When A Non-Healing Wound Has A Dermatologic Origin

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. Reference 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.