- Email: [email protected]
A 54-Year-Old Man With Lingual Granuloma and Multiple Pulmonary Excavated Nodules
[
Pulmonary, Critical Care, and Sleep Pearls
]
A 54-Year-Old Man With Lingual Granuloma and Multiple Pulmonary Excavated Nodules Julien Dang, MD; Noémie Chanson, MD; Caroline Charlier, MD, PhD; Christine Bonnal, PharmD; Gregory Jouvion, PhD; Tiphaine Goulenok, MD; Thomas Papo, MD; and Karim Sacre, MD, PhD
A 54-year-old French man was admitted for evaluation of a chronic nodular lesion of the tongue and mandibular lymphadenopathy. He reported active tobacco and cannabis smoking as well as excessive alcohol use. He also reported frequent use of cocaine for several months and a past addiction to IV heroin. He had traveled abroad as a journalist and lived for several months in Columbia and Venezuela 12 years ago. His medical history included chronic hepatitis C infection successfully treated with interferon and ribavirin 6 years ago and high BP. CHEST 2017; 151(1):e13-e16
Physical Examination Findings The patient was afebrile. The lingual lesion was indurated, slightly painful, nonulcerated, and measured between 1 and 2 cm. Enlarged lymph nodes were palpable under the chin. A perforation of the nasal septum was noticed. Physical examination was otherwise normal.
Diagnostic Studies Results of routine blood tests were normal with the exception of an elevated C-reactive protein level at 20 mg/L (normal value, <5 mg/L). A CT scan of
AFFILIATIONS: From the Université Paris-Diderot (Drs Dang, Chanson, Goulenok, Papo, and Sacre), Assistance Publique Hôpitaux de Paris, Département de Médecine Interne, Hôpital Bichat-Claude Bernard, Paris, France; Université Paris Descartes (Dr Charlier), Assistance Publique Hôpitaux de Paris, Département des Maladies Infectieuses et Tropicales, Hôpital Necker-Enfants malades, Paris, France; Université Paris-Diderot (Dr Bonnal), Assistance Publique Hôpitaux de Paris, Laboratoire de mycologie et de Parasitologie, Hôpital Bichat-Claude Bernard, Paris, France; Institut Pasteur (Dr Jouvion), Unité d’Histopathologie Humaine et Modèles Animaux,
journal.publications.chestnet.org
the neck and chest confirmed the presence of cervical lymphadenopathy and revealed multiple cavitary pulmonary nodules (Fig 1). Bronchoscopic examination results were grossly normal. BAL fluid analysis and culture results were negative for infectious pathogens, including mycobacteria and fungal elements. Serum test results for HIV infection were negative. Screening for antineutrophil cytoplasmic antibodies by immunofluorescence was positive with an atypical pattern. Enzyme-linked immunosorbent assay for antineutrophil cytoplasmic antibody antigens (including myeloperoxidase,
Paris, France; and Unite INSERM U1149 (Drs Papo and Sacre), Paris, France. CORRESPONDENCE TO: Karim Sacre, MD, PhD, Departement de Medecine Interne, Hôpital Bichat-Claude Bernard, 46 rue Henri Huchard, 75018 Paris, France; e-mail: [email protected] Copyright Ó 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved. DOI: http://dx.doi.org/10.1016/j.chest.2016.07.026
e13
proteinase 3, lactoferrin, elastase, and cathepsin G) was negative. A biopsy of the lingual lesion was performed and revealed multifocal granulomas associated and numerous microabscesses containing yeast stained positively with Grocott methenamine silver (Fig 2).
What is the diagnosis?
Figure 1 – Chest CT scan shows multiple and disseminated pulmonary nodules with cavitation.
Figure 2 – A-D, Biopsy of the tongue lesion. A, Multifocal to coalescing granulomatous inflammation, centered on the chorion, associated with (B) intra-epithelial abscesses containing refringent microorganisms (arrowhead). C, D, GomoriGrocott staining reveals the presence of variable size yeasts (diameter between 4 and 30 mm) with multiple buds surrounding the parent cell, described as the “pilot” wheel.
e14 Pulmonary, Critical Care, and Sleep Pearls
[
151#1 CHEST JANUARY 2017
]
Diagnosis: Chronic paracoccidioidomycosis Discussion Paracoccidioidomycosis (PCM) is a chronic granulomatous infectious disease caused by a dimorphic fungus, Paracoccidioides brasiliensis. Endemic in Latin America (where PCM is the most prevalent invasive mycosis), the infection has been occasionally reported outside South America. Thus, the diagnosis of such infection may be highly challenging in nonendemic regions. The fungus spreads via inhalation of aerosolized spores or traumatic inoculation through the skin. As with other endemic mycoses, no human-to-human transmission has been described. Approximately 10 million people are reported to be infected in Brazil but only 2% develop symptoms. Alcohol and tobacco consumption and immunodeficiency increase the risk for disseminated infection. Untreated, the infection is associated with a high mortality rate. After inhalation, the fungus may be contained or eventually spread, and the disease evolves in an acute or chronic pattern. The clinical manifestations depend on the virulence of the infecting strain of P brasiliensis, the degree and type of immune response, the tissue involved, and intrinsic characteristics of the host. The acute form usually affects children, adolescents, and young adults up to 30 years old of both sexes; it is responsible for a disseminated severe infection with diffuse lymphadenopathy, liver and spleen enlargement, fever, and weight loss. The chronic form accounts for > 90% of the reported cases and may be due to the reactivation of a latent infection that has occurred up to 60 years earlier. Chronic PCM mostly affects male subjects in rural areas. In most cases, the infection involves the lung and is manifested by progressive dyspnea and dry cough. Chest CT scans show alveolar or interstitial infiltrate that may be associated with multiple cavitary nodules. Mucosal involvement is reported in 50% of cases, including indurated, painful, and often ulcerated lesions of the tongue, palate, gingiva, or oropharynx. Enlarged lymph nodes may also be noted. In approximately 10% of the cases, the CNS is involved, resulting in brain abscess or meningoencephalitis. The diagnosis is based on the identification of P brasiliensis in a specimen, such as lymph node aspirates or BAL fluid, by using direct microscopy and culture. Results of a tissue biopsy reveal granuloma with a nodular arrangement of epithelioid cells and multinucleated giant
journal.publications.chestnet.org
cells. Giant cells contain fungi that appear as yeast-like spherical elements, from 2 to 30 mm in diameter, with a typical pattern of peripheral “pilot wheel” multibudding from the mother cell. By virtue of its high sensitivity and specificity, polymerase chain reaction performed on any affected biological tissue has become an important diagnostic tool. Misdiagnosis as pulmonary tuberculosis or other dimorphic fungi infections (eg, histoplasmosis, coccidioidomycosis, blastomycosis) is possible because these entities share clinical and radiologic features. In addition to infectious diseases, the differential diagnosis includes necrotizing sarcoid granulomatosis, granulomatosis with polyangiitis, and neoplasia or lymphoma. The type and length of the treatment are dictated by the clinical severity of the infection and the comorbidities of the patient. For mild or moderate forms of the disease, itraconazole or the combination of sulfamethoxazole plus trimethoprim are the indicated drugs. Voriconazole is used for neurologic forms because of better CNS penetration. Most severe forms are treated with IV amphotericin B. Late relapse may occur. Clinical Course
The patient had a chronic PCM infection that could be traced back to a trip to Latin America 12 years earlier. The final diagnosis was confirmed by molecular detection according to polymerase chain reaction analysis of P brasiliensis DNA extracted from the biopsy specimen of the tongue lesion. The patient had no underlying immunosuppression such as HIV infection, diabetes, immunosuppressive therapies, hematologic malignancies, or organ transplantation. The medical treatment was discussed with the French National Reference Centre for Invasive Mycoses. Itraconazole 200 mg daily was given for 12 months with subsequent good clinical evolution, including almost complete resolution of the tongue lesion and adenopathy 8 weeks after starting therapy.
Clinical Pearls 1. PCM is endemic in Latin America and should be considered when patients who have lived or visited this region present with comparable features. 2. Chronic infection can appear > 60 years after traveling to an endemic area. 3. Because of its rarity outside of endemic areas, PCM can be misdiagnosed as tuberculosis, other fungal infections, vasculitis, or neoplasm.
e15
4. Treatment depends on severity and extent of infection. Azoles are the drugs of choice for mild to moderate infection; amphotericin is the drug of choice for severe infection.
Acknowledgments
Almeida OP, Jacks J, Scully C. Paracoccidioidomycosis of the mouth: an emerging deep mycosis. Crit Rev Oral Biol Med. 2003;14(5): 377-383. Lupi O, Tyring SK, McGinnis MR. Tropical dermatology: fungal tropical diseases. J Am Acad Dermatol. 2005;53(6):931-951. Ramos-e-Silva M, Saraiva Ldo ES. Paracoccidioidomycosis. Dermatol Clin. 2008;26(2):257-269.
Financial/nonfinancial disclosures: None declared.
Ameen M, Talhari C, Talhari S. Advances in paracoccidioidomycosis. Clin Exp Dermatol. 2010;35(6):576-580.
Other contributions: The author obtained patient permission to publish this information. CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met.
Barreto MM, Marchiori E, Amorim VB, et al. Thoracic paracoccidioidomycosis: radiographic and CT findings. Radiographics. 2012;32(1):71-84.
Suggesting Readings
de Abreu e Silva MA, Salum FG, Figueiredo MA, Cherubini K. Important aspects of oral paracoccidioidomycosis—a literature review. Mycoses. 2013;56(3):189-199.
Franco M, Montenegro MR, Mendes RP, Marques SA, Dillon NL, Mota NG. Paracoccidioidomycosis: a recently proposed classification of its clinical forms. Rev Soc Bras Med Trop. 1987;20(2):129-132.
Marques SA. Paracoccidioidomycosis: epidemiological, clinical, diagnostic and treatment up-dating. An Bras Dermatol. 2013;88(5): 700-711.
e16 Pulmonary, Critical Care, and Sleep Pearls
[
151#1 CHEST JANUARY 2017
]
Pulmonary, Critical Care, and Sleep Pearls
]
A 54-Year-Old Man With Lingual Granuloma and Multiple Pulmonary Excavated Nodules Julien Dang, MD; Noémie Chanson, MD; Caroline Charlier, MD, PhD; Christine Bonnal, PharmD; Gregory Jouvion, PhD; Tiphaine Goulenok, MD; Thomas Papo, MD; and Karim Sacre, MD, PhD
A 54-year-old French man was admitted for evaluation of a chronic nodular lesion of the tongue and mandibular lymphadenopathy. He reported active tobacco and cannabis smoking as well as excessive alcohol use. He also reported frequent use of cocaine for several months and a past addiction to IV heroin. He had traveled abroad as a journalist and lived for several months in Columbia and Venezuela 12 years ago. His medical history included chronic hepatitis C infection successfully treated with interferon and ribavirin 6 years ago and high BP. CHEST 2017; 151(1):e13-e16
Physical Examination Findings The patient was afebrile. The lingual lesion was indurated, slightly painful, nonulcerated, and measured between 1 and 2 cm. Enlarged lymph nodes were palpable under the chin. A perforation of the nasal septum was noticed. Physical examination was otherwise normal.
Diagnostic Studies Results of routine blood tests were normal with the exception of an elevated C-reactive protein level at 20 mg/L (normal value, <5 mg/L). A CT scan of
AFFILIATIONS: From the Université Paris-Diderot (Drs Dang, Chanson, Goulenok, Papo, and Sacre), Assistance Publique Hôpitaux de Paris, Département de Médecine Interne, Hôpital Bichat-Claude Bernard, Paris, France; Université Paris Descartes (Dr Charlier), Assistance Publique Hôpitaux de Paris, Département des Maladies Infectieuses et Tropicales, Hôpital Necker-Enfants malades, Paris, France; Université Paris-Diderot (Dr Bonnal), Assistance Publique Hôpitaux de Paris, Laboratoire de mycologie et de Parasitologie, Hôpital Bichat-Claude Bernard, Paris, France; Institut Pasteur (Dr Jouvion), Unité d’Histopathologie Humaine et Modèles Animaux,
journal.publications.chestnet.org
the neck and chest confirmed the presence of cervical lymphadenopathy and revealed multiple cavitary pulmonary nodules (Fig 1). Bronchoscopic examination results were grossly normal. BAL fluid analysis and culture results were negative for infectious pathogens, including mycobacteria and fungal elements. Serum test results for HIV infection were negative. Screening for antineutrophil cytoplasmic antibodies by immunofluorescence was positive with an atypical pattern. Enzyme-linked immunosorbent assay for antineutrophil cytoplasmic antibody antigens (including myeloperoxidase,
Paris, France; and Unite INSERM U1149 (Drs Papo and Sacre), Paris, France. CORRESPONDENCE TO: Karim Sacre, MD, PhD, Departement de Medecine Interne, Hôpital Bichat-Claude Bernard, 46 rue Henri Huchard, 75018 Paris, France; e-mail: [email protected] Copyright Ó 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved. DOI: http://dx.doi.org/10.1016/j.chest.2016.07.026
e13
proteinase 3, lactoferrin, elastase, and cathepsin G) was negative. A biopsy of the lingual lesion was performed and revealed multifocal granulomas associated and numerous microabscesses containing yeast stained positively with Grocott methenamine silver (Fig 2).
What is the diagnosis?
Figure 1 – Chest CT scan shows multiple and disseminated pulmonary nodules with cavitation.
Figure 2 – A-D, Biopsy of the tongue lesion. A, Multifocal to coalescing granulomatous inflammation, centered on the chorion, associated with (B) intra-epithelial abscesses containing refringent microorganisms (arrowhead). C, D, GomoriGrocott staining reveals the presence of variable size yeasts (diameter between 4 and 30 mm) with multiple buds surrounding the parent cell, described as the “pilot” wheel.
e14 Pulmonary, Critical Care, and Sleep Pearls
[
151#1 CHEST JANUARY 2017
]
Diagnosis: Chronic paracoccidioidomycosis Discussion Paracoccidioidomycosis (PCM) is a chronic granulomatous infectious disease caused by a dimorphic fungus, Paracoccidioides brasiliensis. Endemic in Latin America (where PCM is the most prevalent invasive mycosis), the infection has been occasionally reported outside South America. Thus, the diagnosis of such infection may be highly challenging in nonendemic regions. The fungus spreads via inhalation of aerosolized spores or traumatic inoculation through the skin. As with other endemic mycoses, no human-to-human transmission has been described. Approximately 10 million people are reported to be infected in Brazil but only 2% develop symptoms. Alcohol and tobacco consumption and immunodeficiency increase the risk for disseminated infection. Untreated, the infection is associated with a high mortality rate. After inhalation, the fungus may be contained or eventually spread, and the disease evolves in an acute or chronic pattern. The clinical manifestations depend on the virulence of the infecting strain of P brasiliensis, the degree and type of immune response, the tissue involved, and intrinsic characteristics of the host. The acute form usually affects children, adolescents, and young adults up to 30 years old of both sexes; it is responsible for a disseminated severe infection with diffuse lymphadenopathy, liver and spleen enlargement, fever, and weight loss. The chronic form accounts for > 90% of the reported cases and may be due to the reactivation of a latent infection that has occurred up to 60 years earlier. Chronic PCM mostly affects male subjects in rural areas. In most cases, the infection involves the lung and is manifested by progressive dyspnea and dry cough. Chest CT scans show alveolar or interstitial infiltrate that may be associated with multiple cavitary nodules. Mucosal involvement is reported in 50% of cases, including indurated, painful, and often ulcerated lesions of the tongue, palate, gingiva, or oropharynx. Enlarged lymph nodes may also be noted. In approximately 10% of the cases, the CNS is involved, resulting in brain abscess or meningoencephalitis. The diagnosis is based on the identification of P brasiliensis in a specimen, such as lymph node aspirates or BAL fluid, by using direct microscopy and culture. Results of a tissue biopsy reveal granuloma with a nodular arrangement of epithelioid cells and multinucleated giant
journal.publications.chestnet.org
cells. Giant cells contain fungi that appear as yeast-like spherical elements, from 2 to 30 mm in diameter, with a typical pattern of peripheral “pilot wheel” multibudding from the mother cell. By virtue of its high sensitivity and specificity, polymerase chain reaction performed on any affected biological tissue has become an important diagnostic tool. Misdiagnosis as pulmonary tuberculosis or other dimorphic fungi infections (eg, histoplasmosis, coccidioidomycosis, blastomycosis) is possible because these entities share clinical and radiologic features. In addition to infectious diseases, the differential diagnosis includes necrotizing sarcoid granulomatosis, granulomatosis with polyangiitis, and neoplasia or lymphoma. The type and length of the treatment are dictated by the clinical severity of the infection and the comorbidities of the patient. For mild or moderate forms of the disease, itraconazole or the combination of sulfamethoxazole plus trimethoprim are the indicated drugs. Voriconazole is used for neurologic forms because of better CNS penetration. Most severe forms are treated with IV amphotericin B. Late relapse may occur. Clinical Course
The patient had a chronic PCM infection that could be traced back to a trip to Latin America 12 years earlier. The final diagnosis was confirmed by molecular detection according to polymerase chain reaction analysis of P brasiliensis DNA extracted from the biopsy specimen of the tongue lesion. The patient had no underlying immunosuppression such as HIV infection, diabetes, immunosuppressive therapies, hematologic malignancies, or organ transplantation. The medical treatment was discussed with the French National Reference Centre for Invasive Mycoses. Itraconazole 200 mg daily was given for 12 months with subsequent good clinical evolution, including almost complete resolution of the tongue lesion and adenopathy 8 weeks after starting therapy.
Clinical Pearls 1. PCM is endemic in Latin America and should be considered when patients who have lived or visited this region present with comparable features. 2. Chronic infection can appear > 60 years after traveling to an endemic area. 3. Because of its rarity outside of endemic areas, PCM can be misdiagnosed as tuberculosis, other fungal infections, vasculitis, or neoplasm.
e15
4. Treatment depends on severity and extent of infection. Azoles are the drugs of choice for mild to moderate infection; amphotericin is the drug of choice for severe infection.
Acknowledgments
Almeida OP, Jacks J, Scully C. Paracoccidioidomycosis of the mouth: an emerging deep mycosis. Crit Rev Oral Biol Med. 2003;14(5): 377-383. Lupi O, Tyring SK, McGinnis MR. Tropical dermatology: fungal tropical diseases. J Am Acad Dermatol. 2005;53(6):931-951. Ramos-e-Silva M, Saraiva Ldo ES. Paracoccidioidomycosis. Dermatol Clin. 2008;26(2):257-269.
Financial/nonfinancial disclosures: None declared.
Ameen M, Talhari C, Talhari S. Advances in paracoccidioidomycosis. Clin Exp Dermatol. 2010;35(6):576-580.
Other contributions: The author obtained patient permission to publish this information. CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met.
Barreto MM, Marchiori E, Amorim VB, et al. Thoracic paracoccidioidomycosis: radiographic and CT findings. Radiographics. 2012;32(1):71-84.
Suggesting Readings
de Abreu e Silva MA, Salum FG, Figueiredo MA, Cherubini K. Important aspects of oral paracoccidioidomycosis—a literature review. Mycoses. 2013;56(3):189-199.
Franco M, Montenegro MR, Mendes RP, Marques SA, Dillon NL, Mota NG. Paracoccidioidomycosis: a recently proposed classification of its clinical forms. Rev Soc Bras Med Trop. 1987;20(2):129-132.
Marques SA. Paracoccidioidomycosis: epidemiological, clinical, diagnostic and treatment up-dating. An Bras Dermatol. 2013;88(5): 700-711.
e16 Pulmonary, Critical Care, and Sleep Pearls
[
151#1 CHEST JANUARY 2017
]