Table 1.
All reports published in the literature so far on surgical treatment of pyoderma gangrenosum with skin graft or negative wound pressure therapy
| Publication No. | Author, Year (References) | Patients | Age, Sex | Localization | Procedural Interventions | Systemic Treatment | Outcome |
|---|---|---|---|---|---|---|---|
| 1 | Ridenhour and Stephenson (1968)91 | 1 | 62, M | Left elbow, both lower legs | STSG | CS, topical aqueous silver nitrate | Successful graft, healed without recurrence |
| 2 | McGarity and Barnett (1977)115 | 1 | 53, F | Abdominal wall | STSG | CS | Successful graft, healed without recurrence |
| 3 | Davis et al. (1987)116 | 4 | 64, M; 62, F; 17, F; 22, F | Legs (lower) 4, elbow 1 | STSG (4), HBO (4) | CS (4), in 3 CS were tapered under HBO and inactive PG grafted without | Successful graft, healed without recurrence |
| 4 | Gérard et al. (1988)117 | 1 | 41, M | Left hand | STSG | CS, plasma exchange | Successful graft, healed without recurrence |
| 5 | Dean et al. (1991)118 | 1 | 71, F | Leg (ankle) | Cultured epithelial autografts | CS | Successful, healed without recurrence |
| 6 | Límová and Mauro (1994)119 | 1 | 44, F | Leg (dorsal food) | Cultured keratinocyte autografts | CS systemic+intralesional | 95% Graft take, healed without recurrence |
| 7 | Maier et al. (1995)120 | 1 | 34, F | Leg | STSG | CS, CyA | Successful graft, healed without recurrence |
| 8 | Vereecken et al. (1997)121 | 1 | 87, F | Leg (right tibia) | STSG | Lymecycline, topical benzoyl peroxide | Successful graft, healed without recurrence |
| 9 | Michel et al. (1998)122 | 1 | 68, F | Leg (calves) | STSG | CS, CyA, MMF | Successful graft, healed without recurrence |
| 10 | Havlik et al. (1998)123 | 1 | 15, F | Breast | STSG | CS | Successful graft, healed without recurrence |
| 11 | Cliff et al. (1999)92 | 4 | 66, M; 36, F; 28, F; 68, F | Legs (lower) 2, abdomen, tight left | STSG (4) | One without immunosuppression (unknown PG), CS (3) | One failed with exacerbation (Patient without immunosuppression), three healed with no recurrence |
| 12 | Sotillo-Gago et al. (1999)124 | 1 | 43, F | Breast (bilateral) | STSG without IS | No IS then CS+CyA | STSG failed without IS, healed under immunosuppression |
| 13 | Rozen et al. (2001)113 | 3 | 61, F; 73, F; 46, M | Legs (all lower) | STSG (3), rectus abdominis flap (1) | CS (3)+AZA/dapsone/Mesalamine 1; +AZA/MMF/Tacrolimus 1 | Successful graft in all, one minor recurrence after 3 months managed conservatively |
| 14 | Kaddoura and Amm (2001)112 | 3 | 13, F; 15, M; 56, M | Legs (right lower leg four ulcers, left lower leg two ulcers) | STSG (3) | CS (3) | Successful in all, one small recurrence managed conservatively with systemic CS |
| 15 | de Imus et al. (2001)125 | 1 | 26, F | Leg | Allogeneic cultured human skin equivalent (Graftiskin) | CS, CyA | Successful, healed without recurrence |
| 16 | Gilmour and Stewart (2001)126 | 1 | 16, M | Leg | Cultured epidermis unsuccessful, followed by NPWT and delayed STSG | CS, CyA, MMF | Healed after 7 months, no recurrence after 10 months |
| 17 | Lifchez and Larson (2002)127 | 1 | 40, F | Breasts | STSG | CS | Successful graft, healed without recurrence |
| 18 | Gulyas and Kimble (2003)128 | 1 | 57, F | Breast | STSG | CS | Successful graft, healed without recurrence |
| 19 | Poucke et al. (2004)129 | 1 | 41, F | Breast | Integra® | CS | Healed without recurrence |
| 20 | Horner et al. (2004)130 | 1 | 21, F | Breast | NPWT, then STSG | First no IS, then CS+CyA | Failed without IS, secondary healing under immunosuppression |
| 21 | Zakhireh et al. (2004)131 | 3 | 64, F; 60, F; 30, F | Legs (all lower) | STSG (3) | CS (3) with CyA (2) one with additional MTX | Successful graft, healed without recurrence |
| 22 | Geller and Longton (2005)101 | 1 | 82, F | Leg (lower) | NPWT | CS | Halted the inflammatory process, healing after 7 months |
| 23 | Niezgoda et al. (2006)132 | 1 | 46, M | Leg (left, tibia) | NPWT, STSG, HBO | CS | Successful graft, healed without recurrence |
| 24 | Keskin et al. (2006)133 | 1 | 9, M | Legs (lower) | STSG | CS | Successful graft, healed without recurrence |
| 25 | Ghersi et al. (2007)134 | 1 | 57, F | Leg (lower left) controlled and slow-healing PG | NPWT | None, previous CS, IVIG, MMF, cyclophosphamide | Healed without recurrence after 6 weeks |
| 26 | Zutt et al. (2007)85 | 1 | 50, F | Legs (right: lower leg and dorsal foot) | NPWT and STSG | CS, AZA, CyA, dapsone, MMF, Iloprost | Successful graft, healed without recurrence |
| 27 | Hoff et al. (2008)135 | 1 | 53, M | Both lower legs | STSG | CS, topical tacrolimus | Successful graft, healed without recurrence |
| 28 | Kim et al. (2008)136 | 1 | 47, F | Legs (left calf) | STSG | CS, CyA | Successful graft, healed without recurrence |
| 29 | Toyozawa et al. (2008)137 | 1 | 69, F | Legs | STSG | CS | Successful graft, healed without recurrence |
| 30 | Descheemaeker et al. (2008)138 | 1 | 31, F | Breast | NPWT and STSG | CS | Successful graft, healed without recurrence |
| 31 | Procianoy et al. (2009)139 | 1 | 19, F | Eyelid | FTSG | CS, dapsone | Successful graft, healed without recurrence |
| 32 | Rajapakse et al. (2010)140 | 1 | 50, F | Breasts | NPWT | CS | Successful graft, healed without recurrence |
| 33 | Wollina et al. (2000)141 | 1 | 50, F | Both lower legs | Hyaluronic acid derivate (Hyalogran) followed by grafting of autologous cultured keratinocytes | CS, MMF | One ulcer healed, second ulcer 60%; recurred shortly thereafter |
| 34 | Rietjens et al. (2010)142 | 1 | 37, F | Breast | FTSG | CS | Successful graft |
| 35 | Schintler et al. (2010)143 | 1 | 45, F | Breasts | NPWT (instill) and free flap | CS, CyA, IVIG | Successful graft, healed without recurrence |
| 36 | Lamet et al. (2010)144 | 1 | 44, F | Legs | STSG | CS | Graft at first successful, then relapsed |
| 37 | Schoemann and Zenn (2010)145 | 1 | 50, F | Abdomen | STSG | CS | Successful graft, healed without recurrence |
| 38 | Melson et al. (2010)114 | 1 | 41, F | Eyelids | FTSG | CS | Successful, recurred after 6 months |
| 39 | Kikuchi et al. (2010)146 | 1 | 28, F | Abdomen | STSG | CS | Successful graft, healed without recurrence |
| 40 | Goshtasby et al. (2010)147 | 1 | 49, F | Breasts | Integra, STSG | CS, infliximab, MTX | Successful graft, healed without recurrence |
| 41 | Andreev (2011)148 | 1 | 30, F | Legs | STSG | CS | Successful graft, healed without recurrence |
| 42 | Hafner et al. (2006)149 | 1 | 64, F | Lower Leg | Cultured autologous epidermis | CS, CyA, AZA | Successful, but recurred within 6 weeks |
| 43 | Mandal et al. (2006)150 | 3 | 72, F; 17, M; 45, F | Leg (right knee) 2, thighs and groin 1 | NPWT (3) and STSG (2) and gastrocnemius muscle flap (1) | CS (3), and CyA (1) | Successful flap (1), partial rejection at the STSG borders healed conservatively (1), improvement with NPWT healed within 6 months; no recurrences |
| 44 | Lambropoulos et al. (2011)96 | 1 | 13, F | Leg (left ankle) and left arm | NPWT, cultured autologous keratinocytes, (Epicel®) | CS, CyA | 90% Graft take, no complete healing after 6 months |
| 45 | Hill et al. (2011)151 | 1 | 63, F | Leg (after knee arthroplasty) | NPWT, muscle flap with STSG, HBO | First none, CS after diagnosis | NPWT ineffective without immunosuppression, flap and graft failure secondary to sepsis, prolonged course healed eventually with HBO, no recurrence |
| 46 | Gámiz and Nielsen (2011)152 | 1 | 58, F | Both legs | NPWT and STSG | CS | Successful graft, healed without recurrence |
| 47a | Saracino et al. (2011)153 | 2 | Not specified (series of 26 mean age 61.5, 65% F) | Legs | Pinch graft (1), STSG (1) | CS (2) | Successful graft, no recurrence |
| 48 | Fraccalvieri et al. (2014)154 | 4 | 53, M; 59, F; 72, F; 45, F | Legs (lower) 3, breasts 1 | NPWT (4) | CS (4), CyA (4), Dapsone (1), IGIV (1), cyclophosphamide (1) | Marked pain reduction, good granulation tissue, no healing reported |
| 49 | Sick et al. (2012)2 | 3 | 62, F; 70, F; 44, M | Legs (all) | STSG (3) and NPWT (1) | CS/AZA (1), CS/CyA (1), MMF/IVIG (1), topical tacrolimus and clobetasol (3) | Successful/one recurrence at a different location |
| 50 | Neiderer et al. (2012)155 | 1 | 76, M | Leg (anterior left) | NPWT, bioengineered skin substitute generated from neonatal foreskin (Apligraf®) | CS | Healed within 6 weeks |
| 51 | Kolios et al. (2012)88 | 1 | 47, F | Breasts | STSG | CS | Successful graft, healed without recurrence |
| 52 | Carrasco Cubero et al. (2012)156 | 1 | 33, M | Leg (right ankle) | STSG | CS, infliximab | Successful graft, healed without recurrence |
| 53 | Das et al. (2012)157 | 1 | 53, F | Legs, right groin | STSG | CS | Successful graft, healed without recurrence |
| 54 | Andrisani et al. (2013)158 | 1 | 76, M | Left breast | STSG | CS, infliximab | Successful graft, healed without recurrence |
| 55 | Araújo et al. (2013)159 | 1 | 50, M | Leg (left) | STSG, HBO | CS, AZA | Over 90% graft take, healed without recurrence |
| 56 | Cabalag et al. (2015)60 | 3 | Not specified (series of 29, 59% F, mean age 71) | Legs | STSG (3) with HBO (2) | CS (3), CyA (1) | Successful graft (3), healed (1), improved (2), died due to sepsis: perforated sigmoid diverticular abscess (1) |
| 57 | Mowlds et al. (2013)160 | 1 | 61, F | Right hand | STSG and NPWT and HBO | Local acetic acid, no immunosuppression (PG diagnosed later) | Healed, second PG at the left hand |
| 58 | Lee et al. (2013)161 | 1 | 47, F | Legs (left foot) | STSG | CS | Successful graft, healed without recurrence |
| 59a | Mooij et al. (2013)162 | 2 | Not specified (series of 6 mean age 49, 83% F) | Legs (6) | STSG (2) | CS (2), infliximab (2) | Successful graft, healed without recurrence |
| 60 | Leonard and Khan (2013)163 | 1 | 47, F | Breast | NWPT+STSG | CS | Successful graft, healed without recurrence |
| 61 | Ratnagobal and Sinha (2013)164 | 1 | 60, F | Leg and food | STSG+HBO | Infliximab | Successful graft, recurrence after 3 months (infection), further STSG failed, primary healing with no recurrence |
| 62 | Fakhar et al. (2013)165 | 1 | 41, F | Breasts (PG after III° burn) | STSG, NPWT after breast amputation | CS | Not successful, eventually healed under prednisolone, MMF, and adalimumab |
| 63 | Aydin et al. (2015)166 | 1 | 32, F | Abdomen (after caesarian delivery) | NPWT and STSG | CS, AZA | Successful graft, healed without recurrence |
| 64 | Ye and Ye (2014)167 | 2 | 51, F; 89, F | Lower leg (1); abdomen, left tights, sacral (1) | STSG (2), primary closure sacral | CS (2), MMF (1) | >90% Graft take, healed without recurrence |
| 65a | Stair-Buchmann et al. (2015)90 | 6 | Not specified (series of 7: 29% F, mean age 65) | Legs (lower) 6 | NPWT and STSG (4), STSG (1), NPWT (1) | CS (6), plus Dapsone (1), infliximab (1) | Three closed (NPWT and STSG 1, STSG 1), one died due to sepsis (NPWT and STSG), two lost to follow-up |
| 66 | Richmond et al. (2014)168 | 5 | 40, F; 50, M; 50, F; 30, F; 80, M | Legs (lower 4, upper 1) | Epidermal grafting with suction blister–harvesting system 5 (Cellutome) | CS (3) with CyA (1); CyA (2) with MMF (1) | All successful, three healed within 3 months, two marked ulcer size reduction |
| 67 | Tay et al. (2014)169 | 1 | 58, F | Legs (lower) | STSG | Sulfasalazine, topical betamethasone | Successful, healed within 3 months |
| 68 | Novo-Torres et al. (2015)170 | 2 | 23, F; 45, F | Leg (lower) (2) | CS+CyA+infliximab (1), no systemic therapy (1) | NWPT+STSG+Integra (2) | Successful, healed within 3 months (1), failed (1) in patient with no immunosuppressive treatment |
| 69 | Snyder et al. (2015)171 | 1 | 77, F | Leg (lower) | NWPT+allograft | CS, Dapsone, MMF | Successful |
| 70 | Cicuto et al. (2015)172 | 1 | 62, F | Breast | NWPT+skin graft (1) | CS | Successful, healed without recurrence |
| 71 | Soncini et al. (2016)173 | 1 | 19, F | Breast bilateral | NWPT | CS | Successful, healed within 4 months |
| 72 | Leitsch et al. (2016)174 | 1 | 54, M | Hand and forearm | STSG+NPWT | CS | Successful graft, healed without recurrence |
| 73 | Zaugg et al. (2016)175 | 1 | 65, F | Leg (lower) | STSG | CS | Successful graft, healed without recurrence |
| 74 | Patel et al. (2017)176 | 1 | 41, F | Breast | First cadaveric allograft, then Integra and STSG | CS+CyA+IVIG | Failed, healed by secondary intention |
| 75 | Hradil et al. (2017)177 | 1 | 72, M | Arm | STSG | CS | Successful graft |
| 76 | Yamaguchi et al. (2018)178 | 2 | 48, M; 51, F | Leg (lower) 2 | NWPT (2) | CS (2)+CyA (1) | Successful, marked improvement within 1 month |
| 77 | Soro-García et al. (2017)179 | 1 | 35, F | Parasternal | NWPT | CS | Healed within 6 months |
| 78 | Domej et al. (2017)180 | 1 | 75, F | Shoulder | NWPT | CS | Improved |
| 79 | Zelones and Nigriny (2017)104 | 1 | 37, F | Abdomen | NWPT | First no treatment, then CS, MMF, infliximab | Worsening without IS, then healed within 5 months |
| 80 | Tanini et al. (2017)181 | 1 | 39, F | Breast | NWPT | CS | Healed within 2 months |
| 81a | Riyaz et al. (2017)182 | 3 | Not specified series of 61 patients, mean age 49.7, 52% male, 3 surgically treated (1 man, 2 woman) | Not specified | STSG (3) | CS (3) | Healed (2), failed (1) |
| 82 | Ishikawa et al. (2015)197 | 1 | 69, M | Abdomen (peristomal) | NPWT and STSG | None | Successful graft, healed without recurrence |
| 83 | Asyyed et al. (2018)183 | 1 | 46, F | Bilateral breast | STSG | CS, CyA, IVIG | 50% Graft take |
| 84 | Choi and Yoo (2018)184 | 1 | 61, F | Leg (lower) | 2 × STSG without IS failed | None, then CS | STSG failed without IS, secondary healing under CS |
| 85 | Ehrl et al. (2018)185 | 1 | NR | Whole thorax after breast augmentation | STSG+Integra | CS | Successful graft, healed without recurrence |
| 86 | Gupta et al. (2018)186 | 1 | 34, F | Scalp | STSG | None | Failed, secondary healing under immunosuppressive therapy |
| 87 | Schwaiger et al. (2018)187 | 5 | 64, F; 80, F; 46, F; 66, M; 65, M | Ankle (1), leg (lower) (4) | STSG (3), STSG+FTSG (1), NWPT (1) | CS (5) | Healed, after 2-year recurrence treated successful with STSG (1), failed with FTSG, healed with STSG (1), healed (3) |
| 88 | Yu et al. (2018)188 | 1 | 51, M | Abdomen peristomal | NWPT+STSG | None | Successful graft, healed without recurrence |
| 89 | Romanelli et al. (2018)189 | 1 | 75, F | Leg (lower) | Cadaver allograft | CS+adalimumab | Successful graft, healed without recurrence |
| 90 | Zheng et al. (2020)190 | 1 | 30, M | Leg (upper) | STSG | CS | Successful graft, healed without recurrence |
| 91 | Dillingham and Jorizzo (2019)191 | 1 | 68, M | Leg (lower) | Porcine urinary bladder matrix+NWPT+STSG | CS | Successful graft, healed without recurrence |
| 92 | Yang et al. (2019)192 | 1 | 54, M | Leg (lower) | NWPT+oxygen irrigation | None | Healed within months |
| 93 | Sousa et al. (2020)193 | 1 | 57, M | Leg (upper) vaginal and perianal | NWPT | CS+infliximab | Healed within months |
| 94 | Shen et al. (2019)194 | 1 | 32, F | Abdomen | NWPT+STSG | CS, IVIG, CyA | Successful graft, healed without recurrence |
| 95 | Borda et al. (2019)195 | 1 | 40, F | Leg (lower) | FTSG | MTX, CyA, infliximab | Wound reduction of 28% after 8 weeks with much improvement |
| 96 | Nieto et al. (2019)75 | 1 | 62, M | Leg (lower) | NWPT | GC+ustekinumab (after failure with infliximab) | Healed within 20 weeks |
| 97 | Grado Sanz et al. (2020)196 | 1 | 31, F | Leg (lower) | NWPT+punch graft | GC, CyA, hydroxychloroquine | Healed within 2 weeks |
| 98–101 | Our published experience: Deluca et al. (2015),56 Larcher et al. (2015),198 Pichler et al. (2016),199 Pichler et al. (2017)200 | 21 | Mean age 62, 67% F (14, F; 7, M) | Legs (19), breast (2), occipital (1) | NPWT and STSG (18), STSG (1), NPWT (2) | CS (21), dapsone (10), infliximab (4), adalimumab (1), MTX (2), IVIG (2), MMF (1), hydroxychloroquine (1), Pentoxifylline (5), Iloprost (4), simvastatin (4) | Completely healed: 16 (76%), with primary healing without recurrence after first treatment cycle in 14 (67%), 2 patients healed after recurrences treated with a second cycle. Over 90% improvement: 3 (14%). Two patients still with larger ulcers (10%): one had healed, but recurred twice, 1 never improved more than 30%. Recurrences observed: 7 (33%), 4 singles, 3 with two or more |
| Preliminary observations in this report | |||||||
| This report | Unpublished data | 1 | 48, F | Lower legs | Porcine xenograft+NPWT, then STSG+NPWT | CS, dapsone, ustekinumab (after failure of infliximab) | STSG 2 weeks after xenotransplant, then successfully healed within 3 weeks after STSG with and IS (CS, dapsone, ustekinumab) |
| This report | Unpublished data | 1 | 47, F | Lower leg | STSG, porcine xenograft (EZ-Derm®) | CS, dapsone, Pentoxifylline, simvastatin | STSG failed 3 × without IS, year-long deep PG healed within 6 months |
| Summary | 101 Articles | 161 Patients | Mean age 52 95% CI 2.6, median 54, minimum 9, maximum 89, F, 115, M, 46 p < 0.001 | Legs 113 (71%), breast 19 (12%), abdomen 10 (6%), other 18 (11%), of those, more than one localization 8 (5%), legs significantly more frequent than all others p < 0.001 | STSG alone 59 (37%), STSG together with HBO, flap or dermal substitute 11 (7%), NPWT alone 22 (14%), NPWT with STSG 41 (26%), NPWT with flaps, punch grafts, dermal substitutes or xenografts 7 (4%), other grafts (FTSG, Pinch, suction blister, cultured cells) 21 (13%) | CS first 149 (93%) after establishment of diagnosis 156 (98%), plus a second IS 41 (26%), plus two or more IS 38 (24%). IS being CyA 31 (19%), dapsone 18 (11%), infliximab or adalimumab 18 (11%), MMF 13 (8%), IVIG 7 (4%), AZA 6 (4%), pentoxifylline 6 (4%), others used in <5 patients | 139 Patients finally healed (86%), of those 17 patients healed, but had one or more recurrences (11%), 16 (10%) improved, 2 died of sepsis (1%). Healing took longer than 2 months in 22 patients (14%), of those, 17 were treated with NPWT, p < 0.001 for longer healing time with NPWT alone. 18 Partially previous, partially recurrent, or primary procedures on 15 patients failed, 12 (67%) of those without IS p < 0.05 |
Author, publication year, number of patients treated with NPWT or grafts, age, gender, localization of PG, procedures performed, systemic treatment, and outcome are reported.
a
In the case of series, where exact data on age and gender were missing (No. 47, 59, 65, and 81), given mean age was utilized and the corresponding sex percentage.
AZA, azathioprine; CI, confidence interval; CS, corticosteroids; CyA, cyclosporine A; F, female; FTSG, full thickness skin graft; HBO, hyperbaric oxygen; IS, immunosuppression; IVIG, intravenous immunoglobulins; M, male; MMF, mycophenolate mofetil; MTX, methotrexate; NPWT, negative pressure wound therapy; NR, not reported; P, patients; PG, pyoderma gangrenosum; STSG, split thickness skin grafting.