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I read with interest the article recently published by Punziet al.1 The results shown in this study demonstrate higher levels of acute phase reaction markers such as ESR and CRP in elderly onset psoriatic arthritis patients (EOPsA) than those displayed by young onset psoriatic arthritis patients (YOPsA). The authors included 16 EOPsA (>60 years) and 50 YOPsA (<60 years).
I would like to comment that the information regarding normal values was restricted to the following words “CRP, normal values <0.6 mg/dl”, no other information is given. It is not possible to know how and from whom these normal values were obtained. Even if a commercial test that includes their own controls was used, it is clear that you will need to test groups of normal subjects that cover the age spectrum of both groups of patients EOPsA and YOPsA. This strategy will allow you to estimate the influence of age in the higher levels of ESR and CRP exhibited by EOPsA. The inclusion of this control group of normal subjects is also recommended because YOPsA does not belong to the same age cohort that EOPsA does, and in fact, EOPsA represents a group of survivors from their original birth cohort more that YOPsA does.
In his comments on our paper,1-1 Dr Nava regrets that little information was given on the normal values of laboratory markers of acute phase response (APR), in particular ESR and CRP, to support the observation that APR is higher in elderly onset psoriatic arthritis (EOPsA) than in younger onset PsA (YOPsA). This criticism probably derives from the possibility that the differences in ESR and CRP may simply be attributable to age rather than disease.
ESR and CRP are the most widely known and commonly used laboratory indices used to investigate APR and disease activity. ESR is a composite measurement depending on several factors, including in particular red cell and serum protein changes. Physiological changes able to influence one or more of these factors, such as sex and age, may in turn influence ESR. Since the first introduction of Westergren's technique, the most recommended method for ESR determination,1-2 many studies have been performed to establish normal values in the elderly: irrespective of sex, upper limits of 20 mm 1st h for subjects under 50 years and 40 mm 1st h for those older than 70 years are considered normal, acceptable values.1-3 Thus, the ESR mean values of 64.2 (35.3) mm 1st h found in our EOPsA patients must be viewed entirely above suspicion.
The differences between our EOPsA and YOPsA were even more evident for the CRP, a protein that best reflects the APR and that is only slightly influenced by age and sex. The normal values we reported (<0.6 mg/dl for any ages and sex) are accepted worldwide and, although some rare healthy subject may reach an upper limit of 1.0 mg/dl,1-4 these values mainly differ from the mean of 3.9 (2.0) mg/dl found in our patients with EOPsA.
In this context, however, another aspect might have seemed surprising: the low values of ESR and CRP found in YOPsA, 30.5 (30.0) mm 1st h and 1.33 (1.3) mg/dl respectively, reflecting difficulties in applying these indices to patients with seronegative spondyloarthritides and in assessing disease activity.1-5 1-6 Furthermore, in a recent, unpublished observation from the Italian Group of Psoriatic Arthritis Study, involving 1306 patients with PsA, CRP values of >1 mg/dl were found in only 52.9% of the patients. As the agents mainly responsible for CRP production are pro-inflammatory cytokines, mainly interleukin (IL) 6 but also IL1 and tumour necrosis factor, and as these cytokines are usually found at low levels in the synovial fluid of YOPsA,1-1 1-7 PsA may be considered a disease characterised by a frequent low synthesis of pro-inflammatory cytokines and usually mild APR. However, factors able to stimulate or deregulate the production of these cytokines, such as aging, trauma, infections or immunogenetic predisposition to severe polyarticular diseases,1-7-1-10 may be responsible for an increased APR and account for a wide spectrum of presentations typical of PsA.
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