Dr. Weyrich's Naturopathic Functional Medicine Notebook is a collection of information on topics of interest to Dr. Weyrich that may be of interest to the world wide audience. Due to limitations of time, not all information that Dr. Weyrich knows or would like to further research is published here. Dr. Weyrich welcomes financial contributions to support specific research topics, as well as copies of non-free access journal articles for him to review on a topic. Constructive criticism is also welcome.


Overview of Pyoderma Gangrenosum

Pyoderma gangrenosum (PG) is a rare (incidence in USA is 1 in 100,000) ulcerating skin disease that may affect any part of the body, but is most common below the knees with preference for the pretibial area. The ulcerative lesions are painful, exhibit sudden onset and rapid progression, and consist of a deep necrotic region up to 4 inches in diameter surrounded by a purple to red pustular base. A common pathognomonic feature is for the margin to be undermined [Wolllina2007], [Habif2004], [ eMedicine2009], [Dermnetnz2009], [ Merck2009], [Wikipedia2009].

The lesions usually show an infiltration of neutrophils suggestive of an immune response to a local infectious agent, but no causative agent has been identified [Habif2004], [eMedicine2009]. In some cases neutrophils are not present [Dermnetnz2009].

PG was first described by dermatologists at Mayo Clinic in 1930 [Mayo2009].

In about half of all cases, PG is associated with some other underlying inflammatory condition or malignancy such as:

However no cause-effect linkage has been established for any of the above, and the remaining half of PG cases have no other apparent associations. Note however, that some of the above disorders are also in the differential diagnoses listed below.

PG lesions can also occur in other organ systems, such as:

Culture-negative pulmonary infiltrates are the most common extracutaneous manifestation [eMedicine2009].

Pathergy is common in cases of PG - new lesions develop at sites of trauma (similar to the Koebner phenomenon seen in psoriasis) [Merck2009].

Links to photos of pyoderma gangrenosum: [Go to Dermnet2009 Dermnet2009 ; Go to Dermis2009 Dermis2009 ; Go to Dermnetnz2009 Dermnetnz2009 ; Go to Dermatlas2009 Dermatlas2009].

Complimentary and alternative treatments for pyoderma gangrenosum that are considered below include:

  • Low Dose Naltrexone

Etiology of Pyoderma Gangrenosum

Since no infectious agent has been isolated from the ulcerating lesions, many researchers speculate that pyoderma gangrenosum is some sort of autoimmune process.

Differential Diagnosis of Pyoderma Gangrenosum

The differential diagnosis of PG may be broken down into six disease categories as follows [Wolllina2007]:
  • Collagen vascular diseases (polyarteritis nodosa [Weenig2002], dermatomyocitis, rheumatoid arthritis, SLE) [Mayo2009]
  • Vasculitic rheumatoid arthritis [Wolllina2007]
  • Antiphospholipid-antibody syndrome [Wolllina2007], [Weenig2002]
  • Adamantiades-Behcet's disease [Wolllina2007]
  • Cryoglobulinemic vasculitis [Weenig2002]
  • Cancer/Malignancy (biopsy) [Weenig2002].
  • Infectious disease (biopsy, culture).
  • Deep fungal infection (most common) [Weenig2002]
  • Deep [tropical] mycoses like sporotrichosis [Wolllina2007]
  • Gangrene [Wolllina2007], [Dermis2009]
  • Deep viral herpetic infections [Wolllina2007]
  • Exogenous tissue injury (biopsy) [Weenig2002].
  • Insect or spider bites [Wolllina2007]
  • Drug reactions (history, biopsy) [Weenig2002].
  • Other/Uncategorized

  • Treatment of Pyoderma Gangrenosum

    Please see conventional, complimentary and alternative medical treatments for important background information regarding the different types of medical treatments discussed below.

    Conventional Treatment

    The standard allopathic treatment is similar to other autoimmune diseases. The first line treatment consists of immune suppression using topical, locally injected, or systemic corticosteroids.

    Small lesions may be treated with:

    Larger lesions require more aggressive immunosuppression. Oral corticosteroids (e.g. prednisone/DELTASONE 60 to 80 mg po once/day) may be required for several months in high dose [Dermnetnz2009], [Merck2009], supplemented if necessary by drugs such as the following:

    • Cyclosporine/NEORAL/SANDIMMUNE 3 mg/kg/day po (immunosuppressive) [Dermnetnz2009], [Mayo2009], [ Wolllina2002; Habif2004], [Merck2009]
    • Azathioprine [Mayo2009], [ Wolllina2002], [Habif2004]
    • Methotrexate (cytotoxic) [Dermnetnz2009]
    • Cyclophosphamide (cytotoxic) [Dermnetnz2009], [ Wolllina2002], [Habif2004]
    • Chlorambucil (cytotoxic) [Wolllina2002], [Habif2004]
    • Mycophenolate mofetil /CELLCEPT [Dermnetnz2009], [ Habif2004], [Merck2009]
    • Infliximab/REMICADE [Merck2009].
    • Clofazimine (immunomodulator) [Mayo2009], [Merck2009].
    • An interesting approach to treatment that appears to be very effective is the intravenous administration of large doses of immunoglobulins [Habif2004]. This decreases the body's production of antibodies and helps remove excess antibodies which provoke immune reactions [Mayo2009].
    • Tumor necrosis factor (TNF-alpha) inhibitors used to treat comorbid Crohn's disease showed a rapid response of PG [Wolllina2007].

    Surgical procedures are rarely used because they can aggravate the condition [Mayo2009].

    Antibiotics such as flucloxacillin are often prescribed as a precaution to prevent secondary infections, or in case the surrounding tissues exhibit cellulitis [Mayo2009], [Dermnetnz2009].

    In some cases, protection of the skin from trauma may prevent a recurrence [Mayo2009].

    PG is a painful disease that may require the use of narcotics [eMedicine2009].

    Naturopathic, Complimentary and Alternative Treatments

    Low Dose Naltrexone (LDN)

    According to the Low Dose Naltrexone home page [LDN], LDN has been seen to benefit many different autoimmune diseases. Although Dr. Weyrich is not aware of any reports of treating pyoderma gangrenosum using LDN, Dr. Weyrich speculates that pyoderma gangrenosum may also respond to LDN.

    Dr. Weyrich has been trained in the use of Low Dose Naltrexone (LDN). However, Dr. Weyrich has not treated any cases of pyoderma gangrenosum with LDN.

    Please see What is Low Dose Naltrexone? for more information.


    Sequelae of Pyoderma Gangrenosum

    Pyoderma gangrenosum often appears at the site of some minor physical trauma or folliculitis. This may lead to abscess formation or leukocytoplasmic vasculitis. The lesions then evolve to suppurative granulamatous dermatitis.

    The prognosis of pyoderma gangrenosum is generally good. PG may regress spontaneously or with treatment, leaving prominent fibroplasia (scarring). [Hurwitz1993], [Mayo2009], [ Habif2004], [eMedicine2009].

    Perhaps the greatest danger with PG is misdiagnosis of infectious or malignant diseases as PG, and consequent inappropriate treatment for PG which may delay proper treatment or even be counterproductive. A review of the charts of 240 patients with a diagnosis of pyoderma gangrenosum found that, out of those misdiagnosed as PG and treated accordingly, "five patients died from overwhelming infection, and four died from progression of disease" [Weenig2002].

    The disease reoccurs in about 30% of all cases [Habif2004].


    Pathophysiology of Pyoderma Gangrenosum

    The mechanism of pyoderma gangrenosum is poorly understood, but dysregulation of the immune system is believed to be involved [eMedicine2009], [Weenig2002]. Specifically, neutrophil dysfunction (defects in chemotaxis or hyperreactivity) [Adachi1988], overexpression of interleukin-8 [Oka2000] and overexpression of interleukin-16 [Lindor1997], [Yeon2000].

    Hypotheses regarding Pyoderma Gangrenosum

    A possible causal linkage between pyoderma gangrenosum and inflammatory bowel disease is suggested by the observation made by Mayo Clinic that some PG patients with ulcerative colitis respond to total colectomy (removal of the colon) [Mayo2009].


    ICD-9 Codes related to Pyoderma Gangrenosum

    ICD9-CodeDescriptionComments
    686.01  

    References for Pyoderma Gangrenosum