Treatment options for pyoderma gangrenosum

Pyoderma gangrenosum (PG) is an orphan disease. While research on such disorders is based on only few randomized multicenter as well as retrospective studies, most of the data comes from case series of small patient groups. Apart from topical and intralesional therapeutic options for early stages and mild disease courses, treatment predominantly involves systemic therapeutic agents. Besides systemic corticosteroids and cyclosporine A (CsA), options also include intravenous immunoglobulins (IVIG) and biologics such as the TNFα inhibitors infliximab, adalimumab, and etanercept; the interleukin (IL) 12/23 antibody ustekinumab; the IL‐1 receptor antagonist anakinra; and the IL‐1β antibody canakinumab. The best evidence‐based study data is available for CsA, prednisolone, and infliximab; the latter especially in patients with concomitant ulcerative colitis or Crohn's disease. A response to IVIG and canakinumab has been reported in smaller case series. First described by Brocq almost 100 years ago, it was soon recognized that PG did in fact require treatment. To this day, however, such treatment remains a clinical challenge. Despite the severe – albeit rare –clinical picture, improvement in therapeutic options may be expected in the future, primarily due to further clinical studies – especially with a greater number of patients, a better understanding of the etiopathogenesis, as well as the use of modern targeted therapies with higher efficacy and a lower rate of side effects than conventional immunosuppressants such as prednisolone and CsA.     

Treatment of pyoderma gangrenosum with intravenous immunoglobulin

BACKGROUND: Intravenous immunoglobulin (IVIG) is increasingly being used to treat inflammatory and autoimmune disease. OBJECTIVES: To elucidate the efficacy of IVIG as an adjunct treatment for pyoderma gangrenosum (PG). PATIENTS/METHODS: Ten patients with PG were treated with IVIG at Johns Hopkins Department of Dermatology. All patients had severe mutilating and/or refractory disease requiring multi-agent therapy. The charts were reviewed retrospectively. RESULTS: Seven of the ten patients had clearance of PG lesions in the setting of IVIG and six of these patients maintained efficacy with repeated IVIG treatment. Five patients complained of nausea with treatment, and in one case nausea was severe and intractable. One patient developed an immune reaction requiring diphenhydramine and methylprednisolone and another experienced aseptic meningitis. CONCLUSIONS: IVIG may be an effective adjuvant in the treatment of PG and has an acceptable side-effect profile. Randomized, placebo-controlled, double-blinded trials are needed to confirm this hypothesis.     

Treatment of pyoderma gangrenosum with cyclosporine.

BACKGROUND AND DESIGN--Pyoderma gangrenosum is a chronic inflammatory ulcerative skin disease of unknown origin, often associated with various diseases including inflammatory bowel disease, inflammatory arthritis, monoclonal gammopathies, hepatitis, and myeloproliferative disorders. Treatment of associated systemic disorders may improve the ulcers, but lesions may be recalcitrant and persist for months to years. Therapy for pyoderma gangrenosum includes high-dose systemic corticosteroids, sulfa drugs such as sulfasalazine, clofazimine, and immunosuppressive agents such as mercaptopurine and azathioprine; these drugs are sometimes ineffective. RESULTS--We present a series of 11 patients with pyoderma gangrenosum, with a wide range of underlying diseases, whose ulcers were refractory to usual therapy and who were treated with low-dose cyclosporine. Ten of the 11 patients cleared rapidly and completely with cyclosporine therapy. CONCLUSIONS--Cyclosporine should be seriously considered as a primary form of treatment for pyoderma gangrenosum.     

Treatment of pyoderma gangrenosum with cyclosporin A

Two patients with recalcitrant pyoderma gangrenosum were treated with oral cyclosporin A (5 mg/kg body-weight/day). Healing of the lesions was achieved in Patient 1 within 1 month of starting treatment, but new areas of ulceration appeared when the dose was reduced to 3 mg/kg body-weight/day. The ulcers showed marked improvement by 3 weeks after the start of treatment in Patient 2 and remained inactive at a maintenance dosage of 100 mg/day, but there was no change in the associated seronegative arthritis. A steroid-sparing effect of CyA was evident in both patients. It is suggested that a lower dose of cyclosporin A than doses used previously in the treatment of pyoderma gangrenosum may be equally effective.     

Treatment of a relapsing facial pyoderma gangrenosum (malignant pyoderma)

A case of rapidly relapsing pyoderma gangrenosum (PG) of the left preauricular area with no undermined borders is described. This might be considered a case of malignant pyoderma (PM), a rare variety of PG. Five months after complete healing obtained with systemic corticosteroids, the preauricular lesion of PG relapsed. As retreatment with oral methylprednisolone induced glucose intolerance and high arterial pressure, sulfa drugs were initially employed with a transitory recovery of the skin lesion. A successive prolonged course with minocycline induced a new complete resolution. To date, at six months' follow‐up, the patient is relapse‐free. This case confirms that sulfa drugs and minocycline may also be considered alternative therapies in PM. PM is a variety of PG characterized by specific morphological features, a higher tendency to relapse, and poor responsiveness to treatment.     

Treatment of severe recalcitrant pyoderma gangrenosum with ustekinumab

An increased expression of interleukin‐23 has been observed in patients with pyoderma gangrenosum, leading to the use of ustekinumab as a therapeutic option. We report the successful use of ustekinumab in three patients with treatment‐resistant pyoderma gangrenosum of varying clinical presentations.     

Treatment of refractory pyoderma gangrenosum with intravenous immunoglobulin

We report a patient with pyoderma gangrenosum successfully treated with intravenous immunoglobulin. He had previously been treated for 4 years with high-dose corticosteroids and had developed insulin-dependent diabetes mellitus. Multiple corticosteroid-sparing agents had failed or were contraindicated. He developed no adverse effects from intravenous immunoglobulin, which allowed reduction of his prednisone to 3 mg/day, and his ulcer has completely healed.     

Pustular pyoderma gangrenosum

Pyoderma gangrenosum (PG) is an idiopathic inflammatory disease of unknown aetiology, frequently associated with an underlying systemic condition such as inflammatory bowel disease or haematological malignancy. Its occurrence tends to parallel exacerbations of the underlying disease. Four clinical variants of PG have been described and these include ulcerative, pustular, bullous and vegetative types. We report two cases of the pustular form, which is an uncommon variant of PG, where the pustules do not progress to form ulcers. Both our patients suffered with inflammatory bowel disease which remained quiescent as the pustular PG developed.     

Pustular pyoderma gangrenosum

A 79-year-old woman was admitted to our hospital with pustular pyoderma gangrenosum and an associated IgG kappa monoclonal gammopathy. The patient is currently being evaluated for possible multiple myeloma. IgG multiple myeloma and IgG monoclonal gammopathies are very rare in patients with pyoderma gangrenosum. The skin lesions are improving with the use of prednisone.     

Penile pyoderma gangrenosum

We present a case of penile pyoderma gangrenosum (PG) that responded dramatically to an 8-week course of prednisone and has not recurred over a 6-month period. Although quite uncommon, penile PG should be a diagnostic consideration in any patient with non-healing ulcerative lesions of the penis. A correct diagnosis in this situation precludes unnecessary or harmful therapeutic interventions and leads to proper management.     

Penile pyoderma gangrenosum

Pyoderma gangrenosum is a rare ulcerating inflammatory skin disease. Genital involvement has been rarely reported. We report a 24-year-old man with penile pyoderma gangrenosum who was treated with systemic corticosteroids.     

Management of pyoderma gangrenosum

The management of pyoderma gangrenosum (PG) requires a structured approach to establishing diagnosis of the disease and assessment of the patient. Clinical management of active PG lesions should be carried out in coordination with other specialists (such as nurses and pain managers) and often necessitates a flexible, innovate attitude to therapy, because the needs of individual patients may vary widely. Although there is no single successful treatment for this disease, certain types of PG lesions are recognized to respond more readily to accepted therapies than others. We outline guidelines to the management of the patient with PG and discuss alternative therapies.     

Treatment of pyoderma gangrenosum with oral Tripterygium wilfordii multiglycoside

Two patients with refractory pyoderma gangrenosum (PG) were treated with oral Tripterygium wilfordii multiglycoside (TWG). TWG is a Chinese medicine extracted from a medicinal herb, Tripterygium wilfordii Hook F, and has potent anti-inflammatory and immunosuppressive effects. The effect of TWG on PG was demonstrated by clinical findings. Improvement of the lesions occurred within two weeks, and the ulcers healed about a month. Mild side effects such as gastrointestinal disturbances were observed in both patients. These side effects were patient-acceptable, and there was no need to stop the treatment. Transient elevation of serum ALT was observed in one patient; the serum ALT returned completely to normal after the discontinuation of TWG. These results suggest that TWG may be an effective alternative for refractory PG and that careful monitoring of liver function during TWG treatment is necessary.