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Chronic infections may mimic antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV). We investigated which markers may help in the diagnosis and the prognosis of infections associated with proteinase 3 (PR3) and myeloperoxidase (MPO)-ANCA. In this study (1993-2008)--with an average follow-up of 5.1 years--we compared 66 AAV patients with 17 PR3 and/or MPO-ANCA-positive patients with protracted bacterial (11/17) or viral (6/17) infections. Seven of 17 patients had subacute bacterial endocarditis (SBE), while six of 17 patients had various autoimmune manifestations of chronic hepatitis C virus (HCV) infection. We determined ANCA, antinuclear antibodies, anti-PR3, anti-MPO, anticardiolipin (aCL), antibeta 2 glycoprotein I (beta2-GP I), cryoglobulins, C3, and C4. Patients with infections were younger than AAV patients (p < 0.01). There was no difference in frequency of renal and skin lesions. AAV patients more frequently had pulmonary and nervous system manifestations (p < 0.01). Patients with infections more frequently had dual ANCA (high PR3, low MPO), aCL, anti-beta2-GP I, cryoglobulins, and hypocomplementemia (p < 0.001). Immunosuppressive therapy (IST) was used in five 17 patients who had persistently high ANCA, cryoglobulinemia, and hypocomplementemia. There was no difference in frequency of lethality and renal failure in the two study groups. In patients who are PR3- and/or MPO-ANCA positive, SBE and HCV infection should be excluded. Although similar in renal and skin manifestations in comparison to AAV, only patients with infections developed multiple serological abnormalities. In patients with infections, concomitant presence of ANCA, cryoglobulins, and hypocomplementemia was associated with severe glomerulonephritis. The serological profile should be repeated after specific antimicrobial or surgical therapy, since some cases might require IST.

We reviewed the clinical, histological and serological parameters of microscopic polyangiitis (MPA) associated with antineutrophil cytoplasmic antibodies (ANCA) specific to myeloperoxidase (MPO). Six girls and one boy aged 12.0+/-2.6 years (7-15 years) met the following inclusion criteria: (1) clinical manifestations of systemic small vessel involvement; (2) histological demonstration of pauci-immune necrotizing glomerulonephritis; and (3) serological findings of increased concentration of MPO-ANCA by ELISA test. The main clinical manifestations were: influenza-like symptoms (100%), hematuria/proteinuria (100%), purpura (100%), pulmonary-renal syndrome (57%), acute renal failure (ARF) (29%), ischemic cerebral insults (29%), and necrotizing vasculitis of the skin (29%). All patients underwent renal biopsy examined by immunohistochemistry with expression of alpha-smooth muscle actin (alpha SMA) in glomerular and interstitial spaces. Patients were followed from 6 months to 5.5 years (35.4+/- 23.2 months). None of the patients died. Two of seven children who had ARF progressed to end stage renal disease; one developed chronic renal failure, and four normalized renal function. ARF and central nervous system involvement at presentation were parameters of poor renal outcome. A high score of fibro-cellular glomerular crescents was associated with worse prognosis. Early treatment enables a favorable prognosis of MPO-ANCA-associated MPA in children.

There are no widely accepted therapy protocols for severe alopecia areata (AA). We treated 65 children/adolescents with AA affecting >30% of scalp. Fourty-three percent of patients had AA plurifocalis (AAP). Fifty-seven percent had AA subtotalis (AAS), AAP+ophiasis (AAP+OPH), and alopecia totalis/universalis (AT/AU). Long-term follow-up (median 96 months) data were available for 69% of patients. Oral dexamethasone (prednisolone 5 mg/kg equivalent) was given once in 4 weeks. Patients received 6, 9, or 12 pulses. Clobetasol propionate 0.05% ointment under plastic wrap occlusion was applied 6 days a week. Hair growth was assessed on a scale ranging 0-100% of regrowth in individual AA lesions. Regrowth >50% was considered good response. Six to twelve months months after the therapy, 56.9% of patients had >75% of hair regrowth. In AAP, 65.5% had complete regrowth. 61.5% of all patients were considered good responders. Significantly, higher percentage of good responders was found in AA lasting ≤12 months. No patients had serious side effects. There was no change in stability of the hair status at the long-term follow-up. Most AA patients had beneficial effects with this protocol. Best results were in AAP and AAP+OPH. Combined topical and oral pulse corticosteroid therapy of AA in children shows long-lasting results, without serious side effects.

Monitoring of DNase I activity simultaneously with SLEDAI-2K might be a useful tool in the follow-up of SLE. An increase of DNase I activity characterized relapse in most SLE patients, although it did not reach the levels of healthy individuals. A decrease of DNase I activity in SLE flare-ups might be a functional biomarker of a subset of patients with specific dysfunction of apoptotic chromatin degradation.

We assessed the relationship between the serum levels of antibodies against double-stranded DNA (dsDNA), C1q, nucleosomes, histones, C3 and C4 complement components with one another, with organ involvement and overall disease activity in patients with systemic lupus erythematosus (SLE). One hundred seventy-five sera from 99 patients with SLE, 31 sera of patients with other connective tissue diseases, and 20 sera from healthy blood donors were tested. SLE disease activity was assessed by modified SLEDAI-2K (M-SLEDAI-2K), not including complement and anti-dsDNA descriptors. Anti-dsDNA antibodies were measured by indirect immunofluorescence on Crithidia luciliae (CLIFT), standard enzyme-linked immunosorbent assay (ELISA) and ELISA for high-avidity antibodies. The most significant risk factor for renal involvement were anti-C1q antibodies (OR = 3.88, p < 0.05), high-avidity anti-dsDNA antibodies for polyserositis (OR = 7.99, p < 0.01), anti-histone antibodies for joint involvement (OR = 2.75, p < 0.05), and low C3 for cytopenia (OR = 11.96, p < 0.001) and mucocutaneous lesions (OR = 3.32, p < 0.01). Multiple linear regression analysis showed that disease activity in SLE could be predicted by the levels of antibodies against dsDNA determined by standard (p < 0.05) and high-avidity (p < 0.001) ELISA, and inversely associated with concentration of C3 (p < 0.001). Using stepwise method, high-avidity anti-dsDNA antibodies were found to be in the closest association to M-SLEDAI-2K. Moreover, positive test for high-avidity anti-dsDNA antibodies appeared as an independent risk factor for moderately to severely active disease (M-SLEDAI-2K>5) (OR = 5.5, p < 0.01). The presence of high-avidity anti-dsDNA antibodies represented a risk for renal, joint, and most importantly for serosal involvement. Our results suggest that simple and reliable ELISA for high-avidity anti-dsDNA antibodies is the test of good clinical utility for the assessment of global SLE activity.

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