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Cryptococcal meningitis transcending immunological barrier in an immunocompetent patient
G Model INJMS 123 No. of Pages 2
Indian Journal of Medical Specialities xxx (2016) xxx–xxx
Contents lists available at ScienceDirect
Indian Journal of Medical Specialities journal homepage: www.elsevier.com/locate/injms
Case report
Cryptococcal meningitis transcending immunological barrier in an immunocompetent patient S. Mahavar* ,1, M. Gupta, S. Bansal, R. Chandra, S. Kumar, R. Sharma Department of Internal Medicine, SMS Medical College & Associated Group of Hospitals, Jaipur 302004, India
A R T I C L E I N F O
Article history: Received 5 February 2017 Accepted 4 March 2017 Available online xxx Keywords: Cryptococcal meningitis Fungal meningitis Cryptococcus neoformans Mycoses Central nervous system fungal infections Cerebrospinal fluid
A B S T R A C T
Meningitis caused by fungal mycosis Cryptococcus neoformans is normally seen in immunocompromised hosts. However, immunocompetent patients are also susceptible to cryptococcal meningitis. In patients with an intact immune system, cryptococcal meningitis presents with the typical signs and symptoms of meningitis: fever, neck stiffness and headache. Our case report becomes unusual and interesting as here Cryptococcus neoformans is the cause of meningitis in a young immunocompetent male. This report also highlights the importance of culture and a need for thorough microbiological work up of CSF samples even in immunocompetent patients without any known risk factors. So care needs to be focussed on minimising sequelae and side effects of treatment and maximising functional recovery. © 2017 Published by Elsevier, a division of RELX India, Pvt. Ltd on behalf of Indian Journal of Medical Specialities.
1. Introduction Cryptococcal meningitis is caused by infection by the encapsulated yeast, Cryptococcus neoformans. However, infections occur when the fungus is inhaled and spores are spread systemically via the lung [1]. Meningitis is the most common presentation but pneumonia, skin infection, and osteomylitis have also been linked to Cryptococcus neoformans [2]. If intact, the immune system forms a mucus capsule around the fungus to isolate it, thus offering some protection to the host. When the yeast spreads to the brain, in immunocompetent hosts, the encapsulated fungus spur a local granulomatous response and the fungus becomes “walled off” which may appear on computed tomography as a ring enhancing lesion [3]. We report here a rare case of Cryptococcus neoformans as the cause of meningitis in a young immunocompetent male. 2. Case Report A 21 year old male, farmer by occupation, educated till 6th standard, and a resident of a village in Kanpur district, presented to the medical emergency with complaints of low grade fever, backache, intermittent headache which was moderate in intensity
* Corresponding author. E-mail address: [email protected] (S. Mahavar). Postal Address: 18-19, Meena Colony, Emli Phatak, Jaipur, India.
1
for the last 4 days. There was no history of seizures, loss of consciousness, weight loss, chronic cough, tuberculosis, diabetes or any other chronic illness like malignancy, etc. He denied any history of chronic diarrhoea, drug abuse including immunomodulator, steroid, blood transfusion or high risk behaviour. On examination, he was febrile. Pulse rate was 100/ min. Blood pressure was 100/60 mm Hg. His BMI was normal i.e. 22 kg/m2. On auscultation, S1 and S2 were normal, with no murmur appreciable. Respiratory examination revealed a respiratory rate of 18 per min, abdominothoracic in nature with bilateral vesicular breath sounds. On musculoskeletal examination, straight leg raising test was negative. There was no neck rigidity. After two days of admission, fever persisted and the patient developed neck rigidity. Routine investigations revealed a haemoglobin level of 10.3 g%, TLC of 18,700/cumm., with 70% neutrophils, 26% lymphocytes, 3% eosinophils and 1% monocytes. Platelet count was 2,24,000/cumm. Serum sodium was 136 meq/l; Serum potassium 4.5 meq/l; Serum calcium 9.8 meq/l; Blood urea 42 mg/dl; serum creatinine 0.4 mg/ dl. Liver function tests and serum albumin were within normal limit. The chest roentgenogram, abdominal and pelvic ultrasound, CECT head and nerve conduction velocity testing were found to be normal. Bone marrow examination showed a megaloblastic picture with no evidence of any granuloma. Cerebrospinal fluid (CSF) examination revealed 5 cells/dl; mainly lymphocytes; CSF protein 200 mg/dl; CSF glucose 56 mg/ dl (corresponding blood sugar 110 mg/dl). There were no
http://dx.doi.org/10.1016/j.injms.2017.03.002 0976-2884/© 2017 Published by Elsevier, a division of RELX India, Pvt. Ltd on behalf of Indian Journal of Medical Specialities.
Please cite this article in press as: S. Mahavar, et al., Cryptococcal meningitis transcending immunological barrier in an immunocompetent patient, Indian J Med Spec. (2017), http://dx.doi.org/10.1016/j.injms.2017.03.002
G Model INJMS 123 No. of Pages 2
2
S. Mahavar et al. / Indian Journal of Medical Specialities xxx (2016) xxx–xxx
microorganisms on Gram staining and Zeil Neelsen staining. Bacterial cultures were sterile and serum adenosine deaminase levels were normal. However, India ink preparation and the latex agglutination test for Cryptococcus neoformans were positive. The patient was tested for HIV antibodies and antigens twice and was found non reactive on both occasions. CD4 and CD8 counts were found to be normal, thus ruling out immunodeficiency. Patient was started on intravenous Amphotericin-B 0.7 mg/kg/ day for a total period of 14 days, with daily monitoring of serum electrolytes. Patient showed symptomatic improvement in 5– 6 days with decrease in frequency and intensity of fever and headache. After completing the course of amphotericin B, patient became absolutely asymptomatic and repeat CSF examination for Cryptococcus neoformans was negative. He was discharged on oral fluconazole 200 mg BD for 10 weeks. On routine follow up examination patient remained asymptomatic.
many soil types particularly soil that has been enriched by animal and bird droppings. Our patient’s India ink and latex agglutination tests revealed the etiological agent to be Cryptococcus neoformans. CT head was normal. Leptomeningeal enhancement on CT and MRI study secondary to cryptococcal meningitis is an uncommon finding and is negative in 50% of such cases [4]. Brisk response to therapy, negative smear and culture after a short period of antifungal therapy and non requirement of long term antifungal maintenance medication are more commonly seen in cryptococcal meningitis affecting non HIV infected patients [5]. In conclusion, high degree of clinical suspicion even in immunocompetent patients, with prominent clinical signs and symptoms of meningitis, as raised intracranial tension, reactive CSF, meticulous microbiological workup of the previous sample of CSF can help in early diagnosis of this infection and can go long way in reducing the morbidity and mortality associated with this disease.
3. Discussion References Cryptococcus neoformans is yeast, most commonly infecting the central nervous system. Resistance to infection is primarily cell mediated immunity. Therefore, most cases of cryptococcal meningitis occur in patients with conditions that weaken this system, such as HIV infection. Cryptococcus neoformans has been sporadically reported in HIV negative patients in the background of organ transplant and chemotherapy related immunosuppression, reticuloendothelial malignancy, corticosteroid therapy and sarcoidosis. Occasionally no underlying cause can be detected. In many regions, up to 20% of cases of Cryptococcosis occur in clinically non-immunocompromised or phenotypically “normal” patients [6]. Our patient was a farmer and belonged to a poor socioeconomic status; so he might get this fungal infection while farming as it is commonly found in decaying organic matter and in
[1] Baddley JW, Dismukes WE. Cryptococcosis. In: Kauffman CA, Pappas PG, Sobel JD, Dismukers WE, editors. Essentials of Clinical Mycology. 2nd ed. New York: Springer; 2011. p. 207–26. [2] Kiertiburanakul S, Wirojtananugoon S, Pracharktam R, et al. Cryptococcosis in human immunodeficiency virus-negative patients. Int J Infect Dis 2006;10 (1):72–8. [3] Jones GA, Nathwani D. Cryptococcal meningitis. Br J Hosp Med 1995;54:439–45. [4] Goldman JD, Vollmer EM, Luks AM. Cryptococcosis in the immunocompetent patient. Respir Care 2010;55:1499–503. [5] Butler WT, Alling DW, Spickard AS, Utz JP. Diagnostic and prognostic value of clinical and laboratory findings in cryptococcal meningitis. N Engl J Med 1964;270:59–67. [6] Pappas PG, Perfect JR, Cloud GA, et al. Cryptococcosis in human immunodeficiency virus-negative patients in the era of effective azole therapy. Clin Infect Dis 2001;33(5):690–9.
Please cite this article in press as: S. Mahavar, et al., Cryptococcal meningitis transcending immunological barrier in an immunocompetent patient, Indian J Med Spec. (2017), http://dx.doi.org/10.1016/j.injms.2017.03.002
Indian Journal of Medical Specialities xxx (2016) xxx–xxx
Contents lists available at ScienceDirect
Indian Journal of Medical Specialities journal homepage: www.elsevier.com/locate/injms
Case report
Cryptococcal meningitis transcending immunological barrier in an immunocompetent patient S. Mahavar* ,1, M. Gupta, S. Bansal, R. Chandra, S. Kumar, R. Sharma Department of Internal Medicine, SMS Medical College & Associated Group of Hospitals, Jaipur 302004, India
A R T I C L E I N F O
Article history: Received 5 February 2017 Accepted 4 March 2017 Available online xxx Keywords: Cryptococcal meningitis Fungal meningitis Cryptococcus neoformans Mycoses Central nervous system fungal infections Cerebrospinal fluid
A B S T R A C T
Meningitis caused by fungal mycosis Cryptococcus neoformans is normally seen in immunocompromised hosts. However, immunocompetent patients are also susceptible to cryptococcal meningitis. In patients with an intact immune system, cryptococcal meningitis presents with the typical signs and symptoms of meningitis: fever, neck stiffness and headache. Our case report becomes unusual and interesting as here Cryptococcus neoformans is the cause of meningitis in a young immunocompetent male. This report also highlights the importance of culture and a need for thorough microbiological work up of CSF samples even in immunocompetent patients without any known risk factors. So care needs to be focussed on minimising sequelae and side effects of treatment and maximising functional recovery. © 2017 Published by Elsevier, a division of RELX India, Pvt. Ltd on behalf of Indian Journal of Medical Specialities.
1. Introduction Cryptococcal meningitis is caused by infection by the encapsulated yeast, Cryptococcus neoformans. However, infections occur when the fungus is inhaled and spores are spread systemically via the lung [1]. Meningitis is the most common presentation but pneumonia, skin infection, and osteomylitis have also been linked to Cryptococcus neoformans [2]. If intact, the immune system forms a mucus capsule around the fungus to isolate it, thus offering some protection to the host. When the yeast spreads to the brain, in immunocompetent hosts, the encapsulated fungus spur a local granulomatous response and the fungus becomes “walled off” which may appear on computed tomography as a ring enhancing lesion [3]. We report here a rare case of Cryptococcus neoformans as the cause of meningitis in a young immunocompetent male. 2. Case Report A 21 year old male, farmer by occupation, educated till 6th standard, and a resident of a village in Kanpur district, presented to the medical emergency with complaints of low grade fever, backache, intermittent headache which was moderate in intensity
* Corresponding author. E-mail address: [email protected] (S. Mahavar). Postal Address: 18-19, Meena Colony, Emli Phatak, Jaipur, India.
1
for the last 4 days. There was no history of seizures, loss of consciousness, weight loss, chronic cough, tuberculosis, diabetes or any other chronic illness like malignancy, etc. He denied any history of chronic diarrhoea, drug abuse including immunomodulator, steroid, blood transfusion or high risk behaviour. On examination, he was febrile. Pulse rate was 100/ min. Blood pressure was 100/60 mm Hg. His BMI was normal i.e. 22 kg/m2. On auscultation, S1 and S2 were normal, with no murmur appreciable. Respiratory examination revealed a respiratory rate of 18 per min, abdominothoracic in nature with bilateral vesicular breath sounds. On musculoskeletal examination, straight leg raising test was negative. There was no neck rigidity. After two days of admission, fever persisted and the patient developed neck rigidity. Routine investigations revealed a haemoglobin level of 10.3 g%, TLC of 18,700/cumm., with 70% neutrophils, 26% lymphocytes, 3% eosinophils and 1% monocytes. Platelet count was 2,24,000/cumm. Serum sodium was 136 meq/l; Serum potassium 4.5 meq/l; Serum calcium 9.8 meq/l; Blood urea 42 mg/dl; serum creatinine 0.4 mg/ dl. Liver function tests and serum albumin were within normal limit. The chest roentgenogram, abdominal and pelvic ultrasound, CECT head and nerve conduction velocity testing were found to be normal. Bone marrow examination showed a megaloblastic picture with no evidence of any granuloma. Cerebrospinal fluid (CSF) examination revealed 5 cells/dl; mainly lymphocytes; CSF protein 200 mg/dl; CSF glucose 56 mg/ dl (corresponding blood sugar 110 mg/dl). There were no
http://dx.doi.org/10.1016/j.injms.2017.03.002 0976-2884/© 2017 Published by Elsevier, a division of RELX India, Pvt. Ltd on behalf of Indian Journal of Medical Specialities.
Please cite this article in press as: S. Mahavar, et al., Cryptococcal meningitis transcending immunological barrier in an immunocompetent patient, Indian J Med Spec. (2017), http://dx.doi.org/10.1016/j.injms.2017.03.002
G Model INJMS 123 No. of Pages 2
2
S. Mahavar et al. / Indian Journal of Medical Specialities xxx (2016) xxx–xxx
microorganisms on Gram staining and Zeil Neelsen staining. Bacterial cultures were sterile and serum adenosine deaminase levels were normal. However, India ink preparation and the latex agglutination test for Cryptococcus neoformans were positive. The patient was tested for HIV antibodies and antigens twice and was found non reactive on both occasions. CD4 and CD8 counts were found to be normal, thus ruling out immunodeficiency. Patient was started on intravenous Amphotericin-B 0.7 mg/kg/ day for a total period of 14 days, with daily monitoring of serum electrolytes. Patient showed symptomatic improvement in 5– 6 days with decrease in frequency and intensity of fever and headache. After completing the course of amphotericin B, patient became absolutely asymptomatic and repeat CSF examination for Cryptococcus neoformans was negative. He was discharged on oral fluconazole 200 mg BD for 10 weeks. On routine follow up examination patient remained asymptomatic.
many soil types particularly soil that has been enriched by animal and bird droppings. Our patient’s India ink and latex agglutination tests revealed the etiological agent to be Cryptococcus neoformans. CT head was normal. Leptomeningeal enhancement on CT and MRI study secondary to cryptococcal meningitis is an uncommon finding and is negative in 50% of such cases [4]. Brisk response to therapy, negative smear and culture after a short period of antifungal therapy and non requirement of long term antifungal maintenance medication are more commonly seen in cryptococcal meningitis affecting non HIV infected patients [5]. In conclusion, high degree of clinical suspicion even in immunocompetent patients, with prominent clinical signs and symptoms of meningitis, as raised intracranial tension, reactive CSF, meticulous microbiological workup of the previous sample of CSF can help in early diagnosis of this infection and can go long way in reducing the morbidity and mortality associated with this disease.
3. Discussion References Cryptococcus neoformans is yeast, most commonly infecting the central nervous system. Resistance to infection is primarily cell mediated immunity. Therefore, most cases of cryptococcal meningitis occur in patients with conditions that weaken this system, such as HIV infection. Cryptococcus neoformans has been sporadically reported in HIV negative patients in the background of organ transplant and chemotherapy related immunosuppression, reticuloendothelial malignancy, corticosteroid therapy and sarcoidosis. Occasionally no underlying cause can be detected. In many regions, up to 20% of cases of Cryptococcosis occur in clinically non-immunocompromised or phenotypically “normal” patients [6]. Our patient was a farmer and belonged to a poor socioeconomic status; so he might get this fungal infection while farming as it is commonly found in decaying organic matter and in
[1] Baddley JW, Dismukes WE. Cryptococcosis. In: Kauffman CA, Pappas PG, Sobel JD, Dismukers WE, editors. Essentials of Clinical Mycology. 2nd ed. New York: Springer; 2011. p. 207–26. [2] Kiertiburanakul S, Wirojtananugoon S, Pracharktam R, et al. Cryptococcosis in human immunodeficiency virus-negative patients. Int J Infect Dis 2006;10 (1):72–8. [3] Jones GA, Nathwani D. Cryptococcal meningitis. Br J Hosp Med 1995;54:439–45. [4] Goldman JD, Vollmer EM, Luks AM. Cryptococcosis in the immunocompetent patient. Respir Care 2010;55:1499–503. [5] Butler WT, Alling DW, Spickard AS, Utz JP. Diagnostic and prognostic value of clinical and laboratory findings in cryptococcal meningitis. N Engl J Med 1964;270:59–67. [6] Pappas PG, Perfect JR, Cloud GA, et al. Cryptococcosis in human immunodeficiency virus-negative patients in the era of effective azole therapy. Clin Infect Dis 2001;33(5):690–9.
Please cite this article in press as: S. Mahavar, et al., Cryptococcal meningitis transcending immunological barrier in an immunocompetent patient, Indian J Med Spec. (2017), http://dx.doi.org/10.1016/j.injms.2017.03.002