30 - HIV, AIDS
Editors: Goldman, Ann; Hain, Richard; Liben, Stephen
Title: Oxford Textbook of Palliative Care for Children, 1st Edition
Copyright 2006 Oxford University Press, 2006 (Chapter 34: Danai Papadatou)
> Table of Contents > Section 3 - Symptom care > 28 - Skin symptoms
28
Skin symptoms
Gillian Watterson
Jacqueline Denyer
Richard Hain
Introduction
The skin can in some ways be considered one of the largest organs of the body, and it can be involved in a wide range of conditions that limit life in childhood. Some are primary dermato-logical diseases that are ultimately fatal because of their effect on the skin itself. Among these, perhaps the most important is epidermolysis bullosa (EB), a painful, debilitating and disfiguring inherited condition of fragile skin. The range of symptoms experienced by children with EB is wide, reflecting both the diverse anatomical locations in which skin is found and the broader psychological and emotional impact of altered self-image.
Because skin is so widely distributed, it is not surprising that it is also involved as an incidental problem in many other, non-dermatological life-limiting conditions. A range of non-malignant and sometimes malignant LLC may be complicated by symptoms attributable to damage to or dysfunction of the skin. These include, for example pruritus associated with cholestasis, dry skin associated with mucopolysaccharidosis and pain or odour associated with pressure sores.
This chapter will consider both the symptoms associated with life-limiting dermatological disease, particularly EB, and those associated with other LLC that manifest in the skin.
Dermatological symptoms in children with life-limiting disorders
Fungating malignant tumours
Aetiology
Fungating tumours are rare in children but when they occur can be an extremely distressing, causing not only pain but emotional and psychological anguish as a result of disfigurement, bleeding and odour. They may occasionally arise from rhabdomyosarcomas, squamous cell carcinomas and lymphomas.
Pathology
Fungating malignant wounds result from infiltration of a tumour into the skin and it blood and lymphatic vessels. Extensive damage to the skin, progressing to necrosis can result, due to the loss of vascularity.
These wounds may produce copious exudate, permitting the invasion of the tissue by both aerobic and anaerobic organisms which can produce an offensive smell.
Thus the emergence of a fungating tumour can be a source of enormous distress producing both physical discomfort as a result of pressure symptoms and devastating psychological problems because of loss of altered body image and loss of dignity.
Management
Management of fungating tumours relies on an interdisciplinary approach for optimum symptom control of pain, irritation, infection and malodour and haemorrhage.
1. Pain: A combination of non-pharmacological approaches (such as guided imagery) and pharmacological methods such as those medications acting to reduce neuropathic pain and nociceptive pain should be considered. Case reports in adult patients describing topical diamorphine applied directly to the wound, suggest it can provide analgesia without systemic opioid adverse effects [1, 2]. This form of topical analgesia would be ideal for the pediatric population and further controlled studies are awaited.
2. Irritation: Continual leakage of exudates is a cause for cutaneous excoriation in fungating tumours. Methods of prevention have included topical anaesthetic agents which had limitations. They did not provide an adequate barrier from the exudate and they contained alcohol which caused stinging. Two products are currently being trialled in adults: Lutrol which is a local anaesthetic gel with lignocaine (lidocaine) and Cavilon, an alcohol free agent [3].
3. Odour: Systemic antibiotics to treat the usual skin pathogens may be required, as well as metronidazole for anaerobic organisms. Topical metronidazole gel [4, 5, 6] may reduce the need for the systemic route, but it is not useful in larger tumours, due to inability to penetrate to the offending bacteria. Debridement of the necrotic tissue would be useful in reduction of malodour but this is a potential cause of spontaneous bleeding and this risk need to be assessed.
4. Haemorrhage: Practical methods of preventing bleeding include, appropriate cleaning techniques, use of non-fibrous materials, good dressing application/removal techniques and maintainance of humidity at the wound/dressing interface. Pharmacological agents used to control bleeding include oral fibrinolytics (such as tranexamic acid), radiotherapy and embolization. Topical adrenaline 1 : 1000 may be applied as an emergency measure.
5. Local wound management: This should be occlusive or semi-occlusive and permeable or semi-permeable. The function of the dressing is to act as a reservoir for the excess exudates and conserve the surface humidity and moisture in order to prevent adherence [1].
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Pruritus
Itching (pruritus) is reported relatively uncommonly in children with life-limiting conditions. When it does occur it can be one of the most uncomfortable symptoms to experience and one of the most challenging to manage. This is partly because, until recently, relatively little was known about the pathophysiology, and therefore the most appropriate therapeutic approaches.
Pruritus has been defined as an unpleasant cutaneous sensation which provokes the desire to scratch [7]. Identifiable causes can include, for example, renal failure, cholestatic jaundice or medications such as morphine itself. In children with life-limiting conditions, there may be no obvious cause. Like pain, it is an illustration of the need for a systematic and rational approach to diagnosis and management of symptoms. Such an approach may fail; pruritus is a difficult symptom to manage.
Mechanisms
The origins of pruritus have been classified as cutaneous, i.e. arising from the skin itself, neuropathic, i.e. caused by damage to the nerves, or neurogenic, i.e. caused by nerves that function well but are acted on by pruritogenic stimuli such as cholestasis. To that could be added pruritus which is of mixed origin, and that which has a largely psychogenic origin [8].
The itch of cutaneous origin shares much of its neural pathway with the sensation of pain. Like pain, pruritus of neurogenic origin is transmitted through C fibres. It is now clear that these are specifically evolved for the transmission of itch. They do not respond, as pain fibres do, to mechanical stimuli but to a number of pruritogens including histamine and acetylcholine. Itch can therefore be seen, not as a low level experience of pain, but a specific modification of it. Its evolutionary significance is not clear.
Another way to categorise types of pruritus is to distinguish between those that result from direct stimulation of these itch specific C fibres (by histamine itself or a small number of other transmitters [8] and causes that are indirect by causing histamine release. It is important to note that while histamine is an important direct stimulator of C fibres it is not the only one. Others include papain, kallikrein and interleukin 2. Even acetylcholine can cause itch through directly stimulating C fibres, though interestingly only in atopic individuals [9].
The observation that specific 5HT3 receptor antagonists such as ondansetron can relieve itch [10, 11] revealed that serotonin can cause pruritus associated with opioid therapy. Peripherally, serotonin is known to act indirectly through the release of histamine in skin mast cells [12, 13]. The extent to which histamine is involved in pruritus associated with opioids, if indeed it is involved at all, is far from clear [8, 14].
Management
As with all symptoms, a rational approach to the management of pruritus requires a structured assessment based on history, examination and laboratory findings. Given their similar pathophysiology, it is perhaps not surprising that an assessment of pruritus should be along the same lines as that of pain. This should start with noting precipitating or relieving factors. The quality of the subjective experience can sometimes include, for example, a burning sensation or that of ants crawling over the affected area (formication). The location and any radiation of the sensation should be noted, and perhaps some measure of its severity. The timing of the symptom can be helpful, whether it is worse during the day or during the night, or whether intermittent or continuous. More specific causes may be identified by taking a thorough drug and travel history.
Examination findings that may point to a cause would include findings of eczema, scabies or jaundice. Psychogenic pruritus should also be considered.
Invasive laboratory investigations are often unnecessary or inappropriate in the palliative phase, but can for example confirm a presumptive diagnosis of pruritus due to cholestatic jaundice. Pruritus can be an early presenting sign of relapse in some lymphomas.
If there is an obvious cause, such as dry skin, this should be managed appropriately. Management can be considered under non-specific and specific approaches.
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Specific measures
Opioid induced
Opioids can induce itch by at least two, apparently unrelated, mechanisms. Intradermal injection of some opioids, including morphine, will cause a typical histamine-like response that is not observed in opioids of a different class such as fentanyl [15]. This localized itch and response is suppressed by H1 antihistamines [16].
More generalized itch is a complication that occurs in some children receiving opioids systemically. In adults, the proportion has been put at 1% [17] but anecdotally it is more frequent in children. It is often manifest by the child repeatedly rubbing the tip of his or her nose. It is not clear why this should be the apparent location of opioid induced itching, nor why it should be commoner in children, but the phenomenon has also been observed in adults [18]. Pruritus is more likely in association with opioids given by the spinal route [17]. This is a relatively uncommon route in paediatric palliative medicine and there are no data yet to compare with other routes.
It is currently felt that pruritus associated with systemic opioids is not caused by histamine [8]. It may be that morphine can stimulate itch through mu receptors while at the same time suppressing it through kappa receptors [19]. Good evidence for the role of opioid receptors is the observation that naloxone will relieve the itch [20] but H1 antihistamines will not. Serotonin clearly plays a part, since serotonin antagonist ondansetron can prevent as well as relieve some opioid induced pruritus [10, 21]. Given their familiarity to paediatricians, and their benign side-effect profile, it seems appropriate to consider serotonin antagonists early to treat the problem in children. Opioid antagonists will also improve pruritus [22] but most also reverse analgesia. Nalbuphine appears to be the exception [23].
The mechanism of pruritus associated with opioid therapy is therefore complex. The observation, however, is that ondansetron and opioid antagonists such as naloxone are more likely to be effective than our traditional approach using H1 antihistamines.
Hodgkin's lymphoma
Pruritus is relatively common in terminal Hodgkin's disease. Steroids and vinblastine or other relatively non-toxic chemotherapy have been reported to be effective [8].
Uraemia
Pruritus associated with uraemia is multi-factorial in nature, including the effect of dry skin, cytokines and immunological mechanisms [8]. Uraemic patients with pruritus demonstrate raised numbers of mast cells [24, 25, 26] and electrolyte imbalances [27]. Imbalances in opioid receptor subtype expression have been postulated [19].
None of these explanations is entirely satisfactory on its own, and there is an apparent contradiction in the consistent observation that histamine levels and numbers of mast cells are high, while H1 antihistamines are ineffective unless they sedate.
The opioid antagonist naltrexone has been studied [28, 29]with inconsistent results. It has been suggested [8, 28, 29] that it may have a place in severe itch associated with uraemia.
Cholestasis
Severe cholestasis as a cause of itch is rather rare in children. In adults, cholestatic pruritus is described as typically commencing on the soles of the feet and the palms of the hands. The mechanism is not clear but is believed to be central [14, 30].
In adults, there has been considerable research which suggests that opioid antagonists may have a useful role [31, 32, 33, 34]. As always, if given to patients who are also receiving opioids, there is a risk that control of pain can be lost. There is some evidence of a paradoxical response of itch to opioids [35, 36]. Drugs that induce hepatic enzymes such as rifampicin [37] and phenobarbital [38] can be effective although both can interfere with hepatic metabolism of other drugs. Phenobarbitone (phenobarbital) is quite widely used in paediatric palliative care for seizures and sedation. Cholestyramine (Colestyramine) has been used in primary biliary cirrhosis [39]on slender evidence [8, 40]. It's effect depends on an intact enteropathic circulation of bile acids and therefore it is ineffective if the bile duct is completely obstructed.
Non-specific measures
Many children with life-limiting conditions have dry skin, related partly to their hydration status and partly to the nature of the underlying condition. This can often be helped using simple topical moisturising creams. There is further benefit to be gained through engaging the family and from the counter irritation of rubbing the cream into the skin.
Damage to the skin due to scratching itch is common, particularly among children with neurodegenerative conditions. The child's nails should be kept short, or if necessary in mittens, to reduce the likelihood of skin damage. Itch can be made worse by an environment that is too warm and carers for children with life-limiting conditions should ensure they are not overdressed and that the room temperature is kept reasonably cool. Treatment with ultraviolet B has many different actions [8] and should be considered in children with HIV AIDS or uraemia [41, 42, 43].
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The pendulum has somewhat swung away from the traditional approach of prescribing an H1 antihistamine, irrespective of the cause of itch. It has been suggested that H1 antihistamines are effective only if they are also significantly sedating, or if the itch is specifically histamine mediated. However, as always in paediatric palliative care, it is important to have an empiric approach to fall back on if more evidence-based approaches such as those outlined earlier in this section have failed.
Although calamine lotion (another paediatric favourite) is more reliably effective due to its phenol content, as it evaporates it can dry the skin which can make pruritus worse. Capsaicin cream is rarely used in children partly because of the mild burning sensation it causes when first used, but can be effective in some sorts of itch [44]. There are also a number of topical H1 antihistamines such as diphenhydramine.
Summary
An approach to pruritus is similar to many of the other symptoms considered in this book that complicate the palliative phase of children with life-limiting conditions. It is often possible to develop a rational and evidence based initial approach, taking into account the probable cause for itch and its pathophysiology. If this first line therapy fails, however, it is important to consider less specific and more empiric approaches such as topical drugs and H1 antihistamines, bearing in mind that these may carry only a small chance of success and bring with them inevitable side-effects.
Pressure sores
The skin is richly innervated, and when it becomes damaged is a powerful source of pain. Furthermore, the impact of skin breakdown on body image can have profound emotional and psychological impact [45]. Managing pressure sores is therefore of critical importance in maintaining good symptom control and quality of life in general in palliative care.
Evaluation of risk
Children with life-limiting conditions are particularly susceptible to skin breakdown. Six groups of factors that can influence the likelihood of a pressure sore have been identified in adults [46, 47]. They include sensory perception, skin moisture, activity, mobility, risk of friction and shear, and finally nutritional status. The nature of life-limiting conditions in childhood means that children needing palliative care will be at risk simultaneously of many of these. Those with non-malignant diseases are typically relatively immobile, needing frequent changes of position by carers, each of which risks friction or shear damage to the skin (shear damage occurs when the skin adheres to an external surface such as bedding while underlying tissue moves [46]. Prolonged moistness is also common: there may be contact with urine soaked nappies or bedding, and hyperhidrosis is a feature of many metabolic conditions in childhood. Furthermore, many children with life-limiting conditions suffer from mild nutritional deficiencies due to practical difficulties with oral or gastrostomy feeding.
Assessment of risk factors for pressure sores is an important step in reducing the likelihood that they will occur. Such an assessment has been formalized in a number of instruments, of which the Braden Scale is probably the best validated [46, 48, 49, 50]. All these studies were carried out in an adult population, but the Braden Scale has been modified for use with children [51]. It has been observed [52] that this paediatric Braden Q Scale does not always accurately identify those at risk in acute hospital paediatric settings.
Assessment of severity
The single term pressure sore or pressure ulcer is used to cover a wide range of damage, varying from the trivial to the life-threatening. The term is therefore of little practical help without further elaboration. A staging system has been devised [53]. Stage 1 simply describes intact skin which has become reddened and is distinguished from a normal response to pressure only in that the erythema is not blanchable.
At stage 2, there is partial thickness skin loss which involves the epidermis and dermis itself. The sore is very superficial, however, and may appear as a blister or shallow ulcer.
Stage 3 pressure sores have loss of the full thickness of skin and some damage or even necrosis to subcutaneous tissues. It looks like a deep crater but does not penetrate underlying fascia.
By the time stage 4 is reached, the most severe form of pressure sore, there is extensive destruction including tissue necrosis and damage to underlying tissues such as muscle, bone, tendons or joint capsules [2].
Clinical management
Where possible, it is clearly desirable to avoid pressure sores developing in the first place. Good nursing care, and in particular regular inspection of the skin over bony prominences and other pressure points, is essential. Prompt intervention to avoid prolonged moistness, infection or immobility can reduce the risk. Simple measures such as regular turning (as appropriate) of the patient and use of pressure relieving mattresses such as Spenco and sheepskin bedding should be considered as an essential part of the care programme. Where moistness of the skin is inevitable, barrier creams or ointments can be helpful to maintain an environment in which the skin can heal. Careful attention to the child's nutritional status in consultation with dieticians can be important.
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During a prolonged palliative phase, a child will usually be at home for most of the time, and the main carers will be the rest of the family, particularly parents, rather than nursing staff. The family may need education in avoiding risk factors and prompt recognition of early skin problems.
The likelihood that a pressure sore will heal is related to the stage. Many stage 1 pressure sores will return to normal skin if carefully managed. This is less likely if the pressure sore has reached stage 4 [54]. Stage is probably less clearly related to the risk of severe symptoms: even superficial sores can be extremely painful.
Pressure sores may give rise to physical symptoms in two main ways:
i Pain: Even a superficial pressure sore can be extremely painful, to an extent that is often disproportionate to its size. In children who appear to be pain but are not able to express an exact location, such as those with impaired cognitive function, it is always important to consider an early pressure sore as the cause. The management of pain has been considered in detail in a separate chapter (cross ref Chapter 21, Pain). The pain of pressure sores is sharp, intense and well localised but there is often an area of hyperalgesia extending well beyond any obvious skin damage. The pain is usually responsive to simple analgesia and opioids, but these should always be offered alongside measures designed to promote skin healing.
There has been increasing interest over recent years in the use of topical analgesics, particularly major opioids, for managing the pain of more serious ulcers [1, 2]. Typically, 2.5 mg 5 mg of diamorphine are mixed with the preferred topical base.
ii Odour: Superinfection of any skin lesion can cause odour. This can be extremely distressing for patient and family alike and should be rigorously treated if possible. Odour is often caused by anaerobic organisms and systemic metronidazole can be very effective. Metronidazole too has been used topically [4, 5, 6] with good effect and less risk of systemic toxicity such as nausea and vomiting.
Ordinary measures such as maintaining cleanliness, always avoiding extreme abrasion and soaps that are strongly alkaline, are also important in reducing the risk of skin damage and infection.
Epidermolysis bullosa and other life-limiting conditions of the skin
Life-limiting skin disorders include:
Restrictive dermopathy, which is a very rare, fatal autosomal recessive genodermatosis, in which tautness of a translucent thin skin is the major clinical sign. The skin is highly vulnerable to tears and all reported cases have been born prematurely. The appearance of skin at birth is thin and shiny and it restricts limb movements and respiratory effort. Early neonatal death results from respiratory insufficiency, as the chest is unable to expand due to constriction from the skin [55].
The ichthyoses are a group of diseases characterised by disorders of cornification. The most severe forms cause a restrictive encasement of skin and affected infants are referred to as collodion babies . A severe form is the harlequin baby, which used to be incompatible with life due to restriction of respiratory effort by the skin. However it has been found to respond to treatment with oral acitrecin and indeed early management could prevent life-threatening events such as temperature dysregulation, disturbance in electrolytes and serious infections [56].
Neu-laxova syndrome is a rare disorder characterised by microcephaly, limb contractures and ichthyosis. Other frequently found features include pulmonary, renal and cardiac abnormalities. Neu-Laxova is a lethal condition; most of the infants have been stillborn or died within the first few days. Those surviving the neonatal period have not lived more than four months with death resulting from pneumonia or respiratory failure [57].
The main focus of this section will be to discuss the largest of this group, EB, but many of the principles can be applied to the care of other serious skin conditions.
EB sub-types and their prognosis
Epidermolysis bullosa is characterized by extreme fragility of the skin and mucosa and its susceptibility to blister and separate from the underlying tissue in response to minimal every day friction and trauma (Figure 28.1).
There are three main categories within the group: simplex, junctional and dystrophic, each varying in severity.
The recessively inherited types of EB, include junctional EB and recessive dystrophic EB and are the most severe. Although there is a wide spectrum of severity within this group many children are severely affected leading to serious morbidity and mortality. The incidence of recessively inherited EB is 1 : 175000 [58].
The most serious type of junctional EB is the Herlitz form. Blistering is generally present at birth or develops within the first few days of life and initially this often presents as a mild form of EB but disease progression can be rapid. It is important that, before the parents are informed, diagnosis is confirmed by analysis of a skin biopsy at a centre experienced in this investigation. Death usually occurs within the first few years of life, with many not surviving beyond the first few months. In this group of children, a support network should
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be formed with the community team, in order to initiate palliative care at the onset of diagnosis.
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Fig.28.1 Intrauterine damage in a neonate with a severe bullous skin disorder. |
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Fig.28.2 Advanced squamous cell carcinoma in an adolescent. |
Recessive dystrophic EB in its severe form, Hallopeau-Siemens results in multiple complications. There is a tendency for blistered areas and wounds to heal with scarring leading to the development of contractures.
Although it is unusual for those affected to die in infancy, the contractures lead to progressive and permanent disability. The survivors of childhood are also at risk of an aggressive form of squamous cell carcinoma as young adults and indeed it has been reported in a child of 13 years [59] (Figure 28.2). There are often multiple primary tumours and the average life expectancy after the tumour diagnosis is 5 years. In this subtype, our approach in the United Kingdom is to establish links with the community multi disciplinary team from diagnosis, including respite provision at a children's hospice.
When required, palliative care can be offered from those who know the child and their family. It is extremely beneficial, if a videotape of the dressing techniques specific for each individual child is supplied as part of their care plan, when admitted for hospice care. It is important that genetic counselling is offered to families following diagnosis, in order that they are aware of prenatal diagnosis for future pregnancies.
Symptoms and their management in EB
Children with life-limiting skin disorders such as EB experience a variety of symptoms which present in a multi-system manner.
Pain
From animal studies of EB, it appears that even in the fetal period, repeated disruption to the skin from minimal trauma within the uterus, leads to skin nerve damage and increased production of nerve growth factor (NGF). This subsequently produces hyperinnervation of the peripheral sensory nerves and hyperalgesia ensues (an exaggerated response to a normal noxious stimulus [60]). Hyperalgesia means that minimal trauma and normal tactile actions, such as hugging, can lead to both acute and chronic inflammatory pain in children with skin disorders.
Pain (see also Chapter 21, Pain management) is individual and encompasses not only the physical sensation but also cultural, social, emotional aspects [61]. This needs to be considered when assessing a baseline pain score of any child who has a chronic illness.
Procedural pain in patients with EB is a major source for pain. In addition, for procedures such as the dressing change or baths, which may occur on a daily basis, the patient appears to have enormous anticipatory fear, which needs to be considered in addition to the actual pain experienced. In fact in some children, bathing is impossible even with adequate analgesia because the exposure of all the wounds simultaneously and pain from being lifted in and out of the bath is unbearable.
Table 28.1 Sources of pain in EB | ||||||||||||||
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The first steps of managing pain, is to assess and formulate a baseline pain score. Prevention of the symptoms such as constipation, osteoporosis and gastroesophageal reflux may be possible with appropriate medication as discussed under the symptoms. Treating superficial skin infections, which seem to exacerbate acute pain, with topical or oral antibiotics is important. Good dressing techniques and regular dressing changes are necessary.
When analgesia is required for mild pain, for example, small blisters requiring a quick dressing change, combining simple analgesia such as paracetamol with a non-steroidal, for example, ibuprofen or piroxicam melt (which just requires once daily administration: 20 mg/melt), is usually sufficient. However with more severe pain associated with dressing changes or baths, opioid analgesia and anxiolytic sedation such as midazolam is usually necessary. In this case, doses of oral morphine should be in the range of 0.3 0.6 mg/kg and midazolam, 0.5 mg/kg given around 30 45 min prior to the procedure [62]. Procedural pain has also been managed by novel methods of analgesia such as Entonox [63] and fentanyl lozenges [64]. Both approaches have the advantage that the child should be able to administer the analgesia to him or herself.
However with Entonox, (nitrous oxide) there have concerns regarding potential for abuse because it is known to be a habit forming drug [65]. It is also known to inactivate vitamin B12 and repeated use affects folate metabolism, impairing DNA synthesis and causing megaloblastic changes in the bone marrow [66].
For the chronic background pain administration of long acting morphine (MST or) on a daily basis may be required . Pain in EB is partly neuropathic in origin and may be relatively opioid-resistant. It may respond to a low dose of amitripty-line, nocte (0.5 mg/kg) [67]. It may take up to two weeks to be effective, it is anticholingergic and there have been reports of blurred visions as an adverse effect. Gabapentin [68], an anti-convulsant drug used in epilepsy, has also been used to manage the neuropathic pain in children. This has an advantage over amitriptyline as it has no interaction with any other medication and it has virtually no reported adverse effects. Well controlled randomised studies are necessary to investigate the efficacy and safety of these agents against pediatric neuropathic pain. Children with lethal skin conditions may also require opioid analgesics, anxiolytic and sedative drugs, often via a syringe driver, when they reach the terminal phase of their illness.
It is essential that as well as the above pharmacological therapies physical treatments such as physiotherapy and hydrotherapy, visualisation and guided imagery should be offered in combination to manage a child's acute and chronic pain.
Gastrointestinal
Blistering may form internally throughout the entire gastrointestinal tract, extending from the oropharyngeal region making eating an unpleasant and painful experience. The oral mucosa is very fragile and blisters readily occur in response to sucking or eating even soft foods. Breast feeding is possible and causes minimal trauma to the mucosa, but friction of the face against the breast can result in blistering. Feeding is therefore a major problem from a very young age.
In dystrophic EB, the tongue becomes fused to the base of the mouth making mastication and removal of debris from the teeth difficult. In time, the repeated blistering and scarring lead to loss of the labial sulcus and microstomia.
Blistering in the lining of the oesophagus, results from trauma from swallowing, even when the diet is restricted to soft foods. This is acutely distressing for the child and gastrooesophageal reflux as well as the formation of webs and strictures ensues.
In the Herlitz subtype, in addition to the problem with feeding, affected infants suffer malabsorption leading to profound failure to thrive even when intake is optimal. This is one of the most distressing components of the disease, as parents watch their child starve. It is not unusual for infants of several months old to die weighing less than their birth-weight.
Measures to improve eating and nutrition include use of specialised teats such as those recommended for infants with cleft lip and palate reduce the need for vigorous sucking and limit trauma to the oral mucosa.
Despite such measures infants often remain reluctant to feed due to pain from intra oral blisters and require analgesia prior to feeding. Use of teething gels can improve comfort. In order to provide adequate nutritional support needed because of the increased requirements and competition for nutrients between wound healing and growth, the insertion of gastrostomy tubes may be necessary in those with severe dystrophic EB [69]. In the longer-term survivors of junctional EB, feeding via a gastrostomy has led to breakdown of the skin on the abdomen with exacerbation from leakage of acid gastrointestinal contents around the device.
Gastroesophageal reflux occurs in severe EB and is usually managed by a combination of medication including, gaviscon, ranitidine or omeprazole and domperidone. Oesophageal strictures are also a feature of dystrophic EB and these can be exacerbated by reflux. Strictures may be successfully relieved using balloon dilatation under expert radiological guidance [70].
At the lower end of the gastrointestinal tract, pain from perianal blistering leads to withholding of stool and faecal retention. This is a common feature in all types of EB. Management is by use of stool softeners and laxatives and adding soluble fibre to supplementary feeds (Figure 28.3).
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Fig.28.3 Extensive chronic skin ulceration associated with cachexia. |
Respiratory
Herlitz junctional EB may also affect the larynx with bullae formation [71]. This is characterised by a hoarse cry in the first few days or weeks of life and subsequently recurrent attacks of stridor occur, each episode carrying a great risk of asphyxiation. Acute stridor responds to nebulised budesenide and oral dexamethasone. However, this is a palliative measure to reduce respiratory distress and has no effect on survival.
Tracheostomy has successfully been carried out in severely affected infants, and may be considered a palliative measure to provide comfort. In the presence of failure to thrive, it is unlikely to alter outcome. Ulceration commonly occurs around the tube and beneath the securing ties. Respiratory tract infections are common in this group of children and may lead to death from pneumonia. Short courses of oral antibiotics may provide short-term resolution of symptoms.
Cardiac
A small number of children with severe EB develop a fatal dilated cardio myopathy [72]. The cause for this is unclear and routine echocardiograms are carried out at regular intervals to monitor the progress.
The child may become tired and tachypnoeic due to a decrease in flow of oxygenated blood from the heart, associated with peripheral oedema. This is exacerbated by fragility of the skin, leading to a progression in the number of open wounds, providing much distress for the child and family. Occasionally acute chest pain secondary to ischemia may ensue.
This can be managed with conventional diuretics, low flow oxygen therapy and often may require the use of strong analgesia such as morphine. It is often important to reduce anxiety in the patients by providing adequate sedation or an anxiolytic such as diazepam.
Anaemia
This is a common and troublesome symptom in children with a skin disorder, in which there is inadequate nutritional intake, but also as a result of chronic blood loss from skin and mucosa. It is most commonly iron deficiency anaemia but normocytic normochromic anaemia may also exist. Symptoms include fatigue, pallor and if it is acutely severe, the child may have signs to suggest a hyperdynamic circulation such as tachycardia and a systolic cardiac murmur. Treatment can include dietary advice, oral iron supplements, intravenous iron and blood transfusions. It is important to judge the management of each patient individually in conjunction with the family; the use of repeated transfusions of blood and iron may not be appropriate.
Renal
Renal complications, although rare, have been described in dystrophic and junctional EB.
Chronic post infectious glomerulonephritis most probably secondary to streptococcal skin infection has been described in dystrophic EB. Nephropathy is a recognised complication of recessive dystrophic EB and this may be secondary to renal amyloidosis and can be fatal [73].
End-stage renal failure is when the glomerular filtration rate is <10 ml/min/1.73 m2. Clinically, the main features are growth failure, anaemia, osteodystrophy leading to severe bone pain and hypertension.
Management of these symptoms include expert nutritional advice, which is mainly protein restriction; 1 alpha hydroxycholecalciferol (hydroxycholecalciferol) supplement for the renal osteodystrophy and sodium bicarbonate if metabolic acidosis persists. Eyrthropoietin and growth hormone injections can also be considered to manage the anaemia and growth failure.
Peritoneal dialysis and haemodialysis is used to achieve control of biochemical abnormalities but the ultimate control of renal failure is transplantation. Children who receive live donor transplants usually have 90% 1 year-graft survival.
Following transplant, growth is improved and indeed the overall quality of life. However a renal transplant is not a cure and in children who have already a life limiting skin disorder, it is vital to give an alternative active choice of symptom control.
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Psychological distress
The birth of a child with severe skin disease can be a distressing perinatal experience. For the family to survive emotionally the initial shock of seeing their baby with open wounds, and the guilt of passing on a previously unknown disease requires support and understanding from all those in contact with them. In view of this, parents of children with rare conditions such as EB should attend a designated centre where questions can be answered and staff has knowledge of the condition, its complications and recommended treatments.
Paediatric community nurses can offer support with dressing changes, but the child often prefers family help to professional help. Large quantities of expensive dressing and enteral feeding materials need to be stored in the family home. Parents are typically in a state of constant anxiety, both about the cost and that there will be disruption in their supply of dressings, with disastrous consequences.
Even from an early age, children with any dermatological disorder are conscious that they are different from their peers because of their physical appearance. In those with dystrophic EB the knowledge that their condition is progressively disabling can lead to depression as they realise loss of previously mastered skills and developmental milestones. They become anxious about school and socialising and it may even cause depression, to such an extent that compliance, especially during the adolescent period, can be a huge problem. In this group of patients, screening for squamous cell carcinoma may not be permitted in a hospital setting and home visiting, in order to allow dressings to take place in familiar surroundings, with respect for privacy is often necessary.
Education
Prior to entry of a child with fragile skin into playgroup or school, everyone who will be in contact with the child should receive advice regarding handling. This must include those involved in transporting the child to and from school.
Children with severe skin disease generally attend mainstream schools, but require input from a non-teaching assistant in order to achieve their full potential and to avoid any unnecessary trauma.
Simple measures such as leaving the classroom immediately before or after the end of the lesson reduce the risk of knocks or shearing forces in crowded corridors. Care-assistants can carry heavy books for the mobile child or are required to push wheel-chairs for more severely affected children.
Provision of a lap top computer or a scribe ensure work is recorded even when the child's hand function may be impaired.
Carers should be trained to apply dressings if the child has an accident during school hours and this releases the burden on parents who may otherwise be called to the school.
Prior to school entry, teaching and non-teaching staff should be offered training by a specialised nurse and written guidelines given.
Mobility
Severe hand deformity in recessive dystrophic EB results from repetitive trauma leading to scarring, contractures and pseudo-syndactyly [74]. Functional improvement of the hand can be achieved by surgical release and application of skin grafts. Following surgery light-weight splints are given to try to maintain function. Unfortunately the effects of surgery are often short-lived before the hand contracts again. Children often become disenchanted with surgery and refuse further intervention.
Progressive scarring in those with dystrophic EB gradually reduces mobility and in combination with a reluctance to move and weight-bear due to pain, children may suffer with osteoporosis [75]. Severe bony pain has been treated with intravenous pamidronate along with calcium supplementation but the efficacy of bisphosphonates in this context has not yet been definitively shown. Children may become dependent on a wheel-chair and it is important that the child is encouraged to retain some mobility, for example being able to transfer in order to avoid excessive lifting at a risk of further skin damage (Figure 28.4).
General principles of skin care in EB
Dressings
Children with severe skin disorders form develop large areas of chronic ulceration, which are often difficult to heal. Whilst wound management is always with the intention of healing, in reality this is often not achievable. In reality dressings should be chosen which would not lead to further ulceration and cause no harm to the surrounding skin.
 |
Fig.28.4 Typical distal skin limb deformity in a child with dystrophic EB. |
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The correct dressing should cause minimal pain on removal. Whilst many dressings are advertised as non-adherent there are only a small number, which are truly atraumatic when used on children with fragile skin.
Dressing changes can take several hours and should be kept to a minimum in order to limit pain and distress. If there is copious exudate, this can be managed by leaving a primary dressing in place and changing the secondary dressing more frequently.
Some children or their carers prefer to use Vaseline gauze or tulle dressings, but these require changing daily as this carries the risk of removal of new epithelium if there has been any adherence and additional distress due to frequent changes of dressing.
Even if removal of dressing is pain free, exposure of the wound is painful and changes of dressings should be done as quickly as possible. When the pattern of the wounds is known, dressings can be pre-cut to speed the procedure.
Dressing changes are considered to be a clean rather than sterile procedure . Wearing gloves can drag on the skin and cause unnecessary trauma, as well as carrying the risk of distressing the child and making them feel dirty and unattractive.
Infection is a common problem with resistant infections being increasingly seen. Surprisingly septicaemia is rarely described in this group of children unless this is secondary to infection from an indwelling central line.
Handling the child with severe skin disease
Handling should be kept to a minimum whilst enabling contact with the infant or child. Parents and other carers should be taught how to lift the children without causing skin damage from friction or shearing forces. Small infants should be lifted using a roll and lift technique . The infant is rolled onto his side, one hand placed on the buttocks, and the other behind the head, or neck if scalp lesions are present; the infant is then rolled back onto the carer's hands and lifted in one movement.
 |
Fig.28.5 Trauma secondary to minimal handling in an infant with fragile skin. |
Older children can be lifted with one hand under their bottom and the other behind the head or neck. The children prefer to move themselves and this should be encouraged when ever possible to avoid skin damage.
No child with fragile skin should ever be lifted under the arms, as this leads to skin loss in an area, which is difficult to dress and has a tendency to heal with stricture formation in those with dystrophic EB.
Name bands cannot be worn as these cause friction and denudes the skin over the ankle or wrist; however labels can be applied over clothing or on the cot or bed.
Despite their skin fragility, children should be able to enjoy gentle cuddles, and kisses will do no harm (Figure 28.5).
Conclusion
Caring for children with life-limiting skin disorders poses a challenge for all involved in their management. It is essential that all professionals involved are familiar with the disease process and the particular symptoms which may arise, in order to provide multidimensional care in accordance with the child and family's request.
Most professionals working in paediatric palliative care will encounter such primary skin diseases only relatively infrequently. Much more often, they will be faced with the need to manage symptoms in the skin that arise from other, more general systemic LLC. The range of these is very wide: this chapter has provided an overview of the pathophysiology and management of some of the commoner symptoms that may manifest in the skin.
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