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Delayed Diagnosis of Disseminated Cryptococcosis with Associated Meningoencephalitis in an Immunocompetent Septuagenarian Host
Accepted Manuscript Delayed Diagnosis of Disseminated Cryptococcosis with Associated Meningoencephalitis in an Immunocompetent Septuagenarian Host Isaac S. Chan, MD, PhD, Rani Chudasama, BS, Adam B. Burrows, MD PII:
S0002-9343(16)30824-5
DOI:
10.1016/j.amjmed.2016.05.044
Reference:
AJM 13647
To appear in:
The American Journal of Medicine
Received Date: 15 May 2016 Revised Date:
28 May 2016
Accepted Date: 31 May 2016
Please cite this article as: Chan IS, Chudasama R, Burrows AB, Delayed Diagnosis of Disseminated Cryptococcosis with Associated Meningoencephalitis in an Immunocompetent Septuagenarian Host, The American Journal of Medicine (2016), doi: 10.1016/j.amjmed.2016.05.044. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Delayed Diagnosis of Disseminated Cryptococcosis with Associated Meningoencephalitis in an Immunocompetent Septuagenarian Host 1
1
1
RI PT
Isaac S. Chan, MD, PhD , Rani Chudasama, BS , and Adam B. Burrows, MD
1
M AN U
Corresponding Author: Isaac S. Chan Boston University Medical Campus, Internal Medicine 72 East Concord Street Evans 124 Boston, MA, USA 02118 Phone: (617) 638-6500 Fax: (617) 638-6501 [email protected]
SC
Department of Medicine, Boston University, Boston, Massachusetts 02118
Conflict of interest: none
TE D
Funding: none
Authorship: All authors had access to the data and played a role in writing this manuscript.
EP
Keywords: medical error, cognitive bias, geriatric infections, Cryptococcus neoformans
AC C
Running head: Disseminated Cryptococcosis in a Geriatric Patient
ACCEPTED MANUSCRIPT
To the editor: Cryptococcus neoformans is an opportunistic pathogen common in immunocompromised hosts, but among immunocompetent patients, incidence is estimated to be as low as 20% of total cases1.
RI PT
Case: A 75-year-old woman with asthma, hypertension, hyperlipidemia, well-controlled Type 2 diabetes mellitus, and migraines was admitted for bitemporal headache and lethargy of nine days. Six days prior, she was evaluated in our emergency department with similar complaints. There, after unrevealing brain imaging, she was treated for migraine headache and discharged.
SC
Afterwards, her geriatrician saw her and started levofloxacin for a urine culture that grew over 100,000 colonies/ml of Escherichia coli, and Tamiflu given exposure to contacts with confirmed influenza.
M AN U
Her continued headaches and worsening functional status prompted her return to the hospital. Her medications included metformin 500mg twice daily, glipizide 5mg daily, diltiazem 240mg daily, simvastatin 20mg daily, montelukast 10mg daily, daily inhaled fluticasone-salmeterol, daily inhaled tiotropium, inhaled albuterol as needed. She last used systemic corticosteroids three years prior.
TE D
On exam, the temperature was 98oF, blood pressure 173/108 mmHg, pulse 94 beats per minute, respiratory rate 18 breaths per minute and oxygen saturation 95%. She demonstrated discomfort in an illuminated room, lack of spontaneous speech, and new palpable purpura on her lower extremities. A chest x-ray revealed increased interstitial markings. Prominent laboratory values included serum sodium of 133 mmol/L. She was diagnosed with a persistent urinary tract infection and a concomitant upper respiratory infection. Headache and photophobia were attributed to her history of migraines. She was given a normal saline bolus and started on ceftriaxone. Subsequently, she became more somnolent and her hyponatremia worsened. The differential was broadened to include meningitis and other primary neurological processes. She received empiric treatment for bacterial and viral meningitis.
AC C
EP
Later, she developed a right third cranial nerve palsy. Magnetic resonance imaging of her brain showed no acute intracranial abnormalities. A lumbar puncture revealed elevated opening pressure and both cerebrospinal fluid culture and serum were positive for Cryptococcus neoformans. Antibacterial and antiviral therapy were discontinued. Amphotericin and flucytosine were started for a six week course and transitioned to fluconazole for consolidation therapy. Workup for immunocompromising conditions, such as human immunodeficiency virus or malignancy, was negative. After treatment, she made a full cognitive, neurologic, and functional recovery. Discussion Cryptococcus neoformans meningoencephalitis in immunocompetent hosts can present nonclassically, complicating diagnosis in these patients. Risks factors for Cryptococcal neoformans meningitis in immunocompetent hosts include diabetes and advanced age1. Inhaled corticosteroid use is also associated with fungal infections, suggesting systemic immunosuppression2. When these patients present with delirium, the infectious differential should remain broad.
ACCEPTED MANUSCRIPT
We highlight the importance of avoiding cognitive biases, or heuristics, which are a source of diagnostic error. Diagnostic errors are estimated to contribute to 10-15% of all medical errors3. Two heuristics are relevant in this case, premature closure and anchoring. Premature closure occurs when clinicians end clinical decision-making early4. This led to the initial diagnosis of migraine headache without considering alternatives.
RI PT
Anchoring occurs when clinicians stick with a diagnosis after the initial impression is formed4. Here, the team continued with a urinary tract infection as the principal etiology of her delirium, thus delaying the diagnosis.
AC C
EP
TE D
M AN U
SC
Recognizing heuristics and having diagnostic “time-outs” may prompt reflection and prevent error5. One feature of this case mitigating against heuristics was recognition that the severity of the patient’s delirium was out of proportion to her intact cognitive baseline and the insult of an otherwise uncomplicated cystitis.
ACCEPTED MANUSCRIPT
References
AC C
EP
TE D
M AN U
SC
RI PT
1. Pappas PG. Cryptococcal infections in non-HIV-infected patients. Trans Am Clin Climatol Assoc. 2013;124:61-79. 2. Barouky R, Badet M, Denis MS, Soubirou JL, Philit F, Guerin C. Inhaled corticosteroids in chronic obstructive pulmonary disease and disseminated aspergillosis. European journal of internal medicine. 2003;14:380-2. 3. Norman GR, Eva KW. Diagnostic error and clinical reasoning. Medical education. 2010;44:94-100. 4. Derauf DD. Cognitive psychology of missed diagnoses. Annals of internal medicine. 2005;142:1026; author reply 5. Trowbridge RL. Twelve tips for teaching avoidance of diagnostic errors. Medical teacher. 2008;30:496-500.
S0002-9343(16)30824-5
DOI:
10.1016/j.amjmed.2016.05.044
Reference:
AJM 13647
To appear in:
The American Journal of Medicine
Received Date: 15 May 2016 Revised Date:
28 May 2016
Accepted Date: 31 May 2016
Please cite this article as: Chan IS, Chudasama R, Burrows AB, Delayed Diagnosis of Disseminated Cryptococcosis with Associated Meningoencephalitis in an Immunocompetent Septuagenarian Host, The American Journal of Medicine (2016), doi: 10.1016/j.amjmed.2016.05.044. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Delayed Diagnosis of Disseminated Cryptococcosis with Associated Meningoencephalitis in an Immunocompetent Septuagenarian Host 1
1
1
RI PT
Isaac S. Chan, MD, PhD , Rani Chudasama, BS , and Adam B. Burrows, MD
1
M AN U
Corresponding Author: Isaac S. Chan Boston University Medical Campus, Internal Medicine 72 East Concord Street Evans 124 Boston, MA, USA 02118 Phone: (617) 638-6500 Fax: (617) 638-6501 [email protected]
SC
Department of Medicine, Boston University, Boston, Massachusetts 02118
Conflict of interest: none
TE D
Funding: none
Authorship: All authors had access to the data and played a role in writing this manuscript.
EP
Keywords: medical error, cognitive bias, geriatric infections, Cryptococcus neoformans
AC C
Running head: Disseminated Cryptococcosis in a Geriatric Patient
ACCEPTED MANUSCRIPT
To the editor: Cryptococcus neoformans is an opportunistic pathogen common in immunocompromised hosts, but among immunocompetent patients, incidence is estimated to be as low as 20% of total cases1.
RI PT
Case: A 75-year-old woman with asthma, hypertension, hyperlipidemia, well-controlled Type 2 diabetes mellitus, and migraines was admitted for bitemporal headache and lethargy of nine days. Six days prior, she was evaluated in our emergency department with similar complaints. There, after unrevealing brain imaging, she was treated for migraine headache and discharged.
SC
Afterwards, her geriatrician saw her and started levofloxacin for a urine culture that grew over 100,000 colonies/ml of Escherichia coli, and Tamiflu given exposure to contacts with confirmed influenza.
M AN U
Her continued headaches and worsening functional status prompted her return to the hospital. Her medications included metformin 500mg twice daily, glipizide 5mg daily, diltiazem 240mg daily, simvastatin 20mg daily, montelukast 10mg daily, daily inhaled fluticasone-salmeterol, daily inhaled tiotropium, inhaled albuterol as needed. She last used systemic corticosteroids three years prior.
TE D
On exam, the temperature was 98oF, blood pressure 173/108 mmHg, pulse 94 beats per minute, respiratory rate 18 breaths per minute and oxygen saturation 95%. She demonstrated discomfort in an illuminated room, lack of spontaneous speech, and new palpable purpura on her lower extremities. A chest x-ray revealed increased interstitial markings. Prominent laboratory values included serum sodium of 133 mmol/L. She was diagnosed with a persistent urinary tract infection and a concomitant upper respiratory infection. Headache and photophobia were attributed to her history of migraines. She was given a normal saline bolus and started on ceftriaxone. Subsequently, she became more somnolent and her hyponatremia worsened. The differential was broadened to include meningitis and other primary neurological processes. She received empiric treatment for bacterial and viral meningitis.
AC C
EP
Later, she developed a right third cranial nerve palsy. Magnetic resonance imaging of her brain showed no acute intracranial abnormalities. A lumbar puncture revealed elevated opening pressure and both cerebrospinal fluid culture and serum were positive for Cryptococcus neoformans. Antibacterial and antiviral therapy were discontinued. Amphotericin and flucytosine were started for a six week course and transitioned to fluconazole for consolidation therapy. Workup for immunocompromising conditions, such as human immunodeficiency virus or malignancy, was negative. After treatment, she made a full cognitive, neurologic, and functional recovery. Discussion Cryptococcus neoformans meningoencephalitis in immunocompetent hosts can present nonclassically, complicating diagnosis in these patients. Risks factors for Cryptococcal neoformans meningitis in immunocompetent hosts include diabetes and advanced age1. Inhaled corticosteroid use is also associated with fungal infections, suggesting systemic immunosuppression2. When these patients present with delirium, the infectious differential should remain broad.
ACCEPTED MANUSCRIPT
We highlight the importance of avoiding cognitive biases, or heuristics, which are a source of diagnostic error. Diagnostic errors are estimated to contribute to 10-15% of all medical errors3. Two heuristics are relevant in this case, premature closure and anchoring. Premature closure occurs when clinicians end clinical decision-making early4. This led to the initial diagnosis of migraine headache without considering alternatives.
RI PT
Anchoring occurs when clinicians stick with a diagnosis after the initial impression is formed4. Here, the team continued with a urinary tract infection as the principal etiology of her delirium, thus delaying the diagnosis.
AC C
EP
TE D
M AN U
SC
Recognizing heuristics and having diagnostic “time-outs” may prompt reflection and prevent error5. One feature of this case mitigating against heuristics was recognition that the severity of the patient’s delirium was out of proportion to her intact cognitive baseline and the insult of an otherwise uncomplicated cystitis.
ACCEPTED MANUSCRIPT
References
AC C
EP
TE D
M AN U
SC
RI PT
1. Pappas PG. Cryptococcal infections in non-HIV-infected patients. Trans Am Clin Climatol Assoc. 2013;124:61-79. 2. Barouky R, Badet M, Denis MS, Soubirou JL, Philit F, Guerin C. Inhaled corticosteroids in chronic obstructive pulmonary disease and disseminated aspergillosis. European journal of internal medicine. 2003;14:380-2. 3. Norman GR, Eva KW. Diagnostic error and clinical reasoning. Medical education. 2010;44:94-100. 4. Derauf DD. Cognitive psychology of missed diagnoses. Annals of internal medicine. 2005;142:1026; author reply 5. Trowbridge RL. Twelve tips for teaching avoidance of diagnostic errors. Medical teacher. 2008;30:496-500.