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.