Mycopathologia DOI 10.1007/s11046-014-9752-6
Primary Cutaneous Mucormycosis Presenting as a Giant Plaque: Uncommon Presentation of a Rare Mycosis Keshavamurthy Vinay • Ariganesh Chandrasegaran • Amrinder J. Kanwar • Uma N. Saikia • Harsimran Kaur M. R. Shivaprakash • Sunil Dogra
•
Received: 22 December 2013 / Accepted: 18 April 2014 Ó Springer Science+Business Media Dordrecht 2014
Abstract Mucormycosis is an uncommon systemic mycosis affecting the immunocompromised individuals. It is usually caused by organisms of the genera Rhizopus and Mucor, although rarely other organisms have also been implicated. Mycoses due to these angioinvasive fungi have an acute onset, rapidly progressive course with high mortality rate. A rare and less well known is the chronic subtype of primary cutaneous mucormycosis (PCM). Herein, we report a case of PCM clinically presenting as a chronic, giant destructive plaque in a young immunocompetent male and coin the term chronic granulomatous mucormycosis. A clinicopathological classification for cutaneous mucormycosis is also proposed.
K. Vinay A. Chandrasegaran A. J. Kanwar S. Dogra (&) Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh 160012, India e-mail: [email protected] U. N. Saikia Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India H. Kaur M. R. Shivaprakash Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
Keywords Acute necrotising mucormycosis Chronic granulomatous mucormycosis Contiguity mucormycosis Mucor irregularis Primary cutaneous mucormycosis Secondary cutaneous mucormycosis
Introduction Zygomycetes are filamentous fungi which encompasses two orders, the Mucorales and the Entomophthorales. Entomophthorales are the causative organisms of subcutaneous zygomycosis, a chronic mycosis seen predominantly in the tropics. Mucorales are a group of angioinvasive fungi responsible for mucormycosis, a rare mycosis affecting the immunosuppressed patients with high mortality. Throughout the literature, the term zygomycosis has been used interchangeably with mucormycosis. However, since zygomycosis includes both mucormycosis and subcutaneous zygomycosis, to avoid confusion, the term mucormycosis has been used in the present article. Mucorales commonly involves the nasal cavity in uncontrolled diabetic patients causing rhinocerebral mucormycosis. Other clinical types include pulmonary, gastrointestinal, cutaneous and disseminated [1]. Cutaneous involvement of mucormycosis is rare, and in a recent series of mucormycosis reported from India, cutaneous involvement accounted for 11 % of
123
Mycopathologia
A 24-year-old male presented with symptoms of a large, itchy plaque involving most of the lower back, buttocks and left upper limb since 17 years. The lesion started during his childhood as a small erythematous plaque over the left buttock which had gradually progressed to attain the present size. Seven years prior
to this presentation, he had developed a similar lesion over the left wrist, which progressively involved most of the left upper limb, extending till the arm. He also complained of recurrent ulceration over the plaque which healed with antibiotics and local dressing. He had difficulty in straightening the fingers and elbow joint and had developed skin contractures at these sites. Patient had previously received fluconazole 150 mg daily for 6 weeks and two courses of itraconazole 200 mg twice daily for 12 weeks with minimum improvement. He had also failed a therapeutic trial of antitubercular treatment consisting of isoniazid 300 mg, rifampicin 450 mg, pyrazinamide 1,500 mg and ethambutol 1,200 mg for 6 weeks under Revised National Tuberculosis Control Programme. There was no history of any significant medical illnesses, intake of systemic corticosteroids or any other systemic immunosuppressive therapy. Patient could not recall any history of trauma prior to onset of skin lesions. On examination, a large, well-defined, erythematous and succulent plaque involving the buttocks, lower back, left abdominal wall and left upper limb was noted (Fig. 1a, b). The plaque showed irregular areas of healing and a well-defined progressive serpiginous margin. The healed areas showed scars and contractures, especially over the joints (Fig. 1c). An ulcer of size 7 9 6 cm with a haemorrhagic base was noted over the left buttocks (Fig. 1a). Similar ulcer was also seen over the left elbow (Fig. 1c). Multiple pinpoint areas of superficial erosions were
Fig. 1 Large, succulent, erythematous plaque with serpiginous margin and irregular areas of scarring involving the buttocks, lower back and thigh (a, b). A non-healing ulcer over the
buttocks with surrounding area of scarring can also be appreciated (a). Similar involvement of the left upper limb with atrophy and areas of scarring (arrow) (c)
the total cases [2]. Cutaneous mucormycosis differs from other systemic mucormycosis in clinical and epidemiological features. Unlike rhinocerebral mucormycosis, a large proportion of patients with cutaneous mucormycosis are immunocompetent (40–50 %) and trauma is the most common predisposing factor in such patients [3]. In a recent series of primary cutaneous mucormycosis (PCM) from North India, eight out of the nine patients were immunocompetent and history of some kind of trauma prior to onset of PCM could be elicited in eight patients [4]. PCM usually presents as reddish purple indurated plaques which soon progresses to a necrotic area with eschar formation. Untreated, it rapidly spreads both by contiguous spread and haematological dissemination with an invariable lethal outcome. However, an indolent, chronic subtype of PCM has also been rarely reported in the literature. Herein, we report a case of PCM clinically presenting as a chronic giant destructive plaque in a young immunocompetent male.
Case Report
123
Mycopathologia
seen over the plaque. There were no palpable lymph nodes, organomegaly, abnormal auscultatory sounds or features of CNS dysfunction. Routine biochemical and haematological investigations revealed no abnormality. Serum IgG, IgA and IgM levels were within normal limits. Tuberculin skin test and ELISA for HIV infection were negative. A skin punch biopsy was obtained from the advancing edge and submitted for histopathological examination and bacterial, mycobacterial and fungal cultures. Histopathological examination revealed a granulomatous inflammation with giant cells containing fungal profiles (Fig. 2a) which were highlighted by PAS stain (Fig. 2b). Direct KOH tissue mount showed aseptate broad ribbon-like hyphae (Fig. 3a). Cottony white colonies, resembling that of Zygomycetes, were isolated on fungal culture. At the microscopic examination with lactophenol cotton blue, sporangia, rhizoids and unbranched sporangiophores were observed, suggesting a Rhizopus spp. No growth was found above 45 °C, thus ruling out Rhizomucor species. No growths were obtained by bacterial and mycobacterial culture. Based on the clinical and laboratory features, a diagnosis of PCM was made. The culture was further subjected to DNA extraction and polymerase chain reaction using ITS1 and ITS4 primers followed by sequencing as described previously [5], identifying as Rhizopus oryzae. The sequence obtained by ITS primers showed 99 % identity with standard strain of R. oryzae (ATCC
11886; GenBank accession no. AY803930). The isolate was deposited at the National Culture Collection of Pathogenic Fungi (NCCPF), PGIMER, Chandigarh, India, with accession no. NCCPF 710197. The nucleotide sequence is deposited in GenBank with accession no. KJ439050. Since the patient had failed to respond to oral antifungals, intravenous liposomal amphotericin was planned. However, because of the financial constraints, patient could not afford amphotericin and he was further lost to follow-up.
Fig. 2 Microphotograph showing granulomatous inflammation with giant cells (arrow head) and lymphocytic infiltrate. Giant cells contain fungal profiles. H&E9 9400 (a).
Microphotograph showing transverse cut of fungal profiles (arrow) within giant cells highlighting the fungal wall, PAS9 9400 (b)
Discussion Mucormycosis presenting as a chronic destructive plaque as in the present case has been rarely reported. Most of the reported cases are from central and eastern China. Lu et al. [6] reported a case of PCM in a 37-year-old female patient, who presented with a destructive plaque over face of 10-year duration. The authors also reviewed six other previously reported cases in the Chinese literature. Most of these patients had long-standing destructive plaque involving the exposed sites, commonly affecting the face and upper limbs. Mucor irregularis (previously known as Rhizomucor variabilis) was isolated from all the seven patients [6]. Few similar cases due to this agent have also been reported outside China from Japan [7], India [8] and America [9, 10]. Similar presentation has also
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Mycopathologia
Fig. 3 Microphotography of direct KOH mount showing aseptate broad ribbon-like hyphae, KOH 9 9400 (a). Lactophenol cotton blue mount of the culture showing presence of sporangia, rhizoids and unbranched sporangiophores,
suggesting it to be Rhizopus genus, 9400 (b). Growth on Sabouraud dextrose agar medium showing cottony white filaments typical of mucormycetes (inset)
been rarely described to be caused by Mucor hiemalis, the neighbour of M. irregularis [11, 12]. Although R. oryzae is the most common causative agent of rhinocerebral mucormycosis, there is only one other reported case of PCM caused by R. oryzae showing widespread granulomatous inflammation as seen in our case [13]. Other interesting feature of chronic granulomatous type of PCM is its occurrence in patients who are immunocompetent or have a mild degree of immune impairment. However, there are two case reports of PCM occurring in patients with untreatable bladder cancer and acute myelogenous leukaemia [7, 10]. Trauma plays an important role in inoculation of the causative organism as evident in the various case reports [6]. In our case, the lesion over the left upper limb occurred 10 years after the onset of lesions over trunk. Since the lesions were extremely itchy, constant scratching might have inoculated the fungus into the limb. Our case is unique from other reported cases in the extent of the cutaneous involvement. A giant lesion involving nearly 20 % of the body surface area has not been reported previously. Such a presentation needs to be clinically differentiated from lupus vulgaris and lupoid leishmaniasis. There is a lack of awareness in the dermatology literature regarding the chronic subtype of PCM. The two recent reviews of PCM do not mention this clinical presentation [1, 14]. This less known clinical presentation of mucormycosis differs from the acute necrotising type of PCM as depicted in Table 1. Currently, both the clinical presentations of mucormycosis are reported as PCM. Because of the clinical
Table 1 Clinical and histopathological differences between acute necrotising mucormycosis and chronic granulomatous mucormycosis (proposed)
123
Acute necrotising mucormycosis
Chronic granulomatous mucormycosis
Onset
Acute
Chronic
Progression Cellular immunity
Rapid Usually impaired
Slow Usually intact
Causative organisms
Rhizopus, Mucor
Rhizomucor, Rhizopus (rarely)
Mode of involvement
Traumatic inoculation Haematogenous dissemination
Traumatic inoculation
Contiguous spread Clinical features
Reddish purple indurated plaques progressing to necrosis and eschar formation
Angioinvasion
Present
Absent
Histopathology
Necrotising inflammation
Granulomatous inflammation
Treatment
Control of predisposing condition, surgical debridement and liposomal amphotericin B
Liposomal amphotericin B
Prognosis and mortality
Poor can lead to mortality
Good, no mortality but causes significant morbidity
Erythematous plaque with a progressive margin and areas of healing and scar formation
Mycopathologia Table 2 Classification (suggested)
of
cutaneous
mucormycosis
1. Primary cutaneous mucormycosis: caused by inoculation of causative organism into the damaged skin Acute necrotising mucormycosis Chronic granulomatous mucormycosis 2. Secondary cutaneous mucormycosis: secondary involvement of the skin due to haematogenous dissemination from other organ system 3. Contiguity mucormycosis: involvement of the skin due to contiguous spread, mainly from rhinocerebral mucormycosis
and histological differences, there is a need to differentiate the two subgroups. Based on the clinical and histological features, we coin the term chronic granulomatous mucormycosis for this rare form of disease and differentiate it from the well-known acute necrotising type of PCM (Table 1). We also propose a classification (Table 2) for cutaneous mucormycosis in line with cutaneous aspergillosis [15]. Conflict of interest
None.
References 1. Mantadakis E, Samonis G. Clinical presentation of zygomycosis. Clin Microbiol Infect. 2009;15(Suppl 5):15–20. 2. Chakrabarti A, Chatterjee SS, Das A, Panda N, Shivaprakash MR, Kaur A, et al. Invasive zygomycosis in India: experience in a tertiary care hospital. Postgrad Med J. 2009;85:573–81. 3. Skiada A, Petrikkos G. Cutaneous zygomycosis. Clin Microbiol Infect. 2009;15(Suppl 5):41–5. 4. Chander J, Kaur J, Attri A, Mohan H. Primary cutaneous zygomycosis from a tertiary care centre in north-west India. Indian J Med Res. 2010;131:765–70.
5. Shivaprakash MR, Appannanavar SB, Dhaliwal M, Gupta A, Gupta S, Chakrabarti A. Colletotrichum truncatum: an unusual pathogen causing mycotic keratitis and endophthalmitis. J Clin Microbiol. 2011;49:2894–8. 6. Lu XL, Liu ZH, Shen YN, She XD, Lu GX, Zhan P, et al. Primary cutaneous zygomycosis caused by Rhizomucor variabilis: a new endemic zygomycosis? A case report and review of 6 cases reported from China. Clin Infect Dis. 2009;49:e39–43. 7. Tomita H, Muroi E, Takenaka M, Nishimoto K, Kakeya H, Ohno H, et al. Rhizomucor variabilis infection in human cutaneous mucormycosis. Clin Exp Dermatol. 2011;36:312–4. 8. Hemashettar BM, Patil RN, O’Donnell K, Chaturvedi V, Ren P, Padhye AA. Chronic rhinofacial mucormycosis caused by Mucor irregularis (Rhizomucor variabilis) in India. J Clin Microbiol. 2011;49:2372–5. 9. Schell WA, O’Donnell K, Alspaugh JA. Heterothallic mating in Mucor irregularis and first isolate of the species outside of Asia. Med Mycol. 2011;49:714–23. 10. Abuali MM, Posada R, Del Toro G, Roman E, Ramani R, Chaturvedi S, et al. Rhizomucor variabilis var. regularior and Hormographiella aspergillata infections in a leukemic bone marrow transplant recipient with refractory neutropenia. J Clin Microbiol. 2009;47:4176–9. 11. de Oliveira-Neto MP, Da Silva M, Fialho Monteiro PC, Lazera M, de Almeida Paes R, Novellino AB, et al. Cutaneous mucormycosis in a young, immunocompetent girl. Med Mycol. 2006;44:567–70. 12. Prevoo RL, Starink TM, de Haan P. Primary cutaneous mucormycosis in a healthy young girl. Report of a case caused by Mucor hiemalis Wehmer. J Am Acad Dermatol. 1991;24:882–5. 13. Song WK, Park HJ, Cinn YW, Rheem I, Pai H, Shin JH. Primary cutaneous mucormycosis in a trauma patient. J Dermatol. 1999;26:825–8. 14. Bonifaz A, Vazquez-Gonzalez D, Tirado-Sanchez A, Ponce-Olivera RM. Cutaneous zygomycosis. Clin Dermatol. 2012;30:413–9. 15. Galimberti R, Kowalczuk A, Hidalgo Parra I, Gonzalez Ramos M, Flores V. Cutaneous aspergillosis: a report of six cases. Br J Dermatol. 1998;139:522–6.
123
Primary Cutaneous Mucormycosis Presenting as a Giant Plaque: Uncommon Presentation of a Rare Mycosis Keshavamurthy Vinay • Ariganesh Chandrasegaran • Amrinder J. Kanwar • Uma N. Saikia • Harsimran Kaur M. R. Shivaprakash • Sunil Dogra
•
Received: 22 December 2013 / Accepted: 18 April 2014 Ó Springer Science+Business Media Dordrecht 2014
Abstract Mucormycosis is an uncommon systemic mycosis affecting the immunocompromised individuals. It is usually caused by organisms of the genera Rhizopus and Mucor, although rarely other organisms have also been implicated. Mycoses due to these angioinvasive fungi have an acute onset, rapidly progressive course with high mortality rate. A rare and less well known is the chronic subtype of primary cutaneous mucormycosis (PCM). Herein, we report a case of PCM clinically presenting as a chronic, giant destructive plaque in a young immunocompetent male and coin the term chronic granulomatous mucormycosis. A clinicopathological classification for cutaneous mucormycosis is also proposed.
K. Vinay A. Chandrasegaran A. J. Kanwar S. Dogra (&) Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh 160012, India e-mail: [email protected] U. N. Saikia Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India H. Kaur M. R. Shivaprakash Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
Keywords Acute necrotising mucormycosis Chronic granulomatous mucormycosis Contiguity mucormycosis Mucor irregularis Primary cutaneous mucormycosis Secondary cutaneous mucormycosis
Introduction Zygomycetes are filamentous fungi which encompasses two orders, the Mucorales and the Entomophthorales. Entomophthorales are the causative organisms of subcutaneous zygomycosis, a chronic mycosis seen predominantly in the tropics. Mucorales are a group of angioinvasive fungi responsible for mucormycosis, a rare mycosis affecting the immunosuppressed patients with high mortality. Throughout the literature, the term zygomycosis has been used interchangeably with mucormycosis. However, since zygomycosis includes both mucormycosis and subcutaneous zygomycosis, to avoid confusion, the term mucormycosis has been used in the present article. Mucorales commonly involves the nasal cavity in uncontrolled diabetic patients causing rhinocerebral mucormycosis. Other clinical types include pulmonary, gastrointestinal, cutaneous and disseminated [1]. Cutaneous involvement of mucormycosis is rare, and in a recent series of mucormycosis reported from India, cutaneous involvement accounted for 11 % of
123
Mycopathologia
A 24-year-old male presented with symptoms of a large, itchy plaque involving most of the lower back, buttocks and left upper limb since 17 years. The lesion started during his childhood as a small erythematous plaque over the left buttock which had gradually progressed to attain the present size. Seven years prior
to this presentation, he had developed a similar lesion over the left wrist, which progressively involved most of the left upper limb, extending till the arm. He also complained of recurrent ulceration over the plaque which healed with antibiotics and local dressing. He had difficulty in straightening the fingers and elbow joint and had developed skin contractures at these sites. Patient had previously received fluconazole 150 mg daily for 6 weeks and two courses of itraconazole 200 mg twice daily for 12 weeks with minimum improvement. He had also failed a therapeutic trial of antitubercular treatment consisting of isoniazid 300 mg, rifampicin 450 mg, pyrazinamide 1,500 mg and ethambutol 1,200 mg for 6 weeks under Revised National Tuberculosis Control Programme. There was no history of any significant medical illnesses, intake of systemic corticosteroids or any other systemic immunosuppressive therapy. Patient could not recall any history of trauma prior to onset of skin lesions. On examination, a large, well-defined, erythematous and succulent plaque involving the buttocks, lower back, left abdominal wall and left upper limb was noted (Fig. 1a, b). The plaque showed irregular areas of healing and a well-defined progressive serpiginous margin. The healed areas showed scars and contractures, especially over the joints (Fig. 1c). An ulcer of size 7 9 6 cm with a haemorrhagic base was noted over the left buttocks (Fig. 1a). Similar ulcer was also seen over the left elbow (Fig. 1c). Multiple pinpoint areas of superficial erosions were
Fig. 1 Large, succulent, erythematous plaque with serpiginous margin and irregular areas of scarring involving the buttocks, lower back and thigh (a, b). A non-healing ulcer over the
buttocks with surrounding area of scarring can also be appreciated (a). Similar involvement of the left upper limb with atrophy and areas of scarring (arrow) (c)
the total cases [2]. Cutaneous mucormycosis differs from other systemic mucormycosis in clinical and epidemiological features. Unlike rhinocerebral mucormycosis, a large proportion of patients with cutaneous mucormycosis are immunocompetent (40–50 %) and trauma is the most common predisposing factor in such patients [3]. In a recent series of primary cutaneous mucormycosis (PCM) from North India, eight out of the nine patients were immunocompetent and history of some kind of trauma prior to onset of PCM could be elicited in eight patients [4]. PCM usually presents as reddish purple indurated plaques which soon progresses to a necrotic area with eschar formation. Untreated, it rapidly spreads both by contiguous spread and haematological dissemination with an invariable lethal outcome. However, an indolent, chronic subtype of PCM has also been rarely reported in the literature. Herein, we report a case of PCM clinically presenting as a chronic giant destructive plaque in a young immunocompetent male.
Case Report
123
Mycopathologia
seen over the plaque. There were no palpable lymph nodes, organomegaly, abnormal auscultatory sounds or features of CNS dysfunction. Routine biochemical and haematological investigations revealed no abnormality. Serum IgG, IgA and IgM levels were within normal limits. Tuberculin skin test and ELISA for HIV infection were negative. A skin punch biopsy was obtained from the advancing edge and submitted for histopathological examination and bacterial, mycobacterial and fungal cultures. Histopathological examination revealed a granulomatous inflammation with giant cells containing fungal profiles (Fig. 2a) which were highlighted by PAS stain (Fig. 2b). Direct KOH tissue mount showed aseptate broad ribbon-like hyphae (Fig. 3a). Cottony white colonies, resembling that of Zygomycetes, were isolated on fungal culture. At the microscopic examination with lactophenol cotton blue, sporangia, rhizoids and unbranched sporangiophores were observed, suggesting a Rhizopus spp. No growth was found above 45 °C, thus ruling out Rhizomucor species. No growths were obtained by bacterial and mycobacterial culture. Based on the clinical and laboratory features, a diagnosis of PCM was made. The culture was further subjected to DNA extraction and polymerase chain reaction using ITS1 and ITS4 primers followed by sequencing as described previously [5], identifying as Rhizopus oryzae. The sequence obtained by ITS primers showed 99 % identity with standard strain of R. oryzae (ATCC
11886; GenBank accession no. AY803930). The isolate was deposited at the National Culture Collection of Pathogenic Fungi (NCCPF), PGIMER, Chandigarh, India, with accession no. NCCPF 710197. The nucleotide sequence is deposited in GenBank with accession no. KJ439050. Since the patient had failed to respond to oral antifungals, intravenous liposomal amphotericin was planned. However, because of the financial constraints, patient could not afford amphotericin and he was further lost to follow-up.
Fig. 2 Microphotograph showing granulomatous inflammation with giant cells (arrow head) and lymphocytic infiltrate. Giant cells contain fungal profiles. H&E9 9400 (a).
Microphotograph showing transverse cut of fungal profiles (arrow) within giant cells highlighting the fungal wall, PAS9 9400 (b)
Discussion Mucormycosis presenting as a chronic destructive plaque as in the present case has been rarely reported. Most of the reported cases are from central and eastern China. Lu et al. [6] reported a case of PCM in a 37-year-old female patient, who presented with a destructive plaque over face of 10-year duration. The authors also reviewed six other previously reported cases in the Chinese literature. Most of these patients had long-standing destructive plaque involving the exposed sites, commonly affecting the face and upper limbs. Mucor irregularis (previously known as Rhizomucor variabilis) was isolated from all the seven patients [6]. Few similar cases due to this agent have also been reported outside China from Japan [7], India [8] and America [9, 10]. Similar presentation has also
123
Mycopathologia
Fig. 3 Microphotography of direct KOH mount showing aseptate broad ribbon-like hyphae, KOH 9 9400 (a). Lactophenol cotton blue mount of the culture showing presence of sporangia, rhizoids and unbranched sporangiophores,
suggesting it to be Rhizopus genus, 9400 (b). Growth on Sabouraud dextrose agar medium showing cottony white filaments typical of mucormycetes (inset)
been rarely described to be caused by Mucor hiemalis, the neighbour of M. irregularis [11, 12]. Although R. oryzae is the most common causative agent of rhinocerebral mucormycosis, there is only one other reported case of PCM caused by R. oryzae showing widespread granulomatous inflammation as seen in our case [13]. Other interesting feature of chronic granulomatous type of PCM is its occurrence in patients who are immunocompetent or have a mild degree of immune impairment. However, there are two case reports of PCM occurring in patients with untreatable bladder cancer and acute myelogenous leukaemia [7, 10]. Trauma plays an important role in inoculation of the causative organism as evident in the various case reports [6]. In our case, the lesion over the left upper limb occurred 10 years after the onset of lesions over trunk. Since the lesions were extremely itchy, constant scratching might have inoculated the fungus into the limb. Our case is unique from other reported cases in the extent of the cutaneous involvement. A giant lesion involving nearly 20 % of the body surface area has not been reported previously. Such a presentation needs to be clinically differentiated from lupus vulgaris and lupoid leishmaniasis. There is a lack of awareness in the dermatology literature regarding the chronic subtype of PCM. The two recent reviews of PCM do not mention this clinical presentation [1, 14]. This less known clinical presentation of mucormycosis differs from the acute necrotising type of PCM as depicted in Table 1. Currently, both the clinical presentations of mucormycosis are reported as PCM. Because of the clinical
Table 1 Clinical and histopathological differences between acute necrotising mucormycosis and chronic granulomatous mucormycosis (proposed)
123
Acute necrotising mucormycosis
Chronic granulomatous mucormycosis
Onset
Acute
Chronic
Progression Cellular immunity
Rapid Usually impaired
Slow Usually intact
Causative organisms
Rhizopus, Mucor
Rhizomucor, Rhizopus (rarely)
Mode of involvement
Traumatic inoculation Haematogenous dissemination
Traumatic inoculation
Contiguous spread Clinical features
Reddish purple indurated plaques progressing to necrosis and eschar formation
Angioinvasion
Present
Absent
Histopathology
Necrotising inflammation
Granulomatous inflammation
Treatment
Control of predisposing condition, surgical debridement and liposomal amphotericin B
Liposomal amphotericin B
Prognosis and mortality
Poor can lead to mortality
Good, no mortality but causes significant morbidity
Erythematous plaque with a progressive margin and areas of healing and scar formation
Mycopathologia Table 2 Classification (suggested)
of
cutaneous
mucormycosis
1. Primary cutaneous mucormycosis: caused by inoculation of causative organism into the damaged skin Acute necrotising mucormycosis Chronic granulomatous mucormycosis 2. Secondary cutaneous mucormycosis: secondary involvement of the skin due to haematogenous dissemination from other organ system 3. Contiguity mucormycosis: involvement of the skin due to contiguous spread, mainly from rhinocerebral mucormycosis
and histological differences, there is a need to differentiate the two subgroups. Based on the clinical and histological features, we coin the term chronic granulomatous mucormycosis for this rare form of disease and differentiate it from the well-known acute necrotising type of PCM (Table 1). We also propose a classification (Table 2) for cutaneous mucormycosis in line with cutaneous aspergillosis [15]. Conflict of interest
None.
References 1. Mantadakis E, Samonis G. Clinical presentation of zygomycosis. Clin Microbiol Infect. 2009;15(Suppl 5):15–20. 2. Chakrabarti A, Chatterjee SS, Das A, Panda N, Shivaprakash MR, Kaur A, et al. Invasive zygomycosis in India: experience in a tertiary care hospital. Postgrad Med J. 2009;85:573–81. 3. Skiada A, Petrikkos G. Cutaneous zygomycosis. Clin Microbiol Infect. 2009;15(Suppl 5):41–5. 4. Chander J, Kaur J, Attri A, Mohan H. Primary cutaneous zygomycosis from a tertiary care centre in north-west India. Indian J Med Res. 2010;131:765–70.
5. Shivaprakash MR, Appannanavar SB, Dhaliwal M, Gupta A, Gupta S, Chakrabarti A. Colletotrichum truncatum: an unusual pathogen causing mycotic keratitis and endophthalmitis. J Clin Microbiol. 2011;49:2894–8. 6. Lu XL, Liu ZH, Shen YN, She XD, Lu GX, Zhan P, et al. Primary cutaneous zygomycosis caused by Rhizomucor variabilis: a new endemic zygomycosis? A case report and review of 6 cases reported from China. Clin Infect Dis. 2009;49:e39–43. 7. Tomita H, Muroi E, Takenaka M, Nishimoto K, Kakeya H, Ohno H, et al. Rhizomucor variabilis infection in human cutaneous mucormycosis. Clin Exp Dermatol. 2011;36:312–4. 8. Hemashettar BM, Patil RN, O’Donnell K, Chaturvedi V, Ren P, Padhye AA. Chronic rhinofacial mucormycosis caused by Mucor irregularis (Rhizomucor variabilis) in India. J Clin Microbiol. 2011;49:2372–5. 9. Schell WA, O’Donnell K, Alspaugh JA. Heterothallic mating in Mucor irregularis and first isolate of the species outside of Asia. Med Mycol. 2011;49:714–23. 10. Abuali MM, Posada R, Del Toro G, Roman E, Ramani R, Chaturvedi S, et al. Rhizomucor variabilis var. regularior and Hormographiella aspergillata infections in a leukemic bone marrow transplant recipient with refractory neutropenia. J Clin Microbiol. 2009;47:4176–9. 11. de Oliveira-Neto MP, Da Silva M, Fialho Monteiro PC, Lazera M, de Almeida Paes R, Novellino AB, et al. Cutaneous mucormycosis in a young, immunocompetent girl. Med Mycol. 2006;44:567–70. 12. Prevoo RL, Starink TM, de Haan P. Primary cutaneous mucormycosis in a healthy young girl. Report of a case caused by Mucor hiemalis Wehmer. J Am Acad Dermatol. 1991;24:882–5. 13. Song WK, Park HJ, Cinn YW, Rheem I, Pai H, Shin JH. Primary cutaneous mucormycosis in a trauma patient. J Dermatol. 1999;26:825–8. 14. Bonifaz A, Vazquez-Gonzalez D, Tirado-Sanchez A, Ponce-Olivera RM. Cutaneous zygomycosis. Clin Dermatol. 2012;30:413–9. 15. Galimberti R, Kowalczuk A, Hidalgo Parra I, Gonzalez Ramos M, Flores V. Cutaneous aspergillosis: a report of six cases. Br J Dermatol. 1998;139:522–6.
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