When A Non-Healing Wound Has A Dermatologic Origin

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Author(s): 
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.

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Eli Regevsays: February 3, 2014 at 1:07 pm

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

Reply to this comment »
William D. Fishcosays: March 2, 2014 at 12:39 pm

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.

References

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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