Serum salusin-α and salusin-ß levels in patients with psoriatic arthritis.

Introduction: Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by skin lesions and joint involvement. Salusin-α and salusin-ß are two new bioactive molecules. It is reported that salusins may have role in regulation of the immune system and inflammation. The aim of our study was to evaluate the serum salusin-α and salusin-ß levels in PsA patients and to establish the possible relationship with the disease features. Material and methods: Our study included 40 PsA patients who fulfilled the CASPAR criteria and 40 healthy volunteers. Demographic, clinical, laboratory and radiological data and disease activity indices (PASI, BASDAI, BASFI, HAQ) were recorded in all patients. The enzyme-linked immunosorbent assay (ELISA) method was used to measure serum salusin-α and salusin-ß levels. Results: The demographic data were as follows: 13 patients (32.5%) were males and 27 (67.5%) were female, mean age was 48.5 years and mean disease duration was 2.4 years. Patients' history was taken and clinical assessment was performed; 20 (50%) patients had a family history, 18 (45%) patients were smoker, 19 (47.5%) patients had HLA-B27 positivity, 33 (82.5%) had sacroiliitis, 36 (90%) had enthesitis, 23 (57.5%) had distal interphalangeal (DIP) joint and nail involvement, 26 (65%) had wrist involvement, and 11 (27.5%) had ankle involvement. Laboratory data of the patients were recorded; 20 (50%) patients had elevated CRP level and 25 (62.5%) patients had an elevated ESR level. The study results showed that PsA patients had an elevated serum salusin-α level when compared with the control group (p = 0.004). The association between serum salusin-α level and ankle arthritis was found (p = 0.04). Serum levels of salusin-ß were similar in PsA patients and controls both (p = 0.285). Conclusions: We found elevated serum salusin-α in PsA patients while the serum salusin-ß levels were normal. Salusin-α may have a possible role in disease pathogenesis and it may be use as a reliable biomarker in PsA patients. Multicenter prospective studies are needed in this regard.

Ustekinumab-induced chronic lymphocytic leukemia in a patient with psoriatic arthritis.

Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by skin and joint involvement. The disease may present with various joint pattern involvement, which sometimes may lead to joint destruction and deformity. Early diagnosis and treatment with disease-modifying anti-rheumatic drugs may prevent joint deformity. Recently there are many new treatment options including biologic drugs. Ustekinumab, an interleukin 12/23 inhibitor, has proven efficacy in the treatment of psoriatic arthritis. Like other biologic drugs (anti-TNF-α), there are contradictory data about the safety of ustekinumab and possible relationship with cancer development. Herein we report the development of chronic lymphocytic leukemia in a patient with PsA treated with ustekinumab.

Evaluation of Right Ventricular Function by Speckle-Tracking Echocardiography in Patients with Ankylosing Spondylitis: A Case-Control Study.

BACKGROUND: We aimed to evaluate the right ventricular (RV) systolic function in patients with ankylosing spondylitis (AS) compared to healthy subjects by using standard echocardiography and speckle-tracking echocardiography (STE) methods. METHODS: This was a case-control study in which 64 patients (mean age, 55.7 ± 9.2 years; male/female, 53/11), who had AS for at least five years (mean disease duration, 7.1 ± 2.6 years) and 70 age-matched healthy subjects (mean age, 54.9 ± 8.5 years; male/female 55/15) were included. Clinical and laboratory signs of cardiac disease were recorded. The RV systolic function was assessed by standard echocardiography and two-dimensional STE method. RESULTS: Case and control groups did not show significant difference in terms of clinical and laboratory signs of cardiac disease. RV function parameters in standard echocardiography were statistically similar between AS patients and control subjects. However, RV parameters in STE revealed significantly impaired RV function in AS patients compared to control group. RV-free wall longitudinal strain, RV-free wall longitudinal systolic strain rate, RV-free wall longitudinal early diastolic strain rate, RV-free wall longitudinal late diastolic strain rate were lower, and RV-early diastolic strain rate/RV-late diastolic strain rate ratio was higher for the patients in the AS group (p < 0.001 for all). CONCLUSIONS: AS is associated with impaired RV function as shown by STE even if there is no clinical or laboratory sign of cardiac abnormality. STE is more effective than standard echocardiography to detect RV function. Therefore we suggest regular evaluation of RV function in patients with AS.

Prevalence and significance of MEFV gene mutations in patients with gouty arthritis.

Gouty arthritis is a chronic erosive autoinflammatory disease. Pyrin has anti-inflammatory effects in the regulation of inflammasome and is encoded by the MEFV gene. The relationship between different rheumatic diseases and the MEFV gene mutations was demonstrated. The aim of this study was to determine the frequency of MEFV gene mutations in patients with gouty arthritis and identify a possible correlation with disease phenotype. Ninety-three patients with gouty arthritis and 102 healthy controls, compatible with age, gender and ethnicity, were included in the study. MEFV gene mutations were investigated by PCR method. Out of 93 patients with gouty arthritis, 36 (38.7 %) showed MEFV gene mutations carriage, whereas 20.6 % in healthy control group. Distribution of mutations identified in patients with gouty arthritis was as; R202Q in 18 (19.3 %), E148Q in 5 (5.4 %), K695R in 4 (4.3 %), M680I in 2 (2.1 %), V726A in 2 (2.1 %), P369S in 2 (2.1 %), R408Q in 2 (2.1 %), M694 V in 1 (1.1 %), respectively. Three patients were identified with compound heterozygosity. Distribution of MEFV gene mutations carriage in healthy controls was; E148Q in 11 (10.7 %), M694 V in 2 (1.9 %), M694I in 1 (0.9 %), M680I in 2 (1.9 %), V726A in 1 (0.9 %), A744S in 1 (0.9 %), K695R in 2 (1.9 %), and P369S in 1 (0.9 %) patients, respectively. Higher MEFV gene mutations carrier frequency was observed in patients with gouty arthritis, compared with the control group (p = 0.009). Heterozygous R202Q was the most common mutation detected in patients with gouty arthritis, while heterozygous E148Q in healthy control group. Statistically significant difference was not detected between clinical findings of gouty arthritis and the MEFV gene mutations (p > 0.05). We determined higher prevalence of MEFV gene mutations in patients with gouty arthritis compared with the healthy control group. The most frequently detected mutation was heterozygous R202Q, whereas E148Q in healthy controls. High carriage rates of MEFV gene mutations in gouty arthritis suggest that it may play an important role in the pathogenesis of the disease and predisposition to the disease.

The efficacy of topical 0.05 % cyclosporine A in patients with dry eye disease associated with Sjögren's syndrome.

Sjögren's syndrome (SS) is an autoimmune epithelitis which usually presents with mouth and eye dryness. Although the place of systemic drugs in keratoconjunctivitis sicca treatment has been discussed, the efficacy of some topical drugs has also been demonstrated; however, there are contradictory results related to topical cyclosporine A. We aimed to investigate the efficacy of 0.05 % topical cyclosporine A in patients with keratoconjunctivitis sicca due to primary and secondary SS. This prospective study included 26 patients with a diagnosis of primary and secondary SS who visited our rheumatology outpatient clinic. Keratoconjunctivitis sicca was diagnosed in all patients after they were examined at the outpatient clinic. Patients were given topical 0.05 % cyclosporine A emulsions for both eyes. We used another 20 patients with SS who were treated with saline solution as a control group. Subjective symptoms reported after 1-week and 1-month follow-up were complaints of burning and pricking sensation, light sensitivity and pain. Objective signs included redness, Schirmer test and tear break-up time. A total of 26 patients (19 female) were enrolled in the study with a mean age of 47.5 years and mean disease duration of 5.2 years. In the first physical examination of patients, 23 patients had burning and pricking sensation, 24 had pain, 23 had light sensitivity, and 24 had red eyes. All subjective symptoms (burning and pricking sensation, light sensitivity and pain) were statistically significantly improved after 1-week and 1-month follow-up examinations (p = 0.0001). All objective signs (Schirmer test, tear break-up time, and redness) were statistically significantly improved after 1-week and 1-month follow-up examinations (p = 0.0001). Compared with the control group, there was significant improvement in all parameters. It is concluded that topical 0.05 % cyclosporine A is an effective treatment option for keratoconjunctivitis sicca due to SS after a 1-month follow-up period.

Chronic monoarthritis and foot-drop as a paraneoplastic syndrome in prostate cancer.

Paraneoplastic rheumatic symptoms, caused by a malignancy, but not directly related to invasion by the tumor or its metastases are the result of a wide variety of tumor-derived biologic mediators. Recognition of paraneoplastic rheumatic syndromes is important, as it may lead to an early diagnosis of cancer. We report a 71-year-old patient with prostate cancer, presented with chronic monoarthritis of the left ankle and foot-drop. Monoarthritis and foot-drop was resistant to non-steroidal anti-inflammatory drugs and corticosteroids. After tumor resection, synovitis resolved and foot-drop disappeared almost totally.

Treat to target and tight control: Could be a new approach in the treatment of sarcoidosis?

Sarcoidosis is a chronic granulomatous disease with multisystemic involvement. Although it is accepted as a benign disease, it can sometimes cause life-threatening organ (heart, brain) involvement that determines the prognosis of the disease. There are conflicting opinions about the treatment of the disease. In the generally accepted treatment approach the "step-by-step" model has gained weight. According to this approach, corticosteroids (CS) drugs alone are preferred in the first step in patients who require treatment. In the second step, immunosuppressive drugs (IS) are used in patients who do not respond to CS and/or have contraindications to CS use, and biologics (TNF-alpha inhibitors) are used in the third step. This treatment approach may be valid in cases with mild sarcoidosis. However, although sarcoidosis is considered a benign and self-limiting disease in some major organ involvement, the "step-by-step" approach may be a treatment option that puts the patient's life in danger. In such selected patients, much more rigorous, early and combined treatment approaches that definitely include CS, IS or biologic drugs may be required. In selected sarcoidosis patients with high risk, early diagnosis, "treat-to-target" (T2T) and "tight control" follow-up of patients seems to be a rational approach. This article reviews the "step-down" treatment regimens in light of recent literature data and hypothesizes that the T2T model may be a probable new treatment approach in patients with sarcoidosis.

VEXAS syndrome: Current clinical, diagnostic and treatment approaches.

VEXAS syndrome, is a hemato-inflammatory chronic disease characterized with predominantly rheumatic and hematologic systemic involvement. It was first described in 2020 by a group of researchers in the United States. VEXAS syndrome is a rare condition that primarily affects adult males and is caused by a mutation in the UBA1 gene located on the X chromosome. Its pathogenesis is related to the somatic mutation affecting methionine-41 (p.Met41) in UBA1, the major E1 enzyme that initiates ubiquitylation. Mutant gene lead to decreased ubiquitination and activated innate immune pathways and systemic inflammation occur. The specific mechanism by which the UBA1 mutation leads to the clinical features of VEXAS syndrome is not yet fully understood. VEXAS is a newly define adult-onset inflammatory syndrome manifested with treatment-refractory fevers, arthritis, chondritis, vasculitis, cytopenias, typical vacuoles in hematopetic precursor cells, neutrophilic cutaneous and pulmonary inflammation. Diagnosing VEXAS syndrome can be challenging due to its rarity and the overlap of symptoms with other inflammatory conditions. Genetic testing to identify the UBA1 gene mutation is essential for definitive diagnosis. Currently, there is no known cure for VEXAS syndrome, and treatment mainly focuses on managing the symptoms. This may involve the use of anti-inflammatory medications, immunosuppressive drugs, and supportive therapies tailored to the individual patient's needs. Due to the recent discovery of VEXAS syndrome, ongoing research is being conducted to better understand its pathogenesis, clinical features, and potential treatment options. In this review article, the clinical, diagnostic and treatment approaches of VEXAS syndrome were evaluated in the light of the latest literature data.

Stairway to Heaven: Do head-to-head Trials Indicate a Need for Definite Criteria for Choosing Biologic Drugs in Rheumatoid Arthritis?

Rheumatoid arthritis (RA) is a chronic disease characterized by joint and systemic involvement that develops with different pathogenetic mechanisms. Treatment of the disease is undertaken with disease-modifying anti-rheumatic drugs (DMARDs). The mechanisms of action of conventional DMARDs generally are based on the inhibition of T and B-cells in the immune system. In recent years, biologic and targeted smart molecules have been used in the treatment of RA. Targeting different cytokines and inflammatory pathways, these drugs have ushered in a new era in RA treatment. The efficacy of these drugs has been demonstrated in many studies; and in the postmarketing period, that is, as the patients who use them say, they are like a "stairway to heaven". However, as every "road to heaven" is challenging and "thorny", the efficacy and reliability of these drugs and whether any one of them is superior to the others, remains a matter of debate. However, the use of biologic drugs with or without cDMARDs, the preference for original vs. biosimilar molecules, and discontinuation of the drugs after achieving sustained remission are other questions that need to be explored. When it comes to the choice of biological drugs by rheumatologists, it is not yet clear on which criteria they base their choices on. Due to the limited comparative studies of these biological drugs, the subjective criteria of the physician gains importance. The selection of these drugs, however, should be based on objective criteria such as efficacy, safety, superiority over each other, and cost. In other words, the determinant of the "path to heaven" should be based on objective criteria and recommendations according to the scientific data generated by controlledprospective studies, not on the initiative of a single physician. In this review, a head-to-head comparison of biological drugs used in the treatment of RA, their efficacy, safety, and which are superior are discussed in light of recent literature data.

SARS-CoV-2 Infection-Induced Necrotising Sarcoid Granulomatosis.

SARS-CoV-2 infection is a pandemic that affects predominantly upper airways and lungs. It may lead to reactivation of known inflammatory rheumatic diseases and/or initiation of various granulomatous disorders. Necrotising sarcoid granulomatosis (NSG) is a rare condition that can be confused with malignancy, granulomatosis with polyangiitis, and sarcoidosis. Herein we reported the development of NSG following a SARS-CoV-2 infection which mimicked granulomatosis with polyangiitis.

Atezolizumab Lung Toxicity and Importance of Combination Treatment: A Case Report.

BACKGROUND: Lung cancer is one of the most common and mortal cancers worldwide. According to pathological and clinical groups, treatments vary, and a tailored approach is considered. Adjuvant therapies, such as chemotherapy, radiation, and immune checkpoint inhibitors (ICI), are recommended by recent guidelines for patients with locally advanced cancer. OBJECTIVE: This study aimed to report the case of a patient with stage 2B squamous cell lung carcinoma who was managed for pulmonary toxicity after receiving adjuvant chemotherapy and atezolizumab treatment. CASE REPORT: A 66-year-old male patient received chemotherapy and immunotherapy after surgery for squamous cell lung cancer. A diagnosis of atezolizumab-associated pneumonitis was made using laboratory tests and imaging due to the patient's worsening dyspnea after treatment. Due to the patient's rapid progression, pulse steroid and MMF therapy were administered concurrently. When Klebsiella pneumoniae growth was detected in the sputum culture during the follow-up, IVIg was used to supplement the medication. The patient showed significant clinical and radiological improvement. CONCLUSION: In this study, we present an atezolizumab-induced pneumonitis case of a squamous cell lung cancer patient. It may be life-saving not to avoid aggressive treatment approaches by combining the steps of guideline recommendations in patients with rapidly progressive pneumonitis.

Increased circulating interleukin-23 level in patients with sarcoidosis.

BACKGROUND: Sarcoidosis is a Th1-mediated chronic inflammatory disease characterized by non-caseating granulomas. Its pathogenesis is not yet clear, but the possible role of various proinflammatory cytokines is being discussed. AIM: This study aims to determine serum cytokine (IL-6, IL-12, IL-17, and IL-23) levels in patients with sarcoidosis, and to determine a possible correlation with clinical and laboratory findings of the disease. MATERIAL AND METHOD: Forty-four biopsy-proven sarcoidosis patients followed up at a single centre and 41 healthy volunteers were included in the study. Demographic, clinical, laboratory, and radiological data of all patients were recorded. Serum samples from the patients and the control group were taken and IL-6, IL-12, IL-17, IL-23 were measured by ELISA method. RESULTS: Of the 44 sarcoidosis patients, 13(29.5%) were male and 31(70.5%) were female. Average patient age was 47.4 years, mean disease duration was 3.2 years. Twenty-one (47.7%) patients had erythema nodosum, three (6.8%) had uveitis, 40(90.9%) had arthralgia, 23(52.3%) had ankle arthritis, 15(34.1%) had enthesitis. Laboratory evaluation showed increased serum ACE levels in 24(54.5%) patients, increased serum calcium levels in 11 (25%) patients, increased serum D3 levels in 5(11.4%) patients, increased ESR and CRP levels in 22(50%) and 23(52.3%) patients, respectively. Compared with the control group higher serum IL-23 levels were found in the patients with sarcoidosis (p=.01). Serum IL-23 was associated with ankle arthritis (p=.02). Serum IL-6, IL-12, and IL-17 levels were similar in the sarcoidosis patients and the control group (p=.128, p=.212, p=.521 respectively). CONCLUSION: In our study, we found increased serum IL-23 in patients with sarcoidosis, while serum IL-6, IL-12, and IL-17 were detected as normal. Although our results are somewhat contradictory to other studies in the literature, the question should still be whether sarcoidosis is a Th1/Th17 disease. Multicentre studies are needed in this regard.

The role of chest X-ray in the early diagnosis and staging of sarcoidosis: Is it really should be done?

BACKGROUND: Sarcoidosis is a chronic granulomatous disease characterized by non-caseating granuloma. The conventional chest X-ray (CXR) has important role in the diagnosis, staging and follow-up of disease. Computed tomography (CT) is a second-line imaging method used to determine the extent, complications and differential diagnosis of sarcoidosis. OBJECTIVES: To determine the role of CXR in the early diagnosis and staging of sarcoidosis and to compare with CT imaging. METHODS: One hundred and nine sarcoidosis patients followed at a single center were included in the study. Demographic, radiological, and clinical data of 81 patients were obtained from a total of 109 patients, and the record data of these 81 patients were evaluated. Patients who could not be reached for all tests were excluded from the study. CXR and CT imaging taken at diagnosis were evaluated retrospectively independently from two radiologists and one rheumatologist. RESULTS: Among 109 patients, eighty-one patients CXR and CT imaging taken at the same center has been reached. Among 81 sarcoidosis patients 23 (28.4%) were male, 58 (71.6%) were female. The mean patients age was 46.4 years and the mean disease duration was 3.8 years. CXR is regarded as normal at diagnosis in 30 patients (37%), while all of these patients had findings consistent with sarcoidosis on CT imaging. CT imaging are more superior than CXR in the early diagnosis and staging of sarcoidosis (p=0.001). Also CT imaging is more superior for detection of disease extent and complications. CONCLUSIONS: In this study, we observed that CT imaging outperforms CXR in terms of early detection and staging of sarcoidosis. The use of CT imaging is important for early diagnosis and staging of sarcoidosis. The low performance of CXR is a condition that requires the discussion of this method. Multicenter prospective study is needed in this regard.

Efficacy and safety of adalimumab in a patient with ankylosing spondylitis on peritoneal dialysis.

The most commonly used treatments in patients with ankylosing spondylitis include nonsteroidal anti-inflammatory and disease modifying anti-rheumatic drugs (DMARDs), but most of these have nephrotoxic effects. In patients who undergo chronic hemodialysis, DMARDs are not widely preferred due to the chance of increased adverse effect incidence and the risk on patient survival, in addition to already present immunosuppression. The efficacy and safety of anti-TNF alpha drugs for the treatment of renal dysfunction that develops associated to secondary amyloidosis in inflammatory rheumatic diseases have been reported in various studies. In this report, the efficacy and safety of adalimumab was shown in patients with active ankylosing spondylitis who undergo peritoneal dialysis because of chronic renal failure.

Budd-Chiari syndrome in Behçet's disease: a retrospective multicenter study.

OBJECTIVE: To compare the clinical features, laboratory findings, and prognosis of Behçet's disease (BD) patients with and without Budd-Chiari syndrome (BCS). METHODS: This multicenter retrospective study investigated 61 (M/F: 41/20) patients with BD, having coexistent BCS, and 169 (M/F:100/69) BD patients as the control group without BCS from 22 different centers of Turkey diagnosed between 1990 and 2017. RESULTS: Of the total 61 BD patients with BCS, the onset of the first symptom and the median age of diagnosis were earlier in contrast to BD patients without BCS (p = 0.005 and p = 0.007). Lower extremity deep vein and inferior vena cava (IVC) thrombosis were more common in patients with BCS (all; p < 0.01) compared to the control group. Mortality was significantly higher in BD-BCS patients with IVC thrombosis than in the controls (p = 0.004). Since most of the cases in our cohort had chronic and silent form of BCS, mortality rate was 14.8%, which was on the lower range of mortality rate reported in literature (14-47%). While all BD-BCS patients received immunosuppressive (IS) agents, only half of them received additional anticoagulant treatments. Among IS agents, interferon treatment was more frequently used in this cohort (19%), compared to other series reported in literature (2.3%). CONCLUSION: To our knowledge, this is the largest series of BD patients with BCS. Our patients had earlier disease onset and diagnosis, higher frequency of IVC thrombosis, and higher mortality rate, compared to BD patients without BCS. Mortality was significantly higher in BD-BCS patients with IVC thrombosis compared to controls. Key Points • Mortality rate is higher in BD-associated BCS patients with IVC involvement. • Chronic and silent form of BD-associated BCS has a better prognosis. • The main treatment options are corticosteroids and immunosuppressive agents, whereas anticoagulant treatment remains controversial.

Intraarticular adalimumab in a patient with pigmented villonodular synovitis.

Pigmented villonodular synovitis is a chronic inflammatory disease progressing with histological villonodular hyperplasia in synovium, fibrosis and accumulation of hemosiderin. Knee joint is frequently involved leading to severe joint damage and disability in untreated cases. Treatment options include surgical intervention or radio-synovectomy with intraarticular yttrium-90. The case presented here includes significant clinical and radiological disease regression after intraarticular adalimumab in a patient diagnosed with radiologically and histologically confirmed pigmented villonodular synovitis who did not consent to surgical intervention.

Coexistence of systemic lupus erythematosus, Hashimoto's thyroiditis and IgA nephropathy in the same patient.

Autoimmune disorders encompass a wide spectrum of diseases that progress with several clinical findings. They can be organ-specific (such as Hashimoto's thyroiditis) or they can involve multiple organs (such as SLE). The common characteristic of all these disorders is the production of different autoantibodies against various autoantigens along with inflammation. IgA nephropathy is the most common non-lupus glomerulopathy. It rarely coexists with SLE and has never been reported to coexist with Hashimoto's thyroiditis. In this case report, a female patient diagnosed with SLE and Hashimoto's thyroiditis and whose renal biopsy revealed IgA nephropathy is presented.

Tofacitinib-induced Ramsay- Hunt Syndrome in a Patient with Rheumatoid Arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint and systemic involvement. Tofacitinib is a JAK- inhibitor that is an effective agent in the treatment of active RA. Varicella zoster virus(VZV) reactivation is among the most important adverse effects of tofacitinib. Ramsay-Hunt syndrome(RHS) is a rare clinical condition that develops as a result of VZV reactivation and progresses with hearing loss, dizziness, and facial nerve paralysis. OBJECTIVE: To present a case of Ramsay-Hunt syndrome due to varicella zoster reactivation in a RA patient using tofacitinib. CASE REPORT: A 63-year-old female RA patient under tofacitinib treatment was admitted to the rheumatology outpatient clinic due to widespread skin rashes on her face and ear, and hearing loss. On inspection widespread erythematous, vesicular rashes on the left side of the face, lips, around the eye and in the ear, and mild facial paralysis on the left side were detected. On laboratory investigations, acute phase reactants were increased. Serological study for specific antibodies against varicella zoster virus showed higher titers. Dermatology and ear nose throat specialist consultations were performed, and varicella zoster lesions on the left inner ear, face, and mild facial paresis were considered. According to clinical and laboratory findings, the patient was diagnosed with RHS triggered by tofacitinib. Tofacitinib and methotrexate were discontinued, and intravenous acyclovir was started. On the control examination, the patient's skin lesions and facial nerve paralysis regressed. CONCLUSION: Herein, we reported the first case of tofacitinib-induced RHS in a patient with RA. This may be another side effect of biologic treatment. New studies are needed on this subject.