- Top of page
- PATIENTS AND METHODS
The present study confirms that biopsy-proven GCA without clinically evident vascular involvement is not exceptional. In our series, these patients presented with isolated PMR or fever of unknown origin.
Former reports pointed out that in a variable proportion of cases, generally 15–20%, temporal artery biopsy samples taken from patients with isolated PMR, without any cranial manifestation related to vascular involvement in the setting of GCA, yielded inflammatory changes of GCA (8). Also in some studies, GCA and PMR exhibited similar HLA–DRB1 genotype associations (10). These observations have supported the concept, maintained by many authorities, that both conditions are the same disease.
More recent studies in different countries, however, have underlined some immunogenetic differences between GCA and PMR, particularly in terms of HLA–DRB1 genotype associations (11), and subtle clinical differences between isolated PMR and PMR associated with biopsy-proven GCA (12). In a previous study (following the same procedure described in the Patients and Methods section here), we reported that the frequency of positive temporal artery biopsy samples in a series of Lugo patients with clinically isolated PMR was 9% (13). Based on the followup of patients with isolated PMR, we have observed that in northwest Spain the potential development of cranial manifestations of GCA in those patients initially diagnosed as having isolated PMR generally occurs within the first 2 years after onset of PMR symptoms. In Lugo, only ∼2% of patients diagnosed as having isolated PMR, who did not exhibit symptoms of GCA within the first 2 years after the diagnosis of PMR, developed features of GCA later during their extended followup (14). Due to this, we do not consider isolated PMR as a clinical feature of vascular involvement in the setting of GCA.
Fever of unknown origin has been reported as a presenting manifestation of silent GCA (3). As with our 2 cases, severe visual complications have been reported to be exceptional in these patients (3, 15). Thus, the presence of this clinical marker of inflammatory response may be considered a protective factor against severe ischemic events in these patients. The very low proportion of fever of unknown origin in our series of biopsy-proven GCA may have 2 possible explanations. We may have opted not to perform temporal artery biopsy in some elderly patients with fever. However, this seems unlikely in our area because, due to our interest in this type of vasculitis, internal medicine staff members from our hospital are aware of this type of vasculitis and temporal artery biopsy is routinely considered in patients with fever of unknown origin. In addition, since the rheumatology division was established in 1987, meticulous history taking and physical examination for GCA is routinely performed in all patients presenting with fever.
In 1980, Strachan et al stated that the delay to reach a diagnosis of GCA was the main factor implicated in the development of serious sequelae in patients with silent GCA (16). In contrast, a longer delay to diagnosis in our unselected patients without overt clinical manifestations of vasculitis was not associated with an increased risk of severe vascular complications.
A few years ago, the group led by Cid reported a negative association between a strong inflammatory response and the risk of developing cranial ischemic complications (17). Further analyses in our population supported that observation (6, 18). In patients from northwest Spain, anemia was a negative predictive factor for the development of ischemic visual manifestations in the setting of GCA (6). However, the reason for a lower risk of severe visual manifestations in GCA patients with protracted inflammatory response remains to be elucidated. It is possible that this subgroup of patients with more protracted disease may have a different cytokine profile (19) and, due to this, a lower risk of ischemic complications. Recently, Cid et al (20) have described an attractive explanation that may shed light to this paradox. These authors examined the clinical relevance of neovascularization in GCA. In their series of 31 GCA patients, those without ischemic complications had significantly higher tissue angiogenesis scores than the patients with ischemic events. Of note, angiogenesis was also significantly more prominent in patients with a strong acute phase response compared with those with a weak systemic inflammatory response (20). According to their results, inflammation-induced angiogenic activity may play a compensatory role for ischemia in GCA patients (20).
In conclusion, isolated PMR and fever of unknown origin are the presenting manifestations of Lugo biopsy-proven GCA patients without clinically evident vascular manifestations. Despite having a longer delay to diagnosis, these patients do not exhibit ischemic complications during their followup. Therefore, they constitute a subgroup of GCA with a good outcome.