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11 Articles in Volume 10, Issue #7
Selecting an Antidepressant for Pain Patients
Use of Opioids in Pain Patients with Psychiatric Disorders
Osteopathic Medicine Approach to Pain Management
Cannabis as Medicine
Pain Management in Patients with Pyoderma Gangrenosum
Occipito-Atlanto (C0-C1) Joints as a Source of Spinal Pain
Treat the Pain First—Worry about Psyche Problems Later
Traditional Chinese Medicine for Fibromyalgia
TMJ Condylar Pain From Parapharyngeal Space Tumor
Contraindications for Use of Therapeutic Laser
Platelet-Rich Plasma Prolotherapy for Low Back Pain Caused by Sacroiliac Joint Laxity

Pain Management in Patients with Pyoderma Gangrenosum

Pyoderma gangrenosum (PG) is an uncommon ulcerative cutaneous condition of uncertain etiology. Pyoderma gangrenosum was first described in 1930 and is associated with systemic diseases in at least 50% of patients who are affected. The diagnosis is usually made by excluding other causes of similar-appearing cutaneous ulcerations—including infection, malignancy, vasculitis, collagen vascular diseases, diabetes, and trauma1.

Typical findings include central necrosis and ulceration of the epidermis and dermis surrounded by an intense acute inflammatory cell infiltrate, with a more peripheral mixed to chronic inflammatory cell infiltrate. PG can have a variety of clinical presentations. The classic presentation begins with small tender papules or pustules that evolve into painful ulcers with characteristic violaceous undermined edges.1 PG most commonly occurs in adults aged 40 to 60 years and typically presents on the lower extremities and trunk.2 Associated symptoms include fever, malaise, myalgia and arthralgia. PG is often a diagnosis of exclusion since laboratory and histopathological findings are variable and nonspecific.1

Of the approximately 50% of patients with PG having an associated disease, the most common is inflammatory bowel disease—both Crohn’s and ulcerative colitis. Between 1.5% and 5% of patients with inflammatory bowel disease develop PG. The two diseases may flare together or run an independent course. Surgical removal of the diseased intestine may lead to complete remission of PG, or lesions may persist or first appear after removal of the affected bowel.2

Treatment Strategies

There is currently no gold standard of treatment for PG. Choice of therapy will depend on multiple factors including size and depth of the lesion, the rapidity of lesion growth, appearance of new lesions, the associated disease (eg, inflammatory bowel disease, arthritis), and the general medical status of the patient. The patient’s level of pain and signs of inflammation (particularly the elevation and redness of the lesion border) help guide response to treatment.3 Systemic corticosteroids—considered by most to be the drugs of choice for the treatment of PG resistant to topical therapy—are particularly effective in treating the acute, rapidly progressive form of the disease. It is not entirely clear whether the beneficial effects of corticosteroids are exerted through an immunosuppressive, anti-inflammatory, or other mechanism.4

Choice of treatment generally depends on disease severity as well as on the presence of associated disease. For early or mild lesions, topical therapy may be sufficient. This includes wet compresses, hydrophilic occlusive dressings, antimicrobial agents and topical corticosteroids. For more severe disease or for PG resistant to topical therapy, oral corticosteroids have been the mainstay of therapy.1

Hyperbaric oxygen therapy has been shown to effectively treat PG ulcers and reduce pain associated with the disease in several case studies. Hyperbaric oxygen therapy is thought to benefit PG by elevating oxygen tension in the ulcers—either through the greater arterial oxygen tension supplied to the deep capillary beds or through the direct local delivery of oxygen to the wound surface. Hyperbaric oxygen therapy demonstrates augmentation of every wound healing stage after coagulation. A very early benefit of hyperbaric oxygen therapy is the cessation of pain noted in multiple patients. The increased comfort not only improves the patients’ quality of life but also increases the rate of patient compliance with this therapy.5 The main benefit of hyperbaric oxygen therapy is the rapid relief of pain, although drawbacks include its expense and lack of easy availability.4

Aggressive surgical debridement is contraindicated because of possible exacerbation of PG by the pathergic response, the phenomenon in which ulcerations may occur after trauma or injury to the skin. However, split-skin grafts and cultured keratinocyte autografting have been demonstrated to be effective if performed while the pathergic response is minimized by prolonged courses of immunosuppressants. Therapy decisions depend on an assessment of the degree of active inflammation as opposed to simple wound healing requirements in refractory ulcers.1

Once a system for monitoring the lesions is in place, a decision regarding wound dressing must be made. Moisture-retentive dressings appear to be superior to desiccative gauzes in that they provide better pain control, induce collagen production, facilitate autolytic debridement and promote angiogenesis.3

Deep ulcerations—extending into the dermis, subcutaneous tissue, and fascia where nerve endings are abundant—result in stabbing, debilitating pain and present challenges for treatment.

Pain Management

Patients with PG almost universally experience debilitating pain, sometimes described as “stabbing” in quality—especially during change of wound coverage. The pain can become so severe that amputation has been implemented when systemic therapy is ineffective.3 The source of the pain is multifactorial, but much of it can be attributed to the inflammatory process of PG in the dermis and the resultant deep ulcer. Repeated manipulation of the wound, inherent with regular dressing changes, is a source of continued discomfort for the patient. Just as it is important to quantify the size and progression of lesions, it is equally important to regularly monitor and document the patient’s level of pain as a marker of treatment efficacy.3

PG ulcerations are deep and extend into the dermis, subcutaneous tissue, and fascia where nerve endings are abundant. Even if full-thickness lesions destroy nerve endings, pain may occur due to the disruption of nerve endings at wound edges or underlying tissue, especially if the lesions are infected. Wound manipulation, due to dressing changes or movement of the affected area, may cause pressure stimulation of proprioceptive receptors in underlying tissue such as muscle, fascia, or tendons. As PG lesions begin to heal and peripheral nerves regenerate, the developing nerve tissue becomes hypersensitive to manipulative stimuli, such as wound care and treatments with topical agents.6

It is recommended that sufficient pain medication be prescribed according to World Health Organization guidelines (e.g., stage I: paracetamol, metamizol, or nonsteroidal anti-inflammatory drugs; stage II: one medication from stage I and tramadol, codeine, dihydrocodeine, or tilidin; stage III: one medication from stage I and morphine, hydromorphone, oxycodone, methadone, buprenorphine, or fentanyl).7 Furthermore, new JCAHO standards calling for initial pain assessment with regular reassessment apply to ambulatory care, behavioral health care, hospitals, home care, long-term care, and health care networks.

Recent research suggests that opioid receptors on peripheral nerve terminals may play an important role in the modulation of pain. It has been long known that opioid analgesics relieve pain through their action on the central nervous system. More recently, research has suggested that they also may produce effective analgesia through action at peripheral sites. That is, opioids may successfully modulate the experience of pain by binding to opioid receptors on sensory nerve terminals located at the periphery. Theoretically, it should be possible to apply extremely small doses of opioids to wounds while achieving significant analgesia with little or no systemic absorption. As a result, patients may achieve superior analgesia, have fewer systemic medications to take (thus increasing treatment adherence), and reduce or eliminate the risk of comorbidity related to constipation, sedation, cognitive slowing, and nausea.8

Case Reports

Twillman et al,8 out of the University of Kansas, reported a consecutive series of cases treated with morphine-infused IntraSite gel (MIG). Nine individuals received the treatment. Eight of the patients were successfully treated, with seven reporting a significant decrease in pain. The ninth individual reported a lesser degree of pain relief. One patient in the study, a 36-year-old white female with a history of Crohn’s disease and chronic ulcers due to PG, had skin grafted from her right hip and buttock to her right arm for a wound that would not heal. She presented to the ER because of pain at the graft site. She had been noncompliant with home health care because of the pain associated with dressing changes and was taking oxycodone/acetaminophen for pain management with little relief. On the seventh day of admission, following a week of poorly controlled pain in which the patient refused dressing changes on two of the days, MIG 0.1% w/w concentration (ap-proximately 1 mg morphine/1 ml IntraSite gel) was recommended BID at dressing changes. After the first application, the patient reported that the pain relief was tremendous. The next day the patient began eating well and her requests for oral analgesics decreased. She began sleeping better and no longer refused dressing changes. On the thirteenth day, she was discharged with MIG to apply topically to the wounds twice a day. Moreover, despite long-standing use of significant doses of systemic opioids, the application of no more than 5 mg of morphine to these painful skin lesions produced up to 12 hours of analgesia.8

In a case report concerning a 15-year-old female with PG of the breast, Havlik et al9 proposed a treatment plan for management of the disease in areas in which healing by secondary intention could be expected to lead to significant physical disfigurement. The plan was based on adequate immunosuppression, the use of allograft skin to assess the adequacy of the wound bed for grafting, and subsequent definitive wound closure with allograft. This led to prompt dramatic improvement in pain, and the graft was uniformly adherent and was revascularized.9

In 2008, a group of physicians in France evaluated, through a randomized cross-over trial, the analgesic efficacy of a nitrous oxide-oxygen mixture vs. morphine during painful bedsore and ulcer care in adult and elderly patients. They explained that the drugs currently used for analgesia often provide insufficient relief and there is no standardized analgesic method for use during the care of adults and the elderly. The usual practice is to administer a short-acting opioid analgesic, such as morphine. They further conveyed that the nitrous oxide-oxygen mixture used leads to conscious sedation; analgesia without anesthesia. The absorption and elimination by the pulmonary route are very quick and results in a very rapid clinical effect. They concluded that analgesia was significantly better with the nitrous oxide-oxygen mixture than with morphine chlorhydrate. Moreover, the tolerability of the nitrous oxide-oxygen mixture was acceptable and there were no more adverse events with nitrous oxide-oxygen mixture than with the morphine chlorhydrate.10

Conclusion

Pyoderma gangrenosum is a rare and often painful skin disease that can be unpredictable in its response to treatment. There is currently no gold standard of treatment or published algorithm for choice of therapy. The majority of data comes from case studies that lack a standard protocol—not only for treatment administration but also for the objective assessment of lesion response to a specific therapy.3 Although pain management is often overlooked in these patients, it is an important aspect of treatment and of the patient’s quality of life. Since there have not been many trials conducted specifically regarding pain management in patients with PG, additional studies in patients with ulcers of any form are warranted.

Last updated on: December 20, 2011
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