Primary cutaneous zygomycosis from a tertiary care centre in north-west India.
Patients who are at high risk of developing cutaneous zygomycosis are those with disruption of the normal protective cutaneous barrier. Local risk factors for cutaneous zygomycosis include trauma, burns, surgery, surgical splints, arterial lines, injection sites, biopsy sites, tattoos, and insect or spider bites (4-8). Systemic risk factors for cutaneous zygomycosis are hyperglycaemia, ketoacidosis, malignancy, leucopenia and immunosuppressive therapy (9,10). Infection in the immunocompetent host, however, is well described (11). The outcome of cutaneous zygomycosis depends, in part, on the prognosis of the underlying disease together with early diagnosis and treatment.
In our centre we diagnosed nine cases of primary cutaneous zygomycosis between November 2001 and September 2007. Here we describe clinical presentation, fungi isolated and management of these cases to raise clinical awareness.
Material & Methods
All patients diagnosed with primary cutaneous zygomycosis at Government Medical College & Hospital, Chandigarh between November 2001 and September 2007 were included in this study. They presented with clinical diagnosis of necrotizing fasciitis. Detailed history of each patient was taken. Clinical presentation, site of involvement, underlying illness and risk factor, if any were noted. Routine laboratory investigations were carried out. Aspirated pus, pus swabs or cutaneous tissue specimens were sent for microbiological examination. Cutaneous tissue specimens were sent for histopathological examination. The diagnosis was established by direct microscopic evidence of broad, aseptate or sparsely septate ribbon-like hyphae with right angle branching in KOH wet mount and histopathological examination of stained sections. To isolate fungi, the specimens were inoculated on to Sabouraud dextrose agar (SDA) and brain heart infusion agar (BHIA) and incubated at 25[degrees]C and 37[degrees]C. The growth obtained on culture was identified by colony characteristics, lactophenol cotton blue preparation and slide culture. For sporulation, agar floation method was used i.e., one cm SDA agar blocks permeated with hyphae and accompanying aerial hyphae were cut and placed on surface of sterile water-yeast extract solution (12). Abundant sporulation was seen within 4 days when grown at 37[degrees]C. Additionally, the samples were inoculated on to the plates of blood agar, MacConkey agar and BHI broth and incubated at 37[degrees]C overnight to look for bacterial growth. The patients were managed surgically and/or medically along with correction of underlying illness, if any (Table). Outcome of the therapy was analysed.
Results & Discussion
The clinical and laboratory details of all nine patients diagnosed of primary cutaneous zygomycosis between November 2001 and September 2007 show that diabetes mellitus was present only in one patient (Table). None of the patients were neutropenic or on immunosuppressive therapy. A history of trauma as a risk factor was available in one patient, three had zygomycosis affecting intramuscular injection sites, one had involvement of appendicectomy wound and one had Plaster of Paris cast as the risk factor. The fungal culture was sterile in three cases, however, KOH wet mount and histopathological examination of stained sections confirmed zygomycosis. In the remaining six cases, fast growing, white and cottony growth was obtained from biopsy tissue, aspirated material or pus. Species identification was done by lactophenol cotton blue preparation, slide culture and spore induction. Apophysomyces elegans was isolated in four cases, Saksenaea vasiformis in one and Absidia corymbifera in one. Mortality rate was high. Only four patients responded well to surgical and/or medical therapy. Five patients expired either because of delay in diagnosis and treatment or septicaemia due to superadded bacterial infections or inability to afford costly antifungal treatment.
Cutaneous zygomycosis is characterized by pain, erythema and induration with varying degrees of central necrosis. More advanced lesions take on the appearance of necrotizing fasciitis which has a mortality approaching 80 per cent (13). Necrotizing fasciitis is mostly bacterial in origin. Progression to the advanced gangrenous or disseminated form may be rapid and occurs most commonly in the immunocompromised host (14).
The agents of zygomycosis are incapable of penetrating intact skin. A typical case results from traumatic implantation of soil (15). In diabetic and immunocompromised patients, cutaneous lesions may also arise at insulin injection or catheter insertion sites (16). Contaminated surgical dressings have also been implicated as a source of cutaneous zygomycosis (17). Cutaneous zygomycosis has also been reported to occur due to contaminated tape used to secure an endotracheal tube in a ventilated patient (18).
A. elegans is being reported with increasing frequency as a cause of infection typically in immunocompetent patients following trauma or invasive procedures. A fatal case of necrotizing fasciitis caused postoperatively by A. elegans in an immunocompetent patient was reported from south India in 1993 (19). In 1997 another case with striking similarity was reported from south India (6). Chakrabarti et al (20) reported three cases of cutaneous and subcutaneous infections due to A. elegans, two of whom were immunocompetent (20). Jain et al (21) reported 18 cases of zygomycotic necrotizing fasciitis, of whom, 15 were immunocompetent and of the eight cases cultured, five were positive for A. elegans. Of the present six cases showing growth, four were positive for A. elegans, and three were immunocompetent. A. elegans gives an excellent mycelial growth on routine culture media within 24 to 48 h but is notorious for not being able to produce asexual spores (12). In general morphology, A. elegans closely resembles Absidia species in producing pyriform, apophyseal, multispored sporangia on sporangiophores which arise on stolons but typically not opposite rhizoids (Fig. 1). It differs from Absidia species in that it has more pronounced apophyses, which are funnel or bell shaped (Fig. 2) and a hyphal segment reminiscent of the foot cells of Aspergillus species. The characteristic darkening and thickening of the sporangiophore wall below the apophyses that narrows the lumen of the sporangiophore differentiates the genus Apophysomyces from related genera.
[FIGURE 1 OMITTED]
[FIGURE 2 OMITTED]
A. Corymbifera grows readily upon subculture on routine mycology media, growing more rapidly at 37[degrees]C than at 25[degrees]C and it is capable of growth at temperatures up to 48 to 52[degrees]C, which distinguishes it from other Absidia species (22). It accounts for perhaps 2 to 3 per cent of culture confirmed cases of zygomycete infection. Subcutaneous infection due to A. corymbifera in a diabetic patient with multiple discharging sinuses has been reported from Chennai (23). Post-traumatic cutaneous and subcutaneous infections due to A. corymbifera have been also reported (24,25).
Saksenaea vasiformis resembles A. elegans in gross colony morphology and in its inability to sporulate on routine culture media. However, the morphology of sporangia (flask shaped) on spore induction differentiates it easily from A. elegans. The first case of subcutaneous zygomycosis caused by S. vasiformis in India was reported in a rice mill worker in 1988 (26). More cases were subsequently been reported from Chandigarh in 1997 (27). A fatal case of necrotising fasciitis due to S. vasiformis has been reported from Visakhapatnam (28).
Diagnosis of cutaneous zygomycosis is based clinically on the rapidly invasive course of the disease and demonstration of broad, aseptate or sparsely septate hyphae with right angle branching often with angioinvasion on histopathology and direct examination. Specimen should be taken from the leading edge rather than the centre of the lesion (29). The tissue biopsy should be large enough to contain viable fungus. Zygomycetous fungi have primitive coenocytic hyphae that will often be damaged and become nonviable during the biopsy procedures or by the chopping up or tissue grinding process in the laboratory. That is why zygomycetous fungi that are clearly visible in direct microscopic or histopathological mounts are often difficult to grow in culture from clinical specimens (29). This could be the reason why three of our cultures turned out to be sterile, despite best efforts to isolate the fungus while direct microscopic and histopathological mounts were positive for fungal hyphae suggestive of zygomycosis. So, in case of clinical suspicion, culture for zygomycetes should specifically be requested for, because homogenization of tissue in the laboratory can result in fungal destruction.
Treatment requires prompt and aggressive surgical debridement supported by administration of systemic antifungals and reversal of underlying risk factors (29). Lipid formulations of amphotericin B are the treatment of choice. Posaconazole, a new triazole, can be a good alternative in patients with amphotericin B associated toxicity (30). Hyperbaric oxygen has been a component of successful therapy in a few cases (31). Cytokines such as gamma interferon and granulocyte-macrophage colony-stimulating factor increase the ability of phagocytes to kill agents of zygomycosis in vitro but their role as adjunctive therapy for zygomycosis is still understudied. Surgical debridement and antifungal therapy should be continued until follow up evaluation shows no residual fungal infection or necrosis (32).
Zygomycosis must be considered in the differential diagnosis in any patient presenting with progressive, necrotic lesion whether immunocompromised or not. There is a need for awareness among the clinicians to have high index of suspicion to establish appropriate diagnosis at an early stage of the disease so that specific treatment can be instituted in time.
Received November 17, 2008
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Reprint requests: Dr Jagdish Chander, Professor & Head, Department of Microbiology, Government Medical College & Hospital Sector 32, Chandigarh 160 030, India e-mail: email@example.com
J. Chander, J. Kaur, A. Attri * & H. Mohan **
Departments of Microbiology, * Surgery & ** Pathology, Government Medical College & Hospital Chandigarh, India
Table. Summary of patients diagnosed of primary cutaneous zygomycosis (November 2001 and September 2007) Age S. Month (yr)/ Area Clinical no. & yr Sex involved presentation 1 Nov 28/ Anterior Fever, swollen 2001 M abdominal necrosed area wall 20x12x4 cm at site of appendicectomy wound 1 wk after operation, underlying muscles, tissues and fascia gangrenous 2 Dec 60/F Right Fever, necrotic 2004 gluteal patch 6x6 cm region with surrounding erythema & swelling extending to ant. abdominal wall 3 April 32/ Anterior Fever, black 2005 F abdominal discoloration wall (left 15x15cm on ant. side) abdominal wall with surrounding oedema and induration 4 August 43/ Anterior 15x15cm 2005 M abdominal debrided wound wall (right on right ant. side) abdominal wall, necrotic fat at margin present, laterally skin discolored 5 August 30/ Left Skin, superficial 2005 F gluteal fascia, fat uptil region gluteal muscle necrosed, covering area of 25x20 cm 6 June 29/ Right arm, Necrosed area 2007 M axilla and on right arm right part at the site of of chest Plaster of Paris wall cast extending to axilla and right part of chest wall 7 August 35/ Left thigh Massive wound 2007 F & anterior on left thigh abdominal & anterior wall abdominal wall with black necrotic areas 8 Sep. 85/ Left leg Necrosed and 2007 M swollen left leg 9 Sep 19/ Right Fever, pain & 2007 M side of progressive black chest and discoloration abdomen of right side of chest and abdomen KOH S. Underlying Risk factor mount & no. illness HPE 1 None Appendicectomy Broad, wound aseptate hyphae with right angle branching 2 None i.m. Broad, injection at aseptate same site 7 hyphae days prior with right angle branching 3 None Massage on Broad, abdomen for aseptate abdominal hyphae pain 10 days with right prior angle branching 4 None H/o of Broad, injection on aseptate right ant. hyphae abdominal with right wall which angle developed branching into small blister 5 None i.m. Broad, injection aseptate over left hyphae gluteal with right region 10 angle days prior branching for fever 6 None Plaster of Broad, Paris cast aseptate applied at hyphae the site for with right fracture angle of right branching humerus 7 Diabetes i.m. Broad, mellitus injection aseptate over left hyphae gluteal with right region 7 angle days prior branching 8 None H/o trauma Broad, on left leg aseptate followed by hyphae redness and with right swelling angle branching 9 Unknown Unknown Broad, aseptate hyphae with right angle branching S. Cultural no. growth Therapy Outcome 1 Absidia Incision & Recovery corymbifera, drainage, within 1 Escherichia local month coli debridement AMB (i.v & topically), KI orally (25 drops tds), Antibiotics 2 Saksenaea Local Expired vasiformis, debridement, after 2 Pseudomonas AMB (50 months aeruginosa, mg/day) due to E. coli Antibiotics bacterial sepsis 3 A. elegans Local Expired debridement, after 7 Antibiotics, days No antifungal Diagnosed postmortem 4 A. elegans Local Recovery debridement, within I.5 AMB (50 months mg/day) Antibiotics 5 Sterile Local Recovery debridement, within I.5 AMB (50 months mg/day) Antibiotics 6 A. elegans Local Expired debridement, within 15 AMB (50 days mg/day) Antibiotics 7 A. elegans Insulin, local Expired debridement after 7 & antibiotics days No antifungal given as patient could not afford 8 Sterile Local Wound debridement, started to antibiotics, recover Irrigation within 15 of wound days with AMB & topical application of AMB (Ambisome) 9 Sterile Patient's Expired condition on day serious, put 1 of on ventilator admission and given adrenaline and effcorlin
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|Author:||Chander, J.; Kaur, J.; Attri, A.; Mohan, H.|
|Publication:||Indian Journal of Medical Research|
|Article Type:||Disease/Disorder overview|
|Date:||Jun 1, 2010|
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