We reviewed the literature to evaluate the role of common laboratory tests and to examine the recent progress in the laboratory diagnosis of pediatric rheumatic diseases.
We used the PubMed database (1950-2008) to search for the keywords "laboratory," "erythrocyte sedimentation rate" (ESR), "C-reactive protein" (CRP), "blood cytology," "procalcitonin" (PCT), "complement system," "ferritin," "antistreptolysin O titer" (ASO), "autoantibodies," "genetic studies," in conjunction with "rheumatic disease in children" and "pediatric autoimmune diseases." All relevant original and review articles in English were reviewed as well as textbooks of pediatric rheumatology.
Laboratory tests (ESR, CRP, blood cytology, complement system, ferritin, ASO titer) play an important role in confirming a diagnosis and in the follow-up of rheumatic diseases in the pediatric age group. The ESR is probably the most widely measured index of the acute phase response. Measurement of CRP is very useful in the rapid diagnosis of infection as a progressive increase can be shown in the first 48 hours. Also, the subsequent fall in serum CRP concentration on resolution of inflammation is useful for monitoring the efficacy of treatment. In chronic diseases, a combination of CRP and ESR may provide the most useful information. Cytopenia and different forms of anemia can be encountered in many rheumatic diseases: they can be related to disease activity or to therapeutic side effects. Determination of complement levels (C3 and/or C4) is useful in the follow-up of systemic lupus erythematosus (SLE) and membranoproliferative glomerulonephritis. Ferritin is a laboratory hallmark of primary and secondary hemophagocytic lymphohistiocytosis. ASO titer should be obtained to confirm a diagnosis of acute rheumatic fever; other important antibody markers of streptococcal infection include antihyaluronidase, antideoxyribonuclease B, and antistreptokinase antibodies. We also found that, in the pediatric age, the main indication for synovial fluid analysis is suspected joint infection. Antinuclear antibodies, anti-Smith antigen, and anti-double-stranded DNA antibodies are important in the diagnosis of SLE, are useful prognostic markers, and facilitate clinical and treatment follow-up. Anti-SSA/Ro and anti-SSB/La antibodies are associated with Sjögren's syndrome and congenital heart block, while the anti-U1 small nuclear ribonucleoprotein antibodies show high specificity for mixed connective tissue disease. Repetitive spontaneous abortions, thrombocytopenia, and many types of venous or arterial thrombosis are associated with antiphospholipid antibodies. The presence of cytoplasmic antineutrophil antibodies is essential in the diagnosis of Wegener granulomatosis. The discovery of underlying single causative gene defects led to the identification of several autoinflammatory diseases, a group of genetic disorders characterized by recurrent attacks of inflammation (hereditary periodic fever syndromes). These include familial Mediterranean fever due to mutations in the Mediterranean fever (MEFV) gene, hyperimmunoglobulinemia D syndrome due to mutations in the MK gene for mevalonate kinase, cryopyrinopathies such as Muckle-Wells syndrome or neonatal-onset multisystemic inflammatory disease (neonatal-onset multisystemic inflammatory disease or chronic infantile neurological cutaneous and articular (CINCA)) associated with cold-induced autoinflammatory syndrome 1 gene mutations, and tumor necrosis factor receptor-associated periodic syndrome due to mutation of TNF receptor I gene.
Laboratory investigations play an important role in the diagnosis and follow-up of inflammatory rheumatic diseases in children. A good history and a complete physical examination are the best screening tests. Routine laboratory tests are useful to confirm a suspected diagnosis, to assess disease activity, and to measure the response and toxicity to treatment. Only a few tests represent diagnostic criteria such as antinuclear antibodies and anti-double-stranded DNA in SLE or cytoplasmic antineutrophil cytoplasmic autoantibodies in Wegener's granulomatosis. Recent advances in molecular genetics have impacted diagnosis, pathogenesis, and treatment in genetic fever syndromes.