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The relationship between primary hematologic disease and rheumatologic manifestations is well known, especially acute lymphocytic leukemia, lymphomas, plasma cell dyscrasias and myelodysplastic syndrome (MDS). Currently, more has been described about autoimmune manifestations in chronic myelomonocytic leukemia (CMML). Many different clinical scenarios may lead a patient with MDS/CMML initially to seek a rheumatological unit. Autoimmune features such as polymyalgia rheumatic symptoms, myositis, neutrophilic dermatosis, cutaneous vasculitis and positive antinuclear antibodies (ANA) are some examples of clinical presentation of MDS/CMML. Moreover, peripheral cytopenias are a common initial presentation both for systemic lupus erythematous (SLE) and MDS/CMML. The aim of this study was to describe a case of an elderly woman with thrombocytopenia and positivity of antibodies to anti-extractable nuclear antigens (anti-ENA) as initial manifestation of CMML mimicking SLE, and to present some clues that encourage the clinician to perform a bone marrow study in such a clinical scenario.

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OBJECTIVE: The aims of this study were to analyze the pulmonary function of childhood-onset systemic lupus erythematosus (cSLE) patients and to identify possible correlations between the high-resolution computed chest tomography (HRCT) score, disease activity, disease cumulative damage, and the participants' quality of life. METHODS: Forty cSLE patients, median age: 14.1 years (range: 7.4-17.9), underwent spirometry and plethysmography. Carbon monoxide diffusing capacity (DLCO), HRCT, disease activity, disease cumulative damage, and quality of life were assessed. RESULTS: Pulmonary abnormalities were evident in 19/40 (47.5%) cSLE patients according to spirometry/DLCO. Forced expired volume in one second (FEV1%) was the parameter most affected (30%). The HRCT showed some abnormality in 22/30 patients (73%), which were minimal in 43%. Signs of airway affects were found in 50%. Twelve patients were hospitalized due to cSLE-related pulmonary complications before the study began (median discharge: 2.1 years earlier). Total lung capacity (TLC%), vital capacity (VC%), forced vital capacity (FVC%), and FEV1% were significantly lower in the group with hospitalization compared to the group without hospitalization (p = 0.0025, p = 0.0022, p = 0.0032, and p = 0.0004, respectively). Of note, DLCO was positively correlated with disease duration (r = +0.4; p = 0.01). The HRCT-score was negatively correlated with FEV1/VC (r = -0.63; p = 0.0002), FEV1 (r = -0.54; p = 0.018), FEF25%-75% (r = -0.67; p < 0.0001), and HRCT-score was positively correlated with resistance (r = +0.49; p = 0.0056). CONCLUSIONS: Almost half of patients with cSLE had subclinical pulmonary abnormalities, especially airway abnormalities. The cSLE-related pulmonary complications seem to determine long-term functional damage.

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INTRODUCTION: Several studies have shown that Hispanic patients generally experience a worse renal prognosis than non-Hispanic white patients with lupus. To date, there is no report on American College of Rheumatology (ACR) renal response criteria (ACR-RRC) in patients from Latin America. OBJECTIVE: To evaluate treatment response in patients with proliferative and membranous lupus nephritis (LN) according to ACR-RRC. METHODS: A retrospective study (2001-2011) was performed in our hospital and the data collected included clinical information, renal assessment and immunological parameters. Details related to treatment received during induction and maintenance therapy were also recorded. RESULTS: The study included forty-three Latin American patients (37 women) from Argentina. Mean follow-up was 54 months. The regimen used for induction therapy included intravenous cyclophosphamide (IV-CYC) for six months in 36 patients and only seven received mycophenolate mofetil (MMF) given twice daily for a total dose of 2.5 ± 0.5 grams a day. For the maintenance period, six patients continued with quarterly IV-CYC, 20 patients received MMF (1.5 ± 0.5 grams a day) and 17 patients received azathioprine (AZA) 1.5 - 2 mg/kg/day. ACR-RRC observed after induction therapy was complete response in 19%, partial response in 9%, improvement in 42%, unchanged in 14%, and 16% had deterioration despite treatment. ACR-RRC observed after maintenance therapy was complete response in 30%, partial response in 23%, improvement in 19%, unchanged in 16%, and 12% had deterioration. Relapse was observed in 11 patients (25%). Ten out of 11 cases (91%) who relapsed did not achieve a complete response at the end of the induction therapy. CONCLUSION: In Latin American patients from Argentina, only 19% could achieve a complete response after induction therapy and 30% achieved a complete response after maintenance therapy. Failing to obtain a complete response after induction therapy was related to an increased risk of relapse during long-term follow-up in our study.

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OBJECTIVE: To examine the characteristics of patients who developed late onset systemic lupus erythematosus (SLE) in the GLADEL (Grupo Latino Americano de Estudio del Lupus) cohort of patients with SLE. METHODS: Patients with SLE of less than two years of disease duration, seen at 34 centers of nine Latin American countries, were included. Late-onset was defined as >50 years of age at time of first SLE-related symptom. Clinical and laboratory manifestations, activity index (SLEDAI), and damage index (SLICC/ACR- DI) were ascertained at time of entry and during the course (cumulative incidence). Features were compared between the two patient groups (<50 and ≥50) using descriptive statistics and hypothesis tests. Logistic regression was performed to examine the association of late-onset lupus, adjusting for other variables. RESULTS: Of the 1480 patients included, 102 patients (6.9 %) had late-onset SLE, 87% of which were female. Patients with late-onset SLE had a shorter follow-up (3.6 vs. 4.4 years, p < 0.002) and a longer time to diagnosis (10.1 vs. 5.8 months, p < 0.001) compared to the younger onset group. Malar rash, photosensitivity, and renal involvement were less prevalent while interstitial lung disease, pleural effusions, and sicca symptoms were more frequent in the older age group (p > 0.05). In multivariable analysis, late onset was independently associated with higher odds of ocular (OR = 3.66, 95% CI = 2.15-6.23), pulmonary (OR = 2.04, 95% CI = 1.01-4.11), and cardiovascular (OR = 1.76, 95% CI = 1.04-2.98) involvement and lower odds of cutaneous involvement (OR = 0.41, 95% CI = 0.21-0.80), number of cumulative SLE criteria (OR = 0.79, 95% CI = 0.64-0.97), use of cyclophosphamide (OR = 0.47, 95% CI = 0.24-0.95), and anti-RNP antibodies (OR = 0.43, 95% CI = 0.20-0.91). A Cox regression model revealed a higher risk of dying in older onset than the younger-onset SLE (OR = 2.61, 95% CI = 1.2-5.6). CONCLUSION: Late-onset SLE in Latin Americans had a distinct disease expression compared to the younger-onset group. The disease seems to be mild with lower cumulative SLE criteria, reduced renal/mucocutaneous involvements, and less use of cyclophosphamide. Nevertheless, these patients have a higher risk of death and of ocular, pulmonary, and cardiovascular involvements.

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Several questions regarding the production and functioning of autoantibodies (AAb) during malaria infection remain open. Here we provide an overview of studies conducted in our laboratory that shed some light on the questions of whether antiphospholipid antibodies (aPL) and other AAb associated with autoimmune diseases (AID) can recognize Plasmodia antigens and exert anti-parasite activity; and whether anti-parasite phospholipid antibodies, produced in response to malaria, can inhibit phospholipid-induced inflammatory responses and protect against the pathogenesis of severe malaria. Our work showed that sera from patients with AID containing AAb against dsDNA, ssDNA, nuclear antigens (ANA), actin, cardiolipin (aCL) and erythrocyte membrane antigens recognize plasmodial antigens and can, similarly to monoclonal AAb of several specificities including phospholipid, inhibit the growth of P. falciparum in vitro. However, we did not detect a relationship between the presence of anti-glycosylphosphatidylinositol (GPI) antibodies in the serum and asymptomatic malaria infection, although we did register a relationship between these antibodies and parasitemia levels in infected individuals. Taken together, these results indicate that autoimmune responses mediated by AAb of different specificities, including phospholipid, may have anti-plasmodial activity and protect against malaria, although it is not clear whether anti-parasite phospholipid antibodies can mediate the same effect. The potential effect of anti-parasite phospholipid antibodies in malarious patients that are prone to the development of systemic lupus erythematosus or antiphospholipid syndrome, as well as the (possibly protective?) role of the (pathogenic) aPL on the malaria symptomatology and severity in these individuals, remain open questions.

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Resumen El compromiso renal en el lupus eritematoso sistémico (LES) es uno de los mayores determinantes del curso y pronóstico de estos pacientes. Existe evidencia de la asociación de anticuerpos anti-C1q y el desarrollo de nefritis lúpica. El objetivo de este estudio fue determinar la prevalencia de anticuerpos anti-C1q y su asociación con nefritis lúpica en pacientes colombianos con LES. Métodos: Estudio de corte transversal en el cual se incluyeron 80 pacientes con diagnóstico de LES según criterios del Colegio Americano de Reumatología. La cuantificación de anticuerpos anti-C1q séricos se realizó por ELISA, se consideraron positivas concentraciones ≥15 U/ml. Resultados: Los pacientes eran predominantemente mujeres (87%) y 43,7% tuvieron proteinuria >0,5 g/día, la cual fue más común en pacientes jóvenes y apareció tempranamente en la enfermedad. Cuarenta y cuatro (55%) de los pacientes tenían anticuerpos anti-C1q positivos, en quienes la proteinuria fue más frecuente (OR=4.3, IC95% 1.7 - 11, p=0.003). Se encontró correlación inversa débil entre los títulos de anti-C1q, el consumo de C3 (r=-0.54, p<0.001) y la depuración de creatinina (r=-0.33, p=0.035); una correlación directa débil, con la proteinuria (r=0.35, p=0.024) y la actividad de la enfermedad, la cual se determinó con el Índice de Actividad de Enfermedad (SLEDAI) (r=0.48, p<0.0001). Conclusiones: Los anticuerpos anti-C1q pueden ser útiles en la evaluación de la nefritis lúpica activa, y podrían ser implementados como un marcador diagnóstico de nefritis lúpica y como un posible marcador de actividad de la enfermedad en pacientes con LES, tal como lo ha sugerido la Liga Europea contra el Reumatismo (EULAR).

Summary Renal involvement in systemic lupus erythematosus (SLE) is one of the major determinants Anti-C1q antibodies of the course and prognosis of these patients. There is evidence of the association of Anti-DNA antibodies anti-C1q antibodies and the development of lupus nephritis. The aim of this study was to determine the prevalence of anti-C1q antibodies and its association with lupus nephritis in Colombian patients with SLE. Methods: 80 SLE patients as defined by the American College of Rheumatology criteria. Quantification of anti-C1q antibodies in patients' sera was performed by ELISA and concentrations greater than 15U/ml were considered positive. Results: Patients were predominantly women (87%) and 43.7% of them had proteinuria > 0.5 g / 24 hours which was more common in younger patients and early in the course of the disease. Forty-four (55%) of patients had positive anti-C1q, in whom, proteinuria was more frequent (OR = 4.3 95% CI 1.7 - 11, p = 0.003). A weak inverse correlation between anti-C1q titers, C3 consumption (r = -0.54, p <0.001) and creatinine clearance was found (r = -0.33, p = 0.035); similarly, we also found a weak direct correlation with proteinuria (r = 0.35, p = 0.024) and disease activity ascertained with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) (r = 0.48, p <0.0001). Conclusions: Anti-C1q antibodies might be valuable for the evaluation of active lupus nephritis, and might be valuable for the evaluation of active lupus nephritis, and could be included as a diagnostic marker of lupus nephritis and maybe as a marker for disease activity, as suggested by the European League Against Rheumatism (EULAR).

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INTRODUCTION: Infections are the leading cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Invasive fungal infections (IFI) comprise a group of diseases caused by Cryptococcus, Histoplasma, Aspergillus and Candida. Few studies of IFI have been published in patients with SLE and associated factors have not been completely defined. OBJECTIVES: The objectives of this paper are to estimate the frequency of IFI in admitted patients with SLE in our hospital, to determine the risk factors associated with IFI in our patients with SLE, and to compare IFI group with a control group (SLE without IFI). METHODS: The medical charts of patients with IFI (EORTC/MSG, 2008) and SLE (ACR, 1997) admitted to our hospital from June 2001 until June 2012 were reviewed. To identify factors associated with IFI, we developed a case-control study (SLE + IFI vs SLE alone) in a one to three ratio adjusted for sex and age and hospitalization for other reasons. Comparison was made of demographic characteristics, duration of disease and disease activity previous to IFI diagnosis, especially three months before fungal infection. We defined severe activity as SLEDAI ≥ 8. Infection by fungi of the genus Candida was considered only in its disseminated form. RESULTS: Ten cases of IFI were identified in 208 patients with SLE admitted between June 2001 and June 2012. We included 40 patients with SLE (10 with IFI and 30 controls). Of the SLE-IFI patients, eight were women and the average age was 27.5 years (range, 19-42 years). Fungal isolation: eight Cryptococcus neoformans, one Histoplasma capsulatum and one Candida albicans. Sites affected: five in peripheral blood, five in central nervous system (CNS), four in skin/soft tissue and one in pleura. Mortality was 40% (p = 0.002), with Cryptococcus neoformans being the most common fungus. The SLE disease activity was severe in 70% of infected patients and no significant difference with the control group was found (p = 0.195). We also found no association with leukopenia, lymphopenia, hypocomplementemia, hypogammaglobulinemia or anti-DNA positivity; neither with meprednisone doses >20 mg/day or intravenous methylprednisolone pulse therapy before fungal infection. The use of immunosuppressive therapy with azathioprine showed a significant association (p = 0.017). Cyclophosphamide (p = 0.100) or mycophenolate mofetil (p = 0.256) did not show similar results. CONCLUSION: The frequency of IFI in hospitalized SLE patients in our hospital was 4.8%. Cryptococcus neoformans was the most common etiologic agent and was primarily responsible for the deaths in this cohort. These data are consistent with publications in East Asia rather than North America where Candida spp. is more common. Unlike other publications, previous immunosuppression with azathioprine was the only risk factor associated with the development of the infection. Invasive fungal infection should be suspected in hospitalized patients with SLE and immunosuppression with CNS or atypical cutaneous manifestation of SLE in order to start appropriate treatment early and obtain better outcome.

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