Addressing the Pain: Relieving the Pain of Stage 4 Graft-versus-Host Disease of the Skin: The Role of Soft Silicone Dressings as Adjuncts to Medical Management

    Allogeneic (nonidentical) hematopoietic stem cell transplant (HSCT) is a potentially curative treatment option for certain hematologic malignancies. The procedure requires the patient to receive a conditioning regimen consisting of moderate to high doses of chemotherapy and/or radiation therapy.

This therapy destroys the patient’s stem cells and suppresses his/her immune system. Donor stem cells, infused into the patient, travel to the bone marrow and begin to produce new blood cells, essentially building a new (transplanted) donor immune system. A graft-versus-leukemia (GVL) or graft-versus-disease (GVD) response can have a desired direct antitumor effect in some allogeneic recipients.¹ Unfortunately, severe clinical complications are often encountered.

    The primary, persistent limitation to the success of HSCT is graft-versus-host disease (GVHD), which affects 40% to 80% of allogeneic transplant recipients depending on the degree of major histocompatibility mismatch between recipient and donor.¹ This common, potentially fatal inflammatory autoimmune process results from the attack of the recipient’s tissues by donor T-cells and natural killer (NK) cells.^{1, 2} Graft-versus-host disease that occurs in the first 100 days post transplant is referred to as acute GVHD (aGVHD), initially observed as early as 7 days but more often appearing around 21 days post stem cell transplant (see Figure 1). Graft-versus-host disease that occurs after 100 days post transplant is referred to as chronic.² Clinical staging and grading of GVHD can be made by evaluating the performance level of the patient and assessing the skin, liver, and gastrointestinal tract, the most commonly affected target organs.

     Skin is typically the first site of aGVHD, clinically presenting as a nonspecific maculopapular rash that can be pruritic or painful. It may present on the palms and soles, and if untreated can quickly spread to form a confluent erythema (erythroderma) on the cheeks, neck, and trunk, further progressing to bullae and skin sloughing (desquamation).^1,3

    The traditionally accepted clinical stages for skin findings are as follows:

Stage 1 — maculopapular rash <25% of body surface
Stage 2 — maculopapular rash 25% to 50% of body surface
Stage 3 — rash on >50% of skin (per revised grading system)
Stage 4 — bullous formation.¹

    The “rule of nines” for burn patients is used to determine the extent of the rash.¹

Case Study

    This case study illustrates the agony patients with grade 4 skin involvement of aGVHD experience and how tandem effective medical and nursing management can achieve patient comfort. The contribution of appropriate dressing selection to the management of the severe pain universally observed in and reported by patients with grade 4 aGVHD of the skin is emphasized with the hope that other oncology practitioners might find it a helpful adjunct in relieving pain, managing fluid loss, preventing infection, and promoting wound healing.

    Mr. L was a 64-year-old man who received a reduced-conditioning, sibling-matched allogeneic peripheral stem cell transplant for the treatment of recurrent Hodgkin’s disease. He received GVHD prophylaxis consisting of ultraviolet light wavelength B and cyclosporine. His past medial history was significant for diabetes mellitus type II, essential hypertension, and hypercholesteremia. During his hospitalization for transplant, he developed an Escherichia coli bacteremia and a bilateral maxillary infectious sinusitis. He also developed nonoliguric acute renal failure secondary to cyclosporine, interstitial nephritis from antibiotics, a cefepime rash, and corticosteroid-induced hyperglycemia. He was initially discharged 19 days post transplant. He returned 2 days later when he developed a new fever and fluconazole was added to his regimen. His fever also was considered to be secondary to the possible onset of aGVHD. He subsequently developed a worsening rash and diarrhea, confirmed as aGVHD of the skin and gut by 40 days post transplant. He received additional GVHD treatment including cyclosporine and methylprednisolone IV along with topical steroid cream and lotion, fluid, and electrolyte replacement.⁴

    Despite treatment, within 4 days the skin GVHD progressed to stage 4 as demonstrated by generalized erythroderma and the formation of bullae, most extensive on the legs and scrotal surface. Remicade (Centocor, Inc., Malvern, Pa.) was added to the aGVHD management regimen⁴ and morphine was administered for pain management with modest relief per self report of decreased intensity from 10/10 to 6/10.

    As the GVHD symptoms persisted, Mr. L began to express a diminishing will to live, largely related to the pain of the extensive skin GVHD. A Clinical Nurse Specialist (CNS) (the author) was consulted on day 7, post appearance of the bullous lesions, when nursing staff efforts to manage the pain and exudate were not making progress toward established goals. Mr. L’s first words to the CNS were, “I am in excruciating pain. Please help me. I’ll try anything.” He held his body rigidly and barely moved even his lips as he spoke. His wife sat tearfully at his bedside. They explained that the lesions were so painful he was unable to even shift his weight in bed, let alone ambulate or get up to the bedside commode, despite now being on a continuous morphine drip at 8 mg/hr. He said he felt “like a monster,” allowing no visitors but his wife, fearing his appearance would terrify people, especially his grandsons. It was quickly apparent that he was suffering both emotionally and physically, that his quality of life was extremely compromised, and that his wife was suffering as well.

    Physical exam revealed epidermal destruction of both legs, with the desquamation extending from his knees to the dorsum of his feet. The lower extremities were extremely edematous. Serous exudate volume was so great that his legs showed evidence of maceration. Desquamation of the scrotum, buttocks, and posterior thighs also was noted. His palms and soles were soft, tender, and demonstrated several bullae. Clearly, Mr. L was exhibiting severe Grade 4 GVHD of the skin.

    The goals related to altered skin integrity were to: 1) bring the GVHD under control, 2) decrease pain, 3) prevent maceration of surrounding skin by managing exudate, 4) stabilize/hasten healing of the desquamated areas, and 5) prevent infection.

    The medical interventions previously mentioned included strategies from all three lines of treatment identified by the author’s institution’s HSCT protocols. Supportive care, consisting of antimicrobial prophylaxis for pneumocystis, fungal, and cytomegalovirus infections also was provided.⁴

    Nursing interventions initially consisted of application of topical preparations to intact skin — desonide lotion to the face and triamcinolone cream to the torso. Silver sulfadiazine cream and Bacitracin ointment were applied to blisters and areas of epidermal erosion and dressed with petrolatum gauze and roller gauze wrap to absorb the serous exudate. Removal of the petrolatum gauze during daily dressing changes was exquisitely painful and the large amount of exudate was requiring frequent changes of the gauze wraps. On the initial CNS exam, Mr. L’s heels were resting in pools of exudative fluid, despite the dressings and absorbent pads placed beneath his legs.

    Wound management was revised as follows:

Step 1: Mr. L was premedicated with analgesic

Step 2: All affected skin surfaces were gently rinsed with normal saline and any loose tissue removed

Step 3:Bacitracin and silver sulfadiazine cream were topically applied to wound surfaces.

Step 4: Mepilex Transfer (Molnlycke Health Care, Newton, Pa.), a soft silicone exudate transfer dressing, was applied to all wound surfaces. The large surface areas involved led to use of the 8 inch x 20 inch product. Two of these dressings were required to achieve coverage with the first dressing application. These dressings are designed to stay in place for up to 5 days, decreasing the frequency of wound bed disruption and the overall cost of care per day.

Step 5: Secondary absorbent dressing layers were applied: roller gauze, then ABD pads (Medline Industries, Inc., Mundeline, Ill.) then roller gauze. The secondary dressings were secured with tape or elastic bandages. No tape was applied to skin. Nursing staff were instructed (verbal and written) to change this absorptive layer whenever wet (saturated), to prevent maceration.

Step 6: An ACUCAIR (Hill-Rom, Batesville, Ind.) mattress overlay continuous airflow system was ordered to decrease the risk of pressure ulcers and to decrease pressure to the posterior thighs — areas the patient identified as the source of greatest pain intensity. The bedside commode seat also was padded with ABD pads to “soften” the toileting surface.

    The plan of care was written in the progress notes and the dressing plan was posted at the patient’s bedside for staff nurse “ready reference” with the goal of maintaining consistency and continuity of care.

    The following results were achieved after initial soft silicone dressing application:

    20 hours — During a secondary dressing change, Mr. L reported “no pain” and said, “My legs feel better today.” The soft silicone dressing transfer layer was intact and undisturbed. Mr. L now required morphine only before sitting up in his chair or using the bedside commode.

    48 hours — Clean wound beds with copious serosanguinous exudate and no signs of infection were noted on both legs. The wounds were gently rinsed with saline and Bacitracin ointment was applied as previously described. Silver sulfadiazine cream use was discontinued per the recommendation of the Dermatology service. Due to a significant amount of autolytic slough, some blood, and topical medication evident on the soft silicone transfer dressing, fresh transfer dressings were applied.

    The scrotal surface was tender and bleeding. Surgicel (Ethicon, Inc., Somerville, NJ), an absorbable hemostat, was applied after consultation with a Wound Ostomy Certified Nurse (WOCN). Lidocaine jelly was topically applied to decrease pain. A cut-to-fit portion of the soft silicone transfer dressing was placed beneath the scrotum with an ABD pad as a secondary layer to prevent friction and shear with movement, as well as to protect the scrotal surface, decrease pain, and promote healing.

    The second round of soft silicone transfer dressings was left intact for 5 days without signs of infection. Lower extremity exudate volume was markedly decreased from 1 week earlier. By this time, edema also had diminished greatly, as evidenced by the ability to cover the affected leg areas with only one 8 inch x 20 inch soft silicone transfer dressing. Mr. L reported that he had no pain with this dressing change.

    Inspection of the lower extremity wounds 2 days later revealed regeneration of the epidermis and no exudate; therefore, the dressing was changed to Mepitel (Mölnlycke Health Care, Newtown, Pa.), a porous net, soft silicone wound contact layer designed to prevent damage to newly formed delicate tissue. In addition, the product is transparent for easy wound inspection and can be left in place for 7 to 10 days, depending on wound condition. The usual skin cleansing and Bacitracin application was followed by application of the soft silicone contact dressing, which was secured with a secondary roller gauze wrap.

    Overall, the goals for wound healing were met. Within 10 days of using the nonadhesive, soft silicone products, all lower extremity wounds had healed and other wound surfaces showed improvement. In aGVHD skin involvement, nonadhesive dressing technology is a useful adjunct to medical management in achieving pain control, wound healing, prevention of infection, and skin maceration. Even more importantly, this patient’s dignity, desire to interact with his family, and hopefulness were restored.

    Mr. L. expressed this best. “It’s a miracle,” he said. “I no longer look like a monster. I can sit and stand now and not be afraid to let my loved ones visit me.”

1. Neumann J. Graft-versus-host disease. In: Buchsel PC, Kapustay PM, eds. Stem Cell Transplant: A Clinical Textbook. Pittsburgh, Pa.: Oncology Nursing Press, Inc.;2004;22.3-22.6.

2. Ngheim P. The “Drug-vs-graft-vs-host disease” conundrum gets tougher, but there is an answer. Arch Dermatol. 2001;137(1):75-76.

3. Kunz M, Wilhelm S, Freund M, Zimmerman R, Gross E. Correspondence: Treatment of severe erythrodermic acute graft-versus-host disease with photochemotherapy. Brit J Dermatol. 2001;144:901-902.

4. Cooper B, Creger RJ, Fisher,Vicki L, eds. Handbook of Blood and Marrow Transplantation, 2nd ed., 2003. Blood & Marrow Transplantation Program. Department of Medicine and Department of Pediatric Medicine. Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University. Available at: www.icc.cwru.edu. Accessed November 12, 2004.