Accepted Article
Received Date : 29-Aug-2013 Accepted Date : 03-Oct-2013 Article type
: Case Report
Running title: Oral histoplasmosis
Oral presentation of histoplasmosis in an immunocompetent patient: a diagnostic challenge
F Iqbal,*† M Schifter,† HG Coleman* *Department of Tissue Pathology and Diagnostic Oncology, Institute for Clinical Pathology and Medical Research, Westmead Hospital, New South Wales. †Department of Oral Medicine, Oral Pathology and Special Needs Dentistry, Westmead Centre for Oral Health, Westmead Hospital, New South Wales.
ABSTRACT Histoplasmosis is a rare systemic fungal infection, primarily affecting the pulmonary system. Oral lesions are usually a manifestation of the disseminated form of the disease and are most frequently observed in severely immunocompromised patients, such as those with advanced human immunodeficiency virus infection and/or frank acquired immune deficiency syndrome. The clinical presentation of the oral lesions may be difficult to distinguish from oral squamous cell carcinoma. The histopathological features are usually characteristic, but occasionally the organisms are scanty and not readily identified, which can preclude obtaining the correct diagnosis and ensuring appropriate management. This is an Accepted Article that has been peer-reviewed and approved for publication in the Australian Dental Journal, but has yet to undergo copy-editing and proof correction. Please cite this article as an “Accepted Article”; doi: 10.1111/adj.12187 This article is protected by copyright. All rights reserved.
Accepted Article
Histoplasmosis is an unusual and rare cause of chronic non-healing ulceration in the oral cavity. A case of histoplasmosis involving the oral cavity in an immunocompetent patient is reported, which was not recognized, resulting in the inappropriate management of the condition. Keywords: Fungus, granuloma, histology, histoplasmosis, immunocompetent. Abbreviations and acronyms: AIDS = acquired immune deficiency syndrome; FBC = full blood count; HIV = human immunodeficiency virus. (Accepted for publication 3 October 2013.)
INTRODUCTION Histoplasmosis is a dimorphic fungal infection, which primarily involves the lungs and rarely affects the oral mucosa. Oral lesions are seen with the disseminated form of the disease and usually only in severely immunocompromised patients with advanced human immunodeficiency virus (HIV) infection and/or frank acquired immune deficiency syndrome (AIDS). A case of histoplasmosis involving the oral cavity in an immunocompetent patient is reported.
CASE REPORT A 58-year-old Caucasian man was referred to the Oral Medicine Unit with a painful, nonhealing ulcer on the right buccal mucosa and gingiva of the right mandible. A biopsy of the gingiva by the referring clinician had demonstrated non-caseating chronic granulomatous inflammation. No foreign material was identified. Special stains (Ziehl–Neelsen and Periodic acid-Schiff) for acid-fast bacilli and fungi were negative. Subsequent serological investigations for Crohn’s disease (serum Anti-Saccharomyces cerevisiae antibodies level), acute inflammatory marker (C-reactive protein), the full blood count (FBC) and serum
This article is protected by copyright. All rights reserved.
Accepted Article
angiotensin converting enzyme level were non-contributory. A clinical diagnosis of seemingly idiopathic orofacial granulomatosis was made. The patient had been initially treated with topical and then systemic corticosteroid therapy for approximately 10 months but he failed to show any improvement. On presentation to the Unit, he had difficulty eating and speaking due to the level of oral discomfort. He had also lost approximately 10 kg in body weight, attributed to an inadequate dietary intake. His remaining medical history was unremarkable. Extraoral examination was non-contributory. There was no cervical lymphadenopathy. Intraoral examination showed extensive ulceration involving the right buccal mucosa, extending from the commissure of mouth to abut the palatoglossal fold, as well as involving the depth of the right mandibular buccal sulcus, the adjacent buccal alveolar mucosa and gingiva of the right mandible (Fig. 1). There was another extensive lesion involving the right lateral aspect of the tongue (Fig. 2). An incisional biopsy of the right buccal mucosa was performed. Histopathological examination demonstrated non-caseating, chronic granulomatous inflammation with numerous intracellular microorganisms surrounded by a clear halo (Fig. 3). Special stains (PAS diastase and Gomori’s methenamine silver) confirmed the presence of small intracellular yeasts consistent with Histoplasma capsulatum (Fig. 4). A definitive diagnosis of oral histoplasmosis was made. Subsequent diagnostic imaging (computed tomography scan) suggested the presence of an infection in the lungs (Fig. 5). Serological investigation for HIV infection was negative and a repeat FBC film was also normal. In light of the diagnosis of probable pulmonary histoplasmosis with demonstrable oral manifestations, the patient was hospitalized and treated with intravenous antifungal therapy (Amphotericin B) for 14 days (total dose of 470 mg) followed by 12 weeks of oral Itraconazole with complete resolution of the pulmonary changes and the oral lesions (Fig. 6).
This article is protected by copyright. All rights reserved.
Accepted Article
It was then determined from the patient that he had previously worked as a wool assessor, often in sheds, in which bats were known to inhabit and roost.
DISCUSSION Histoplasmosis is caused by the fungal organism Histoplasma capsulatum. It is a dimorphic fungus, growing as yeast in the human host and as a mould in the natural environment. Bird and bat excrement enhance their growth in soil. Human exposure occurs as a result of activities that generate an aerosol containing the fungal spores. The primary site of infection is usually the lungs. Air-borne spores (microcondia) of the fungus are usually inhaled. They germinate in the lungs causing a ‘patchy’ pneumonitis. Haematogenous dissemination usually then occurs within the first two weeks of infection. Disseminated infection may involve the central nervous system, gastrointestinal tract, including oral mucosa, liver, spleen, kidneys, adrenal glands and lymph nodes.1,2 Oral histoplasmosis has rarely been documented in Australia and most cases were disseminated foci of infection in severely immunocompromised patients with AIDS.3,4 Common sites for oral involvement are the buccal mucosa, the tongue and palate. These oral lesions may appear as chronic, non-healing ulcers with a variable degree of pain. The ulcers usually have a firm, rolled margin and may be difficult to distinguish from malignancy. Diagnosis is made by identification of the organisms in tissue or in culture. Newer molecular techniques such as specific fungal polymerase chain reaction may also be useful. Histopathological examination of the infected tissues usually demonstrates chronic noncaseating granulomatous inflammation. Numerous small (1–2 μm diameter) microorganisms, which are surrounded by the characteristic clear halo, may be seen within the macrophages, multinucleated giant cells or within the fibrous tissue. Special stains such as PAS diastase or
This article is protected by copyright. All rights reserved.
Accepted Article
Gomori’s methenamine silver are then required to confirm the microorganism within the tissues. Initial pulmonary infection may resolve spontaneously after the development of cellular immunity to the microorganism. Untreated disseminated infections are associated with a mortality rate of up to 90%.2 The infection can be treated successfully with systemic antifungal therapy with intravenous Amphotericin B supplemented by prolonged, orally administered therapy with the later generation azole agents, such as Itraconazole. Histoplasmosis is an unusual and rare cause of non-healing ulceration in the oral cavity, especially in immunocompetent patients. The rarity of the condition, as well as inadequate sampling posed a challenge in obtaining the correct diagnosis and therefore the management was inappropriate for the patient’s condition.
REFERENCES 1. Wheat LJ, Kauffman CA. Histoplasmosis. Infect Dis Clin North Am 2003;17:1-19. 2. Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and Maxillofacial Pathology. 3rd edn. St Louis: Mosby, 2009:224-226. 3. O'Sullivan MV, Whitby M, Chahoud C, Miller SM. Histoplasmosis in Australia: a report of a case with a review of the literature. Aust Dent J 2004;19:94-97. 4. McLeod DSA, Mortimer RH, Perry-Keene DA, et al. Histoplasmosis in Australia: report of 16 cases and literature review. Medicine 2011;90:61-68.
This article is protected by copyright. All rights reserved.
Accepted Article
Address for correspondence: Dr Firoz Iqbal PO Box 599 Westmead NSW 2145 Email: [email protected]
Figure legends Fig. 1 Photograph showing ulceration involving the right buccal mucosa. Fig. 2 Photograph showing ulceration with crenated appearance of the right lateral tongue. Fig. 3 Photomicrograph showing macrophages with intracellular microorganisms surrounded by clear halo (arrows) (H & E stain). Fig. 4 Grocott-Gomori methenamine silver stain showing microorganisms (arrows). Fig. 5 CT scan showing patchy opacities involving both lungs (arrows). Fig. 6 Follow-up photograph showing the right buccal mucosa with complete healing of ulceration after antifungal therapy.
This article is protected by copyright. All rights reserved.
Accepted Article This article is protected by copyright. All rights reserved.
Accepted Article This article is protected by copyright. All rights reserved.
Accepted Article This article is protected by copyright. All rights reserved.
Received Date : 29-Aug-2013 Accepted Date : 03-Oct-2013 Article type
: Case Report
Running title: Oral histoplasmosis
Oral presentation of histoplasmosis in an immunocompetent patient: a diagnostic challenge
F Iqbal,*† M Schifter,† HG Coleman* *Department of Tissue Pathology and Diagnostic Oncology, Institute for Clinical Pathology and Medical Research, Westmead Hospital, New South Wales. †Department of Oral Medicine, Oral Pathology and Special Needs Dentistry, Westmead Centre for Oral Health, Westmead Hospital, New South Wales.
ABSTRACT Histoplasmosis is a rare systemic fungal infection, primarily affecting the pulmonary system. Oral lesions are usually a manifestation of the disseminated form of the disease and are most frequently observed in severely immunocompromised patients, such as those with advanced human immunodeficiency virus infection and/or frank acquired immune deficiency syndrome. The clinical presentation of the oral lesions may be difficult to distinguish from oral squamous cell carcinoma. The histopathological features are usually characteristic, but occasionally the organisms are scanty and not readily identified, which can preclude obtaining the correct diagnosis and ensuring appropriate management. This is an Accepted Article that has been peer-reviewed and approved for publication in the Australian Dental Journal, but has yet to undergo copy-editing and proof correction. Please cite this article as an “Accepted Article”; doi: 10.1111/adj.12187 This article is protected by copyright. All rights reserved.
Accepted Article
Histoplasmosis is an unusual and rare cause of chronic non-healing ulceration in the oral cavity. A case of histoplasmosis involving the oral cavity in an immunocompetent patient is reported, which was not recognized, resulting in the inappropriate management of the condition. Keywords: Fungus, granuloma, histology, histoplasmosis, immunocompetent. Abbreviations and acronyms: AIDS = acquired immune deficiency syndrome; FBC = full blood count; HIV = human immunodeficiency virus. (Accepted for publication 3 October 2013.)
INTRODUCTION Histoplasmosis is a dimorphic fungal infection, which primarily involves the lungs and rarely affects the oral mucosa. Oral lesions are seen with the disseminated form of the disease and usually only in severely immunocompromised patients with advanced human immunodeficiency virus (HIV) infection and/or frank acquired immune deficiency syndrome (AIDS). A case of histoplasmosis involving the oral cavity in an immunocompetent patient is reported.
CASE REPORT A 58-year-old Caucasian man was referred to the Oral Medicine Unit with a painful, nonhealing ulcer on the right buccal mucosa and gingiva of the right mandible. A biopsy of the gingiva by the referring clinician had demonstrated non-caseating chronic granulomatous inflammation. No foreign material was identified. Special stains (Ziehl–Neelsen and Periodic acid-Schiff) for acid-fast bacilli and fungi were negative. Subsequent serological investigations for Crohn’s disease (serum Anti-Saccharomyces cerevisiae antibodies level), acute inflammatory marker (C-reactive protein), the full blood count (FBC) and serum
This article is protected by copyright. All rights reserved.
Accepted Article
angiotensin converting enzyme level were non-contributory. A clinical diagnosis of seemingly idiopathic orofacial granulomatosis was made. The patient had been initially treated with topical and then systemic corticosteroid therapy for approximately 10 months but he failed to show any improvement. On presentation to the Unit, he had difficulty eating and speaking due to the level of oral discomfort. He had also lost approximately 10 kg in body weight, attributed to an inadequate dietary intake. His remaining medical history was unremarkable. Extraoral examination was non-contributory. There was no cervical lymphadenopathy. Intraoral examination showed extensive ulceration involving the right buccal mucosa, extending from the commissure of mouth to abut the palatoglossal fold, as well as involving the depth of the right mandibular buccal sulcus, the adjacent buccal alveolar mucosa and gingiva of the right mandible (Fig. 1). There was another extensive lesion involving the right lateral aspect of the tongue (Fig. 2). An incisional biopsy of the right buccal mucosa was performed. Histopathological examination demonstrated non-caseating, chronic granulomatous inflammation with numerous intracellular microorganisms surrounded by a clear halo (Fig. 3). Special stains (PAS diastase and Gomori’s methenamine silver) confirmed the presence of small intracellular yeasts consistent with Histoplasma capsulatum (Fig. 4). A definitive diagnosis of oral histoplasmosis was made. Subsequent diagnostic imaging (computed tomography scan) suggested the presence of an infection in the lungs (Fig. 5). Serological investigation for HIV infection was negative and a repeat FBC film was also normal. In light of the diagnosis of probable pulmonary histoplasmosis with demonstrable oral manifestations, the patient was hospitalized and treated with intravenous antifungal therapy (Amphotericin B) for 14 days (total dose of 470 mg) followed by 12 weeks of oral Itraconazole with complete resolution of the pulmonary changes and the oral lesions (Fig. 6).
This article is protected by copyright. All rights reserved.
Accepted Article
It was then determined from the patient that he had previously worked as a wool assessor, often in sheds, in which bats were known to inhabit and roost.
DISCUSSION Histoplasmosis is caused by the fungal organism Histoplasma capsulatum. It is a dimorphic fungus, growing as yeast in the human host and as a mould in the natural environment. Bird and bat excrement enhance their growth in soil. Human exposure occurs as a result of activities that generate an aerosol containing the fungal spores. The primary site of infection is usually the lungs. Air-borne spores (microcondia) of the fungus are usually inhaled. They germinate in the lungs causing a ‘patchy’ pneumonitis. Haematogenous dissemination usually then occurs within the first two weeks of infection. Disseminated infection may involve the central nervous system, gastrointestinal tract, including oral mucosa, liver, spleen, kidneys, adrenal glands and lymph nodes.1,2 Oral histoplasmosis has rarely been documented in Australia and most cases were disseminated foci of infection in severely immunocompromised patients with AIDS.3,4 Common sites for oral involvement are the buccal mucosa, the tongue and palate. These oral lesions may appear as chronic, non-healing ulcers with a variable degree of pain. The ulcers usually have a firm, rolled margin and may be difficult to distinguish from malignancy. Diagnosis is made by identification of the organisms in tissue or in culture. Newer molecular techniques such as specific fungal polymerase chain reaction may also be useful. Histopathological examination of the infected tissues usually demonstrates chronic noncaseating granulomatous inflammation. Numerous small (1–2 μm diameter) microorganisms, which are surrounded by the characteristic clear halo, may be seen within the macrophages, multinucleated giant cells or within the fibrous tissue. Special stains such as PAS diastase or
This article is protected by copyright. All rights reserved.
Accepted Article
Gomori’s methenamine silver are then required to confirm the microorganism within the tissues. Initial pulmonary infection may resolve spontaneously after the development of cellular immunity to the microorganism. Untreated disseminated infections are associated with a mortality rate of up to 90%.2 The infection can be treated successfully with systemic antifungal therapy with intravenous Amphotericin B supplemented by prolonged, orally administered therapy with the later generation azole agents, such as Itraconazole. Histoplasmosis is an unusual and rare cause of non-healing ulceration in the oral cavity, especially in immunocompetent patients. The rarity of the condition, as well as inadequate sampling posed a challenge in obtaining the correct diagnosis and therefore the management was inappropriate for the patient’s condition.
REFERENCES 1. Wheat LJ, Kauffman CA. Histoplasmosis. Infect Dis Clin North Am 2003;17:1-19. 2. Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and Maxillofacial Pathology. 3rd edn. St Louis: Mosby, 2009:224-226. 3. O'Sullivan MV, Whitby M, Chahoud C, Miller SM. Histoplasmosis in Australia: a report of a case with a review of the literature. Aust Dent J 2004;19:94-97. 4. McLeod DSA, Mortimer RH, Perry-Keene DA, et al. Histoplasmosis in Australia: report of 16 cases and literature review. Medicine 2011;90:61-68.
This article is protected by copyright. All rights reserved.
Accepted Article
Address for correspondence: Dr Firoz Iqbal PO Box 599 Westmead NSW 2145 Email: [email protected]
Figure legends Fig. 1 Photograph showing ulceration involving the right buccal mucosa. Fig. 2 Photograph showing ulceration with crenated appearance of the right lateral tongue. Fig. 3 Photomicrograph showing macrophages with intracellular microorganisms surrounded by clear halo (arrows) (H & E stain). Fig. 4 Grocott-Gomori methenamine silver stain showing microorganisms (arrows). Fig. 5 CT scan showing patchy opacities involving both lungs (arrows). Fig. 6 Follow-up photograph showing the right buccal mucosa with complete healing of ulceration after antifungal therapy.
This article is protected by copyright. All rights reserved.
Accepted Article This article is protected by copyright. All rights reserved.
Accepted Article This article is protected by copyright. All rights reserved.
Accepted Article This article is protected by copyright. All rights reserved.
