Post by LymeEnigma on Jun 1, 2008 18:05:38 GMT -8
Chronic Chlamydia pneumoniae Infection: A Treatable
Cause of Chronic Fatigue Syndrome
Chronic fatigue syndrome (CFS), an elusive and controversial
illness, has been a difficult management problem for clinicians. A
number of infectious agents have been implicated as the cause of
CFS, although consistent and compelling evidence is still lacking
[1]. Few well-documented infections could cause persistent inflammatory
reaction leading to the symptomatology of CFS [2, 3].
Chlamydia pneumoniae is a common cause of respiratory infection
and has been demonstrated within plaques of the coronary arteries
years after initial infection [4]. Recently demonstrated replication
of C. pneumoniae within human macrophages and endothelial cells
[5] and a potent inducer of proinflammatory cytokines, such as
TNF-a and IL-1 [6], raised the possibility of chronic infection that
leads to persistent inflammatory response. A previous study failed
to demonstrate elevated titers of antibody to C. pneumoniae in 50
patients with CFS [7], although fatigue is a common symptom
reported by patients for whom sputum cultures are persistently
positive for C. pneumoniae [8].
Over the past 3 years, we encountered 10 of 171 patients with
symptoms of chronic fatigue who had elevated titers of antibody to
C. pneumoniae long after initial respiratory infection. Most patients
had favorable clinical and serological responses to a 1- to
2-months course of azithromycin therapy, although relapse was
common. The clinical symptoms of and titers of antibody to
C. pneumoniae for our 10 patients over the course of treatment are
summarized in table 1.
A 32-year-old female developed pharyngitis, cough, cervical
lymphadenopathy, low-grade fevers, severe fatigue, and myalgia
in January 1993 (patient 1). A medical evaluation showed a normal
complete blood cell count and normal results of thyroid function
test and serum chemistry analysis. IgG antibody to Epstein-Barr
virus was positive. During the following 3 years, the patient had
frequent relapses of severe fatigue, diffuse myalgia, night sweats,
pharyngitis, headaches, insomnia, and painful, swollen cervical
lymph nodes (especially following exertion) that resulted in total
disability.
Repeated evaluation in August 1996 revealed small nontender
anterior cervical lymph nodes. Results of routine laboratory studies
and serologies for several viruses were unremarkable. The titer of
IgG antibody to C. pneumoniae was 1:256. Magnesium sulfate
injections and salt loading failed to alleviate symptoms. One
month later, when the patient was having increasing fatigue, the
titer of antibody to C. pneumoniae rose to 1:1,024. Azithromycin
(500 mg) was administered by mouth the first day, followed by
250-mg doses for the subsequent 4 days. The patient’s condition
improved by day 3 of therapy, although her symptoms relapsed 12
days later.
Similar improvement and relapse followed a second 5-day
course of azithromycin treatment. Thereafter, 250 mg of azithromycin
was given daily for a total of 30 days; this therapeutic
course resulted in a marked decrease in her symptoms. She returned
to full-time work as a manager at her company and maintained
an energy level of 8–9 of 10 for the next 2 years. Follow-up
antibody titers are shown in table 1.
Most of our patients had symptoms referable to the upper or
lower respiratory tracts, but radiographic studies of the sinuses
and chest were unremarkable. Seven of the 10 patients had high
levels of total antibody to C. pneumoniae 0.5 to 3 years following
an episode of symptomatic respiratory infection. Three
patients had low antibody titers of 1:128 and 1:256, but their
symptoms did decrease with antibiotic therapy. Low or absent
antibody response to C. pneumoniae was documented for patients
with persistently positive respiratory cultures [8]. Comparatively,
the mean titers 6 SD for 90 controls were 32 6 36
(range, ,8 or 4 to 256). Only two of 19 fatigued patients with
reciprocal titers between 32 to 64 responded to 1 month of
azithromycin treatment (data not shown).
The spontaneous rise of titers for several patients correlated with
an increased severity of fatigue and a concomitant increase in
respiratory symptoms. This observation suggests that relapses of
symptoms could be due to persistent infection with periodic reactivation
rather than reinfection. All of the patients with relapses
responded to additional azithromycin treatment.
C. pneumoniae is a common copathogen in patients with respiratory
infection [9]. Symptoms of acute purulent sinusitis and mastoiditis
in patients 7 and 8, respectively, did decrease after 2–3 weeks of
ceftriaxone treatment, but severe fatigue persisted for the next 2 years;
fatigue resolved only after 2 months of azithromycin treatment.
Recently, Falck et al. [10] found C. pneumoniae DNA in throat
secretions from 10 of 11 patients with chronic rhinorrhea, fatigue,
and throat biopsies positive for C. pneumoniae. Seventy percent of
the patients had elevated titers of IgG (1:512) or IgA (1:128)
antibody. All of their patients responded to prolonged courses of
macrolide therapy, but symptoms frequently recurred.
Collectively, these results suggest that C. pneumoniae is an
uncommon yet treatable cause of chronic fatigue. The sensitivity,
specificity, and interlaboratory variability of the DNA test will
need to be better defined. Although seemingly less sensitive and
prone to interlaboratory variation, the widely available microimmunofluorescence
test may be a practical screening test for this
entity before throat biopsy is performed.
John K. S. Chia and Laura Y. Chia
Torrance Memorial Medical Center, Torrance, California
References
1. Fukuda K, Straus SE, Hickie I, et al. The chronic fatigue syndrome: a
comprehensive approach to its definition and study. Ann Intern Med
1994;121:953–9.
2. Lerner MA, Zervos M, Dworkin HJ, et al. New cardiomyopathy: pilot
study of intravenous ganciclovir in a subset of chronic fatigue syndrome.
Infect Dis Clin Prac 1997;6:110 –7.
3. Jacobson K, Daly JS, Thorne M, Mcintosh K. Chronic parvovirus B19
infection resulting in chronic fatigue syndrome: case history and review.
Clin Infect Dis 1997;24:1048 –51.
4. Thom DH, Grayston JT, Siscovick DS, Wang SP, Weiss NS, Daling JR.
Association of prior infection with Chlamydia pneumoniae and angiographically
demonstrated coronary artery disease. JAMA 1992;268:68–72.
5. Gaydos CA, Summersgill JT, Sahney NN, Ramirez JA, Quinn TC.
Replication of C. pneumoniae in vitro in human macrophages, endothelial
cells, and aortic artery smooth cells. Infect Immun 1996;
64:1614 –20.
6. Leinonen M, Toivanen P, Tenkanen L, Manttari M, Saikku P. Chlamydia
pneumoniae and metabolic syndrome as a risk factor for coronary events
in the Helsinki heart study [abstract no L-18]. In: Program and abstracts
of the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy
(San Diego). Washington, DC: American Society for Microbiology,
1998.
7. Komaroff AL, Wang SP, Lee J, Grayston JT. No association of chronic
Chlamydia pneumoniae infection with chronic fatigue syndrome. J Infect
Dis 1992;165:184.
8. Grayston JT. Infection caused by Chlamydia pneumoniae strain TWAR.
Clin Infect Dis 1992;15:757– 63.
9. Falck G, Gnarpe J, Gnarpe H. Prevalence of Chlamydia pneumoniae in
healthy children and in children with respiratory tract infections. Pediatr
Infect Dis J 1997;16:549 –54.
10. Falck G, Engstrand I, Gnarpe J, Gnarpe H. Chlamydia pneumoniae and
chronic rhinitis [abstract no L-99]. In: Program and abstracts of the 38th
Interscience Conference on Antimicrobial Agents and Chemotherapy
(San Diego). Washington, DC: American Society for Microbiology,
1998.
www.journals.uchicago.edu/doi/pdf/10.1086/520248
p. 452-3
Cause of Chronic Fatigue Syndrome
Chronic fatigue syndrome (CFS), an elusive and controversial
illness, has been a difficult management problem for clinicians. A
number of infectious agents have been implicated as the cause of
CFS, although consistent and compelling evidence is still lacking
[1]. Few well-documented infections could cause persistent inflammatory
reaction leading to the symptomatology of CFS [2, 3].
Chlamydia pneumoniae is a common cause of respiratory infection
and has been demonstrated within plaques of the coronary arteries
years after initial infection [4]. Recently demonstrated replication
of C. pneumoniae within human macrophages and endothelial cells
[5] and a potent inducer of proinflammatory cytokines, such as
TNF-a and IL-1 [6], raised the possibility of chronic infection that
leads to persistent inflammatory response. A previous study failed
to demonstrate elevated titers of antibody to C. pneumoniae in 50
patients with CFS [7], although fatigue is a common symptom
reported by patients for whom sputum cultures are persistently
positive for C. pneumoniae [8].
Over the past 3 years, we encountered 10 of 171 patients with
symptoms of chronic fatigue who had elevated titers of antibody to
C. pneumoniae long after initial respiratory infection. Most patients
had favorable clinical and serological responses to a 1- to
2-months course of azithromycin therapy, although relapse was
common. The clinical symptoms of and titers of antibody to
C. pneumoniae for our 10 patients over the course of treatment are
summarized in table 1.
A 32-year-old female developed pharyngitis, cough, cervical
lymphadenopathy, low-grade fevers, severe fatigue, and myalgia
in January 1993 (patient 1). A medical evaluation showed a normal
complete blood cell count and normal results of thyroid function
test and serum chemistry analysis. IgG antibody to Epstein-Barr
virus was positive. During the following 3 years, the patient had
frequent relapses of severe fatigue, diffuse myalgia, night sweats,
pharyngitis, headaches, insomnia, and painful, swollen cervical
lymph nodes (especially following exertion) that resulted in total
disability.
Repeated evaluation in August 1996 revealed small nontender
anterior cervical lymph nodes. Results of routine laboratory studies
and serologies for several viruses were unremarkable. The titer of
IgG antibody to C. pneumoniae was 1:256. Magnesium sulfate
injections and salt loading failed to alleviate symptoms. One
month later, when the patient was having increasing fatigue, the
titer of antibody to C. pneumoniae rose to 1:1,024. Azithromycin
(500 mg) was administered by mouth the first day, followed by
250-mg doses for the subsequent 4 days. The patient’s condition
improved by day 3 of therapy, although her symptoms relapsed 12
days later.
Similar improvement and relapse followed a second 5-day
course of azithromycin treatment. Thereafter, 250 mg of azithromycin
was given daily for a total of 30 days; this therapeutic
course resulted in a marked decrease in her symptoms. She returned
to full-time work as a manager at her company and maintained
an energy level of 8–9 of 10 for the next 2 years. Follow-up
antibody titers are shown in table 1.
Most of our patients had symptoms referable to the upper or
lower respiratory tracts, but radiographic studies of the sinuses
and chest were unremarkable. Seven of the 10 patients had high
levels of total antibody to C. pneumoniae 0.5 to 3 years following
an episode of symptomatic respiratory infection. Three
patients had low antibody titers of 1:128 and 1:256, but their
symptoms did decrease with antibiotic therapy. Low or absent
antibody response to C. pneumoniae was documented for patients
with persistently positive respiratory cultures [8]. Comparatively,
the mean titers 6 SD for 90 controls were 32 6 36
(range, ,8 or 4 to 256). Only two of 19 fatigued patients with
reciprocal titers between 32 to 64 responded to 1 month of
azithromycin treatment (data not shown).
The spontaneous rise of titers for several patients correlated with
an increased severity of fatigue and a concomitant increase in
respiratory symptoms. This observation suggests that relapses of
symptoms could be due to persistent infection with periodic reactivation
rather than reinfection. All of the patients with relapses
responded to additional azithromycin treatment.
C. pneumoniae is a common copathogen in patients with respiratory
infection [9]. Symptoms of acute purulent sinusitis and mastoiditis
in patients 7 and 8, respectively, did decrease after 2–3 weeks of
ceftriaxone treatment, but severe fatigue persisted for the next 2 years;
fatigue resolved only after 2 months of azithromycin treatment.
Recently, Falck et al. [10] found C. pneumoniae DNA in throat
secretions from 10 of 11 patients with chronic rhinorrhea, fatigue,
and throat biopsies positive for C. pneumoniae. Seventy percent of
the patients had elevated titers of IgG (1:512) or IgA (1:128)
antibody. All of their patients responded to prolonged courses of
macrolide therapy, but symptoms frequently recurred.
Collectively, these results suggest that C. pneumoniae is an
uncommon yet treatable cause of chronic fatigue. The sensitivity,
specificity, and interlaboratory variability of the DNA test will
need to be better defined. Although seemingly less sensitive and
prone to interlaboratory variation, the widely available microimmunofluorescence
test may be a practical screening test for this
entity before throat biopsy is performed.
John K. S. Chia and Laura Y. Chia
Torrance Memorial Medical Center, Torrance, California
References
1. Fukuda K, Straus SE, Hickie I, et al. The chronic fatigue syndrome: a
comprehensive approach to its definition and study. Ann Intern Med
1994;121:953–9.
2. Lerner MA, Zervos M, Dworkin HJ, et al. New cardiomyopathy: pilot
study of intravenous ganciclovir in a subset of chronic fatigue syndrome.
Infect Dis Clin Prac 1997;6:110 –7.
3. Jacobson K, Daly JS, Thorne M, Mcintosh K. Chronic parvovirus B19
infection resulting in chronic fatigue syndrome: case history and review.
Clin Infect Dis 1997;24:1048 –51.
4. Thom DH, Grayston JT, Siscovick DS, Wang SP, Weiss NS, Daling JR.
Association of prior infection with Chlamydia pneumoniae and angiographically
demonstrated coronary artery disease. JAMA 1992;268:68–72.
5. Gaydos CA, Summersgill JT, Sahney NN, Ramirez JA, Quinn TC.
Replication of C. pneumoniae in vitro in human macrophages, endothelial
cells, and aortic artery smooth cells. Infect Immun 1996;
64:1614 –20.
6. Leinonen M, Toivanen P, Tenkanen L, Manttari M, Saikku P. Chlamydia
pneumoniae and metabolic syndrome as a risk factor for coronary events
in the Helsinki heart study [abstract no L-18]. In: Program and abstracts
of the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy
(San Diego). Washington, DC: American Society for Microbiology,
1998.
7. Komaroff AL, Wang SP, Lee J, Grayston JT. No association of chronic
Chlamydia pneumoniae infection with chronic fatigue syndrome. J Infect
Dis 1992;165:184.
8. Grayston JT. Infection caused by Chlamydia pneumoniae strain TWAR.
Clin Infect Dis 1992;15:757– 63.
9. Falck G, Gnarpe J, Gnarpe H. Prevalence of Chlamydia pneumoniae in
healthy children and in children with respiratory tract infections. Pediatr
Infect Dis J 1997;16:549 –54.
10. Falck G, Engstrand I, Gnarpe J, Gnarpe H. Chlamydia pneumoniae and
chronic rhinitis [abstract no L-99]. In: Program and abstracts of the 38th
Interscience Conference on Antimicrobial Agents and Chemotherapy
(San Diego). Washington, DC: American Society for Microbiology,
1998.
www.journals.uchicago.edu/doi/pdf/10.1086/520248
p. 452-3