Hereditary haemorrhagic telangiectasia (HHT), also known as Rendu–Osler–Weber syndrome (ORPHA774), is an autosomal dominant condition characterized by the presence of arteriovenous malformations (AVMs) in different locations including the gastrointestinal tract, the central nervous system, the lungs, and the skin.1 HHT can be diagnosed either clinically or through molecular gene testing. For clinical diagnosis, Curaçao criteria (recurrent epistaxis, mucocutaneous telangiectasia, vascular visceral involvement, and a first-degree family member) are used: meeting three or more of these criteria implies a definitive diagnosis of HHT.2,3 Mucocutaneous AVMs of HHT, commonly known as telangiectases, are prone to severe bleeding, mainly epistaxis. Facial and digital lesions are stigmatizing, with a profound impact on quality of life (QoL). Despite these major functional and aesthetic concerns, evidence on treatment of mucocutaneous telangiectases is scarce. Neodymium: yttrium-aluminium-garnet (Nd:YAG) laser has proved its efficacy for the treatment of HHT, but safety is a major concern.

The use of dual wavelength sequential laser (DWSL) with pulsed dye laser (PDL) – Nd:YAG laser could be a safer and more effective alternative than Nd:YAG alone.4,5 DWSL has the advantage of sequentially emitting 595nm PDL and 1064nm Nd:YAG wavelengths from the same handpiece. Thus, PDL first transforms oxyhemoglobin into methemoglobin, increasing three-to-five-fold the absorption of Nd:YAG by the targeted structure. Consequently, it allows the use of lower fluencies of Nd:YAG laser, therefore considerably reducing the risk of side effects.5 DWSL has been used with good results in multiple vascular conditions.5 Also, it has been used to treat HHT with very good responses, similar or even superior to those of other lasers6 (Table 3). However, to our knowledge, no comparative studies between Nd:YAG laser and DWSL for treatment of HHT telangiectases have been published to date.

Table 3.

Treatment results.

Shaded areas indicate absence of treatment. Improvement was categorized using a 5-point ordinal relative scale: 0–20%, no response (0); 21–40% poor response (1); 41–60%, partial response (2); 61–80%, good response (3); and 81–100%, excellent response (4).

Abbreviations: DWSL: dual wavelength sequential PDL-Nd:YAG laser; YAG: neodymium-doped: yttrium-aluminium-garnet; PDL: pulsed dye laser; V0: baseline visit; VF: endpoint visit; NA: not applicable/available.

The aim of this study was to compare the efficacy and safety of DWSL versus Nd:YAG for the treatment of mucocutaneous telangiectasia in HHT patients. Secondary aims were to evaluate global laser therapy satisfaction, QoL improvement with laser treatment, and differences in response and tolerance among different therapeutic areas (hands, mouth and face).

Twenty-nine clinical records were retrieved, and three patients were excluded due to loss of follow-up. Eventually, data from 26 patients (17 women and 9 men) with cutaneous and/or mucosal telangiectases were analyzed (Table 2). Their median age was 58 years (interquartile range [IQR] 45–66). Telangiectases were predominantly located on the mouth (24 patients), followed by face (20 patients) and hands (13 patients). In total, 111 treated areas (55 treated with DWSL and 56 with Nd:YAG laser) were analyzed. Laser therapy on the setting of this study was the first treatment for most (20, 76.9%) patients. Four patients had previously been treated with laser (Nd:YAG or DWSL), one with electrosurgery and one with surgery.

The number of laser sessions in our study was similar for Nd:YAG and DWSL: median 2, IQR 2–4 mean 2.88 vs 2.9, respectively. The laser parameters are detailed in Table 2. The median laser parameters in DWSL treatments were spot 7mm, fluence 8J and 50J, duration 10ms and 15ms, for PDL and Nd:YAG, respectively, and spot 3mm, 150J and 17.5ms for Nd:YAG laser. There was no significant correlation between fluence and improvement for either DWSL or Nd:YAG (p=0.45 and 0.92, respectively).

The median global severity scores at baseline were 2 (IQR 2–3; mean 2.4) for DWSL and 2 (IQR 2–3; mean 2.3) for Nd:YAG laser; at the endpoint they were 1 (IQR 0–1; mean 0.74) vs 0 (IQR 0–1; mean 0.52), respectively. There was a statistical trend for correlation between patients’ age and severity at baseline (p=0.078). There were no statistical differences of severity at baseline, between DWSL and Nd:YAG treatments. However, there was a statistical tendence for differences in severity between Nd:YAG group and DWSL (p=0.067) at endpoint. The severity score data by treatment areas are provided in Table 3. The change in severity from baseline to the endpoint was significant both overall (DWSL and Nd:YAG subgroups), for each subgroup (p<0.0001), and for each location considered separately (p<0.0005).

The median improvement score, irrespective of location, was 2 (IQR 2–3; mean 2.32) in DWSL vs 3 (IQR 2–3; mean 2.61) in Nd:YAG treatment (Fig. 1). Differences in improvement between Nd:YAG subgroup and DWSL were statistically significant (p=0.03). By treatment areas, improvement rates are detailed in Table 3. There were no significant differences between areas as regards improvement (Kruskal–Wallis p=0.299). There was no correlation between number of sessions and improvement, regardless of laser modality (p=0.142), for Nd:YAG (p=0.384), or for DWSL (p=0.188).

Figure 1.

Hereditary haemorrhagic telangiectasia. Patient treated each body side with DWSL laser (D) and Nd:YAG laser (Y), respectively. (A) Pre-treatment clinical photograph (above, a–c), (B) post-treatment clinical photograph (below, d–f), after 4 sessions.

(0.31MB).

Twenty-four out of 26 patients reported a high degree of satisfaction with laser treatment (NRS score≥8; median 10 (IQR 9–10, mean 8.9). Pain was bearable in all cases, with a median NRS value of 5 (IQR 4–7, mean 5.65) in DWSL vs 5 (IQR 3–6, mean 4.86) in the Nd:YAG treatment sides. Pain was significantly more intense in DWSL treated sides (p=0.003). By treatment areas, pain was most intense on the hands (median 6, IQR 5–7, mean 6), followed by the mouth (median 5.5, IQR 3.5–7, mean 5.38) and face (median 5, IQR 3–5, mean 4.59) regions. Differences between regions were close to statistical significance (p=0.054). No severe adverse events were recorded. Some patients reported transient oedema and mild pain during the first days, following treatment of mouth lesions (eleven patients out of 24). Patient 2 had a palpable slightly-visible scar on the lip in Nd:YAG side. Patient 4 and 11 had transient oedema and crusts on the lips, only in Nd:YAG side, while patient 13 only crusts on the hands in DWSL side. Three out of 13 patients reported crusts on hands. No other adverse events were recorded. One patient had scarring from previous treatments that persisted at the endpoint visit (patient 20).

In terms of QoL impairment, the median score of FACE-Q test was 28.5 out of 100 (IQR 0.75–47, mean 28.85) at baseline and 0 (IQR 0–13, mean 12.69) by the end of the study. On the other hand, median global skindex-29 score was 21.5 (IQR 7–42, mean 27.65) at baseline and 3.5 (IQR 2–14, mean 14.73) by the end of the study. For both FACE-Q index and Skindex-29 test, differences between baseline and final scores were statistically significant (p<0.001). Adverse events, satisfaction and quality of life evaluation results are detailed in Table 4.

Nd:YAG laser may be considered the gold standard of treatment for HHT mucocutaneous telangiectases, since it reaches a depth of 5–6mm, corresponding to the usual location of HHT telangiectases.8 However, despite the proven benefits of Nd:YAG laser for the treatment of HHT, with more than 50 reported patients,9–11 safety concerns limit its use. Its small therapeutic window may lead to potential tissue necrosis and scarring due to unwanted thermal damage.5 Thus, it would be convenient to find an equally effective but safer alternative.

Even though DWSL seemed to be a good candidate according to the available evidence,6 in our study the Nd:YAG laser had better response rates, together with better tolerability (less pain) and slightly lower safety (more side effects as scarring, oedema, etc.). Our patients severity improved from a median of 2 in Nd:YAG subgroup to a median of 0, compared to the improvement of 2 to 1 in DWSL group respectively, after a median number of 2 sessions at the endpoint. Our responses with Nd:YAG laser may be comparable to those in available studies9–11 (Table 5), even though the evaluation criteria differ, limiting their comparison. However, the responses to DWSL in our study were lower compared to published evidence with the same evaluation criteria.6 This might be explained by the lower number of sessions, with similar fluences, in our study compared to previous publications (mean number of sessions, 2.77 vs 3.73).6 As previously reported,12 less sessions may decrease the response scores, which may explain our results. In the current study, differences in response between DWSL and Nd:YAG may be accounted on lower fluences of Nd:YAG in DWSL compared to Nd:YAG alone (52.31J vs 156.54J). Despite the theoretic proposal that methemoglobin would increase the absorbance of Nd:YAG, this effect might be insufficient to account for such a fluence difference. In our opinion, Nd:YAG would be the main player of DWSL in treating the thicker lesions of HHT patients. Published pictures from patients treated with Nd:YAG alone9–11 suggest their lesions are thicker than those of patients treated with PDL.13,14 Consequently, lower fluences of Nd:YAG in DWSL may have a lower overall efficacy, even though the responses achieved would be considered satisfactory. Comparisons with the published reports on other laser modalities (Table 5) are not possible due to different evaluation criteria.

As regards tolerability, pain NSR was lower with Nd:YAG (mean 4.86 vs 5.65, p=0.046). Data from published studies is inconsistent: some authors found no differences in pain,15,16 others reported more pain with Nd:YAG17 and others more with PDL alone.18 In our experience, tolerance to DWSL may be affected by the sequential two laser shots compared with just one shot in Nd:YAG.18 By topographic regions, treatment of hand lesions was the most painful (p=0.054). Differences in referred pain may be explained by differences in nociception, since pain sensitivity is higher in glabrous skin.19

Overall, no severe adverse events were reported by our patients in either group. Crusting or oedema were less severe and frequent on the face. According to our results a lower risk of scarring might be expected with DWSL, but even in the Nd:YAG group only one patient (patient 2) had a small slightly visible palpable scar. This is consistent with a higher risk of tissue damage caused by photothermolysis when higher fluences of the Nd:YAG laser are used alone, which can lead to scar formation.

Impairment of QoL in HHT patients, in most cases related to epistaxis, is occasionally reported in the literature.16,20–22 In the current study, the effects of each laser treatment on QoL were not compared due to difficulty in discerning effects on QoL for each laser subtype (and body side). Considering the Skindex-29 cut-offs described by Prinsen et al.,23 our HHT patients would be considered as having mild to moderate QoL impairment. However, there is no currently standard approach defined to evaluate Skindex-29.23 On the other hand, FACE-Q® test obtained high values at the beginning of the study which confirm the high aesthetic impact and psychological distress that HHT patients suffer, mainly when the face is affected, as specifically assessed by FACE-Q® test. Differences from baseline to the end of the study were found to be statistically significant for tests, which proves that laser therapy can improve the QoL impairment of HHT patients. Probably, this improvement is related not just to the benefit on general aesthetics and physical appearance, but also to the decreased frequency and intensity – and even disappearance – of bleeding of mucocutaneous telangiectases, as reported by patients. This might also partially account for the high satisfaction rates in our study.

Our study has some strengths and limitations that should be mentioned. This is the first randomized double-blinded study including QoL assessment on laser therapy of telangiectases in HHT patients. The low prevalence of HHT and the concurrent COVID-19 pandemic explained the small number of patients recruited and limited their follow-up.

Both DSWL and Nd:YAG are safe, effective and satisfactory treatment options for treating mucocutaneous telangiectases in HHT patients. However, Nd:YAG provided better results with better tolerability, but a slightly lower safety profile in our study. Satisfaction rates were high and improvement in QoL significant with both laser modalities.

The authors declare that they have no conflict of interest.