Our literature search identified 1326 records. Duplicates were removed. Based on title and abstract, 985 articles were screened. Full texts of 71 articles were assessed for eligibility of which 37 studies were selected with a total of 1911 participants (Fig. 1). The included studies comprised 6 RCTs, 6 CCTs, 16 prospective cohorts, 5 retrospective cohorts, and 4 case series. The studies investigated needle-free jet injector-assisted intralesional treatments for atrophic and hypertrophic scars, keloids, alopecia areata, hyperhidrosis, nail diseases (psoriasis, lichen planus, and idiopathic onycholysis), non-melanoma skin cancer (basal cell carcinoma (BCC), squamous cell carcinoma (SCC), Bowen’s disease, and Paget’s disease), common warts, granuloma annulare, lichen simplex chronicus, psoriasis, seborrheic dermatitis, aesthetic indications (wrinkles, rejuvenation, rhytides, facelift), and local anesthesia.

Fig. 1

Study flow diagram of exclusion process resulting in 37 included studies

Scars and keloids

Seven studies, investigated jet injections to treat various scar types (Table 1) [20,21,22,23,24,25,26,27,28]. Compared to baseline, spring-loaded jet injections with triamcinolone acetonide (TCA) and silicone sheets showed significant scar thickness reduction in hypertrophic scars, while silicone sheets alone did not (3–5 treatments; p < 0.05; p > 0.05) [21]. Moreover, pneumatic jet injector-assisted treatment with a mixture of hyaluronic acid and hypertonic glucose led to a reduction in mean scar volume of 0.4 mm3 compared to the untreated side in atrophic facial acne scars (single treatment; p < 0.05) [23]. Spring-loaded jet injections with bleomycin in keloids and hypertrophic scars led to reduced pain and pruritus with respectively 88% and 89% (2–6 treatments; no comparative intervention; no statistical analyses reported) [26]. Furthermore, pneumatic jet injections with 5-fluorouracil (5-FU) diluted in corticosteroids (TCA or methylprednisolone acetate) and lidocaine led to a significant reduction of pain and pruritus in patients with keloids, with respectively 69% and 79% compared to baseline (7 treatments; no comparative intervention; p < 0.01; p < 0.05) [27]. Pneumatic jet injections of hypertonic glucose resulted in a mean Global Aesthetic Improvement Scale (GAIS) of 2.3 ± 0.8 in atrophic scars, striae, and wrinkles compared to baseline (1–5 treatments; no comparative intervention; no statistical analyses) [24]. In comparison, jet injections with non-crosslinked and crosslinked hyaluronic acid injections in acne and hypertrophic scars resulted in overall GAIS of 1.9 and 1.8 respectively (mean 2.5 treatments; no statistical analyses) [25]. Jet injections (unknown injector type) with triamcinolone hexacetonide resulted in “good,” “acceptable,” and “negative” results in respectively 68.2%, 15.9%, and 15.9% of children with burn scars (1–4 series, no comparative intervention; no statistical analyses) [28].

Table 1 Characteristics and summary of results of included studies using needle-free jet injectors in scars and keloids, alopecia areata, hyperhidrosis, nail diseases, non-melanoma skin cancer, and wartsAlopecia areata

Four studies investigated jet injections to treat alopecia areata (Table 1) [29,30,31,32]. Jet injections with betamethasone dipropionate sodium phosphate vs. saline in group A and cyclosporine A vs. saline in group B resulted in hair regrowth in respectively 88.2%, 11.7%, 66.6%, and 16.6% of the patients (4 treatments; no statistical analyses) [29]. Spring-loaded jet injections with TCA resulted in hair regrowth in 62% of the patients (3 treatments; no comparative intervention; no statistical analyses) [30]. TCA with spring-loaded jet injections resulted in hair regrowth in 75% of the patients (3–4 treatments; no comparative intervention; no statistical analyses) [31]. Spring-loaded jet injections with TCA resulted in hair regrowth in 43–49% (≤ 3 treatments; no comparative intervention; no statistical analyses) [32].

Hyperhidrosis

Four studies investigated a single jet injector treatment for hyperhidrosis (Table 1) [33,34,35,36]. Pneumatic powered jet injections compared to needle injections with onabotulinumtoxinA were administered to treat palmar hyperhidrosis and reduced hyperhidrosis disease severity (HDSS) compared to baseline with respectively 1.6 (p = 0.031) and 1.25 (p = 0.1925) and no significant difference in pain between treatments [33]. Botulinum neurotoxin-A administered with spring-loaded jet injections and needle injections significantly reduced sweat production with respectively 24.7 mg/ml vs. 54.1 mg/ml in palmar and axillar hyperhidrosis compared to baseline (p < 0.05; p < 0.0001). However, pain was “unacceptable” in half of the patients treated with needle injections and in none of the patients treated with jet injections [34]. Pneumatic jet injections with botulinum neurotoxin-A, resulted in HDSS reduction of 2 and 3 compared to baseline, respectively in patients with axillar and palmoplantar hyperhidrosis (no comparative intervention; p < 0.001 in both groups) [35]. Spring-loaded jet injections with botulinum toxin type A resulted in a complete relief of symptoms in 70% of the patients with plantar hyperhidrosis (no comparative intervention; no statistical analyses) [36].

Nail diseases

Three studies investigated jet injections to treat nail diseases (Table 1) [37,38,39]. Pneumatic jet injections with TCA were administered periungual to treat nail psoriasis, showing a Nail Psoriasis Severity Index (NAPSI) reduction of 3.7 compared to baseline (4 treatments; no comparative intervention; p = 0.0007) [37]. Spring-loaded jet injections with TCA in the posterior nail fold improved nail matrix psoriasis and hyponychial varying from “slight or marked improvement” to “normal nail” in 26% and 90% of the patients respectively (3 treatments; no statistical analyses) [38]. In comparison, the same device with TCA injections in the posterior nail fold showed “matrix improvement” in 73–95%, in psoriasis or lichen planus nails, and “onycholysis improvement” in 47–70% in psoriasis or idiopathic onycholysis nails (≥ 3 treatments, no comparative intervention; no statistical analyses) [39].

Nonmelanoma skin cancer

Two studies investigated jet injections to treat non-melanoma skin cancer (superficial and nodular BCC, SCC, Bowen’s disease, and Paget’s disease) with 5-aminolevulinic acid (5-ALA) in combination with photodynamic therapy (PDT) (Table 1) [40, 41]. Spring-loaded jet injections with 5-ALA with PDT resulted in an 81% complete response (6 treatments; no comparative intervention; no statistical analyses) [40]. Treatment of PDT with 5-ALA administered with pneumatic injection compared to needle injections resulted in a 77% vs. 65% complete response rate (6 treatments; p = 0.012) [41].

Common warts

Two studies investigated spring-loaded jet injectors to treat palmar and plantar warts (Table 1) [42, 43]. Jet injections with bleomycin resulted in a complete response in 77.5% of the patients (5 treatments; no comparative intervention; no statistical analyses) [42]. Jet injections composed of interferon alfa-n3 resulted in a complete response in 73% of the patients (mean 15 treatments; no comparative intervention; no statistical analyses) [43].

Other dermatological indications

Four studies investigated jet injections in granuloma annulare, lichen simplex chronicus, psoriasis, and seborrheic dermatitis (Table 2) [44,45,46,47]. Spring-loaded jet injection with TCA vs. normal saline resulted in complete response in 68% vs. 44% of the granuloma annulare lesions (2–4 treatments; no statistical analyses) [45]. Spring-loaded jet injections with TCA or placebo showed “excellent” results in respectively 66% vs. 46% of the lichen simplex chronicus patients (8 treatments, p = 0.80) [46]. In psoriasis patients, 13.3% of the patients had “better” results with spring-loaded jet injections (Port-O-Jet), 6.7% had “better” results with needle injections and 80% had “equal” results (1 treatment; no statistical analyses) [44]. Spring-loaded jet injections composed of vitamin B6, glycyrrhizin, metronidazole and hyaluronic acid resulted in a mean Investigator Global Assessment (IGA) reduction of 1.2 points, in patients with seborrheic dermatitis (3 treatments; no comparative intervention; p < 0.05) [47].

Table 2 Characteristics and summary of results of included studies using needle-free jet injectors in other dermatological indications (granuloma annulare, psoriasis, seborrheic dermatitis, local anesthesia, and aesthetics)Local anesthesia

Three studies investigated local anesthesia administered by a spring-loaded jet injector before suturing or performing dermatological surgery (Table 2) [48,49,50]. Jet injections with mepivacaine chloride resulted in “no pain” in 79.6% of the lesions during surgery (no comparative intervention; no statistical analyses) [50]. Lidocaine administered with a jet injector compared to injections with a hypodermic needle resulted in a mean anesthesia-related Visual Analogue Scale (VAS) score of 1.1 vs. 4.4 respectively (p < 0.0001), while suturing-related pain was not significantly different (p > 0.05) [48]. Lidocaine administered with a jet injector vs. needle injections resulted in “no pain” during suturing in respectively 94% vs. 83% of the children [49].

Aesthetics

Six studies investigated intralesional pneumatic jet injections in the face or neck for aesthetic purposes (Table 2) [51,52,53,54,55,56]. Jet injections with hypertonic glucose compared to isotonic glucose improved GAIS with a mean score of respectively 2.5 ± 0.7 vs. 3.1 ± 0.9 (3 treatments; p = 0.005) [51]. To compare, jet injections with non-crosslinked hyaluronic acid resulted in “improved” and “much improved” GAIS in 42.9% and 57.1% of the patients respectively (5 treatments; no comparative intervention; no statistical analyses) [54]. Crosslinked hyaluronic acid using jet injections reduced mean Fitzpatrick–Goldman Wrinkle Classification with 21.2% and 27.6%, respectively in the neck and face (1–4 treatments; no comparative intervention; p < 0.05; p < 0.05) [56]. Hyaluronic acid with jet injections or multi-needle injections and placebo with jet injections or multi-needle injections reduced Wrinkle Severity Rating Scale compared to baseline with 1.0 ± 0.6 vs. 1.5 ± 0.6 vs. 0.5 ± 0.8 vs. 0.5 ± 0.6, respectively (3 treatments; p < 0.05; p < 0.01; p > 0.05; p > 0.05) [52]. Jet injections with hyaluronic acid reduced Mean Lemperle Rating Score with one point in all areas (2.5 treatments; no comparative intervention; no statistical analyses) [53]. Jet injections with hypertonic glucose showed “slight” or “notable” improvement in 91% of the patients (1 treatment; no comparative intervention; no statistical analyses) [55].

Adverse reactions

The majority of the adverse reactions were mild and the most common were local erythema, pain, hypo- and hyperpigmentation, bruising, hematoma, atrophy, swelling, and itching (Tables 1 and 2). No serious adverse events were reported. However, two studies that investigated bleomycin or interferon alfa-n2 delivered with a spring-loaded jet injector for palmar and plantar warts reported severe events including cellulitis, lymphangitis, and large hematomas, which needed surgical drainage and debridement [42, 43]. Also, TCA administered by a spring-loaded jet injector for the treatment of alopecia areata resulted in bleeding from the arteria temporalis in one patient, which was controlled by firm pressure [32].

Methodological quality assessment

Overall risk of bias assessed with Cochrane’s ROB 2.0 tool was “high” in six RCTs and CCTs, “some concerns” in four studies, and “low” in two studies (Fig. 2a). Methodological quality was particularly poor due to deviations from the intended intervention and selection bias (Fig. 2b). According to the Newcastle–Ottawa Scale, overall risk of bias in the included cohorts and case series was “high” in eleven, “some concerns” in another eleven, and “low” in three studies (Fig. 3a) [16]. Methodological quality was particularly poor due to lack of comparative cohorts, lack of blinding, and short follow-up time (Fig. 3b).

Fig. 2

a Risk of bias in the included (non) randomized controlled trials was categorized as high, low or some concerns according to the Cochrane risk-of-bias 2.0 assessment tool. Overall, risk of bias was high because of poor methodological quality, particularly in domain 2 and 5. b Methodological quality of the (non) randomized controlled trials according to the Cochrane Collaborations risk-of-bias 2.0 tool assessment

Fig. 3

a Risk of bias in the included cohort studies and case series was categorized as high, low, some concerns or not applicable according to the Newcastle–Ottawa Scale. Overall, risk of bias was high because of poor methodological quality, particularly in domains 2, 6, and 7. b Methodological quality of the included cohort studies and case series according to the Newcastle–Ottawa Scale