In order to understand the psychosocial impact of skin disorders on pediatric palliative care patients, it is important to understand how skin disorders affect body image. Body image is a central part of self-concept and self-esteem, which is broadly defined as “the composite of thoughts, values, and feelings that one has for one’s physical and personal self at any given time.”¹ Reactions to physical changes in the body often depend on whether the change involves an emotionally loaded body part or function or whether it results in a visible disfigurement. Physical appearance and attractiveness are major issues confronting adolescents, and their body image becomes a central aspect of their identity development.² As a result of physical changes in appearance, others may stare or avoid looking at a child. Thereafter, the affected child may suffer emotionally and may withdraw socially. Although psychosocial research has been limited, studies have suggested that altered body image can interfere with daily functioning and has been associated with grief, anxiety, depression, social introversion, social avoidance behaviors, negative self-esteem, and avoidance of intimate relationships.^3,⁴

A common diagnosis causing dermatologic symptoms in pediatric palliative care patients is cancer. The diagnosis of cancer is frequently associated with psychosocial and emotional issues. Studies indicate that children of all ages experience distress due to the effects of cancer treatment.⁵ A diagnosis of cancer often leads to multiple changes in physical appearance. These changes frequently include hair loss, presence of a central venous catheter, weight changes, and scars from surgery. The body-altering side effects of cancer have been reported by adolescents as the worst aspect of their disease.⁶ The adolescents’ sense of self-worth can be affected to such a degree that they withdraw socially from their friends and family. Physical changes due to cancer or its treatment can be devastating to a child’s self-image and can place the child at an increased risk for psychological and adjustment issues.⁷^–⁹

Regardless of the underlying medical diagnosis, intact skin allows for intimacy and the ability to touch and be touched. Many teams that provide palliative care include massage or healing touch treatments to provide moments in which the child feels relaxed. Furthermore, touch is an important means for a child’s family to express their emotions and care. Any change in a child’s body image is likely to change closeness and intimacy through touch. Loss of intimacy may elicit psychological responses that become enduring and pathological, such as depressive symptoms and social anxiety. It should, however, be kept in mind that psychological responses subsequent to the development of dermatological conditions may not be simply the result of the skin condition, but be part of the child dealing with a life-threatening illness.¹⁰

Another important consideration is the psychological impact of pain that can be caused by the treatment of skin conditions. Painful treatments may include such things as changing wound dressings and physical therapy. The wound is a constant reminder that one’s body has been changed and nurses need to be attentive and sensitive to patient responses during wound care.¹¹ Moreover, patients with wounds often report symptoms of depression and anxiety due to the pain.¹² Another important factor to consider is that effects of dermatologic conditions such as pain, skin breakdown, and scarring may lead to limitation of motion and activity. These limitations may become a major cause of distress for the child.¹³ Young children particularly cope with distressing situations by engaging in play therapy. If the child’s play routine is limited due to a skin symptom, coping may be limited, too.

A skin disorder may also affect a child’s sense of self-competence as well as relationships with parents, siblings, or friends. Children and adolescents rely on different sources of social support. Children rely more on their parents and siblings, whereas adolescents obtain much of their support from peers. Peers are influential in the adolescents’ self-definition and self-evaluation. If adolescents become isolated from their peers, this may contribute to a sense of social deprivation and can put the adolescent at increased risk for depressive symptoms. Also, older adolescents facing changes in body image may be less likely to establish intimate relationships.¹⁴ If children or adolescents have less social contact, this may have significant implications on their ability to cope with the skin disease and their overall quality of life. It is important to facilitate and encourage connections between family members and peers. This can be done by open communication and by encouraging interactions with friends. These interactions may be face to face, through e-mails or social networking websites, or by phone calls between the child and his or her friends.

Adjustment to dermatologic symptoms is influenced by individual needs and coping behaviors, family support, palliative medicine treatment team, sex, age, and location of the injury.¹⁵ A powerful mediator of psychological problems is good communication among the care team, family, and child.¹⁶ Many of the problems experienced by the child require a combination of psychosocial and integrative medicine interventions. Possible psychological interventions are assisting the child to explore activities in which he or she is able to expose thoughts and feelings without feeling vulnerable. This includes validating their feelings, rationalizing, and developing a sense of acceptance. The treatment could be a combination of counseling and art therapy. Further, it may be helpful to allow the family to incorporate integrative modalities, such as guided imagery, healing touch, hypnosis, acupuncture, aromatherapy, or other mind-body skills. However, keep in mind that caring for children with skin conditions should not be separated from educating and helping families cope with the impact of the conditions.

There is a large range of psychosocial impacts of dermatologic symptoms in pediatric palliative care patients, and this makes generalizations difficult. Unfortunately, only a limited empirical database exists and little is known regarding the experiences that children encounter with dermatological symptoms. Possible psychosocial problems include coping with grief, change in body image, functional losses, depressive symptoms, and social anxiety. Despite the limited research, the palliative care team can guide children in adjusting to the changes in their physical appearance by providing verbal and nonverbal messages that validate the experience and help them to develop a sense of acceptance. Further, the palliative care team can offer integrative treatments, as well as educating the family on how to support their child. Greater attention to understanding the impact and effective interventions for children with skin disease in palliative care are needed to ease the suffering and increase the child’s’ overall well-being.

Generalized Pruritus

Pruritus is an unpleasant cutaneous sensation that provokes the desire to scratch. It can be distressing and sometimes difficult to treat. It may lead to sleep disturbance, difficulty concentrating, anxiety, depression, and agitation. Left inadequately managed, it can have a significantly negative impact on a child’s quality of life.¹

A recent position paper by the International Forum for the Study of Itch identifies six categories for the classification of pruritus based on its etiology: dermatologic disease, systemic disease, neurologic, psychiatric, and/or psychosomatic, mixed, and others.² The causes of pruritus are numerous, and an extensive list is included in the paper published by the International Forum. Identifying the etiology of pruritus can be helpful when formulating a therapeutic approach. This chapter will address only the most common causes of pruritus in the palliative care setting.

Pathophysiology of pruritus

The neuronal pathways for the transmission of pruritus are thought to be closely related to, but distinct from, pain pathways. The skin is densely innervated by afferent C-fibers. These C-fibers transmit signals that lead to both the perception of pain and pruritus. About 80% of the C-fibers are activated by mechanical stimuli, being mechano-sensitive, while the remaining 20% are activated by chemical stimuli, including histamine, called mechano-insensitive. It is likely that some combinations of mechano-insensitive and mechano-sensitive C-fibers are responsible for the transmission of the itch signal to the dorsal root ganglia.³ Dorsal horn neurons then carry the itch signal up the spinal cord to the thalamus. Functional MRI imaging of the brain has shown activity in multiple areas of the brain, which encode sensory, emotional, attention-dependent, cognitive, and motivational aspects of itch.⁴ The perception of itch causes the response of scratching. Scratching creates a mild pain stimulus, which activates fast-conducting low-threshold nerve fibers that inhibit itch. It is believed that itch is under tonic inhibitory control of pain-related signals. It has also been demonstrated that μ-opioid receptor antagonists can have antipruritic effects but may intensify pain (Fig. 35-1).⁵^–⁸

Fig. 35-1 Neuroanatomy of itch. Itch and pain transmission occurs via unmyelinated C nerve fibers that excite the lamina I subset of neurons in the dorsal horn of the spinal cord. Studies have demonstrated specific C fibers that convey itch. Information on both itch and pain is conducted through the lateral spinothalamic tract, with projections to the thalamus and subsequently the cerebral cortex. Processing of itch activates several regions of the brain that are similar to those involved in pain, such as the primary somatosensory cortex, the anterior cingulate cortex, and the premotor cortex. The latter validates the clinical observation that itch is inherently linked to a desire to scratch. Of note, some studies on the central processing of itch have failed to demonstrate stimulation of somatosensory areas. Unlike itch, pathways of pain perception activate the secondary as well as primary somatosensory cortex. Concomitant painful stimuli can reduce the sensation of itch, possibly by a descending inhibitory mechanism resulting from activation of the periaqueductal gray matter.

(Adapted from Yosipovitch G. Pruritis: an update. Curr Probl Dermatol. 2003;15:137-64. In Bolognia, Jorizzo, editors: Dermatology, ed 2, Saunders: an Imprint of Elsevier Science, 2008, Fig 6-1.)

When pruritus is caused by dermatologic disease, peripheral C-fibers must be activated to transmit an itch signal. Histamine is the itch-stimulating substance, pruritogen, that is most typically targeted when treating itch, but there are other substances that stimulate itch including acetylcholine, bradykinin, endothelins, interleukins, leukotrienes, neurotrophins, prostaglandins, proteases, and kallikreins. These pruritogens can be released from various intracutaneous cell types. When these substances stimulate C-fibers, neuropeptides, such as substance P, are released. The neuropeptides then act on a variety of non-neuronal cell types, such as mast cells, which release further pruritogens thus creating a positive feedback loop and increases itch. Itch leads to scratching, which causes inflammation and the release of more pruritogens. Breaking this itch-scratch cycle can be particularly challenging. Recently investigators have identified ion channels, called transient receptor potential channels, that when stimulated, desensitize sensory afferents by depleting neuropeptides such as substance P. This interrupts the interplay between sensory neurons and mast cells and is a promising focus for the development of future therapies for pruritus.³ Capsaicin, which is being used in adults to treat pruritus, is an example of a medication that works through this mechanism.

The pathophysiology of pruritus caused by systemic disease is not fully understood, but it is often caused by increased levels of pruritogens, including endogenous and exogenous opioids. Itch of the neurological classification arises secondary to damage of nerves anywhere along the afferent pathway. Nerve damage can be seen in peripheral neuropathies, nerve compression or cerebral processes such as tumors, abscess, or thrombosis. Itch caused by psychiatric and/or psychosomatic disease can occur in disorders such as obsessive-compulsive disorder and parasitophobia. It is believed that both acute and chronic stress can trigger or enhance pruritus.⁹

Assessment

In the palliative care setting the most likely etiologies of a pruritus include underlying medical disorders, drug therapy, and dry skin. The etiology of pruritus can frequently be determined by history and physical exam. History should include localized versus generalized location, description, temporal profile, provoking factors, effect of medications, current medication list, atopic history, and travel history. Physical exam should include evaluation for dry skin, scabies, icteric conjunctivae, weight loss, and mental status changes. Radiologic and laboratory workup can be considered based on clinical presentation and goals or care.

There are few assessment tools to evaluate the severity of pruritus in children. The tools that do exist are designed to be used in specific conditions, such as atopic dermatitis.¹⁰ In older children visual analog scales can be used to evaluate itch intensity. In the research setting a quantitative measure of pruritus can be obtained by a device that is able to measure the vibrations of the fingernails in the act of scratching.¹¹

Management of Specific Conditions

The most effective treatment for pruritus is treating the underlying cause of the itch. This is not always possible, and even when it is possible the itch often does not resolve immediately. For this reason it is important to identify treatments specifically aimed at quickly and effectively relieving itch regardless of the state of patient’s underlying condition. In this section we will review the management of pruritus that is caused by conditions frequently seen in pediatric palliative care.

Some simple practical steps can be taken in the treatment of pruritus regardless of the etiology. Simple interventions such as restricting time in the bath or shower, bathing in cool or lukewarm water instead of hot water, and applying emollients to the skin after bathing and on a regular basis can be helpful. Some children may find oatmeal baths to be soothing to itchy skin. High skin surface pH has been noted in several skin disorders, including atopic dermatitis and uremia. Using low pH cleanser and moisturizers can address this issue. Baths can also be prepared with sodium bicarbonate added to the bath water. Using a humidifier, maintaining a cool ambient temperature and avoiding rapid changes in environmental temperature and humidity can all be helpful general measures.

It can be quite difficult to keep children from scratching areas that itch. Children often scratch irritated areas in their sleep or without thinking about it. It is crucial to keep a child’s fingernails cut short to prevent significant damage to the skin from scratching. Gloves or mittens can be place on children’s hands but they are often difficult to keep in place and can limit the child’s function. Case reports have suggested that hypnosis can be effective in reducing pruritus. This therapy may be a helpful adjuvant therapy for itch that is difficult to treat.¹²^–¹⁴

Xerosis

Children with serious medical conditions can be predisposed to the development of dry skin related to dehydration. Dry skin can be the primary cause of pruritus or can exacerbate pruritus of a different etiology. In any patient with pruritus, it is important to keep the skin moist by applying emollients on a regular basis. Common over-the-counter emollients may contain water and alcohol; for serious xerosis, products that are predominately oil applied immediately after bathing when skin is moist will be most effective.

Opioid-induced pruritus

Generalized pruritus that may localize to the face and trunk is a common complication of parenteral or neuraxial opioid administration. Pruritus can also be seen with the administration of oral opioids. It is difficult to estimate the incidence of opioids-induced pruritus in children for several reasons including limited data, variation between opioids and routes of administration, and lack of uniformity in methods of evaluation of pruritus. The incidence has been reported to be as high as 77% with parenteral administration of opioids in the postoperative setting.¹⁵ Among children with cancer-related pain, the incidence has been reported to be 28% with administration of oral or parenteral opioids.¹⁶ It is generally accepted that the incidence of pruritus is higher in neuroaxial administration of opioids than in parenteral administration. One 2006 study shows an incidence of 18% with parenteal opioids and 30% with epidural opioids.⁸

The mechanism of opioid-induced pruritus is not fully understood. It is known that orally and parenterally administered morphine can cause the release of histamine from mast cells, but fentanyl does not.¹⁷^–¹⁹ Because both morphine and fentanyl are known to cause pruritus, this argues against histamine playing a significant role in opioid-induced pruritus. Furthermore, in studies done in primates, the administration of a histamine antagonist did not attenuate scratch induced by morphine.²⁰ Any reported benefit of the use of H1-antihistamines in the treatment of opioid-induced pruritus is most likely related to the sedative properties of the medication. It is likely that opioid-induced pruritus is mediated centrally through μ-opioid receptors.²⁰

In the initial management of pruritus caused by morphine, it may be helpful to change from morphine to an alternative opioid such as hydromorphone or fentanyl. If this is not effective, an opioid receptor antagonist can be administered in conjunction with the patient’s opioid. It is important, however, that the opioid antagonist be used in a low enough dose that it does not reverse the analgesia achieved by the opioid. Both naloxone and naltrexone have been studied. Naloxone can be administered at a starting dose of 0.25 mcg/kg/hr to 1 mcg/kg/hr. It is believed that doses of more than 2 mcg/kg/hr are likely to cause an unacceptable degree of reversal of the analgesic effect of the opioid. A pilot study done in children in sickle cell crisis found that patients tolerated co-administration of naloxone and morphine.⁵ A second study of 46 pediatric postoperative patients found that concomitant administration of low-dose naloxone and morphine PCA significantly reduced opioid-associated pruritus.¹⁵

Opioid agonist-antagonists, including nalbuphine and butorphanol, have also been studied as agents to reduce pruritus. Results of these studies have been mixed and studies are limited in the pediatric population. One study of 184 pediatric patients found that nalbuphine 50 mcg/kg IV given as a one-time dose was not effective in the treatment of postoperative opioid-induced pruritus.⁸ Nonetheless, additional studies are warranted. While these drugs have conceptual advantages over pure opioid antagonists in that they do not reverse the analgesic effect to the opioid, in combination with pure agonist opioids, they risk the precipitation of an opioid withdrawal syndrome and worsened pain. These medications act as antagonists at the μ-receptor and as agonists at the kappa-receptor. It appears that activation of kappa receptors attenuates morphine-induced itch without interfering with analgesia.²¹

Opioid-induced pruritus remains difficult to treat, and new approaches are being evaluated. Along with opioid receptors, serotonin receptors, dopamine D₂ receptors, and prostaglandins have been implicated in the mechanism of opioids-induced pruritus. For this reason serotonin 5-HT₃ receptor antagonists, such as ondansetron and mirtazapine, are being studied. D₂ receptor antagonists, such as droperidol and prostaglandin-blocking non-steroidal anti-inflammatory agents, are also being studied as possible treatments for opioid-induced pruritus. Studies of these agents in adults have not shown dramatically positive results. Few studies have been done in children and many trials have included only subjects receiving intrathecal or epidural opioids. These two factors make it difficult to predict the effect that these medications may have in the treatment of opioid-induced pruritus in children in the palliative care setting.

Cancer-specific

Many children with cancer experience pruritus. In order to be able to choose the most appropriate treatment, it is important to carefully consider the cause of the symptom. The pruritus may be a direct result of the cancer or may be a side effect of the child’s treatment. Children with cancer may experience xerosis, radiation desquamation, drug reactions, side effects from chemotherapy and biologic agents, or graft versus host reactions, all of which can cause pruritus.

The most common types of cancers that cause pruritus in the pediatric population are leukemias and lymphomas. Hodgkin lymphoma often causes burning and itching in localized areas, while other leukemias and lymphomas cause more generalized pruritus. Adenocarcinoma and squamous cell carcinoma of various organs, as well as carcinoid tumors, are less common in children, but may also cause pruritus. The exact mechanism by which cancer causes pruritus is unknown, but it is likely that it is mediated through the release of pruritogenic substances, including histamine, leukopeptidase, kininogen, bradykinin, and serotonin.

The most effective treatment for cancer-related pruritus is anticancer therapy. In palliative care, however, many patients are responding poorly to or are no longer receiving disease- modifying therapies. In these patients, other approaches to the treatment of the pruritus must be identified. There is very limited data on the treatment of pruritus associated with cancer. In Hodgkin lymphoma there are case reports suggesting that the H2-receptor antagonist, cimetidine, is effective in treating pruritus.²² Corticosteroids typically given in conjunction with palliative chemotherapy can also relieve itch in late-stage Hodgkin lymphoma. Case series that have included pediatric patients suggested that pruritus caused by solid tumors may respond to the serotonin selective reuptake inhibitor paroxetine.²³ While paroxetine’s antidepressant effects can take weeks to see, its antipruritic effects may be seen in as little as 24 hours after administration. In carcinoid tumors, blocking serotonin with a 5-HT³ receptor antagonist, such as odansetron, may be helpful.

Cholestastis

Cholestasis occurs in children of all ages, but it is particularly common in the neonatal period. The incidence of neonatal cholestasis is estimated to be approximately 1 in 2500 live births.²⁴ The mechanism by which cholestasis causes pruritus is unclear, but elevated levels of circulating bile acids and endogenous opioids are both believed to play a role. It is also probable that the serotonin neurotransmitter system is involved. Recently the role that the serotonin neurotransmitter system plays in pruritus caused by cholestasis has been explored. There are studies in adults suggesting that the 5-HT₃ receptor antagonist ondansetron, the selective serotonin reuptake inhibitors paroxetine and sertraline, and the noradrenalin and specific serotonin antagonist mirtazapine can be effective therapies.²⁵^–²⁹ The pruritus of cholestasis is not thought to be mediated by histamine. Any relief that patients perceive with the administration of antihistamines is likely related to the sedating effects of the medication. It is of interest to note that if a patient progresses to liver failure, then pruritus often resolves.

First line therapy for pruritus caused by cholestasis is typically a medication directed at decreasing the level of circulating bile acids. Medications that can be used to achieve this result include nonabsorbable anion exchange resins such as cholestyramine, the hydrophilic bile acid ursodeoxycholic acid, and the hepatic enzyme inducers rifampin and phenobarbital.^26,³⁰^–³³ Nonabsorbable anion exchange resins are not effective in the case of complete biliary obstruction because the bile acids must reach the intestine for the medication to be effective. They are usually avoided in infants with portoenterostomy for biliary atresia because of concern about accumulation of the drug at the anastomosis causing obstruction.

If decreasing the level of circulating bile acids is ineffective or only partially effective, an opioid antagonist can be administered. The opioid antagonists naloxone, nalmefene, and naltrexone have all been shown to be helpful.³⁴^–³⁷ Tolerance to these medications may develop over time, requiring dose escalation. Patients may experience symptoms of opioid withdrawal if they are treated with opioids; this can limit the medications’ usefulness.

Surgical interventions may also be helpful if medical management has not been successful and surgery makes sense within the goals of care. Procedures including partial external biliary diversion and terminal ileal exclusion have been shown to decrease pruritus in some children with intrahepatic cholestasis.^38,³⁹ In pruritus caused by extrahepatic disease, stenting the bile duct is often the best treatment for pruritus. In extreme cases of pruritus that is refractory to treatment and that is causing significant negative effects on a patient’s quality of life, liver transplant can be considered.

Uremia

Pruritus from uremia is seen in patients with chronic renal failure, but rarely in those with acute renal failure. The rate of pruritus is higher in patients receiving dialysis than in those not receiving dialysis. In adults, the presence of severe uremic pruritus is a predictive factor for death.⁴⁰ The mechanism by which uremia causes pruritus is not fully understood, but as in other systemic illnesses it is likely caused by the accumulation of pruritrogens in the blood.

There is very little research that has been done in the pediatric population on pruritus secondary to uremia, so the treatment options are based on the adult literature. Initial management in patients on dialysis includes enhancing the dialysis regimen and correcting the patient’s calcium, phosphorus, and magnesium. Xerosis, which is very common in uremic patients, should be aggressively treated.⁴¹ If a patient is found to have hyperparathyroidism secondary to renal failure, pruritus can sometimes completely resolve after parathyroidectomy.⁴² Beyond these steps, UV-B therapy has been shown to be effective, but it has potential carcinogenic side effects.⁴³ In recent studies, gabapentin has been shown to be a helpful treatment.⁴⁴ Kappa-opioid receptor agonists have shown promise, but they have not been studied in children.⁴⁵ As in pruritus caused by most other systemic diseases, the only role that antihistamines play in treatment are as sedatives.

Pruritus caused by renal failure can frequently be localized. This fact may allow for the use of topical agents. There has been recent interest in the use of capsaicin cream because it has been shown to deplete substance P from C-fibers when repeatedly applied.⁴⁶ Its use may be limited in young children because it causes a burning sensation for the first few days it is applied. To make capsaicin more tolerable the skin can be anesthetized with a topical anesthetic, such as eutectic mixture of local anesthetics (EMLA), before the capsaicin is applied. Other topical agents, as well as systemic medications, are being studied for the treatment of pruritus caused by uremia, but the lack of clarity about the pathogenesis of the condition makes identifying new treatments difficult.

HIV/AIDS

Pruritus is very common in patients with HIV infection. It can be secondary to multiple etiologies, including infection, infestation, peripheral neuropathy, xerosis, a primary skin condition, systemic disease, drug reaction, or elevated levels of cytokines. A thorough evaluation for the most likely causes of the pruritus should be done and should direct treatment. Idiopathic HIV pruritus is uncommon and is diagnosed by the exclusion of other causes. Phototherapy can be an effective treatment, and one study in adults suggests that indomethacin may also be helpful ⁴⁷ (Table 35-2).

TABLE 35-2 Treatment of Pruritus by Cause

Cause	Treatment
Xerosis	Oil-based emollients
Opioid induced	Opioid rotation Opioid receptor antagonist Opioid receptor agonist-antagonists 5-HT₃ receptor antagonists D₂ receptor antagonists Non-steroidal anti-inflammatory agents

H₂ receptor antagonists

Corticosteroids

Serotonin selective reuptake inhibitors

5HT₃ receptor antagonists

Cholestastis

Extrahepatic cholestasis

Intrahepatic cholestasis

Partial biliary obstruction

Any cause

Stenting of the bile duct

Surgical intervention

Nonabsorbable anion exchange resins

Hydrophilic bile acid ursodeoxycholic acid

Hepatic enzyme inducers

Opioid antagonists

5HT₃ receptor antagonists

Selective serotonin reuptake inhibitors

Noradrenalin and specific serotonin antagonist mirtazapine

Uremia

Enhance dialysis regimen

Correct calcium, phosphorus, and magnesium

Treat hyperparathyroidism

UV-B therapy

Gabapentin

Kappa-opioid receptor agonists

Capsaicin cream

HIV/AIDS

Phototherapy

Indomethacin

Mucositis

Oral and gastrointestinal mucositis, referred to collectively as alimentary tract mucositis, is very common in children receiving chemotherapy and/or radiation to areas encompassing the gastrointestinal tract including the head and neck. Younger patients develop both oral mucositis more frequently and heal more quickly than older patients receiving similar treatments. This is thought to be secondary to an increased rate of basal cell turnover in children as compared to adults. Mucositis of the alimentary tract increases morbidity and mortality by predisposing the affected child to bleeding, local infections, and sepsis. It is often the dose-limiting factor in the administration of chemotherapy.

Mucositis of the oral cavity and esophagus can lead to considerable oral pain, while mucositis of the gastrointestinal tract can lead to abdominal pain, diarrhea, and bloating. These symptoms can compromise both a patient’s nutritional status and quality of life. Because mucositis causes serious complications, limits treatment, and leads to significant symptom burden, increasing attention has been paid to how best to prevent and manage it. Most studies have focused on how to prevent the development of or minimize the severity of mucositis in chemotherapy and radiation. Few studies have focused on how to treat the symptoms associated with mucositis.

In 2004 the Multinational Association of Supportive Care in Cancer and the International Society for Oral Oncology published evidence-based guidelines on the treatment of cancer therapy-induced oral and gastrointestinal mucositis. These guidelines were then revised in 2006.^48,⁴⁹ Recommendation for the prevention of mucositis in patients receiving 5-fluorouracil, bolus doses of edatrexate, and high-dose melphalan included the use of oral cryotherapy. Unfortunately, very few recommendations about symptomatic treatment of oral mucositis could be made because of the limited evidence base. The group was able to recommend the use of patient-controlled analgesia with morphine for oral mucositis pain in those undergoing high-dose chemotherapy with hematopoietic stem cell transplantation. Because of the paucity of evidence, clinical experience is the primary basis for treatment of mucositis.

Gastrointestinal mucositis primarily causes diarrhea, and it is important to ensure that adequate hydration is maintained. Diarrhea can be treated with standard anti-diarrheal medications including loperamide. If loperamide is not effective, then octreotide can be used.

Particular attention has been paid to the prevention and treatment of oral mucositis. In patients receiving chemotherapy that is likely to lead to mucositis, cryotherapy can be used to minimize mucositis. This involves having the child suck on ice for 20 to 45 minutes while receiving chemotherapy. The ice cools the mucosal tissue and leads to vasoconstriction, decreasing the exposure of the tissue to the chemotherapeutic agent. The approach has been found to be modestly effective.

The mainstay of treatment of oral mucositis, regardless of the cause, is the use of systemic opioids. Opioids can be very helpful, but they frequently do not completely control the pain and their use may be limited by side effects. For this reason many oral rinses have been used as adjuvant therapy. Topical agents are often mixed in different combinations and referred to by various colloquial names such as magic mouthwash. Topical agents that have been tried include anesthetics such as viscous lidocaine, and benzocaine. Anesthetics are frequently combined with other analgesic drugs such as morphine, diphenhydramine, and anti-inflammatory agents such as topical benzydamine hydrochloride, which is not FDA approved in the United States, or dexamethasone. Coating agents such as aluminum hydroxide and magnesium hydroxide containing liquid antacids are also frequently included in oral rinses. Some combination of these agents are often combined and ordered for topical use by swishing the solution around the oral cavity and then spitting it out. Caution needs to be taken when considering the use of topical anesthetics due to the theoretical concern over an increased risk of aspiration secondary to the numbing effects of the drugs and concern over systemic absorption through damaged mucosal surfaces. Topical ketamine has shown promise as an effective treatment for oral pain. In one study, topical ketamine and morphine were shown to be safe, easy to use, and effective treatments for post-tonsillectomy pain in children 3 to 12 years of age.⁵⁰

The most promising therapy being investigated for the prevention and treatment of oral mucositis is low-level laser therapy. Laser therapy has trophic, anti-inflammatory, and analgesic effects. One pilot study showed that laser therapy in children with chemotherapy-induced oral mucositis resulted in decreased severity of the mucositis and marked pain relief.⁵¹ Another study showed a significant decrease in the duration of chemotherapy-induced oral mucositis in children.⁵²

One of the major complications of mucositis is secondary infection, which often causes increased oral pain. Oral cultures from one study of children with lymphoblastic leukemia and oral mucositis showed that fungal organisms were isolated in 39% of episodes and bacterial organisms were isolated 28% of the episodes. Herpes serology from the same patients was positive in 16% of the episodes as compared with 2% of controls. In patients with mucositis, evaluation should be done for any signs of infection. Identified infections should be treated appropriately. Frequently an antifungal, such as nystatin or fluconazole, and/or an antibiotic, such as tetracycline, is added to the oral rinse. It is unclear if this is effective. In immunosuppressed patients, including patients on systemic steroids, topical treatment of oral infections is typically not sufficient and systemic treatment should be considered.

Finally, there is consensus among experts that oral care is critical in the management of oral mucositis. Its goal is to reduce the impact of oral microbial flora, prevent infection of the oral soft tissues and help alleviate bleeding and pain. Basic oral care includes brushing teeth with a soft toothbrush, flossing, using mouth moisturizers, and rinsing with bland agents such as sterile water, normal saline and sodium bicarbonate. It is helpful to follow an oral care protocol and to provide education about appropriate oral care to patients and their families.

Diaper dermatosis

Children with chronic and life-threatening diseases are often especially prone to diaper dermatosis due to long-term bed rest, illness-related incontinence, and/or immunosupression. Irritant contact dermatitis is probably one of the most commonly seen dermatoses in this group and presents with erythematous papules and plaques, characteristically sparing the folds. If skin breakdown occurs, then this area is at risk for development of secondary infection. Both fungal and bacterial infections are common and early recognition and treatment can prevent complications and serious life-threatening sequelae. Candidiasis commonly presents as erythematous papules or plaques with satellite pustules. Microscopic slide examination (KOH) or fungal smear and culture can aid with diagnosis. Usually if the patient is afebrile without systemic symptoms, cutaneous infectious can be easily treated with topical nystatin cream. Combination barrier creams, such as zinc oxide with antifungal creams, can also be helpful for prophylaxis in predisposed individuals. Bacterial infections in the diaper area can also present with vesiculopustular lesions often mistaken for fungal infection. For instance, bullous impetigo most commonly caused by Staphylococcus aureus often presents as large bullae that break down, leaving collarettes of scale behind. Newborns are especially prone to development of bullous impetigo, and this can be treated with appropriate antibiotic therapy tailored to bacterial culture results and organism susceptibility profiles. Allergic contact dermatitis (ACD) may also occur due to sensitivity to topical creams or their components. ACD may occur to topical medications including neomycin, antifungals, and steroids. Components of creams such as the lanolin in aquaphor or the formaldehyde releasers in moisturizers can also cause ACD. Even preservatives such as benzalkonium chloride used in baby wipes can cause an allergic or irritant contact dermatitis.

For erosions and/or ulcerations of perineal area, the mainstay of treatment is barrier creams, such as zinc oxide. That can be combined with creams, such as silver sulfadiazine, to help encourage re-epitheliazation and prevent secondary infection. Combination products such as Vusion, or topical miconazole, zinc oxide, and petrolatum, as well as creams, such as Biafine, containing growth factors may also be good treatment choices.

Immunocompromised states may predispose children to perianal abscesses. Palpation may be necessary to detect the abscess. In some cases these lesions drain on their own and in other cases incision and drainage is required.

For persistent dermatoses that present in the diaper area, and are unresponsive to conventional treatment, dermatologic consultation along with skin biopsy might be indicated. Skin diseases such as inverse psoriasis or inverse pityriasis rosea as well as viral exanthems may present with prominent groin involvement. It is also important to exclude eruptions such as Langerhan cell histiocytosis (LCH), which generally presents as scaly papules or plaques with a predilection for intertriginous and scalp areas (Fig. 35-2).

Fig. 35-2 Diaper dermatitis.

Wounds

There are several causes for wounds that occur in children receiving palliative care. Pressure ulcers, malignant wounds, and wounds caused by blistering skin conditions are the most common. Only minimal literature is available regarding treatment of pediatric versus adult wounds, because the majority of data has focused on the compromised and elderly patient. Lack of scientific data has contributed to ongoing use of modalities that are not optimal in managing wounds in the pediatric population, including saline gauze and leaving wounds open to air so that they can breathe.⁸

Unlike wound management in the general population, the first determination that should be made when managing a wound in a child receiving palliative care is the goal of the treatment. Frequently the goal is to heal the wound, but in some cases, particularly when the child is near the end of life, there may not be time to heal the wound. The goal then becomes to stabilize the wound and control the symptoms associated with the wound including pain, odor, bleeding, and excessive exudate.

Types of wounds

Pressure Ulcers

Pressure ulcers in the pediatric population, while not as prevalent as in adults, are still a significant dermatologic occurrence that must be appropriately addressed. The incidence of pressure ulcers in the pediatric population ranges from 20% to 43% in outpatients with spina bifida to 23% in children in neonatal intensive care.¹^–⁴ Minimal data is available on the overall incidence of pediatric pressure ulcers. The exception is a national survey of healthcare institutions⁵ that suggests a pressure ulcer incidence of 0.29% and a prevalence rate of 0.47%, while Dixon and Ratcliff list incidence and prevalence of pressure ulcers in pediatric patients as between 7% to 27% and 0.47% to 6.5%, respectively.⁶ Data on the incidence and point prevalence of pediatric pressure ulcers in different care settings, such as the home setting versus the hospital, are not available.

Children who are bed or chair bound or who have limited ability to reposition themselves are at particularly high risk for developing pressure ulcers. Poor nutritional status and conditions leading to moist skin, such as incontinence, are also compounding risk factors. It is very important to identify patients who are at high risk and take steps to prevent ulcer formation. If a child is identified as being high risk for ulcer formation his or her skin should be inspected daily so that issues can be identified before they become problematic. A bed-bound patient should be repositioned every two hours and a chair-bound patient every hour. Pressure-reducing mattresses and chair cushions should also be used. Donut-type cushions should be avoided because they reduce blood flow to the tissue within the donut. Children should be lifted with the help of a draw sheet or trapeze when repositioned to prevent shearing forces. Pillows or foam wedges should be used to prevent boney prominences such as the heels and ankles from coming into contact with each other. A pressure-reducing device such as a gel pad should be placed below the child’s heels, or a pillow should be placed under the calf to raise the heels off of the bed. When patients are in a side-lying position, pressure directly on the trochanter should be avoided. When a child is incontinent, an absorbent diaper or brief should be used and it should be changed as soon as the child becomes wet or soiled. In addition, a barrier cream should be used to protect the skin from moisture. Prevent excessively dry skin by using emollients and humidifying air. When a child is being cared for at home it is important that the parents and other caregivers are educated on how to prevent pressure ulcers and how to identify ulcers at their earliest stage.

Pressure ulcers occur in similar locations in both adults and children. The most common locations are the heels, neck, sacrum, and scalp. Spina bifida and other diseases requiring immobilization may result in wounds over bony protrusions and popliteal areas.⁷

The primary concern, regardless of location of the ulcer, is addressing and eliminating the source of the pressure. Pressure-relieving mattresses and other devices are designed to assist with reducing pressure but may not always be effective. Examination of pressure sources includes evaluation of support surfaces, splints, braces, clothing, and any other material or device that come in contact with the skin. Failure to address the source of pressure will result in the failure of adjunctive treatments and may lead to continued tissue damage. Whenever using any product on a child, whether a pressure reducing surface, device, or other product, it is important to review the information related to age-specific use.

When a child complains of pain from a cast, splint, or other supportive device, the complaint should always be taken seriously pending complete review of the source of the pain. If in doubt, the supportive device should always be removed to allow for a full assessment. Sources of pressure that may require removal include but are not limited to casts, other immobilization devices and boards, masks, pressure cuffs and tubing.

Identification of the ulcer etiology is critical to optimal outcomes. When treating pressure ulcers it is important to rule out other potential etiologies. These etiologies include fluid extravasation; surgery-related wounds; electrical, thermal, and chemical burns, incontinence-related lesions; congenital abnormalities; trauma from dressings, adhesives, and clothing; and systemic diseases. Abuse should also be included in the differential diagnosis based on the presentation and history. Failure to treat underlying pathophysiology will delay or prevent closure of the wound.

Malignant wounds

Malignant wounds can be caused by a primary skin cancer, invasion of a primary or metastatic tumor through the skin, or the cutaneous infiltration of a tumor via the bloodstream or lymphatics. Many of the cancers in adults that most commonly cause these types of wounds include skin, breast, lung, head and neck, melanoma, colorectal, cervical and ovarian. Sarcomas can also cause fungating malignant wounds and are more common in children than the other cancers typically associated with malignant wounds.

Malignant wounds alter the perfusion of the involved tissue. There is often significant tumor necrosis. Necrotic tissue can become infected with anaerobic bacteria leading to pain and odor. The challenges in the management of a malignant wound are controlling the infection, exudate, odor and bleeding, and addressing the psychological impact of the wound on the child. Malignant wounds may affect the child’s body image and the associated odor may be embarrassing and lead to isolation because family and friends are repulsed.

Generally, the principles of management of malignant wounds are the same as those for advanced pressure ulcers. In malignant wounds there may be a role for antineoplastic treatments in reducing tumor size and managing symptoms. Radiation may be used to reduce bleeding, pain, and exudate. These wounds are not expected to heal and the focus of treatment should be on controlling the symptoms associated with the wound.

Blistering Dermatoses

Genetic inherited blistering disorders, such as epidermolysis bullosa (EB), present a spectrum of disease severity and prognosis depending on type and defect in cell adhesion molecules. EB simplex is due to defects in keratin 5 and 14 represents a mild phenotype, which does not usually affect patients’ lifespan, whereas patients with junctional or dystrophic EB have significant morbidity and mortality associated with their diseases. The emphasis in these patients is adequate nutrition and wound care along with infection prophylaxis when necessary.

An attempt to minimize the formation of wounds is important in this group of patients. Minor trauma and shearing forces can cause blistering. Using gentle handling techniques is critical. The seams of clothing and elastic on disposable diapers can cause trauma. Loose clothing should be chosen and should be turned inside out when worn. Cloth diapers can be used or the elastic can be cut out of disposable diapers. Fusion of the digits can be a problem in children with EB and children’s figures and toes can be individually wrapped in an attempt to prevent this from occurring. It is important to avoid adhesives that are frequently used to attach medical devices, such as cardiac monitors and pulse oximeters, to the skin. When necessary, children should be bathed in a tub and gently patted dry or allowed to air dry. Breast feeding and bottle feeding can cause trauma to the lips. Petroleum should be used to lubricate lips prior to feeding, or syringe or dropper feeds should be considered. Trauma to the anal area caused during bowel movements can be minimized by keeping the child’s stools soft. Controlling the child’s environment by avoiding heat and high humidity can also be helpful in preventing blister formation.

When large blisters do form they may need to be aspirated without removal of the roof of the blister, which provides a natural dressing. When there are open wounds the general principles of wound care discussed in this chapter can be applied. Open wounds are often treated with an antibiotic cream and covered with a non-adherent dressing. Dressings can be held in place with stretchy tubular gauze netting (Figs. 35-3 and 35-4).

Fig. 35-3 Epidermolysis bullosa of the arm.

Fig. 35-4 Epidermolysis bullosa of the leg.

Documentation and education

An important component of the treatment of problematic pediatric wounds is the documentation of the findings, the treatment applied, and the family education provided. Documentation in conjunction with family and patient education is an intrinsic component of the care process, and may be more difficult and time consuming than care of the wound itself. Initial documentation requires measurements, a description including unusual characteristics, photos, staging, past treatments, and response to treatments. A thorough history including a review of systems, past medical history, and history of past therapies is a requirement for the development of an appropriate treatment plan. Subsequent documentation should reflect a complete evaluation done at each examination. Risk assessment is also part of documentation.

Family education may be difficult as the expectations for rapid recovery and optimal outcomes may be unreasonable. Underestimation of time to closure, lack of clarity about expected outcomes and non-disclosure of treatment complications and their advantages and disadvantages may lead to frustration on the part of the patient and family. A clear, concise, compassionate explanation of the treatment and the expected outcome establishes credibility and collaboration. Risk assessment and prevention practices are outlined by various associations, organizations, and publications.⁹^–¹¹

Staging of pressure ulcers is the same in adult and pediatric populations. The accepted stages presented by the National Pressure Ulcer Advisory Panel (NPUAP) are listed in Box 35-1. The description and identification listed for each stage has not been modified for the pediatric population.

BOX 35-1 Pressure Ulcer Staging System from the National Pressure Ulcer Advisory Panel (NPUAP)

From National Pressure Ulcer Advisory Panel. Updated Staging System 2007. Accessed June 28, 2010. www.npuap.org/pr2.htm.

Stage I: Intact skin with non-blanchable redness of a localized area, usually over a bony prominence. Darkly pigmented skin may not have visible blanching; its color may differ from surround area.

The area may be painful, firm, soft, warmer or cooler as compared with adjacent tissue. Stage I may be difficult to detect in individuals with dark skin tones. May indicate at risk persons.

Stage II: Partial-thickness loss of epidermis or dermis presenting as a shallow open ulcer without slough. May present as an intact or open and/or ruptured serum-filled blister.

Presents as a shiny or dry shallow ulcer without slough or bruising, which would indicate a suspected deep-tissue injury. This stage should not be used to describe skin tears, tape burns, perineal dermatitis, maceration, or excoriation.

Stage III: Full-thickness tissue loss. Subcutaneous fat may be visible but bone, tendon, or muscle are not exposed. Slough may be present, but does not obscure the depth of tissue loss. May include undermining and tunneling.

The depth of a stage III pressure ulcer varies by anatomic location. The bridge of the nose, ear, occiput, and malleolus do not have subcutaneous tissue and stage III ulcers can be shallow. In contrast, areas of significant adiposity can develop extremely deep stage III pressure ulcers. Bone and/or tendon is not visible or directly palpable.

Stage IV: Full-thickness tissue loss with exposed bone, tendon, or muscle. Slough or eschar may be present on some parts of the wound bed. Other characteristics often include undermining and tunneling.

The depth of a stage IV pressure ulcer varies by anatomic location. The bridge of the nose, ear, occiput and malleolus do not have subcutaneous tissue and these ulcers can be shallow. Stage IV ulcers can extend into muscle and/or supporting structures such as the fascia, tendon or joint capsule, making osteomyelitis possible. Exposed bone and/or tendon is visible or directly palpable.

DTI (Suspected Deep Tissue Damage): Purple or maroon localized area of discolored intact skin or blood-filled blister due to damage of underlying soft tissue form pressure and/or shear. The area may be preceded by tissue that is painful, firm, mushy, boggy, warmer, or cooler compared with adjacent tissue.

Deep-tissue injury may be difficult to detect in individuals with dark skin tones. Evolution may include a thin blister over a dark wound bed. The wound may further evolve and become covered by thin eschar. Evolution may be rapid exposing additional layers of tissue even with optimal treatment.

Unstageable: Full-thickness loss in which the base of the ulcer is covered by yellow, tan, gray, green, or brown slough and/or tan, brown, or black eschar in the wound bed.

Until enough slough and/or eschar is removed to expose the base of the wound, the true depth, and therefore stage, cannot be determined. Stable, that is dry, adherent, and intact without erythema or fluctuance, eschar on the heels serves as the body’s natural cover and should not be removed.

Treatment

Six primary general principles of wound care can be applied when initiating the treatment of any wound.

• Identify and treat underlying pathophysiology if possible

• Debride non-viable tissue if healing is expected

• Provide nutritional support if healing is expected

• Identify and treat infection

• Use appropriate topical therapy

• Consider advanced modalities

Along with managing the wound it is also crucial to manage the symptoms that are often associated with wounds including pain, odor, bleeding, and exudate. When these symptoms are left untreated they have the potential to affect a child’s quality of life by leading to anxiety, embarrassment, and social isolation.

When formulating a treatment plan there must be a clear definition about whether the goal is to heal the wound or control the symptoms associated with the wound. For example, when the goal is to heal a wound, debridement is critical to allow wound healing. When the goal is to control symptoms associated with a wound, debridement is only important to the extent that it is required to control odor. Nutritional support is also critical to wound healing, but when a wound won’t heal, the child is near the end of life, and the goal is to control the symptoms associated with the wound, then nutrition is not important. Children who are close to the end of life may have poor appetites. In these cases there is no need to encourage any more nutritional intake than the child can comfortably tolerate.

Debridement

Extensive literature discusses the importance of removing non-viable or infected tissue from a wound bed because it may delay wound closure and contribute to infection.¹⁸^–²⁰ The data is largely derived from adult literature, but the principles can be applied to the pediatric population. Unless surgical debridement is necessary due to extensive damage that is not easily addressed by conservative approaches, topical wound debridement outside the operating room may be successfully performed by application of a topical anesthetic such as EMLA followed by gentle curettage or cautious debridement with a sharp instrument. Enzymes have also been used successfully in cases where sharp or more aggressive debridement may not be possible or indicated. As with many products related to wound care, minimal data is available establishing safety and efficacy of enzymes in the pediatric population. Establishing the risk-benefit ratio and reviewing the patient medical history is imperative prior to prescription of any enzyme. No documentation is available regarding use of this drug category in neonates, therefore, application in this population cannot be recommended.

The primary enzyme available on the U.S. market is collagenase, because papain-urea products are not available. Use of medicinal honey as an antimicrobial and debridement- promoting agent has been documented for pediatric use, although not in well-designed randomized controlled and adequately powered trials. It appears to have been well tolerated and effective in the limited data presented.²¹

Autolytic debridement, the use of occlusion and a moist environment to promote debridement through the body’s own macrophages, presents an alternative approach to topical drug or medication therapy. In the presence of normal cell and immune response activity, preventing desiccation of the wound bed allows for a natural debridement accomplished by macrophage activity, wound bed enzymes and subsequent autolytic activity. Thin films, hydrocolloids, hydrogels, and other dressings that maintain a moist environment may benefit the autolytic process.

Nutrition

The adverse effects of poor nutritional status on tissue repair, infection rates, morbidity and mortality are well documented in the literature.²⁵^–²⁷ Understanding the overall nutritional status of the pediatric patient by reviewing markers, including but not limited to albumin and pre-albumin levels, is a key component of wound healing. Despite relieving pressure, addressing the underlying wound etiology and choosing an adequate dressing, tissue repair may not occur in the absence of adequate nutrition. Including a nutritionist in the interdisciplinary team caring for the patient may be useful.

Topical therapy

Myriad topical dressings, ointments, and treatment modalities are available. The variety of products and manufacturers’ claims creates confusion rather than clarity as to which treatment is most appropriate and effective. It is important to explore in greater depth the information provided with each product, particularly indications and contra-indications, before product selection. This overview is intended to categorize each of the primary dressing types. Table 35-3 provides a concise list of advantages and disadvantages of each product in a category. The data listed are meant as a guideline since individual medical status needs and considerations will vary among patients. Similar products within each category have never been compared with each other in any published Level I or credible trial. Based on the lack of research, it may be justly assumed that the major differences between products within a dressing category are based on cost considerations, qualitative features, patient tolerance, availability, and educational support provided by the industry. Each patient’s wound requirements, medical status, tolerance to product components, reaction to adhesives, and other features should be considered before choosing a product in any category.

Zinc is another heavy metal with antimicrobial properties. While some benefit has been suggested when applied topically,¹³ pediatric data is not available. There is no reason to suspect that limited use of a product with topical zinc on a superficial lesion poses any risk, yet caution is still warranted. Topical antimicrobials, including Neosporin, are commonly prescribed and are also available over the counter. Neosporin and similar agents are known to cause sensitizing reactions.¹⁴ Available data suggests they may be of benefit in reducing surface colonization, however simple daily cleansing with a liquid antimicrobial cleanser and water, followed by occlusion with gauze, is inexpensive and effective.¹⁵ A comparative study on incision and drainage of simple lesions in adults randomized to either an oral antibiotic or placebo showed no difference in outcomes, thereby suggesting that good wound cleaning is effective in preventing infection in the non-compromised patient.¹⁶

Topical gels with metronidazole offer the benefits of a hydrogel as listed above, while assisting with odor control caused by anaerobes. Other antimicrobial ointments, including mupirocin ointment, address gram-positive organisms in the wound environment. A review of the literature ¹⁷ reviews differences in effectiveness and cytotoxicity levels of different topical antimicrobial agents. The data presented are from studies in the adult population and should be interpreted with caution when applied to the pediatric wound patient.

Infection control

All wounds are colonized by bacteria, fungi, and other infectious agents. It is not until the infectious agent is present in sufficient quantities that the wound is considered infected. Staphylococcus epidermis and Corynebacterium are the most common wound colonizers while Proteus, Klebsiella, Pseudomonas, and Candida are the most common infectious agents. The presence of pathogens at critically colonized levels are known to delay the tissue repair process.²²,²³ They can also lead to purulent exudate, pain, and odor. Clinical and systemic signs of infection must be carefully reviewed to ensure the wound and peri-wound skin condition is consistent with infection. Swabs and wound cultures are most accurate when taken post debridement or following gentle cleansing with a non-antimicrobial agent. Use of antimicrobial agents may result in no growth from the culture. Unless superficial debris and contaminants have been removed, the swab culture may not be indicative of deep-tissue pathogens.²⁴ Simple contamination may be addressed through superficial debridement and wound cleansing and may not require the use of antibiotic therapy. Antimicrobial dressings may be used with caution as previously mentioned. The larger the wound surface area, the greater the need becomes to determine risk of systemic absorption of any agent that may be incorporated into a dressing, including silver, polyhexamethybutylene, iodine, or other antimicrobial. Antibiotic selection will be based on numerous factors, including identification of pathogens, spectrum of coverage of the antibiotic, and patient tolerance.