LUPUS NEPHRITIS AND PREGNANCY. THE RHEUMATOLOGIST’S OPINION

In the presence of lupus nephritis, the pregnancy remains a challenging problem, requiring a multidisciplinary monitoring. Such pregnancies are considered as high risk similar to those with maternal and fetal potential complications. Thus, these pregnancies must be planned, after a multidisciplinary evaluation, performed by obstetrician, rheumatologist and nephrologist. Inactive disease for at least 6 months before conception, absence of hypertension, heavy proteinuria or important renal dysfunction are associated with good maternal-fetal outcomes. Lupus nephritis flare and preeclampsia may occur, associating a poor prognosis. Therapeutic regimens must be adapted, taking into account the teratogenic effects of the drugs

OSTEOPOROSIS IS ASSOCIATED WITH A LOWER PREVALENCE OF BODY MASS INDEX-DEFINED OBESITY IN RHEUMATOID ARTHRITIS

Objective. The objective of this initial phase of the study is to retrospectively screen rheumatoid arthritis (RA) phenotype characteristics associated with osteoporosis. Methods. The study included all RA patients who randomly came to the university rheumatology department between January and July 2018. Demographic data, anthropometric data, RA-specific variables, osteoporosis data and comorbidities were collected retrospectively and cross-sectionally from the first (and most frequently the only) observation sheet of each patient within the study timeframe. Correlations and comparison were analyzed using appropriate non-parametric tests, all of the reported being significant (p<0.05). Results. The sample included 149 RA patients (60.8 years mean age; 81.2% women), 40 (26.8%) of which had osteoporosis and 31 (20.8%) were obese. Compared to RA patients without osteoporosis, RA patients with osteoporosis were significantly older (56.0 respectively 71.0 years) and had: lower body mass index (BMI; 23.8 kg/m2 respectively 29.6 kg/m2 ), longer disease duration (11.0 respectively 17.0 years), higher prevalence of rural dwelling (prevalence ratio – PR=2.46), smoking (PR=3.71), inflammation (PR=1.35), anti-citrullinated protein antibody positivity (PR=1.51), glucocorticoids (PR=1.85) and carotid artery disease (PR=3.01), but a lower prevalence of obesity (PR=3.43). Lumbar bone mineral density was significantly correlated with BMI (rho=0.294) and with rheumatoid factor titers (rho=0.311), controlling for age, gender and disease duration. Conclusions. BMI-defined obesity seems to be associated with a lower prevalence of osteoporosis among RA patients, while disease severity (treatment with glucocorticoids, inflammation and ACPA positivity) is associated with a higher prevalence of osteoporosis. Gain of adipose tissue and loss of bone tissue seem to be antagonistic and parallel body composition alterations in RA

A RARE CASE OF PYODERMA GANGRENOSUM WITH COMPLETE SOFT PALATE DESTRUCTION

We present the case of a 24 year old male who was admitted to Sf. Maria Clinical Hospital’s Internal Medicine and Rheumatology Department having an impressive soft palate destruction and necrotic ulcers of the posterior oropharynx wall and left palatine tonsil, as well as a gigantic skin ulcer on the left calf. His disease started in 2010, at age 17, with an apfhtous ulceration on his left tonsil and evolved with multiple ulcerations: firstly, in the oral cavity and in time, on skin (face, vermillion, scalp, upper and lower limbs) with bacterial colonisation, and also aseptic arthritis of his both knees. Throughout the past 7 years he was evaluated in many departments and clinics and several diagnoses were raised into question, such as amigdalitis, tonsil tumour, lymphoma, Wegener’s disease, Pyoderma Gangrenosum, PAPA, incomplete SAPHO, Crohn’s disease, Behcet’s disease. Despite the fact that he received multiple therapies, including cDMARDs and bDMARDs, the mucosal and skin lesions had a good response only to corticosteroid treatment and flaired up at the attempt of stoping it

TESTING ANTINUCLEAR ANTIBODIES IN RELATIVES OF PATIENTS WITH SYSTEMIC LUPUS ERITHEMATOSUS

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies, which deposit within tissues and fix complement leading to systemic inflammation (1). Is a heterogeneous disease with a continuum of disease activity. Some patients can have predominant skin and joint involvement, whereas others can present with organ-threatening diseases such as nephritis, cardiac involvement or even neurologic manifestations. Relatives of patients with SLE appear to be at higher risk of SLE and other autoimmune diseases, but estimates of individual familial risks are largely unavailable or unreliable (2,3). The purpose of ANA (antinuclear antibody) determination is generally to screen patients suspected from generalised autoimmune diseases, that is, systemic lupus erythematosus (SLE), rheumatoid arthritis, Sjögren’ s syndrome, scleroderma, polymyositis, or mixed connective tissue disease. Clinical and paraclinical studies are needed to reach a definitive diagnosis

ONE CASE OF TOXIC EPIDERMAL NECROLYSIS AFTER TREATMENT WITH BELIMUMAB IN A PATIENT WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Belimumab is a human immunoglobulin G1-lambda-1 (IgG1-λ) monoclonal antibody that targets the soluble BLyS human protein, also known as B-cell activating factor (BAFF) approved for the treatment of systemic lupus erythematosus (SLE). Serious and sometimes fatal infections have been reported in patients receiving novel immunosuppressive agents, including belimumab. Thus, physicians should exercise caution when considering belimumab in patients with SLE. A 50-year-old woman with SLE presented with a severe, diffuse rash two months after initiating treatment with belimumab. A skin biopsy revealed epidermal necrolysis with keratinocyte detachment and apoptosis in the basal layer of the epidermis, suggestive for toxic epidermal necrolysis (TEN). Belimumab was discontinued and 500 mg of pulse IV methylprednisolone therapy every day for 3 days were administered, with resolution of the skin lesions in the following days. To the best of our knowledge, this is the first case of belimumab-associated TEN

BASELINE INFLAMMATORY MARKERS AND DISEASE ACTIVITY INDICES PREDICT TAPERING OF BIOLOGIC AGENTS IN ANKYLOSING SPONDYLITIS

Rationale. Clinicians need to have evidence-based information regarding the feasibility of tapering biologics in ankylosing spondylitis (AS). Objective. The study aims to identify significant predictors of tapering in clinical practice. Methods and results. AS patients on their first tumor necrosis factor alpha inhibitor (iTNFα) were enrolled between 2015-2017 and followed until the end of the observation or until tapering or switch of their iTNFα. Binary logistic regression was used to predict tapering (“0” for “non-tapering”, meaning switches and original posology; “1” for “tapering”), significant if p < 0.05. Of the 120 included patients, 50.8% had adalimumab, 21.7% etanercept, 4.2% golimumab and 23.3% infliximab. During follow-up, 40.8% tapered their initial iTNFα, 40.8% remained on its original posology, 16.7% switched it and 1.7% were lost. Judging by odds ratios (OR), inflammatory markers (e.g. odds ratio ORCRP = 0.936, p = 0.014) and activity scores (ORBASDAI = 0.565, p = 0.005) significantly reduced the chance for tapering. Compared to patients on the original posology, patients on tapering had a significantly lower prevalence of uveitis ever (6.8% compared to 11.0%, p = 0.008, post-hoc χ2 test). Discussion. In a real life setting, no more than half of AS patients treated with TNFα inhibitors can undergo tapering. High baseline inflammatory markers and disease activity indices significantly lower the chance of tapering. From a therapeutic point of view, a non-responsive disease phenotype of AS can be hypothesized and it includes extra-spinal manifestations such as uveitis

CARDIOVASCULAR RISK ASSESSMENT IN RHEUMATOID ARTHRITIS WITH NODULOSIS: APPROACH TO PRIMARY PREVENTION

Cardiovascular risk assessment in patients with rheumatoid arthritis (RA) is challenging. Not all risk calculators adjust for RA status, yielding discording results. A 56-year-old woman with RA presented for bilateral pain and swelling in the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints. She was diagnosed with RA 10 years ago, currently treated with methotrexate (MTX), sulfasalazine, and hydroxychloroquine. She has a history of type 2 diabetes mellitus, a total abdominal hysterectomy with bilateral salpingo-oophorectomy for an epidermoid carcinoma of the cervix, and surgical excision of a pulmonary rheumatoid nodule. Multiple subcutaneous nodules are seen bilaterally on the MCP and PIP joints. MTX may be associated with nodulosis in RA patients, which in turn is related to a further increase in cardiovascular risk compared to RA alone. MTX was discontinued. Abatacept was the biologic of choice, due to recent evidence suggesting superior efficacy in decreasing cardiovascular risk compared to anti-TNF therapies, especially in patients with diabetes and with positive rheumatoid factor. Initiating high-dose statin and abatacept may be a useful primary prevention strategy in complex RA patients that require biologic therapy.

A RARE ASSOCIATION: ANKYLOSING SPONDYLITIS AND A GENETIC DISEASE

Ankylosing spondylitis (AS) is a chronic systemic inflammatory disease that affects the axial skeleton and sometimes the peripheral joints, leading to the development of bone bridges and ankyloses with impaired joint mobility and quality of life. The HLA B27 antigen, which occurs in approximately 97% of patients, is an important risk factor and also a diagnostic element to consider. The typical onset of the disease is in the 3rd-4th decade of life; juvenile onset of AS under 16 years is associated with the predominant involvement of peripheral joints and multiple complications (coxitis, acute anterior uveitis) which influence the evolution of the disease under treatment being related with a negative prognosis. Noonan syndrome is a genetic disease with dominant autosomal transmission characterized by a small stature and other phenotypic features associated with congenital heart defects, especially pulmonary stenosis and atrial septal defect. Multiple genes within the RAS subfamily involved in various cellular signaling pathways such as signal transmission via mitogen-activated protein kinases are responsible for the occurrence of the disorder. Different hematological diseases such as myeloproliferative syndrome and neoplastic disease, particularly affecting the lung, may be correlated with Noonan syndrome. We present the case of a young patient with juvenile onset AS and Crohn’s disease who has Noonan syndrome with operated pulmonary stenosis and septal atrial defect, the association of these diseases bringing together cumulative complications that required multiple therapies and surgical interventions with strict monitoring

N-TERMINAL PRO-BRAIN NATRIURETIC PEPTIDE IN SYSTEMIC SCLEROSIS PATIENTS: CORRELATION WITH NAILFOLD CAPILLAROSCOPY FINDINGS

Background. Pulmonary arterial hypertension (PAH) is an important cause of morbidity and mortality in patients with systemic sclerosis (SSc). This condition is diagnosed by cardiac Doppler ultrasonography, right-heart catheterization, or by serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP). The aim of this study was to assess the association between serum NT-proBNP and nailfold capillaroscopic patterns in SSc patients. We also analyzed the association between pulmonary function parameters, NT-proBNP, and nailfold capillary findings in patients diagnosed with SSc and PAH. Material and methods. We retrospectively analyzed SSc patients and healthy controls from our institution between July 2016 - December 2018. We assessed by chart review: pulmonary artery systolic pressure (PASP), forced vital capacity (FVC), forced expiratory volume in 1 sec/forced vital capacity ratio (FEV1/FVC ratio), the number of nailfold capillaries/mm and NT-proBNP. Statistical analyses were performed using the Student’s t-test, ANOVA test and the Pearson’s correlation. Results. Seventeen patients with SSc and 17 healthy controls matched for age and gender were included. Among SSc patients, 13 had diffuse cutaneous SSc (dcSSc) and 4 patients had limited cutaneous SSc (lcSSc). PAH was identified in 10 SSc patients. In SSc patients, significant correlations have been identified between PASP and NT-proBNP (r=0.9, p<0.0001), nailfold capillaries density and PASP (r=-0.95, p<0.0001), and nailfold capillaries density and NT-proBNP (r=-0.84, p<0.0001). Conclusion. We suggest that in patients with SSc, NT-proBNP is significantly correlated with PASP and nailfold capillaroscopic findings

Abnormalities in soluble CD147 / MMPs / TIMPs axis in Ankylosing Spondylitis patients with and without a history of Acute Anterior Uveitis / Anomalii ale axei CD147 solubil / MMPs / TIMPs la pacienții cu spondilită anchilozantă cu sau fără uveită acută anterioară

Spondilita Anchilozantă (SA) este prototipul formei axiale a spondiloartritelor. În pofida studiilor extinse, sunt încă incomplet înțelese mecansimele complexe legate de procesele celulare și moleculare anormale din SA. Printre mediatorii inflamației, cum ar fi citokinele proinflamatoare, NOS-2, chemokinele, care conduc la inflamație, metaloproteinazele de matrice (MMPs) joacă un rol important în procesele inflamatoare care caracterizează SA. De aceea, ne-am propus să evaluăm dacă perturbări ale homeostaziei inductorului extracelular de MMPs (EMMPRIN/CD147), MMPs și inhibitorilor tisulari ai MMPs (TIMPs) joacă un rol în evoluția SA în special la pacienții care au în istoricul lor Uveită Acută Anterioară (UAA). În acest scop seruri de la pacienți cu SA și de la donatori sănătoși (DS) au fost analizate pentru nivelurile de CD147 solubil (sCD147), MMP-3 și TIMP-1 prin tehnica imunoenzimatica ELISA și pentru activitatea gelatinazelor MMP-2 si MMP-9 folosind gelatin zimografia. Rezultatele experimentale au arătat că nivelurile de sCD147, MMP-3 si TIMP-1 sunt semnificativ crescute la pacienții cu SA comparativ cu DS. sCD147 ca și raportul MMP-2/sCD147 a diferențiat pacienții cu UAA de cei fără UAA în istoricul lor. La pacienții cu SA rapoartele MMP-2/sCD147, MMP-3/sCD147 și MMP-3/TIMP-1 au sugerat dezechilibrul dintre MMPs și reglatorii lor. Aceste rezultate sugerează că rapoartele MMPs/sCD147 pot deveni biomarkeri potențiali pentru întărirea caracterizării pacienților cu SA și pentru a prognoza evoluția bolii. Corelațiile pozitive și negative dintre anumite caracteristici experimentale și/sau clinice ale pacienților cu SA și terapie subliniază de asemenea utilitatea evaluării acestor biomarkeri pentru a identifica o terapie individualizată și eficientă