- Email: [email protected]
Pneumocystis pneumonia revisited: Delayed diagnosis in an HIV infected individual with high blood and low lung CD4 T cell counts
Journal of Infection (2006) 53, e159ee160
www.elsevierhealth.com/journals/jinf
CASE REPORT
Pneumocystis pneumonia revisited: Delayed diagnosis in an HIV infected individual with high blood and low lung CD4 T cell counts Ben Killingley*, Ronan Breen, Marc Lipman, Margaret Johnson The Royal Free Centre for HIV Medicine, Royal Free Hospital, London, United Kingdom Accepted 4 November 2005 Available online 3 January 2006
KEYWORDS Pneumocystis pneumonia; CD4 count; Bronchoalveolar lavage
Summary The peripheral blood CD4 count is a useful marker of immunological status in HIV infection. However, it makes up only 1% of total body CD4 cells [Parslow T. Lymphocytes and lymphoid tissue. In: Stites D, Terr A, Parslow D, editors. Basic and clinical immunology. Appleton and Lange; 1994. p. 22e40.] has a wide intra- and inter-individual variability [Turner BJ, Hecht FM, Ismail RB. CD4þ Tlymphocyte measures in the treatment of individuals infected with human immunodeficiency virus type 1. A review for clinical practitioners. Arch Intern Med 1994;154:1561e73.] and CD4 cell pathology is just one of the immune defects caused by HIV [Fauci S. Multifactorial nature of human immunodeficiency virus disease. Science 1993;262:1011e8.]. Thus a given value should always be interpreted within a specific clinical context. We describe an individual with Pneumocystis pneumonia (PCP) who was reviewed by HIV medical services several times before the correct diagnosis was made. On each occasion the possibility of PCP was discounted as he had a well-preserved blood CD4 count. Subsequent examination of his pulmonary T-lymphocyte subsets revealed marked CD4 lymphopenia. ª 2005 The British Infection Society. Published by Elsevier Ltd. All rights reserved.
A 36-year-old asymptomatic Caucasian homosexual male was diagnosed with HIV infection in August 2003. In June 2004 he had a CD4 count of * Corresponding author. c/o Dr Marc Lipman’s secretary, Department of Thoracic Medicine, Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG, United Kingdom. Tel.: þ44 0207 941 1831; fax: þ44 0207 941 1830. E-mail address: [email protected] (B. Killingley).
425 cells/ml (18% of total lymphocytes) and was well. He remained treatment na€ıve and attended in January 2005 for routine follow up complaining of a sore throat. Oral thrush and an enlarged cervical lymph node were noted. His blood CD4 count was 360 cells/ml (20%). Amoxycillin and nystatin mouth wash were prescribed. Four weeks later he re-presented complaining of a 4-day history of fever, breathlessness and malaise. On
0163-4453/$30 ª 2005 The British Infection Society. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jinf.2005.11.004
e160 examination no abnormalities were noted. He was reassured and discharged without specific therapy. He revisited the clinic 4 days later with progressive breathlessness, fatigue and headache. Again, examination detected no abnormality and given his well-maintained blood CD4 count he was not investigated further. He presented to our centre 2 days after this with worsening symptoms. Oral thrush was again noted. An arterial blood gas taken at rest with the patient breathing air revealed hypoxemia (pH 7.41, PaCO2 4.8 kPa and PaO2 6.8 kPa). His chest radiograph showed mild bilateral air space shadowing. A clinical diagnosis of PCP was suspected and he was started on high dose co-trimoxazole, broadspectrum antibiotics and steroids. Bronchoalveolar lavage (BAL) was performed. Using flow cytometry, absolute leucocyte and lymphocyte numbers, as well as the percentages of CD3þ, CD4þ and CD8þ T-cells were determined using CD45, CD4 and CD8 antibodies. This demonstrated an elevated BAL lymphocyte percentage of 43% but severe CD4 lymphopenia with a reduced CD4/CD8 lymphocyte ratio amongst CD3þ lymphocytes of 0.02 (normal value for HIV negative > 1).1 Cytological examination confirmed the presence of Pneumocystis jiroveci.
Discussion As a population-based measure, the blood CD4 count has been shown to be one of the most useful surrogate markers in HIV disease.2 However, as our case demonstrates, using this without reference to clinical status to predict individual risk of opportunistic infections can be misleading. The patient described had risk factors and symptoms consistent with PCP, yet these were ignored, we feel, largely because of his high blood CD4 count. While PCP is 10 times more likely in subjects with a blood CD4 below 200 cells/ml; it is also seen at higher
B. Killingley et al. counts, often in association with a history of recurrent fever, night sweats, weight loss or oral thrush.3 Our patient had candidiasis despite a blood CD4 count of 360. Impaired local immunity was confirmed by his pulmonary T cell subset analysis which revealed a profound BAL CD4 lymphopenia (one-tenth of that in his peripheral blood count). Measuring cellular responses at the typical site of opportunistic infection can predict the presence of disease. For example, analysis of BAL fluid from patients with PCP reveals very low CD4/CD8 ratios.4,5 Thus investigation of local immunity may be helpful in cases where there is some discrepancy between clinical findings and standard laboratory results such as blood CD4 count. Examination at the site of disease also enables one to obtain diagnostic pathology samples. In our case, BAL confirmed the clinical suspicion of PCP as well as demonstrating the gross impairment of pulmonary immunity which led to this.
References 1. Young KR, Rankin JA, Naegel GP, Paul ES, Reynolds HY. Bronchoalveolar lavage cells and proteins in patients with the acquired immunodeficiency syndrome. Ann Intern Med 1985;103:522e33. 2. Rathbun R. Surrogate markers for assessing treatment response in HIV disease. Ann Pharmacother 1993;27:450e5. 3. Stansell JD, Osmond DH, Charlbois E, LaVange L, Wallace JM, Alexander BV, et al. Predictors of Pneumocystis carini pneumonia in HIV-infected persons. Pulmonary Complications of HIV Infection Study Group. Am J Respir Crit Care Med 1997;155:60e6. 4. Wallace JM, Barbers RG, Oishi JS, Prince H. Cellular and T-lymphocyte subpopulation profiles in bronchoalveolar lavage fluid from patients with acquired immunodeficiency syndrome and pneumonitis. Am Rev Respir Dis 1984;130: 786e90. 5. Venet A, Clavel F, Israe ¨l-Biet D, Rouzloux C, Dennewald G, Stern M, et al. Lung in acquired immune deficiency syndrome: infectious and immunological status assessed by bronchoalveolar lavage. Bull Eur Physiopathol Respir 1985;21:535e43.
www.elsevierhealth.com/journals/jinf
CASE REPORT
Pneumocystis pneumonia revisited: Delayed diagnosis in an HIV infected individual with high blood and low lung CD4 T cell counts Ben Killingley*, Ronan Breen, Marc Lipman, Margaret Johnson The Royal Free Centre for HIV Medicine, Royal Free Hospital, London, United Kingdom Accepted 4 November 2005 Available online 3 January 2006
KEYWORDS Pneumocystis pneumonia; CD4 count; Bronchoalveolar lavage
Summary The peripheral blood CD4 count is a useful marker of immunological status in HIV infection. However, it makes up only 1% of total body CD4 cells [Parslow T. Lymphocytes and lymphoid tissue. In: Stites D, Terr A, Parslow D, editors. Basic and clinical immunology. Appleton and Lange; 1994. p. 22e40.] has a wide intra- and inter-individual variability [Turner BJ, Hecht FM, Ismail RB. CD4þ Tlymphocyte measures in the treatment of individuals infected with human immunodeficiency virus type 1. A review for clinical practitioners. Arch Intern Med 1994;154:1561e73.] and CD4 cell pathology is just one of the immune defects caused by HIV [Fauci S. Multifactorial nature of human immunodeficiency virus disease. Science 1993;262:1011e8.]. Thus a given value should always be interpreted within a specific clinical context. We describe an individual with Pneumocystis pneumonia (PCP) who was reviewed by HIV medical services several times before the correct diagnosis was made. On each occasion the possibility of PCP was discounted as he had a well-preserved blood CD4 count. Subsequent examination of his pulmonary T-lymphocyte subsets revealed marked CD4 lymphopenia. ª 2005 The British Infection Society. Published by Elsevier Ltd. All rights reserved.
A 36-year-old asymptomatic Caucasian homosexual male was diagnosed with HIV infection in August 2003. In June 2004 he had a CD4 count of * Corresponding author. c/o Dr Marc Lipman’s secretary, Department of Thoracic Medicine, Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG, United Kingdom. Tel.: þ44 0207 941 1831; fax: þ44 0207 941 1830. E-mail address: [email protected] (B. Killingley).
425 cells/ml (18% of total lymphocytes) and was well. He remained treatment na€ıve and attended in January 2005 for routine follow up complaining of a sore throat. Oral thrush and an enlarged cervical lymph node were noted. His blood CD4 count was 360 cells/ml (20%). Amoxycillin and nystatin mouth wash were prescribed. Four weeks later he re-presented complaining of a 4-day history of fever, breathlessness and malaise. On
0163-4453/$30 ª 2005 The British Infection Society. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jinf.2005.11.004
e160 examination no abnormalities were noted. He was reassured and discharged without specific therapy. He revisited the clinic 4 days later with progressive breathlessness, fatigue and headache. Again, examination detected no abnormality and given his well-maintained blood CD4 count he was not investigated further. He presented to our centre 2 days after this with worsening symptoms. Oral thrush was again noted. An arterial blood gas taken at rest with the patient breathing air revealed hypoxemia (pH 7.41, PaCO2 4.8 kPa and PaO2 6.8 kPa). His chest radiograph showed mild bilateral air space shadowing. A clinical diagnosis of PCP was suspected and he was started on high dose co-trimoxazole, broadspectrum antibiotics and steroids. Bronchoalveolar lavage (BAL) was performed. Using flow cytometry, absolute leucocyte and lymphocyte numbers, as well as the percentages of CD3þ, CD4þ and CD8þ T-cells were determined using CD45, CD4 and CD8 antibodies. This demonstrated an elevated BAL lymphocyte percentage of 43% but severe CD4 lymphopenia with a reduced CD4/CD8 lymphocyte ratio amongst CD3þ lymphocytes of 0.02 (normal value for HIV negative > 1).1 Cytological examination confirmed the presence of Pneumocystis jiroveci.
Discussion As a population-based measure, the blood CD4 count has been shown to be one of the most useful surrogate markers in HIV disease.2 However, as our case demonstrates, using this without reference to clinical status to predict individual risk of opportunistic infections can be misleading. The patient described had risk factors and symptoms consistent with PCP, yet these were ignored, we feel, largely because of his high blood CD4 count. While PCP is 10 times more likely in subjects with a blood CD4 below 200 cells/ml; it is also seen at higher
B. Killingley et al. counts, often in association with a history of recurrent fever, night sweats, weight loss or oral thrush.3 Our patient had candidiasis despite a blood CD4 count of 360. Impaired local immunity was confirmed by his pulmonary T cell subset analysis which revealed a profound BAL CD4 lymphopenia (one-tenth of that in his peripheral blood count). Measuring cellular responses at the typical site of opportunistic infection can predict the presence of disease. For example, analysis of BAL fluid from patients with PCP reveals very low CD4/CD8 ratios.4,5 Thus investigation of local immunity may be helpful in cases where there is some discrepancy between clinical findings and standard laboratory results such as blood CD4 count. Examination at the site of disease also enables one to obtain diagnostic pathology samples. In our case, BAL confirmed the clinical suspicion of PCP as well as demonstrating the gross impairment of pulmonary immunity which led to this.
References 1. Young KR, Rankin JA, Naegel GP, Paul ES, Reynolds HY. Bronchoalveolar lavage cells and proteins in patients with the acquired immunodeficiency syndrome. Ann Intern Med 1985;103:522e33. 2. Rathbun R. Surrogate markers for assessing treatment response in HIV disease. Ann Pharmacother 1993;27:450e5. 3. Stansell JD, Osmond DH, Charlbois E, LaVange L, Wallace JM, Alexander BV, et al. Predictors of Pneumocystis carini pneumonia in HIV-infected persons. Pulmonary Complications of HIV Infection Study Group. Am J Respir Crit Care Med 1997;155:60e6. 4. Wallace JM, Barbers RG, Oishi JS, Prince H. Cellular and T-lymphocyte subpopulation profiles in bronchoalveolar lavage fluid from patients with acquired immunodeficiency syndrome and pneumonitis. Am Rev Respir Dis 1984;130: 786e90. 5. Venet A, Clavel F, Israe ¨l-Biet D, Rouzloux C, Dennewald G, Stern M, et al. Lung in acquired immune deficiency syndrome: infectious and immunological status assessed by bronchoalveolar lavage. Bull Eur Physiopathol Respir 1985;21:535e43.