Hyperbaric Oxygen Therapy for the Adjunctive Treatment of Pyoderma Gangrenosum: A Case Report
Pyoderma gangrenosum (PG) is a neutrophilic dermatosis of unknown etiology characterized by an ulcerative skin condition and confirmed through a diagnosis of exclusion. Management usually consists of systemic drug therapy, such as corticosteroids, sulfones, or immunosuppressants, either alone or in combination. Long-term use of these medications often has untold side effects. Hyperbaric oxygen therapy (HBOT) has been shown effective in the treatment of PG, reducing pain and tempering the need for medication.
A case is presented of a 54-year-old woman with diabetes, hypertension, and a peptic ulcer who presented with painful, purulent ulcers on her buttocks, hands, and lower extremities of 2 weeks’ duration. She was ultimately diagnosed with PG and provided 20 mg/day of oral prednisone for 1 week, tapered to 10 mg/day in the next week and then stopped. In addition, she received 12 sessions of HBOT — she breathed in 100% oxygen under 2.5 atmospheres absolute pressure for 90 minutes over 2 weeks. Her wounds healed without scarring. This excellent outcome including good wound healing, decreased pain, and reduced doses of systemic corticosteroids warrants additional study of the adjunctive use of HBOT for PG.
Pyoderma gangrenosum (PG) is a painful ulcerative neutrophilic disease of the skin with unknown origin. It was first described by Brunsting et al1 in 1930. von den Driesch2 presented a study of 44 patients with PG with follow-up. Initially, PG clinically presents as a sterile pustule with an inflamed base, an erythematous nodule, or a hemorrhagic bulla on a violaceous base, mostly involving the lower extremities. These lesions evolve to form shallow or painful ulcers with a purulent undermined base and a violaceous gunmetal-colored border that spreads peripherally. With treatment, the borders flatten and the ulcer heals to form a thin cribriform scar. Based on Ruocco et al’s3 and Dabade and Davis’4 reviews, the incidence of PG is 3 to 10 cases per million persons per year globally. Patients are generally between 25 and 50 years of age with a slight female predominance. Oka et al5 found interleukin-8 (IL-8) overexpression in skin specimens from patients with PG, and their animal studies suggest an etiologic role of IL-8 in the pathogenesis of PG.
The etiology of PG remains poorly understood, but a predominantly immunological pathogenesis involving neutrophil dysfunction seems most likely. According to Dabade and Davis’4 and Alavi et al’s6 reviews, half of the patients with PG have associated systemic diseases, including inflammatory bowel disease, rheumatoid arthritis, myeloproliferative disorders, and connective tissue disease.
In reviews7,8 of several prospective, randomized, controlled studies, hyperbaric oxygen therapy (HBOT), the administration of 100% oxygen at 2 to 3 atmospheres absolute pressure, has shown benefits in treating acute and chronic wounds; because multiple cellular mechanisms are triggered by reactive oxygen and reactive nitrogen species, wounds treated with HBOT show improved neovascularization, decreased peripheral edema, and diminished inflammatory and immune responses. Complications (in <0.04% of cases) of HBOT include barotrauma, claustrophobia, myopia, and seizures. These are rare and usually reversible7,8; however, irreversible nuclear cataracts have been described with HBOT exceeding 150 hours.9 Several case reports reviewed by Tutrone et al10 have shown HBOT to effectively treat PG ulcers and reduce pain associated with PG.
Treatment of PG with prolonged high-dose systemic corticosteroids (0.5–1 mg/kg/day; more than 1 month) or other immunosuppressants, in addition to careful local wound care, characterizes the mainstay of management.12-14 The following case study is presented to demonstrate that HBOT plays a role in moderating the dosage of steroids and reducing pain.
Ms. J is a 54-year-old woman weighing 65 kg with a history of type 2 diabetes mellitus, peptic ulcer disease, and hypertension controlled with oral medication. She presented at the authors’ dermatology department with a 2-week history of multiple painful ulcers with violaceous undermined borders and purulent bases located on her buttocks, both hands, and lower extremities (see Figure 1). She was afebrile and denied any history of skin disease or trauma. She was provided surgical debridement using a Goulian knife; wound dressings included povidone-iodine and gauze. Ms. J’s lesions quickly expanded laterally and developed a necrotic ulcerated center, worsening after 1 week of treatment. She rated her pain 8 out of 10 on a subjective visual analogue scale (VAS) and was given tramadol (50 mg) 6 times a day. She was referred to a plastic surgeon in a tertiary hospital for further evaluation who performed a skin biopsy of the lower extremities, 0.5 mm in diameter and deep to subcutaneous fat. All wounds were covered with alginate dressings to address absorption and possible infection.
Pathology revealed neutrophilic dermatoses (see Figure 2). In order to eliminate other causes of cutaneous ulcers, laboratory testing was performed and included a complete blood cell count, levels of C-reactive protein, fasting blood sugar and lipids, hepatitis screening, evaluation of renal function, and urinalysis. Ms. J’s levels were all normal except for hyperglycemia. Screenings for hypercoagulability factors such as anticardiolipin antibodies, proteins C and S, antithrombin III, Factor V Leiden, and toxicology panel also were negative. Immunological tests including those for antinuclear antibody, rheumatic factor complement, cryoglobulinemia, and anti-SCL-70 and anticentromere antibodies were unremarkable. Wound cultures revealed negative results. PG was diagnosed based on clinical, histopathology, and laboratory findings.11 Colonoscopy and blood tests for hematologic disorders showed no inflammatory bowel disease or hematologic disorders. Ms. J denied having arthritis. She was treated with 20 mg/day of oral prednisone for 1 week; this was tapered down to 10 mg/day in the next week and then stopped.
The plastic surgeon, also an expert in HBOT, added HBOT to the treatment protocol immediately after receiving the biopsy result. Ms. J breathed 100% oxygen under 2.5 atmospheres absolute pressure for 90 minutes through a facemask. Twelve (12) HBOT sessions were performed daily except on weekends. The pain decreased to a VAS pain score of 2 after 1 week, and Ms. J received no analgesics. The lesions were completely healed with scarring in 2 weeks (see Figure 3).
Ms. J continued to be monitored at the outpatient department and showed no evidence of relapse over 6 months. Considering the extensive PG observed at presentation, the cosmetic results were excellent with unapparent scars.
PG is a rare form of neutrophilic dermatosis that presents as an inflammatory and ulcerative disorder of the skin. Because no diagnostic criteria have been established for clinical use, PG is a diagnosis of exclusion. In their review, Su et al11 proposed major and minor criteria for the diagnosis of PG: the major criteria are rapid progression of a painful, necrolytic cutaneous ulcer and exclusion of other cutaneous disease; the minor criteria are pathergy, systemic disease-associated PG (ie, inflammatory bowel disease, arthritis, IgA gammopathy, or malignancy), and/or rapid response to systemic glucocorticoid treatment. To be considered a definite case of PG, the condition should meet the 2 major criteria and at least 2 minor criteria. von den Driesch2 independently used inclusion criteria for the diagnosis of PG patients that are almost identical to Su et al.11
Based on Oka et al’s5 study and Ahronowitz et al’s12 review, neutrophil dysfunction, genetic factors, and dysregulation of the immune system might contribute to PG. The condition requires multiple treatment modalities to reduce inflammation and optimize wound healing, in addition to treating any underlying diseases. Prednisone and cyclosporine have been mainstays of the systemic treatment for PG, although several clinical trials12 support the use of biological therapies such as tumor necrosis factor-α inhibitors for refractory cases of PG. According to Prystowsky et al’s13 summary of the management of 22 cases of PG over 4 years and Chow et al’s14 review of current PG treatment, experience suggests patients should receive 0.5–1 mg/kg per day of oral prednisone or its equivalent. The glucocorticoid treatments should be tapered off and discontinued within 4–10 weeks.
Bennett et al15 performed a retrospective analysis of the medical records of 86 patients with PG who were evaluated and treated over 12 years at 2 university-based dermatology departments. Although clinical signs of improvement might be evident within a few days of initial treatment, the 86 PG patients reviewed required a mean 11.5 ± 11.1 months of treatment to achieve complete healing.
Results of Dodiuk-Gad et al’s16 review included an evidence-based, strategic approach to the general risk management of systemic glucocorticoid use. Although the potent anti-inflammatory and immunosuppressive effects of systemic glucocorticoids have led to their wide use in the treatment of dermatologic diseases, long-term therapy of weeks or months with systemic glucocorticoids is associated with significant adverse effects, such as osteoporosis, myopathy, peptic ulcer disease, hyperglycemia, hypertension, and edema. For Ms. J, given her medical history, continued use of prednisone could have led to poor control of her diabetes and hypertension, and her peptic ulcer disease could have recurred.
Wound treatment with HBOT is well established. According to a Cochrane database systematic review,7 HBOT significantly improved the chance of healing foot ulcers in persons with diabetes mellitus. Dauwe et al9 conducted a systematic review of HBOT in the treatment of complicated acute wounds, flaps, and grafts: a total of 8 studies (4 prospective, randomized, controlled trials; 3 prospective, nonrandomized, controlled trials; and 1 retrospective, controlled trial) addressed the use of HBOT for wounds in humans. The results showed HBOT can augment healing in complicated acute wounds, such as skin graft survival, healing of burn injuries, and crush injuries.
For Ms. J, hypertension, diabetes mellitus, and a history of peptic ulcer precluded long-term steroid use. Using adjuvant HBOT, the wounds heal rapidly in 2 weeks, allowing clinicians to decrease steroid dosage and duration. More studies are needed to increase the evidence base for this treatment approach.
PG is an uncommon inflammatory and ulcerative skin disorder characterized histopathologically by the accumulation of neutrophils in the skin. For patients with extensive PG, systemic glucocorticoids are used as first-line agents. For a patient with diabetes, hypertension, and a history of peptic ulcers, treatment of PG with a systemic glucocorticoid and HBOT allowed a decreased dosage and duration of steroid usage. Wound pain was diminished after 1 week and the wounds were healed after 2 weeks of treatment. Additional research is needed to determine the safety, efficacy, and effectiveness of this treatment approach for patients with PG.
The authors thank the Civilian Administration Division of Tri-Service General Hospital, National Defense Medical Center and Shuang-Ho Hospital, Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, Republic of China.
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Dr. Chiang is a plastic resident, Division of Plastic Surgery, Department of Surgery; Dr. Liao is a pathologist resident, Department of Pathology; Dr. Dai is vice-professor, Chief, and attending plastic physician; Dr Chiao and Dr. Chou are plastic residents; Dr. SG Chen is a vice-president of Tri-Service General Hospital, professor, and attending plastic physician; and Dr. TM Chen is a professor and attending plastic physician, Division of Plastic Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China. Dr. Chang is an assistant professor, Chief, and attending physician, Division of Plastic Surgery, Department of Surgery, Hyperbaric Oxygen Therapy Center, Shuang-Ho Hospital, Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, Republic of China. Please address correspondence to: Shun-Cheng Chang, No.291, Zhongzheng Rd, Zhonghe Dist, New Taipei City 235, Taiwan, Republic of China; email: firstname.lastname@example.org.
Potential Conflicts of Interest: none disclosed