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Case Reports Indian Pediatrics 2002; 39:381-385 |
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Rhino-orbital Mucormycosis in Acute Renal Failure |
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Mucormycosis is a fulminant, often lethal, fungal infection, caused by Mucorales, belonging to class Zygomycetes. Full blown disease usually occurs only in the presence of certain specific predisposing factors. It is a relatively uncommon condition and to our knowledge only four reports(1-4) of rhinocerebral mucormycosis (RCM), comprising of eight cases have been published from India so far, only one of which belongs to the pediatric age group. We present a case of rhino-orbital mucormycosis associated with acute renal failure in a child. Case Report An eight-year-old boy, resident of village Bhatsana in Haryana, presented with the complaints of fever and common cold for one week, difficulty in breathing for five days and decreased urine output for three days. There was no history of loose motions, vomiting, frequency of micturition, dysuria, hematuria, skin rash, bleeds from any site, convulsions or trauma. There was no major illness in the past. On examination, the patient was of average build and nutrition, drowsy and had a toxic look. He had pallor, generalized edema, and some chemosis, proptosis and periorbital swelling of the left eye, but ocular movements and pupillary reactions were preserved. Chest had normal breath sounds and air entry on both sides. Cardiovascular examination showed an ejection systolic murmur. Abdomen was soft, with mild hepatomegaly, no splenomegaly and no free fluid. Neurologically, the patient was drowsy and disoriented but without any focal deficit, meningeal signs or evidence of raised intracranial tension. Blood pressure was raised (160/110 mm Hg). Investigations showed deranged kidney functions (urea 210 mg/dl and creatinine 4.1 mg/dl), severe anemia (Hb 5.0 g/dl) and moderate thrombocytopenia (70,000/mm3). Peripheral smear showed neutrophilic leuko-cytosis with toxic granules, thrombocytopenia, reticulocytosis (4.1%) and normocytic, normochromic RBCs with anisopoikilocytosis and occasional fragmented cells. PT and APTT were within normal limits. Cultures from all its sites including eye swabs were sterile. Urine analysis showed microscopic hematuria and mild proteinuria (1+). Urine culture was initially sterile but subsequently grew Klebsiella sensitive to aminoglycosides. Ultrasonography of the abdomen showed slightly enlarged kidneys with no other changes. Diagnosis of acute renal failure was made on the basis of clinical picture (oliguria) and investigations. Treatment was started with peritoneal dialysis, intravenous antibiotics, oxygen, blood transfusion and anti-hypertensives. Over the next week, the patient’s condition gradually improved and he began to pass urine, and urea and creatinine values improved somewhat but still remained deranged. After two weeks, peritoneal dialysis was stopped. But in view of persistently deranged kidney functions (urea 90 mg/dl, creatinine 2.0 mg/dl), kidney biopsy was done which showed thickened capillary deposits and creas of necrosis, diagnostic of hemolytic uremic syndrome. Proptosis and chemosis of the left eye however continued to increase over this period and soon the patient developed extra-ocular muscle paralysis. The swelling spread to the maxillary area and he developed black nasal discharge and a gangrenous area over the infra-orbital region and cheek. Ultrasound showed diffuse infiltration of the orbit with choroidal effusion and CT scan showed a normal cranium and a retro-orbital mass, the nature of which could not be determined. Surgical debridement of the area was done and the material sent for biopsy. It showed large foci of necrosis and granuloma formation with giant cells and abundant wide fungal hyphae which were of irregular width, non septate and branching at rights angles. Based on biopsy report, a diagnosis of rhino-orbital mucor-mycosis was made and the patient was started on Amphotericin-B. After instituting Amphotericin, the patient began to show improvement in the facial lesion. However, two weeks later, he developed massive gastro intestinal hemorrhage. Platelet counts were low (7000/mm3). Blood and platelets were transfused but he continued to bleed and expired within three days. Autopsy could not be done as parental consent was not available. Discussion Mucormycosis is a fulminant infection caused by fungi of the order mucorales. The commonest species are Mucor, Rhizopus, Rhizomucor, and Absidia. The fungus is a common ubiquitous saprophyte found in farms, gardens, forests, etc. and unlike Candida and Aspergillus it is not found in the hospital environment. Spores are acquired by inhalation, ingestion or penetrating trauma. Germination is favored by low oxygen, high glucose, acidic medium and high iron levels. Following entry of spores in the body, full blown disease occurs only in presence of certain predisposing factors (Table I). "Angioinvasion" is the hall mark of pathogenesis and consists of thrombosis of vessels resulting in tissue necrosis and formation of black eschars and gangrenous masses which have low tendency to bleed during surgery(8). This was evident in our case also. The disease may present as any of the following seven clinical syndromes - (i) rhino-cerebral, (ii) pulmonary, (iii) gastrointestinal, (iv) CNS, (v) cutaneous, (vi) disseminated, and (vii) miscellaneous (bones, joints, heart, kidney, mediastinum). Rhinocerebral mucor-mycosis (RCM) is the commonest form of phycomycosis and has been reported worldwide since 1943(9). It occurs in immunocompromised and diabetic patients. It has also been reported in association with renal failure, both acute and chronic. Chetchotisakd et al.(10) reported 11 cases of RCM of which 5 were associated with chronic renal failure. Similarly Desai and Deshpande from India(2) reported 4 adult cases of RCM, all of which were associated with chronic renal failure and terminated fatally. The disease has been reported in associaltion with acute renal failure by Melnick et al.(7) and Utas et al.(11), the case in the former report having a fatal outcome. In our patient it was associated with acute renal failure due to HUS. The mechanism by which uremic patients fall prey to mucormycosis is not clear. Probably, the altered immunologic state, acidosis and leucopenia, all play a role in providing the required milieu for tissue invasion(2).
RCM is a rhino-cerebral, rhino-orbital, paranasal syndrome. Smith and Krichner(12) gave the following criteria for the clinical diagnosis of mucormycosis: (i) a blood tinged nasal discharge and facial pain, both on the same side, (iii) soft peri-orbital or peri-nasal swelling, going on to discoloration, induration and progressive vascular occlusion, (iii) ptosis of the eyelid, proptosis of the eyeball and complete ophthalmoplegia, (iv) multiple unrelated cranial nerve palsies, and (v) black, necrotic turbinates, easily mistaken for dried, crusted blood. These features were present in our patient, though he did not have any other cranial nerve palsy except for the ocular nerves. Other less common features are retinal infarction, cavernous sinus and internal carotid thrombosis, terminating in seizures and death. A high index of suspicion must be maintained for diagnosis. The gold standard for diagnosis is biopsy of the affected area with direct microscopy of the specimen using eosin haematoxylin, PAS or Grocott-Gomori methenamine silver stain, which shows characteristic broad (10-20 micron), irregular, non septate hyphae with right angled branching(13). Direct plating of the biopsy specimen is best for isolation in culture, but because of lack of awareness of the condition, fungi have been isolated in relatively few patients during life or even at autopsy and there are numerous instances where definitive diagnosis has been made on microscopy alone(1,10,14). In our case also, the abundance of fungal elements seen in tissue specimen, compensates for our failure to culture the fungus. A combination of surgical debridement and high dose amphotericin-B (1.0-1.5 mg/kg/d) is the treatment of choice(15). Duration of therapy is empirical. Toxicity of the drug is mainly characterized by fever with rigors and nephrotoxicity. Pancytopenia may also occur and this may have been the cause of terminal thrombocytopenia and bleed in our patients. The use of liposomal Amphotericin-B reduces nephrotoxicity. Since the drug does not diffuse into the peritoneal cavity, no dosage modification is needed in patient on peritoneal dialysis(16). Hyperbaric oxygen is a good adjunct to therapy in the rhinocerebral form(17). Correction of underlying disorder is of paramount importance. However, despite the best treatment, mortality is high, ranging from 21% to 70% in the rhinocerebral form(18). Other forms of mucormycosis are pulmonary, gastrointestinal, CNS, etc. and occur in patients with the above mentioned predisposing factors. Involvement of the kidneys in the disseminated variety results in thromboses of large vessels resulting in tissue infarction and necrosis and hyphae are seen in tissue sections(19). Our patient had acute renal failure as the only predisposing factor. Initially kidney biopsy showed only features of HUS without any evidence of mucor in the tissue. So mucormycosis was not the cause of renal failure. Whether dissemination later occured or not cannot be said with certainty as autopsy could not be done. The case is being highlighted as the infection is a relatively rare one and a high index of suspicion must be maintained and the condition suspected whenever a debilitated pateint developes necrotizing infection with the formation of black eschars. Contributors: MSR was involved in patient care, did review of literature and drafted the manuscript. VK supervised patient care and critically reviewed the manuscript. NKD supervised patient care and criti-cally reviewed the manuscript. He will act as guarantor for the article. DJ was involved in patient care and review of literature. Funding: None. Competing interests: None stated.
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