Sanaz Dehghani

Bio: Sanaz Dehghani is an academic researcher from Shiraz University of Medical Sciences. The author has contributed to research in topics: Prostaglandin analog & Cost effectiveness. The author has co-authored 1 publications.

A 4-week comparison of capillaroscopy changes, healing effect, and cost-effectiveness of botulinum toxin-A vs prostaglandin analog infusion in refractory digital ulcers in systemic sclerosis

Abstract: Systemic sclerosis (SSc) is a systemic multi-organ disease. Raynaud’s phenomenon (RP) and digital ulcers (DUs) in SSc patients can be resistant to usual treatments. We studied the clinical benefits, capillaroscopy changes, and cost-effectiveness of local injection of botulinum toxin-A (BTX-A) and intravenous prostaglandin analogs (iloprost/alprostadil) in patients with SSc with resistant DUs. In a clinical trial study, we evaluated 26 patients fulfilling the ACR/EULAR SSc criteria with resistant DUs. Visual analog scale of pain and RP, skin color and type of ulcers, and capillaroscopy were assessed before and 1 month after treatment. In the first group, 20 units of BTX-A was injected at the base of each involved fingers by a dermatologist. In the second group, 20 µg iloprost or 60 µg alprostadil was infused daily. The cost of these treatments was compared. In 26 patients (43 fingers), there were 16 patients (22 fingers) in the BTX-A and 10 patients (21 fingers) in the prostaglandin group. In 95.5% of the BTX-A and 90.5% of the prostaglandin group, the ulcers were healed. In both groups, a significant decrease in pain was seen (p < 0.0001). Capillaroscopy patterns in both groups were not changed although the microhemorrhages disappeared significantly (p value: BTX-A: 0.03 and prostaglandin: 0.002). The cost was significantly lower in the BTX-A injection group (p < 0.0001). Both BTX-A and prostaglandins helped in the healing and pain control of DUs. In capillaroscopy, microhemorrhages were significantly decreased in both groups. In the BTX-A group, the cost was significantly lower as an outpatient treatment and was more time-saving. • BTX-A and prostaglandin analogs both contributed to the healing of digital tip ulcers and improving the pain • In capillaroscopy, microhemorrhages were significantly decreased or disappeared after both treatments • There was no significant side effect in both groups • Comparing both groups, in the BTX-A group, the cost was significantly lower when performed on an outpatient treatment and more time-saving.

Treatment of digital ulcers in systemic sclerosis: recent developments and future perspectives

Abstract: Abstract Digital ulcers (DUs) comprise the main manifestation of vasculopathy and are a major cause of disability in patients with systemic sclerosis (SSc). A literature search in Web of Science, PubMed and Directory of Open Access Journals was performed in December 2022 to identify articles published in the last decade regarding the management of DUs. Prostacyclin analogues, endothelin antagonists and phosphodiesterase 5 inhibitors have shown promising results both as a stand-alone treatment and in combination for the treatment of existing and prevention of new DUs. Moreover, autologous fat grafting and botulinum toxin injections, although not readily available, can be of use in recalcitrant cases. Many investigational treatments with promising results could pave the way for a paradigm shift in the treatment of DUs in the future. Despite these recent advances, challenges remain. Better-designed trials are of paramount importance to optimise DU treatment in the years to come. Key Points • DUs are a major cause of pain and reduced quality of life in patients with SSc. • Prostacyclin analogues and endothelin antagonists have shown promising results both as a stand-alone treatment and in combination for the treatment of existing and prevention of new DUs. • In the future, a combination of more powerful vasodilatory drugs, perhaps in conjunction with topical approaches, may improve outcomes.

Copeptin as a Biomarker of Microcirculation Alterations in Systemic Sclerosis

Abstract: Systemic sclerosis is a connective tissue disease characterized by vasculopathy and progressive fibrosis, leading to multiorgan dysfunction. Given the complex and not fully elucidated pathogenesis, biomarkers of rapid disease progression and therapeutic response are lacking. Copeptin, which reflects vasopressin activity in serum, is used in diagnosing or prognosing different cardiometabolic conditions.The aim of study was to investigate the concentration of copeptin in patients with systemic sclerosis and correlate it with specific clinical symptoms.Serum copeptin was measured in patients with systemic sclerosis (34 women and 3 men; mean age 57.6 years) and in healthy individuals (n=30) using commercially available ELISA kits. According to the criteria of LeRoy our systemic sclerosis cohort consisted of 17 patients with limited cutaneous systemic sclerosis (45.9%) and 20 diffuse cutaneous systemic sclerosis patients (54.1%). According to the criteria of LeRoy our systemic sclerosis cohort consisted of 17 patients with limited cutaneous systemic sclerosis (45.9%) and 20 diffuse cutaneous systemic sclerosis patients (54.1%). The median duration of the disease was 10 [4-14] years.We found significantly higher copeptin concentration in patients with systemic sclerosis (4.21 pmol/L [3.04-5.42]) in comparison to control group (3.40 pmol/L [2.38-3.76], p<0.01). Copeptin significantly correlated with Raynaud's condition score (r=0.801, p<0.05). Patients with "late" capillaroscopic patterns had higher copeptin concentrations (5.37 pmol/L [4.29-8.06]) than patients with "early" (2.43 pmol/L [2.25-3.20], p<0.05) and "active" patterns (3.93 pmol/L [2.92-5.16], p<0.05]). Copeptin was found to be significantly higher in SSc patients with DUs (5.71 pmol/L [IQR 4.85-8.06]) when compared to SSc patients without DUs (3.31 pmol/L, [2.28-4.30], p<0.05). Additionally, copeptin concentration had good diagnostic accuracy in discriminating between patients with and without digital ulcers (AUC=0.863). Alprostadil decreased copeptin concentration from 4.96 [4.02-6.01] to 3.86 pmol/L [3.17-4.63] (p<0.01) after 4-6 cycles of administration.Our findings suggest that copeptin may be a promising biomarker of microcirculation alterations in systemic sclerosis.

Treatment of Vascular Complications in Systemic Sclerosis: What Is the Best Approach to Diagnosis and Management of Renal Crisis and Digital Ulcers?

Abstract: Vasculopathy as exemplified by scleroderma renal crisis (SRC) and digital ulcers (DUs) is a cardinal feature of systemic sclerosis (SSc) and is associated with significant morbidity, including in patients with early disease. Prompt recognition and management is required to alleviate potentially irreversible damage from SSc-associated vasculopathy. Both SRC and DUs share many etiopathogenic drivers which inform the therapeutic strategy. The aim of our review was to describe the diagnosis and management of SRC and DUs in SSc, and to discuss unmet needs for future research.

Botulinum Toxins for the Treatment of Raynaud Phenomenon

Abstract: Botulinum toxin (Btx) therapy has emerged as a potential treatment for patients with Raynaud phenomenon (RP) in recent years. This study aimed to investigate the efficacy and safety of Btx treatment for RP.Databases of PubMed, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from their inception up to August 2022. Studies that reported Btx use for the treatment of RP were included. A meta-analysis was conducted for the Shortened version of the Disabilities of the Arm, Shoulder, and Hand (Quick DASH) score and visual analog scale pain score using a random-effects model.Thirteen full-text studies were included. The pooled standard mean changes for the visual analog scale pain score and QuickDASH score were -3.82 (95% confidence interval, -6.62 to -1.02) and 0.83 (95% confidence interval, -1.47 to -0.19), respectively. The 2 most common complications were injection site pain and intrinsic hand weakness.The effect of Btx treatment on RP is promising based on current evidence. Nevertheless, more studies and randomized clinical trials with larger sample sizes are needed to confirm the current results.

Botulinum toxin injection for refractory Raynaud phenomenon and digital ulcers in systemic sclerosis

Abstract: Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by tissue and organ fibrosis and vasculopathy.1 Digital ulcers (DU) and Raynaud phenomenon (RP) are the presentations of vasculopathy found in SSc. Raynaud phenomenon is a process in which extremities undergo an episodic color change upon cold exposure. As a result, patients suffer from severe pain and disability, which markedly impairs their life quality. The mechanism of SSc-related RP comprises amplified sympathetic-mediated vasoconstriction and dysfunctional endothelial cells.2 Digital ulcers occur in around half of SSc cases, they result in complications such as pain, impaired function, and even gangrenous changes.1 Nowadays, calcium-channel blockers, prostacyclin analogs, endothelin receptor antagonists, and phosphodiesterase inhibitors are the primary pharmacological treatments for DU and RP.3 Surgical intervention such as sympathectomy is indicated for severe cases that are refractory to medical management. Nevertheless, intractable RP and DU still pose a significant challenge in clinical practice. There is preliminary evidence that SSc-related peripheral vasculopathy benefits from local injections of botulinum toxin (BTX). Studies propose that BTX could target sympathetic adrenergic vasoconstriction and endothelial exocytosis to induce therapeutic effects on RP/DU.2 In the past two decades, several clinical trials have been conducted to determine if local injections with BTX into hands could be efficacious in controlling intractable RP/DU in patients with SSc.4-8 BTX injection protocol differed between clinical trials. Most clinical trials used BTX-A, whereas Motegi et al chose BTX-B.5 Both dorsal and palmar approaches were introduced regarding injection sites on hands. Some studies selected injection sites near the neurovascular plexus. BTX dosages in former clinical trials were heterogeneous, ranging from 20 to 100 units per hand; however, whether the efficacy of BTX injections was dose-dependent required further investigation. Motegi et al5 suggested that the improvements in RP/DU were more remarkable in the intervention group with higher doses. Most clinical trials selected participants who were refractory to traditional drug therapy, and vasoactive drugs were continued during the trials. Hence, whether BTX injection efficacy is derived from BTX alone or combined with other vasoactive drugs needs to be clarified. Follow-up time points varied between trials, ranging from 1 to 4 months. Different follow-up time points may affect the study results because the effects of RP/DU might decrease with time. For example, Motegi et al proposed that the efficacy of local BTX injections could sustain for 4 months, whereas Dhaliwal et al found that hand function decreased by 3 months after BTX injections.5, 9 The outcome assessments use aspects such as RP severity, tissue perfusion, and hand function (Table 1). Standard measures for RP severity include the Raynaud condition score and visual analog scale. Most clinical trials reported a statistically significantly faster decline of Raynaud condition score in patients with BTX injections, including clinical trials published in 2022.7, 8 An improved pain score was presented in several studies, but some did not reach statistical significance. As for tissue perfusion, it was measured by methods such as change in blood flow with laser Doppler imaging and pulse oximetry. Picasso et al10 suggested that a newly developed ultrasound technique using ultra-high frequency has the potential to disclose subtle abnormalities in distal digital arterioles. The study by Bello et al4 was one of the best-conducted studies in which blood flow change was set as the primary outcome. However, the results showed that local BTX injections did not significantly improve blood flow to the patients’ hands. Decreased DU number after BTX injection therapy was reported in many clinical studies.5, 6 Regarding hand function, the “Quick Disabilities of the Arm, Shoulder and Hand” questionnaire (QuickDASH) was the most used outcome measure. Many clinical trials also reported significantly improved QuickDASH scores after BTX therapy. It is noteworthy that the ethnicity of enrolled participants differed between clinical trials. Emil et al11 proposed that the ethnic, genetic, and population variables could affect the onset, prevalence, and outcomes of SSc. As a result, the role of ethnicity and genetic background cannot be ignored when evaluating the outcomes of BTX injections. Local BTX injections seem to be safe in most trials. Reported complications included pain and weakness over injected hands. Shenavandeh et al6 suggested that BTX injections were cost-effective and time-saving. Local injections could be performed at outpatient departments, which is especially convenient during the COVID-19 pandemic. In conclusion, a few clinical trials support the efficacy of BTX local injections for RP/DU in SSc patients. Local BTX injections have emerged as a safe and cost-effective nonsurgical treatment for refractory SSc-related RP/DU. However, more extensive double-blinded randomized controlled trials are still required to confirm the benefits of BTX injections and propose the optimal injection protocol.