Surgical treatment of pyoderma gangrenosum with negative pressure wound therapy and split thickness skin grafting under adequate immunosuppression is a valuable treatment option: Case series of 15 patients

To the Editor: Pyoderma gangrenosum (PG) is a rare inflammatory disease of unknown etiology. Only about 50% of patients achieve remission after 6 months of immunosuppressive therapy and even when patients respond well to treatment, relapses can occur in 30% to 60% of cases.1Ormerod A.D. Thomas K.S. Craig F.E. et al.UK Dermatology Clinical Trials Network's STOP GAP team. Comparison of the two most commonly used treatments for pyoderma gangrenosum: results of the STOP GAP randomised controlled trial.BMJ. 2015; 350: h2958Crossref PubMed Scopus (146) Google Scholar, 2Cabalag M.S. Wasiak J. Lim S.W. Raiola F.B. Inpatient management of pyoderma gangrenosum: treatments, outcomes, and clinical implications.Ann Plast Surg. 2015; 74: 354-360Crossref PubMed Scopus (34) Google Scholar, 3Binus A.M. Qureshi A.A. Li V.W. Winterfield L.S. Pyoderma gangrenosum: a retrospective review of patient characteristics, comorbidities and therapy in 103 patients.Br J Dermatol. 2011; 165: 1244-1250Crossref PubMed Scopus (235) Google Scholar Progression of existing lesions or development of new lesions after trauma is reported in up to 30% of PG (pathergy phenomenon).3Binus A.M. Qureshi A.A. Li V.W. Winterfield L.S. Pyoderma gangrenosum: a retrospective review of patient characteristics, comorbidities and therapy in 103 patients.Br J Dermatol. 2011; 165: 1244-1250Crossref PubMed Scopus (235) Google Scholar Therefore the role of surgical interventions is controversially discussed in that they might further aggravate the condition, especially if performed without immunosuppression.2Cabalag M.S. Wasiak J. Lim S.W. Raiola F.B. Inpatient management of pyoderma gangrenosum: treatments, outcomes, and clinical implications.Ann Plast Surg. 2015; 74: 354-360Crossref PubMed Scopus (34) Google Scholar On the other hand, PG ulcers without skin grafting require a prolonged time to heal, being prone to secondary infection, which potentially represents an additional trigger for pathergy. In addition, long-term systemic immunosuppressive therapy is associated with adverse reactions in about 65% of patients.2Cabalag M.S. Wasiak J. Lim S.W. Raiola F.B. Inpatient management of pyoderma gangrenosum: treatments, outcomes, and clinical implications.Ann Plast Surg. 2015; 74: 354-360Crossref PubMed Scopus (34) Google Scholar, 3Binus A.M. Qureshi A.A. Li V.W. Winterfield L.S. Pyoderma gangrenosum: a retrospective review of patient characteristics, comorbidities and therapy in 103 patients.Br J Dermatol. 2011; 165: 1244-1250Crossref PubMed Scopus (235) Google Scholar Therefore an urgent clinical need exists to close open wounds in these patients as fast as possible. Negative pressure wound therapy (NPWT) has become an important tool in the management of complex wounds and is used to secure split thickness skin grafts (STSG) in difficult recipient wound beds.4Webster J. Scuffham P. Stankiewicz M. Chaboyer W.P. Negative pressure wound therapy for skin grafts and surgical wounds healing by primary intention.Cochrane Database Syst Rev. 2014; 10: CD009261PubMed Google Scholar Here we report a multicenter case series of 15 patients with PG who were treated successfully with surgery under adequate immunosuppression, with STSG secured by NPWT after effective conditioning with NPWT (Fig 1). Patient details, treatment, and outcomes are reported in Table I. All patients were hospitalized before surgical intervention to initiate immunomodulatory therapy. NPWT (VAC) was begun up to 1 week before surgical intervention. All interventions were performed under local tumescence anesthesia as previously described.5Pichler M. Deluca J. Tappeiner L. Eisendle K. Reconstruction of large rectangular infraorbital and malar skin defects in elderly patients with a modified “reading man flap” using local tumescent anesthesia.Int J Dermatol. 2014; 53: 1520-1525Crossref PubMed Scopus (16) Google Scholar STSGs were secured by NPWT for 3 to 5 days. Ten patients healed completely and primary healing without recurrence after the first treatment cycle occurred in 9 of those patients, while patient 5 healed after 2 recurrences. One local recurrence healed after modification of the immunosuppressive treatment with NPWT alone and a second PG at a different localization healed after a second cycle of NPWT followed by STSG, secured by NPWT. In 3 patients, there was marked improvement of more than 90% of the wound surface healed; minor recurrence developed in 2 of those patients, which was managed with local wound dressings and increased immunosuppression, resulting in 95% improvement seen at follow-up. Two patients still have ulcers: ulcers healed in patient 4 but recurred twice after successful treatment cycles with NPWT followed by STSG secured by NPWT. Patient 11 never improved more than 30% despite treatment. No pathergy or reactivation of PG was observed, neither in the vicinity of the PG ulcers nor at the skin graft donor sites. NPWT followed by STSG secured by NPWT induced healing within 1 month after grafting in 67% (10/15) of cases and improvement of more than 90% in 4 (27%) cases, being significantly superior to the reported healing rates of 50% after 6 months when a conservative approach is performed while showing a similar recurrence rate of 30%.1Ormerod A.D. Thomas K.S. Craig F.E. et al.UK Dermatology Clinical Trials Network's STOP GAP team. Comparison of the two most commonly used treatments for pyoderma gangrenosum: results of the STOP GAP randomised controlled trial.BMJ. 2015; 350: h2958Crossref PubMed Scopus (146) Google Scholar, 2Cabalag M.S. Wasiak J. Lim S.W. Raiola F.B. Inpatient management of pyoderma gangrenosum: treatments, outcomes, and clinical implications.Ann Plast Surg. 2015; 74: 354-360Crossref PubMed Scopus (34) Google Scholar, 3Binus A.M. Qureshi A.A. Li V.W. Winterfield L.S. Pyoderma gangrenosum: a retrospective review of patient characteristics, comorbidities and therapy in 103 patients.Br J Dermatol. 2011; 165: 1244-1250Crossref PubMed Scopus (235) Google ScholarTable IPatient details and summary of 15 patients treated surgically for pyoderma gangrenosum (PG) with negative pressure wound therapy (NPWT) and split thickness skin grafts (STSGs) secured by NPWT. Age, gender, comorbidities, duration of PG, type of PG (superficial/deep), activity of PG at hospital admission (active/inactive), previous treatments, applied immunosuppression, localization and dimension of PG, time of hospitalization, procedural intervention with NPWT preconditioning time, primary outcome, and follow-up of 15 patients are reportedNrAgeSexComorbidityDuration (time) type and activity of PGPrevious immune-suppression/treatmentApplied immune-suppressionLocalization and dimension (cm)Hospitalization (time)Surgical treatment (preconditioning time)Graft take at discharge/primary outcomeDisease-free follow-up/recurrences163MDiabetes mellitus type 2, arterial hypertension, chronic renal failure, monoclonal gammopathy, hypothyroidism2 months, deep, activeNoneMP 0.5 mg/kg, Daps 50 mg tid, Infxmb 5 mg/kg (week 0, 2, 6), IloprostBoth distal legs involving the whole circumference or more than the half 30 × 25 cm2 monthsNPWT (5 days) followed by STSG secured by NPWT100% graft take/healed1 year239Fbilateral congenital radioulnar synostosis1.5 years, deep, activeNoneMP 0.5 mg/kg, Daps 50 mg bidRight lower leg 10 × 8 cm and 5 × 4 cm3 weeksNPWT (5 days) followed by STSG secured by NPWT100% graft take/healed1 year349FSystemic lupus erythematosus (SLE)2 months, deep, activePHQMP 0.5 mg/kg, HQ, Daps 50 mg bidLeft lower leg 10 × 5 cm1 monthNPWT (7 days) followed by STSG secured by NPWT100% graft take/healed1 year and 3 months472FCongenital cataract, polyarthrosis, hypothyroidism, osteoporosis, reduced oral glucose tolerance, monoclonal gammopathy30 years, deep, inactiveP, CyA, NPWTMP 0.5 mg/kg, Pntxph 400 mg bid2/3 of both lower legs involving the whole circumference and dorsal foot both 30 × 25 cm, inactive stable PG ulcers3 monthsNPWT right (5 days), negatively charged polystyrene microspheres (Polyheal) left, followed by 3 STSG secured by NPWT100% graft take/healed4 months, then minor relapse, successfully retreated and healed within 6 weeks with NPWT followed by STSG secured by NPWT + simvastatin; second minor relapse after 9 months managed conservatively, after 6 months still minor nonpainful ulcers on both malleoli543FMonoclonal gammopathy, osteoporosis, depression13 years, superficial, activeMP, AZA, MMF, Daps, InfxmbMP 0.5 mg/kg, MTX 15 mg weekly, Pntxph 400 mg bidRight lower leg 20 × 20 cm1 monthNPWT (5 days) followed by STSG secured by NPWT80% graft take, >95% within 4 weeks' follow-up11 months, minor recurrence after trauma, markedly improved after 5 days NPWT + Daps 50 mg bid, with a healing of 99% within 2 months, after 2 months second pyoderma at her left breast successfully treated and healed within 4 weeks with NPWT followed by STSG secured by NPWT + ustekinumab, now 2 months' disease-free (breast and leg)689FChronic heart failure, atrial fibrillation, severe valvular aortic stenosis, monoclonal gammopathy5 months, superficial, activeNoneMP 0.5 mg/kg, Daps 50 mg, simvastatinRight lower leg 19 × 16 cm2 weeksNPWT (3 days) followed by STSG secured by NPWT100% graft take/healed7 months784FMonoclonal gammopathy, depression7 months, deep, activeNoneMP 1 mg/kg, Daps 50 mg bid, Pntxph 600 mg, simvastatin, iloprostBoth distal legs: right 15 × 8 and 1 × 2 cm; left 15 × 15, 3 × 3, 2 × 2, 1 × 1, and 2 × 2 cm4 weeksNPWT (7 days) followed by STSG secured by NPWT75% graft take, 100% healed 4 weeks after surgery6 months867MArterial hypertension, peripheral artery occlusive disease, osteoporosis, bilateral hip replacement, chronic alcohol abuse2 months, deep, activeNoneMP 0.5 mg/kgRight lower leg 15 × 10 cm1 monthNPWT (7 days) followed by STSG secured by NPWT95% graft take/>95% in follow up2 months, then minor relapse managed conservatively (local wound therapy, MP up to 0.5 mg/kg), with a healing of 97% within 5 months977MDiabetes mellitus type 2, arterial hypertension, ischemic cardiomyopathy, artificial heart valve, pacemaker1 month, superficial, activeNoneMP 0.5 mg/kg, Daps 50 mg bid, local tacrolimus 0.1%Left lower leg 13 × 10 cm1 monthNPWT (5 days) followed by STSG secured by NPWT100% graft take/healed7 months1056FSepsis, arterial hypertension, obesity, fatty liver, breast cancer, colorectal cancer7 weeks, deep, activeMPMP 1 mg/kg, Daps 50 mg bid, IVIG 1 mg/kg (4 weekly)Both distal legs 25 × 15 cm and 23 × 14 cm7 monthsNPWT (5 days) followed by STSG secured by NPWT90% graft take/99% in follow-up5 months' follow-up, managed conservatively (local wound therapy, MP reduced gradually), with a healing of 99%1163FArterial hypertension, osteoporosis, infrarenal aortic aneurysm, stroke7 months, deep, activeMPMP 0.5 g/kg, Infxmb 4 mg/kg (week 0, 2, 6), local clobetasol propionate, local tacrolimus 0.1%Left lower leg 12 × 8 cm and 5 × 5 cm5 monthsNPWT (7 days) followed by STSG secured by NPWT20% graft take1 month, then relapsed, managed conservatively (local wound therapy, Infxmb, MP up to 0.5 mg/kg) and with NPWT/STSG after 5 months, first improved (30% graft take), but second relapse after 1 month, with new ulcers, still not healed1250FDiabetes mellitus type 2, arterial hypertension, obesity, bronchial asthma, stroke5 months, superficial, activeMPMP 0.5 mg/kgInfxmb 4 mg/kg (week 0, 2, 6), local tacrolimus 0.1%Left lower leg 13 × 10 cm7 monthsNPWT (5 days) followed by STSG secured by NPWT90% graft take/>95% in follow-up3 months, then relapsed, managed conservatively (local wound therapy, MP up to 0.5 mg/kg, Infxmb, begin with IVIG 1 mg/kg), with a healing of 95% in 6 months, then died at home due to fatal pulmonary embolism1347MAnemia, arterial hypertension, hyperlipidemia, chronic obstructive pulmonary disease8 months, deep, activePDapsInfxmbP 5 mg qdDaps 50 mg bidleft lower leg 8 × 3 cm2 weeksNPWT (3 days) followed by STSG secured by NPWT100% graft take/healed1 year1475FCardiomyopathy, arterial hypertension, renal failure, obesity, goiter6 months, deep, activeNoneMP 10 mg qdMTX 10 mg weeklyInflxmb 5 mg/kgOccipital 8 × 16 cm4 weeksNPWT (7 days) followed by STSG secured by NPWT100% graft take/healed7 months1564MArterial hypertension, hyperlipidemia, atrial fibrillation, sigmoid colon cancer3 years, deep, inactiveMP, IVIG, MMFMP, IVIG, MMFRight lower leg 7 × 12 cm2 weeksNPWT (3 days) followed by STSG secured by NPWT100% graft take/healed1 yearSummary: Median (range) where appropriate or (quantity)63 (39-89)10F, 5MRelevant: Monoclonal gammopathy (5), sigmoid cancer (1), SLE (1), atrial hypertension (9), obesity/impaired glucose tolerance/diabetes (6)5 months (1 week-30 years)CS (8), Daps (2), MMF (2), Infxmb (2), CyA (1), HQ (1), AZA (1), IVIG (1)CS (15), Daps (8), Infxmb (4), MTX (2), Ptxph (3), Iloprost (2), IVIG (2), MMF (1), HQ (1)Legs (15), Occipital (1)4 weeks (2-28)NPWT 5 days (3-7) and STSG secured by NPWT (15)Healing: Completely healed 10 (67%) with primary healing without recurrence after first treatment cycle in 9 patients and 1 patient healed after 1 recurrence and 1 second PG at a different localization. Over 90% improvement: 3 (20%).Two patients still with ulcers (13%): 1 of them had healed but recurred twice, one never improved more than 30% because of recurrences.Recurrences observed 5 (33%): 2 single recurrences managed conservatively with 95% improvement; 3 patients with 2 recurrences, 1 of them healed and 2 still with ulcers.AZA, Azathioprine; bid, twice daily; CS, corticosteroids; CyA, cyclosporine A; Daps, dapsone; HQ, hydroxychloroquine; Infxmb, infliximab; IVIG, intravenous immunoglobulins; MMF, mycophenolate mofetil; MP, methylprednisolone; MTX, methotrexate; NPWT, negative wound pressure therapy; P, prednisolone; Pntxph, pentoxyphylline; qd, daily; STSG, split thickness skin graft; tid, 3 times daily. Open table in a new tab AZA, Azathioprine; bid, twice daily; CS, corticosteroids; CyA, cyclosporine A; Daps, dapsone; HQ, hydroxychloroquine; Infxmb, infliximab; IVIG, intravenous immunoglobulins; MMF, mycophenolate mofetil; MP, methylprednisolone; MTX, methotrexate; NPWT, negative wound pressure therapy; P, prednisolone; Pntxph, pentoxyphylline; qd, daily; STSG, split thickness skin graft; tid, 3 times daily. This large case series of surgical intervention in PG confirms that wound preparation with NPWT and surgical treatment with gentle debridement and STSG secured by NPWT under adequate immunosuppression is a potential treatment option for PG.