Printer Friendly

Primary cutaneous zygomycosis from a tertiary care centre in north-west India.

Zygomycosis is a serious and often rapidly fatal infection usually seen in immunocompromised individuals. It is caused by fungi belonging to class Zygomycetes, order Mucorales. The genera reported to cause invasive infection are Absidia, Mucor, Rhizomucor, Rhizopus, Apophysomyces, Saksenaea, Cunninghamella, Cokeromyces and Syncephalastrum. Commonly reported infections belong to the first three genera, Rhizopus, Absidia and Rhizomucor (1-3). These fungi are ubiquitous in environment and although humans have a strong natural resistance to infection, they can cause a rapidly progressive and fatal disease in compromised hosts. The spectrum of diseases described includes rhinocerebral, pulmonary, gastrointestinal, cutaneous and disseminated infections (3).

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

References

(1.) Edwards JE. Clinical aspects of mucormycosis. Ann Inter Med 1980; 93 96-9.

(2.) Marchevsky AM, Bottone EJ, Geller SA, Giger DK. The changing spectrum of disease, etiology and diagnosis of mucormycosis. Hum Pathol 1980; 11 457-64.

(3.) Rinaldi MG. Zygomycosis. Infect Dis N Am 1989; 3 19-41.

(4.) Cocanour CS, Miller-Crotchett P, Reed Rl II, Johnson PC, Fischer RP. Mucormycosis in trauma patients. Trauma 1992; 32 12-5.

(5.) Cooter RD, Lim IS, Ellis DH, Leitch IOW. Burn wound zygomycosis caused by Apophysomyces elegans. J Clin Microbiol 1990; 28 2151-3.

(6.) Mathews MS, Raman A, Nair A. Nosocomial zygomycotic post-surgical necrotizing fasciitis in a healthy adult caused by Apophysomyces elegans in south India. J Med Vet Mycol 1997; 35 61-3.

(7.) Parker C, Kaminski G, Hill D. Zygomycosis in a tattoo caused by Saksenaea vasiformis. J Dermatol 1986; 27 107-11.

(8.) Blair JE, Fredrikson LJ, Barbara A, Lucaire CS. Locally invasive cutaneous Apophysomyces elegans infection acquired from snapdragon patch test. MFMER 2002; 77 717-20.

(9.) Tomford JW, Whittlesey D, Ellner JJ, Tomashefski Jr. Invasive primary cutaneous phycomycosis in diabetic leg ulcers. Arch Surg 1980; 115 770-1.

(10.) St-Germain G, Robert A, Ishak M, Tremblay C, Claveau S. Infection due to Rhizomucor pusillus: Report of four cases in leukemia and review. Clin InfectDis 1993; 16 640-5.

(11.) Weinberg WG, Wade BH, Cierny G III, Stacy D, Rinaldi MG. Invasive infection due to Apophysomyces elegans in immunocompetent hosts. Clin Infect Dis 1993; 17 881-4.

(12.) Padhye AA, Ajello L. Simple method of inducing sporulation by Apophysomyces elegans and Saksenaea vasiformis. J Clin Microbiol 1988; 26 1862-3.

(13.) Prasad RM, Bose SM, Vaiphei K, Verma GR. Post operative abdominal wall mucormycosis mimicking as bacterial necrotising fasciitis. J Postgrad Med 2003; 49 187-8.

(14.) Boyd AS, Wiser B, Sams HH, King LE. Gangrenous cutaneous mucormycosis in a child with a solid organ transplant: a case report and review of the literature. Pediatr Dermatol 2003; 20 411-5.

(15.) Burrell SR, Ostlie DJ, Saubolle M, Dimler M, Barbour SD. Apophysomyces elegans infection associated with cactus spine injury in an immunocompetent pediatric patient. Pediatr Infect Dis J 1998; 17 663-4.

(16.) Quinio D, Karam A, Leroy JP, Moal MC, Bourbigot B, Masure O, et al. Zygomycosis caused by Cunninghamella bertholletiae in a kidney transplant recipient. Med Mycol 2004; 42 177-80.

(17.) Mead JH, Lupton GP, Dillavou CL, Odom RB. Cutaneous Rhizopus infection. Occurrence as a postoperative complication associated with an elasticized adhesive dressing. JAMA 1979; 242 272-4.

(18.) Alsuwaida K. Primary cutaneous mucormycosis complicating the use of adhesive tape to secure the endotracheal tube. Can JAnaesth 2002; 49 880-2.

(19.) Lakshmi V, Rani TS, Sharma S, Mohan VS, Sundaram C, Rao RR, et al. Zygomycotic necrotizing fasciitis caused by Apophysomyces elegans. J Clin Microbiol 1993; 31 1368-9.

(20.) Chakrabarti A, Ghosh A, Prasad GS, David JK, Gupta S, Das A, et al. Apophysomyces elegans: An emerging Zygomycete in India. J Clin Microbiol 2003; 41 783.

(21.) Jain D, Kumar Y, Vasishta RK, Rajesh L, Pattari SK, Chakrabarti A. Zygomycotic necrotizing fasciitis in immunocompetent patients: a series of 18 cases. Mod Path 2006; 19 1221-6.

(22.) Flores M, Welch D. Culture media. In: Isenberg HD, editor. Clinical microbiology procedures handbook. Washington DC: ASM Press; 1992. p. 6.72.

(23.) Kindo AJ, Shams NR, Srinivasan V, Kalyani J, Mallika M. Multiple discharging sinuses: An unusual presentation caused by Absidia corymbifera. Indian J Med Microbiol 2007; 25 291-3.

(24.) Seguin P, Musellec H, Le Gall F, Chervrier S, Le Bouquin V, Malledant Y. Post-traumatic course complicated by cutaneous infection with Absidia corymbifera. Eur J Clin Microbial Infect Dis 1999; 18 737-9.

(25.) Scalise A, Brachiesi F, Viviani MA, Arzeni D, Bertani A, Scalise G. Infection due to Absidia corymbifera in a patient with a massive crush trauma of the foot. J Infect 1999; 38 191-2.

(26.) Padhye AA, Koshi G, Anandi V, Ponniah J, Sitaram V, Jacob M, et al. First case of subcutaneous zygomycosis caused by Saksenaea vasiformis in India. Diagn Microbiol Infect Dis 1988; 9 69-77.

(27.) Chakrabarti A, Kumar P, Padhya AA, Chatha L, Singh SK, Das A, et al. Primary cutaneous zygomycosis due to Saksenaea vasiformis and Apophysomyces elegans. Clin Infect Dis 1997; 24 580-3.

(28.) Padmaja IJ, Ramani TV, Kalyani S. Cutaneous zygomycosis--Necrotising fasciitis due to Saksenaea vasiformis. Indian J Med Microbiol 2006; 24 58-60.

(29.) Sugar AM. Agents of mucormycosis and related species. In: Mandell GL, Bennett JE, Dolin R, editors. Principles and practice of infectious diseases, 6th ed. Philadelphia: Elsevier Churchill Livingstone; 2005. p. 2973-84.

(30.) Tobon AM, Arango M, Fernandez D, Restrepo A. Mucormycosis (Zygomycosis) in a heart-kidney transplant recipient: recovery after posaconazole therapy. Clin Infect Dis 2003; 36 1488-91.

(31.) Bentur Y, Shapak A, Ramon Y, Abramovich A, Wolfin G, Stein H, et al. Hyperbaric oxygen therapy for cutaneous/soft-tissue zygomycosis complicating diabetes mellitus. Plast Reconstr Surg 1988; 102 822-4.

(32.) Kimura M, Smith MB, McGinnis MR. Zygomycosis due to Apophysomyces elegans: report of 2 cases and review of the literature. Arch Pathol Lab Med 1999; 123 386-90.

Reprint requests: Dr Jagdish Chander, Professor & Head, Department of Microbiology, Government Medical College & Hospital Sector 32, Chandigarh 160 030, India e-mail: jchander@hotmail.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
COPYRIGHT 2010 Indian Council of Medical Research
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2010 Gale, Cengage Learning. All rights reserved.

 
Article Details
Printer friendly Cite/link Email Feedback
Author:Chander, J.; Kaur, J.; Attri, A.; Mohan, H.
Publication:Indian Journal of Medical Research
Article Type:Disease/Disorder overview
Geographic Code:9INDI
Date:Jun 1, 2010
Words:3044
Previous Article:Isolation of Legionella pneumophila from clinical & environmental sources in a tertiary care hospital.
Next Article:Induction of metalloproteinases expression by TLR ligands in human fibroblast like synoviocytes from juvenile idiopathic arthritis patients.
Topics:

Terms of use | Privacy policy | Copyright © 2018 Farlex, Inc. | Feedback | For webmasters