Pyoderma gangrenosum is a rare, inflammatory skin disease where painful

pustule A skin condition, also known as cutaneous condition, is any medical condition that affects the integumentary system—the organ system that encloses the body and includes skin, nails, and related muscle and glands. The major function of this s ...

s or nodules become

ulcer An ulcer is a discontinuity or break in a bodily membrane that impedes normal function of the affected organ. According to Robbins's pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caused by sloughing o ...

s that progressively grow. Pyoderma gangrenosum is not infectious. Treatments may include

corticosteroids Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invol ...

ciclosporin Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is a natural product. It is taken orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disease ...

infliximab Infliximab, a chimeric monoclonal antibody, sold under the brand name Remicade among others, is a medication used to treat a number of autoimmune diseases. This includes Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing spon ...

, or

canakinumab Canakinumab ( INN), sold under the brand name Ilaris, is a medication for the treatment of systemic juvenile idiopathic arthritis (SJIA) and active Still's disease, including adult-onset Still's disease (AOSD). It is a human monoclonal antibod ...

. The disease was identified in 1930. It affects approximately 1 person in 100,000 in the population. Though it can affect people of any age, it mostly affects people in their 40s and 50s.

Types

There are two main types of pyoderma gangrenosum: * the 'typical' ulcerative form, which occurs in the legs * an 'atypical' form that is more superficial and occurs in the hands and other parts of the body Other variations are: * Peristomal pyoderma gangrenosum comprises 15% of all cases of pyoderma *

Bullous A skin condition, also known as cutaneous condition, is any medical condition that affects the integumentary system—the organ system that encloses the body and includes skin, nails, and related muscle and glands. The major function of thi ...

pyoderma gangrenosum * Pustular pyoderma gangrenosum * Vegetative pyoderma gangrenosum

Presentation

Associations

The following are conditions commonly associated with pyoderma gangrenosum: * Inflammatory bowel disease: **

Ulcerative colitis Ulcerative colitis (UC) is a long-term condition that results in inflammation and ulcers of the colon and rectum. The primary symptoms of active disease are abdominal pain and diarrhea mixed with blood (hematochezia). Weight loss, fever, and ...

Crohn's disease Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea (which may be bloody if inflammation is severe), fever, abdominal distensi ...

* Arthritides: **

Rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are inv ...

Seronegative arthritis Spondyloarthropathy or spondyloarthrosis refers to any joint disease of the vertebral column. As such, it is a class or category of diseases rather than a single, specific entity. It differs from spondylopathy, which is a disease of the vertebr ...

* Hematological disease: **

Myelocytic leukemia Myeloid leukemia is a type of leukemia affecting myeloid tissue. Types include: * Acute myeloid leukemia * Chronic myelogenous leukemia * Acute megakaryoblastic leukemia * Blastic plasmacytoid dendritic cell neoplasm See also * Hematological mali ...

Hairy cell leukemia Hairy cell leukemia is an uncommon hematological malignancy characterized by an accumulation of abnormal B lymphocytes. It is usually classified as a subtype of chronic lymphocytic leukemia (CLL). Hairy cell leukemia makes up about 2% of all leu ...

Myelofibrosis Primary myelofibrosis (PMF) is a rare bone marrow blood cancer. It is classified by the World Health Organization (WHO) as a type of myeloproliferative neoplasm, a group of cancers in which there is growth of abnormal cells in the bone marrow. ...

** Myeloid metaplasia **

Monoclonal gammopathy Monoclonal gammopathy, also known as paraproteinemia, is the presence of excessive amounts of myeloma protein or monoclonal gamma globulin in the blood. It is usually due to an underlying immunoproliferative disorder or hematologic neoplasms, espec ...

* Autoinflammatory disease: ** Pyogenic sterile arthritis, and acne syndrome (

PAPA syndrome PAPA syndrome is an acronym for pyogenic arthritis, pyoderma gangrenosum and acne. It is a rare genetic disorder characterised by its effects on skin and joints. Signs and symptoms PAPA syndrome usually begins with arthritis at a young age, with t ...

)

Causes

Though the cause is not well understood, the disease is thought to be due to

immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...

dysfunction, and particularly improper functioning of

neutrophil Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying ...

s. In support of an immune cause, a variety of immune mediators such as interleukin (IL)-8,

IL-1β Interleukin-1 beta (IL-1β) also known as leukocytic pyrogen, leukocytic endogenous mediator, mononuclear cell factor, lymphocyte activating factor and other names, is a cytokine protein that in humans is encoded by the ''IL1B'' gene."Catabolin ...

, IL-6, interferon (IFN)-γ,

granulocyte colony-stimulating factor Granulocyte colony-stimulating factor (G-CSF or GCSF), also known as colony-stimulating factor 3 (CSF 3), is a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream. Functiona ...

tumor necrosis factor alpha Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homolo ...

, matrix metalloproteinase (MMP)-9,

MMP10 Stromelysin-2 also known as matrix metalloproteinase-10 (MMP-10) or transin-2 is an enzyme that in humans is encoded by the ''MMP10'' gene. Function Proteins of the matrix metalloproteinase ( MMP) family are involved in the breakdown of extrace ...

, and elafin have all been reported to be elevated in patients with pyoderma gangrenosum. Also in support of an immune cause is the finding that at least half of all pyoderma gangrenosum patients suffer from immune-mediated diseases. For instance,

ulcerative colitis Ulcerative colitis (UC) is a long-term condition that results in inflammation and ulcers of the colon and rectum. The primary symptoms of active disease are abdominal pain and diarrhea mixed with blood (hematochezia). Weight loss, fever, and ...

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are inv ...

, and

multiple myeloma Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibodies. Often, no symptoms are noticed initially. As it progresses, bone pain, ...

(MM) have all been associated with pyoderma gangrenosum. It can also be part of a syndromes such as

. One hallmark of pyoderma gangrenosum is

pathergy Pathergy is a skin condition in which a minor trauma such as a bump or bruise leads to the development of skin lesions or ulcers that may be resistant to healing. Pathergy can also lead to ulcerations at the site of surgical incisions. Pathergy is ...

, which is the appearance of new lesions at sites of trauma, including surgical wounds.

Diagnosis

Diagnosis of PG is challenging owing to its variable presentation, clinical overlap with other conditions, association with several systemic diseases, and absence of defining histopathologic or laboratory findings. Misdiagnosis and delayed diagnosis are common. It has been shown that up to 39% of patients who initially received a diagnosis of PG have an alternative diagnosis. In light of this, validated diagnostic criteria have recently been developed for ulcerative pyoderma gangrenosum.

Diagnostic criteria

In addition to a biopsy demonstrating a neutrophilic infiltrate, patients must have at least 4 minor criteria to meet diagnostic criteria. These criteria are based on histology, history, clinical examination and treatment. * Histology: Exclusion of infection (including histologically indicated stains and tissue cultures) * Pathergy (ulcer occurring at sites of trauma, with ulcer extending past area of trauma) * Personal history of inflammatory bowel disease or inflammatory arthritis * History of papule, pustule, or vesicle that rapidly ulcerated * Clinical examination (or photographic evidence) of peripheral erythema, undermining border, and tenderness at site of ulceration * Multiple ulcerations (at least 1 occurring on an anterior lower leg) * Cribriform or “wrinkled paper” scars at sites of healed ulcers * Decrease in ulcer size within 1 month of initiating immunosuppressive medications

Treatment

First-line therapy for disseminated or localized instances of pyoderma gangrenosum is systemic treatment with

and

. Topical application of clobetasol, mupirocin, and

gentamicin Gentamicin is an antibiotic used to treat several types of bacterial infections. This may include bone infections, endocarditis, pelvic inflammatory disease, meningitis, pneumonia, urinary tract infections, and sepsis among others. It is not ...

alternated with

tacrolimus Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After allogeneic organ transplant, the risk of organ rejection is moderate. To lower the risk of organ rejection, tacrolimus is given. The drug can also ...

can be effective. Pyoderma gangrenosum ulcers demonstrate

, that is, a worsening in response to minor trauma or surgical debridement. Significant care should be taken with dressing changes to prevent potentially rapid wound growth. Many patients respond differently to different types of treatment, for example some benefit from a moist environment, so treatment should be carefully evaluated at each stage. Papules that begin as small "spouts" can be treated with Dakin's solution to prevent infection and wound clusters also benefit from this disinfectant. Wet to dry applications of Dakins can defeat spread of interior infection. Heavy drainage can be offset with Coban dressings. Grafting is not recommended due to tissue necrosis. If ineffective, alternative therapeutic procedures include systemic treatment with corticosteroids and

mycophenolate mofetil Mycophenolic acid (MPA) is an immunosuppressant medication used to prevent rejection following organ transplantation and to treat autoimmune conditions such as Crohn's disease and lupus. Specifically it is used following kidney, heart, and liv ...

; mycophenolate mofetil and ciclosporin; tacrolimus;

thalidomide Thalidomide, sold under the brand names Contergan and Thalomid among others, is a medication used to treat a number of cancers (including multiple myeloma), graft-versus-host disease, and a number of skin conditions including complications o ...

;

; or plasmapheresis.

References

External links

{{Paraneoplastic syndromes Reactive neutrophilic cutaneous conditions Rare diseases Gangrene Necrosis