Etiology of Pyoderma Gangrenosum
Etiology of pyoderma gangrenosum is unknown, but it can be associated with various systemic illnesses, including inflammatory bowel disease Overview of Inflammatory Bowel Disease Inflammatory bowel disease (IBD), which includes Crohn disease and ulcerative colitis, is a relapsing and remitting condition characterized by chronic inflammation at various sites in the gastrointestinal... read more , rheumatoid arthritis Rheumatoid Arthritis (RA) Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that primarily involves the joints. RA causes damage mediated by cytokines, chemokines, and metalloproteases. Characteristically... read more , cancers, and hematologic disorders (eg, monoclonal gammopathy of undetermined significance Monoclonal Gammopathy of Undetermined Significance (MGUS) Monoclonal gammopathy of undetermined significance (MGUS) is the production of M-protein by noncancerous plasma cells in the absence of other manifestations typical of multiple myeloma. (See... read more , myelodysplastic syndrome Myelodysplastic Syndrome (MDS) The myelodysplastic syndrome (MDS) is group of disorders typified by peripheral cytopenia, dysplastic hematopoietic progenitors, a hypercellular or hypocellular bone marrow, and a high risk... read more , polycythemia vera Polycythemia Vera Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by an increase in morphologically normal red cells (its hallmark), but also white cells and platelets. Ten to 30%... read more ). It is thought to be mediated by an abnormal immune response. Most patients are age 25 to 55. It can manifest in various subtypes.
Pathophysiology of Pyoderma Gangrenosum
Pathophysiology of pyoderma gangrenosum is poorly understood but may involve problems with neutrophil chemotaxis. Interleukin-8 is overexpressed in lesions. Ulcerations of pyoderma gangrenosum occur after trauma or injury to the skin in about 30% of patients; this process is termed pathergy.
Symptoms and Signs of Pyoderma Gangrenosum
Most often, pyoderma gangrenosum begins as an inflamed erythematous papule, pustule, or nodule. The lesion, which may resemble a furuncle or an arthropod bite at this stage, then ulcerates and expands rapidly, developing a swollen necrotic base and a raised dusky to violaceous border. An undermined border (ie, loss of underlying support tissue at the border) is common, if not pathognomonic. Systemic symptoms such as fever and malaise are common. The ulcers can coalesce to form larger ulcers, often with cribriform or sieve-like scarring.
Symptoms and signs can vary with the subtype.
Ulcerative (classic) subtype
In this most common subtype, ulcers form as described above, most commonly on the lower extremities or trunk, particularly the buttocks and perineum.
Bullous (atypical) subtype
This less common subtype often develops in patients with hematologic disorders. Lesions usually begin as bullae that erode, becoming superficial ulcers. The arms and face are most often involved.
This subtype tends to develop during exacerbations of inflammatory bowel disease. Painful pustules develop, surrounded by erythema. Arthralgias are common.
Vegetative (superficial granulomatous pyoderma) subtype
In this subtype, a single, indolent, mildly painful plaque or superficial ulcer develops, most often on the head or neck. The border is not undermined and the base is not necrotic.
Pyoderma gangrenosum can also develop at other sites, such as around a stoma in patients who have inflammatory bowel disease (peristomal pyoderma gangrenosum), on the genitals (genital pyoderma gangrenosum), or in sites other than the skin, such as the bones, cornea, central nervous system, heart, intestine, liver, lungs, or muscle (extracutaneous pyoderma gangrenosum).
Diagnosis of Pyoderma Gangrenosum
Diagnosis of pyoderma gangrenosum is clinical and is a diagnosis of exclusion after other causes of ulceration have been ruled out. Expansion of ulceration after surgical debridement strongly suggests pyoderma gangrenosum. Biopsies of lesions are not often diagnostic but may be supportive; 40% of biopsies from a leading edge show vasculitis with neutrophils and fibrin in superficial vessels.
Patients who have bullous (atypical) pyoderma gangrenosum should be monitored with periodic clinical assessment and complete blood count for development of a hematologic disorder.
Treatment of Pyoderma Gangrenosum
Tumor necrosis factor (TNF)-alpha inhibitors
Sometimes other anti-inflammatory drugs or immunosuppressants
Avoidance of surgical debridement
Wound healing can be promoted with moisture-retaining occlusive dressings for less exudative plaques and absorptive dressings for highly exudative plaques. Biologic and other specialized dressings may be needed in refractory cases. Wet-to-dry dressings should be avoided. Topical therapy with high-potency corticosteroids or tacrolimus can help with superficial and early lesions.
For more severe manifestations, prednisone 60 to 80 mg orally once a day is a common first-line therapy. TNF-alpha inhibitors (eg, infliximab, adalimumab, etanercept) are effective, particularly in patients who have inflammatory bowel disease Overview of Inflammatory Bowel Disease Inflammatory bowel disease (IBD), which includes Crohn disease and ulcerative colitis, is a relapsing and remitting condition characterized by chronic inflammation at various sites in the gastrointestinal... read more . Cyclosporine 3 mg/kg orally once a day is also quite effective, particularly in rapidly progressive disease. Dapsone, azathioprine, cyclophosphamide, methotrexate, clofazimine, thalidomide, and mycophenolate mofetil have also been used successfully. Antimicrobials such as minocycline have also been used for vegetative (superficial) pyoderma gangrenosum.
Surgical treatments are avoided because of the risk of wound extension (1 Treatment reference Pyoderma gangrenosum is a chronic, neutrophilic, progressive skin necrosis of unknown etiology often associated with systemic illness and sometimes skin injury. Diagnosis is clinical. Treatment... read more ).
Pyoderma gangrenosum is often associated with a systemic disorder and is probably immune-mediated.
There are several subtypes; the ulcerative subtype (ie, necrotic base and raised violaceous border with undermined edge on a lower extremity, buttock, or perineum) is most common.
Diagnose pyoderma gangrenosum clinically.
Optimize wound care and avoid surgical debridement.
Use potent topical corticosteroids or tacrolimus to treat early lesions and use systemic corticosteroids, tumor necrosis factor (TNF)-alpha inhibitors, or other anti-inflammatories or immunosuppressants to treat more severe manifestations.