eMedicine Specialties > Dermatology > Reactive & Inflammatory Dermatoses

Pyoderma Gangrenosum

J Mark Jackson, MD, Assistant Clinical Professor, Department of Internal Medicine, Division of Dermatology, University of Louisville
Jeffrey P Callen, MD, Professor of Medicine, Chief, Division of Dermatology, University of Louisville School of Medicine

Updated: Oct 30, 2008

Introduction

Background

Pyoderma gangrenosum (PG) is an uncommon ulcerative cutaneous condition of uncertain etiology. Pyoderma gangrenosum was first described in 1930. It is associated with systemic diseases in at least 50% of patients who are affected. The diagnosis is made by excluding other causes of similar appearing cutaneous ulcerations, including infection, malignancy, vasculitis, collagen vascular diseases, diabetes, and trauma. Ulcerations of pyoderma gangrenosum may occur after trauma or injury to the skin in 30% of patients; this process is termed pathergy.

The 2 primary variants of pyoderma gangrenosum are the classic ulcerative form, usually observed on the legs, and a more superficial variant known as atypical pyoderma gangrenosum that tends to occur on the hands. Patients with pyoderma gangrenosum may have involvement of other organ systems that manifests as sterile neutrophilic abscesses. Culture-negative pulmonary infiltrates are the most common extracutaneous manifestation.¹ Other organs systems that may be involved include the heart, the central nervous system, the GI tract, the eyes,^2,3 the liver, the spleen, bones, and lymph nodes. The prognosis of pyoderma gangrenosum is generally good; however, recurrences may occur and residual scarring is common. Therapy of pyoderma gangrenosum involves the use of anti-inflammatory agents, such as corticosteroids, and immunosuppressive agents.

Pathophysiology

The pathophysiology of pyoderma gangrenosum is poorly understood, but dysregulation of the immune system, specifically altered neutrophil chemotaxis, is believed to be involved.

Frequency

United States

Pyoderma gangrenosum occurs in about 1 person per 100,000 people each year.

Mortality/Morbidity

Death from pyoderma gangrenosum is rare, but it may occur due to an associated disease or as the result of therapy. Pain is a usual complaint of patients and may require narcotics. Pathergy, or the development of pyoderma gangrenosum – like lesions at the site of skin trauma, may create problems with wound healing, especially after surgical procedures.

Race

No racial predilection is apparent.

Sex

Pyoderma gangrenosum affects both sexes. A slight female predominance may exist.

Age

All ages may be affected, but pyoderma gangrenosum predominantly occurs in the fourth and fifth decades of life. Children may be affected, but they account for only 3-4% of the total number of cases. Pyoderma gangrenosum may affect children and adolescents. Nothing is clinically distinctive about these patients other than their age.⁴

Clinical

History

• Patients with pyoderma gangrenosum usually describe the initial lesion as a bite reaction, with a small, red papule or pustule changing into a larger ulcerative lesion. Often, patients give a history of a brown recluse or other spider bite, but they have no evidence that a spider actually caused the initial event.
• Pain is the predominant historical complaint.
• Arthralgias and malaise may often be present.
• A complete history should be taken with special focus on the organ systems listed below to determine any underlying systemic disease. Systemic illnesses are seen in 50% of patients with pyoderma gangrenosum and may occur prior to, concurrently or following the diagnosis.
  • Commonly associated diseases include inflammatory bowel disease, either ulcerative colitis or regional enteritis/Crohn disease, and a polyarthritis that is usually symmetric and may be either seronegative or seropositive; and hematologic diseases/disorders, such as leukemia or preleukemic states, predominantly myelocytic in nature or monoclonal gammopathies (primarily immunoglobulin A [IgA]).
  • Less common associated diseases include other forms of arthritis, such as psoriatic arthritis, osteoarthritis, or spondyloarthropathy; hepatic diseases, including hepatitis and primary biliary cirrhosis; myelomas (IgA type predominantly); and immunologic diseases, such as lupus erythematosus and Sjögren syndrome.

Physical

• Two main variants of pyoderma gangrenosum exist: classic and atypical. Several other variants may exist.
  • Classic pyoderma gangrenosum is characterized by a deep ulceration with a violaceous border that overhangs the ulcer bed. These lesions of pyoderma gangrenosum most commonly occur on the legs, but they may occur anywhere on the body (see Media File 1).
  • Atypical pyoderma gangrenosum has a vesiculopustular "juicy" component. This is usually only at the border, is erosive or superficially ulcerated, and most often occurs on the dorsal surface of the hands, the extensor parts of the forearms, or the face (see Media File 2).
  • Classic pyoderma gangrenosum may occur around stoma sites; this type is known as peristomal pyoderma gangrenosum. This form is often mistaken for a wound infection or irritation from the appliance (see Media File 3).
  • Pyoderma gangrenosum may occur on the genitalia; this form is termed vulvar or penile pyoderma gangrenosum. This variant must be differentiated from sexually transmitted diseases.⁵
  • An intraoral form of the disease, known as pyostomatitis vegetans, has been reported and occurs primarily in patients with inflammatory bowel disease.
  • Extracutaneous neutrophilic disease may be evident upon ocular examination and has also been reported in the lungs, liver, and bones.

Causes

No specific causes of pyoderma gangrenosum have been identified, but trauma to the skin in patients with pyoderma gangrenosum may induce new lesions. This is called pathergy.

Differential Diagnoses

Other Problems to Be Considered

Antiphospholipid antibody syndrome
Anthrax
Arterial insufficiency
Acute febrile neutrophilic dermatosis (Sweet syndrome)
Blastomycosis
Factitial disease
Traumatic ulceration
Tuberculosis gumma

Workup

Laboratory Studies

• Routine blood work to evaluate for an underlying systemic illness in persons with pyoderma gangrenosum (PG) includes a CBC count; a comprehensive chemistry profile, including a liver function test; and a urinalysis.
• A hepatitis profile should be performed to rule out hepatitis.
• Serum and/or urine protein electrophoresis, peripheral smear, and bone marrow aspiration should be performed if indicated to evaluate for hematologic malignancies.
• Other serum studies include a Venereal Disease Research Laboratory (VDRL) test, antineutrophil cytoplasmic antibody test, partial thromboplastin time test, and antiphospholipid antibody test to rule out Wegener granulomatosis, vasculitis, and antiphospholipid antibody syndrome. Serum protein electrophoresis is helpful to determine if a monoclonal gammopathy is present. If present, it is often of the IgA subtype.
• Cultures of the ulcer/erosion for bacteria, fungi, atypical mycobacteria, and viruses are needed. The exact cultures to be performed depend on the individual situation. The cultures should be held for 6 weeks because some of the potential agents may take that long to grow in culture.

Imaging Studies

• Chest radiography may be performed.
• Colonoscopy or other tests to exclude associated inflammatory bowel disease or ulcerative colitis may be useful in patients with symptoms. The evaluation of patients with pyoderma gangrenosum and no symptoms of bowel disease is still uncertain.
• Angiography or Doppler studies may be performed in patients suspected of having arterial or venous insufficiency.

Other Tests

• The following tests may be performed:
  • Flexible sigmoidoscopy or colonoscopy in selected patients
  • Bone marrow aspiration or biopsy in selected patients
  • Culture of the ulceration and possibly of the biopsy material

Procedures

• A skin biopsy should be performed.

Histologic Findings

The histopathologic findings in pyoderma gangrenosum are not specific. However, a biopsy is suggested in almost all instances because it is useful in the exclusion of other diseases. Microscopic features include massive neutrophilic infiltration, hemorrhage, and necrosis of the overlying epidermis. Histologically, this finding may simulate an abscess or cellulitis. Neutrophils are often around and within the vessel walls, but the full picture of vasculitis is generally absent. In early disease, a mixed cell infiltrate may be present. Late in the process, granulation tissue may be present, but granuloma formation is generally believed to be incompatible with the diagnosis of pyoderma gangrenosum.

Treatment

Medical Care

No specific therapy is uniformly effective for patients with pyoderma gangrenosum (PG). In patients with an associated underlying disease, the effective therapy of the associated condition may be associated with a control of the cutaneous process as well.

• Topical therapies include local wound care and dressings, superpotent topical corticosteroids,⁶ cromolyn sodium 2% solution, nitrogen mustard, and 5-aminosalicylic acid. The new topical immune modifiers tacrolimus and pimecrolimus may have some benefit in certain patients.
• Systemic therapies include corticosteroids, cyclosporine,^7,8,9 mycophenolate mofetil,¹⁰ azathioprine,¹¹ dapsone, tacrolimus, cyclophosphamide, chlorambucil,¹² thalidomide, tumor necrosis factor-alpha (TNF-alpha) inhibitors, and nicotine.
• Intravenous therapies include pulsed methylprednisolone,¹³ pulsed cyclophosphamide,¹⁴ infliximab,^15,16,17 and intravenous immune globulin.
• Other therapy includes hyperbaric oxygen.

Surgical Care

• Surgery should be avoided, if possible, because of the pathergic phenomenon that may occur with surgical manipulation or grafting, resulting in wound enlargement. In some patients, grafting has resulted in the development of pyoderma gangrenosum at the harvest site. In the cases in which surgery is required, the best plan, if possible, is to have the patient on therapy in order to prevent pathergy.
• Some patients with ulcerative colitis have responded to total colectomy; however, in others, the disease is peristomal and occurs following bowel resection.

Consultations

• Depending on the findings in the patient, other specialists may be consulted. Working with the primary care physician is wise for all patients.
  • Gastroenterologist or GI surgeon, proctorectal surgeon, or general surgeon in patients with inflammatory bowel disease
  • Rheumatologist for patients with arthritis
  • Ophthalmologist if ocular disease is present
  • Hematologist/oncologist when preleukemia, leukemia, monoclonal gammopathy, or other neoplasm is associated
  • Plastic surgeon or general surgeon when debridement or grafting is deemed necessary

Diet

No special dietary needs are required.

Activity

Patients should maintain their range of motion and perform all activities that they are able to tolerate.

Medication

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Glucocorticoids

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. In addition, these agents modify the body's immune response to diverse stimuli.

Prednisone (Deltasone, Sterapred, Orasone)

DOC; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Methylprednisolone IV may be used in some patients.

Dosing

Adult

0.5-2 mg/kg/d PO; taper as condition improves; single morning dose is safer for long-term use, but divided doses have more anti-inflammatory effect

Pediatric

4-5 mg/m²/d PO; alternatively, 0.05-2 mg/kg PO divided bid/qid; taper over 2 wk as symptoms resolve

Interactions

Coadministration with estrogens may decrease clearance; when used with digoxin, digitalis toxicity secondary to hypokalemia may increase; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics

Contraindications

Documented hypersensitivity; viral, fungal, connective tissue, or tubercular skin infections; peptic ulcer disease; hepatic dysfunction; GI disease

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Closely monitor blood sugar levels in patients with diabetes; patients with potentially long course of therapy should have a PPD placed and read prior to therapy or within first 2 wk of therapy; routinely check blood pressure in patients with high blood pressure; caution in history of tuberculosis, osteoporosis, peptic ulcer disease, and psychological problems; aseptic necrosis may occur

Immunosuppressives

These agents have immunomodulatory effects.

Cyclosporine (Sandimmune, Neoral)

Demonstrated to be helpful in a variety of skin disorders. Most effective steroid-sparing agent. Also used as primary therapy in some patients.

Dosing

Adult

3-5 mg/kg/d PO/IV, sometimes initial loading therapy at 10-12 mg/kg/d is useful for first 3-5 d

Pediatric

Administer as in adults

Interactions

Carbamazepine, phenytoin, isoniazid, rifampin, and phenobarbital may decrease concentrations; azithromycin, itraconazole, nicardipine, ketoconazole, fluconazole, erythromycin, verapamil, grapefruit juice, diltiazem, aminoglycosides, acyclovir, amphotericin B, and clarithromycin may increase toxicity; acute renal failure, rhabdomyolysis, myositis, and myalgias increase when taken concurrently with lovastatin; high-dose methylprednisolone may increase risk of seizures when used concomitantly; concomitant use of ACE inhibitors and cyclosporine may decrease renal function

Contraindications

Documented hypersensitivity; uncontrolled hypertension or malignancies; do not administer concomitantly with PUVA or UV-B radiation in psoriasis because it may increase risk of cancer

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Main adverse effects include, anaphylaxis (with IV use), hypertension, hepatotoxicity, nephrotoxicity, malignancy (lymphoproliferative type), gingival hyperplasia, hypomagnesemia, hyperkalemia, and hypertrichosis; check blood pressure at least monthly; monitor renal function by measuring serum creatinine levels at least monthly; reserve IV use only for patients who cannot take PO; infectious disease, pancreatitis, and paresthesia may occur; associated with arteriopathy and Raynaud phenomenon; vasoconstriction leading to mesenteric ischemia may occur
Optic disc edema, including papilledema, with possible visual impairment secondary to intracranial hypertension, has been reported in transplant patients (product information for Sandimmune oral soft gelatin cap, oral solution, injection for infusion, 2005)

Azathioprine (Imuran)

Another drug that may be effective as a steroid-sparing agent. Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. May decrease proliferation of immune cells, which results in lower autoimmune activity.

Dosing

Adult

1-2 mg/kg/d (50-200 mg) PO

Pediatric

Administer as in adults

Interactions

Toxicity increases with allopurinol; concurrent use with ACE inhibitors may induce severe leukopenia; may increase levels of methotrexate metabolites and decrease effects of anticoagulants, neuromuscular blockers, and cyclosporine; live virus vaccines may have a greater systemic effect; coadministration with other immunosuppressive agents may increase bone marrow suppression; increases in uric acid levels reported when administered concomitantly with tacrolimus

Contraindications

Documented hypersensitivity; low levels of serum TPMT; history of treatment with alkylating agents

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Reduce dose in patients with low TPMT levels; bone marrow suppression may occur; nausea and vomiting are commonly noted; may increase risk of lymphoproliferative disorders in patients treated with long-term therapy; cancer, hepatotoxicity, infectious disease, leukopenia, megaloblastic anemia, pancreatitis, and thrombocytopenia may occur

Mycophenolate (CellCept)

Inhibits purine synthesis and proliferation of human lymphocytes. May be used as steroid-sparing agent or as primary agent in patients that do not respond to first-line agents.

Dosing

Adult

1-2 g/d PO

Pediatric

Not established

Interactions

May elevate acyclovir and ganciclovir levels; antacids and cholestyramine decreases absorption, reducing levels (do not administer together); probenecid may increase levels; salicylates may increase toxicity

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Risk of lymphoma may increase in patients on long-term therapy; slightly higher rate of viral and bacterial infections is present while on therapy; GI disturbance and dose-related hematologic effects, including leukopenia, may occur; CellCept brand of oral susp contains aspartame, which is metabolized to phenylalanine (care should be taken if administered to patients with phenylketonuria)

Cyclophosphamide (Cytoxan)

Alkylating agent that depresses B-cell and T-cell function. Chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.

Dosing

Adult

1-2 mg/kg/d PO

Pediatric

Administer as in adults

Interactions

Allopurinol may increase risk of bleeding or infection and enhance myelosuppressive effects; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones; chloramphenicol may increase half-life of cyclophosphamide while decreasing metabolite concentrations; may increase effect of anticoagulants; coadministration with high doses of phenobarbital may increase rate of metabolism and leukopenic activity; thiazide diuretics may prolong cyclophosphamide-induced leukopenia and neuromuscular blockade by inhibiting cholinesterase activity

Contraindications

Documented hypersensitivity; severely depressed bone marrow function; pregnancy

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

GI upset and oral stomatitis may occur in up to 70% of patients; hemorrhagic cystitis possible, particularly if drug is given without hydration; azoospermia or anovulation may occur after prolonged therapy; alopecia and hyperpigmentation of nails and skin may occur; perform routine CBC counts and urinalysis; cardiomyopathy, infectious disease, interstitial pneumonia, Stevens-Johnson syndrome, and toxic epidermal necrolysis may occur; possibility of increased toxicity in adrenalectomized patients; be aware of possibility of cross-sensitivity with other alkylating agents
Patients with moderate renal failure (glomerular filtration rate [GFR] 10-50 mL/min) should receive 75% of normal dose given at usual dosage interval and patients with severe renal failure (GFR <10 mL/min) receive 50% of normal dose given at usual dosage interval (no dosage reduction required for mild renal failure (GFR >50 mL/min), although dosing interval should be increased to q12h; dosage may also be adjusted by increasing dosing interval as follows: GFR >10 mL/min, increase interval to >12 h; GFR <10 mL/min, increase interval to q18-24h; data show that patients with hepatic failure develop more toxicity with cyclophosphamide as opposed to patients with normal hepatic function

Chlorambucil (Leukeran)

Alkylates and cross-links strands of DNA, inhibiting DNA replication and RNA transcription. Used as primary or steroid-sparing agent.

Dosing

Adult

4-6 mg/d PO

Pediatric

Not established

Interactions

Additive effect with other immunosuppressive agents

Contraindications

Documented hypersensitivity; previous resistance to this medication; pregnancy

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Decreases immune response to live viral vaccines; lymphopenia and neutropenia may occur (monitor CBC counts regularly); metabolism is decreased in patients with impaired hepatic function; hepatotoxicity; infertility, leukemia, myelosuppression, pancytopenia, peripheral neuropathy, pneumonitis, and secondary malignant neoplastic disease may occur; avoid administration of live vaccines to immunocompromised persons; do not administer full dosage within 4 wk of completion of full course of radiation therapy or chemotherapy (risk of bone marrow damage)

Tacrolimus (Prograf)

Suppresses humoral immunity (T-lymphocyte) activity.

Dosing

Adult

0.05 mg/kg/d IV or 0.15-0.30 mg/kg/d PO divided bid

Pediatric

0.1 mg/kg/d IV or 0.3 mg/kg/d PO

Interactions

Diltiazem, nicardipine, clotrimazole, verapamil, erythromycin, ketoconazole, itraconazole, fluconazole, bromocriptine, grapefruit juice, metoclopramide, methylprednisolone, danazol, cyclosporine, cimetidine, and clarithromycin may increase levels; coadministration of rifabutin, rifampin, phenobarbital, phenytoin, and carbamazepine may reduce levels

Contraindications

Documented hypersensitivity; hypersensitivity to tacrolimus products or hydrogenated castor oil (if IV formulation used)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Do not administer simultaneously with cyclosporine (tonic clonic seizures may occur); cardiomegaly, diabetes mellitus, hyperglycemia, hyperkalemia, hypertension, hypomagnesemia, prolonged QT interval, and malignant lymphoma may occur

Blood products

These agents are used to improve the clinical and immunologic aspects of the disease. They may decrease autoantibody production and increase solubilization and removal of immune complexes.

Immune globulins intravenous (Sandoglobulin, Gammagard, Gamimune)

Neutralize circulating myelin antibodies through anti-idiotypic antibodies; down-regulates proinflammatory cytokines, including INF-gamma; blocks Fc receptors on macrophages; suppresses inducer T and B cells and augments suppressor T cells; blocks complement cascade; and promotes remyelination. May increase CSF IgG (10%).

Dosing

Adult

2 g/kg IV over 2-5 d

Pediatric

Administer as in adults

Interactions

Increases toxicity of live virus vaccine (MMR) (do not administer within 3 mo of vaccine)

Contraindications

Documented hypersensitivity; IgA deficiency; anti-IgE/IgG antibodies

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Check serum IgA before IVIG (use an IgA-depleted product, eg, Gammagard S/D); infusions may increase serum viscosity and thromboembolic events; infusions may increase risk of migraine attacks, aseptic meningitis (10%), urticaria, pruritus, or petechiae (2-30 d postinfusion); increases risk of renal tubular necrosis in elderly patients and in patients with diabetes, volume depletion, and preexisting kidney disease; laboratory result changes associated with infusions include elevated antiviral or antibacterial antibody titers for 1 mo, 6-fold increase in ESR for 2-3 wk, and apparent hyponatremia

Immunomodulators

These agents have effects on the activity of the immune system.

Thalidomide (Thalomid)

Immunomodulatory agent that may suppress excessive production of TNF-alpha and may down-regulate selected cell-surface adhesion molecules involved in leukocyte migration. In patients <50 kg (110 lb), start at low end of dose regimen.

Dosing

Adult

50-300 mg/d PO qd with water, preferably hs and at least 1 h pc; 50-200 mg usually yields results

Pediatric

Not established

Interactions

May increase sedation of alcohol, barbiturates, chlorpromazine, and reserpine; because of teratogenic effects, women must use 2 additional methods of contraception or abstain from intercourse

Contraindications

Documented hypersensitivity; sexually active males not using latex condom (risk to fetus from semen of patients taking thalidomide unknown), women of childbearing potential not using 2 forms of contraception

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

May cause sedation and an increase in vasoocclusive events; perform pregnancy test within 24-h period prior to initiating therapy (qwk during first month, followed by qmo tests in women with regular menstrual cycles or q2wk with irregular menstrual cycles); bradycardia may occur; use protective measures (eg, sunscreens, protective clothing) against exposure to sunlight or UV light (eg, tanning beds); prescribing physician must register with the "System for Thalomid Education and Prescribing Safety " (STEPS) program established by manufacturer; aplastic anemia, pancytopenia, anemia, leukopenia, neutropenia, thrombocytopenia, cancer, tuberculosis recurrence, and optic neuritis may occur

Etanercept (Enbrel)

Soluble p75 TNF receptor fusion protein (sTNFR-Ig). Inhibits TNF binding to cell surface receptors, thereby, decreasing inflammatory and immune responses.

Dosing

Adult

50-100 mg SC qwk

Pediatric

0.4 mg/kg SC qwk

Interactions

None reported

Contraindications

Documented hypersensitivity, sepsis, concurrent live vaccination, active granulomatous infection, heart failure, patients with demyelinating diseases

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Serious infections may develop and therapy should be discontinued if they occur; possible adverse effects include injection site pain, redness and swelling at injection site, and headaches; rare cases of lupuslike symptoms and heart failure reported (discontinue treatment if symptoms develop)

Infliximab (Remicade)

Chimeric IgG1k monoclonal antibody that neutralizes cytokine TNF-alpha and inhibits its binding to TNF-alpha receptor. Reduces infiltration of inflammatory cells and TNF-alpha production in inflamed areas

Dosing

Adult

3-5 mg/kg IV infusion over 2-4 h
Initial induction dose then repeat at week 2, then week 6, then q6-8wk
May increase to 10 mg/kg IV q8wk for patients who respond, then lose their response; discontinue treatment in those who do not response by week 14

Pediatric

Administer as in adults

Interactions

Crohn disease patients (adolescent and young adult) on concomitant treatment with azathioprine or 6-mercaptopurine have developed fatal hepatosplenic T-cell lymphomas; concomitant immunosuppressive therapy (risk of serious infection, including sepsis and pneumonia [some fatal cases]); concomitant use of infliximab and anakinra not recommended (increased risk for serious infection)

Contraindications

Documented hypersensitivity, congestive heart failure, active granulomatous disease, patients with history of tuberculosis or positive PPD test and are untreated, sepsis

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

TNF-alpha modulates cellular immune responses; anti-TNF therapies (eg, infliximab) may adversely affect normal immune responses and allow development of superinfections; more cases of lymphoma were observed in TNF-alpha blockers compared with control groups; may increase risk of reactivation of tuberculosis in patients with particular granulomatous infections; has been associated with lupus erythematosus; acute coronary syndrome, congestive heart failure, demyelinating disease of CNS or seizure disorder, hepatotoxicity, leukopenia, neutropenia, thrombocytopenia, and pancytopenia may occur; serum sickness – like reactions may occur upon reinstitution of infliximab therapy after extended period without therapy

Adalimumab (Humira)

TNF-alpha inhibitor. Fully human inhibitor of TNF-alpha administered by SC injection.

Dosing

Adult

40 mg SC qwk or every other wk

Pediatric

Not established

Interactions

Concomitant use of adalimumab and anakinra not recommended (serious infections have occurred with concomitant use); risk for severe infection with concurrent immunosuppressive therapy (live vaccines should not be given concurrently)

Contraindications

Documented hypersensitivity; rheumatoid arthritis, ulcerative colitis, psoriatic arthritis

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Aplastic anemia, cancer, demyelinating disease of CNS, erythrocytosis, formation of autoantibodies; systemic lupus – like syndrome, infectious disease, leukopenia, malignant lymphoma, pancytopenia, tuberculosis recurrence, paresthesia, and subdural hematoma may occur

Clofazimine (Lamprene)

Inhibits mycobacterial growth, binds preferentially to mycobacterial DNA. Has antimicrobial properties, but mechanism of action is unknown.

Dosing

Adult

200-400 mg/d PO qd

Pediatric

1 mg/kg/d PO qd

Interactions

Dapsone may inhibit anti-inflammatory activity; coadministration with antacids can result in reduced clofazimine bioavailability; may increase phenytoin clearance

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Severe abdominal symptoms may require exploratory laparotomies; caution in patients with GI problems (eg, abdominal pain, diarrhea); skin discoloration due to drug may result in depression or suicide; apply oil to skin for dryness and ichthyosis

Follow-up

Further Outpatient Care

• Patients with pyoderma gangrenosum (PG) should receive follow-up care on a regular basis to monitor the drug therapy and to measure the size of the lesion or lesions. Multiple methods of wound care are available.

Inpatient & Outpatient Medications

• Therapy with corticosteroids is often prescribed initially. Sometimes, an immunosuppressive agent is also initiated later or simultaneously, particularly in those patients for whom high-dose long-term therapy is anticipated. Some physicians select cyclosporine as the initial therapy. The TNF inhibitors are showing promise in the treatment of pyoderma gangrenosum.

Transfer

• Care of the patient with pyoderma gangrenosum is often referred from the general dermatologist to tertiary centers where such patients are seen more frequently.

Prognosis

• The prognosis of pyoderma gangrenosum is generally good; however, recurrences may occur, and residual scarring is common.
• Many patients with pyoderma gangrenosum improve with initial immunosuppressive therapy and require minimal care afterwards; however, many patients follow a refractory course and multiple therapies fail. These patients pose a difficult clinical problem that requires frequent follow-up and long-term care.
• Some patients demonstrate pathergy, and, in such instances, protection of the skin from trauma may prevent a recurrence.

Miscellaneous

Medicolegal Pitfalls

• Pyoderma gangrenosum is often misdiagnosed and multiple attempts at grafting often occur prior to the diagnosis being made. The breakdown at the harvest site is a clue to the diagnosis and is an indicator of pathergy often seen in active pyoderma gangrenosum patients.
• Pyoderma gangrenosum is a diagnosis of exclusion because no specific criteria have been determined to confirm the diagnosis. All other potential causes of similar lesions must be excluded prior to making the diagnosis.

Special Concerns

The Medscape Medical Malpractice and Legal Issues Resource Center may be of interest.

Multimedia

Media file 1: Classic or typical pyoderma gangrenosum. This patient did not have an associated disease, and the condition responded well to cyclosporine.

Media file 2: Atypical pyoderma gangrenosum.

Media file 3: Peristomal pyoderma gangrenosum.

References

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2. Ayyala RS, Armstrong S. Corneal melting and scleromalacia perforans in a patient with pyoderma gangrenosum and acute myeloid leukemia. Ophthalmic Surg Lasers. Apr 1998;29(4):328-31. [Medline].

3. Happle R, Schiffer HP, Kövary PM. Ocular involvement in pyoderma gangrenosum. Arch Dermatol. Nov 1977;113(11):1612. [Medline].

4. Graham JA, Hansen KK, Rabinowitz LG, Esterly NB. Pyoderma gangrenosum in infants and children. Pediatr Dermatol. Mar 1994;11(1):10-7. [Medline].

5. McCalmont CS, Leshin B, White WL, Greiss FC Jr, Jorizzo JL. Vulvar pyoderma gangrenosum. Int J Gynaecol Obstet. Jun 1991;35(2):175-8. [Medline].

6. Nybaek H, Olsen AG, Karlsmark T, Jemec GB. Topical therapy for peristomal pyoderma gangrenosum. J Cutan Med Surg. Jul-Aug 2004;8(4):220-3. [Medline].

7. Fedi MC, Quercetani R, Lotti T. Recalcitrant pyoderma gangrenosum responsive to cyclosporine. Int J Dermatol. Feb 1993;32(2):119. [Medline].

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Keywords

pyoderma gangrenosum, PG, classic PG, classic pyoderma gangrenosum, atypical PG, atypical pyoderma gangrenosum, pyostomatitis vegetans, vulvar pyoderma gangrenosum, penile pyoderma gangrenosum, peristomal pyoderma gangrenosum

Contributor Information and Disclosures

Author

J Mark Jackson, MD, Assistant Clinical Professor, Department of Internal Medicine, Division of Dermatology, University of Louisville
J Mark Jackson, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Kentucky Medical Association, and Texas Medical Association
Disclosure: Nothing to disclose.

Coauthor(s)

Jeffrey P Callen, MD, Professor of Medicine, Chief, Division of Dermatology, University of Louisville School of Medicine
Jeffrey P Callen, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and American College of Rheumatology
Disclosure: Amgen Honoraria Consulting; Abbott Honoraria Consulting; Electrical Optical Sciences Honoraria Consulting; Centocor Honoraria Consulting; Genetech Honoraria Consulting; Celgene Honoraria Consulting

Medical Editor

David P Fivenson, MD, Associate Director, St Joseph Mercy Hospital Dermatology Program, Ann Arbor, Michigan
David P Fivenson, MD is a member of the following medical societies: American Academy of Dermatology, Medical Dermatology Society, Michigan Dermatological Society, Michigan State Medical Society, Photomedicine Society, Society for Investigative Dermatology, and Wound Healing Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center
Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Warren R Heymann, MD, Head, Division of Dermatology, Professor, Department of Internal Medicine, University of Medicine and Dentistry of New Jersey
Warren R Heymann, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

CME Editor

Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania
Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology
Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds None; Genentech Consulting fee Consulting; Centocor Consulting fee Consulting; Centocor Grant/research funds None; Covance Consulting fee Consulting; Shire  Consulting

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

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