# Treatment Strategies in Neutrophil Dermatoses: A Comprehensive Review
## 3 Pydedema Gangrenosum
### Treatment
#### 3.3.2 Systemic Treatment  
Glucocorticoids  
Prednisone is usually administered at a dose of 0.5-1 mg/kg/day up to 2 mg/kg/day, with a gradual decrease between 4 and 6 weeks, and can be prolonged until completion at 4-6 months. Some authors recommend methylprednisolone pulses (250-1000 mg) for 3-5 consecutive days with consequent transition to the oral route, thus achieving a faster effect. Immunosuppressants  
The commencement of corticosteroid-sparing drugs should be performed as quickly as possible, because high doses of prednisone are associated with high mortality rates [25]. Among them, oral cyclosporine has emerged as the main immunosuppressiveant at doses of 2-3 to 4-5 mg/kg/day, and could be used both alone and in combination with glucocorticoids. The choice of using cyclosporine against corticosteroids depends on the patient's comorbidities. Pre-existing conditions that favor the use of corticosteroids over cyclosporine include renal failure or oncology history. However, patients with obesity, diabetes mellitus, osteoporosis, or peptic ulcer will benefit from cyclosporine [26]. In the same way, during the reduction in corticosteroids, dapsoe 50-200 mg, azithromycin 100-300 mg/day, methotrexate 10-30 mg/week, cyclophosphamide 1.5-3.0 mg/kg/day, mycophenolate mofetil 2-3 g/day, mercaptopurine, melphalan, thalidomide, and IVIG could be used. In addition, there are case series described in patients with PG refractory to conventional treatment who responded to the association of glucocorticoids with tracrolimus [27; 28]. TNF-\(\alpha\) Inhibitors  
Infliximab, adalimumab, etanercept, certolizumab, and golimumab have recognized efficacy in refractory PG and are associated with IBD [26], according to a semi-systematic review published by [PERSON] et al. After analyzing 222 articles that included 356 patients with PG treated with TNF-\(\alpha\) inhibitors, an 87% response rate and 67% complete remission were described, without finding significant differences between different drugs in terms of effectiveness [23]. **Infliximab**  
In a double-blind randomized clinical trial, [PERSON] et al. compared infliximab with a placebo, for which 30 patients with PG and IBD were recruited. Subjects were randomized to receive infliximab 5 mg/kg for 2 weeks. After two weeks of treatment, a response rate of 46% was observed in the infliximab group vs. 6% in the placebo group. Subsequently, given the obtained results, an open label trial was carried out that included the rest of the untreated patients; it was observed that at week 6, 90% had presented remission, with complete resolution in 21% of the patients treated with infliximab [29]. In the review published by [PERSON] et al., wherein 22 articles with 85 patients with a diagnosis of PG associated with IBD being treated with infliximab were analyzed, the efficacy of the treatment in cases of corticosteroid resistance and ulcerative phenotype was concluded [30]. [PERSON] et al. also carried out a retrospective analysis of a cohort of subjects with PG, in which they showed response rates of 92% and 100% with infliximab and adalimumab, respectively [31]. In total, 58 cases of PG without IBD treated with anti-TNF-\(\alpha\) have been reported in the literature, of which 41% were idiopathic PG, 17% were associated with rheumatoid arthritis, 10% were post-surgical/traumatic, 7% were associated with hidradenitis suppurativa, 4% were associated with monoclonal gammopathy, and 3.5% were related to cocaine use (levimasol) [32]. There is robust evidence supporting the use of infliximab in PG, both associated with and unrelated to IBD [29; 30; 31; 32]. See Table 2.  
**Adalimumab**  
The use of adalimumab has been shown to be effective in cases of recalcitrant PG, as demonstrated in some cases reported in the literature [33; 34]. Similarly, the case of a patient diagnosed with rheumatoid arthritis treated with methotrexate and etanercept, who developed refractory PG after 2 months of orthopedic surgery, has recently been published [35].