**Author details**

inhibitors included different forms of vasomotor reactions, myalgias, allergic reaction, chest pain, dyspepsia, nasal stuffiness, and visual abnormalities. Considering long-term experience and good safety profile, EULAR experts recommend CCBs as first-line therapy for SSc-related RP and phosphodiesterase-5 inhibitors for SSc with severe RP and/or in cases with insufficient

*Intravenous iloprost* possesses proven efficacy for reduction of the frequency and severity of SSc-related RP. Considering costs and feasibility, it is recommended after failure of oral therapies (CCBs and phosphodiesterase-5 inhibitors). Intravenous iloprost is also efficacious in the treatment of digital ulcers in SSc that is proved in randomized, placebo-controlled clinical trials [86, 87]. However, the need for hospitalization, the prolonged intravenous infusion (6 hours at the dose of 0.5–2 ng/kg/min), side effects, and high price are limiting factors for the administration of iloprost. Adverse effects include headache, nausea, vomiting, diarrhea, myalgia, arthralgia, chills, fever, arrhythmia, hypotension, chest pain (especially in patients with coronary heart disease), erythema, and pain at the infusion site. Thus, concomitant pathology should be assessed and hemodynamic parameters of the patients closely observed, e.g., blood pressure, heart rate, and pulse at the beginning and at every increase of the infusion rate. The risk for orthostatic hypotension should be also considered. Apart from its properties as a vasodilator, iloprost inhibits platelet aggregation, leukocyte chemotaxis, and adhesion to the endothelium. Iloprost also downregulates the expression of adhesion molecules on

In addition, in the most recent EULAR recommendation, *fluoxetine* (a serotonin-specific reuptake inhibitor and antidepressant) is suggested as an option in SSc-related RP despite the scarce published evidence [82]. In a small study that included 26 patients with primary RP and 27 with SSc-related RP, fluoxetine (20 mg daily) showed superior efficacy vs. nifedipine (40 mg daily). Observed side effects of fluoxetine were apathy, lethargy, and impaired concentration [89]. Despite the relatively low quality of published evidence, EULAR experts suggest fluoxetine as a useful alternative for treatment of SSc-related RP, especially in SSc

In SSc patients, in whom RP has complicated with digital ulcers, EULAR experts recommend *intravenous iloprost* and *phosphodiesterase-5 inhibitors* for treatment of digital ulcers and *bosentan* 

Being a first symptom in a number of CTD, the presence of RP requires regular follow-up that includes clinical, laboratory, immunological, and capillaroscopic assessment. The appearance of pathological capillaroscopic picture inherits a higher positive predictive value (47%) for the development of CTD vs. the predictive value of the positive ANA test (30%) [15]. Thus, nailfold capillaroscopy is the key investigation for monitoring RP patients. The interval of follow-up is 6 months, because a longer period of time is usually necessary for the development of morphological capillaroscopic changes, but this period may be shorter in cases with

*(endothelin receptor antagonist)* for reduction of the number of new digital ulcers [82].

endothelial cells and phagocytes and enhances fibrinolytic activity [86–88].

patients who do not tolerate or fail to respond to vasodilators [82].

**9. Prognosis**

newly appeared alarming symptoms.

effect from the treatment with CCBs [82].

38 Newest Updates in Rheumatology

Sevdalina Nikolova Lambova

Address all correspondence to: sevdalina\_n@abv.bg

Department of Propaedeutics of Internal Diseases, Faculty of Medicine, Medical University, Plovdiv, Bulgaria
