Skin and lung fibrosis induced by bleomycin in mice: a systematic review.

OBJECTIVE: Scleroderma, or systemic sclerosis (SSc), is a chronic autoimmune connective disease with an unknown etiology and poorly understood pathogenesis. The striking array of autoimmune, vascular, and fibrotic changes that develop in almost all patients makes SSc unique among connective tissue diseases. Although no animal model developed for SSc to date fully represents all features of human disease, some animal models that demonstrate features of SSc may help to better understand the pathogenesis of the disease and to develop new therapeutic options. In this review, we aimed to evaluate skin fibrosis and lung involvement in a bleomycin (BLM)-induced mouse model and to evaluate the differences between studies. METHODS: A systematic literature review (PRISMA guideline) on PubMed and EMBASE (until May 2023, without limits) was performed. A primary literature search was conducted using the PubMed and EMBASE databases for all articles published from 1990 to May 2023. Review articles, human studies, and non-dermatological studies were excluded. Of the 38 non-duplicated studies, 20 articles were included. RESULTS: Among inducible animal models, the BLM-induced SSc is still the most widely used. In recent years, the measurement of tissue thickness between the epidermal-dermal junction and the dermal-adipose tissue junction (dermal layer) has become more widely accepted. CONCLUSIONS: In animal studies, it is important to simultaneously evaluate lung tissues in addition to skin fibrosis induced in mice by subcutaneous BLM application, following the 3R (replacement, reduction, and refinement) principle to avoid cruelty to animals.

Does arterial stiffness predict mortality in patients with scleroderma: a long-term follow-up study.

OBJECTIVE: Subclinical macrovascular impairment, which has been evaluated with various arterial stiffness (AS) parameters, has been defined in patients with systemic sclerosis (SSc). However, studies investigating the relationship between AS and clinical endpoints in SSc are lacking. This study aims to determine the prognostic value of AS parameters to predict all-cause mortality in SSc patients. PATIENTS AND METHODS: AS parameters [carotid-radial pulse wave velocity (PWV) and augmentation index (AIx)] were assessed via applanation tonometry. The prognostic value of these parameters was quantified in patients with SSc (n=60) without pulmonary arterial hypertension (PAH) and obvious cardiac involvement against survival. RESULTS: The overall median follow-up time was 10.3 years, and a 29.4% (n=20) mortality was observed. Four significant predictors of mortality were observed: lung involvement (HR 2.608, p=0.04), the lower level of predicted carbon monoxide diffusing capacity (HR 0.978, p=0.03), lower level of estimated glomerular filtration rate (HR 0.979, p=0.04), and elevated serum C reactive protein (CRP) levels (HR 1.066, p<0.001). Among these variables, elevated CRP was found to be an independent predictor of all-cause mortality. AS parameters were not associated with all-cause mortality (HR 1.014, p=0.6 for AIx and HR 0.737, p=0.19 for PWV, respectively). CONCLUSIONS: Long-term data failed to demonstrate the prognostic value of AS parameters in predicting all-cause mortality in SSc patients. The exact mechanisms of cardiovascular (CV) mortality in SSc patients deemed to be atherosclerotic in origin needs to be determined in large-scale studies.

Adult-onset still's disease, an unusual cause of severe acute liver injury: A case report.

Adult-onset Still's disease is a systemic inflammatory disease that often presents with spiking fever, typical rash, arthritis, and serositis. However, adult-onset-Still's-disease associated liver injury and acute liver failure are rare. Herein, we report a case of acute liver injury in a 23-year-old female patient with adult-onset Still's disease. She presented to the emergency department with a high fever and sore throat. She was then admitted to the department of infectious diseases with a preliminary diagnosis of an atypical respiratory infection. After being treated with antibiotics and antiviral agents, she was discharged. A few days later, she returned to the emergency department with jaundice and was rehospitalized. This time, she was admitted to the department of gastroenterology, where she was diagnosed with adult-onset Still's disease-associated acute liver injury. Eventually, the patient responded to immunosuppressive treatment with significant clinical improvement.

Risk factors for malignancy in systemic sclerosis patients.

Systemic sclerosis (SSc) is an autoimmune connective tissue disease with multisystem involvement. An increased incidence of cancer in SSc patients compared with the general population has been reported in several reports. Our aims in this study were to determine the most common malignancies and to investigate the possible risk factors for the development of malignancy in patients with SSc. Three hundred forty SSc patients from 13 centers were included to the study. Data of the patients were obtained by evaluating their medical records retrospectively. A total of 340 patients with SSc were evaluated. Twenty-five of the patients had 19 different types of malignancy. Bladder cancer was the most common type of cancer with four patients and was followed by breast cancer with three patients, and cervix cancer and ovarian cancer with two patients each. Other types of cancers such as squamous cell skin cancer, adenocancer with an unknown origin, multiple myeloma, chronic myeloid leukemia, papillary thyroid cancer, larynx cancer, non-small cell lung cancer, follicular type non-Hodgkin lymphoma (NHL), endometrium cancer, colon cancer, uterus cancer, neuroendocrine tumor, glioblastoma multiforme, and soft tissue sarcoma were diagnosed in one patient each. The only cancer type that showed an association with cyclophosphamide dose was bladder carcinoma. Other malignancies did not show a correlation with age, sex, smoking, type and duration of the disease, autoantibodies, organ involvement, and dose and duration of cyclophosphamide therapy. Cancer may develop in any organ in patients with SSc. Continuous screening of the patients during a follow-up period is necessary for the early detection of the tumor development.

The prevalence of gout in an urban area of Izmir, Turkey: a population-based epidemiological study.

OBJECTIVES: This study aimed to determine the prevalence of gout in a general Turkish population, according to the American College of Rheumatology (Wallace) criteria proposed for gout classification. METHODS: This study was conducted in two districts of Izmir Province in Turkey, and involved 2835 subjects of ≥ 20 years of age. In the first stage, face-to-face interviews were performed at the subjects' registered households. In the second stage, subjects who gave positive answers in the screening questionnaire were invited to the hospital for a full examination, which included a detailed medical history, medication use and blood tests. RESULTS: A total of 2887 subjects were contacted, and complete interviews were obtained for 2835 (1551 women, 1284 men). A total of 312 subjects (227 women, 85 men) reported experiencing a short period of joint pain accompanied by swelling, redness or reduced range of movement, and 247 (79%) of these patients underwent a detailed clinical examination in the hospital. Gout was diagnosed in 11 patients (8 men, 3 women). We found minimum age- and sex-adjusted prevalence rates of gout of 0.31% (95% CI: 0.16-0.61) in subjects of ≥ 20 years of age, and 0.72% (95% CI: 0.37-1.24) in subjects of ≥ 40 years of age. CONCLUSIONS: Our data suggest that the estimated prevalence of gout (0.31%) is lower than the previously published estimated prevalence of rheumatoid arthritis (0.36%) in the same study population (14 definite rheumatoid arthritis cases among the 2835 subjects).

The effect of orthodontic extraoral appliances on depression and the anxiety levels of patients and parents.

BACKGROUND: Psychosocial consequences and post-operative anxiety in patients after fixed orthodontic treatment are important parameters that must be evaluated by clinicians not to effect patient and their parent's psychosocial mood negatively. OBJECTIVE: The aim of this study was to evaluate the changes in depression and anxiety levels of orthodontic patients and their parents before the extraoral appliance therapy, and at a 1-year follow-up. MATERIALS AND METHODS: Patients and one of their parents responded to a series of questionnaires and evaluation scales in order to assess depression and anxiety levels. Two groups of patients and their parents were surveyed; one group that had not yet embarked on the treatment and another that had commenced extra-oral appliance therapy 1 year prior to the study. RESULTS: The 1-year-treatment group scored significantly higher than the pre-treatment group on the depression scale and the trait-anxiety scale. State-trait anxiety inventory scores did not differ significantly between the groups. The parents of the 1-year-treatment group also scored significantly higher on the Beck depression inventory than those of the pre-treatment group. CONCLUSION: The results of this study emphasize the need for due consideration of psychological parameters before and during treatment with extra-oral appliances, particularly with regard to depression and anxiety.

Prevalence of primary Sjogren's syndrome in Turkey: a population-based epidemiological study.

OBJECTIVES: The aim of this study was to determine the prevalence of primary Sjogren's syndrome (pSS) in a general Turkish population according to the latest proposed American-European Consensus Group (AECG) criteria and European-1 (EU-1) criteria. METHODS: The study was conducted in two districts of Izmir and involved 2835 subjects 20 years of age and older. In the first stage, face-to-face interviews were performed at the registered households. In the second stage, subjects reporting symptoms of both dry eye and dry mouth were invited to the hospital for a full examination, which included Schirmer-1, sialometry and serologic tests. In the third stage, a minor salivary gland biopsy was performed as required. RESULTS: A total of 2887 subjects were contacted and a complete interview was obtained for 2835 (1551 female, 1284 male) subjects. A total of 159 subjects (126 female, 33 male) confirmed oral and ocular dryness, and 86 of these patients (54.1%) underwent a detailed clinical examination in the hospital. pSS was diagnosed in 10 patients (nine females) according to the EU-1 criteria, and in six patients (six females) according to the AECG criteria. We found a minimum crude prevalence of 0.21% [95% confidence interval (CI): 0.03-0.29] in the sample population and an age-sex adjusted prevalence of 0.16% (95% CI: 0.06-0.35), according to AECG criteria. According to EU-1 criteria, these prevalence rates were found to be 0.35% (95% CI: 0.10-0.45) and 0.28% (95% CI: 0.13-0.51) respectively. CONCLUSION: The pSS prevalence rates found in the Turkish population in this study were lower than the estimated prevalence rate in a general population.

Frequency and severity of musculoskeletal symptoms in humans during an outbreak of trichinellosis caused by Trichinella britovi.

Musculoskeletal symptoms such as myalgia are well-known features in the course of trichinellosis; however, the characteristics of musculoskeletal findings have been described in detail in only 1 study. The present study was aimed to determine the joint and muscle symptoms in subjects diagnosed with acute trichinellosis at our rheumatology unit during a Trichinella britovi outbreak that occurred in Izmir, Turkey, in 2004. In total, 98 patients (55 females, 43 males; mean age 32.3 +/- 10.9 yr) were included in the study. A detailed history and full musculoskeletal examination were obtained in each patient. A self-administered questionnaire developed for recording the musculoskeletal symptoms was completed monthly until all the symptoms were resolved. Pain at the joints, restriction of movements (in shoulders, elbows, wrists, knees, ankles, and temporomandibular joints), myalgia, and muscle weakness (neck and shoulder girdle, muscles of the upper and forearm, back, thigh, and calf muscles) were assessed in every patient. Eosinophil counts, serum levels of creatine kinase, and lactate dehydrogenase also were analyzed. The most frequent musculoskeletal symptoms were muscle pain (86 cases [87.8%]), joint pain (83 [84.7%]), subjective muscle weakness (75 [76.5%]), and restriction of joint movements (63 [64.3%]). Calves, upper arm, neck and shoulder girdle, and forearms were the most affected muscle groups. Muscle pain was reported more frequently in the upper than in the lower extremities and during activity. The most frequent painful joints were shoulders, knees, wrists, and ankles. Upper extremity joints were affected more frequently than the lower extremity joints (77.6 vs. 70.4%). Joint pain occurred more frequently at rest. Both muscle weakness and restriction of joint movements were reported in and around the most frequently affected regions. No evidence of arthritis and objective muscle weakness was noted on physical examination in any patient. Musculoskeletal symptoms in the course of T. britovi infection are frequent but with an excellent prognosis. Joint pain in people suffering from acute trichinellosis may occur more frequently than reported previously.

Impaired endothelial function in patients with ankylosing spondylitis.

OBJECTIVE: In recent years, accelerated atherosclerosis and increased risk of cardiovascular events have been described in patients with rheumatic disease, particularly for rheumatoid arthritis and systemic lupus erythematosus. However, the link between inflammation, atherosclerosis and ankylosing spondylitis is controversial. We evaluated the degree of atherosclerosis and endothelial function of ankylosing spondylitis patients ultrasonographically. METHODS: Fifty-four patients with ankylosing spondylitis (37 +/- 11 yr, 29 males, 25 females) and 31 healthy controls (35 +/- 9 yr, 16 males, 15 females) were consecutively enrolled in the study. Serum lipids, creatinine, glucose, and acute-phase proteins were assessed. The Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were also evaluated. Flow-mediated dilatation and endothelium-independent dilatation of the brachial artery and intima-media thickness of the common carotid artery were measured sonographically. RESULTS: Left, right and averaged intima-media thickness of the common carotid artery did not show a statistically significant difference between the ankylosing spondylitis and control groups. However, flow-mediated dilatation was significantly lower in the ankylosing spondylitis patients (14.1 +/- 6.7 vs 17.6 +/- 8%; P = 0.03). Likewise, nitroglycerin-induced dilatation was lower in the patient group, but the difference was not significant (16.4 +/- 6.8 vs 19.8 +/- 10%; P = 0.07). No correlation was detected between flow-mediated dilatation and age, sex, serum lipids, CRP, ESR, smoking habits and disease activity scores. Intima-media thickness of the common carotid artery was positively correlated with age and BASMI score (r = 0.55, P = 0.00; r = 0.22, P = 0.04, respectively). CONCLUSION: This study demonstrates impairment of endothelial function in ankylosing spondylitis.

The prevalence of rheumatoid arthritis in an urban population of Izmir-Turkey.

OBJECTIVE: To estimate the prevalence of rheumatoid arthritis (RA) in an urban area in Izmir, Turkey. METHODS: The study was conducted in the Balcova and Narlidere districts of Izmir and a total of 2,887 people aged 20 years or older were contacted with a 98.2% acceptance rate. Nine medical doctors administered an RA questionnaire by face-to-face interview. Subjects reporting a history of swelling in at least 2 joints lasting more than 4 continuous weeks or a history of a diagnosis of rheumatoid arthritis, inflammatory joint rheumatism or joint rheumatism were considered as screening positive and they were invited to come in for an examination. RA cases were defined by the 1987 American College of Rheumatology (ACR) criteria modifiedfor use in population studies. RESULTS: A total of 301 subjects (243 women, 58 men), or 10.6% of those who received the questionnaire were screening positive. 240 (79.7%) of these agreed to undergo a clinical examination either in the clinic or at home. Among these, 14 (12 female, 2 male) patients fulfilled the ACR criteria for RA. The prevalence of RA was 0.49% (95% CI 0.27-0.83) in the total population interviewed, 0.77% (95% CI 0.40-1.35) in women and 0.15% (95%CI 0.02-0.60) in men. The age- and sex-adjusted prevalence for the general population was estimated as 0.36%. Five of the 14 RA (36%) cases had not been diagnosed previously CONCLUSION: These data are consistent with the results of other Mediterranean countries. A significant proportion of RA cases remain undiagnosed in the community.

Gemcitabine-induced vasculitis in advanced transitional cell carcinoma of the bladder.

BACKGROUND: Gemcitabine (GEM) is an alternative chemotherapeutic agent for patients with metastatic bladder cancer. It is believed to be a well-balanced agent, having acceptable toxicity and enhanced antitumor activity. The integration of GEM into the initial chemotherapy plan for these patients is still being developed. CASE REPORT: The patient, male, aged 56 years, was suffering from a transitional cell carcinoma of the bladder. Due to frequent local superficial recurrences, radical cystectomy with pelvic lymphadenectomy and continent ileal diversion was performed. Four years after the operation a left inguinal lymphadenopathy was noted and metastatic bladder carcinoma was confirmed on biopsy. Cytotoxic therapy combining GEM and cisplatin and local external irradiation therapy was initiated. The patient developed extensive necrotising vasculitis with muscle damage after the second course of therapy. Chemotherapy was stopped immediately but this was not enough to relieve the symptoms of severe myalgia and swelling, and additional treatment consisting of cyclophosphamide and prednisolone was initiated. CONCLUSION: Although GEM seems to be relatively safe, some unexpected complications may occur during treatment. This case is not common, but it reinforces the need for careful attention to any new symptoms that seem to be unassociated with the primary disease. Prompt evaluation of such symptoms should be carried out in patients receiving GEM therapy.

A case of recurrent pancreatitis due to hyperlipidemia misdiagnosed as familial Mediterranean fever.

Familial Mediterranean fever (FMF) is prevalent among Arabic, Turkish, Armenian, and Jewish people and it must always be considered in the differential diagnosis of patients from these ethnic groups presenting with recurrent abdominal pain with fever. In cases of fever and recurrent abdominal pain, acute pancreatitis is an important clinical condition, which should be considered in the differential diagnosis. Serum amylase concentration in acute pancreatitis is usually more than three times the upper limit of normal. However, in recurrent pancreatitis secondary to hypertriglyceridemia, serum amylase levels, for reasons that are not well understood, may be normal or mildly elevated. Recurrent pancreatitis secondary to hypertriglyceridemia may thus pose a problem in the differential diagnosis and may lead to an erroneous diagnosis of FMF. Measurement of serum triglyceride along with amylase levels should be required for a suspected diagnosis. Computerized examination of the abdomen may need to be undertaken to exclude acute pancreatitis in the presence of hypertriglyceridemia since serum amylase levels may be normal or slightly elevated.

Coexistence of familial Mediterranean fever with sacroiliitis and Behçet's disease: a rare occurrence.

Familial Mediterranean fever (FMF) and Behçet's disease are relatively rare but may still coexist in the same patient. Sacroiliitis is another feature whose significance is controversial in either of the diseases. We report a case of longstanding FMF with sacroiliitis who later developed typical characteristics of Behçet's disease. Although occurrence by chance cannot be ruled out, this unusual patient may enhance the claims that FMF and Behçet's disease have common aetiopathogenetic mechanisms. It would be appropriate to include this coexistence in the list of differential diagnoses of the two diseases.