Refractory steroid‐resistant pyoderma gangrenosum successfully treated with intravenous immunoglobulins

Dear Editor, Pyoderma gangrenosum (PG) is a rare, autoinflammatory neutrophilic dermatosis, characterized by a spectrum of clinical presentations, painful necrotic ulcerations being the most frequent ones. The complex pathophysiology is likely multifactorial. Standardized therapeutic approach is lacking. Corticosteroids (CS) (0.5-1 mg/kg) and cyclosporine (CSA) (5 mg/kg) are considered first-line treatments. Combination of multiple therapeutic modalities appears more effective than monotherapy; biologics (tumor necrosis factor-α antagonists, antiinterleukin [IL]-1 and anti-IL-12/23 antibodies) and intravenous immunoglobulins (IVIG) are used as adjacent and alternative options. We report a patient with aggressive PG resistant to multiple therapeutic options; complete remission was attained with IVIG. A 57-year-old Caucasian woman presented with a 2-month history of deep ulcers on her right gluteal region and lower extremity (Figure 1). She denied previous trauma or surgery. Laboratory tests and clinical features are listed in Table 1. Extensive workup revealed no associated diseases. Multiple cutaneous biopsies were taken along lesion margins and histology corresponded to PG (Figure 2). Combination of prednisone 60 mg daily (0.9 mg/kg/d), with subsequent tapering, and dapsone 100 mg daily were initiated. Numerous wound cultures isolated a plethora of pathogens and the patient was septic on multiple occasions. Despite treatment, new ulcers appeared and previous wounds expanded and penetrated deeper structures (Figure 3A, B). Due to lack of efficacy and side effects, dapsone (hemolysis), methotrexate and azathioprine (anemia) were discontinued. Twenty sessions of hyperbaric oxygen therapy were introduced. Intravenous pulse dexamethasone (IVPD) therapy (100 mg/d, 3 d monthly) was initiated. Owing to further clinical deterioration, high-dose IVIG (2g/kg over 3 d monthly) was instituted with continued IVPD and oral prednisone in between. Within 3 weeks of IVIG introduction, remarkable improvement was noted which continued for the next 3 months (Figure 3C). Monthly cycles of high-dose IVIG and IVPD were continued for 4 and 5 months, respectively, resulting in complete remission. No IVIG-related side effects occurred. During our 5-year follow-up period, no recurrences occurred (Figure 4). Immunosuppression is the backbone of PG treatment. While CSA and CS are first-line treatments, other immunosuppressive therapy is reported. Patients treated with IVIG, infliximab, adalimumab and ustekinumab demonstrated higher percentage of complete remission or improvement than with CS or CSA. IVIG, despite its efficacy but due to its cost, is usually used in lifesaving situations. Our patient failed to respond to all previously introduced therapeutic modalities while also developing various drugrelated side effects. Most literature doses of IVIG are 2 g/kgduring 2 to 5 days. Some authors have used lower (0.5 and 1.5 g/kg or higher (2.5 g/kg) doses. In most published cases, marked improvement is seen quickly within the first or second IVIG cycles, which is in line with our case. IVIG works multifold by modulating innate immune system, and augments glucocorticoid effectiveness. This could prove why IVPD demonstrated efficacy only after IVIG institution. A systemic review found a higher incidence of associated diseases in IVIG-treated PG cases vs PG in general (82% vs 50%). Surprisingly, we did not find any associated diseases during workup or follow-up, making this case all the more confounding and rare. IVIG is effective, with good tolerability and safety profile in severe PG cases. We believe in its use earlier in the disease course in patients at increased risk of infection or with rapid progression as