Pyoderma Gangrenosum

Dr. Weyrich's Naturopathic Functional Medicine Notebook

Overview

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: [Dermnet2009 ; Dermis2009 ; Dermnetnz2009 ; Dermatlas2009].

Etiology

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

The differential diagnosis of PG may be broken down into six disease categories as follows [Wolllina2007]:
  1. Vascular occulusive or venous disease (biopsy) [Weenig2002]
  2. Vasculitis (biopsy) [Weenig2002].
  3. Cancer/Malignancy (biopsy) [Weenig2002].
  4. Infectious disease (biopsy, culture).
  5. Exogenous tissue injury (biopsy) [Weenig2002].
  6. Drug reactions (history, biopsy) [Weenig2002].
    • Propylthiouracil [Wolllina2007].
    • Pegfilgastrim (granulocyte-stimulating factor) [Wolllina2007].
    • Gefinib (inhibitor of epidermal growth factor receptor) [Wolllina2007].
  7. Other/Uncategorized
    • Hypersensitivity Angiitis (Zeek) [Dermis2009]
    • Sweet disease [Dermnetnz2009]
    • a href='http://www.dermis.net/dermisroot/en/27149/diagnose.htm'>Chancriform Pyoderma [Dermis2009]
    • < href='http://www.dermis.net/dermisroot/en/25885/diagnose.htm'>Ulcus Cruris Mixtum [Dermis2009]
    • Allergy, Type III Reaction [Dermis2009]
    • Antiphopholipide-Antibody Syndrome [Dermis2009]

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:

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].

Sequelae

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

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

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

ICD9-CodeDescriptionComments
686.01  

References

Unless specifically noted above, references used in the construction of this web page include the following:

[FDM] Lecture notes from Functional Medicine University.

[SCNM] Lecture notes from Southwest College of Naturopathic Medicine.

[UT] Lecture notes from the University of Tennessee graduate programs in Chemistry and Biochemistry.

[Adachi1988] Adachi Y, Kindzelskii AL, Cookingham G, et al. Aberrant neutrophil trafficking and metabolic oscillations in severe pyoderma gangrenosum. J. Invest. Dermatol. 1998;111:259-268. Cited by [Weenig2002].

[Dermatlas2009] DermAtlas Online Dermatology Image Library. Web page http://dermatlas.med.jhmi.edu/derm/result.cfm?Diagnosis=47670916 accessed December 3, 2009.

[Dermis2009] DermIS - Pyoderma Gangrenosum. Web page http://www.dermis.net/dermisroot/en/25427/diagnose.htm accessed December 3, 2009.

[Dermnet2009] Pyoderma Gangrenosum Pictures. Web page http://www.dermnet.com/Pyoderma-Gangrenosum/ accessed December 3, 2009.

[Dermnetnz2009] Pyoderma Gangrenosum\Pyoderma gangrenosum - DermNet NZ. Web page http://www.dermnetnz.info/reactions/pyoderma-gangrenosum.html accessed December 3, 2009.

[eMedicine2009] Pyoderma Gangrenosum - eMedicine Dermatology. Web page ' http://emedicine.medscape.com/article/1123821-overview accessed December 3, 2009.

[Habif2004] Thomas P. Habif. Clinical Dermatology: A Color Guide to Diagnosis and Therapy, 4th Edition. Mosby (2004), pg 653.

[Hurwitz1993] RM Hurwitz & JH Haseman. The evolution of pyoderma gangrenosum: a clinicopathologic correlation. Am. J. Dermatopathol. 25:28 (1993). Cited by [Habif2004].

[Lindor1997] Lindor NM, Arsenault TM, Solomon H, Seidman CE, McEvoy MT. A new autosomal dominant disorder of pyogenic sterile arthritis, pyoderma gangrenosum, and acne: PAPA syndrome. Mayo Clin Proc 1997;72:611-615. Cited by [Weenig2002].

[Mayo2009] Pyoderma Gangrenosum - Diagnosis and Treatment Options at Mayo Clinic. Web page http://www.mayoclinic.org/pyoderma-gangrenosum/ accessed December 3, 2009.

[Merck2009] Pyoderma Gangrenosum: Hypersensitivity and Inflammatory Disorders - Merck Manual Professional. Web page http://www.merck.com/mmpe/sec10/ch117/ch117h.html accessed December 3, 2009.

[Nasr2000] I Nasr. Topical tacrolimus in dermatology. Clin. Exp. Dermatol. 25(3):250 (2000).

[Oka2000] Oka M, Berking C, Nesbit M, et al. Interleukin-8 overexpression is present in pyoderma gangrenosum ulcers and leads to ulcer formation in human skin xenografts. Lab Invest 2000;80:595-604. Cited by [Weenig2002].

[Weenig2002] Roger H. Weenig, Mark D.P. Davis, Patrick R. Dahl, & W.P. Daniel Su. Skin Ulcers Misdiagnosed as Pyoderma Gangrenosum. N. Engl. J. Med. 347:1412 (2002). Web site http://content.nejm.org/cgi/content/full/347/18/1412 accessed December 3, 2009.

[Wikipedia2009] Pyoderma gangrenosum. Web page http://en.wikipedia.org/wiki/Pyoderma_gangrenosum accessed December 3, 2009.

[Wolllina2002] U. Wolllina. Clinical management of pyoderma gangrenosum. Am. J. Clin. Dermatol. 3(3):149 (2002). Cited by [Habif2004].

[Wolllina2007] U. Wolllina. Pyoderma gangrenosum – a review. Orphanet Journal of Rare Diseases 2007, 2:19 doi:10.1186/1750-1172-2-19.

[Yeon2000] Yeon HB, Lindor NM, Seidman JG, Seidman CE. Pyogenic arthritis, pyoderma gangrenosum, and acne syndrome maps to chromosome 15q. Am J Hum Genet 2000;66:1443-1448. Cited by [Weenig2002].

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