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  IN THIS Article
 ::  Abstract
 ::  Introduction
 ::  Discussion
 ::  References

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PAPERS
Year : 1995  |  Volume : 41  |  Issue : 2  |  Page : 40-2

Disseminated mucormycosis in healthy adults.


Department of Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India., India

Correspondence Address:
G R Verma
Department of Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
India
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Source of Support: None, Conflict of Interest: None


PMID: 0010707707

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 :: Abstract 

Three patients of disseminated mucormycosis are described. None had predisposing factors. Two of them presented with nonspecific symptoms along with acute renal failure and peritonitis. Third patient had fulminating primary cutaneous mucormycosis which disseminated later. Development of acute renal failure with smooth enlargement of both kidneys in an apparently healthy individual or appearance of mould in a wound should raise the suspicion of mucormycosis. The hallmark of the infection was vascular invasion and thrombosis. Antemortem diagnosis could be made in one patient only. All patients had progressive downhill course despite supportive treatment, antibiotic and amphotericin in-B in one patient.


Keywords: Adult, Antifungal Agents, administration &dosage,Autopsy, Case Report, Fatal Outcome, Fungemia, diagnosis,drug therapy,Human, Immunocompetence, Male, Middle Age, Mucormycosis, diagnosis,drug therapy,Treatment Outcome,


How to cite this article:
Verma G R, Lobo D R, Walker R, Bose S M, Gupta K L. Disseminated mucormycosis in healthy adults. J Postgrad Med 1995;41:40

How to cite this URL:
Verma G R, Lobo D R, Walker R, Bose S M, Gupta K L. Disseminated mucormycosis in healthy adults. J Postgrad Med [serial online] 1995 [cited 2019 Dec 7];41:40. Available from: http://www.jpgmonline.com/text.asp?1995/41/2/40/501





  ::   Introduction Top


Mucorales are ubiquitous saprophytic filamentous fungi that belong to the class Zygomycetes. The common pathogens are Rhizopus, Absidia and Mucor. They have a low intrinsic pathogenicity, but can cause fulminant and fatal infection in immunocompromised hosts[1] suffering from diabetic ketoacidosis, malnutrition or malignancy and also in organ transplant recipients[2]. The diagnosis is usually not made during life due to non-specificity of symptoms. Rarely the disease may affect healthy individuals[3].

We describe three cases of fatal disseminated mucormycosis in healthy patients. Antemortem diagnosis could be made only in one patient. Final diagnosis was confirmed by histo-pathology in all the cases. Non-specific symptoms and virulent systemic invasion of the disease warrants awareness.

Case 1: A 26 years old male presented with a 15 days history of high grade, intermittent fever associated with chills and rigors. He also complained of a generalised dull abdominal ache for the past 8 days. This was associated with progressive abdominal distension and repeated bilious vomiting. He had oliguria for two days prior to presentation. His haemoglobin was 10.5 g/dl. The total leucocyte count (TLC) was 19,000/cu mm with 82% neutrophils. The blood urea was 176 mg/dl (normal 20-40) and the serum creatinine 9.0 mg/dl (normal upto 1.2 mg/dl). Urine examination revealed mild albuminuria, numerous pus cells, isolated red blood cells and hyaline casts. The blood gas analysis showed hypoxia with metabolic acidosis. Examination of the fluid obtained by abdominal paracentesis revealed numerous red blood cells and a leucocyte count of 60 cells/cu mm. Fluid amylase was normal and Gram stain was negative. The prothrombin index was 56% the platelet count 1,75,000/cu mm and fibrin degradation products (FDP) were absent.

Abdominal ultrasonography revealed hepatosplenomegaly and gross bilateral smooth enlargement of the kidneys, suggestive of renal parenchymal disease. The chest X-ray was normal and abdominal X-ray was suggestive of paralytic ileus. Blood, urine and peritoneal fluid cultures were sterile. Patient remained febrile and oliguria (< 100 ml/day). He was put on conservative treatment and underwent repeated hemo-dialysis. However. his general condition continued to deteriorate and he succumbed on seventh day after admission due to renal and respiratory failure.

A partial autopsy was performed. The liver and spleen were uniformly enlarged while the stomach, duodenum, small and large bowel and pancreas were normal. The kidneys were grossly enlarged. On cut section there was loss of corticomedullary distinction and there were areas of necrosis and haemorrhage. Renal vessels were noted to be thromosed. There was microscopic evidence of vasculitis and acute inflammation in its segmental branches [Figure:1]. There was also associated cortical necrosis along with invasion of renal parenchyma by broad aseptate fungal hyphae having right angle branching [Figure:2]. Grocott’s modification of silver methenamine stain confirmed the morphology of the fungus. Mucor was also identified within the liver and spleen.

Case 2: A 32 years old male patient underwent appendicectomy outside. Postoperatively, he developed fever. jaundice and oliguria and was referred to us. He was febrile, toxic, dyspnoeic and icteric. The abdomen was distended and there was evisceration of small bowel loops from infected appendicectomy wound. He had diffuse abdominal tenderness and ascites. Bilateral renal angle tenderness was also present. The haemoglobin was 8.2 g/dl and TLC 24,000 cells/cu mm. The serum electrolytes were normal. The blood urea was 200 mg/dl and serum creatinine 7.3 mg/dl. Serum transaminases levels were normal and the serum bilirubin was 8.0 mg/dl. The blood gas analysis showed hypoxia with metabolic acidosis. Abdominal X-ray was unremarkable and the chest X-ray revealed patchy areas of consolidation. An abdominal ultrasound examination showed bilateral renal enlargement suggestive of acute parenchymal disease with perinephric fluid collection. Blood culture grew acinetobacter resistant to all antibiotics. Urine culture was sterile. Fungal serology and fungal blood cultures were negative.

The patient was managed conservatively with broad spectrum antibiotics and supportive treatment. The urine output was less than 150 ml/day. He underwent tri-weekly haemodialysis. His condition progressively deteriorated. He developed hepatic encephalopathy and expired after 3 weeks of hospitalisation. A partial autopsy was performed. There was a 2 cms perforation in the caecum with an organised abscess (approx. 300 ml) in ileocaecal region. Both kidneys were enlarged and adherent to perinephric structures. On cut section cortex and medulla were studded with multiple abscesses. The lining of pelvicalyceal system was ulcerated with yellowish exudate, over it. Microscopically in addition to acute inflammatory infiltrate, the blood vessels showed thrombosis along with broad aseptate hyphae with irregular division at right angle, consistent with the morphology of mucor. Numerous similar fungal hyphae were also noted in the sections taken from ileocaecal region, urinary bladder, adrenals, heart and lung.

Case 3: A 45 years old male had a fall from a height and sustained multiple abrasions on the anterior abdominal wall. He subsequently had fever and noticed a gradual discoloration of the skin to black. He was febrile. There was an 8 x 6 cm area of cutaneous necrosis with surrounding erythema on the anterior abdominal wall.

Investigations revealed haemoglobin of 14.5 g/ dl and TLC of 9600/cu mm. Initially renal function tests were normal. But later on blood urea and creatinine rose to 120 mg % and 4.6 mg % respectively. Blood gas analysis revealed persistent hypoxia and metabolic acidosis. Abdominal ultrasound, chest and abdominal roentgenograms were normal.

The debridement of anterior abdominal wall wound was done till the normal tissue was visualised and patient was put on high doses of penicillin, amikacin and metronidazole. As the tissue necrosis progressed and the floor of the wound was noticed to be covered by mould, he underwent repeated debridements and dressing with topical antifungal ointment. Although tissue and blood culture for fungi were negative, the fungal serology was positive and the tissue biopsy from abdominal wall wound revealed nonseptate fungal hyphae with right angle branching invading the blood vessels, characteristic of mucormycosis. Wound swab and blood culture also grew E.coli and Staph aureus sensitive to amikacin and ampicillin. Patient was put on amphotericin-B and amikacin in renal doses. His urine output dropped and he became progressively dyspnoeic and finally died of renal and respiratory failure after 20 days of hospitalisation.


  ::   Discussion Top


Disseminated mucormycosis accounts for 9% cases of the mucormycosis[4] and it carries high mortality. The disease presents with non-specific clinical symptoms and is usually diagnosed at autopsy[5], Renal involvement is seen frequently in disseminated disease[6]. Isolated renal mucormycosis is distinctly rare[7],[8].

All three of our patients were apparently in normal health prior to the onset of symptoms and they had no underlying systemic disease. Two of them who presented with features of peritonitis and renal failure, had smooth enlargement of both kidneys, a finding often seen in renal mucormycosis[7]. History of trauma preceding dermal mucormycosis is a common observation[4]. It is followed by the change in the colour of the skin to black. One of our patients had similar presentation in this patient, failure to obtain microscopically clear margins during repeated debridement, virulent systemic invasion of mucor and perhaps delay in administration of amphotericin-B due to want of diagnosis seems to be the cause of death. Finding of bacteria in the wound swab and blood is not surprising, as in 73% patients of disseminated mucormycosis, concomitant infection has been reported[9].

The underlying factors for increased pathogenicity of fungi in apparently healthy patient could be alteration of bacterial flora due to preceding antibiotics or sepsis induced altered immune response as majority of patients of disseminated disease have bacterial infection. The pathognomic feature of mucormycosis is vascular invasion with thrombosis of large and small arteries resulting into infarction, necrosis and accumulation of acute inflammatory exudate[1]. The definitive diagnosis is made on demonstration of invasion of hypae. Blood and tissue culture for mucor are often negative[9] and this accounts of infrequent ante-mortem diagnosis. Moreover even if culture is positive it may merely indicate the presence of this ubiquitous saprophyte and not necessarily the invasion. Therefore, whenever there is a clinical suspicion, the diagnosis should be confirmed by tissue biopsy as was done in our third case, The prognosis of disseminated mucormycosis is poor with mortality ranging from 27%[4] to 100%[5].

All three cases demonstrate that mucormycosis can occur in healthy individuals without any contributory factors. The ante-mortem diagnosis is either difficult or made late which leads to rapid systemic dissemination and death. Any hope of survival depends on high index of clinical suspicion early diagnosis, adequate surgical excision/debridement and administration of amphotericin-B.

 
 :: References Top

1. Aw S, Merrel RC, Edwards MF. Mucormycosis in patients with multiple organ failure. Arch Surg 1984; 119:1189-1191.  Back to cited text no. 1    
2.MeNulty JS. Rhinocerebral mucormycosis: predisposing factors, Laryngoscope 1982; 92:1140-1143.  Back to cited text no. 2    
3.Record NB Jr, Ginder DR. Pulmonary phycomycosis without obvious predisposing factor. JAMA 1976; 235:1256-1257.  Back to cited text no. 3    
4.Parfrey NA. Improved diagnosis and prognosis of mucormycosis: a clinicopathologic study of 33 cases. Medicine 1986; 65:113-123.  Back to cited text no. 4    
5.Gupta KL, Radotra B, Sakhuja V, Banerjee AK, Chugh KS. Mucormycosis in patients with renal failure. Renal Failure 1989-90; 11:195-199.  Back to cited text no. 5    
6.Meyer RD, Rosen P, Armstrong D. Phycomycosis complicating leukemia and lymphoma. Ann Intern Med 1972; 77:871-879.  Back to cited text no. 6    
7.Davila RM, Moser SA, Grosso LE. Renal mucormycosis: a case report and review of the literature. J Urol 1991; 145:1242-1244.  Back to cited text no. 7    
8.Stratsma BR, Zimmerman LE, Gass JDM. Phycomycosis: a clinicopathologic study of 51 cases. Lab Invest 1962; 11:963-985.  Back to cited text no. 8    
9.Bhaduri S, Kurrie E, Vanek E, Spanel R. Mucormycosis in the immunocompromised host, Infection 1983; 11:170-172.   Back to cited text no. 9    



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