ARTICLE IN PRESS
YBJOM-4354; No. of Pages 3
Available online at www.sciencedirect.com
British Journal of Oral and Maxillofacial Surgery xxx (2014) xxx.e1–xxx.e3
Short communication
Lingual necrosis caused by mucormycosis in a patient with aplastic anaemia: case report M. Pajpani a,∗ , R. Webb b a b
Oral and Maxillofacial Surgery, Queen Mary’s Hospital, Frognal Avenue, Sidcup DA14 6LT, United Kingdom Oral and Maxillofacial Surgery, King’s College Hospital, Denmark Hill, London SE5 9RS, United Kingdom
Accepted 16 September 2014
Abstract Mucormycosis is a rare but aggressive fungal infection that predominantly affects immunocompromised patients. We report a case that highlights the importance of knowledge to enable prompt diagnosis and management of an otherwise fatal phenomenon. Crown Copyright © 2014 Published by Elsevier Ltd. on behalf of The British Association of Oral and Maxillofacial Surgeons. All rights reserved.
Keywords: Mucormycosis; Zygomycosis; Lingual necrosis; Aplastic anaemia; Tongue
Introduction Zygomycosis and mucormycosis are used interchangeably to describe a group of invasive and lethal fungal infections that are most commonly seen in immunocompromised patients. The Zygomycetes class of fungi consists of the orders Mucorales and Entomophthorales. The former causes most cases in humans.1 Case report An 82-year-old woman with severe aplastic anaemia, which was diagnosed in 2004, was admitted with Neutropenic sepsis. She had been treated with antilymphocyte globulin and ciclosporin until 2011 when she relapsed, and was on supportive care with weekly transfusions of platelets and blood. She began to complain of a swelling and discomfort in the
∗
Corresponding author. Tel.: +44 7866026341. E-mail address: meera [email protected] (M. Pajpani).
tongue, and found it difficult to eat, but just managed to swallow liquids. The haematology team had reached a differential diagnosis of mucormycosis, as the clinical picture was consistent with the condition. She was started on amphotericin B intravenously before mucormycosis was confirmed histopathologically. Initial clinical examination showed some oedema to the right side of the tongue, but there was little to see clinically. One week later, a black, large, well defined lesion of about 3–4 cm with a centrally necrotic area was noted (Fig. 1). The area was debrided and the sample sent for histopathological and microbiological examination (Fig. 2). Reaction to drugs or metastatic disease was still a consideration at this stage. Oral mucormycosis was confirmed, reported as Rhizopus sp found in the sample. Amphotericin B was discontinued after 16 days and replaced with posaconazole orally 4 times daily, along with benzydamine hydrochloride spray (Difflam, 3M) topically to ease the symptoms. Subsequent blood culture showed Escherichia coli. Her condition continued to deteriorate, and she died 43 days after admission. The cause of death was septicaemia secondary to E. coli, and long-term aplastic anaemia.
http://dx.doi.org/10.1016/j.bjoms.2014.09.012 0266-4356/Crown Copyright © 2014 Published by Elsevier Ltd. on behalf of The British Association of Oral and Maxillofacial Surgeons. All rights reserved.
Please cite this article in press as: Pajpani M, Webb R. Lingual necrosis caused by mucormycosis in a patient with aplastic anaemia: case report. Br J Oral Maxillofac Surg (2014), http://dx.doi.org/10.1016/j.bjoms.2014.09.012
YBJOM-4354; No. of Pages 3
xxx.e2
ARTICLE IN PRESS
M. Pajpani, R. Webb / British Journal of Oral and Maxillofacial Surgery xxx (2014) xxx.e1–xxx.e3
Fig. 1. Large, black, necrotic lesion on the tongue one week after initial presentation.
Fig. 2. Tongue after debridement under local anaesthetic.
Patients with uncontrolled diabetes mellitus, particularly with ketoacidosis, those on corticosteroid treatment, those with neutropenia, trauma and burns, malignant haematological disorders, and who are severely immunocompromised, including those who have had haematopoietic stem cell transplants,6 are at high risk of mucormycosis. Based on its clinical presentation and anatomical site, invasive mucormycosis can be classified into one of 6 forms: rhinocerebral, pulmonary, cutaneous, gastrointestinal, disseminated, and uncommon rare forms. One-third to a half of all cases are rhinocerebral, and symptoms include sinusitis or periorbital cellulitis, eye or facial pain, and numbness.7 Successful management depends on 4 key areas: recognition of patients at risk through the early signs of infection to enable rapid diagnosis; removal or reduction of any risk factors such as the level of immunosuppression; and provision of appropriate antifungal treatment and surgical debridement, which improves survival. The relative rarity of the infection means that more information on evidence-based treatment is needed. Amphotericin B still seems to be widely supported as the treatment of choice.2 However, more recently, posaconazole has been used after reports of success from individual cases, or a combination of the 2 in refractory cases.8 The role of hyperbaric oxygen, iron chelators such as deferasirox, gamma interferon, and granulocyte-macrophage colonystimulating factor, all show promising results but are still in their relative infancy.9 Although less common than other fungal infections such as Candida spp, which is more often encountered by the maxillofacial team, an awareness of its incidence is essential for prompt diagnosis and successful management.
Discussion Most human infections of these causative fungi include Rhizopus, Mucor, Rhizomucor, Cunninghamella and Absidia spp.2 They are present in environments such as soil and dust, and their infectious spores are initially inhaled and can establish a route of infection in the sinuses. Other routes include ingestion through the digestive tract, or inoculation through breaches in the skin.3 Rhizopus oryzae is the most common organism and is responsible for around 70% of all cases of mucormycosis. The pathogenicity of the disease process is multifaceted. An impaired host defence, which includes deficiencies of circulating neutrophils and impaired phagocyte function, has a vital role in infection. Other factors such as the ability to acquire iron from the host to facilitate growth add to its success as a pathogen.4 Ultimately the hallmark of the disease is the capability to cause angioinvasion, which results in thrombosis and ultimately in tissue necrosis. This also contributes to the capacity of the organism to disseminate rapidly in the blood to other organs.5
Conflict of interest We have no conflicts of interest.
References 1. Ribes JA, Vanover-Sams CL, Baker DJ. Zygomycetes in human disease. Clin Microbiol Rev 2000;13:236–301. 2. Spellberg B, Edwards Jr J, Ibrahim A. Novel perspectives on mucormycosis: pathophysiology, presentation, and management. Clin Microbiol Rev 2005;18:556–69. 3. Rogers TR. Treatment of zygomycosis: current and new options. J Antimicrob Chemother 2008;61:i35–40. 4. Ibrahim AS, Spellberg B, Walsh TJ, et al. Pathogenesis of mucormycosis. Clin Infect Dis 2012;54:S16–22. 5. Skiada A, Rigopoulos D, Larios D, et al. Global epidemiology of cutaneous zygomycosis. Clin Dermatol 2012;30:628–32. 6. Grossman ME, Fox LP, Kovarik C, et al. Cutaneous manifestations of infection in the immunocompromised host. 2nd ed. New York: Springer; 2012.
Please cite this article in press as: Pajpani M, Webb R. Lingual necrosis caused by mucormycosis in a patient with aplastic anaemia: case report. Br J Oral Maxillofac Surg (2014), http://dx.doi.org/10.1016/j.bjoms.2014.09.012
YBJOM-4354; No. of Pages 3
ARTICLE IN PRESS
M. Pajpani, R. Webb / British Journal of Oral and Maxillofacial Surgery xxx (2014) xxx.e1–xxx.e3 7. Petrikkos G, Skiada A, Lortholary O, et al. Epidemiology and clinical manifestations of mucormycosis. Clin Infect Dis 2012;54:S23–34. 8. Spellberg B, Ibrahim A, Roilides E, et al. Combination therapy for mucormycosis: why, what, and how. Clin Infect Dis 2012;54:S73–8.
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9. Gil-Lamaignere C, Simitsopoulou M, Roilides E, et al. Interferongamma and granulocyte-macrophage colony-stimulating factor augment the activity of polymorphonuclear leukocytes against medically important zygomycetes. J Infect Dis 2005;191:1180–7.
Please cite this article in press as: Pajpani M, Webb R. Lingual necrosis caused by mucormycosis in a patient with aplastic anaemia: case report. Br J Oral Maxillofac Surg (2014), http://dx.doi.org/10.1016/j.bjoms.2014.09.012
YBJOM-4354; No. of Pages 3
Available online at www.sciencedirect.com
British Journal of Oral and Maxillofacial Surgery xxx (2014) xxx.e1–xxx.e3
Short communication
Lingual necrosis caused by mucormycosis in a patient with aplastic anaemia: case report M. Pajpani a,∗ , R. Webb b a b
Oral and Maxillofacial Surgery, Queen Mary’s Hospital, Frognal Avenue, Sidcup DA14 6LT, United Kingdom Oral and Maxillofacial Surgery, King’s College Hospital, Denmark Hill, London SE5 9RS, United Kingdom
Accepted 16 September 2014
Abstract Mucormycosis is a rare but aggressive fungal infection that predominantly affects immunocompromised patients. We report a case that highlights the importance of knowledge to enable prompt diagnosis and management of an otherwise fatal phenomenon. Crown Copyright © 2014 Published by Elsevier Ltd. on behalf of The British Association of Oral and Maxillofacial Surgeons. All rights reserved.
Keywords: Mucormycosis; Zygomycosis; Lingual necrosis; Aplastic anaemia; Tongue
Introduction Zygomycosis and mucormycosis are used interchangeably to describe a group of invasive and lethal fungal infections that are most commonly seen in immunocompromised patients. The Zygomycetes class of fungi consists of the orders Mucorales and Entomophthorales. The former causes most cases in humans.1 Case report An 82-year-old woman with severe aplastic anaemia, which was diagnosed in 2004, was admitted with Neutropenic sepsis. She had been treated with antilymphocyte globulin and ciclosporin until 2011 when she relapsed, and was on supportive care with weekly transfusions of platelets and blood. She began to complain of a swelling and discomfort in the
∗
Corresponding author. Tel.: +44 7866026341. E-mail address: meera [email protected] (M. Pajpani).
tongue, and found it difficult to eat, but just managed to swallow liquids. The haematology team had reached a differential diagnosis of mucormycosis, as the clinical picture was consistent with the condition. She was started on amphotericin B intravenously before mucormycosis was confirmed histopathologically. Initial clinical examination showed some oedema to the right side of the tongue, but there was little to see clinically. One week later, a black, large, well defined lesion of about 3–4 cm with a centrally necrotic area was noted (Fig. 1). The area was debrided and the sample sent for histopathological and microbiological examination (Fig. 2). Reaction to drugs or metastatic disease was still a consideration at this stage. Oral mucormycosis was confirmed, reported as Rhizopus sp found in the sample. Amphotericin B was discontinued after 16 days and replaced with posaconazole orally 4 times daily, along with benzydamine hydrochloride spray (Difflam, 3M) topically to ease the symptoms. Subsequent blood culture showed Escherichia coli. Her condition continued to deteriorate, and she died 43 days after admission. The cause of death was septicaemia secondary to E. coli, and long-term aplastic anaemia.
http://dx.doi.org/10.1016/j.bjoms.2014.09.012 0266-4356/Crown Copyright © 2014 Published by Elsevier Ltd. on behalf of The British Association of Oral and Maxillofacial Surgeons. All rights reserved.
Please cite this article in press as: Pajpani M, Webb R. Lingual necrosis caused by mucormycosis in a patient with aplastic anaemia: case report. Br J Oral Maxillofac Surg (2014), http://dx.doi.org/10.1016/j.bjoms.2014.09.012
YBJOM-4354; No. of Pages 3
xxx.e2
ARTICLE IN PRESS
M. Pajpani, R. Webb / British Journal of Oral and Maxillofacial Surgery xxx (2014) xxx.e1–xxx.e3
Fig. 1. Large, black, necrotic lesion on the tongue one week after initial presentation.
Fig. 2. Tongue after debridement under local anaesthetic.
Patients with uncontrolled diabetes mellitus, particularly with ketoacidosis, those on corticosteroid treatment, those with neutropenia, trauma and burns, malignant haematological disorders, and who are severely immunocompromised, including those who have had haematopoietic stem cell transplants,6 are at high risk of mucormycosis. Based on its clinical presentation and anatomical site, invasive mucormycosis can be classified into one of 6 forms: rhinocerebral, pulmonary, cutaneous, gastrointestinal, disseminated, and uncommon rare forms. One-third to a half of all cases are rhinocerebral, and symptoms include sinusitis or periorbital cellulitis, eye or facial pain, and numbness.7 Successful management depends on 4 key areas: recognition of patients at risk through the early signs of infection to enable rapid diagnosis; removal or reduction of any risk factors such as the level of immunosuppression; and provision of appropriate antifungal treatment and surgical debridement, which improves survival. The relative rarity of the infection means that more information on evidence-based treatment is needed. Amphotericin B still seems to be widely supported as the treatment of choice.2 However, more recently, posaconazole has been used after reports of success from individual cases, or a combination of the 2 in refractory cases.8 The role of hyperbaric oxygen, iron chelators such as deferasirox, gamma interferon, and granulocyte-macrophage colonystimulating factor, all show promising results but are still in their relative infancy.9 Although less common than other fungal infections such as Candida spp, which is more often encountered by the maxillofacial team, an awareness of its incidence is essential for prompt diagnosis and successful management.
Discussion Most human infections of these causative fungi include Rhizopus, Mucor, Rhizomucor, Cunninghamella and Absidia spp.2 They are present in environments such as soil and dust, and their infectious spores are initially inhaled and can establish a route of infection in the sinuses. Other routes include ingestion through the digestive tract, or inoculation through breaches in the skin.3 Rhizopus oryzae is the most common organism and is responsible for around 70% of all cases of mucormycosis. The pathogenicity of the disease process is multifaceted. An impaired host defence, which includes deficiencies of circulating neutrophils and impaired phagocyte function, has a vital role in infection. Other factors such as the ability to acquire iron from the host to facilitate growth add to its success as a pathogen.4 Ultimately the hallmark of the disease is the capability to cause angioinvasion, which results in thrombosis and ultimately in tissue necrosis. This also contributes to the capacity of the organism to disseminate rapidly in the blood to other organs.5
Conflict of interest We have no conflicts of interest.
References 1. Ribes JA, Vanover-Sams CL, Baker DJ. Zygomycetes in human disease. Clin Microbiol Rev 2000;13:236–301. 2. Spellberg B, Edwards Jr J, Ibrahim A. Novel perspectives on mucormycosis: pathophysiology, presentation, and management. Clin Microbiol Rev 2005;18:556–69. 3. Rogers TR. Treatment of zygomycosis: current and new options. J Antimicrob Chemother 2008;61:i35–40. 4. Ibrahim AS, Spellberg B, Walsh TJ, et al. Pathogenesis of mucormycosis. Clin Infect Dis 2012;54:S16–22. 5. Skiada A, Rigopoulos D, Larios D, et al. Global epidemiology of cutaneous zygomycosis. Clin Dermatol 2012;30:628–32. 6. Grossman ME, Fox LP, Kovarik C, et al. Cutaneous manifestations of infection in the immunocompromised host. 2nd ed. New York: Springer; 2012.
Please cite this article in press as: Pajpani M, Webb R. Lingual necrosis caused by mucormycosis in a patient with aplastic anaemia: case report. Br J Oral Maxillofac Surg (2014), http://dx.doi.org/10.1016/j.bjoms.2014.09.012
YBJOM-4354; No. of Pages 3
ARTICLE IN PRESS
M. Pajpani, R. Webb / British Journal of Oral and Maxillofacial Surgery xxx (2014) xxx.e1–xxx.e3 7. Petrikkos G, Skiada A, Lortholary O, et al. Epidemiology and clinical manifestations of mucormycosis. Clin Infect Dis 2012;54:S23–34. 8. Spellberg B, Ibrahim A, Roilides E, et al. Combination therapy for mucormycosis: why, what, and how. Clin Infect Dis 2012;54:S73–8.
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9. Gil-Lamaignere C, Simitsopoulou M, Roilides E, et al. Interferongamma and granulocyte-macrophage colony-stimulating factor augment the activity of polymorphonuclear leukocytes against medically important zygomycetes. J Infect Dis 2005;191:1180–7.
Please cite this article in press as: Pajpani M, Webb R. Lingual necrosis caused by mucormycosis in a patient with aplastic anaemia: case report. Br J Oral Maxillofac Surg (2014), http://dx.doi.org/10.1016/j.bjoms.2014.09.012
