Luis Alonso González

Impact of Race and Ethnicity in the Course and Outcome of Systemic Lupus Erythematosus

Genetic factors seem to play a more important role early in the course of systemic lupus erythematosus (SLE), whereas nongenetic factors seem to play a more important role over the course of the disease. SLE is more frequent with less favorable outcomes in nonwhite populations. To overcome these differences and reduce the immediate-term, mediate-term, and long-term impact of SLE among disadvantaged populations, it is essential to increase disease awareness, to improve access to health care and to provide care to these patients in a consistent manner regardless of the severity of their disease.

Epidemiología de la osteoporosis

Resumen La osteoporosis se define como una entidad esqueletica caracterizada por baja masa osea y deterioro de la microarquitectura osea, lo cual lleva a una mayor fragilidad osea y riesgo de fractura. Todas las fracturas osteoporoticas aumentan la morbilidad de los pacientes; sin embargo, las fracturas de cadera y vertebrales tambien estan asociadas con una mayor mortalidad. Estas fracturas por fragilidad tambien son una carga considerable para el sistema de salud y tienen un gran impacto economico. Por lo tanto, el conocimiento de la epidemiologia de la enfermedad es fundamental para tratar de desarrollar estrategias que esten orientadas a disminuir esta carga.

Cryptococcosis in systemic lupus erythematosus: a series of six cases

The aims of this study were to describe the clinical features of patients with systemic lupus erythematosus (SLE) who developed cryptococcal infection and ascertain their outcomes when treated with glucocorticoids and immunosuppressive agents in conjunction with long-term maintenance antifungal therapy. Six cases of cryptococcal infection in SLE were reviewed retrospectively. The mean age at the time of infection was 26.3 (11.7) years. Three patients had active SLE and all were receiving glucocorticoids [median prednisone dose of 40 (21.2—60.0) mg/day] at the time of infection diagnosis. Concomitant cytotoxic agents were used in five patients. Meningitis was the most common clinical manifestation (n = 5) and cryptococcemia was found in three cases. The patient, who developed pulmonary cryptococcosis, died from respiratory distress syndrome. All patients received induction anti-fungal therapy with amphotericin B and the five surviving patients switched to oral fluconazole indefinitely as maintenance therapy and none of them has had relapses of cryptococcal infection to last medical evaluation. As SLE patients have intrinsic abnormalities of cell-mediated immunity and receive immunosuppressive therapy, indefinite maintenance therapy with fluconazole is recommended in SLE patients with cryptococcosis. Lupus (2010) 19, 639—645.

Primary biliary cirrhosis/autoimmune hepatitis overlap syndrome developing in a patient with systemic lupus erythematosus: a case report and review of the literature

Sir, More than 80% of primary biliary cirrhosis (PBC) patients have at least one associated autoimmune condition. Among these conditions, the most frequent are Sjögren’s syndrome, scleroderma, rheumatoid arthritis and Hashimoto’s thyroiditis. The association of PBC with systemic lupus erythematosus (SLE) is rare and only a few cases have been reported. In contrast, among PBC patients the association with autoimmune hepatitis (AIH) has a prevalence of up to 9.2%. We report an unusual occurrence of PBC/AIH overlap syndrome in a SLE patient. A 50-year-old woman was diagnosed with SLE in 1986 at the age of 27 because of positive antinuclear (1:1280, homogeneous pattern) and anti-dsDNA (1:640) antibodies, malar rash, photosensitivity, non-erosive polyarthritis and lymphopenia. In 1989, urinalysis disclosed nephroticrange proteinuria (4 g/day) and microhaematuria. Diffuse proliferative lupus glomerulonephritis was confirmed by renal biopsy. Prednisolone (50mg/day) with seven monthly oral cyclophosphamide pulses (500mg each) were prescribed and then followed by eight quarterly oral cyclophosphamide pulses. Autoimmune hypothyroidism was diagnosed on the basis of high thyroid-stimulating hormone (TSH) levels (9 uUI/ml) and positive antithyroid antibodies. In March 2009, she complained of fatigue, pruritus, polyarthralgias and unquantified weight loss. Laboratory evaluations revealed: 2200/mm leukocytes, 91,000/mm platelets, and high liver enzyme levels [alkaline phosphatase (1090 U/l), g-glutamyltransferase (2116 U/l), ALT (300 U/l) and AST (232 U/l)]. Anti-mitochondrial antibodies (AMA) were positive (1:160) and anti-dsDNA and smooth-muscle antibodies (SMA) were negative. Serology for hepatitis C and B viruses was negative and serum ceruloplasmin levels were within normal limits. She had no history of alcohol consumption or hepatotoxic drug use. Abdominal ultrasonography showed a liver of micronodular aspect and splenomegaly. Upper digestive endoscopy revealed oesophageal varices. Histological features of liver biopsy revealed: portal inflammatory infiltrate consisting of lymphocytes and plasmocytes, marked loss of bile ducts, and mononuclear cell inflammatory infiltrate of the limiting plate (interface hepatitis). These findings were compatible with PBC and AIH (Figure 1). Ursodeoxycholic acid and azathioprine were started whereas prednisolone dose was increased to 30mg/day. Although abnormal liver function tests are frequent in SLE (25–50%), clinically significant liver disease is uncommon. Liver function tests abnormalities in SLE result from disease activity in 3–23% of patients, adverse drug effects, fatty infiltration, heart failure with passive liver congestion, viral hepatitis or extrahepatic disorders such as myositis. Since liver histology in most studies of SLE patients is missing, it is difficult to attribute the abnormalities in liver function to a specific disorder. In a pathologic series of SLE patients, the most typical finding was hepatic arteritis presenting features of polyarteritis nodosa (15.1%), whereas PBC was found in 2.7%. The linkage between SLE and PBC is rare. Only a few cases of SLE–PBC associations have been reported, one of them reported as AMA-negative PBC (Table 1). AMA are found in 90–95% of PBC patients and its targets are members of a family of enzymes, the 2-oxo-acid

Lupus Eritematoso Sistémico Ampolloso: dramática respuesta a la terapia con dapsona

Resumen El lupus ampolloso es una manifestacion poco frecuente del lupus eritematoso sistemico (LES). Otras enfermedades ampollosas tales como el penfigoide ampolloso, epidermolisis ampollosa adquirida, dermatosis ampollosa Ig A lineal y dermatitis herpetiforme tambien han sido informadas en LES. Describimos un paciente que desarrollo lesiones ampollosas 14 dias luego de iniciar terapia con altas dosis de glucocorticoides y ciclofosfamida para manifestaciones severas del LES (nefritis y hemorragia alveolar). Se confirmo el diagnostico de lupus ampolloso. La respuesta al tratamiento con dapsona fue notable a las 48 horas. En este articulo revisamos la epidemiologia, hallazgos clinicos, histopatologicos e inmunopatologicos; el diagnostico diferencial y el tratamiento del LES ampolloso.

The evolving concept of SLE comorbidities

ABSTRACT Introduction: The survival of SLE patients has improved significantly over the past few decades placing them at increased risk of cardiovascular disease (CVD), malignancies, and osteoporosis, among other comorbidities. The aim of this review was to assess the incidence and prevalence of comorbidities in these patients as well as their prevention and treatment focusing in CVD, malignancies and osteoporosis. Areas covered: We focused on CVD, malignancies and osteoporosis as SLE comorbidities. A literature search (PubMed database) was performed using the words ‘comorbidities’, ‘cardiovascular disease’, ‘osteoporosis’, ‘malignancy’, ‘cancer’ and ‘lupus’ between January 1976 and December 2016. No language restrictions were placed. More than 100 full-length articles were reviewed. Expert commentary: The therapeutic approach in SLE should aim not only at achieving disease remission but also at treating all conditions affecting the patients and, consequently, their outcomes. These patients should be treated as coronary artery disease (CAD) equivalent with rigorous modifiable CV risk factors management in addition to the optimal treatment of their lupus. Furthermore, modifiable osteoporosis traditional risk factors and SLE-related risk factors should be modified to ameliorate bone loss and fracture risk. Cancer preventive measures (smoking cessation and screening programs for cervical cancer) constitute also essential components of the management of these patients.

Infiltrating CD16+ Are Associated with a Reduction in Peripheral CD14+CD16++ Monocytes and Severe Forms of Lupus Nephritis

Our aim was to characterize glomerular monocytes (Mo) infiltration and to correlate them with peripheral circulating Mo subsets and severity of lupus nephritis (LN). Methods. We evaluated 48 LN biopsy samples from a referral hospital. Recognition of Mo cells was done using microscopic view and immunohistochemistry stain with CD14 and CD16. Based on the number of cells, we classified LN samples as low degree of diffuse infiltration (<5 cells) and high degree of diffuse infiltration (≥5 cells). Immunophenotyping of peripheral Mo subsets was done using flow cytometry. Results. Mean age was 34.0 ± 11.7 years and the mean SLEDAI was 17.5 ± 6.9. The most common SLE manifestations were proteinuria (91%) and hypocomplementemia (75%). Severe LN was found in 70% of patients (Class III, 27%; Class IV, 43%). Severe LN patients and patients with higher grade of CD16+ infiltration had lower levels of nonclassical (CD14+CD16++) Mo in peripheral blood. Conclusions. Our results might suggest that those patients with more severe forms of LN had a higher grade of CD14+CD16+ infiltration and lower peripheral levels of nonclassical (CD14+CD16++) Mo and might reflect a recruitment process in renal tissues. However, given the small sample, our results must be interpreted carefully.

Treatment Algorithms for Patients with Systemic Lupus Erythematosus: Comment on the Article by Muangchan et al.

We read with interest the thought-provoking article by Muangchan et al, published recently in Arthritis Care & Research, in which the authors proposed different algorithms for the treatment of systemic lupus erythematosus (SLE) patients (1). We would respectfully like to offer some comments. To begin with, we were a bit surprised that the authors chose to only include physicians who were involved in SLE randomized-controlled trials (RCTs) for the development of these algorithms; it can be argued that these physicians are not representative of the universe of specialists treating patients with SLE across the world. Rheumatologists not involved in RCTs may have a different perception of what is the best for these patients. Furthermore, in a multisystemic disease like lupus, other specialists (nephrologists, dermatologists, and neurologists, among others) could have contributed to these algorithms. Also important is the fact that the bulk of the participants (77%) were from North America; this could have significantly impacted on the selection of specific treatment options. Regarding the development of the algorithms per se, we were surprised at the participants’ low retention rate from the first to the third round, i.e., from the original 37 participants in the first round to 13 (35.1%) in the third round. Furthermore, respondents indicated agreement (

Transferrina y ceruloplasmina en orina de pacientes con lupus eritematoso sistémico. ¿Son útiles para diferenciar pacientes con nefritis lúpica?

70%) in only 6 of the 16 organs (37.5%) for which algorithms were constructed. Taking these facts altogether causes us to wonder how valid these algorithms really are. As to the specificities of the algorithms, we do take exception with the fact that hydroxychloroquine was not considered a first-line therapy for some SLE manifestations when in fact there is ample evidence that antimalarials should be used in all SLE patients, unless there is a contraindication because they have proven to prevent disease flares (2) and damage accrual (3), and to prolong survival (4,5). A second concern regarding the algorithms is the fact that the patients’ race/ethnicity was not considered. This is an important point, given that data from clinical trials, particularly in lupus nephritis, suggest that ethnicity and geographic region may influence treatment response (6,7). When comparing the efficacy of mycophenolate mofetil (MMF) and intravenous cyclophosphamide (IVC) as induction therapy for lupus nephritis by race and ethnicity, more African descendants and Hispanic patients responded to MMF than IVC, while response rates with MMF and IVC were comparable in Asians and whites (6,7). Therefore, race/ethnicity should be taken into account when therapeutic decisions are made, particularly in lupus nephritis. In conclusion, the algorithms presented by Muangchan et al (1) constitute, in our view, the opinion of a relatively reduced number of lupus experts, and therefore they should be interpreted and applied with great caution. Given the heterogeneity of the disease, the fact that mild/moderate, severe, or life-threatening lupus manifestations may occur concomitantly, clinicians treating these patients need to, first and foremost, exercise their clinical judgement.

Tuberculous sacroiliitis in a patient with systemic lupus erythematosus: a case report and literature review:

BACKGROUND AND OBJECTIVE Diagnosis of lupus nephritis (LN) is usually based on renal biopsy, which is an invasive technique that involves multiple risks. Therefore, different biomarkers have emerged as alternatives for the diagnosis of LN. Nonetheless, studies regarding urinary biomarkers in Latin American patients are limited. The objective of this study was to assess the diagnostic value of urinary transferrin and ceruloplasmin to differentiate patients who have renal involvement from those who do not. MATERIALS AND METHODS Systemic lupus erythematosus (SLE) patients that met the revised American College of Rheumatology (ACR) classification criteria were recruited. Patients with another autoimmune disease, active infection (urinary tract or systemic infection), renal replacement therapy, human immunodeficiency virus infection or pregnancy were excluded. A urine sample was collected from each patient. LN was diagnosed according to ACR criteria. The activity and chronicity of LN were measured using the Austin indices. Urinary transferrin and ceruloplasmin levels were measured using commercial enzyme-linked immunosorbent assay (ELISA) kits. Mann-Whitney U test and Students t-test were used to compare data. Spearmans rank correlation was used to determine associations. Lastly, receiver operating characteristic (ROC) curves were created. RESULTS The study involved 120 SLE patients. In all, 85% were female, 76% mestizo, the mean age was 32.8±12.1years and mean systemic lupus erythematosus disease activity index (SLEDAI) was 8.4±8.9; 64% had renal involvement. Urinary levels of the two biomarkers were significantly higher in patients with LN compared to those without LN. Similarly, urinary levels of both biomarkers were significantly higher in patients with active LN compared to those with inactive LN. Furthermore, urinary transferrin levels were significantly higher in Afro-Latin American patients. On the other hand, urinary transferrin levels correlated with SLEDAI and proteinuria, and transferrin and ceruloplasmin levels correlated with each other. The diagnostic value of ROC curves for these urinary biomarkers for LN were good. CONCLUSIONS In our cohort of SLE patients, we found that transferrin and ceruloplasmin were potential biomarkers for LN, and can even differentiate active LN.