Human necrotizing vasculitis: immunoglobulins and complement in vessel walls of cutaneous lesions and normal skin.

Immunoglobulins and C3 were detected by immunofluorescence in the blood vessel walls of biopsies of clinically normal skin in patients with active necrotizing vasculitis. Of the 13 patients studied, 9 had C3 and 6 of these had IgM or IgA in biopsies of lesions of vasculitis. In adjacent clinically normal skin, 7 patients had C3 and 3 of these also had IgM or IgA. These findings support the hypothesis that immunoglobulins and complement are present in vessels of some patients prior to chemotaxis of polymorphonuclear leukocytes and the resulting inflammatory purpuric lesions so characteristic of necrotizing vasculitis.     

Treatment of pyoderma gangrenosum

Critical to the proper management of pyoderma gangrenosum are correct diagnosis, identification and treatment of any underlying disorder, and the proper choice of topical and systemic therapy. Many agents are available for the treatment of pyoderma gangrenosum. We review the current therapeutic options, their efficacy and side effects, and we offer some guidelines for their proper selection.     

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.     

Giant cells in pyoderma gangrenosum

It has been claimed that pyoderma gangrenosum (PG) lesions may contain granulomatous foci when associated with Crohn's disease. To test this assertion, we obtained clinical histories and archived cutaneous biopsies from 34 PG patients. Thirteen of these patients had inflammatory bowel disease (IBD). Immunostaining with PGM1, a macrophage marker, revealed well-formed giant cells with three or more nuclei in biopsies from 6 of 13 patients with IBD. Five of the 6 biopsies came from patients with Crohn's disease and one from a patient with ulcerative colitis. Two were peristomal. In the 21 patients who had PG without IBD, no giant cells were seen. Thus, PGM1+ histiocytic giant cells within a PG lesion may be indicative of associated IBD (p = 0.006), particularly Crohn's disease.     

Periungual lesions in pyoderma gangrenosum

Pyoderma gangrenosum (PG) is a progressive cutaneous necrosis of unknown origin. We report a case of PG presenting with periungual lesions. A 57-year-old woman was on treatment with ciclosporin A for PG. During tapering of the ciclosporin A dose, proliferating periungual lesions developed on the third and fourth finger of the left hand, the fourth finger of the right hand, and on the right great toe and the left fifth toe. All lesions appeared within a 4-week period. These abnormalities were ulcerated, involved about one-third of the distal part of the lateral nail folds including the part of nail fold bordering on the free edge of the nails, and were very painful. The skin biopsy was consistent with that seen in PG. Increasing the ciclosporin A dose led to significant improvement in the periungual lesions within the next few weeks and complete resolution within 6 months.     

Cutaneous tuberculosis and pyoderma gangrenosum

A 59‐year‐old woman with multiple myeloma at stage IA exhibited recurrent pyoderma gangrenosum of 13 years’ duration. She also had a history of mitral regurgitation and cerebral infarction, but no significant family history was present. In September 1994, she noted a painful erythematous papule on her left foot, which was treated with a topical injection of triamcinolone. It responded well to this treatment at the time, but a similar eruption developed in the same place in February 1995, and enlarged to form an irregularly shaped, punched‐out ulcer with surrounding infiltrative erythema despite topical treatment ( Fig. 1 ). Further, since November 1994, she had noted pain in the right dorsal foot.

Figure 1 Open in figure viewer PowerPoint Necrotic ulcer with an elevated purulent border and pustules on the left foot     

Mycophenolate mofetil in pyoderma gangrenosum

Recently, the use of mycophenolate mofetil (MMF) has expanded in dermatological practice. Three patients with PG received MMF in conjunction with prednisone and a fourth patient received MMF monotherapy daily. MMF in combination with prednisone in three of our patients and alone in our fourth patient induced healing of their ulcers. The first patient tolerated MMF apart from gastrointestinal upset, while treatment in our second patient was complicated by staphylococcal and pseudomonal sepsis. The third patient complained of palpitations and headaches.     

Direct immunofluorescence in pyoderma gangrenosum

Direct immunofluorescence was done in fifty-one cases of pyoderma gangrenosum. Biopsy specimens were taken from the peripheral erythematous zone of the lesion. In thirty-one cases (61%), there was positive immunofluorescence, with perivascular deposition of immune reactants being the most frequent pattern (twenty-seven cases). These findings support a vasculitic pathogenesis of pyoderma gangrenosum.     

Deposits of complement and immunoglobulins in dermal and synovial vessels in psoriasis.

Deposits of complement C3 and/or immunoglobulin were found in the vessel walls and/or at the dermal-epidermal junction in skin lesions of all of 11 patients with psoriatic arthritis and guttate psoriasis. Similar deposits were seen in 6 out of 15 patients with psoriasis vulgaris. Synovial tissue available from 2 patients revealed deposits in the vessel walls.     

Use of infliximab in pyoderma gangrenosum

A 57-year-old man, with a 2-year history of Crohn's disease, presented with a rapidly progressive abdominal ulcer. It was clinically and histologically consistent with pyoderma gangrenosum but it did not respond to either high-dose oral prednisolone or intravenous hydrocortisone. Infliximab resulted in an early, dramatic and sustained improvement. His bowel symptoms, which flared a few weeks prior to the onset of pyoderma gangrenosum, only partially improved. Despite six infliximab infusions, the inflammatory bowel disease is poorly controlled, whereas the pyoderma gangrenosum remains healed.     

Optimal treatment of pyoderma gangrenosum

The optimal treatment of pyoderma gangrenosum includes a combination of local wound care and systemic medications. Oral and pulse intravenous corticosteroids have traditionally been the most commonly recommended first-line systemic therapies. Cyclosporine, with or without corticosteroids, has more recently emerged as a first-line systemic treatment. A multitude of immunosuppressive and immune-modulating medications, as well as antimicrobial agents with anti-inflammatory properties have also been widely prescribed. Often, it is difficult to achieve control of aggressive cases of pyoderma gangrenosum, necessitating administration of a combination of systemic therapies. Furthermore, patients recalcitrant to one or many medications are frequently reported. Concomitant disease, intolerance to a class of medications, and the patient's response to prior therapies can help guide a practitioner in choosing the optimal treatment of pyoderma gangrenosum.