When A Non-Healing Wound Has A Dermatologic Origin

William Fishco, DPM, FACFAS

A 60-year-old Hispanic female presented with the chief complaint of severe pain associated with a large wound on her left leg, which had been present for four years. She had received treatment at another local hospital prior to her admission to Maricopa Medical Center in Phoenix and the previous treatment recommended to her was a below-knee amputation. Her prior treatment while living in Mexico included application of topical antibiotics and a wet-to-dry dressing. She had never had any type of debridement of the wound.

   Her past medical history was remarkable for hypertension. She denied any psychiatric disorders. The patient had no history of illicit drug use or alcohol abuse, but had a past history of smoking. Her family history was unremarkable.

   The patient’s physical exam revealed a seemingly healthy looking woman consistent with her stated age. Her vitals on admission were blood pressure 95/55, pulse 98, respirations 20, temperature 38.2ºC and oxygen saturation of 92 percent. She had strong, palpable pulses without any neurologic deficits.

   The dermatologic exam revealed a large, well-demarcated wound on the medial aspect of her leg. The wound encompassed the region from the tibialis anterior tendon on the lateral margin to the Achilles tendon posteriorly. Inferiorly, the wound started at the superior aspect of the heel and extended to the distal third junction of the lower leg. The wound had a mixed granular and fibrotic appearance with red and yellow tissue. There was no accompanying cellulitis. The leg was not particularly edematous.

   The complete workup on this patient included a complete blood count (CBC) with differential; chemistry panel; coagulation studies; tuberculosis and coccidioidomycosis screens; hepatitis B and C screen; thyroid-stimulating hormone levels; rheumatic panel including erythrocyte sedimentation rate (ESR), rheumatoid factor, and anti-nuclear antibodies; serum levels of immunoglobulins, anti-proteinase 3 antineutrophil cytoplasmic antibodies; perinuclear antineutrophil cytoplasmic antibodies; wound and blood cultures; X-rays of the leg; magnetic resonance imaging (MRI) of the leg; venous Doppler ultrasound of the leg; and biopsy of the wound. The biopsy included a 1 cm x 3 cm triangular tissue segment to include normal and abnormal tissue to the level including muscle.

   Pending results of the ordered tests, I initially placed her on empiric antibiotic coverage, which included vancomycin and piperacillin/tazobactam (Zosyn, Pfizer). She received narcotic analgesics for pain. I obtained podiatry, vascular and dermatology consults.

Key Questions To Consider

1. What are the main characteristics of this condition?
2. What is the most likely diagnosis?
3. What is your differential diagnosis?
4. How can one make a definitive diagnosis?
5. What is the treatment?

Answering The Key Diagnostic Questions

1. The patient had a large, well-demarcated wound on the medial aspect of her leg with a mixed granular and fibrotic appearance with red and yellow tissue.
2. Pyoderma gangrenosum
3. Venous stasis ulceration, vasculitis, ulceration due to arterial insufficiency, carcinomas, granulomatous diseases associated with vasculitis, pyoderma gangrenosum, anthrax or sporotrichosis
4. Biopsy and exclusion
5. Oral and topical corticosteroids, immunosuppressive agents, sulfa drugs and/or cytotoxic drugs

Keys To The Differential Diagnosis

The differential diagnosis for a chronic wound on the lower leg includes: venous stasis ulceration, vasculitis, ulceration due to arterial insufficiency, carcinomas, granulomatous diseases associated with vasculitis, pyoderma gangrenosum, and rare infectious diseases such as anthrax and sporotrichosis.

   Venous stasis ulcerations are the most common wounds that occur on the medial aspect of the lower leg due to the course of the great saphenous vein. Venous stasis ulcerations are typically shallow/superficial, have an irregular border, often look weepy and wet, and are usually not painful. There is typically concomitant edema on the leg. In addition to the ulceration, the skin color is usually discolored purple or brown, superficial varicosities may be visible, there is often hardening (induration) of soft tissues, and accompanying dry scaling skin may be visible (venous stasis dermatitis).

   One confirms the diagnosis with an ultrasound test to determine the degree of venous reflux. Treatment includes wound care and compression. Mechanical compression can occur with dressings, compression hosiery and/or lymphedema pumps. Surgical treatments may include endovenous laser treatment and/or skin grafting of the wound. Ultimately, one needs to address the swelling disorder or the risk of recurring ulcers is great.

   A group of granulomatous diseases that include vasculitis can cause skin ulcerations. These conditions include Wegener’s granulomatosis and Churg-Strauss syndrome.

   Wegener’s granulomatosis is also known as granulomatosis with polyangiitis. Patients with this syndrome typically have kidney and lung disease. The main serological marker is anti-proteinase 3 antineutrophil cytoplasmic antibodies. This marker can aid in the diagnosis of Crohn’s disease and inflammatory bowel disease.

   Churg-Strauss syndrome is also known as eosinophilic granulomatosis with polyangiitis. This is an autoimmune disorder in patients with atopy (allergic hypersensitivity). Symptoms include upper respiratory disorders including asthma and reactive airway disease. There may be history of hay fever, allergic rhinitis and sinusitis. Elevations of perinuclear anti-neutrophil cytoplasmic antibodies may be present in about 50 percent of the cases of Churg-Strauss syndrome.1 In a complete blood count with differential, the eosinophils will typically be 10 percent or higher whereas a normal differential of eosinophils should be between 1 and 4 percent.

   Non-melanoma carcinomas may cause chronic wounds that do not respond to wound care. A common non-melanoma carcinoma affecting the skin is squamous cell carcinoma. Carcinomas are skin cancers that are typically slow growing and affect sun-exposed areas. Sites of skin that have been burned, scarred or ulcerated for a long period of time are susceptible to cancerous changes. Less common non-melanoma skin cancers include Kaposi’s sarcoma, which is common in patients with HIV infection or in otherwise healthy elderly males from Mediterranean ancestry. Also, primary cutaneous lymphoma (mycosis fungoides), which is a low-grade lymphoma, can be associated with ulcerations and tumors. One can confirm these conditions through biopsy and histodiagnosis.

   Ulcerations of skin can occur from arterial insufficiency. Unlike venous stasis ulcers, arterial ulcers are painful and deeper. A classic arterial ulcer has a “punched out” appearance. Contrary to venous stasis wounds, these ulcers are more likely to be on the lateral side of the leg/ankle (or on the foot). The skin is usually cool to touch and other signs of peripheral arterial disease (such as loss of hair growth or pale color of skin surrounding the wound) are present. The skin may be thin, atrophic and shiny. Testing to rule out arterial insufficiency includes ankle-brachial index, Doppler studies and angiography.

   Infectious diseases can also be the cause of the wound. Sporotrichosis is a fungal infection caused by Sporothrix schenckii. The fungus is ubiquitous throughout the world and is present in the soil. The organism is most commonly introduced through the skin by a rose thorn prick. The classic infection includes suppurating nodules along a lymphatic channel. A less common presentation is pulmonary sporotrichosis that disseminates to organs including skin to cause lesions.

   Anthrax is caused by a bacterium called Bacillus anthracis. Humans can become infected with the spore-forming bacteria by close contact with farm animals that are infected. The bacterium typically enters the body through an open skin lesion. Active infection not only includes skin breakdown but there is typically nausea, vomiting, malaise, fever and sore throat.

What You Should Know About Pyoderma Gangrenosum

Pyoderma gangrenosum is a non-infectious neutrophilic dermatosis. Typically, the wounds start with vesicles, bullae and/or pustules. Later in the disease process, the skin breaks down to full-thickness ulcerations of skin with undermined violaceous borders.

   Ulcers associated with pyoderma gangrenosum are painful. Legs are the most common anatomic region associated with pyoderma gangrenosum but all skin including mucous membranes can be affected. In many cases, pyoderma gangrenosum may be associated with an underlying medical condition. These conditions include inflammatory bowel disease, rheumatologic disorders, hepatitis C, leukemia, lymphoma and drug-induced cases.

   One can make the diagnosis via biopsy and exclusion. There are no laboratory parameters to aid in the diagnosis. Histopathology is typically non-specific. Suppurative folliculitis and dense neutrophil infiltrates are typically visible. Treatment of pyoderma gangrenosum lesions is usually more medically oriented versus surgical. Debridement of a pyoderma gangrenosum wound can trigger pathergy and the wound can worsen. Medical treatment usually includes oral and topical corticosteroids, immunosuppressive agents, sulfa drugs and/or cytotoxic drugs.

   For review of the laboratory data from our patient, she had a white blood cell count of 7.2 with a normal differential. Her hemoglobin was 9.8 g/dL. All serology markers were negative. Her radiographs showed mild periosteal reaction of the leg, the MRI was negative for osteomyelitis and Doppler studies were negative for venous reflux or obstruction. The cultures of the wound and blood were negative. The biopsy of the wound revealed no vasculitis and various stages of ulceration and granulation tissue.

   Despite not having classic neutrophil infiltrates in the biopsy, I made the diagnosis of pyoderma gangrenosum by exclusion. The patient is currently undergoing medical treatment and has shown improvement over the past six months. Initially, she took methylprednisolone (Solu-Medrol, Pfizer) 1 g daily for three days and the wound showed immediate improvement. She is currently on a regimen of minocycline and dapsone. She is applying clobetasol (Temovate, GlaxoSmithKline) ointment and Adaptic (Systagenix) with a light dressing daily. Every other day, she is performing a bleach bath of the leg, which is composed of 1 tablespoon of bleach per gallon of water.

In Conclusion

Pyoderma gangrenosum can be a limb- and life-threatening dermatosis. The diagnosis occurs by biopsy and exclusion of other dermatologic conditions. If one suspects pyoderma gangrenosum, be cautious with any surgical debridement, which can make the ulcer worse. This difficult case’s diagnosis and management entailed a multidisciplinary approach including podiatry, internal medicine, vascular specialists and dermatology. Ultimately, the definitive diagnosis occurred with negative serological markers and biopsy that ruled out carcinoma and infection.

   Dr. Fishco is board-certified in foot surgery and reconstructive rearfoot and ankle surgery by the American Board of Podiatric Surgery. He is in private practice in Phoenix. Dr. Fishco is also a faculty member of the Podiatry Institute.


1. Savige J, Davies D, Falk RJ, et al. Antineutrophil cytoplasmic antibodies and associated diseases: A review of the clinical and laboratory features. Kidney International. 2000; 57(3):846–862.


Thank you presenting this interesting case for us. Pyoderma gangrenosum is a cutaneous manifestation of internal diseases as you mentioned and especially IBD.
In the following case, neither the skin biopsy or the clinical background support this diagnosis. What was the reaction to biopsies? Was there was any deterioration in wound condition due to this wound biopsies? Was there any pathergy sign?

What do you think? Is the disease causing this skin ulceration? Any way, the steroids she received are non significant and may be not enough if pyoderma gangrenosum is the correct diagnosis.

(The side effects of minocycline and Dapsone are small generally so they are acceptable even there is no definitive diagnosis._

I think topical treatment with "bleach" is unnecessary (I use it very rarely in my practice) and can be harmful, further retarding the healing of this wound. Modern dressings and especially silver dressing s(e.g.Acticoat-3, Smith and Nephew) can make a big difference in my hands.

I wonder what is the basic disease causing this ulceration?
if no deterioration occurred after skin biopsies and if there is no pathergy sign, I would consider skin grafting this wound or using a skin substitute

I will be happy to obtain further information about this patient.

Best regards,

Eli Regev, MD
Plastic Surgery
Wound management

Tel-Aviv, Israel

Thank you for your comments. I will try to respond/answer all of your questions and comments.

1. Skin biopsy/pathergy/clinical background. Histological biopsy will usually be non-specific and difficult to differentiate from other inflammatory diseases. However, its benefit is to rule out suspicion of malignancy. Biopsy is performed only if clinical suspicion of malignancy exists, due to the risk for pathergy. May also culture for fungal or mycobacterial infection prior to initiation of immunosuppressive treatment. Our patient did not have pathergy from the biopsy. However, pathergy occurs in 20-40% of those with the disease, leaving the other 60-80% without any pathergy. Systemic therapy: corticosteroids are the gold standard tx for PG. Methotrexate, cyclosporine and antibiotics can be complementary to therapy. IV immunoglobulin for intractable PG. However, this can be cost prohibitive and only used if all else fails. Infliximab can also be used.

2. Topical bleach treatments. The bleach baths were prescribed by the dermatology service and we have since discussed this with them and had them discontinued. We switched to Aquacel Ag (another silver dressing). The patient recently had serial debridements and application of Integra grafts.

3. What is the underlying disease? Certainly, we have so far ruled out any underlying malignancies. The diagnosis is essentially made by exclusion. Considering the clinical improvement with a reasonable algorithm for PG, we are confident with the diagnosis of PG without a clear underlying etiology.

Some final thoughts regarding PG. There are two variants of PG. There is the classic ulcerative form, which usually occurs on lower limbs (and trunk, vulva, penis, head, neck and breast). There is also the atypical form, which occurs on the upper limbs and consists of three subtypes. These subtypes are as follows:
a) Pustular. This is most often associated with patients who have coexisting inflammatory bowel disease. Usually, this PG resolves in line w/ resolution of the active mucosal disease of the gut. However, only 50% of the pustular PG have an underlying systemic disease.
b) Bullous. This is associated with myeloid malignancies (i.e. leukemia or myelofibrosis). This presents as painful, superficial blistering with eroded dermatosis. The ulcer can be deep with violaceous erythema in the surrounding area. Treatment of the underlying malignancy can result in simultaneous resolution of the PG.
c) Vegetative. This is confined to the skin with no associated systemic disease. It presents as raised, verrucous, well-defined plaques that are studded with small pustules. Ulcerations occur on the trunk without a violaceous border, pustular base or undermining.

Thank you again for your comments and suggestions. As you know, PG can be a challenging to diagnose and treat.


Callen JP, Jackson JM. Pyoderma Gangrenosum: An Update. Rheumatic Disease Clinics of North America. 33(2007) 787-802.

Ratnagobal S, Sinha S. Pyoderma Gangrenosum: Guideline For Wound Practioners. Journal of Wound Care 22(2), February 2013.

Brooklyn T, Dunnil G, Probert C. Diagnosis and Treatment of Pyoderma Gangrenosum. Clinical Review. BMJ 333, July 22, 2006.

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