Current Perspectives in Giant Cell Arteritis: Can We Better Connect Pathogenesis and Treatment?

Giant cell arteritis (GCA) is a large-vessel vasculitis affecting elderly patients and targeting the aorta and its main branches, leading to cranial and extracranial manifestations. The mechanism behind the ischemia is a granulomatous-type inflammation with potentially critical lesions, including visual loss involving the ophthalmic artery. Despite significant progress in unraveling the pathophysiology of this disease, treatment options still rely on glucocorticoids (GCs) to overcome active vascular lesions and disease flares. However, uncertainty still revolves around the optimal dose and tapering rhythm. Few corticosteroid-sparing agents have proven useful in GCA, namely, methotrexate and tocilizumab, benefiting cumulative GC dose and relapse-free intervals. The future looks promising with regard to using other agents like abatacept and Janus-kinase inhibitors or blocking the granulocyte-macrophage colony-stimulating factor receptor.

Calcinosis in Rheumatic Disease Is Still an Unmet Need: A Retrospective Single-Center Study.

Patients with immune-mediated rheumatic disease-related calcinosis comprise a subgroup at risk of encountering a more severe clinical outcome. Early assessment is pivotal for preventing overall disease progression, as calcinosis is commonly overlooked until several years into the disease and is considered as a 'non-lethal' manifestation. This single-center retrospective study explored the prevalence, clinical associations, and impact on survival of subcutaneous calcinosis in 86 patients with immune-mediated rheumatic diseases (IMRD). Calcinosis predominantly appeared in individuals with longstanding disease, particularly systemic sclerosis (SSc), constituting 74% of cases. Smaller calcinosis lesions (≤1 cm) were associated with interstitial lung disease, musculoskeletal involvement, and digital ulcerations, while larger lesions (≥4 cm) were associated with malignancy, severe peripheral artery disease, and systemic arterial hypertension. The SSc calcinosis subgroup exhibited a higher mean adjusted European Scleroderma Study Group Activity Index score than those without. However, survival rates did not significantly differ between the two groups. Diltiazem was the most commonly used treatment, and while bisphosphonates reduced complications related to calcinosis, complete resolution was not achieved. The findings underscore current limitations in diagnosing, monitoring, and treating calcinosis, emphasizing the need for further research and improved therapeutic strategies to improve patient care and outcomes.

The Translation, Validation and Cultural Adaptation of Questionnaires Assessing the Quality of Life and Fatigue among Patients with Sjogren's Syndrome for the Romanian Context.

About 70% of patients with Sjogren's syndrome suffer from fatigue, and for a large proportion of patients, it is one of the most noticeable manifestations leading to disability. To date, no study has been conducted in Romania to determine the quality of life of patients and the impact of fatigue in patients with Sjogren's syndrome. The present work proposes the translation, cultural adaptation, and validation of two questionnaires for the Romanian context, namely the 'Profile of Fatigue and Discomfort-Sicca Symptoms Inventory' (PROFAD-SSI-SF) and 'Primary Sjogren's Syndrome-Quality of Life' (PSS-QoL), whose purpose is to assess quality of life and fatigue in patients with Sjogren's syndrome. These two questionnaires were administered to 52 patients with Sjogren's syndrome diagnosed according to the 2016 ACR-EULAR criteria. Subsequently, the conceptual, semantic, and operational analyses of the data were performed with the aim of cultural adaptation. The data obtained were statistically analyzed using indices of measurement accuracy such as internal consistency. Based on statistical analyses, this pilot study shows that the Romanian versions of the PROFAD-SSI and PSS-QoL questionnaires are as reliable as their English counterparts.

A "Mix and Match" in Hemochromatosis-A Case Report and Literature Focus on the Liver.

Hemochromatosis is a genetic disorder characterized by increased iron storage in various organs with progressive multisystemic damage. Despite the reports dating back to 1865, the diagnosis of hemochromatosis poses a challenge to clinicians due to its non-specific symptoms and indolent course causing significant delay in disease recognition. The key organ that is affected by iron overload is the liver, suffering from fibrosis, cirrhosis or hepatocellular carcinoma, complications that can be prevented via early diagnosis and treatment. This review aims to draw attention to the pitfalls in diagnosing hemochromatosis. We present a case with multiorgan complaints, abnormal iron markers and a consistent genetic result. We then examine the relevant literature and discuss hemochromatosis subtypes and liver involvement, including transplant outcome and treatment options. In summary, hemochromatosis remains difficult to diagnose due to its symptom heterogeneity and rarity; thus, further education for practitioners of all disciplines is useful in facilitating its early recognition and management.

Refractory Takayasu's Arteritis with Severe Coronary Involvement-Case Report and Literature Review.

This report presents the case of a female patient diagnosed with Takayasu arteritis from childhood, with severe, refractory coronary involvement, leading to two acute coronary syndromes and multiple anginous episodes. Consequently, the patient suffered aorto-bicarotid bypass two times, multiple interventional procedures with stent implantation, balloon angioplasty, and up to ten repeated in-stent restenosis that required reinterventions, despite being on maximal immunosuppressive treatment. In recent years, various studies have been reported that aim to best characterize this particular type of vascular damage and to indicate optimal therapeutic options for treatment. The latter should be based on the activity of the underlying disease; however, no reliable markers are available in TA. The management of TA patients with coronary involvement continues to be a challenge and requires both drug and interventional techniques to avoid life-threatening events.

Myopathic syndrome revealing a rare condition: Sheehan syndrome, a case-based review.

This report presents a case of a Sheehan syndrome diagnosed with a delay of 29 years after occurrence of first symptoms, following a laborious birth ended with dead fetus and massive hemorrhage. The 50-year-old patient, with early menopause from the age of 21, is referred to our rheumatology department to investigate the etiology of a myopathic syndrome, which started 2 months before and gradually worsened. The differential diagnosis took into consideration the autoimmune, infectious, paraneoplastic, endocrinological, and drug-induced myopathic syndrome. Paraclinical investigations revealed panhypopituitarism, and cerebral magnetic resonance imaging detected empty-sella. The etiology of a myopathic syndrome is often multifactorial; therefore, it is important to continue the investigations even after identifying one possible etiological factor, especially when it does not seem to fully explain the clinical-paraclinical picture. Usually, the multiple dimensions of panhypopituitarism bring the patient to various medical specialties depending on the dominant symptomatology. Given the rarity of the above-mentioned syndrome in the present, and the long gap between the initial event and the final diagnosis, its identification continues to be a challenge.

Interferon in systemic lupus erythematosus-A halfway between monogenic autoinflammatory and autoimmune disease.

Although perceived as an adaptative immune disorder, mainly related to Lymphocyte B and T, last years focus on Systemic Lupus Erythematosus (SLE) pathogeny emphasised the important role of innate immunity. This should not take us by surprise since the lupus cell described by Hargraves and colleagues in 1948 was a neutrophil or macrophage with specific aspect after coloration with haematoxylin related to cell detritus engulfment (Hargraves et al., 1948) [1] (Presentation of two bone marrow elements; the tart. Hargraves M, Ricmond H, Morton R. 1948, Proc Staff Meet Mayo Clinic, pp. 23:25-28). Normal immune system maintains homeostasis through innate and adaptative response that are working together to prevent both infection and autoimmunity. Failure of the immune mechanisms to preserve the balance between these two will initiate and propagate autoinflammation and/or autoimmunity. It is well known now that autoinflammation and autoimmunity are the two extremes of different pathologic conditions marked with multiple overlaps in many diseases. Recent findings in SLE demonstrated that innate immune system initiates the abnormal autoimmunity and starts the continuous inflammatory reaction after that, interferon being one of the key cytokines in innate immunity and SLE. Understanding this mechanism might offer a better clue for an efficient treatment in SLE patients. The purpose of this review is to highlight the enormous impact of innate immunity and mostly interferons in SLE.

Preparing for Pregnancy in Women with Systemic Lupus Erythematosus-A Multidisciplinary Approach.

Pregnancy is one of the most challenging processes the human body is exposed to: the healthy mother can carry to term a genetically different new-born, while her immune system adapts to tolerate this new status and avoids rejection. In autoimmune disorders, motherhood is even more challenging, with additional medical counselling, mother care, and foetus development checks being necessary. While the aspects of supplementary mother care and pregnancy progress tracking are associated with well-established medical procedures and protocols, counselling, be it pre- or post-conception, is still underestimated and scarcely applied. Indeed, over the past decades, medical counselling for this particular population has changed significantly, but from a healthcare's provider point of view, more is required to ensure a smooth, controllable pregnancy evolution. One of the most frequent autoimmune diseases affecting young females during their fertile years is Systemic Lupus Erythematosus (SLE). Like other heterogenous diseases, it exposes the mother to severe, organ-threatening complications and unpredictable evolution. Both the disease and its treatment can significantly affect the mother's willingness to engage in a potentially risky pregnancy, as well as the likeliness to carry it to term without any impairments. A good collaboration between the patient's rheumatologist and obstetrician is therefore mandatory in order to: (a) allow the mother to make an informed decision on pursuing with the pregnancy; (b) ensure a perfect synchronization between pregnancy terms and treatment; and (c) avoid or minimize potential complications. The best approach to achieve these outcomes is pregnancy planning. Moreover, knowing one desired prerequisite for a successful pregnancy evolution in SLE mothers is a stable, inactive, quiescent disease for at least six months prior to conception, planning becomes more than a recommended procedure. One particular aspect that requires attention before conception is the treatment scheme applied before delivery as autoantibodies can influence significantly the course of pregnancy. In this view, future SLE mothers should ideally benefit from preconception counselling within their agreed care pathway. A multidisciplinary team including at least the rheumatologist and obstetrician should be employed throughout the pregnancy, to decide on the appropriate timing of conception and compatible medication with respect to disease activity, as well as to monitor organ involvement and foetus development progress.

Do We Have Good Activity Indices in Systemic Sclerosis?

BACKGROUND: No fully validated index is available for assessing overall disease activity in systemic sclerosis (SSc). OBJECTIVES: To estimate the effect of disease activity as measured by different disease activity indices on the risk of subsequent organ damage. METHODS: The European Systemic sclerosis study group activity index (EScSG AI), the European Scleroderma Trials and Research Group Activity Index (r-EUSTAR AI), 12 point activity index proposed by Minier (12point AI) were calculated for 91 patients; the CRISS (The Composite Response Index for Systemic Sclerosis) for patients included after 2016. Data were analysed by parametric and non-parametric tests and logistic regression. RESULTS: EscSG AI, r-EUSTAR AI and 12point AI correlated with lung involvement. EScSG AI and r-EUSTAR AI correlated with diffuse skin involvement. EscSG AI correlated with digital ulcers and diffuse cutaneous involvement and r-EUSTAR AI with a renal crisis. Bivariate analysis showed an inverse correlation between the three disease activity scores and forced vital capacity (FVC) (p<0.001) and diffusing capacity for carbon monoxide (DLCO) (p<0.001) and positive correlation with pulmonary fibrosis (p<0.001), modified Rodnan skin score (mRSS) (p<0.001), health assessment questionnaire (HAQ) (p<0.001), systolic pulmonary pressure (sPAP) (p<0.001), C-reactive protein (CRP) (p<0.001) and capillaroscopy scoring (p<0.001) at both baseline visit and the 3-year follow-up visit. Logistic regression revealed that baseline EScSG AI adjusted for gender and age and that baseline 12-point AI both adjusted and unadjusted predicted worse skin involvement at 3-year follow-up; while adjusted EScSG AI predicted decreasing DLCO. Also, 12-point AI predicted a decline of FVC and higher HAQ scores at 3-year follow up; while baseline r-EUSTAR AI was able to predict muscular deterioration, decline of FVC and the increase of HAQ score during 3 years of following. An active disease according to EScSG AI at first visit predicted progression of joint involvement while an active disease at baseline showed by r- EUSTAR AI predicted muscular deterioration, FVC and DLCO worsening, as well as an increase in HAQ score during the follow-up period. r-EUSTAR AI was the only score to predict the decrease of FVC in a multiple regression prediction model (OR= 1.306 (1.025, 1.665), p=0.31) while baseline EScSG AI best predicted worsening of DLCO (OR=1.749 (1.104, 2.772), p=0.017). CONCLUSION: Our study could not establish a gold standard to assess disease activity in SSc; especially EscSG AI and r-EUSTAR AI could quantify and predict major organ involvement in daily practice. CRISS can be useful as an outcome measure for patients with short disease duration included in clinical studies.

Low vitamin D status in systemic sclerosis and the impact on disease phenotype.

OBJECTIVE: Vitamin D has pleiotropic effects including immunomodulatory, cardioprotective, and antifibrotic properties and is thus able to modulate the three main links in scleroderma pathogenesis. The aim of the study was to evaluate the level of vitamin D in patients with systemic sclerosis and to analyze the associations between the concentration of vitamin D and the features of systemic sclerosis. MATERIAL AND METHODS: Fifty-one consecutive patients were evaluated for visceral involvement, immunological profile, activity, severity scores, and quality of life. The vitamin D status was evaluated by measuring the 25hydroxy-hydroxyvitamin D serum levels. RESULTS: The mean vitamin D level was 17.06±9.13 ng/dL. Only 9.8% of the patients had optimal vitamin D levels; 66.66% of them had insufficient 25(OH)D levels, while 23.52% had deficient levels. No correlation was found between vitamin D concentration and age, sex, autoantibody profile, extent of skin involvement, or vitamin D supplementation. Vitamin D levels were correlated with the diffusing capacity of the lung for carbon monoxide (p=0.019, r=0.353), diastolic dysfunction (p=0.033, r=-0.318), digital contractures (p=0.036, r=-0.298), and muscle weakness (p=0.015, r=-0.377) and had a trend for negative correlation with pulmonary hypertension (p=0.053, r=-0.29). CONCLUSION: Low levels of vitamin D are very common in systemic sclerosis. Poor vitamin status seems to be related with a more aggressive disease with multivisceral and severe organ involvement, especially pulmonary and cardiac involvement.

Clinical Phenotype of Endothelial Dysfunction in Romanian Scleroderma Patients.

OBJECTIVE: To identify the particularities of the clinical phenotype of endothelial dysfunction in a lot of Romanian patients from a reference center and compare it to data reported by international registries. MATERIAL AND METHODS: 51 patients were included in a cross-sectional study. The patients were evaluated for the pattern of disease, main visceral involvement, serum markers of disease. RESULTS: 41.2% patients had history of digital ulcers, 27.45% had pulmonary arterial hypertension; cardiovascular involvement also included: diastolic dysfunction in 31.1% of the patients, global systolic dysfunction in 9.8%, rhythm and conduction disturbances in 19.6%, peripheral vascular disease in 19.6%. Scleroderma renal crisis was identified in 2 patients. CONCLUSION: Vascular complications are a major cause of morbidity and mortality in systemic sclerosis. Earlier therapeutic intervention demands improved screening and diagnosis in all cases.

Clinical Phenotype of Endothelial Dysfunction in a Lot of Romanian Scleroderma Patients.

OBJECTIVES: to identify the particularities of the clinical phenotype of endothelial dysfunction in a lot of Romanian patients from a reference center and compare it to data reported by international registries. MATERIALS AND METHODS: 51 patients were included in a cross sectional study. The patients were evaluated for the pattern of disease, main visceral involvement, serum markers of disease. RESULTS: 41.2% patients had history of digital ulcers, 27.45% had pulmonary arterial hypertension; cardiovascular involvement also included: diastolic dysfunction in 31.1% of the patients, global systolic dysfunction in 9.8%, rhythm and conduction disturbances in 19.6%, peripheral vascular disease in 19.6%. Scleroderma renal crisis was identified in 2 patients. CONCLUSION: Vascular complications are a major cause of morbidity and mortality in systemic sclerosis. Earlier therapeutic intervention demands improved screening and diagnosis in all cases.

Monitoring drug and antidrug levels: a rational approach in rheumatoid arthritis patients treated with biologic agents who experience inadequate response while being on a stable biologic treatment.

Clinical response in patients with rheumatoid arthritis (RA) treated with biologic agents can be influenced by their pharmacokinetics and immunogenicity. The present study evaluated the concordance between serum drug and antidrug levels as well as the clinical response in RA patients treated with biological agents who experience their first disease exacerbation while being on a stable biologic treatment. 154 RA patients treated with rituximab (RTX), infliximab (IFX), adalimumab (ADL), or etanercept (ETN) were included. DAS28, SDAI, and EULAR response were assessed at baseline and reevaluated at precise time intervals. At the time of their first sign of inadequate response, patients were tested for both serum drug level and antidrug antibodies level. At the next reevaluation, patients retreated with RTX that had detectable drug level had a better EULAR response (P = 0.038) with lower DAS28 and SDAI scores (P = 0.01 and P = 0.03). The same tendency was observed in patients treated with IFX and ETN regarding EULAR response (P = 0.002 and P = 0.023), DAS28 score (P = 0.002 and P = 0.003), and SDAI score (P = 0.001 and P = 0.026). Detectable biologic drug levels correlated with a better clinical response in patients experiencing their first RA inadequate response while being on a stable biologic treatment with RTX, IFX, and ETN.