Stephen A. Paget, MD, FACP, FACR

Disclosures

February 18, 2003

Question

Have any data shown a correlation between the level of rise of CRP and inflammatory diseases like temporal arteritis/polymyalgia rheumatica? (Since ESR is affected by anemia, are there any factors that affect CRP besides infection?) Has anyone ever published data for follow-up and titration of treatment based on CRP levels?

Response from Stephen A. Paget, MD, FACP, FACR

Polymyalgia rheumatica (PMR) and temporal arteritis (TA) are companion systemic inflammatory disorders that occur in older patients (mean age, 70 years) and are diagnosed on clinical grounds, based on their characteristic presenting features. Certainly, most patients with PMR and TA have elevated or markedly elevated erythrocyte sedimentation rates (ESRs) and c-reactive proteins (CRPs), but you must appreciate that a low ESR (< 40 mm/hour) in active TA and PMR is not a rare occurrence and 2% may have a normal ESR. Similar findings exist with the CRP.

Both the ESR and the CRP are acute-phase reactants and commonly reflect the state of the immune and inflammatory response. However, some patients may be unable to mount an acute-phase response with regard to tests but surely have a disorder that demands treatment. In TA, this could be vision-saving if instituted immediately. Also, in some patients, the ESR is markedly elevated and the CRP is low or normal and vice versa. The next question is what is a normal ESR. The most common method of calculating the normal ESR is by dividing a male patient's age by 2 and by adding 10 to a female patient's age before dividing by 2.

CRP is typically present in trace amounts in normal human serum and its concentration commonly rises after tissue injury. The production of CRP is stimulated by interleukin 6 (IL-6), an inflammatory cytokine generated by immunologically active cells in inflammatory disorders such as PMR and TA. An elevated concentration of CRP has been reported in 91% of patients with biopsy-proven TA, compared with 44% of control patients. Some studies conclude that CRP is more sensitive (100%) than the ESR (92%) in detecting TA and that a combination of the ESR and the CRP offers the best specificity -- 97%. Of interest is the fact that a Mayo clinic study demonstrated that plasma IL-6 is more sensitive than the ESR for indicating disease activity in untreated and treated TA patients.

Both the ESR and the CRP can be elevated by similar factors, such as infection, malignancy, and tissue trauma. They are nonspecific tests and must be placed in clinical context. There is no stronger "test" than a complete history and physical performed by an astute clinician. Make sure that your elderly patients are up-to-date on their malignancy screens and, when they are taking steroids, you should always have a high index of suspicion for infections. Remember, steroids can cover a "multitude of sins," and can suppress the characteristic clinical tip-offs of infection.

Most important, the physician must appreciate the fact that diagnosis and treatment in PMR and TA should be guided primarily by the clinical facts. Laboratory tests such as the ESR and CRP should be placed in the context of the clinical presentation, but one should not "chase the ESR or CRP" with steroids because patients will remain on inappropriately high levels for too long. You do not treat an ESR or CRP, you treat a person with an illness.

An example will be helpful here. A patient's TA was manifest by headache, PMR soreness and stiffness, fatigue, fever, and weight loss, as well as an ESR of 100 mm/hour and a CRP of 5. With 60 mg of prednisone, all of the symptoms and signs normalize or resolve, including the ESR and CRP. As the steroids are eventually tapered to 10 mg/day of prednisone, the patient remains totally asymptomatic but the ESR rises from 10 mm/hour to 32 mm/hour and the CRP rises from normal to 1.5. In this situation, while you may not further decrease the steroid dosage, you certainly do not need to raise the dose because the symptoms that initially heralded the disorder did not flare. Similarly, if that same patient redeveloped PMR symptoms and fatigue when you reached that 10-mg prednisone level, you might raise the dose of prednisone to 15 mg, even if the ESR and CRP remain normal.

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