Marco Ulises Martínez-Martínez

Invasive fungal infections in patients with systemic lupus erythematosus.

Objective. Invasive fungal infections (IFI) are catastrophic diseases associated with a high mortality. Relatively few cases of IFI have been described in systemic lupus erythematosus (SLE) and their related factors have not been completely explored. We evaluated factors associated with IFI in patients with SLE. Methods. All patients with both IFI and SLE admitted to our hospital in the last 7 years were evaluated and each was compared with 5 hospitalized patients with SLE (controls). Demographic factors, duration of SLE, and treatment in the previous month were compared. Results. Sixty patients with SLE were evaluated (10 with IFI and 50 controls). Median age was 29 years. High C-reactive protein levels were associated with IFI, along with other factors such as high disease activity, mechanical ventilation, treatment with antibiotics, hemodialysis, high doses of glucocorticoids (GC), and treatment with mycophenolate mofetil. Mortality was 4 times more frequent in patients with IFI than in SLE patients without the deep fungal infection. Conclusion. IFI is a rare infection observed in patients with rheumatic diseases. We describe factors associated with IFI in patients with SLE. IFI is associated with elevated morbidity and mortality. Early diagnosis and treatment are desirable.

Factors associated with mortality and infections in patients with systemic lupus erythematosus with diffuse alveolar hemorrhage.

Objective. To evaluate factors associated with mortality and infections in patients with systemic lupus erythematosus (SLE) and diffuse alveolar hemorrhage (DAH). Methods. A retrospective chart review was carried out for medical admissions of patients with a diagnosis of SLE and DAH in 9 hospitals. Clinical and laboratory data were recorded for each patient at DAH diagnosis. Results. We included 57 episodes of DAH of 50 patients (7 recurrences), 49 women (86%), 14 juvenile SLE (24.6%); 24 had died (42.1%). In the chart review we detected infection in 22 episodes (38.6%): 8 invasive fungal infections, 16 bacterial infections, and 2 patients had both types. In the bivariate analysis, factors associated with mortality were high Acute Physiology and Chronic Health Evaluation II scores, requirement of mechanical ventilation (OR 15.0, 95% CI 1.9 to 662.2), infections (fungal or bacterial; OR 3.2, CI 0.9 to 11.1), renal failure (OR 4.9, CI 1.4 to 18.0), and thrombocytopenia (OR 4.3, CI 1.2 to 15.6). We found similar mortality between children and adults. Infections were associated with treatment for SLE, requirement of mechanical ventilation, hypocomplementemia, and high levels of C-reactive protein. Conclusion. Infection is a frequent finding in patients with DAH and SLE; we found similar mortality between adult SLE and juvenile SLE. Factors that we describe associated with infections may influence the therapeutic selection for these patients.

Clinical outcomes and risk factors for posterior reversible encephalopathy syndrome in systemic lupus erythematosus: a multicentric case–control study

Background Posterior reversible encephalopathy syndrome (PRES) is a well-known but rare complication in patients (<1%) with systemic lupus erythematosus (SLE). However, current epidemiological data are quite scant. The aim of the present study was to describe potentially unrecognised risk factors. Patients and methods We performed a multicentre, retrospective case–control study in Mexico between 1999 and 2014. We included a total of 168 patients who accounted for 77 episodes of PRES, as follows: SLE/PRES, 43 patients with 48 episodes; SLE without PRES, 96 patients; and PRES without SLE, 29 patients. SLE diagnosis was considered when patients fulfilled ≥4 American College of Rheumatology criteria. PRES was defined by reversible neurological manifestations and MRI changes. Results Patients with SLE/PRES were younger, presented with seizures as the most common manifestation (81%) and 18% had the typical occipital MRI finding. Hypertension (OR=16.3, 95% CI 4.03 to 65.8), renal dysfunction (OR=6.65, 95% CI 1.24 to 35.6), lymphopenia (OR=5.76, 95% CI 1.36 to 24.4), Systemic Lupus Erythematosus Activity Index ≥ 6 points (OR=1.11, 95% CI 1.01 to 1.22) and younger age (OR=0.86, 95% CI 0.81 to 0.91, p<0.001) were independent risk factors for development of PRES in SLE. Furthermore, dyslipidemia also characterised the association between PRES and SLE (OR=10.6, 95% CI 1.17 to 96.4). Conclusions This is the largest reported series of patients with SLE and PRES. We were able to corroborate the known risk factors for of PRES, and found two previously undescribed factors (lymphopenia and dyslipidemia), which suggests that endothelial dysfunction is a key element in PRES pathogenesis in lupus patients.

Enfermedades relacionadas con IgG4, diagnóstico histopatológico retrospectivo. Prevalencia en un hospital universitario

INTRODUCTION IgG4 related diseases (IgG4-RD) are characterized mainly by organic dysfunction and inflammation with lymphoplasmacytic cells infiltration. METHODS We conducted a retrospective study. We analyzed patients with a diagnosis of IgG4-RD through histopathologic registries. We divided the study into three phases: (i)extraction of data from the registries of the Pathology Department, including specimens reported with: non-specific inflammation with plasmatic cell infiltration, inflammatory pseudo-tumors and storiform fibrosis, and excluding any report of cancer or infection; (ii)from the selected specimens, three pathologists microscopically re-analyzed these biopsies and included only those who had at least two of the inclusion criteria cited above; (iii)finally, immunostaining was performed in the specimens selected in the second phase. The selected biopsies were catalogued as compatible for IgG4-RD if they had at least 3 inclusion criteria and as probable if they had 2 inclusion criteria. RESULTS On the first phase of the study we analyzed 23,720 biopsies, from which we included 71 and excluded 29 specimens; the rest of the specimens (n=41) underwent immunostaining. From the biopsies included, 41.4% (n=17/71) were positive to IgG4, with the most common histological diagnosis for the positive specimens being granulomatous mastitis, which represented 12.1% of the specimens catalogued initially as probable. The rest of the positive biopsies were from aortitis, dacrioadenitis and/or sialoadenitis, lung pseudo-inflammatory tumor, pericarditis and chronic pancreatitis. CONCLUSIONS The suspicion of IgG4 related disease should not be based solely on clinical manifestations or serology. In the present study we confirm the characteristic changes of IgG4-RD in patients without initial clinical suspicion.

Manifestaciones pulmonares de la granulomatosis con poliangitis

OBJECTIVE To describe the clinical and laboratory data, with special emphasis on thoracic imaging findings, in 14 patients with a definitive diagnosis of granulomatosis with polyangiitis (GPA). METHODS The clinical and tomographic data of 14 patients with a definitive diagnosis of GPA are presented. Patients with thoracic manifestations suggestive of GPA were evaluated in 3 hospitals from 2000 to 2012. All patients had a sputum analysis and bronchoalveolar lavage for bacterial, mycobacterial and fungal stains and cultures; antineutrophil cytoplasmic antibodies, antinuclear-antibodies, rheumatoid factor, and a biopsy of involved organs. RESULTS A total of 13 patients had at least two organs involved. The most frequent thoracic findings were pulmonary nodules, ground glass opacities and patches of consolidation; other abnormalities were tracheal stenosis, diffuse alveolar hemorrhage, lung masses with organized pneumonia. More than three-quarters (78%) of patients had positive antineutrophil cytoplasmic antibodies (ANCA). Ten patients had respiratory tissue biopsy (8 open lung, one tracheal, and one nasal). In 4 patients the diagnosis was made with the classic organ involvement in GPA, positive ANCA, and renal or skin biopsy, and response to treatment on follow-up. At 6-12 months all patients showed clinical and radiological improvement, with 54% showing a recurrence of disease. DISCUSSION The majority of thoracic findings described in GPA are presented in this study. A complete diagnostic approach with invasive diagnostic procedures to rule out other more prevalent respiratory diseases with similar thoracic manifestations must be performed. The positivity of ANCA in this study was high, and the recurrence of the disease was frequent.

Laboratory Biomarkers for Guiding Therapy with Methotrexate in Rheumatoid Arthritis

Methotrexate (MTX) is a first-line drug for the treatment of several rheumatic diseases. However, it is difficult to predict the response to this drug based on clinical manifestations. Although different mechanisms of action have been proposed for the antiinflammatory and immunosuppressive effects of MTX, the best characterized are blockade of the de novo synthesis of purines and pyrimidines, which inhibits DNA synthesis, and induction of adenosine release, which downregulates the effector functions of different immune cells. Thus, variants of the enzymes and other molecules involved in these metabolic pathways are expected to play a relevant role in the therapeutic effect or toxicity of MTX in patients with rheumatoid arthritis (RA). Accordingly, polymorphisms of the genes encoding these proteins have been widely associated with the response to or discontinuation of MTX. In addition, variants of the genes involved in the transportation of MTX inside and outside cells and in its metabolism have also been associated with the efficacy or toxicity of this drug in patients with RA. However, published results are contradictory, and no consensus regarding the best laboratory markers of MTX efficacy has been reached. Therefore, additional prospective studies with a large number of patients are necessary to identify the combination of genetic and nongenetic factors that can predict, with a reasonable level of confidence, the efficacy and toxicity of MTX in patients with RA.

Prevalence of Chronic Rheumatic Diseases in Mexico

To the Editor: We read with interest the recent report from Pelaez-Ballestas, et al 1 related to the epidemiology of rheumatic disease in Mexico, which included 5 regions. Most of the study population was from urban areas, which could make the study not as exact as desirable. The findings are similar to our data from the city of San Luis Potosi, population 2,410,414, located in the center of the … Address correspondence to Dr. Abud-Mendoza; E-mail: c_abud{at}hotmail.com

Triple therapy with non-biologic DMARDs for rheumatoid arthritis or biologic therapy. Is it the same?

The goals for rheumatoid arthritis (RA)—remission or low isease activity— are achieved through combination therapy with isease-modifying antirheumatic drugs (DMARDs) or biologic theapy. DMARDs combination therapy achieve the goals in higher ercentage than DMARD monotherapy1,2. Recently O’Dell et al. ompared triple therapy with three non-biologic DMARDs, and iologic therapy with etanercept-methotrexate in RA3. This comarison is important for developing countries because the poor vailability through social security4. O’Dell and colleagues did not find significant differences in AS28 (using erythrocyte sedimentation ratio, ESR or C reactive rotein, CRP). Even DAS28 is considered the “gold standard” for evauating disease activity, other clinical measures such as ultrasound r MRI might improve sensitivity for the targets in RA patients5–8. he study reported that patients receiving biologic therapy achieed American College of Rheumatology ACR50 and ACR70 almost 0% higher than triple therapy. Previous studies informed improed productivity of daily work8 and slow or not radiographic rogression in patients under biologics therapy, although the sigificance related with the structural differences is not clinically efined1,9,10. It is clear that there are benefits for patients receiving iologic therapy. The clinical benefits of triple therapy previously mentioned are elevant in most RA patients when compared to efficacy of DMARD ombination. This is especially an attractive treatment because of he lower cost of triple therapy compared to biologics, particularly n developing countries. Although we do not have official data relaed with social security in México, approximately 20% of RA patients overed by ISSSTE (11% of total Mexican population), and less than % of IMSS (59% of total Mexican population) are receiving a bioloical therapy; Mexican population with no social security is a rare vent to prescribe biologic therapy. However, although triple theapy can be more accessible than biologics, the latter treatment ecomes necessary for at least in 20-30% of RA patients partiularly when individual treatment is refractory to methotrexate. onetheless, treatments with higher doses of methotrexate11,12, n combination with prednisone13 or with another combination

Cutaneous papillomavirus infection in patients with rheumatoid arthritis or systemic lupus erythematosus. A case-control study

Previous studies informed an increased prevalence of cutaneous papillomavirus (cHPV) infection in patients with systemic lupus erythematosus (SLE). The main objective of our study was to evaluate factors associated with cHPV infection in patients with either rheumatoid arthritis (RA) or SLE, and to determine whether SLE itself is an independent risk factor for cHPV infection. We included 670 patients (in consecutive selection) in this cross-sectional study (550 with RA and 120 with SLE). All patients were evaluated by a dermatologist; patients with cHPV infection were selected as cases (63) and the other 607 patients were selected as controls. The prevalence of cHPV infection was increased 2.8-fold in SLE patients (20%) compared with RA patients (7.1%). When comparing cases with controls, bivariate analysis showed statistically significant differences for: age, having SLE, and treatment with mycophenolate mofetil (MMF). When all of the potential risk factors identified using bivariate analysis (age, having SLE, and MMF) were included into a multivariate model, independent risk factors for cHPV infection were: having SLE (odds ratio: 2.16, 95% confidence interval: 1.04–4.48) and MMF therapy (odds ratio: 2.91, 95% confidence interval: 1.18–7.14).

Should Tuberculin Skin Test Be Positive to Give Latent Tuberculosis Treatment Before Tumor Necrosis Factor-α Inhibitors in Selected Patients in Developing Countries?

To the Editor: We read with interest the report by Malaviya, et al about tuberculosis (TB) and inflammatory rheumatic disease (IRD) patients receiving tumor necrosis factor-α (TNF-α) inhibitor agents1. Mexico also has a “high TB burden,” with estimated prevalence of at least 23 per 100,0002. The tuberculin skin test (TST) has low sensitivity, including in high-risk population groups such as men and patients older than 50 years, in addition to those who have disseminated TB3,4. In immunosuppressed patients (such as those with human immunodeficiency virus), tuberculin anergy is reported to be > 40%, particularly in those with poor body mass index and/or severe lymphopenia5. This could also be true about other immunodeficient persons, including patients with rheumatic disease who are taking disease-modifying antirheumatic drugs (DMARD) and corticosteroids6,7. One … Address correspondence to Dr. Abud-Mendoza; E-mail: c_abud{at}hotmail.com