18 Cutaneous lupus

Case 1: 35-year-old Mestizo female Bernardo Pons-Estel A 35-year-old Mestizo female was diagnosed with systemic lupus erythematosus (SLE) in 2005 based on polyarthritis, malar rash, photosensitivity, mucosal ulcerations, positive ANA and anti-dsDNA, and low complement. She was treated with prednisone 20–30 mg/day and hydroxychloroquine (HCQ) 400 mg/day. In June 2010, lupus pneumonitis was diagnosed. In July 2018, she was first admitted to our hospital. She was cushingoid and had fever, fatigue, malar rash, oral ulcers, alopecia, polyarthritis, oedema, multiple purplish-red streaks, and active erythematous, palpable and painful subcutaneous indurated nodules/plaques located on her face, proximal lower extremities and abdomen; some were ulcerated. Laboratory tests RBC 3.8 (x1012/L), hemoglobin 11.8 g/dl, WBC 2,3 (x109/L), platelets 62 (x109/L), ESR 8 mm, CRP 0.8 mg/L, serum ferritin 1,487 ng/ml, ALAT 70 UI/ml, ASAT 26 UI/ml, GGT 64 U/L, BUN 43 mg/dl, serum creatinine 1.54 mg/dl, GFR 67 mL/min, cholesterol 186 mg/dL, triglycerides 149 mg/dl, proteinuria 210 mg/24 h, ANA 1/320, speckled pattern, anti-Sm (+) and anti-dsDNA, anti-U1RNP, anti-Ro and anti-La all (-). C3 75 mg/dl, C4 10, Coombs test (-), procalcitonin 0.29 ng/ml ( She was treated with IV methylprednisolone (500 mg/day/3 days), and high-dose intravenous immunoglobulin, and discharged with mycophenolate mofetil 1 g/day, HCQ 400 mg/day, prednisone 20 mg/day and TMS-SMX 860/160 BID for 5 days. A week later she was re-admitted with fever, pancytopenia, hepatosplenomegaly, lymphadenopathy and several painful, indurated erythematous lesions. Her SLEDAI was 13. A bone marrow aspiration and biopsy was interpreted as a macrophage activated syndrome in the context of SLE exacerbation and treated with IV dexamethasone, colony stimulating factor, and rituximab 1000 mg. Despite treatment, she remained severely ill with fever, asthenia, petechiae and purpura on her abdomen and thighs, and pancytopenia. Due to disease severity, treatment with etoposide was indicated. Finally, the patient presented an acute episode of respiratory distress followed by death. Discussion Points Interpreting the different skin manifestations in a patient with SLE Analyzing complications and differential diagnoses with other associated diseases Case 2: 28-year-old Caucasian female Annegret Kuhn A 28-year-old Caucasian female was diagnosed with systemic lupus erythematosus (SLE) in 1996 and presented with severe, erythematous, scarring discoid lesions on the scalp, face, and hands. She had been resistant to a high number of therapeutic agents including hydroxychloroquine, chloroquine, methotrexate, isotretinoin, and cyclophosphamide for several years and had developed various side effects. Moreover, the long-term medication for SLE had not influenced her skin lesions in the past months. In December 2009, the patient received alitretinoin, which was administered orally with a daily dose of 30 mg. The patient showed continuous improvement of the discoid skin manifestations over a period of 5 months and finally a total clearance of most lesions. No serious adverse events were recorded during treatment with alitretinoin; however, the patient experienced recurring headache, which was successfully treated with nonsteroidal anti-inflammatory drugs. Therefore, alitretinoin was reduced to a daily dose of 10 mg. The vitamin-A derivative, alitretinoin, has been approved for use in severe chronic hand eczema unresponsive to treatment with potent topical corticosteroids. This case suggests that alitretinoin could also be an effective alternative in the treatment of cutaneous manifestations in SLE; however, randomized controlled trials are needed to prove the efficacy and evaluate the safety of alitretinoin in this disease. Discussion Points Treatment of therapy-resistant cutaneous manifestations in SLE Therapeutic guidelines in cutaneous lupus erythematosus Learning Objectives Explain different possible skin manifestations in patients with SLE Discuss complications, differential diagnosis with allied diseases and treatment approaches Describe the spectrum of manifestations in cutaneous lupus, including: ACLE, CCLE, SCLE and ICLE Explain the therapeutic guidelines in cutaneous lupus Describe preventive strategies in cutaneous lupus including photoprotection Describe topical treatment options in cutaneous lupus Discuss common and experimental systemic treatment options in cutaneous lupus Reference Kuhn A, Patsinakidis N, Luger TA. Alitretinoin for cutaneous lupus erythematosus. J Am Acad Dermatol 2012;67:123–126

First Latin American clinical practice guidelines for the treatment of systemic lupus erythematosus : Latin American Group for the Study of Lupus (GLADEL, Grupo Latino Americano de Estudio del Lupus)–Pan-American League of Associations of Rheumatology (PANLAR)

Systemic lupus erythematosus (SLE), a complex and heterogeneous autoimmune disease, represents a significant challenge for both diagnosis and treatment. Patients with SLE in Latin America face special problems that should be considered when therapeutic guidelines are developed. The objective of the study is to develop clinical practice guidelines for Latin American patients with lupus. Two independent teams (rheumatologists with experience in lupus management and methodologists) had an initial meeting in Panama City, Panama, in April 2016. They selected a list of questions for the clinical problems most commonly seen in Latin American patients with SLE. These were addressed with the best available evidence and summarised in a standardised format following the Grading of Recommendations Assessment, Development and Evaluation approach. All preliminary findings were discussed in a second face-to-face meeting in Washington, DC, in November 2016. As a result, nine organ/system sections are presented with the main findings; an ’overarching’ treatment approach was added. Special emphasis was made on regional implementation issues. Best pharmacologic options were examined for musculoskeletal, mucocutaneous, kidney, cardiac, pulmonary, neuropsychiatric, haematological manifestations and the antiphospholipid syndrome. The roles of main therapeutic options (ie, glucocorticoids, antimalarials, immunosuppressant agents, therapeutic plasma exchange, belimumab, rituximab, abatacept, low-dose aspirin and anticoagulants) were summarised in each section. In all cases, benefits and harms, certainty of the evidence, values and preferences, feasibility, acceptability and equity issues were considered to produce a recommendation with special focus on ethnic and socioeconomic aspects. Guidelines for Latin American patients with lupus have been developed and could be used in similar settings

History of autoimmunity. First Part. The immunology From where and to where?

La inmunología nace especialmente a finales del siglo XIX y en las primeras dos décadas del siglo XX, pero su expansión y desarrollo acelerado se realiza a finales del siglo XX y exponencial-mente en el siglo XXI. Se origina de la microbiología y de la bacteriología, al buscar resultados rápidos de la aplicación inmediata en la prevención y curación de las infecciones bacterianas, que para esa época eran los problemas cruciales dela medicina. Desde ese inicio, la inmunología está conectada desde el área básica con todas las ramas de la medicina, de la biología y la ingenie-ría, originando una nueva especialidad como loes la Ingeniería Biomédica.Q411-3

Experiencia sobre el proceso de salud-enfermedad-atención en pacientes con artritis reumatoidea pertenecientes a la comunidad Wichí de Misión Chaqueña “El Algarrobal”, Salta

Introducción: se ha reportado que la prevalencia de artritis reumatoidea (AR) en la comunidad Wichí representa la más alta informada por el Grupo Latinoamericano para el Estudio de las Enfermedades Reumáticas en los Pueblos Originarios (GLADERPO). El objetivo de este estudio fue describir la experiencia sobre el proceso de salud- enfermedad-atención de pacientes con AR de la comunidad Wichí de Misión Chaqueña “El Algarrobal”, Salta. Materiales y métodos: estudio narrativo. Diseño de corte etnográfico. Se realizaron entrevistas semiestructuradas y observaciones registradas. Se utilizaron guías de entrevistas y observación. Los aspectos incluidos fueron: concepción del proceso salud-enfermedad, percepción de la AR en la vida diaria, el acceso al sistema de salud, utilización de recursos tradicionales y de medicina tradicional.

Genetically determined Amerindian ancestry correlates with increased frequency of risk alleles for systemic lupus erythematosus

Objective To assess whether genetically determined Amerindian ancestry predicts increased presence of risk alleles of known susceptibility genes for systemic lupus erythematosus (SLE). Methods Single-nucleotide polymorphisms (SNPs) within 16 confirmed genetic susceptibility loci for SLE were genotyped in a set of 804 Mestizo lupus patients and 667 Mestizo healthy controls. In addition, 347 admixture informative markers were genotyped. Individual ancestry proportions were determined using STRUCTURE. Association analysis was performed using PLINK, and correlation between ancestry and the presence of risk alleles was analyzed using linear regression. Results A meta-analysis of the genetic association of the 16 SNPs across populations showed that TNFSF4 , STAT4 , ITGAM , and IRF5 were associated with lupus in a Hispanic Mestizo cohort enriched for European and Amerindian ancestry. In addition, 2 SNPs within the major histocompatibility complex region, previously shown to be associated in a genome-wide association study in Europeans, were also associated in Mestizos. Using linear regression, we predicted an average increase of 2.34 risk alleles when comparing an SLE patient with 100% Amerindian ancestry versus an SLE patient with 0% Amerindian ancestry ( P < 0.0001). SLE patients with 43% more Amerindian ancestry were predicted to carry 1 additional risk allele. Conclusion Our results demonstrate that Amerindian ancestry is associated with an increased number of risk alleles for SLE.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78480/1/27753_ftp.pd

Fine mapping and conditional analysis identify a new mutation in the autoimmunity susceptibility gene BLK that leads to reduced half-life of the BLK protein

OBJECTIVES: To perform fine mapping of the autoimmunity susceptibility gene BLK and identify functional variants involved in systemic lupus erythematosus (SLE). METHODS: Genotyping of 1163 European SLE patients and 1482 controls and imputation were performed covering the BLK gene with 158 single-nucleotide polymorphisms. Logistic regression analysis was done using PLINK and conditional analyses using GENABEL's test score. Transfections of BLK constructs on HEK293 cells containing the novel mutation or the wild type form were analysed for their effect on protein half-life using a protein stability assay, cycloheximide and western blot. CHiP-qPCR for detection of nuclear factor κ B (NFkB) binding. RESULTS: Fine mapping of BLK identified two independent genetic effects with functional consequences: one represented by two tightly linked associated haplotype blocks significantly enriched for NFκB-binding sites and numerous putative regulatory variants whose risk alleles correlated with low BLK mRNA levels. Binding of NFkBp50 and p65 to an associated 1.2 Kb haplotype segment was confirmed. A second independent genetic effect was represented by an Ala71Thr, low-frequency missense substitution with an OR=2.31 (95% CI 1.38 to 3.86). The 71Thr decreased BLK protein half-life. CONCLUSIONS: These results show that rare and common regulatory variants in BLK are involved in disease susceptibility and both, albeit independently, lead to reduced levels of BLK protein

Seguridad de las drogas biológicas y sintéticas dirigidas utilizadas en pacientes con enfermedades reumáticas inmunomediadas. Datos del registro BIOBADASAR 3.0

Introducción: conocer la seguridad de las drogas actualmente disponibles para el tratamiento de las enfermedades reumáticas es muy importante al momento de tomar decisiones terapéuticas objetivas e individualizadas en la consulta médica diaria. Asimismo, datos de la vida real amplían el conocimiento revelado por los ensayos clínicos. Objetivos: describir los eventos adversos (EA) reportados, estimar su frecuencia e identificar los factores relacionados con su desarrollo. Materiales y métodos: se utilizaron datos BIOBADASAR, un registro voluntario y prospectivo de seguimiento de EA de tratamientos biológicos y sintéticos dirigidos en pacientes con enfermedades reumáticas inmunomediadas. Los pacientes son seguidos hasta la muerte, pérdida de seguimiento o retiro del consentimiento informado. Para este análisis se extrajeron datos recopilados hasta el 31 de enero de 2023. Resultados: se incluyó un total de 6253 pacientes, los cuales aportaron 9533 ciclos de tratamiento, incluyendo 3647 (38,3%) ciclos sin drogas modificadoras de la enfermedad biológicas y sintéticas dirigidas (DME-b/sd) y 5886 (61,7%) con DME-b/sd. Dentro de estos últimos, los más utilizados fueron los inhibidores de TNF y abatacept. Se reportaron 5890 EA en un total de 2701 tratamientos (844 y 1857 sin y con DME-b/sd, respectivamente), con una incidencia de 53,9 eventos cada 1000 pacientes/año (IC 95% 51,9-55,9). La misma fue mayor en los ciclos con DME-b/sd (71,1 eventos cada 1000 pacientes/año, IC 95% 70,7-77,5 versus 33,7, IC 95% 31,5-36,1; p<0,001). Las infecciones, particularmente las de la vía aérea superior, fueron los EA más frecuentes en ambos grupos. El 10,9% fue serio y el 1,1% provocó la muerte del paciente. El 18,7% de los ciclos con DME-b/sd fue discontinuado a causa de un EA, significativamente mayor a lo reportado en el otro grupo (11,5%; p<0,001). En el análisis ajustado, las DME-b/sd se asociaron a mayor riesgo de presentar al menos un EA (HR 1,82, IC 95% 1,64-1,96). De igual manera, la mayor edad, el mayor tiempo de evolución, el antecedente de enfermedad pulmonar obstructiva crónica, el diagnóstico de lupus eritematoso sistémico y el uso de corticoides se asociaron a mayor riesgo de EA. Conclusiones: la incidencia de EA fue significativamente superior durante los ciclos de tratamientos que incluían DME-b/sd

Trans-Ancestral Studies Fine Map the SLE-Susceptibility Locus TNFSF4

We previously established an 80 kb haplotype upstream of TNFSF4 as a susceptibility locus in the autoimmune disease SLE. SLE-associated alleles at this locus are associated with inflammatory disorders, including atherosclerosis and ischaemic stroke. In Europeans, the TNFSF4 causal variants have remained elusive due to strong linkage disequilibrium exhibited by alleles spanning the region. Using a trans-ancestral approach to fine-map the locus, utilising 17,900 SLE and control subjects including Amerindian/Hispanics (1348 cases, 717 controls), African-Americans (AA) (1529, 2048) and better powered cohorts of Europeans and East Asians, we find strong association of risk alleles in all ethnicities; the AA association replicates in African-American Gullah (152,122). The best evidence of association comes from two adjacent markers: rs2205960-T (P = 1.71×10-34, OR = 1.43[1.26-1.60]) and rs1234317-T (P = 1.16×10-28, OR = 1.38[1.24-1.54]). Inference of fine-scale recombination rates for all populations tested finds the 80 kb risk and non-risk haplotypes in all except African-Americans. In this population the decay of recombination equates to an 11 kb risk haplotype, anchored in the 5′ region proximal to TNFSF4 and tagged by rs2205960-T after 1000 Genomes phase 1 (v3) imputation. Conditional regression analyses delineate the 5′ risk signal to rs2205960-T and the independent non-risk signal to rs1234314-C. Our case-only and SLE-control cohorts demonstrate robust association of rs2205960-T with autoantibody production. The rs2205960-T is predicted to form part of a decameric motif which binds NF-κBp65 with increased affinity compared to rs2205960-G. ChIP-seq data also indicate NF-κB interaction with the DNA sequence at this position in LCL cells. Our research suggests association of rs2205960-T with SLE across multiple groups and an independent non-risk signal at rs1234314-C. rs2205960-T is associated with autoantibody production and lymphopenia. Our data confirm a global signal at TNFSF4 and a role for the expressed product at multiple stages of lymphocyte dysregulation during SLE pathogenesis. We confirm the validity of trans-ancestral mapping in a complex trait. © 2013 Manku et al