In the present study, we identified that approximately 6% of the patients awaiting treatment by the rheumatologist were referred due to an isolated alteration in the ANA result and that the vast majority of these patients did not present any other classification criteria (clinical or laboratory) for systemic lupus erythematosus (SLE), data is similar to that found in another study[9].
A large percentage of patients who underwent the ANA survey did not undergo easily accessible tests that are essential in suspected SLE, such as blood count and urine1 to assess hematological and renal manifestations, respectively.
In addition, the complementary request for autoantibodies in the investigation of autoimmunity requires correlating them with the epidemiology and symptoms presented. Late-onset SLE is described in patients older than fifty years-old but the referral of a 93-year-old patient with suspected of autoimmunity is noteworthy, considering that this is not the age range usually affected by the disease [10]. Among the patients included in the study, 17 were 65 years old or older, an age group that exceeds that expected for a given condition. Requesting ASLO, rheumatoid factor, and ANA for the same patient reinforces the fact that there is no clear diagnostic hypothesis for the presented complaints. The ASLO survey is performed to document previous Streptococcus pyogenes infections in suspected rheumatic fever, a nonpyogenic complication of this bacterial infection, which is found most often in individuals between 5 and 15 years of age [11].
Although the ANA assessment is not used evolutionarily, the patients repeated the test at the AME laboratory due to the reliability of the result. It is clear that more than 70% of patients did not have any other classification criteria (ACR 1987 and SLICC 2012) for SLE other than ANA positivity. That is, autoantibodies were requested for the diagnostic investigation even in the absence of clinical alterations that would strengthen it. Before applying such criteria, careful clinical judgment is needed, and the exclusion of autoimmunity mimics that include infectious, metabolic, and neoplastic diseases [8, 12]. Few patients in this study were tested for chronic viral infections. Two patients met the 4 classification criteria for SLE but had clinical conditions that justified the manifestations presented. The patient who had the maximum score in the 1987 ACR criteria also had photosensitivity, known as a manifestation with lower specificity for SLE. Those who scored the 2012 SLICC criteria were diagnosed as coinfection HIV and hepatitis C only at the rheumatologist’s appointemnnt, which justified the laboratory alterations presented (leukocyturia, hematuria, leukopenia, and thrombocytopenia), as well as the complaint of oral ulcers.
Another relevant aspect is the distribution of the ANA title and patterns. In this study, there was a higher prevalence of low ANA titers (1:80 and 1:160), which are often associated with healthy individuals [13]. Interestingly, both patients with higher scores on the SLE classification criteria did not have a high ANA titer. Of the amount studied, the most frequent pattern was the dense fine speckled nuclear. Studies indicate that antibodies related to this pattern are not associated with the development of systemic rheumatological diseases and have a low prevalence in patients with SLE (1.1%) [13]. Although 24 patients had the homogeneous or coarse speckled nuclear ANA patterns, no patient was positive for autoantibodies in the solid phase assay (ELISA), such as anti-DNA and anti-SM, that have high specificity for SLE [13].
Blood count analysis is fundamental for the evaluation of the hematological manifestations of SLE. Anemia, leukopenia, and thrombocytopenia are prevalent changes that can affect around 50%, 75%, and 30% of patients, respectively [14]. However, 4/9 patients with cytopenia already had portal hypertension, which justified the hematological findings [15]. Although the ANA request is part of the investigation of patients with liver cirrhosis to rule out autoimmune hepatitis [16], this test was requested to assess cytopenia and not to investigate chronic liver disease, and patients were diagnosed with portal hypertension only in rheumatological appointment.
Our study has some limitations. One of them is the retrospective analysis of the medical records, interfering specially in the identification of exact reason for referring physician requesting the ANA test, because most of them were already asymptomatic at the moment of the clinical assessment. Moreover, it is now well established that ANA and some disease-specific autoantibodies (anti-dsDNA antibodies in SLE, for example) can antedate the clinical diagnosis of autoimmune rheumatic disease by as many as two decades. Different HEp-2 IFA patterns indicate different autoantibodies and we have to take it in count to judge its clinical relevance before advising patients that only some are associated with a specific disease [17, 18].
The strong point of our study is that it is a large national cohort of Brazilian Public Health System patients, which brought to light the weaknesses in the interpretation and propaedeutics related to musculoskeletal complaints and the use of laboratory tests, resulting in inappropriate’s referrals and a waste of health care resources.