Journal of Infection (1991) 22, 187-189
CASE R E P O R T Acute rheumatic
fever in human immunodeficiency infection
virus
K. W. R a d c l i f f e , * K. A. M c L e a n * a n d A. G. B e n b o w t
Departments of * Genitourinary Medicine and t Medicine, Charing Cross Hospital, London, U.K. Accepted for publication 24 August I99o Summary A 25-year-old homosexual man with a childhood history of rheumatic heart disease presented with painful joints, fever and chest pain. He was diagnosed as having acute rheumatic fever and was found to be HIV antibody-positive. His illness responded to conventional treatment but he had a persistently low CD 4 lymphocyte count and was started on zidovudine. Interpretation of the significance of a low CD 4 lymphocyte count is problematic in a patient with coincident rheumatic fever and HIV infection as both conditions can cause CD4 lymphopenia.
Introduction W e report a case of acute r h e u m a t i c fever (ARF) in a m a n infected with the h u m a n i m m u n o d e f i c i e n c y virus (HIV) and discuss possible interactions between the two conditions.
Case report A 25-year-old Brazilian m a n presented with a 4 days' history of fever, night sweats, dyspnoea and chest pain suggestive of pericarditis. H e also complained of pains in both hips, his left knee and right ankle joints. Antibiotic t h e r a p y had been prescribed by his general practitioner. H e was homosexual and a d m i t t e d to several recent sexual partners b u t h a d not been tested for H I V antibodies. In Brazil he had suffered f r o m recurrent sore throats and arthritis from the age of 3 years. A heart m u r m u r was detected w h e n he was 6 years old and r h e u m a t i c heart disease was diagnosed. H e u n d e r w e n t tonsillectomy and c o m m e n c e d penicillin prophylaxis which he continued until the age of 2z years. Positive findings on examination were: t e m p e r a t u r e 39 °C; tachycardia; apex beat displaced to the anterior axillary line a m u r m u r characteristic of mitral r e g u r g i t a t i o n ; painful restriction of m o v e m e n t of both hip joints. Other joints were normal. T w o days later the s y m p t o m s and signs related to his left hip had resolved but tenderness, e r y t h e m a and painful restriction of m o v e m e n t were present in the right ankle. Blood taken on several occasions w h e n the patient was not on antibiotics showed no growth on culture. Electrocardiography at the time of admission o163-4453/9I/O2OZ87+o3 $03.00/0
© 1991 The British Society for the Study of Infection
I88
K.W. RADCLIFFE
ET AL.
showed a sinus tachycardia but first-degree heart block developed later. A chest X-ray confirmed cardiomegaly. T h e ESR was 6 o m m / h and the aspartate aminotransferase was 3oo IU/1. Pharyngeal culture was negative for fl-haemolytic streptococci but the antistreptolysin o titre peaked at 440 I U indicating recent streptococcal infection. Echocardiography showed evidence of mitral regurgitation and a small pericardial effusion. T h e H I V antibody test was positive. A diagnosis of ARF was made on the basis of the revised Duckett Jones criteria? Treatment with high-dose aspirin and phenoxymethyl penicillin resulted in a satisfactory clinical response. Shortly after admission the patient's absolute CD4 lymphocyte count was found to be markedly reduced at 189/mm ~ (normal > 4oo/mm3). Serum was negative for H I V pz4 antigen. Six months later the CD4 lymphocyte count remained persistently low at around I 4 o / m m a and in view of this, treatment with zidovudine was started. During 7 months of follow-up there has been no evidence of any HIV-associated condition and the patient remains well. His CD4 lymphocyte count has been measured on six occasions whilst on zidovudine and has fluctuated between I i8 and I 6 3 / m m 3. H I V p24 antigen has not been detected in the serum on repeated testing. Discussion
A case of rheumatic heart disease has been reported as a post-mortem finding in a patient with A I D S , 2 but to our knowledge this is the first report of a case of ARF in an HIV-seropositive patient who remains well. Acute rheumatic fever should be added to the list of previously recognised causes of arthritis associated with H I V infection) ARF may have been coincidental to this patient's H I V infection but there are theoretical grounds for supposing that these conditions might interact. H I V selectively infects and destroys CD4 lymphocytes. A low CD4 lymphocyte count in H I V infection correlates with a poor prognosis and susceptibility to opportunistic infections. Five 4-8 of the IO 4-13 studies of T lymphocyte subsets in ARF have shown significant reductions of CD 4 lymphocyte counts. In those studies which involved follow-up varying results were obtained. In one study the CD4 lymphopenia had resolved at 3o days 6 whereas in another it persisted beyond 3 Years.s It is possible that an episode of ARF in an H I V infected patient may cause an additional reduction of CD4 lymphocytes for a variable period during which there may be an increased susceptibility to opportunistic infections. Since the fall in the CD4 cell count due to ARF may be reversible its use as a criterion for initiating zidovudine therapy may be unreliable in this situation. It is of interest that examination of cardiac tissue obtained during surgery on patients with rheumatic heart disease has shown the lymphoid infiltrate to consist predominantly of T-helper (CD4) lymphocytes. 14 H I V infected patients are at increased risk of infections due to pyogenic bacteria. 1~ Pharyngeal infection with Lancefield group A fl-haemolytic streptococci is a necessary antecedent to acute rheumatic fever. A person with a childhood history of rheumatic heart disease who is subsequently infected
A c u t e r h e u m a t i c f e v e r in H I V
infection
I89
w i t h H I V m a y b e at i n c r e a s e d risk o f s t r e p t o c o c c a l p h a r y n g i t i s a n d , as a result, o f f u r t h e r e p i s o d e s o f r h e u m a t i c h e a r t disease. I t w o u l d be a d v i s a b l e for s u c h p a t i e n t s to r e m a i n o n p e n i c i l l i n p r o p h y l a x i s indefinitely. W o r l d - w i d e , r h e u m a t i c f e v e r is m o s t c o m m o n in d e v e l o p i n g c o u n t r i e s in m a n y o f w h i c h H I V i n f e c t i o n is also a m a j o r p r o b l e m . H o w e v e r , t h e o b s e r v a t i o n t h a t r h e u m a t i c f e v e r is r e s u r g e n t in p a r t s o f t h e U . S . A . , 16 w h e r e H I V is also w i d e s p r e a d , m a y i n d i c a t e t h a t m o r e cases o f c o n c u r r e n t disease will be seen in b o t h d e v e l o p i n g a n d d e v e l o p e d c o u n t r i e s . F u r t h e r w o r k is r e q u i r e d to clarify t h e i n t e r a c t i o n s b e t w e e n t h e s e t w o c o n d i t i o n s w i t h p a r t i c u l a r r e f e r e n c e to p a t i e n t m a n a g e m e n t .
References i. Denny FW. T. Duckett Jones and rheumatic fever in 1986. Circulation 1987; 76: 5: 963-97o. 2. DiCarlo FJ, Anderson DW, Virmani R et al. Rheumatic heart disease in a patient with acquired immunodeficiency syndrome. Hum Pathol 1989; 2o: 9: 917-92o. 3. Kaye BR. Rheumatologic manifestations of infection with human immunodeficiency virus (HIV). Ann Intern Med I989; I I I : 158-167. 4- Ganguly NK, Anand IS, Khanna AK et al. T cells and T cell subsets in rheumatic heart disease. Indian J Med Res I982; 76: 854-858. 5- Williams RC, Raizada V, Prakash K et al. Changes in T-lymphocyte subsets during acute rheumatic fever. J Clin Immunol 1982 ; Z: 3: I 6 6 - I 7 2 . 6. Garraud O, Ribiere O, Bach JF. T cell subsets in rheumatic fever in New Caledonia. Immunol Lett 1986; 13: 75-77. 7. Bhatnagar PK, Nijhawan R, Prakash K. T ceil subsets in acute rheumatic fever, rheumatic heart disease and acute glomerulonephritis cases. Immunol Lett 1987; I5: 217-219. 8. Hafez M, E1-Shannawy F, E1-Salab SH et al. Studies of peripheral blood T lymphocytes in assessment of disease activity in rheumatic fever. Br J Rheumatol I988; 27: I8I-I86. 9. Hsieh KH, Lue HC. Immunoregulation in rheumatic fever. Asian Pac J Allergy Immunol 1985; 3: 23-29. IO. Bhatia R, Narula J, Reddy KS et al. Lymphocyte subsets in acute rheumatic fever and rheumatic heart disease. Clin Cardiol 1989; I2: 34-38. I I. Etzioni A, Benderley A, Levy Jet al. Transient immunoregulatory perturbation during the acute phase of rheumatic fever. J Clin Lab Immunol I986; 2o: 7-9. 12. Benatar A, Beatty DW, Human DG. Immunological abnormalities in children with acute rheumatic carditis and acute post-streptococcal glomerulonephritis. I n t J Cardio11988 ; 2I : 5I--5 8,
13. Alarcon-Riquelme ME, Alarcon-Segovia D, Loredo-Abdala A et al. T lymphocyte subsets, suppressor and contrasuppressor cell functions, and production of interleukin-2 in the peripheral blood of rheumatic fever patients and their apparently healthy siblings. Clin Immunol Immunopathol 199o; x: I2O--I28. 14. Raizada V, Williams RC, Chopra Pet al. Tissue distribution of lymphocytes in rheumatic heart valves as defined by monoclonal anti-T cell antibodies. A m J Med 1983 ; 74 : 9o-96. I5. Witt D J, Craven DE, McCabe WR. Bacterial infections in adult patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. A m JA/Ied 1987; 82: 9oo-9o6. 16. Kaplan EL, Makowitz M. The fall and rise of rheumatic fever in the United States: a commentary. Int J Cardiol I988 ; 2 I : 3-10.
CASE R E P O R T Acute rheumatic
fever in human immunodeficiency infection
virus
K. W. R a d c l i f f e , * K. A. M c L e a n * a n d A. G. B e n b o w t
Departments of * Genitourinary Medicine and t Medicine, Charing Cross Hospital, London, U.K. Accepted for publication 24 August I99o Summary A 25-year-old homosexual man with a childhood history of rheumatic heart disease presented with painful joints, fever and chest pain. He was diagnosed as having acute rheumatic fever and was found to be HIV antibody-positive. His illness responded to conventional treatment but he had a persistently low CD 4 lymphocyte count and was started on zidovudine. Interpretation of the significance of a low CD 4 lymphocyte count is problematic in a patient with coincident rheumatic fever and HIV infection as both conditions can cause CD4 lymphopenia.
Introduction W e report a case of acute r h e u m a t i c fever (ARF) in a m a n infected with the h u m a n i m m u n o d e f i c i e n c y virus (HIV) and discuss possible interactions between the two conditions.
Case report A 25-year-old Brazilian m a n presented with a 4 days' history of fever, night sweats, dyspnoea and chest pain suggestive of pericarditis. H e also complained of pains in both hips, his left knee and right ankle joints. Antibiotic t h e r a p y had been prescribed by his general practitioner. H e was homosexual and a d m i t t e d to several recent sexual partners b u t h a d not been tested for H I V antibodies. In Brazil he had suffered f r o m recurrent sore throats and arthritis from the age of 3 years. A heart m u r m u r was detected w h e n he was 6 years old and r h e u m a t i c heart disease was diagnosed. H e u n d e r w e n t tonsillectomy and c o m m e n c e d penicillin prophylaxis which he continued until the age of 2z years. Positive findings on examination were: t e m p e r a t u r e 39 °C; tachycardia; apex beat displaced to the anterior axillary line a m u r m u r characteristic of mitral r e g u r g i t a t i o n ; painful restriction of m o v e m e n t of both hip joints. Other joints were normal. T w o days later the s y m p t o m s and signs related to his left hip had resolved but tenderness, e r y t h e m a and painful restriction of m o v e m e n t were present in the right ankle. Blood taken on several occasions w h e n the patient was not on antibiotics showed no growth on culture. Electrocardiography at the time of admission o163-4453/9I/O2OZ87+o3 $03.00/0
© 1991 The British Society for the Study of Infection
I88
K.W. RADCLIFFE
ET AL.
showed a sinus tachycardia but first-degree heart block developed later. A chest X-ray confirmed cardiomegaly. T h e ESR was 6 o m m / h and the aspartate aminotransferase was 3oo IU/1. Pharyngeal culture was negative for fl-haemolytic streptococci but the antistreptolysin o titre peaked at 440 I U indicating recent streptococcal infection. Echocardiography showed evidence of mitral regurgitation and a small pericardial effusion. T h e H I V antibody test was positive. A diagnosis of ARF was made on the basis of the revised Duckett Jones criteria? Treatment with high-dose aspirin and phenoxymethyl penicillin resulted in a satisfactory clinical response. Shortly after admission the patient's absolute CD4 lymphocyte count was found to be markedly reduced at 189/mm ~ (normal > 4oo/mm3). Serum was negative for H I V pz4 antigen. Six months later the CD4 lymphocyte count remained persistently low at around I 4 o / m m a and in view of this, treatment with zidovudine was started. During 7 months of follow-up there has been no evidence of any HIV-associated condition and the patient remains well. His CD4 lymphocyte count has been measured on six occasions whilst on zidovudine and has fluctuated between I i8 and I 6 3 / m m 3. H I V p24 antigen has not been detected in the serum on repeated testing. Discussion
A case of rheumatic heart disease has been reported as a post-mortem finding in a patient with A I D S , 2 but to our knowledge this is the first report of a case of ARF in an HIV-seropositive patient who remains well. Acute rheumatic fever should be added to the list of previously recognised causes of arthritis associated with H I V infection) ARF may have been coincidental to this patient's H I V infection but there are theoretical grounds for supposing that these conditions might interact. H I V selectively infects and destroys CD4 lymphocytes. A low CD4 lymphocyte count in H I V infection correlates with a poor prognosis and susceptibility to opportunistic infections. Five 4-8 of the IO 4-13 studies of T lymphocyte subsets in ARF have shown significant reductions of CD 4 lymphocyte counts. In those studies which involved follow-up varying results were obtained. In one study the CD4 lymphopenia had resolved at 3o days 6 whereas in another it persisted beyond 3 Years.s It is possible that an episode of ARF in an H I V infected patient may cause an additional reduction of CD4 lymphocytes for a variable period during which there may be an increased susceptibility to opportunistic infections. Since the fall in the CD4 cell count due to ARF may be reversible its use as a criterion for initiating zidovudine therapy may be unreliable in this situation. It is of interest that examination of cardiac tissue obtained during surgery on patients with rheumatic heart disease has shown the lymphoid infiltrate to consist predominantly of T-helper (CD4) lymphocytes. 14 H I V infected patients are at increased risk of infections due to pyogenic bacteria. 1~ Pharyngeal infection with Lancefield group A fl-haemolytic streptococci is a necessary antecedent to acute rheumatic fever. A person with a childhood history of rheumatic heart disease who is subsequently infected
A c u t e r h e u m a t i c f e v e r in H I V
infection
I89
w i t h H I V m a y b e at i n c r e a s e d risk o f s t r e p t o c o c c a l p h a r y n g i t i s a n d , as a result, o f f u r t h e r e p i s o d e s o f r h e u m a t i c h e a r t disease. I t w o u l d be a d v i s a b l e for s u c h p a t i e n t s to r e m a i n o n p e n i c i l l i n p r o p h y l a x i s indefinitely. W o r l d - w i d e , r h e u m a t i c f e v e r is m o s t c o m m o n in d e v e l o p i n g c o u n t r i e s in m a n y o f w h i c h H I V i n f e c t i o n is also a m a j o r p r o b l e m . H o w e v e r , t h e o b s e r v a t i o n t h a t r h e u m a t i c f e v e r is r e s u r g e n t in p a r t s o f t h e U . S . A . , 16 w h e r e H I V is also w i d e s p r e a d , m a y i n d i c a t e t h a t m o r e cases o f c o n c u r r e n t disease will be seen in b o t h d e v e l o p i n g a n d d e v e l o p e d c o u n t r i e s . F u r t h e r w o r k is r e q u i r e d to clarify t h e i n t e r a c t i o n s b e t w e e n t h e s e t w o c o n d i t i o n s w i t h p a r t i c u l a r r e f e r e n c e to p a t i e n t m a n a g e m e n t .
References i. Denny FW. T. Duckett Jones and rheumatic fever in 1986. Circulation 1987; 76: 5: 963-97o. 2. DiCarlo FJ, Anderson DW, Virmani R et al. Rheumatic heart disease in a patient with acquired immunodeficiency syndrome. Hum Pathol 1989; 2o: 9: 917-92o. 3. Kaye BR. Rheumatologic manifestations of infection with human immunodeficiency virus (HIV). Ann Intern Med I989; I I I : 158-167. 4- Ganguly NK, Anand IS, Khanna AK et al. T cells and T cell subsets in rheumatic heart disease. Indian J Med Res I982; 76: 854-858. 5- Williams RC, Raizada V, Prakash K et al. Changes in T-lymphocyte subsets during acute rheumatic fever. J Clin Immunol 1982 ; Z: 3: I 6 6 - I 7 2 . 6. Garraud O, Ribiere O, Bach JF. T cell subsets in rheumatic fever in New Caledonia. Immunol Lett 1986; 13: 75-77. 7. Bhatnagar PK, Nijhawan R, Prakash K. T ceil subsets in acute rheumatic fever, rheumatic heart disease and acute glomerulonephritis cases. Immunol Lett 1987; I5: 217-219. 8. Hafez M, E1-Shannawy F, E1-Salab SH et al. Studies of peripheral blood T lymphocytes in assessment of disease activity in rheumatic fever. Br J Rheumatol I988; 27: I8I-I86. 9. Hsieh KH, Lue HC. Immunoregulation in rheumatic fever. Asian Pac J Allergy Immunol 1985; 3: 23-29. IO. Bhatia R, Narula J, Reddy KS et al. Lymphocyte subsets in acute rheumatic fever and rheumatic heart disease. Clin Cardiol 1989; I2: 34-38. I I. Etzioni A, Benderley A, Levy Jet al. Transient immunoregulatory perturbation during the acute phase of rheumatic fever. J Clin Lab Immunol I986; 2o: 7-9. 12. Benatar A, Beatty DW, Human DG. Immunological abnormalities in children with acute rheumatic carditis and acute post-streptococcal glomerulonephritis. I n t J Cardio11988 ; 2I : 5I--5 8,
13. Alarcon-Riquelme ME, Alarcon-Segovia D, Loredo-Abdala A et al. T lymphocyte subsets, suppressor and contrasuppressor cell functions, and production of interleukin-2 in the peripheral blood of rheumatic fever patients and their apparently healthy siblings. Clin Immunol Immunopathol 199o; x: I2O--I28. 14. Raizada V, Williams RC, Chopra Pet al. Tissue distribution of lymphocytes in rheumatic heart valves as defined by monoclonal anti-T cell antibodies. A m J Med 1983 ; 74 : 9o-96. I5. Witt D J, Craven DE, McCabe WR. Bacterial infections in adult patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. A m JA/Ied 1987; 82: 9oo-9o6. 16. Kaplan EL, Makowitz M. The fall and rise of rheumatic fever in the United States: a commentary. Int J Cardiol I988 ; 2 I : 3-10.
