Fibroblast growth factor-23 in patients with systemic sclerosis: A case–control study

AbstractBackgroundFibroblast growth factor-23 (FGF-23) is actively involved in phosphate homeostasis and skeletogenesis.Aim of the workTo assess the serum level of FGF-23 in systemic sclerosis (SSc) patients (both diffuse dSSc and limited lSSc subtypes) in order to find if it has a role in the pathogenesis of the disease and study its relation to the clinical manifestations.Patients and methodsThe study included 30 dSSc patients, 30 lSSc and 28 age and sex matched controls. In patients, clinical examination and laboratory investigations were performed and Medsger severity scale assessed. Serum FGF-23 was measured using ELISA.ResultsThe age of dSSc patients was 36.94±9.89years and the lSSc 38.36±10.04years. The serum FGF-23 level was 23.44±14.86pg/ml in dSSc patients, 20.01±13.92pg/ml in lSSc patients and 23.09±11.45pg/ml in the control (p=0.58). No significant difference in the FGF-23 level was found according to the presence of lung fibrosis (p=0.6). There was no significant difference in FGF levels among patients according to the severity (p=0.39). In SSc patients there was a significant correlation between FGF and serum phosphorus especially in dSSc patients (r=0.6, p=0.003). Serum urea significantly correlated with FGF-23 in those with dSSc (r=0.46, p=0.037). There was no significant difference in the FGF-23 levels (p=0.18) between those with a normal and impaired glomerular filtration rate.ConclusionThe mean serum level of FGF-23 in this study showed no significant difference between systemic sclerosis patients and their subtypes with the normal subjects. It seems to have no role in the clinical manifestations of the disease

Three atypical manifestations of granulomatosis with polyangiitis: lateral medullary syndrome, anterior cheek mass and melting scleritis of eye

Granulomatosis with polyangiitis (GPA, formerly Wegener granulomatosis) is a vasculitis with various organ involvement. There have been a few cases of CNS stroke and rare cases of lateral medullary infarction (LMI) as a manifestation of GPA. Also there have been reports of sinuses, nose and laryngeal masses mistakenly referred as carcinomas and subsequently GPA was diagnosed in their pathological reports. Another severe fulminant manifestation can be necrotizing scleritis leading to perforation of sclera. Therefore, here we present some rare and fulminant manifestations of GPA in 3 separate cases for further emphasis of the unusual manifestations of GPA that should always be kept in mind

Assessment of hospitalization and mortality of scleroderma in-patients: a thirteen-year study

Objective: Systemic sclerosis (SSc) is an uncommon non-hereditary sporadic disease that increases the risk of premature death, especially in diffuse type. We determined the prevalence of SSc in the last 13 years in our rheumatologic hospitals as a referral center for southern Iranian patients, the causes of hospitalization, the average length of stay (LOS), the mortality rate, and the reason for their mortality. Material and methods : A cross-sectional study was performed in Shiraz University of Medical Sciences, Iran. The studied population included all patients diagnosed with systemic sclerosis. We calculated the hospitalization rates, in-hospital mortality rates, and mean LOS. Results: There were 446 admissions by 181 patients with SSc. The female to male ratio was about 10.7 : 1. The overall mean LOS was 5.95 days. Digital ulcer and interstitial lung disease (ILD) were the most common causes of hospitalizations among the SSc-related events. For those with a non-SSc-related condition, infection was the most prevalent event. Most of the deaths were due to ILD and pulmonary artery hypertension(PAH), and the overall in-hospital mortality rate was 16.5%. Conclusions : Women with SSc had higher rates of hospitalization but lower in-hospital mortality than men.There were some differences between our study and other similar studies in the causes of hospitalization and in-hospital death among SSc patients, especially the lower age of death. The patients with digital ulcers and those with intestinal lung disease or pulmonary hipertension were most commonly admitted to the hospital in our study group. Probably, increasing the skin care of these patients and asking other specialty groups to cooperate will decrease the high rate of hospitalizations in our population

Glomerulopathy in patients with dermatomyositis in early active disease: clinical, pathological and capillaroscopic manifestations, and response to treatment

Introduction Idiopathic inflammatory myopathies (IIMs) are a group of systemic connective tissue diseases that present with muscular and extra-muscular manifestations. There are few reports on kidney involvement, especially in dermatomyositis (DM) patients. We evaluated the clinical, laboratory, capillaroscopy, and kidney pathology of patients with DM, who presented with proteinuria during the first year, and followed them for response to treatment. Material and methods We evaluated 205 patients with proximal muscle weakness or high muscle enzymes, who referred to the nailfold capillaroscopy clinic from April 2010 to October 2021. Seventy-four patients fulfilled the New 2017 EULAR/ACR Classification Criteria for adult and juvenile IM with probability of ≥ 90% for DM with duration of ≤ 12 months and proteinuria > 350 mg/24 hours. All manifestations of patients with glomerulopathy and their kidney biopsies were reviewed, and they were followed for their treatment response. Results From 74 patients with DM, 52 female and 22 male, median age 37 (19–65) years, and disease duration of median 4.5 (1–12) months, 2 (2.7%) patients (25- and 28-year-old male) had proteinuria. Their kidney biopsy showed mesangioproliferative glomerulonephritis (GN). There was no case of acute or chronic kidney damage or rhabdomyolysis. Both had high disease activity, high erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), abnormal capillaroscopy, and high anti-Ro positivity with good early response of their kidney function, muscle weakness, and laboratory tests after immunosuppressive treatment for 3–6 months. One patient had capillaroscopy follow-up, and all abnormalities were resolved in 8 fingers. One patient, due to poor follow-up, after 8 months had recurrence of his disease. Conclusions We found mesangioproliferative GN as a rare extra-muscular manifestation in patients with DM in the active and early phase of the disease. Full immunosuppressive treatment showed early complete recovery in these patients

Huge femoral artery pseudoaneurysm in a patient with Behçet’s disease

Background: Behçet’s disease (BD) is a variable vessel vasculitis and vascular involvement is one of its life threatening manifestations. Arterial involvement frequently occurs with male predominance with pseudoaneurysms being the most common presentation. Immunosuppressive therapy is the mainstay of treatment in vascular involvement. Case presentation: The case we report here is a 40 year old Iraqi BD patient with manifestations of recurrent oral and genital ulcers, bilateral anterior uveitis, and deep vein thrombosis. The pathergy test was positive. The HLA-B51 was negative, erythrocyte sedimentation rate 102 mm/1st h and C-reactive protein was 48 mg/L. After discontinuation of his medications for about 9 months, the disease presented with leg pain and swelling that was diagnosed as huge left superficial femoral artery pseudoaneurysm by Doppler ultrasonography. CT angiography revealed a 90 × 88 × 70 mm pseudoaneurysm with partial mural thrombosis. He was scheduled for emergency surgery due to severe intractable pain. he received a pulse of methylprednisolone 1 g/day for 3 days and then surgery was done in the form of exclusion, repair and femorofemoral bypass were done. Post-operatively, the patient had an uneventful course; distal pulses became palpable, pain and swelling subsided. Post-operation, prednisolone 1 mg/kg was continued and he received cyclophosphamide 750 mg intravenously. His blood homocysteine level was higher than normal 23.8 μmol/L. He was discharged with a high dose of steroid and monthly cyclophosphamide treatment. Conclusion: Arterial pseudoaneurysm is life-threatening in BD and should be kept in mind to prevent major complications. Vascular involvement in BD patients is probably associated with hyperhomocysteinemia

Serum vascular endothelial growth factor (VEGF), soluble VEGF receptor-1 (sVEGFR-1) and sVEGFR-2 in systemic sclerosis patients: Relation to clinical manifestations and capillaroscopy findings

Introduction: The role of angiogenesis in the pathogenesis of systemic sclerosis (SSc) is well known. The imbalance between vascular endothelial growth factor (VEGF) and their anti-angiogenic soluble receptors (sVEGFR-1 and VEGFR-2) has been proposed as a possible cause of microangiopathy. Aim of the work: To determine the levels of VEGF, sVEGFR-1 and sVEGFR-2 and the VEGF/sVEGFR1 and VEGF/sVEGFR2 ratios in SSc patients and to study their relation with clinical manifestations and capillaroscopy findings. Patients and methods: The study included 44 SSc patients and 44 controls. The sclerosis severity was assessed by the modified Rodnan skin score (mRss) and capillaroscopy performed in patients. Serum VEGF, sVEGFR-1 and sVEGFR-2 were measured in patients and control. Results: SSc patients had a mean age of 40.7 ± 12.8 years, M:F (1:9) and disease duration was 56.2 ± 60.6 months. 27 patients (61.4%) had diffuse-SSc and 17 (38.6%) limited. The mean VEGF was significantly higher (363.4 ± 133.9 pg/ml) and sVEGFR-2 lower (2039.6 ± 109 pg/ml) in patients compared to control (93.9 ± 25.2 pg/ml and 2366 ± 116.5 pg/ml; p = 0.05 and p = 0.04, respectively). Serum levels of sVEGFR-2 in patients with early, active and nonspecific scleroderma pattern of capillaroscopy was higher in comparison to patients with late scleroderma pattern (p = 0.05). There were no significant differences in the studied parameters between those patients with and without digital ulcerations and interstitial pulmonary fibrosis. A significant correlation was found between mRss and VEGF (p = 0.04). Conclusion: An overproduction of VEGF, a potent angiogenic molecule or down regulated production of its natural inhibitors (sVEGFR-2) might be involved in the development of vasculopathy in SSc patients

Conjunctivitis as a manifestation of Wegener's Granulomatosis

Purpose: To report a case of prolonged conjunctivitis as the manifestation of Granulomatosis with polyangiitis (GPA). Methods: A 37-year-old man presented with prolonged conjunctivitis which had persisted for one month. He was taking medication for his conjunctivitis without any response. A slit-lamp examination revealed conjunctivitis and scleritis in the right eye. Conjunctivitis, 360-degree peripheral corneal thinning, corneal perforation, and scleritis were seen in the left eye. Results: Emergency penetrating keratoplasty was performed to treat the patient's corneal perforation. After a consultation with the Internal Medicine Department, the patient was suspected of having GPA with positive cytoplasmic anti-neutrophil cytoplasmic antibodies (C-ANCA). Functional endoscopic sinus surgery was performed to treat right maxillary sinusitis, and a biopsy of the maxillary sinus mucosa was obtained. The pathology report showed granuloma and vasculitis with severe acute and chronic inflammation and few eosinophils; thus, the diagnosis was confirmed. Conclusion: Because prolonged conjunctivitis occurs only rarely in association with systemic disease, ophthalmologists should be aware of this potential, particularly in patients with GPA. Keywords: Granulomatosis with polyangiitis, Prolonged conjunctivitis, Scleritis, Keratiti

Reporting items for capillaroscopy in clinical research on musculoskeletal diseases: A systematic review and international Delphi consensus

Objectives: The level of detail included when describing nailfold videocapillaroscopy (NVC) methods varies among research studies, making interpretation and comparison of results challenging. The overarching objective of the present study was to seek consensus on the reporting standards in NVC methodology for clinical research in rheumatic diseases and to propose a pragmatic reporting checklist. Methods: Based on the items derived from a systematic review focused on this topic, a three-step web-based Delphi consensus on minimum reporting standards in NVC was performed among members of the European League against Rheumatism (EULAR) Study Group on Microcirculation in Rheumatic Diseases and the Scleroderma Clinical Trials Consortium. Results: A total of 319 articles were selected by the systematic review, and 46 items were proposed in the Delphi process. This Delphi exercise was completed by 80 participants from 31 countries, including Australia and countries within Asia, Europe, North America and South America. Agreement was reached on items covering three main areas: Patient preparation before NVC (15 items), device description (5 items) and examination details (13 items). Conclusion: Based on the available evidence, the description of NVC methods was highly heterogeneous in the identified studies and differed markedly on several items. A reporting checklist of 33 items, based on practical suggestions made (using a Delphi process) by international participants, has been developed to provide guidance to improve and standardize the NVC methodology to be applied in future clinical research studies

Reporting items for capillaroscopy in clinical research on musculoskeletal diseases: A systematic review and international Delphi consensus

Objectives: The level of detail included when describing nailfold videocapillaroscopy (NVC) methods varies among research studies, making interpretation and comparison of results challenging. The overarching objective of the present study was to seek consensus on the reporting standards in NVC methodology for clinical research in rheumatic diseases and to propose a pragmatic reporting checklist. Methods: Based on the items derived from a systematic review focused on this topic, a three-step web-based Delphi consensus on minimum reporting standards in NVC was performed among members of the European League against Rheumatism (EULAR) Study Group on Microcirculation in Rheumatic Diseases and the Scleroderma Clinical Trials Consortium. Results: A total of 319 articles were selected by the systematic review, and 46 items were proposed in the Delphi process. This Delphi exercise was completed by 80 participants from 31 countries, including Australia and countries within Asia, Europe, North America and South America. Agreement was reached on items covering three main areas: Patient preparation before NVC (15 items), device description (5 items) and examination details (13 items). Conclusion: Based on the available evidence, the description of NVC methods was highly heterogeneous in the identified studies and differed markedly on several items. A reporting checklist of 33 items, based on practical suggestions made (using a Delphi process) by international participants, has been developed to provide guidance to improve and standardize the NVC methodology to be applied in future clinical research studies