Rheumatology 2001; 40: 349-350
© 2001 British Society for Rheumatology
Letters to the Editor |
Pyrexia and normal C-reactive protein (CRP) in patients with systemic lupus erythematosus: always consider the possibility of infection in febrile patients with systemic lupus erythematosus regardless of CRP levels
Leicester Royal Infirmary NHS Trust, Leicester, UK
SIR, Patients with active systemic lupus erythematosus (SLE) often have normal C-reactive protein (CRP) levels. However, bacterial infections can elicit CRP production in these patients [1, 2]. It has therefore been proposed that measuring the CRP levels in pyrexial patients with SLE can help to differentiate between active disease and infection [1, 2]. We describe two patients with SLE with systemic bacterial infection who presented with normal CRP levels.
The first patient was a 30-yr-old Asian woman with SLE who presented to the Medical Admissions Unit with headache, diarrhoea, vomiting, fever and abdominal pain. Problems started on the day before admission. She had been discharged from hospital 9 days previously after treatment for known Salmonella septicaemia. She had also been admitted a month before this for a possible flare of SLE. At the time of admission she was on azathioprine, nizatidine, prednisolone and co-codamol.
On examination, she was pyrexial with a temperature of 38°C, a regular pulse of 100/min and a blood pressure of 105/55 mmHg. Examination of the cardiovascular, abdominal and respiratory systems did not reveal any abnormalities.
Haemoglobin was 10.7 g/dl, mean corpuscular volume (MCV) 87 fl, white cell count 1.8x103/l and platelet count 227x109/l. Blood biochemistry was normal, with a CRP of less than 0.3 mg/dl (normal range 0–1 mg/dl). This resulted in a diagnostic dilemma because both Salmonella sepsis and an exacerbation of SLE can cause anaemia and leucopenia. In view of the low CRP value, it was decided that an exacerbation of SLE was more likely to be the cause of this patient's problems. However, a decision was made not to increase the dose of steroids until the result of the blood cultures became available.
On day 2 of the current admission, Salmonella sp. was isolated from her blood. She was started on 400 mg of intravenous ciprofloxacin twice daily. Fever subsided and she improved rapidly.
The CRP was never above 1 mg/dl at any stage during her illness. The focus of her Salmonella infection remains unknown. Abdominal ultrasound, chest X-ray, echocardiogram, stool culture, white cell scan, bone scan and urine culture did not reveal any possible foci of infection.
The second patient was a 35-yr-old woman known to have had SLE for the past 8 yr. She was admitted because of fatigue, arthralgia and pyrexia, and was on azathioprine, bendrofluazide and hydroxychloroquine. On examination, she was visibly swollen around the eyes and had the butterfly rash of SLE. There were no abnormal systemic signs. Temperature was 38.3°C, blood pressure 138/80 mmHg and pulse a regular 100/min.
Haemoglobin was 9.2 g/dl, MCV 86 fl and white cell count 2.6x103/l. Blood biochemistry was normal apart from a low albumin concentration of 24 g/l. CRP was less than 1 mg/dl. Urine examination showed no abnormality and culture was sterile. Chest X-ray and echocardiogram were normal.
On day 2 of the admission, Staphylococcus aureus was cultured from her blood. Intravenous flucloxacillin 1 g four times daily was started and she improved rapidly. As with case 1, the focus of infection remains unknown.
Many studies show that CRP levels are often increased in both infections and exacerbations of SLE [1–3]. The median level of CRP in patients with SLE flares without serositis appears to be around 1.4–1.6 mg/dl, with a range of 0–6 mg/dl [1, 2]. In infection, the median CRP level appears to lie between 6.0 and 8.2 mg/dl, with a range of 0.1–40.0 mg/dl. In SLE patients with active serositis, the median CRP level is 7.6 mg/dl with a range of 0.2–37.5 mg/dl. These observations led ter Borg et al. [1] to conclude that CRP levels above 6.0 mg/dl in febrile SLE patients without serositis almost always indicate infection.
CRP levels were not increased in two cases of bacterial infections out of a series of 30 proven cases [1]. A possible explanation is that the concomitant use of corticosteroids in these patients suppressed the production of CRP. Another possible explanation attributes this phenomenon to the formation of immune complexes containing CRP. Indeed, autoantibodies to the denatured CRP molecule have been described in patients with SLE [4]. The exact relevance of these antibodies with regard to a low CRP level, however, remains unknown.
The treatment of febrile patients with SLE must be based primarily on the clinical features of the patient's illness and not on the CRP level. The presence of infection should always be actively sought in all SLE patients with pyrexia of unknown origin, even if the CRP level is low or normal. Conversely, the presence of a high CRP level in a patient with serositis does not always indicate the presence of infection.
Notes
Correspondence to: S. Roy, Department of Rheumatology, Leicester Royal Infirmary, Leicester LE1 5WW, UK. 
References
- ter Borg EJ, Horst G, Limburg PC, van Rijswijk MH, Kallenberg CGM. C-reactive protein levels during disease exacerbations and infections in systemic lupus erythematosus: A prospective longitudinal study. J Rheumatol1990;17:1642–8.[Web of Science][Medline]
- Becker GJ, Waldburger M, Hughes GRV, Pepys MB. Value of serum C-reactive protein measurement in the investigation of fever in systemic lupus erythematosus. Ann Rheum Dis1980;39:50–2.
[Abstract/Free Full Text] - Zein N, Gannuza C, Kushner I. Significance of serum C-reactive protein elevation in patients with systemic lupus erythematosus. Arthritis Rheum1979;22:7–12.[Medline]
- Bell SA, Faust H. Autoantibodies to C-reactive protein and other acute phase proteins in systemic autoimmune diseases. Clin Exp Immunol1998;113:327–32.[Medline]
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