Clinical Review & Education
JAMA Clinical Challenge
Pustulonodular Lesion on the Nose Praveen Gundelly, MD; Michael Young, MD
A
A
B
R
L
P Figure 1. A, Patient with pustulonodular lesion on nose and a Penrose drain. B, Computed tomography scan of the chest, without contrast.
A 32-year-old man from Kentucky with a history of type 1 diabetes mellitus, hypertension, stage 3 chronic kidney disease, and chronic hepatitis C presented with a 1-month history of swelling and pain over his nose. He originally developed a pustule inside the nares, which gradually spread to involve the nose (Figure 1A). The patient reported no fever, chills, headache, diplopia, cough, dyspnea, or hemoptysis. He did report a history of injection drug use, opioid drug snorting, and tobacco abuse. He also reported working as a gardener and having 2 dogs as pets. Physical examination revealed an erythematous and deformed nose with small Quiz at jama.com pustules and a perforated nasal septum. A complete blood cell count showed a white blood cell count of 19 000 cells/μL; a chemistry panel showed a serum creatinine level of 1.7 mg/dL (150.3 μmol/L) and mildly elevated liver enzyme levels. Results of a human immunodeficiency virus screening test were negative. A computed tomography scan of the head, facial sinuses, and chest showed soft tissue swelling of the nose and several large cavitary lesions in the lungs (all lobes), with multiple bilateral nodular opacities (Figure 1B), but no intracranial lesions.
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WHAT WOULD YOU DO NEXT?
A. Perform skin biopsy for histopathology and culture B. Treat with intravenous broad spectrum antibiotics C. Treat with topical metronidazole D. Treat with topical steroid
JAMA December 17, 2014 Volume 312, Number 23
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a SUNY Binghamton User on 05/15/2015
jama.com
JAMA Clinical Challenge Clinical Review & Education
Diagnosis
A
Blastomycosis
B
What To Do Next? A. Perform skin biopsy for histopathology and culture A key clinical feature in this case is the persistent skin lesion in a person from a region with endemic fungal infections. Skin biopsy with histopathology examination and mycological culture establishes the diagnosis.
Discussion BlastomycosisiscausedbyBlastomycosisdermatitidis,adimorphicfungus existing in yeast form at 37°C and in mycelial form at 25°C to 30°C. Yeast cells are 8 to 15 μm in diameter, with a highly refractile cell wall. Blastomycosis is predominantly seen in North America, especially in theOhioandMississippirivervalleys,Midwesternstates,andCanadian provinces that border the Great Lakes. Infection in humans occurs through inhalation of conidia, causing asymptomatic or symptomatic infection. Primary cutaneous blastomycosis can occur after accidental inoculation or dog bites.1 Blastomycosis can occur in both immunocompetent and immunocompromised hosts, but disseminated infection is more common in immunocompromised hosts, such as people with a history of human immunodeficiency virus, organ transplants, or recent chemotherapy.2 The lungs are the most common site of infection, followed by skin, bone, and genitourinary system. Blastomycosis may mimic malignancy because it can present as a dense mass.3 There should be a high index of suspicion in endemic regions for blastomycosis. Blastomycosis is diagnosed by isolating B dermatitidis from respiratory specimens or tissue cultures. On histopathologic examination, it appears as a yeast with broad base budding. Blastomycosis can also be diagnosed by detection of blastomyces antigen in urine and blood. Blastomyces antigen shows crossreactivity with histoplasma antigen.4 Blastomyces antigen levels can be tracked to monitor response to treatment. Infectious Diseases Society of America guidelines recommend 1 or 2 weeks of intravenous lipid formulation of amphotericin or amphotericin deoxycholate for moderate to severe disease, followed by oral therapy with itraconazole for 6 to 12 months.5 Therapeutic drug monitoring of itraconazole is recommended because of wide interpatient variability. Itraconazole serum concentration of more than 1 μg/mL is recommended. Alternative treatments for patients who cannot tolerate itraconazole include ketoconazole and fluconazole. However, these are less effective than itraconazole. ARTICLE INFORMATION Author Affiliations: Department of Infectious Diseases, University of Kentucky, Lexington. Corresponding Author: Praveen Gundelly, MD, Department of Infectious Diseases, University of Kentucky, 740 S Limestone, K-512, Lexington, KY 40536 ([email protected]). Section Editor: Mary McGrae McDermott, MD, Senior Editor. Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. Additional Contributions: We thank the patient for providing permission to share his information.
Figure 2. Tissue specimens obtained from biopsy of the core of the nose lesion showing A, acanthotic squamous epithelium with hyperkeratosis and parakeratosis overlying a focus of abscess and granulation tissue (hematoxylineosin, original magnification ×400) and B, broad-based budding yeast consistent with Blastomycosis dermatitidis (Gomori methenenamine stain, original magnification ×400).
Voriconazole and posaconazole have activity against B dermatitidis in vitro and in animal models and can be used as alternative therapies, especially in central nervous system blastomycosis.6,7
Patient Outcome The patient was treated with broad-spectrum antibiotics and taken to the operating room for debridement. A biopsy specimen of nose tissue showedafocusofabscessandgranulationtissue(Figure2A)andbroadbasedbuddingyeastconsistentwithblastomycosis(Figure2B).ThepatientstartedthelipidformulationofamphotericinB,andantibioticswere stopped. A fungal culture grew B dermatitidis. Results of urine blastomycesantigentestingwerepositiveat0.8ng/mL.Althoughthepatient did not have any respiratory symptoms, there were significant radiological abnormalities (Figure 1B). Most patients with pulmonary blastomycosis have a solid, mass-like lesion on radiological imaging. However,blastomycosiscanalsopresentasareticulonodularpatternorwith cavitary lesions.3 It is difficult to ascertain if the nose lesion in this patient was from disseminated blastomycosis or traumatic inoculation of nasal mucosa during drug snorting. The patient received 6 days of amphotericin, which then was changed to oral itraconazole. The patient showed clinical improvement during his hospital stay and was discharged with a plan to continue oral itraconazole for 6 months and to receive follow-up in the outpatient infectious diseases clinic. However, he was lost to follow-up.
Submissions: We encourage authors to submit papers for consideration as a JAMA Clinical Challenge. Please contact Dr McDermott at [email protected]. REFERENCES 1. Gnann JW Jr, Bressler GS, Bodet CA III, Avent CK. Human blastomycosis after a dog bite. Ann Intern Med. 1983;98(1):48-49. 2. Pappas PG, Threlkeld MG, Bedsole GD, Cleveland KO, Gelfand MS, Dismukes WE. Blastomycosis in immunocompromised patients. Medicine (Baltimore). 1993;72(5):311-325. 3. Saccente M, Woods GL. Clinical and laboratory update on blastomycosis. Clin Microbiol Rev. 2010; 23(2):367-381.
jama.com
4. Connolly P, Hage CA, Bariola JR, et al. Blastomyces dermatitidis antigen detection by quantitative enzyme immunoassay. Clin Vaccine Immunol. 2012;19(1):53-56. 5. Chapman SW, Dismukes WE, Proia LA, et al. Clinical practice guidelines for the management of blastomycosis: 2008 update by the Infectious Diseases Society of America. Clin Infect Dis. 2008; 46(12):1801-1812. 6. Sugar AM, Liu XP. Efficacy of voriconazole in treatment of murine pulmonary blastomycosis. Antimicrob Agents Chemother. 2001;45(2):601-604. 7. Borgia SM, Fuller JD, Sarabia A, El-Helou P. Cerebral blastomycosis: a case series incorporating voriconazole in the treatment regimen. Med Mycol. 2006;44(7):659-664.
JAMA December 17, 2014 Volume 312, Number 23
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a SUNY Binghamton User on 05/15/2015
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JAMA Clinical Challenge
Pustulonodular Lesion on the Nose Praveen Gundelly, MD; Michael Young, MD
A
A
B
R
L
P Figure 1. A, Patient with pustulonodular lesion on nose and a Penrose drain. B, Computed tomography scan of the chest, without contrast.
A 32-year-old man from Kentucky with a history of type 1 diabetes mellitus, hypertension, stage 3 chronic kidney disease, and chronic hepatitis C presented with a 1-month history of swelling and pain over his nose. He originally developed a pustule inside the nares, which gradually spread to involve the nose (Figure 1A). The patient reported no fever, chills, headache, diplopia, cough, dyspnea, or hemoptysis. He did report a history of injection drug use, opioid drug snorting, and tobacco abuse. He also reported working as a gardener and having 2 dogs as pets. Physical examination revealed an erythematous and deformed nose with small Quiz at jama.com pustules and a perforated nasal septum. A complete blood cell count showed a white blood cell count of 19 000 cells/μL; a chemistry panel showed a serum creatinine level of 1.7 mg/dL (150.3 μmol/L) and mildly elevated liver enzyme levels. Results of a human immunodeficiency virus screening test were negative. A computed tomography scan of the head, facial sinuses, and chest showed soft tissue swelling of the nose and several large cavitary lesions in the lungs (all lobes), with multiple bilateral nodular opacities (Figure 1B), but no intracranial lesions.
2564
WHAT WOULD YOU DO NEXT?
A. Perform skin biopsy for histopathology and culture B. Treat with intravenous broad spectrum antibiotics C. Treat with topical metronidazole D. Treat with topical steroid
JAMA December 17, 2014 Volume 312, Number 23
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a SUNY Binghamton User on 05/15/2015
jama.com
JAMA Clinical Challenge Clinical Review & Education
Diagnosis
A
Blastomycosis
B
What To Do Next? A. Perform skin biopsy for histopathology and culture A key clinical feature in this case is the persistent skin lesion in a person from a region with endemic fungal infections. Skin biopsy with histopathology examination and mycological culture establishes the diagnosis.
Discussion BlastomycosisiscausedbyBlastomycosisdermatitidis,adimorphicfungus existing in yeast form at 37°C and in mycelial form at 25°C to 30°C. Yeast cells are 8 to 15 μm in diameter, with a highly refractile cell wall. Blastomycosis is predominantly seen in North America, especially in theOhioandMississippirivervalleys,Midwesternstates,andCanadian provinces that border the Great Lakes. Infection in humans occurs through inhalation of conidia, causing asymptomatic or symptomatic infection. Primary cutaneous blastomycosis can occur after accidental inoculation or dog bites.1 Blastomycosis can occur in both immunocompetent and immunocompromised hosts, but disseminated infection is more common in immunocompromised hosts, such as people with a history of human immunodeficiency virus, organ transplants, or recent chemotherapy.2 The lungs are the most common site of infection, followed by skin, bone, and genitourinary system. Blastomycosis may mimic malignancy because it can present as a dense mass.3 There should be a high index of suspicion in endemic regions for blastomycosis. Blastomycosis is diagnosed by isolating B dermatitidis from respiratory specimens or tissue cultures. On histopathologic examination, it appears as a yeast with broad base budding. Blastomycosis can also be diagnosed by detection of blastomyces antigen in urine and blood. Blastomyces antigen shows crossreactivity with histoplasma antigen.4 Blastomyces antigen levels can be tracked to monitor response to treatment. Infectious Diseases Society of America guidelines recommend 1 or 2 weeks of intravenous lipid formulation of amphotericin or amphotericin deoxycholate for moderate to severe disease, followed by oral therapy with itraconazole for 6 to 12 months.5 Therapeutic drug monitoring of itraconazole is recommended because of wide interpatient variability. Itraconazole serum concentration of more than 1 μg/mL is recommended. Alternative treatments for patients who cannot tolerate itraconazole include ketoconazole and fluconazole. However, these are less effective than itraconazole. ARTICLE INFORMATION Author Affiliations: Department of Infectious Diseases, University of Kentucky, Lexington. Corresponding Author: Praveen Gundelly, MD, Department of Infectious Diseases, University of Kentucky, 740 S Limestone, K-512, Lexington, KY 40536 ([email protected]). Section Editor: Mary McGrae McDermott, MD, Senior Editor. Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. Additional Contributions: We thank the patient for providing permission to share his information.
Figure 2. Tissue specimens obtained from biopsy of the core of the nose lesion showing A, acanthotic squamous epithelium with hyperkeratosis and parakeratosis overlying a focus of abscess and granulation tissue (hematoxylineosin, original magnification ×400) and B, broad-based budding yeast consistent with Blastomycosis dermatitidis (Gomori methenenamine stain, original magnification ×400).
Voriconazole and posaconazole have activity against B dermatitidis in vitro and in animal models and can be used as alternative therapies, especially in central nervous system blastomycosis.6,7
Patient Outcome The patient was treated with broad-spectrum antibiotics and taken to the operating room for debridement. A biopsy specimen of nose tissue showedafocusofabscessandgranulationtissue(Figure2A)andbroadbasedbuddingyeastconsistentwithblastomycosis(Figure2B).ThepatientstartedthelipidformulationofamphotericinB,andantibioticswere stopped. A fungal culture grew B dermatitidis. Results of urine blastomycesantigentestingwerepositiveat0.8ng/mL.Althoughthepatient did not have any respiratory symptoms, there were significant radiological abnormalities (Figure 1B). Most patients with pulmonary blastomycosis have a solid, mass-like lesion on radiological imaging. However,blastomycosiscanalsopresentasareticulonodularpatternorwith cavitary lesions.3 It is difficult to ascertain if the nose lesion in this patient was from disseminated blastomycosis or traumatic inoculation of nasal mucosa during drug snorting. The patient received 6 days of amphotericin, which then was changed to oral itraconazole. The patient showed clinical improvement during his hospital stay and was discharged with a plan to continue oral itraconazole for 6 months and to receive follow-up in the outpatient infectious diseases clinic. However, he was lost to follow-up.
Submissions: We encourage authors to submit papers for consideration as a JAMA Clinical Challenge. Please contact Dr McDermott at [email protected]. REFERENCES 1. Gnann JW Jr, Bressler GS, Bodet CA III, Avent CK. Human blastomycosis after a dog bite. Ann Intern Med. 1983;98(1):48-49. 2. Pappas PG, Threlkeld MG, Bedsole GD, Cleveland KO, Gelfand MS, Dismukes WE. Blastomycosis in immunocompromised patients. Medicine (Baltimore). 1993;72(5):311-325. 3. Saccente M, Woods GL. Clinical and laboratory update on blastomycosis. Clin Microbiol Rev. 2010; 23(2):367-381.
jama.com
4. Connolly P, Hage CA, Bariola JR, et al. Blastomyces dermatitidis antigen detection by quantitative enzyme immunoassay. Clin Vaccine Immunol. 2012;19(1):53-56. 5. Chapman SW, Dismukes WE, Proia LA, et al. Clinical practice guidelines for the management of blastomycosis: 2008 update by the Infectious Diseases Society of America. Clin Infect Dis. 2008; 46(12):1801-1812. 6. Sugar AM, Liu XP. Efficacy of voriconazole in treatment of murine pulmonary blastomycosis. Antimicrob Agents Chemother. 2001;45(2):601-604. 7. Borgia SM, Fuller JD, Sarabia A, El-Helou P. Cerebral blastomycosis: a case series incorporating voriconazole in the treatment regimen. Med Mycol. 2006;44(7):659-664.
JAMA December 17, 2014 Volume 312, Number 23
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a SUNY Binghamton User on 05/15/2015
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