We searched for articles on light-based therapies used alone or with a photosensitizer (PDT) to treat HS. Articles had to be published between August 2015 and March 1, 2019. Additional limiters were set to select studies in humans that were published in either Spanish or English. We started the search with August 2015 because a systematic review in the Cochrane Library was updated at that time. Our intention was to update that review with the results of more recent studies.

We also searched backwards from the reference lists to identify any cited articles meeting our inclusion criteria.

The following databases were used: MEDLINE (through PubMed), EMBASE, the Centre of Reviews and Dissemination (University of York), the Cochrane Library (in the Cochrane Database of Systematic Reviews), the Cochrane Skin Group, the Centre of Evidence Based Dermatology (University of Nottingham), and TESEO (the Andalusian database of PhD theses). The following trial registries were also consulted: ClinicalTrials.gov, reec.aemps.es, and Clinicaltrialsregister.eu.

Finally, the PROSPERO register was searched for systematic reviews on HS. We specified reviews that included light-based therapies.

Search terms were chosen from the list of Medical Subject Headings (English) and its equivalent in Spanish (Descriptores en Ciencias de la Salud), as follows: photochemotherapy, photodynamic therapy, hidradenitis suppurativa, suppurative hidradenitis, light, lasers, laser therapy, intense pulsed light therapy.

Article inclusion criteria were as follows:

• •

  Type of study: randomized controlled clinical trials (RCTs), systematic reviews, observational studies with a control group, and observational studies without a control group (case series)

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  Population: adults with HS regardless of sex, ethnicity, comorbidity, or prior treatment

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  Limiter: inclusion of patients whose HS was treated with PDT (using any type of laser or other light source)

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  Limiter: publication in Spanish or English

Article exclusion criteria were as follows:

• •

  Publication outside the time frame

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  Studies not using accepted, validated HS evaluation tools (eg, the Hidradenitis Suppurativa Clinical Response criterion, the modified Sartorius score, and/or the Physician Global Assessment [PGA] of HS)

• •

  Case series with fewer than 5 patients

• •

  Editorials and narrative reviews

Search results were downloaded with Mendeley reference management software, with titles and abstracts in separate fields. All duplicate, discarded, and selected references were recorded (Fig. 1). The literature searchers were not blinded to authors’ names or institution or the publishing journal.

Figure 1.

Flow chart of the literature search for this systematic review. TESEO is the database of doctoral theses in Andalusia, Spain.

(0.27MB).

The scale of Jadad et al13 was used to evaluate RCTs. Critical analysis was based on the CONSORT guidelines (Consolidated Standards for Reporting Clinical Trials).14 The tool of the Basque Office for Health Technology Assessment (OSTEBA, its Spanish acronym)15 was used to assess the quality of evidence afforded by several types of studies and build a table synthesizing the results.

Of the 199 studies found, we excluded 164 after removing duplicates and assessing the titles and abstracts. We evaluated 35 full texts, excluding 24 that did not meet the inclusion criteria. Some did not have 5 patients.9,12,16–37 (See Appendix B, supplementary material.) Because few clinical trials and systematic reviews were found, we included case series even though their evaluation of efficacy and effectiveness is limited.

Thus, we evaluated 6 case series (5 prospective and 1 retrospective). The evidence level was low in 4 of the series and moderate in 2 of them.

Most studies were carried out in Europe (Spain, the United Kingdom, France, and Italy), the United States, and Egypt. The remaining inclusions were 2 moderate-quality RCTs and 3 high-quality systematic reviews. The reviews included 4 trials and 5 case series on light-based treatments and are analyzed in depth in the present systematic review: Fadel and Tawfik,38 Highton et al,11 Tierney et al,39 Calzavara-Pinton et al,40 Schweiger et al,41 Sotiriou et al,42 Mahmoud et al,43 Madan et al,44 and Xu et al.45

Tables 1–3 summarize the studies’ periods of follow-up, numbers of patients and losses, population characteristics and interventions. One relevant study2 was found in a backward citation search of references.

Table 2.

Summary of Articles on Intralesional PDT for HS

Reference, y	Study Design, Aim and Period	Study Population	Intervention and Follow-up	Results	Conclusions	Comments	Quality of evidence
Valladares-Narganes et al,51 2015	Design: prospective case seriesObjective: To apply PDT with intralesional light probes that can reach different depths with light at the lowest energy level possibleStudy period: March–November 2013	No. of patients:27 (single group)Characteristics:	Intralesional 1% ALA solution (dose, 0.2mL/cm3).By cannula inserted into fistulous tracts, or needle injection into the diseased area if cannulation was impossible.The entrance to and exit from the fistula was covered for an incubation period of 3h. Next, the fistula was irradiated intralesionally with a continuous diode laser (630nm, fiberoptic probe 1mm in diameter; 1W/cm3; 180J)/cm2). Light was transmitted through a 1-mm needle.If response was suboptimal or new lesions appeared nearby, an additional session was given.Follow-up: 1, 3, and 6 moLosses: 1	Results on the modified Sartorius scale: 10 (37%) complete, 11 (41%) good, and 5 (19%) partial.Best results in the armpits (complete response in 6 of 8), including patients requiring treatment of both armpits.Moderate pain in 4 patients (VAS, 6–9)Most patients (22 of 27) tolerated the procedure well (VAS scores under 6).Adverse effects included postprocedural pain, erythema and slight swelling.	Intralesional PDT may be an effective and long-lasting treatment for HS.The best results are in isolated lesions in the armpits or sacral and breast regions, where most lesions are found. Multiple, interconnected fistulas require more sessions.	RCTs would be a good step toward adequate assessment of therapies alone or in combination. Trials should include dose detection and patient-relevant outcome measures.	Moderate
Agut-Busquet et al,1 2016	Design: respective case seriesObjective: To describe the experience with 7 patients with HS treated with PDT using intralesional MB and light (635nm)Study period: 8 mo	No. of patients: 7Characteristics: HS clinical type 2, Hurley stage 3, at least 1 active zone	Intralesional 1% MB solution injected with or without ultrasound guidance.After incubation (15min), irradiation with a 635-nm LED light (37J/cm2)1–2 sessions, intervals of 15 d.Follow-up: 1, 2, 4, and 6 moLosses: 1	Hurley stage-2 patients responded better than stage-3 patients (99% vs 87% improvement); best results in the groin.DQLI improvement in 6 patients: 78% (1), 80% (1), 90% (2), and 99% (2).Evaluation, Sartorius score and PGA: 78% (1 patient), 80% (1), 90% (2), 99% (2).Good response (86% improvement) to antibiotic in only 1 patient.Adverse effects: mild in 6 cases (86%); serious in 1 patient (cellulitis at treatment site, attributed to patient’s manipulation of the area after therapy)	Intralesional PDT with MB gives good results in HS but is more effective in Hurley stage 2 than stage 3.RCTs are necessary to improve the quality of evidence.	Few patients, making extrapolation to the general population (external validation) difficult.	Low
Suárez Valladares et al,50 2017	Design: prospective case seriesObjective: To evaluate the efficacy of intralesional PDT for the local management of HS in the short and medium term in different sitesStudy period: March 2011–November 2015	No. of patients: 38Characteristics:Sex: 20 women, 18 menAge: 30–44 yWeight: 67.25–90kgMean (SD) BMI: 26.87 (4.89)BMI >27: 20Smokers: 34Prior treatments: 2, none; 1, topical; 23, oral antibiotics; 2, oral retinoids; 1, biologic; 9, surgery.Hurley stages: 1, 4 patients; 2, 21 patients; 3, 13 patients.Direct measures of severity: Hurley, baseline/total HSS, and DLQI indicated high disease activity.	After local anesthesia, 5% ALA gel was injected through a cannula to fill the fistulous tracts. Thus, all walls of fistulous tracts were treated regardless of depth. A lyophilized 1% solution was injected into nodules. Incubation under occlusion for 2h before irradiation. Irradiation (1.2W; fluence, 180J/cm2) with an intralesional 630-nm laser through a 400-mm fiberoptic probe inserted through a needle.Follow-up visits every 5–7 wkFollow-up: 26.1 (21.7–68.57) moLosses: 0	Single session regardless of site, but the median energy used was greater in the armpits.Complete remission in 76.3%, mean disease-free period of 168 wk. New lesions at untreated sites were observed in 9 patients (23.7%); 6 of them had complete remission.Recurrence or no remission after treatment in 9 patients, in whom the percentages of obesity (33.% vs 58.6%) and smoking (66.7 vs 96.6%) were lower but disease severity was greater (44.4% vs 31%), modified Sartorius score was higher (36 vs 22) and DLQI poorer (16 vs 10) than in those with a good response to PDT.	Intralesional PDT might offer a new alternative treatment for HS lesions, alone or in combination;a high rate of complete remission was achieved and was long-lasting.No complications observed.Rapid recovery after treatment, with the possibility of repeating sessions.		Moderate

Abbreviations: BMI, body mass index; DLQI, Dermatology Life Quality Index; E, energy ; HS, hidradenitis suppurativa; HSS, hidradenitis severity score; IR, irradiation; MB, methylene blue; PDT, photodynamic therapy; PGA, Physician’s Global Assessment; RCT, randomized clinical trial; VAS, visual analog scale.

The number of participants in the included studies ranged widely. The maximum was 3846 and the minimum was 5,2,42 for a total of 248 patients (mean, 15.5 patients).

All the studies included men and women older than 18 years with a clinical diagnosis of HS.

One study included only Hurley stage 1 patients (Zerbinati et al47) and 1 included only Hurley stage 2 patients (Mahmoud et al43). Two studies included both Hurley 1 and 2 stages (Abdel Azim et al48 and Fabbrocini et al49). Six studies required moderately severe HS (Hurley stages 2 or 3) at baseline (Andino Navarrete et al,2 Agut-Busquet et al,1 Highton et al,11 Tierney et al,39 Xu et al,45 and Sotiriou et al42). One study included any stage of severity (stages 1, 2, or 3) (Suárez Valladares et al50). Finally, 5 studies did not specify stage (Valladares-Narganes et al,51 Fadel and Tawfik,38 Calzavara-Pinton et al,40 Madan et al,44 and Schweiger et al41).

We included 3 systematic reviews for this systematic update (Ingram et al,3 John et al,52 and Robert et al53) and 2 clinical trials (Fadel and Tawfik38 and Abdel Azim et al48). The remaining studies were case series.

The systematic review of Ingram et al3 included 3 RCTs comparing topical PDT, IPL and Nd:YAG laser therapy.11,38,39 Fadel and Tawfik38 used an active comparator in the control group. Controls were untreated in Highton et al,11 whereas Tierney et al39 applied 1% clindamycin cream in the control group. The systematic review of John et al52 included 22 studies. Three provided high-quality evidence (and were also included by Ingram et al). The only additional inclusion that met our criteria was that of Xu et al,45 which assessed Nd:YAG laser treatment. The most up-to-date systematic review was by Robert et al,53 who included 64 articles about the nonsurgical treatment of HS (with medications or light therapies). Studies of light-based treatments that were not included in the aforementioned reviews were those of Calzavara-Pinton et al40 (PDT with methyl aminolevulinate [MAL]) and Schweiger et al41 and Sotiriou et al42 (PDT with ALA). This third systematic review also included two case series of patients treated with Nd:YAG laser (Mahmoud et al43) and CO2 laser (Madan et al44).

Only 2 RCTs were retrieved. One was by Fadel and Tawfik,38 which was found by backwards searching of citations as described above. The other was by Abdel Azim et al,48 which evaluated a combined treatment with CO2 laser followed by Nd:YAG laser.

One of the case series we included studied the use of PDT with 20% ALA as the photosensitizer and 635-nm laser (Andino Navarrete et al2). Three studies analyzed intralesional PDT. Two used ALA at concentrations of 5% and 1% and a 630-nm laser light source.50,51 The third used MB and a 635-nm light-emitting diode (LED) lamp (Aktilite).1

Zerbinati et al47 analyzed case series in which Nd:YAG laser was used, and Fabbrocini et al49 evaluated the efficacy of diode laser irradiation in mild to moderate HS.

The included studies assessed outcomes in somewhat different ways. Most used the Sartorius score of 2003,1,2,11,38,39,41–43,45,47,49 but 2 studies used the modified version of this score.50,51 Five (Agut-Busquet et al,1 Abdel Azim et al,48 Calzavara-Pinton et al,40 Fabbrocini et al,49 and Madan et al44) used the PGA.

Six evaluated changes in quality of life with the Dermatology Life Quality Index (DLQI) published by Finlay in 1994).1,2,41,42,49,50 General satisfaction was evaluated by Highton et al11 with an unvalidated Likert scale and by Madan et al44 with a score of 0 (very unsatisfied) to 10 (very satisfied).

Two studies assessed pain during and after treatment using a visual analog scale (VAS).2,51

Four studies provided information about adverse effects,1,2,51 although Highton et al11 only reported such effects if treatment had to be interrupted.

Finally, 5 studies reported recurrence rates. Agut-Busquet et al1 emphasized recurrence, explaining each case. Suárez Valladares et al50 reported recurrence in 9 patients. Highton et al11 found that HS tended to recur 12 months after treatment. Recurrence 3 and 12 months after treatment was assessed by Abdel Azim et al48 and Madan et al,44 respectively.

Tables 1–3 summarize the research designs used and quality of evidence obtained by researchers studying the use of conventional PDT, intralesional PDT, and laser treatments. As explained above, the 3 systematic reviews we consulted included patients treated with both PDT and laser therapy. Therefore, to avoid repetition, one table (Table 1) presents the studies that applied laser treatments and IPL in bold face type.

Andino Navarrete et al2 treated 5 patients with a 20% ALA solution for 1.5h and then irradiated the area with a 635-nm LED lamp at a fluence of 37J/cm2 and intensity of 70mW/cm2 per session. The patients experienced improvements (Sartorius score, DLQI, and VAS) that was maintained at 8 weeks, although the differences were not statistically significant.

Fadel and Tawfik38 used PDT with a 0.01% MB gel (formulation in liposomes with surfactants to increase penetration) and compared it to placebo (MB-free) gel. The area was irradiated with IPL (630nm) for 20ms at a fluence of 25J/cm2. The participants were authorized to receive treatment at every affected area of the body (armpits, buttocks, groin, and under the breasts). Results showed a Sartorius score reduction of 77.3% (liposome MB gel formulation) and 44.1% (MB-free placebo) (P<.01). The authors concluded that PDT with MB in this formulation is superior to irradiation after MB-free gel.38

Calzavara-Pinton et al40 studied patients with various diseases treated with MAL-PDT; 6 patients with HS were among them. The authors irradiated with red light (635nm) every 2 weeks for 4 weeks and reported a PGA assessment of more than 75% in 33% of the cases, moderate improvement in half, and a poor response in 1 patient.

Schweiger et al41 described 12 patients treated with ALA-PDT with blue light and IPL weekly for 4 weeks. Four weeks after treatment they observed a reduction in the Sartorius score of 50.8%. At 8 weeks the reduction was 29.9%. The DLQI score fell from 17.3 to 13.1. Blue light was tolerated better than IPL.

Finally, Sotiriou et al42 applied a 20% ALA formulation in 5 sessions in 5 patients with Hurley stage 2 or higher HS. The mean Sartorius score decreased from 18.8% to 17.2%, and DLQI impact fell 6.4% on average. These results are summarized in Table 1.

Valladares-Narganes et al51 administered 1% ALA (0.2mL/cm3) into lesions followed by light exposure, as noted above, in a series of 27 patients with 1 to 3 lesions each. After 26.21 months (range, 21.07–68.57 months), responses were complete in 10 patients (37%), moderate in 11 (41%), and partial in 5 (19%). The authors saw the best results in armpit lesions (Table 2).

Agut-Busquet et al1 injected a 1% MB solution into lesions under ultrasound guidance in 7 patients. After incubation (15minutes), the lesions were irradiated with an LED lamp (Aktilite, 635nm, 37J/cm2). After 6 months the global assessment of response was 78% in 1 patient, 80% in 1, 90% in 2, and 99% in 2. Patients with Hurley stage 2 HS responded better (99%) than those with Hurley stage 3 (87%), and the best results were observed in groin lesions. DLQI improved significantly for 6 patients, coinciding with excellent response to treatment. Mild adverse effects (swelling or erythema) were observed in 6 patients (86%), but they resolved within a week (Table 2).

Suárez Valladares et al50 injected a 5% ALA gel into lesions through a cannula placed along the sinus tract in 38 patients. After incubation under opaque occlusion for 2hours, intralesional laser irradiation (630nm, 1.2W; fluence, 180J/cm2) was applied with a fiberoptic probe (400mm). All regions treated improved according to modified Sartorius scale results. There were 53 complete responses, 7 good responses, and 4 partial responses. However, the differences were not statistically significant (Table 2).

Tierney et al39 compared Nd:YAG treatments with 10% benzoyl peroxide and daily application of 1% clindamycin versus application of the topical antibiotic alone. Seventeen patients were enrolled and 4 laser sessions were given at intervals of 1 month (Table 1). The reduction in severity according to modified Sartorius assessment was 65.3% at 3 months on average over all regions (73.4% in the groin, 62% in the armpits, and 53.1% under the breasts). Improvement was significant in laser-treated patients, but not in the control group (topical clindamycin only) (P<.02).

Xu et al45 published a prospective, controlled histopathologic study in 19 patients with Hurley stage 2 HS. The patients were treated in 2 monthly sessions of Nd:YAG laser therapy (1064nm). The percent response to treatment on the Sartorius score after 2 months was 31.6% (P=.001). Greater improvement was recorded in groin lesions (Table 1).

Zerbinati et al47 observed a mean improvement of 85.3% in the Sartorius score with Nd:YAG treatment of very early Hurley stage 1 HS in 12 patients (Table 3). In a similar study, but with 22 patients with more severe HS (Hurley stage 2), Mahmoud et al43 evaluated the response at 6 months to 4 sessions of a series of 1 long-pulse Nd:YAG treatment per month for 4 months. They also observed a decrease in the Sartorius score (−72%) (Table 1).

An RCT of CO2 laser treatment was carried out by Abdel Azim et al48 in 20 patients over the age of 18 years who had Hurley stage 1 or 2 HS. The aim was to assess the safety and efficacy of combining fractional CO2 irradiation with long-pulse Nd:YAG laser irradiation (1064nm) in 4 sessions separated by 2 weeks. On the intervention side the patients received fractional CO2 laser treatment followed by long-pulse Nd:YAG laser (1064nm) in the same session. On the control side, only the Nd:YAG treatment was used. The authors concluded that improvement and satisfaction were greater with the combined treatment of early (Hurley stage 1 and 2) disease and that the recurrence rate was lower (Table 3).

Of 9 patients with medically and surgically refractory HS who received CO2 laser treatments from Madan et al,44 7 had achieved complete remission at 12 months. Satisfaction was high (Table 1).

Finally, Fabbrocini et al49 used laser diode light in a group with Hurley stage 1 or 2 HS and mild to moderate disease according to PGA. The patients received 4 sessions spaced every 2 weeks. A significant reduction of 31% was seen in the Sartorius scores, which changed from 28.55 (SD, 13.04) to 19.75 (SD, 12.29) (P<.05). The authors also reported a direct association between improvement and better quality of life (Table 3).

Considering the limited evidence available for light-based treatments for HS, it is difficult to draw conclusions about the efficacy of either intralesional versus topical approaches, or IPL or Nd:YAG laser. Variation in study designs makes comparison difficult.

We identified 3 photosensitizers being used in PDT: ALA, MAL, and MB. All of them were applied at different concentrations from 1% to 20% for ALA, 16% for MAL, and 0.01% to 1% for MB. Which concentration leads to a better response rate is difficult to establish because evaluation methods differ. Moreover, the type of light used to irradiate lesions also varies, as some groups use LED lamps,1,40,42 while others apply external2 or intralesional laser50,51 and still others use IPL.38,41 The possibility of treating deep HS lesions is an important factor in efficacy, yet these light sources have frank differences in penetration. The light doses also differ, although the wavelength applied is similar at 630 or 635nm.

The studies also treated lesions at different sites, for different durations and numbers of sessions (from 150 to 1238). The main difference in technique, however was between the use of topical versus intralesional application of both the photosensitizer (ALA, MAL, or MB) and the light source (LED, laser, or IPL).

We found that intralesional treatment approaches also differed between authors. Suárez Valladares et al50 and Valladares-Narganes et al51 used 630-nm diode lasers and ALA at different concentrations. They assessed response with the modified Sartorius score, finding that response was better with a 5% ALA gel and a 400-nm diode laser (1.2W and 180J/cm2). Agut-Busquet et al,1 on the other hand, used a 1% MB formulation and a 635-nm LED with a fluence of 37J/cm2. They assessed efficacy with the DQLI and the Sartorius score, reporting responses that varied from 99% for cases involving Hurley stage 1 to 87% in Hurley stage 3.

The single study of IPL we found reported that statistically significant improvement was maintained for 12 months and that the risk of complications was low.11

The RCT of Nd:YAG laser treatment by Tierney et al39 demonstrated efficacy. Later case series describing this treatment have reported reduction in the number of exacerbations and in severity.43,47 Efficacy has been reported to be greater in the groin.45

Very few studies have been published on other types of lasers, but all of them report promising results. The combination of CO2 and Nd:YAG lasers obtained better results than Nd:YAG irradiation alone and patient satisfaction was higher.48 Madan et al44 showed that CO2 laser therapy and marsupialization also led to high rates of complete remission in spite of adverse effects, such as hypertrophic scarring.

We found a single study of diode laser therapy for HS that was considered mild to moderate according to the PGA.48 The authors reported clinical and quality-of-life improvement after therapy.

In summary, the evidence supporting the use of light-based therapies for HS is limited. There are 2 major groupings of these therapies according to whether a photosensitizer is used or not. In 1 group, for which only a low-moderate level of evidence is available, the authors applied Nd:YAG laser, CO2 laser, or IPL. In the other, for which the quality of evidence is also low-moderate, PDT (with photosensitizer) was used. Thus, all the treatments reviewed used light but they are not comparable: different techniques have different mechanisms of action. However, results for individual treatments do seem to suggest that approaches that offer greater penetration — whether by means of intralesional application or lasers — lead to better results.

RCTs are necessary to confirm the efficacy of these treatments. We also need to see standardized research protocols applying the design that is most appropriate for providing stronger evidence for the efficacy and safety of each technique.