has an invasive and destructive nature. It progresses rapidly with a very high mortality rate. Ochi et al.
0001-706X/01/$ - see front matter © 2001 Elsevier Science B.V. All rights reserved. PII: S 0 0 0 1 - 7 0 6 X ( 0 1 ) 0 0 1 7 4 - 7
178
Table 1 Age, sex, side of disease, underlying medical problem, sites involved other than sinuses and other organ involvement or disease Age in year
Sex
Side
Underlying medical problem/risk group
Sites involved other than sinuses
Other organ/disease
1
28
Female
Left
Diabetes
and
Blindness, ophthalmoplegia, facial paralysis
2
40
Male
Left
of
Meningitis
3
48
Male
Left
of
Meningitis
4
60
Female
Left
Renal failure/renal transplant Renal failure/renal transplant Diabetes
of
Facial paralysis
5
63
Male
Right
Diabetes
6
18
Male
Right
Leukemia
7
45
Female
Left
8
55
Female
Right
Renal failure/renal transplant Diabetes
9
38
Male
Left
Diabetes
Orbit, soft tissue skin of cheek Orbit, soft tissue cheek Orbit, soft tissue cheek Orbit, soft tissue cheek Orbit, soft tissue cheek Orbit, soft tissue skin of cheek Orbit, soft tissue cheek Orbit, soft tissue skin of cheek Orbit, soft tissue cheek
of and
Blindness, ophthalmoplegia
of and
Facial paralysis
of
Blindness, ophthalmoplegia, facial paralysis , cavernous sinus involvement
M.A. Sohail et al. / Acta Tropica 80 (2001) 177–185
Case
M.A. Sohail et al. / Acta Tropica 80 (2001) 177–185
(1988) and Denning (1996) report mortality rates of 82% and 66% repsectively. These patients often present with visual and neurologic features: survivors may have permanent disability. A better understanding of presenting clinical features in high-risk individuals will prompt early relevant investigations, early diagnosis and appropriate surgical and medical intervention This study reviews cases of acute fulminant fungal sinusitis, identifies early clinical features, and evaluates diagnostic methods.
2. Material and methods Retrospective review of case records, CT and MRI scans, operation notes and follow-up records of cases of acute fulminant fungal sinusitis seen in ENT Department, treated at Al Nahdha Hospital over a period of 8 years. Criteria for inclusion in study were as follows: 1. Symptoms suggestive of acute sinusitis or orbital cellulitis. 2. Clinical and radiological evidence of sinusitis. 3. Histological evidence of fungal hyphae in nasal or sinus mucosa or soft tissues of cheek or orbit.
3. Results Nine cases were identified from our records: all had undergone clinical examination, nasal endoscopy and CT scanning: a MRI scan was performed in Case 9. Endoscopic or combined
179
endoscopic external surgery was performed in seven cases. In two cases (2 and 3) surgery was limited to endoscopic examination and biopsy from nose. Both patients died before definitive surgery could be done. Mucor spp (Zygomycetes) was identified on culture or histopathology in all cases. Age, sex, risk factor, sites involved other than sinuses and other organ/disease are presented in Table 1. Disease was unilateral in all cases. The symptoms and signs are presented in Table 2. Fever, nasal obstruction, headache, facial induration, and proptosis were found in all cases (Fig. 1). Neurological involvement included ophthalmoplegia and blindness in three cases, facial paralysis in four cases, and meningitis leading to coma in two cases. Except in Case 8 neurological deficits were irreversible. Necrosis of skin was seen in three cases (Fig. 2).
3.1. Endoscopic findings All patients had swelling of the lateral wall of the nose on endoscopic examination. This was due to soft tissue swelling of the cheek and nasal vestibule. Necrosis and discoloration of the middle turbinate was seen in three cases. Cases also had necrosis of facial skin. Biopsies were taken endoscopically in two cases: (A) from the middle turbinate; and (B) from soft tissues of nasal vestibule and cheek. Biopsies from the middle turbinate were negative for hyphae whereas biopsies from soft tissues of cheek were positive. Swabs taken from the middle meatus during endoscopic examination were negative for fungus.
Table 2 Symptoms and clinical signs Symptoms
No of patients
Signs
No. of patients
Nasal obstruction Facial swelling Headache Fever Nasal discharge Loss of vision Loss of consciousness
9 9 9 9 4 3 2
Facial induration Proptosis Ophthalmoplegia, blindness Facial paralysis Skin necrosis Comatose
9 9 3 4 3 2
180
M.A. Sohail et al. / Acta Tropica 80 (2001) 177–185
3.3. Surgical findings In seven cases affected sinuses were cleaned and ventilated endoscopically. In all cases necrotic bone was found in ethmoids. Necrotic tissue was also found in maxillary sinus in five cases. In one case, the orbital apex was exposed endoscopically, orbital periostium was incised and fungus was curetted out from around the medial rectus muscle. ‘Fungal mucin’ as commonly seen in AFS was not seen in any of these cases. Endoscopic surgery was combined with external debridement in three cases to remove the fungus from soft tissues of cheek. In one case it was needed to debride necrosed skin.
3.4. Medical treatment and follow up Table 3 presents details of medical treatment. This includes drug used, dose regime and duration
Fig. 1. Photograph showing facial swelling and induration, proptosis and facial paralysis.
3.2. Radiological findings CT scan of paranasal sinuses with 4 mm cuts showed varying degree of mucosal edema in ethmoid and maxillary sinus in all cases. The frontal sinus was not involved in any case. Sphenoid opacification was found in one case. Bony destruction either in the region of the lamina paprycea or floor of orbit was seen in all cases. Soft tissue swelling of orbit and cheek was seen in all cases. Hyperdense shadow (double density sign) was seen in the soft tissue swelling in five cases (Fig. 3). Such high attenuation areas were not seen in the sinus cavities. In one case a hyper dense shadow was seen near the orbital apex (Fig. 4). Although CT scan failed to show the involvement of cavernous sinus it was demonstrated on MRI scan in one case (Fig. 5).
Fig. 2. Photograph showing necrosis of facial skin.
M.A. Sohail et al. / Acta Tropica 80 (2001) 177–185
181
with facial palsy recovered facial nerve function: neither of the two blind patients receovered facial nerve function (Table 1). None of the patients showed any sign of recurrence at the end of followup.
4. Discussion
Fig. 3. CT scan showing edema of orbit and hyperdense shadow in the edematous tissue of check.
of treatment for each case. It also shows surgical treatment, follow-up period, and outcome. Four patients received amphotrecin B (Case 1, 2, 3, 4): AmBisome was not available at that time. AmBisome which is less toxic than amphoteracin was used in four cases (Case 5– 8). In Case 9, AmBisome was not tolerated and therapy was switched to amphotericin B after 4 days. In Case 4, therapy had to be stopped after 30 days (1 g of total amphotericin B) due to liver impairment. In three cases, patients died within 10 days of starting therapy: the cause of death was meningitis in Cases 2 and 3. In Case 6 death was due to uncontrollable hemorrhage from multiple sites in a leukaemic patient. Surprisingly the bleeding was minimal from the operated site. Surviving patients were followed for an average range of 4– 12 months. Only one of 4 patients
Fig. 4. CT scan showing hyperdense shadow at orbital apex.
Fungi incriminated in acute fulminant fungal sinusitis include Actinonycete eg. Aspergillus (Talbot et al., 1991) or Zygomycetes eg. Rhizopus and Mucor (Baker, 1957). These saprophytic fungi reproduce and grow in soil, decaying food, grain, and plants. They thrive in any environment with an acidic pH and an abundance of glucose. After becoming airborne, Mucor spores may settle onto the mucosa of a susceptible host. They penetrate into the tissue, allowing angioinvasion to occur. Mucor has a predilection for the internal elastic lamina of the arteries. The invasion produces thrombosis, with secondary ischemic infarction and hemorrhagic necrosis. The fungus thrives in this environment and spreads along injured vessels. Acute fulminant fungal sinusitis is characterized by its acute symptoms, rapid progress and high mortality. Patients at highest risk for acute fulminating fungal sinusitis are poorly controlled diabetics and those with conditions that predispose to metabolic acidosis such as chronic renal failure or diarrhea. Immunosuppressive states secondary to chemotherapy, hematologic disorders, transplantation, and AIDS also place their hosts at risk for opportunistic infection. Blitzer et al. (1980) found the prevalence of diabetes as high as 70% in his series of 179 cases. Gillespie et al. (1998) has also cited increased incidence in those patients who are using heavy dose of prednisolone or multiple IV antibiotics for long time. Patients in the present study either had uncontrolled diabetes (five cases) or were immunocompromised due medications received after a renal transplant (three cases). One of our patients had leukemia (Table 1). Most common clinical symptoms in our patients were facial swelling, nasal obstruction, fever, headache and proptosis. Similar findings were reported by Blitzer and Lawson (1993),
182
Table 3 Drug used, dosage, duration of treatment, surgical treatment, follow up period and final outcome Case no.
Medical treatment
Dose (mg/kg)
Duration (days)
1
Amphotericin B
0.1–1
43
2 3 4
Amphotericin B Amphotericin B Amphotericin B
0.1 0.1 0.1–1
3 5 30
5
AmBisome
1–3
26
6
AmBisome
3
A7
AmBisome
1–3
25
8
AmBisome
1–3
25
9
AmBisome
1–2
4
0.1–0.7
40
Amphotericin B
9
Follow-up (month)
Outcome
External and endoscopic debridement Endoscopic biopsy Endoscopic biopsy External and endoscopic debridement Endoscopic debridement Endoscopic debridement External and endoscopic debridement Endoscopic debridement Endoscopic debridement
8
Recovered with permanent disability
0 0 4
Died Died Medicine stopped due to poor liver function. Recovered with permanent disability
6
Fully recovered
0
Died
12
Fully recovered
12
Fully recovered
5
Chills, rigor and vomiting AmBisome stopped. Recovered with permanent disability
Permanent disability: (1) blindness in two surviving cases (Case 1 and 9); (2) facial paralysis in three cases (Case 1, 4, 9); (3) facial nerve functions recovered in Case 8.
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Drug used
Surgery
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Fig. 5. MRI scan showing infiltration of left cavernous sinus and narrowing of internal carotid artery.
Blitzer and Lawson (1993), Schwartz and Thiel (1997), Schwartz and Thiel (1997) and Gillespie et al. (1998). However, with the exception of Blitzer and Lawson (1993) they less commonly noted ophthalmologic complaints. In comparison this we found proptosis in all our cases (Table 2). Either the disease was more aggressive in our cases or the treating physician failed to recognize early acute fulminant fungal sinusitis. Five of our 9 cases were initially referred to an ophthalmologist as cases of suspected bacterial orbital cellulitis. Unlike Gillespie et al. (1998), we did not find nasal endoscopic examination helpful in early diagnosis. The most common finding was swelling of the lateral wall, which was due to soft tissue swelling of cheek; necrosis of middle turbinate was found in three cases but necrosis of skin was also present. Hence endoscopy did not add any information. However, in order to reach an early diagnosis we advocate early endoscopic examination in all cases and biopsies should be taken from
suspicious areas, middle turbinate and from soft tissue of cheek in case of swelling. The tissues should be subjected for histopathological examination and fungal culture. Wiatrak et al. (1991) found that CT scans of invasive fungal rhinosinusitis are non-specific and do not correlate well with surgical and pathological findings. In the present series, areas of high attenuation within the sinus cavities, so commonly found in allergic fungal sinusitis, were singularly absent. However, there was some amount of opacification of sinuses, bony destruction and soft tissue edema in all cases. This may not be specific to invasive fungal sinusitis but indicates severe inflammatory process in sinuses. We also found areas of high density within the soft tissue in five cases (Fig. 3) and within the orbit in one case (Fig. 4). Presence of fungus in these areas was confirmed during surgery. (Fig. 6). We feel that such areas of high density shadow in soft tissues strongly indicate invasive fungus. Silverman and Mancuso (1998) state: ‘‘Infiltration of
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the periantral fat planes may represent the earliest imaging evidence of invasive fungal disease. When encountered as the sole radiologic finding, periantral soft-tissue infiltration should suggest the possibility of invasive fungal sinusitis in the appropriate clinical setting’’. MRI scan may provide new information about intracranial extention. We found evidence of involvement of the cavernous sinus and the internal carotid artery on MRI scan in one case (Fig. 5). CT scan alone cannot obtain this information. Most authors feel that a combination of surgical debridement and high dose amphotrecin B gives the best chance of survival (Talbot et al., 1991; Gillespie et al., 1998; Goering et al., 1988). Surgical debridement should be tailored according to the extent of disease. It may involve an external approach to clear disease form soft tissue of cheek or to debride skin. Extent of disease also influences final outcome. Of three deaths in our cases two patients died due to meningitis. Similar findings were noted by Gillespie et al. (1998). In their study eight of nine patients who died had disease that extended to the base of skull and out of 10 patients who survived, nine had disease limited to the nasal cavity or sinuses. Even when patients survived, neurological deficits (blindness, opthalmoplegia: two cases facial paralysis: three cases) were not reversible in the majority. The underlying medical problem needs to be addressed because it confers important prognostic implications. According to Blitzer et al. (1980),
Fig. 6. Endoscopic surgical finding of fungal debris at the orbital apex as seen in Fig. 4.
diabetic patients have an overall survival rate of 60%, compared with 70% in patients with no underlying disease and 20% in patients with other systemic disorders. All diabetic patients in our series survived whereas only one out of three renal transplant patients survived.
4.1. Conclusion Acute fulminant fungal sinusitis is associated with high mortality and morbidity. Fever, nasal obstruction, headache and facial swelling in an immunocompromised patient may be the earliest indication of this problem. Nasal endoscopy with biopsies and CT scan may contribute to confirmation of diagnosis. Treatment involves surgical debridement, high dosage amphoteracin B, and management of underlying medical problems.
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