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Pyoderma gangrenosum (PG) is one of the several rare diseases that are classified under the broader cluster of neutrophilic dermatoses. XOMA's pilot study is designed to enroll up to eight patients who are experiencing acute inflammatory PG.

Pyoderma gangrenosum is a rare disease, occurring in approximately one person per 100,000, which causes inflammation and ulceration of the skin. Its incidence is usually associated with systemic diseases in approximately 50 percent of patients.

Pyoderma gangrenosum (PG) is a rare noninfectious neutrophilic dermatosis. Clinically it starts with sterile pustules that rapidly progress and turn into painful ulcers of variable depth and size with undermined violaceous borders. The legs are most commonly affected but other parts of the skin and mucous membranes may also be involved. Course can be mild or malignant, chronic or relapsing with remarkable morbidity. In many cases PG is associated with an underlying disease, most commonly inflammatory bowel disease, rheumatic or haematological disease and malignancy. Diagnosis of PG is based on history of an underlying disease, typical clinical presentation, histopathology, and exclusion of other diseases that would lead to a similar appearance. The peak of incidence occurs between the ages of 20 to 50 years with women being more often affected than men. Aetiology has not been clearly determined yet.

The treatment of PG is a challenge. Randomized, double-blinded prospective multicenter trials for PG are not available. The best documented treatments are systemic corticosteroids and ciclosporin A. Combinations of steroids with cytotoxic drugs are used in resistant cases. The combination of steroids with sulfa drugs or immunosuppressants has been used as steroid-sparing modalities. Anti-tumor necrosis alpha therapy in Crohn's disease showed a rapid response of PG. Skin transplants and the application of bioengineered skin is useful in selected cases as a complement to the immunosuppressive treatment. Topical therapy with modern wound dressings is useful to minimize pain and the risk of secondary infections. Despite recent advances in therapy, the prognosis of PG remains unpredictable.

In larger series, about 50% of patients show an underlying disorder. Ulcerative colitis is found in 10–15% of cases. Another associated disease is Crohn's regional enteritis with a frequency close to that of ulcerative colitis [2,21,22]. On the other hand, less than 3% of patients with Crohn's disease or ulcerative colitis develop PG [23,24]. Hepatitis C, seronegative rheumatoid arthritis, spondylitis, and a broad spectrum of lymphoproliferative disorders including monoclonal gammopathies, leukaemia, lymphoma, and myelodysplastic syndrome have been described in association with PG [2,4,25,26].

The PG-ulcers associated with arthritis seem to have a poorer prognosis than others. In a study covering 2 years 78.9% of PG-ulcers in general healed versus only 23.4% in arthritis-associated PG [27]. In such cases PAPA syndrome has to be considered [28]. PG involvement of the hands shows a higher percentage of lymphoproliferative than chronic inflammatory bowel disease [29].

PG is a typical clinical presentation of the PAPA syndrome also known as familial recurrent arthritis [28]. The autosomal dominant inherited disease is characterized by nonaxial destructive arthritis, severe cystic acne and PC. PAPA syndrome is caused by mutations in the PSTPIP1 gene on chromosome 15 involved in regulation of inflammatory response [30].

PG can arise as a consequence of drug therapies. Recent examples of drug-induced PG include compounds such as propylthiouracil [31], pegfilgastrim – a granulocyte-stimulating factor [32], and gefinib – an inhibitor of epidermal growth factor receptor [33].

Etiology and pathogenesis
PG was initially thought to be caused by bacterial infection in the immunocompromised host [1]. Fulbright et al. [20] hypothesized that PG results from an aberrant immune response to yet unidentified factors. Depositions of proteins in skin vessels in PG lesions have suggested an Arthus-like reaction [34]. Since inflammatory bowel disease is the most common underlying disorder, cross-reacting antigens in the bowel and the skin could be responsible for secondary cutaneous manifestation [2].

Cellular analysis in PG demonstrated aberrant integrin oscillations on neutrophils and aberrant neutrophil tracking of patients with PG [35,36]. Pathways to protect the epidermis from neutrophil infiltration seem to be insufficient in PG resulting in tissue necrosis.

http://www.ojrd.com/content/2/1/19