| Bi10) (2016) | 130(65/65)A:21/44; 38.2±3.6; 3mon-5yrB:19/46; 39.7±3.9; 3mon-6yr | A(n=65):HM (Gamisoyo-san, 6g PO BID), plus B | B(n=65):WM(Minocycline hydrochloride, 50㎎ PO BID) | 1. Effective rate2. Changes in the skin lesion score (10-points scale) | 1. RR1.17 [1.04, 1.31], p<0.052. MD-2.06 [-2.31, -1.81], p<0.05 | 6wks | Diarrhea: A(1), B(1)Dizziness: A(1), B(2)Rash:A(0), B(1) |
| Lai11) (2016) | 159(80/79)A:37/43; 43.68±5.47; 10.08±8.38yrB:38/41; 44.75±5.58; 9.73±3.49yr | A(n=80):HM(NR, dose NR PO BID), plus B | B(n=79):Laser Therapy(Wave length 595㎚, Width 5-7㎜, Energy dose 4-7J/㎠, 3-5 times/wk) | 1. Effective rate2. Changes in the skin lesion score (4-points scale, after 1, 2, 3, 4 wk) | 1. RR1.08 [1.01, 1.17], p<0.052. MD-0.50 [-0.58, -0.42], at 1wk(p>0.05), at 2, 3, 4 wk(p<0.05) | 4wks | Abdominal pain : A(2), B(0)Transient erythema : A(1), B(0)Blister:A(0), B(1) |
| Ren12) (2017) | 120(60/60)A:23/37; 40.1±2.9; 18.3±5.7monB:25/35; 40.6±2.2; 18.5±5.4mon | A(n=60):HM (Ryanghyeolsamultang, dose NR, PO BID), plus B | B(n=60):WM(Vitamin B2, 10㎎; Vitamin B6, 20㎎ PO TID; Tetracycline, 0.5g PO QID for 3wks→ 0.25g BID for 1wk; Metronidazole, 0.2g PO TID for 2wks→ 0.2g BID for 2wks)EM (Chlorsulfuric acid, PRN apply) | 1. Effective rate2. Changes in the skin lesion score(4-points scale, after 1, 2, 3, 4 wk) | 1. RR1.16 [1.04, 1.29], p=0.0122. MD-0.70 [-0.80, -0.60], at 1wk(p=0.221) at 2 wk (p=0.002), at 3, 4 wk(p=0.001) | 4wks | Diarrhea: A(2), B(0)Nausea: A(0), B(1)Abdominal pain : A(0), B(1) (p=0.156) |
| Wan13) (2017) | 92(48/44)A:21/27; 34.2±2.6; 2.11±0.42yrB:17/27; 34.8±2.9; 2.14±0.45yr | A(n=48):HM(Ryang hyeolcheongpye-san, dose NR PO BID), plus B | B(n=44):WM(Minocycline hydrochloride, 100㎎ PO QD) | 1. Effective rate2. Changes in the skin lesion score (4-points scale, after 2, 4, 8wk) | 1. RR1.30 [1.06, 1.60], p<0.052. MD-1.30 [-1.89, -0.71], at 2, 4, 8wk (p<0.05) | 8wks | Dizziness: A(4), B(5) (p=0.891)Gastric discomfort: A(2), B(3), (p=0.920)Pigmentation: A(0), B(1) (p=0.965) |
| Liang14) (2018) | 122(62/60)A:9/53; 37.36±9.86; 1mon-15yrB:8/52; 35.36±8.43; 1mon-16yr | A(n=62):HM(Sopunghaedok-capsules, 2.08g PO TID), plus B | B(n=60):WM(Minocycline hydro-chloride, 50㎎ PO BID)EM(Clindamycin phos-phate gel, PRN apply) | 1. Effective rate2. Changes in the skin lesion score (4-points scale, after 2, 4, 6wk; ①Itching②Non transient erythema③Flushing④Papules⑤Pustules⑥Telangiectasia) | 1. RR1.21 [1.05, 1.40], p<0.052. MD-2.00 [-2.69, -1.31], p＜0.05①MD-0.22 [-0.39, -0.05], p＜0.05②MD-0.01 [-0.23, 0.21], p＜0.05③MD-0.18 [-0.34, -0.02], p＜0.05④MD-0.40 [-0.65, -0.15], p＜0.05⑤MD-1.06 [-1.36, -0.76], p＜0.05⑥MD-0.50 [-0.68, -0.32], p＜0.05 | 6wks | Diarrhea: A(1), B(2)Dizziness: A(0), B(1) |
| Zhang15) (2018) | 69(35/34)A:5/30; 37.9±3.5; 3.2±0.5yrB:6/28; 35.6±2.7; 3.1±0.6yr | A(n=35):HM(Zhu's Piyeom-bang, dose NR PO BID), plus B | B(n=34):WM(Doxycycline, 100㎎ PO BID)EM(Samhwang seje, BID apply) | 1. Effective rate (follow up 3mon) | 1. RR1.12 [0.91, 1.37], p<0.05 | 4wks | Gastric discomfort by WM: A(4), B(0)Desquamation by EM: A(0), B(3) |
| Jiang16) (2019) | 98(49/49)A&B:(NR); 42.21±1.17; 2.39±0.37yr | A(n=49):HM(Ryanghyeol cheongpye-san, dose NR PO QD), plus B | B(n=49):WM(Minocycline hydrochloride, 50㎎ PO QD) | 1. Effective rate2. DLQI | 1. RR1.23 [1.00, 1.51], p<0.052. MD-5.71 [-6.12, -5.30], p<0.05 | 8wks | Nausea or Vomiting: A(10), B(3)Headache: A(2), B(1)Dizziness: A(1), B(1)Rash: A(1), B(0) (p>0.05) |
| Sheng17) (2019) | 70(35/35)A:15/20; (NR); (NR)B:16/19; (NR); (NR) | A(n=35):HM(Bipadanggwi-eum, 300㎖ PO BID), plus B | B(n=35):WM(Isotretinoin, 1T PO TID for 2wks→ BID for 2kws→ QD for 4wks)EM(Woohwang seje 100㎖ apply) | 1. Effective rate | 1. RR1.28 [1.01, 1.62], p<0.05 | 8wks | Chapped lips and Desquamation: A(0), B(30) |
| Xu18) (2019) | 120(60/60)A:16/44; 25-48; 5mon-3yrB:12/48; 24-47; 4mon-2yr | A(n=60):HM (Ryanghyeolsopung-san, dose NR PO BID), plus B | B(n=60):WM(Minocycline hydrochloride, 50㎎ PO BID) | 1. Effective rate2. Changes in the skin lesion score (4-points scale, after 2, 4, 8wk①Non transient erythema②Flushing③Papules④Pustules⑤Telangiectasia) | 1. RR1.24 [1.07, 1.44], p<0.052. MD-3.63 [-4.93, -2.33], p<0.05①MD-0.85 [-1.09, -0.61], p<0.05②MD-0.83 [-1.16, -0.50], p<0.05③MD-0.84 [-1.08, -0.60], p<0.05④MD-0.84 [-1.18, -0.50], p<0.05⑤MD-0.27 [-0.42, -0.12], p<0.05 | 8wks | Dizziness by WM: A(1), B(1) (p>0.05) |
| Yang19) (2019) | 99(50/49)A:20/30; 38.42±2.31; 1.69±0.48yrB:20/29; 38.45± 2.35; 1.67±0.44yr | A(n=50):HM (Piyeom-bang, 450㎖ PO TID), plus B | B(n=49):WM(Metronidazole, 0.2g PO TID) Laser Therapy(Wave length 630.00±10.00㎚, Intensity 110㎽/㎠, Energy dose 132J/㎠, 20min, 2times/wk) | 1. Effective rate2. Changes in the skin lesion score (4-points scale, ①Erythema②Papules or Pustules③Burning or Itching④Dry appearance)3. Acne-QOL(①Role-emotional, ②Self-perception, ③Role-social, ④skin symptoms)4. Treatment satisfaction | 1. RR1.18 [1.02, 1.36], p<0.052. ①MD-0.68 [-0.76, -0.60], p<0.05 ②MD-0.78 [-0.91, -0.65], p<0.05 ③MD-0.69 [-0.78, -0.60], p<0.05 ④MD-0.55 [-0.59, -0.51], p<0.053. ①MD3.88 [3.12, 4.64], p<0.05 ②MD4.11 [3.86, 4.36], p<0.05 ③MD1.99 [1.05, 2.93], p<0.05 ④MD4.42 [3.62, 5.22], p<0.054. RR1.20 [1.05, 1.38], p<0.05 | 4wks | Nausea: A(1), B(0)Dryness: A(0), B(1)Vomiting: A(0), B(1) |
| Zhu20) (2019) | 96(32/32/32)A:(NR); 33.47±9.05; 2.33±1.80yrB1:(NR); 32.53±9.58; 2.94±2.07yrB2:(NR); 31.31±6.75; 2.36±1.77yr | A(n=30):B1 and B2 | B1(n=31):DPL(Wave length 500-600㎚, spot diameter 10㎜×20㎜, Pulse width intensity 12㎳, 15㎳, 40㎳, Energy dose 8-11J/㎠, 3-5times/4wk) B2(n=27): HM(Cheongwi-san, dose NR PO BID) | 1. Effective rate | 1. A>B1>B2 (p<0.05)A>B1: RR1.88 [1.10, 3.22], p<0.05B1>B2: RR2.40 [0.86, 6.65], p<0.05A>B2: RR4.50 [1.76, 11.51], p<0.05 | 6mons | Gastric discomfort: A(2), B1(0), B2(2) (p>0.05)Burning or itching or dryness: A(2), B1(3), B2(0) (p>0.05) |
| Ding21) (2020) | 80(40/40)A:10/30; 37.89±5.78; 3.42±1.01yrB:8/32; 37,11±5.18; 3.41±0.71yr | A(n=40):HM(Cheongyeolhaedok Ryanghyeolcheongpye-bang, 150㎖ PO BID), plus B | B(n=40):WM(Isotretinoin, 10㎎ PO BID)EM(Clindamycin phosphate gel, BID apply) | 1. Effective rate2. Changes in the skin lesion score (4-points scale,①Dry appearance②Itching③Erythema④Burning⑤Telangiectasia⑥Papules or Pustules)3. Changes in Erythema Index, IL－37 | 1. RR1.28 [1.03, 1.57], p<0.052. ①MD-0.54 [-0.68, -0.40], p<0.05②MD-0.45 [-0.63, -0.27], p<0.05③MD-0.49 [-0.67, -0.31], p<0.05④MD-0.45 [-0.58, -0.32], p<0.05⑤MD-0.31 [-0.42, -0.20], p<0.05⑥MD-0.31 [-0.43, -0.19], p<0.053. Erythema Index:MD-44.51 [-58.93, -30.09], p<0.05IL－37(ρ/ng·L－1): MD-2.45 [-3.73, -1.17], p<0.05 | 6wks | NR |
| Lu22) (2020) | 62(31/31)A:13/18; 27.5±5.3; 17.8±9.8monB:12/19; 27.3±5.2; 18.2±9.2mon | A(n=31):HM(Hanghong-tang, 200㎖ PO BID), plus B | B(n=31):WM(Doxycycline hydrochloride, 100㎎ PO BID) | 1. Effective rate2. Changes in the skin lesion score (4-points scale①Non transient erythema②Telangiectasia③Papules or Pustules) | 1. RR0.96 [0.76, 1.21], p>0.052. ①MD0.20 [-0.10, 0.50], p>0.05②MD0.10 [-0.30, 0.50], p>0.05③MD0.10 [-0.30, 0.50], p>0.05 | 6wks | Anorexia or Vomiting or Abdominal pain: A(0), B(6) |
| Shao23) (2020) | 69(34/35)A:4/30; 37.47±8.046; 20.59±19.73monB:5/30; 37.86±8.531; 21.40±16.84mon | A(n=34):HM(Ryanghyeol honghwa-tang, dose NR PO BID), plus B | B(n=35):WM(Minocycline hydrochloride, 50㎎ PO BID) | 1. Effective rate2. Changes in the skin lesion score (4-points scale, ①Flushing②Non transient erythema③Papules or Pustules④Telangiectasia) | 1. RR1.39 [1.07, 1.80], p>0.052. ①MD-0.54 [-0.87, -0.21], p=0.011②MD-0.43 [-0.80, -0.06], p=0.032③MD0.10 [-0.23, 0.43], p=0.633④MD0.11 [-0.34, 0.56], p=0.083 | 6wks | Gastric discomfort: A(1), B(0)Dizziness:A(0), B(1) |
| Song24) (2020) | 100(50/50)A:10/40; 42.15±8.77; 6.53±3.42yrB:8/42; 43.44±7.54; 6.80±3.55yr | A(n=50): HM(Ryanghyeol samul-tang, dose NR, PO BID), plus B | B(n=50): IPL(Wave length 500-1200㎚, 1time/4wks) | 1. Effective rate2. Changes in the quality of life (3-points scale) | 1. RR1.22 [1.00, 1.49], p=0.0152. MD-5.43 [-5.83, -5.03], p<0.05 | 8wks | Erythema: A(2), B(3)Dryness: A(1), B(2)Stinging: A(1), B(2) |
| Wu25) (2020) | 100(50/50)A:24/26; 34.88±2.91; 2.16±0.47yrB:23/27; 34.25±2.68; 2.14±0.44yr | A(n=50):HM(Sopunghaedok-capsules, 4T PO TI D), plus B | B(n=50):WM(Minocycline hydrochloride, 50㎎ PO BID) | 1. Effective rate2. Changes in the skin lesion score (10-points scale) | 1. RR1.18 [1.00, 1.40], p<0.052. MD-2.06 [-2.36, -1.76], p<0.05 | 6wks | NR |
| Zhang TL26) (2020) | 140(70/70)A:23/47; 35.89±3.98; 2.45±0.37yrB:24/46; 35.67±4.11; 2.71±0.32yr | A(n=70):HM(Baekgeumhaedokriseup-tang, dose NR PO TID), plus B | B(n=70):Laser Therapy(Wave length 585㎚, Frequency 1.5㎐, Energy dose 5-20J/㎠, spot diameter 3-10㎜ 1time/mon) | 1. Effective rate2. Changes in the skin lesion score (4-points scale)3. Changes in NT-pro BNP, IL-10, hs- CRP4. SF-36(①Mental Health②Role-Emotional③Physical Functioning④Social Functioning⑤General Health⑥Vitality⑦Bodily pain⑧Role-Physical) | 1. RR1.16 [1.01, 1.34], p<0.052. MD-1.47 [-2.02, -0.92], p<0.053. NT-pro BNP(㎎/Ｌ):MD-31.61 [-62.60, -0.62], p<0.05IL-10(pg/mL): MD-1.79 [-3.28, -0.30],p<0.05 hs-CRP(㎎/Ｌ): MD-1.61[-2.08, -1.14], p<0.054. ①MD11.50 [9.83, 13.17], p<0.05②MD17.81 [16.17, 19.45], p<0.05③MD10.79 [9.08, 12.50], p<0.05④MD18.24 [16.67, 19.81], p<0.05⑤MD16.69 [14.84, 18.54], p<0.05⑥MD10.25 [8.61, 11.89], p<0.05⑦MD11.62 [9.86, 13.38], p<0.05⑧MD16.16 [14.43, 17.89], p<0.05 | 2mons | Mild Pigmentation: A(0), B(3)Fatigue: A(0), B(1) (p>0. 05) |
| Yuan27) (2021) | 70(35/35)A:2/33; 40.37±8.65; 4.33±3.42yrB:4/31; 40.46±9.88; 4.51±2.44yr | A(n=35):HM(Gamisoyo-san, 200㎖ PO BID), plus B | B(n=35):WM(Doxycycline hydrochloride, 100㎎ PO BID) | 1. Effective rate2. Changes in the skin lesion score (4-points scale)3. DLQI and HAMD scores | 1. RR1.35 [1.03, 1.76], p<0.052. MD-1.06 [-2.33, 0.21], p<0.053. DLQI: MD-1.45 [-2.88, -0.02], p<0.05HAMD: MD-1.66 [-2.75, -0.57], p<0.05 | 8wks | No adverse events |