Hemicellulose Dressing for Skin Lesions Caused by Herpes Zoster in a Patient With Leukemia—An Alternative Dressing

Abstract: Herpes zoster is a painful disease that can develop in immunosuppressed children. Prolonged immunosuppression in leukemia patients can substantially delay healing of herpetic lesions. The purpose of this report was to evaluate the use of hemicellulose dressings as an alternative treatment for extensive herpetic lesions in an immunosuppressed child with leukemia. The hemicellulose dressing was applied to the lesions on the second day after debridement. After 36 days, the lesions were completely healed. The hemicellulose dressing was an effective resource for promoting complete epithelial healing.

Address correspondence to: Julieta Chacon, RN, MS Disciplina de Cirurgia Plástica, UNIFESP Rua Napoleão de Barros 715, 4˚ andar CEP 04024-002 São Paulo Brazil Phone: 55 11 5576 4118 E-mail: julieta.chacon@uol.com.br

     The varicella-zoster virus (VZV) belongs to the herpes virus group. It causes varicella (chicken pox) and herpes zoster (shingles) as a result of viral reactivation. This virus can remain latent for years without causing any clinical symptoms.^1,2 Individuals affected by VZV may not develop complete immunity against the virus, which remains latent in the ganglia. When conditions are favorable, the virus is reactivated and spreads along peripheral nerve fibers reaching the skin. ^1,2 It affects men and women, and occurs more frequently in adults and the elderly. ³      Before skin lesions appear, painful symptoms and localized paresthesias are observed simultaneously with cutaneous hyperalgesia caused by nerve inflammation.⁴ Cutaneous manifestations start with vesicles, which may coalesce along a nerve pathway. Crusts typically begin to form after a few days. This process is followed by epithelialization, which leaves pigmented skin patches that tend to disappear. The cutaneous manifestations are limited to one side of the body where the affected nerve is located; bilateral manifestations are rare.^5–7      The occurrence of herpes zoster may be indicative of decreased immune response. The disease will manifest in almost 15% of children with leukemia. These patients rarely experience painful conditions resulting from postherpetic neuralgia, which is difficult to treat and may persist for months or years after the cutaneous manifestations have resolved.^2,4,8,9 Herpes zoster is a self-limiting disease with time to resolution of about 15 days. However, prolonged immunosuppression in patients with leukemia can substantially delay healing of herpetic lesions, leading to more severe lesions, and longer time for disease resolution—a condition that may be aggravated by the presence of infection.      The treatment of any lesion needs to be individualized. Careful evaluation must take place with respect to indications and contraindications, efficacy, cost, and benefits before a dressing is selected. The need for or selection of treatment of lesions depends on the cause of the disease and systemic and local factors such as level of contamination and type of exudate. Since healing is a systemic and dynamic process, an effective dressing should support this process.^1,10      Topical acyclovir is commonly used to treat simple herpes zoster lesions. However, for the treatment of more extensive lesions, other coverage options that provide pain relief and prevent infections need to be considered to avoid complications during the healing process. Although we have no knowledge of the use of cellulose dressings in the treatment of herpetic lesions, this type of dressing may be beneficial in patients with herpes zoster because it provides a moist wound environment, pain relief, and an antibacterial barrier. However, secondary dressings are required and need to be changed every 42–72 hours. Another option is the use of biofilm dressings, which may not require replacement or secondary dressings.      Recent technological advances have motivated changes in traditional concepts in the treatment of lesions in general. Studies have shown that the hemostatic, bactericidal, and absorptive properties of hemicellulose films support their use as an alternative dressing for skin graft donor sites, positively influencing the wound healing process.^8,11 A biofilm is produced from sugarcane by a biotechnological process, which in a culture medium, the bacterium Acetobacter xylinum synthesizes pure cellulose. This cellulose film is transparent and selectively semipermeable, allowing gas exchange and water vapor transmission, which prevents liquid strike-through and bacterial penetration (Figure 1). It is indicated for partial-thickness skin wounds that involve both the dermis and epidermis.      The hemicellulose dressing maintains wound moisture, is easy to apply, allows mobility without being torn or displaced and direct inspection of the lesioned area, and reduces pain. It has small voids to improve drainage and adhesion, and in the absence of exudate, may stay in place for 7 days, on average, without the need for replacement.¹²      To the best of our knowledge, no study has reported on the use of hemicellulose dressings on extensive bullous lesions caused by herpes zoster in an immunosuppressed patient. For the previously described reasons, hemicellulose film was chosen for the treatment of skin lesions caused by VZV.

Methods

     The intensity of pain was assessed using the Verbal Numeric Scale (VNS) that ranges from 0 (no pain) to 10 (the worst pain imaginable), which was shown to the patient who was asked to rate his pain.¹³      The debridement of the necrotic areas was performed, blisters were punctured releasing large amounts of exudate, and lesions were cleansed with warm 0.9% saline solution. Hemicellulose dressings were applied to the lesions on the post-lateral thigh and covered with sterile gauze and bandages. The procedure was repeated daily with aseptic technique until the patient was discharged from the hospital on the 20th day after debridement. Following discharge, the dressing was changed once weekly at an outpatient facility until the lesions healed completely. The hemicellulose dressing was not applied to the gluteal region or to the foot—surfaces that are subject to friction or abrasion and can affect dressing adherence. ⁸ These areas were treated conventionally with essential fatty acids.      The study was evaluated and approved by the Research Ethics Committee (CEP) of the Federal University of São Paulo (UNIFESP). Written informed consent was obtained from the child’s parents.

Case Report

     A 15-year-old boy with acute lymphocytic leukemia was admitted at the Darcy Vargas Pediatric Hospital (São Paulo, Brazil) in June 2006 complaining of pain and alterations in tactile sensitivity on the lower left limb. He was also walking with a limp. He had connected vesicles on the lower left limb and darkened areas covering the gluteus, post-lateral thigh, and foot.      The skin lesions were superficial, showing loss of skin thickness with total involvement of the epidermis and partial involvement of the dermis, affecting approximately 50% of the gluteal region, and 80% of the post-lateral thigh and foot areas. They were accompanied by erythema, and had irregular borders, some darkened areas and no signs of infection or bleeding. Lesions were considered very painful with VNS scores ranging from 8 to 10.      The patient had pancytopenia and was placed in contact and respiratory isolation. Day 1 was defined as the day of admission. The patient received acyclovir (750-mg intravenously [IV] every 8 hours) as antiretroviral medication; analgesia was maintained with tramadol (100-mg IV every 6 hours), morphine (4.5-mg IV every 4 hours), and meperidine (20-mg IV) was given before dressing changes due to intense pain at the site of the lesions. On day 2, the patient was started on carbamazepine (200-mg orally every 12 hours), and amitriptyline (12.5-mg orally at night) as a result of the intense neuritic pain on the lower left limb. On day 3, cefepime (2400 mg) was administered IV every 8 hours due to two febrile events (38˚C, 100.4˚F). In the first week, the lesions were dressed with saline solution, acyclovir, and rayon creams, gauze, and sterile bandages. On day 5, the vesicles and necrotic areas were debrided (Figure 2) and dressed with calcium alginate, gauze, and sterile bandages, which were changed once daily due to the large amount of exudate. The patient was then started on antibiotic vancomycin (500-mg IV every 6 hours). On day 7, the patient developed neuralgia and retraction of the left knee joint due to intense pain, received benzodiazepine diazepam (5-mg IV at night), and morphine dosage was increased to 7.5-mg IV every 3 hours. There was a reduction in exudate, but a necrotic area remained on the gluteal region and the entire foot; the patient was given antibiotic meropenem (1800-mg IV every 8 hours), and the use of hemicellulose dressing was started.      Twenty-four hours after hemicellulose dressing application, adherence was observed at the base of the lesion, as well as reduction of local pain, as evidenced by the patient-reported VNS scores ranging from 3 to 5. The transparency of the film allowed for daily monitoring of the lesion site, during which exudate absorption, absence of bleeding and infection, tissue granulation, and gradual reduction of pain were observed.      After 10 days of using hemicellulose dressing, the patient no longer needed analgesia before dressing changes, reported no pain at the lesion site, and recorded zero on the VNS. The patient was discharged after 18 days of treatment with the hemicellulose dressing. At this point, some areas of the lesions had healed and granulated. There were necrotic crusts that spontaneously desquamated. After 29 days, the dressing change was performed at an outpatient facility, and the examination of the lesions showed a healed area of 95% on the thigh (Figure 3), and of 90% on the gluteal region; the darkened areas on the foot showed desquamation.      After 36 days of using hemicellulose, the lesions were completely healed (Figure 4). Lesions on the gluteal region showed some crusts. Crusts and desquamation also formed on the foot. Complete healing of these lesions occurred on days 7 and 17, respectively, after healing of the thigh lesions to which the hemicellulose dressing was applied.

Discussion

     Wound treatment is intended to protect lesions from external physical, mechanical, and biological agents. Potential risks of exogenous contamination of the lesion by microorganisms prompted the development of dressing techniques. As a basic principle, such techniques incorporate the use of antiseptic solutions in an effort to keep the dressing clean and dry. Several studies have raised doubts about the principle of using a dry dressing on open wounds, indicating that maintaining moist conditions between the base of the lesion and the dressing creates an ideal environment for the healing process. ^14,15      Patients with leukemia are treated with immunosuppressive therapy, which compromises the production and function of neutrophils and leukocytes, affects humoral and cell immunity, and increases the risk of bacterial, viral, and fungal infection—the result of which is the introduction of broad-spectrum antibiotic, antiviral, and antifungal therapies.      Immunosuppressed patients with herpes zoster may have extensive skin involvement associated with a viremic phase. ¹⁶ The mechanisms by which infectious diseases modulate cutaneous homeostasis involve alterations in the central nervous, endocrine, and immunological systems, resulting in the lack of immunological response. As a consequence, inflammatory cells that participate in the healing process, such as leukocytes, macrophages, and mastocytes, show changes that usually inhibit growth factors, cytokines, and histamines, resulting in mitosis in the healing area. ^17–20 Therefore, the healing process will be delayed and cellular immunity will not improve. ^2,16,19,21 Coordinated multidisciplinary care results in improved treatment efficacy and reduced length of hospital stay, both of which are a result of the interaction between the multidisciplinary team and the patient. ^19,20,22      Temporary skin substitutes are efficient for treating superficial burns and protecting superficial wounds before skin grafting.²² The main properties of skin substitutes are adherence, water vapor transport, elasticity, durability, low antigenicity and toxicity, hemostatic capacity, and antibacterial action.²²      Topical acyclovir is commonly used in the treatment of simple lesions caused by herpes zoster. However, for the treatment of more extensive lesions, other coverage options that provide pain relief and prevent infections need to be considered to avoid complications in the healing process.      In our healthcare facility (Darcy Vargas Pediatric Hospital) topical acyclovir is used to treat simple bullous lesions in patients with herpes zoster, while silver or calcium alginate, and essential fatty acids are used in the treatment of exudative lesions during the re-epithelialization phase. Although we have no knowledge of the use of cellulose dressings in the treatment of herpetic lesions, cellulose dressings, such as Prisma™, Promogran®, and Surgicel® (Systagenix Wound Management, Warren, NJ) among others, may be beneficial for the treatment of herpetic lesionsbecause they provide a moist wound environment, pain relief, and work as an antibacterial barrier.      However, they require secondary dressings, such as transparent polyurethane films, hydropolymer dressings, or gauze, and need to be changed every 42–72 hours. Another option is the use of biofilm dressings, such as Veloderm® (Nordic Group, Paris, France), Bionext™ (Bionext, Sao Paulo, Brazil), and Nexfill® (Fibrocell BioTech Products, Ibipora-PR, Brazil) among others, which may not require replacement or secondary dressings.      Research on cellulose has been ongoing for decades. Cellulose as a source material is becoming commercially viable. Brazilian researcher, Luiz Fernando Farah, was able to select a high-yield strain of the bacterium Acetobacter xylinum, which can synthesize cellulose faster than other strains. This material has become economically viable with improved industrial processing and purification. ²³ Hemicellulose dressings consist of a natural biofilm with a polymeric structure based on cellulose and hemicellulose microfibrils obtained through a biotechnological process. They are recommended as temporary skin substitutes for epidermal and superficial dermal loss, such as superficial first- and second-degree burns, dermabrasions, skin graft donor sites, ulcers, and flat lesions. It is contraindicated for exudative and infected wounds. ¹²      After carefully evaluating the patient presented in this case and assessing the characteristics of the various types of dressings available in the market, it was decided that the use the hemicellulose film was justifiable. The purpose of this report was to evaluate the use of hemicellulose dressings as an alternative treatment for extensive herpetic lesions in an immunosuppressed child with leukemia. Previous studies reported the efficacy and tolerance of hemicellulose dressings combined with nitrofurazone (Furacin) and calcium alginate in skin graft donor sites.^8,11 However, to the best of our knowledge, no study has reported on the use of hemicellulose dressings on extensive herpetic lesions in an immunosuppressed patient, probably due to dressing’s difficulty to absorb and adhere in the presence of exudate or infected secretions. ¹¹

Conclusion

     The hemicellulose dressing was an effective treatment that contributed to the re-epithelialization of the extensive lesions and promoted complete epithelial healing in a leukemia patient with herpes zoster after 36 days of use. Complete healing of the lesions on the gluteal region and foot, which were treated conventionally with essential fatty acids, occurred 7 and 17 days, respectively, after the thigh lesions, which were treated with the hemicellulose dressing. However, prospective, controlled, randomized, clinical, and experimental studies should be conducted to verify the efficacy of hemicellulose film on blistering lesions. Acknowledgement. The authors thank Laboratório Cristália in São Paulo for providing the dressings used in this study.