Kawasaki disease and juvenile systemic lupus erythematosus

Kawasaki disease (KD) is a common vasculitis in childhood. To the authors' knowledge, only one case of juvenile systemic lupus erythematosus (JSLE)-like onset mimicking KD and another case of KD and JSLE association have previously been described. However, the prevalence of this association of the two diseases was not reported. Therefore, over 27 consecutive years, 5419 patients were followed at the Pediatric Rheumatology Unit and 271 (5%) of them met the ACR classification criteria for JSLE. Two (0.7%) of them were female. These also had KD according to European League against Rheumatism / Paediatric Rheumatology European Society (EULAR/PReS) consensus criteria and are described in this report. One case was a 13-year-old who presented all six KD criteria. Echocardiogram showed pericardial effusion, dilatation and tortuosity of right and left coronary, and her symptoms promptly improved after treatment with intravenous immunoglobulin (IVIG). Lupus diagnosis was established a few days later. Another case was a 4-year-old who had also met all six KD criteria, with improvement after IVIG, and lupus diagnosis was made 1 year later. In conclusion, the frequency of the association between these two autoimmune diseases was rare. The occurrence of a second autoimmune systemic disease in a patient with a history of KD should also be considered. Furthermore, the initial presentation of lupus may mimic KD. Lupus (2012) 21, 89-92.

Chronic mucocutaneous candidiasis and systemic lupus erythematosus: a new variant of chronic mucocutaneous candidiasis?

Chronic mucocutaneous candidiasis (CMC) is characterized by susceptibility to Candida infection of skin, nails, and mucous membranes. Autoimmune endocrinopathies are common in CMC patients, but there are no reports of the involvement of systemic autoimmune disorders. We present here the first case of this kind of association in a patient with an autosomal dominant variant of CMC. The individual had had this disorder since childhood and systemic lupus erythematosus with secondary antiphospholipid syndrome, as well as renal, articular and hepatic manifestations without thymoma.

Subclinical impairment of ovarian reserve in juvenile systemic lupus erythematosus after cyclophosphamide therapy

Objective To perform systematic assessment of ovarian reserve markers using a combination of tests in juvenile systemic lupus erythematosus (JSLE) patients without amenorrhoea. Methods Twenty-seven consecutive JSLE female patients and 13 healthy controls without amenorrhoea were evaluated for 6 months. Ovarian reserve was assessed during early follicular phase by serum levels of follicle stimulating hormone (FSH), luteinising hormone (LH), estradiol, inhibin A, inhibin B and anti-Mullerian hormone (AMH). Ovarian size was measured by abdominal ultrasonography. Demographic data, disease activity, damage and treatment were also analysed. Results The median of current age was similar in ISLE patients and controls (16.5 vs. 15years, p=0.31) with a significantly higher age at menarche (13 vs. 12years, p=0.03). A trend of lower median total antral follicle count was observed in JSLE compared to controls (9 vs. 14.5, p=0.062) with similar median of other ovarian reserve parameters (p>0.05). Further evaluation of patients treated with cyclophosphamide and those without this treatment revealed a higher median FSH levels (6.4 vs. 4.6 IU/L, p=0.023). Inhibin B, AMH levels and ovarian volume were also lower but did not reach statistical significance (10.8 vs. 27.6 pg/mL, p=0.175; 0.6 vs. 1.5 ng/mL, p=0.276; 3.4 vs. 5 cm(3), p=0.133; respectively). LH (2.7 vs. 2.9 IU/L, p=0.43), estradiol (50 vs. 38 pg/mL, p=0.337) and inhibin A (1.1 vs. 0 pg/mL, p=0.489) levels were comparable in both groups. Conclusions Our study suggests that ovarian reserve after cyclophosphamide treatment may be hampered in spite of the presence of menstrual cycles emphasising the relevance of gonadal protection during the use of this alkylating agent.

Organ-specific autoantibodies and autoimmune diseases in juvenile systemic lupus erythematosus and juvenile dermatomyositis patients

Objectives To our knowledge, no study assessed simultaneously a variety of organ-specific autoantibodies and the prevalence of organ-specific autoimmune diseases in juvenile systemic lupus erythematosus (ISLE) and juvenile dermatomyositis (JDM). Therefore, the purpose of this study was to evaluate organ-specific autoantibodies and autoimmune diseases in JSLE and JDM patients. Methods Forty-one JSLE and 41 JDM patients were investigated for autoantibodies associated with autoimmune hepatitis, primary biliary cirrhosis, type I diabetes mellitus (TIDM, autoimmune thyroiditis (AT), autoimmune gastritis and coeliac disease (CD). Patients with positive antibodies were investigated for the respective organ-specific autoimmune diseases. Results Mean age at diagnosis was higher in ISLE compared to JDM patients (10.3 +/- 3.4 vs. 7.3 +/- 3.1 years, p=0.0001). The frequencies of organ-specific autoantibodies were similar in JSLE and JDM patients (p>0.05). Of note, a high prevalence of TIDM and AT autoantibodies was observed in both groups (20% vs. 15%, p=0.77 and 24% vs. 15%, p=0.41; respectively). Higher frequencies of ANA (93% vs. 59%, p=0.0006), anti-dsDNA (61% vs. 2%, p<0.0001), anti-Ro, anti-Sm, anti-RNP, anti-La and IgG-aCL were observed in JSLE (p<0.05). Organ-specific autoimmune diseases were evidenced only in ISLE patients (24% vs. 0%, p=0.13). Two ISLE patients had TIDM associated with Hashimoto thyroiditis and another had subclinical thyroiditis. Another JSLE patient had CD diagnosis based on iron deficiency anaemia, anti-endomysial antibody, duodenal biopsy compatible to CD and response to a gluten-free diet. Conclusions Organ-specific diseases were observed solely in ISLE patients and required specific therapy. The presence of these antibodies recommends the evaluation of organ-specific diseases and a rigorous follow-up.

Lupus erythematosus panniculitis in children and adolescents

Introduction: Lupus erythematosus panniculitis (LEP) or lupus erythematosus profundus is a rare form of chronic cutaneous manifestation affecting both adults and pediatric patients. The prevalence of this manifestation was seldom reported in juvenile systemic lupus erythematosus (JSLE). Case reports: From January 1983 to December 2010, 5,506 patients were followed at the Pediatric Rheumatology Unit of our University Hospital and 278 (5%) of them met the American College of Rheumatology classification criteria for JSLE. Two (0.7%) of them had LEP at JSLE onset. These two cases had tender deep inflammatory subcutaneous nodules or plaques at the time of diagnosis, and the histopathologic pattern evidenced lobular or mixed panniculitis with lymphocytic inflammatory cells of the fat lobule. Treatments for LEP included mainly antimalarials, systemic corticosteroids and sunscreen protection. One male patient required thalidomide and immunosuppressive drugs, including mycophenolate mofetil, cyclosporin and intravenous cyclophosphamide. However, skin lesions improved only after rituximab treatment. Discussion: LEP was rarely observed in our cohort of JSLE patients as the first lupus manifestation. Anti-CD20 monoclonal antibody therapy may be an option for refractory LEP treatment in children.

Disseminated histoplasmosis in a juvenile lupus erythematosus patient

Introduction: Histoplasmosis is an infection caused by dimorphic fungus, Histoplasma capsulatum, and it has not been reported in juvenile systemic lupus erythematosus (JSLE) patients, particularly progressive disseminated histoplasmosis (PDH) subtype. Case report: We reported herein a 14-year old girl who was diagnosed with JSLE. Six months later, she had abdominal distension and received prednisone, hydroxychloroquine and azathioprine. Computer tomography evidenced hepatosplenomegaly and multiple mesenteric, mediastinal and retroperitoneal enlarged lymph nodes, forming large conglomerates at the mesentery, suggestive of lymphoproliferative disorder. After 10 days, she had acute surgical abdominal, and underwent a laparotomy and intestinal perforation and conglomerates of lymph nodes were observed. The jejunum biopsy showed perforated acute enteritis with hemorrhage and necrosis, and Grocott staining identified Histoplasma sp. and the culture showed a heavy growth of Histoplasma capsulatum. At that moment liposomal amphotericin B (1.0 mg/Kg/day) was introduced. Despite this treatment she died due to septic shock eight days later. Diffuse Histoplasma capsulatum was evidenced at autopsy. Conclusion: We reported a severe opportunistic infection in JSLE patient with adenopathy and multiple intestinal perforations. This study reinforces the importance of early diagnosis and antifungal therapy, especially in patients with these uncommon clinical manifestations.

Monocyte Chemoattractant-1 as a Urinary Biomarker for the Diagnosis of Activity of Lupus Nephritis in Brazilian Patients

Objective. Monocyte chemotactic protein (MCP-1), involved in the pathogenesis of lupus nephritis (LN), has recently been indicated as a new biomarker of kidney activity in systemic lupus erythematosus (SLE). Our aim was to assess urinary MCP-1 (uMCP-1) as a biomarker of renal activity in patients with SLE and to compare it to other disease activity markers, using the ELISA. Methods. Seventy-five female Brazilian patients with SLE and a control group participated in our study. Patients with SLE were distributed among 3 groups according to kidney involvement and classified according to disease activity based on clinical and laboratory measures such as urinary sediment, proteinuria, kidney function, C3, C4, anti-dsDNA, disease activity index, and renal SLE disease activity index. The serum and uMCP-1 concentrations were measured by sandwich ELISA. Results. In the A-LN group (active lupus nephritis: SLE with kidney involvement), the concentration of uMCP-1 was significantly higher than in other groups. A cutoff point was established using the results of the control group to apply this test in the detection of LN. A-LN had a higher frequency of positive results for uMCP-1 in comparison to the other groups (p < 0.001). To detect disease activity in patients with LN, a new cutoff was determined based on the results of patients with SLE with kidney involvement. Setting specificity at 90%, the sensitivity of the test was 50%. Conclusion. The high specificity makes uMCP-1 a useful test as a predictor of kidney activity in SLE, especially when associated to other measures used in clinical practice. (First Release Sept 1 2012; J Rheumatol 2012;39:1948-54; doi :10.3899/jrheum.110201)

Fluctuation of Anti-Endothelial Cell Antibody Titers in Mixed Connective Tissue Disease

Background: Antibodies directed against endothelial cell surface antigens have been described in many disorders and have been associated with disease activity. Since the most prominent histopathologic feature in mixed connective tissue disease (MCTD) is the widespread and unique proliferative vascular lesion, our aim was to evaluate the frequency of anti-endothelial cell antibodies (AECA) in this condition. Objectives: To evaluate the frequency of AECA in this disease and assess its clinical and laboratory associations. Methods: Seventy-three sera from 35 patients with MCTD (Kasukawa's criteria), collected during a 7 year period, were tested for immunoglobulins G and M (IgG and IgM) AECA by cellular ELISA, using HUVEC (human umbilical vein endothelial cells). Sera from 37 patients with systemic lupus erythematosus (SLE), 22 with systemic sclerosis (SSc) and 36 sera from normal healthy individuals were used as controls. A cellular ELISA using HeLa cells was also performed as a laboratory control method. Results: IgG-AECA was detected in 77% of MCTD patients, 54% of SLE patients, 36% of SSc patients and 6% of normal controls. In MCTD, IgG-AECA was associated with vasculitic manifestations, disease activity and lymphopenia, and was also a predictor of constant disease activity. Immunosuppressive drugs were shown to reduce IgG-AECA titers. Since antibodies directed to HeLa cell surface were negative, AECA was apparently unrelated to common epitopes present on epithelial cell lines. Conclusions: AECA are present in a large proportion of patients with MCTD and these antibodies decrease after immunosuppressive treatment. IMAJ 2012; 14:84-87

Influenza A/H1N1 vaccination of patients with SLE: can antimalarial drugs restore diminished response under immunosuppressive therapy?

Objective. To assess the efficacy and safety of pandemic 2009 influenza A (H1N1) in SLE under different therapeutic regimens. Methods. A total of 555 SLE patients and 170 healthy controls were vaccinated with a single dose of a non-adjuvanted preparation. According to current therapy, patients were initially classified as SLE No Therapy (n = 75) and SLE with Therapy (n = 480). Subsequent evaluations included groups under monotherapy: chloroquine (CQ) (n = 105), prednisone (PRED) epsilon 20 mg (n = 76), immunosuppressor (IS) (n = 95) and those with a combination of these drugs. Anti-H1N1 titres and seroconversion (SC) rate were evaluated at entry and 21 days post-vaccination. Results. The SLE with Therapy group had lower SC compared with healthy controls (59.0 vs 80.0%; P < 0.0001), whereas the SLE No Therapy group had equivalent SC (72 vs 80.0%; P = 0.18) compared with healthy controls. Further comparison revealed that the SC of SLE No Therapy (72%) was similar to the CQ group (69.5%; P = 0.75), but it was significantly reduced in PRED epsilon 20 mg (53.9%; P = 0.028), IS (55.7%; P = 0.035) and PRED epsilon 20 mg + IS (45.4%; P = 0.038). The concomitant use of CQ in each of these later regimens was associated with SC responses comparable with SLE No Therapy group (72%): PRED epsilon 20 mg + CQ (71.4%; P = 1.00), IS + CQ (65.2%; P = 0.54) and PRED epsilon 20 mg + IS + CQ (57.4%; P = 0.09). Conclusion. Pandemic influenza A H1N1/2009 vaccine response is diminished in SLE under immunosuppressive therapy and antimalarials seems to restore this immunogenicity.

Lupus nephritis is more severe in children and adolescents than in older adults

Objective: To evaluate clinicopathological features and treatment response in patients with lupus nephritis (LN), comparing the childhood- and late-onset forms of the disease. Methods: We retrospectively analyzed clinical presentation, treatment and evolution in patients diagnosed with LN by renal biopsy between 1999 and 2008. Patients were grouped by age-<= 18 years (n = 23); and >= 50 years (n = 13)-and were followed for the first year of treatment. Results: The baseline features of the childhood- and late-onset groups, respectively, were as follows: mean age, 15 +/- 2 and 54 +/- 5 years; female gender, 87% and 92%; hypertension, 87% and 77%; Systemic Lupus Erythematosus Disease Activity Index, 29 +/- 9 and 17 +/- 7 (p = 0.002); estimated glomerular filtration rate (eGFR), 86 +/- 66 and 70 +/- 18 ml/min; concurrent SLE/LN diagnosis, 90% and 15% (p < 0.001); crescents on biopsy, 74% and 30% (p = 0.02); activity index on biopsy, 4.8 +/- 2.6 and 3.3 +/- 1.9 (p = 0.10); and interstitial fibrosis (> 10%), 39% and 61% (p = 0.08). Treatment consisted mainly of methylprednisolone, prednisone and intravenous cyclophosphamide, average cumulative doses being similar between the groups. After 12 months of treatment, the eGFR in the younger and older patients was 116 +/- 62 and 78 +/- 20 ml/min, respectively (p = 0.005). Three of the younger patients progressed to dialysis at 12 months, compared with none of the older patients. Conclusion: Childhood-onset LN seems to be more severe than is late-onset LN. Lupus (2012) 21, 978-983.

Systemic sclerosis sine scleroderma associated with antiphospholipid syndrome

The antiphospholipid syndrome (APS) can be primary, when it occurs alone, or secondary, when it is associated with another autoimmune disease, mainly systemic lupus erythematosus and rarely other autoimmune diseases. Cases described in literature (Medline 1966 to December 2009) associate the presence of antiphospholipid antibodies with the presence of APS and systemic sclerosis (SS). Currently, however, no cases of the SS variant sine scleroderma with APS have been described. In this study, the authors describe the case of a patient with APS characterised by thrombosis of the retinal veins, in May 2006, the presence of lupus anticoagulant and an anticardiolipin IgG antibody. In May 2007, this patient developed Raynaud's phenomenon, a lack of oesophageal motility and nailfold capillaroscopy with a scleroderma pattern. The patient was positive for the anti-centromere antibody but lacked any evidence of cutaneous thickening or involvement. In summary, the authors describe the first case of a patient with APS associated with SS sine scleroderma.