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Clinical REVIEW

Presentation of childhood lymphoedema

Fiona Connell, Glen Brice, Sahar Mansour, Peter Mortimer

Childhood lymphoedema is a relatively rare condition, uncommon outside of specialist clinics, but which has a significant effect on the affected individual and the family. As a lifelong condition with, at present, no cure, management of the condition by dedicated lymphoedema therapists is of paramount importance. Increasingly, the underlying molecular genetic cause of some forms of childhood lymphoedema are being elucidated, which has lead to a more precise diagnosis and may, in the future, lead to novel treatments. This paper describes the ways in which the condition may present, ways it can be investigated and the current forms of management.

diagnostic difficulty to clinicians and distress 2003). A specific prevalence figure for Key words to parents. It is essential to obtain a rapid primary lymphoedema in the paediatric diagnosis and to implement correct population has been estimated at 1.15 Lymphoedema treatment at the earliest opportunity. In per 100,000 population, but these Lymphatic the UK many physicians and surgeons will numbers are based on those attending Milroy see less than 10 cases of lymphoedema in a single US clinic (Smeltzer et al, 1985). Distichiasis a year (Tiwari et al, 2006). It is therefore A female preponderance (M:F – 1:3) is imperative that patients are referred documented, although this may represent at an early stage to a clinic with wide ascertainment bias. Primary impairment experience and expertise in diagnosis of the lymphatic drainage system can and treatment. occur as a non-syndromic mendelian The main function of the condition or as part of a more complex is to return rich fluid, which has Phenotyping childhood lymphoedema syndromic disorder. exited from the capillaries, back to the Primary lymphoedema venous system (Damstra and Mortimer, Primary lymphoedema is chronic oedema Well recognised forms of primary 2008). Lymphoedema is a chronic, and caused by a developmental abnormality childhood lymphoedema often progressive swelling due to failure of the lymphatic system (Mortimer, 1995) Over the past few years the underlying of the lymphatic system to drain this fluid and is the most common type seen in molecular defects in two types from the interstitial spaces. This causes the paediatric population. In primary of lymphoedema have been well abnormal accumulation of tissue fluid in lymphoedema, fluid accumulates due to characterised; Milroy disease and the interstitial spaces and can be due to either abnormal function or structure lymphoedema distichiasis syndrome. This a number of causes both primary and of the lymphatic system. In most cases, has given a greater understanding not secondary (Rockson and Rivera, 2008). It oedema will be present from birth but only of the particular individual’s disease, usually affects the extremities as a result in some cases, although the lymphatic but also of the developmental pathways of abnormal regional drainage, abnormality is presumed to be present involved in the embryonic growth of although visceral drainage can also be congenitally, the swelling does not develop the lymphatic system in the embryo. impaired. Lymphoedema in children, while until some time later. It is thought that In the longer term, it is hoped that this not common, can cause considerable the lymphatic system normally functions new-found understanding will allow the at about 10% capacity and it is presumed development of novel medical treatments that this functional redundancy allows and perhaps one day the ‘Holy Grail’ of homeostasis to be maintained for some therapy to eradicate the disease in Fiona Connell is Clinical Research Fellow in Lymphoedema, time in this group of patients. an individual. St George’s University of London; Glen Brice is Genetics Counsellor at South West Thames Regional Genetics Service, St George’s University of London; Sahar Mansour A population prevalence of 1.33 per Other forms of primary lymphoedema is Consultant Geneticist, St George’s University of London; 1000 for all ages has been reported are also well recognised but the Peter Mortimer is Professor of Dermatological Medicine, but the authors acknowledge that this pathogenesis is less well understood. Cardiac and Vascular Sciences (Dermatology Unit), St is probably an under estimation of the In the past there has been a tendency George’s University of London true burden of disease (Moffatt et al, for all congenital lymphoedema to be

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incorrectly labelled as Milroy disease. et al, 2006; Connell et al, 2009b). For this Due to the increased risk of both The clinical and molecular findings in true reason, it is always worthwhile testing cleft palate and congenital heart Milroy disease are now clear, and the term the parents of an affected child before disease, additional pre-natal scans may should be reserved for the small group of calculating recurrence risks. be recommended for a fetus at risk of individuals and families fitting the specific inheriting the condition. phenotype (Brice et al, 2005; Connell et al, Lymphoedema distichiasis 2009b). In addition to Milroy disease and Lymphoedema distichiasis syndrome is lymphoedema distichiasis there are many a rare, dominantly inherited condition other forms of primary lymphoedema; for which the underlying genetic cause the phenotypic entities of primary was identified by Fang et al (2000). lymphoedema vary in age of onset, Almost all individuals with lymphoedema site of the oedema, associated features, distichiasis syndrome have in inheritance patterns and the underlying FOXC2 (Sholto-Douglas-Vernon et al, genetic cause. It is therefore important 2005). This condition is the association of ‘Ski jump’ toenail that when assessing a child presenting primary, pubertal, or post-pubertal, onset with lymphoedema that it is not only the lymphoedema with aberrant eyelashes Figure 1: Adult patient with Milroy disease showing lymphoedematous limb that is addressed. arising from the Meibomian glands in pedal oedema, ‘ski jump’ nails and papillomatosis A careful examination of the child is the eyelids (distichiasis – from Greek for due to congenital lymphatic abnormalities. essential. Other clinical features or aspects ‘two rows’) (Figure 3). Other associations of the history may enable recognition of include; cleft palate, congenital heart a specific diagnosis that has implications disease, varicose veins and ptosis (Brice for management. A detailed family medical et al, 2002). Half of affected individuals history should also be sought. will have clinically evident varicose veins from an early age, while 100% have Milroy disease venous abnormalities when assessed Milroy disease is congenital onset by ultrasound scanning (Mellor et al, lymphoedema which classically affects the 2007). A lymphoscintigram showing lower half of the legs only (Milroy, 1892). It lymph reflux (Figure 10) is suggestive of can, although rarely, affect the entire of the a diagnosis of lymphoedema distichiasis. lower limbs but is not reported to affect If distichiasis is not present in the the arms. Males and females are affected patient or a family member, the chance equally. In males, are common, of finding a in the causative affecting up to 30% of those carrying gene, FOXC2, is extremely unlikely. As the altered gene. Other characteristic distichiasis can be difficult to see, slit clinical findings include upslanting ‘ski-jump’ lamp examination by an ophthalmologist Figure 2. Prominent veins, commonly seen in toenails (Figure 1) and prominent large is advised wherever possible. Milroy disease. calibre veins in the legs (Figure 2), most commonly the great (long) saphenous veins (Brice et al 2005).

The causative gene was first located on chromosome 5q in 1998 (Ferrell et al, 1998) and subsequently numerous causative mutations in the VEGFR3 gene have been described (Evans et al, 2003; Ghalamkarpour et al, 2006; Ferrell and Finegold, 2008). In those individuals not conforming to the Milroy phenotype, molecular testing of VEGFR3 is not warranted (Connell et al, 2009b).

Inheritance of Milroy disease is autosomal dominant with a penetrance of approximately 85%. This gives up to a 50% recurrence risk for siblings if a parent carries the gene change. De novo mutations have been reported so a family Figure 3. Distichiasis on upper and lower lids. Note presence of more than one row of normal lashes but history is not mandatory (Ghalamkarpour anterior to, and clearly separate from the abnormal lashes (arrowed) growing from the Meibomian gland.

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Syndromic lymphoedema limb[s], lower limb[s], face, genitalia or Lymphoedema can be seen as part conjunctiva) is a recognised phenotype in of a syndromic diagnosis. Assessment the paediatric population. Facial, genitalia of a child with primary lymphoedema and conjunctival lymphoedema tend to requires obtaining a full personal be seen in association with lymphoedema and family history along with clinical of one or more limbs. Unisegmental examination, as other clinical signs may lymphoedema (affecting one segment point towards a specific diagnosis. Turner, only) usually affects a limb (Figure 4). This Noonan, Prader-Willi and CHARGE group of patients do not have systemic (Coloboma, heart defect, atresia choanae, involvement of their lymphoedema and retarded growth and development, the family history is usually negative, Figure 4. Unisegmental oedema in a child. genital hypoplasia, ear anomalies/ suggestive of a sporadic form of primary deafness) are all well recognised lymphoedema, with a low recurrence risk conditions in which lymphoedema is (Connell et al, 2009b). known to form part of the phenotype. Generalised lymphatic dysplasia (types I and II) Primary lymphoedema can Generalised lymphatic dysplasia is also be seen in rarer syndromes a form of primary lymphoedema including microcephaly-lymphoedema- in which systemic involvement is a chorioretinopathy, hypotrichosis- feature. Recognising systemic lymphatic telangiectasia-lymphoedema and problems has important implications Hennekam syndrome. In patients with for management. The lymphoedema in lymphoedema and other congenital these patients can be: multisegmental anomalies and/or dysmorphic features, a (type I), affecting upper and lower review by a geneticist should be sought. limb(s), face, conjunctiva and genitalia in a Karyotype analysis is appropriate in segmental, asymmetrical pattern, with any all dysmorphic patients with primary combination of body parts being affected; lymphoedema as chromosome or generalised, affecting the whole body abnormalities have been identified (type II) as seen in Figure 5 (Connell et in a proportion of these patients al, 2009a). These patients can present in (Radhakrishnan and Rockson, 2008). utero with signs of oedema or hydrops. Other molecular investigations should A full family and antenatal history should be targeted at confirmation of a specific be obtained as, particularly in type II syndromic diagnosis. Accurate recognition generalised lymphatic dysplasia, in which of a syndromic diagnosis has implications mendelian inheritance patterns are for prognosis, management and genetic recognised, a positive family history has counselling for the patient and family in an impact on the risk of having another terms of risks to other family members affected child. Figure 5. Widespread lymphatic dysplasia with four having affected offspring. limb oedema and . Secondary lymphoedema Lymphoedema in association with vascular Secondary lymphoedema is the or travelled in areas where is malformations/overgrowth commonest form of oedema affecting prevalent. Lymphoedema can be seen in association adults. In developed countries this is with vascular malformations or as part most often following for Secondary lymphatic impairment as of an overgrowth syndrome such as during which lymph nodes are either a side-effect of drug treatment is not Proteus or Klippel-Trenaunay syndromes. removed or damaged. Further insults uncommon in adults but rarely seen This group of patients tend to have a can occur to the lymphatic system with in children. Treatment with calcium low recurrence risk, given the sporadic, radiotherapy treatment, leading to channel blocking drugs and sirolimus, mosaic nature of these conditions. The of lymphatics in the treated field. Other an anti rejection medication, have been phenotyping and management of these causes of secondary lymphoedema implicated in the development or conditions is not straightforward and may include injury and . In those exacerbation of oedema (Sahney, 2006; require specialist input (Brouillard and parts of the world in which filariasis is Desai et al, 2009; ). Vikkula, 2007). Management of overgrowth endemic, this is the leading cause of may require orthopaedic input. lymphoedema (Szuba and Rockson, Diagnosis of lymphoedema 1998). Lymphoedema due to filarial The diagnosis of lymphoedema is Segmental lymphoedema infection is rarely seen in the UK and predominantly a clinical one. It is Primary lymphoedema affecting one or Europe but should always be considered important at the outset to distinguish more body segments (segment = upper when assessing a patient who has lived lymphoedema from other conditions

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there is a range of lymphatic function yet available (Schmeller and Meier- and establishing an accurate history will Vollrath, 2006). facilitate an accurate diagnosis. Clinical features of lymphoedema Lipoedema (Figure 6) deserves special Features typically seen in lymphoedema mention as it is often misdiagnosed as patients, whether primary or secondary, morbid or lymphoedema and include; cutaneous and subcutaneous therefore needs to be included in the thickening, pitting oedema which does list of differential diagnoses. Lipoedema, not improve significantly on elevation, first described by Allen and Hines (1940), positive Kaposi-Stemmer sign (inability describes a condition in which excess to pinch a fold of skin at the base of fat is preferentially stored in the legs the second toe (Figure 7; Stemmer, Figure 6. Lipoedema, note relative sparing of and buttocks, and is often erroneously 1976) and skin changes including fibrosis, the feet. diagnosed as lymphoedema. Lipoedema , papillomatosis (Figure 1) almost exclusively affects females and and . Papillomatosis is with overlapping phenotypes. This is presents at, or after . It is not the occurrence of the out-pouching of necessary as the treatments, long-term often seen in paediatric clinics but should pockets of skin between the fibrosed outcomes and reproductive risks may be considered when seeing a teenage areas of tissue. Lymphangiectasia are vary according to the diagnosis. Incorrect girl with recent onset of lower limb ‘blister-like’ lesions on the surface of the diagnoses can be dangerous and delay enlargement. In addition to symmetrical skin that represent engorged lymphatic the institution of specific treatments. An lower limb enlargement, there is often a vessels. Leakage of lymph from these incorrect diagnosis can also be expensive history of easy bruising and tenderness vesicles is termed lymphorrhoea. Many of in that unhelpful investigations and in the affected limbs. Lymphoedema the skin changes are dependent on the treatments may be undertaken. can complicate lipoedema, particularly severity of oedema, efficacy of treatment when it is longstanding, and then and, in particular, duration of swelling, so Differential diagnoses to be considered lymphoscintigraphy may become are not often evident in the paediatric when faced with a patient with oedema abnormal (Bilancini et al, 1995). A recent lymphoedema population. include; cardiac failure, venous reflux, report using MR lymphangiography venous obstruction, e.g. thrombosis, drug- suggests covert Systemic involvement can be a induced oedema, low albumin levels, dilatation may exist in lipoedema before feature of a more widespread lymphatic recurrence of carcinoma, lipoedema and lymphoedema development (Lohrmann problem. It includes problems such as any circumstances of increased capillary et al, 2009). pleural and pericardial effusions, ascites, filtration overwhelming lymph drainage chylous effusions, and pulmonary and (Levick and Mortimer, 2004). Management is difficult but intestinal lymphangiectasia. The latter essentially is similar to that prescribed can cause malabsorption from the gut. Lymphoedema can be seen in for lymphoedema patients. This is most often a clinical diagnosis association with or be misdiagnosed is sometimes recommended, although as invasive tests for this condition are as hemi-hypertrophy or segmental large scale, long-term follow up is not rarely diagnostic. A history of symptoms overgrowth. This is an important diagnosis to make in the paediatric population due to the increased risk of Wilms tumour, and the need for renal screening in this group (Scott et al, 2006). The co-existence of vascular malformations and overgrowth should point towards differential diagnoses including Klippel-Trenaunay syndrome and Proteus syndrome.

It should always be considered that primary lymphoedema can co-exist with, or be exposed by, any of the secondary causes. The finding of a secondary cause does not rule out an underlying primary ‘weakness’ of the lymph system. Lymph drainage may be adequate until Figure 7. Demonstration of positive Stemmer sign, the inability to pick up a fold of skin at the base of the an inherent weakness is unmasked by second toe, indicating thickening of the skin. This is useful in differentiating lymphoedema from other forms a secondary event. This suggests that of oedema. Also known as Kaposi-Stemmer sign.

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of diarrhoea/steatorrhoea and failure to areas. is the most uptake of the tracer (Wheatley et al, thrive should be specifically asked when commonly associated malignancy. This is 1996) (Figures 8–10). Various protocols assessing paediatric patients. Respiratory not reported in the paediatric population are used, but generally a comparison is and cardiac complications can arise from but information regarding the risks of these made with known normal control values. pleural or pericardial effusions caused by should form part of the long-term A low uptake is generally indicative abnormal thoracic lymphatics and may health advice given to patients by medical of a lymphatic abnormality while an require treatment. staff and lymphoedema therapists. unusually high uptake of tracer can be suggestive of increased filtration, e.g. Complications Investigations venous disease. Further evaluation of Complications associated with For many years the lymphatic system the images can, sometimes, give more lymphoedema are common and often has been difficult to visualise both in vitro information as to the underlying cause dependent on the degree of oedema and in vivo. In vitro analysis has in the past of the abnormality (Mortimer, personal present. More severe oedema is likely to been hampered by a lack of lymphatic- communication). The sensitivity and be associated with a greater number and specific markers which is slowly being specificity of this type of scanning is not severity of complications. remedied with an increasing number now 100%. A normal scan does not rule out being available for laboratory use. These a lymphatic abnormality but an abnormal Psychological morbidity can be new markers can help to differentiate scan indicates an underlying lymphatic significant and is one of the major between lymphatics and other elements abnormality. Lymphoscintigraphy in reasons given for presenting for of the vascular system, allowing for children is not often necessary to make medical attention. Lymphoedema can the first time the ability to understand a diagnosis and can be performed be very disfiguring and the perception the embryological development of using anaesthetic gel to avoid injection of disfigurement contributes to the the lymph system. Lymphatic vessel discomfort. Scans can give added psychological morbidity. It can also be markers of interest in humans include; information in cases where there appears physically disabling and for this reason can LVYE1, VEGFR3, PROX1, Podoplanin, to be widespread lymphatic abnormalities impact on quality of life. In the paediatric Neuropilin-2, and FOXC2 (Baluk and (Bellini et al, 2008). population this can be particularly McDonald, 2008). evident during school years with teasing Magnetic resonance imaging (MRI) by peers a common problem. Functional imaging of the lymphatic has rarely been used for diagnosis of system has improved with advances in lymphoedema but can be used to and are technology and knowledge of molecular differentiate from hypertrophy and common complications of lymphoedema. markers. may identify an obstruction to lymph Impaired immune function due to drainage. Clinical examination can disturbed cellular trafficking from In vivo investigations are not sometimes suggest tissue hypertrophy abnormal lymph drainage encourages always necessary to make a diagnosis and, in these cases, MRI is the definitive infection. An initial local infection can but can at times add to the overall test to differentiate between the two quickly become septicaemia with understanding of the condition in conditions, for example, fat hypertrophy systemic symptoms, requiring intravenous an individual and can help to classify in lipoedema or muscle enlargement antibiotics and hospitalisation. Recurrent them into a diagnostic group. As in Klippel-Trenaunay syndrome. In the cellulitis not only leads to acute illness, more is understood about the paediatric population MRI scanning can but causes further damage to an underlying molecular abnormalities in be problematic as the patient is required already compromised lymphatic system, lymphoedema, the ability to classify to remain still for a considerable period predisposing to further infective episodes. patients correctly will become of time during the scanning process and It is imperative that this cycle of events is increasingly important if specific they may need a general anaesthetic arrested to prevent rapid deterioration in therapies are developed. or sedation. function of the lymphatics. Lymphoscintigraphy is currently Newer MRI techniques, such as MR A consensus document outlining the ‘gold standard’ for investigating the lymphangiography, are currently being agreed treatment and prophylaxis lymph system. It has the advantage of developed in an effort to improve for adults has been published and is being relatively non-invasive and, other imaging of lymphatic vessels and available online at: www.lymphoedema. than mild discomfort as the radioactive lymphatic function. org/lsn. While this was developed for tracer is injected, is not unpleasant the adult population it can be adapted for the patient. Lymphoscintigraphy Ultrasound scanning of the lymphatic for use in children. is a radionuclide-based method of system is rarely used, as visualisation of investigating lymphatics. An injection of the lymph vessels is difficult. The use of Tumours technetium-99 is placed subcutaneously ultrasound scanning is usually restricted In the adult lymphoedema population into the web spaces of the limb and to ruling out secondary causes of there is reportedly an increase in tumours gamma camera imaging is undertaken oedema such as tumours, venous disease, developing in the lymphoedema-affected at various time points to visualise the and cardiac failure (echocardiography).

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Figure 9. Lymphoscintigram scan as seen in Milroy Figure 10. Lymphoscintigram showing characteristic disease patient with one leg affected. Note uptake of ‘dermal backflow’ in lymphoedema distichiasis. trace to groin on right side but no uptake on left side.

and pre-natal diagnosis/pre-implantation papillomatosis, lymphorrhoea and genetic diagnosis. discouraging tissue fibrosis 8 Pain and psychosocial management. Management of childhood lymphoedema Management of lymphoedema is lifelong Therapy assessment will also include and multidisciplinary. Parents should be setting the benchmarks against which Figure 8. Normal lymphoscintigram, note significant encouraged to take an active role in the improvement can be judged, e.g. limb tracer collection in groin and evidence of major day-to-day provision of and volume measurement, mobility and lymph vessels in legs. application of garments as required. They functional asessments. A treatment plan will also take on a major part of the will depend on the site and severity of tests can be used to rule out health education which is an important the lymphoedema. some secondary causes of oedema such part of lymphoedema care, and as low albumin and filariasis. essential to reduce complications. From Physical therapy the outset, the concept of long-term Physical methods of treating Genetic tests management, rather than cure, must lymphoedema have been practised The VEGFR3 and FOCX2 can be be emphasised. for many years. Therapy essentially sequenced to look for mutations that aims to control lymph formation and are pathogenic for Milroy disease and Lymphoedema therapist to improve lymph drainage through lymphoedema distichiasis, respectively. In All children with a diagnosis of existing lymphatics and collateral routes well-phenotyped patients, there is a high lymphoedema should be referred to a by enhancing what lymphatic function likelihood of finding a mutation (Bell et al, trained lymphoedema therapist. A list is present. It should be appreciated that 2001; Connell et al, 2009b). Identification of trained therapists can be accessed lymph flow still exists in lymphoedema, of a mutation means an unequivocal through the website of the British otherwise swelling would be a diagnosis and molecular diagnosis Lymphology Society (UK) (www. relentlessly progressive process. can then be offered to other family lymphoedema.org/bls). Currently in members. Prenatal diagnosis would be the UK, therapy provision for primary Physical treatment can, in the feasible, although rarely requested. In paediatric lymphoedema is patchy majority of cases, improve quality the future, if therapies specific to the and those affected may need to travel of life considerably and reduce the underlying molecular abnormality are considerable distances to access incidence of complications such as developed, this form of testing will services. cellulitis and papillomatosis. Key to become more important. management is assisting patients and Best practice for management will parents to understand their condition Genetic counselling focus on the needs of each individual and to become partners in their care. While identification of the causative patient. This will include: Doing no harm and allowing any genetic fault is unusual in lymphoedema 8 Swelling reduction and improvement natural improvement through further conditions, genetic counselling can be of shape development of the lymphatic system extremely useful in providing better 8 Treatment and prevention of infection are important. With an enhanced quantification of the recurrence risks 8 Treating skin problems such as understanding of their condition and

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the need for treatment a high level requires high compression and double of motivation and compliance can be hoses may occasionally be required. generated (Mortimer and Todd, 2007). Most garments last no more than six

months. Two garments (or pairs) should Key points Main elements of physical therapy be provided; one to wear and one for Care of the skin and prevention of infection the wash. The correct technique for 8 Always take a comprehensive Skin changes are not only unsightly, but application, removal and care of garments family history. Lymphoedema can lead to problems such as infection, are crucial for a successful outcome. can occur as part of several well fibrosis and lymphorrhoea. Regular described syndromes and it is application of an emollient is important Multilayer bandaging is rarely vital to recognise these as the for hydrating any hardened skin, thus required in the paediatric lymphoedema natural history and recurrence making it more supple and discouraging population. It can be used for limb risks are well described. hyperkeratosis. Tinea pedis is almost reduction, but also has the advantage of invariably because of the closely apposed restoring limb shape so that subsequent 8 If in doubt about the diagnosis swollen toes (not helped by elastic use of compression garments (hosiery) or best treatment, seek advice hosiery). Modern antifungal creams is more effective at controlling swelling from your local lymphoedema unfortunately macerate skin further and (Badger, 2000). The digits are also clinic, genetics department or therefore it is suggested that Terbinafine bandaged to control swelling of fingers the Lymphoedema Support cream is applied for two weeks followed and toes. The strategic positioning Network (LSN). by an alcohol wipe, assuming the skin is of rubber pads ‘irons out’ pockets of not broken. For deep cracks and crevices swelling and deep skin folds. Multilayer 8 Methods for visualising the which bacteria may readily colonise, bandaging is a skill which takes time to lymphatics are not readily regular cleaning is necessary followed learn and should not be undertaken available and most diagnoses by an antiseptic soak, e.g. potassium without appropriate training. rely on clinical examination and permanganate. Prevention of infection, medical history. particularly lymphangitis/cellulitis, is crucial Pneumatic compression therapy to the control of lymphoedema. Care (intermittent/sequential pneumatic 8 Management by a of the skin, good hygiene, control of compression) should not be used in lymphoedema therapist with tinea pedis and good antisepsis following preference to exercise and compression, experience of paediatric abrasions and minor wounds are but can be useful when exercise is lymphoedema is vital. important to reduce the risk of cellulitis. difficult. An inflatable boot, legging or sleeve is connected to a motor-driven Exercise pump and lymph is displaced towards stimulus to lymph flow. The practice Exercise and movement are crucial to the root of the limb. If hosiery is not that encourages such flow, referred lymph drainage (Roddie, 1990) and fitted immediately following compression to as manual lymphatic drainage should be encouraged. Dynamic muscle therapy, the swelling readily recurs. therapy (MLD), is directed at normally contractions encourage both passive Pneumatic compression softens the draining regions; this and active phases of lymph drainage. tissues and reduces limb volume during ‘siphons’ or ‘milks’ lymph away from Overexertion and excessive static treatment, but it is doubtful that any congested lymphoedematous areas, so exercise increase blood flow, which long-term benefit is gained over hosiery complementing attempts to improve therefore tends to increase oedema. and exercise alone. drainage ‘upstream’ by exercise and external compression. Continuous MLD External compression (hosiery, bandaging or Massage (manual lymphatic drainage therapy, MLD) delivered by a therapist is expensive pneumatic compression) Massage is an important component and few healthcare providers will fund. External compression complements the of treatment, particularly for midline Once a patient or parent has been exercise programme. Such compression lymphoedema where there are seldom taught the techniques, it is possible is not intended to ‘squeeze’ oedema effective alternatives. The problem to do a simplified version of MLD at but to act as a counterforce to muscle is that there are different forms of home. This is sometimes called simple activity and so generate higher tissue massage, used mostly for increasing lymphatic drainage. pressures during contractions. This blood flow and therefore of vigorous provides the most powerful stimulus to nature. In lymphoedema patients Monitoring treatment lymph drainage. Compression also limits tissue movement needs to be gentle, Monitoring of efficacy of treatment in capillary filtration by opposing capillary as a stimulus to lymph flow without children differs somewhat from adults; pressure. Without exercise, compression increasing blood flow (Mortimer et volumetric measurement is usually is much less effective. al, 2000). Indeed, in the absence of unsuitable as a parameter because of lymphatic contractility, massaging of natural growth in length and weight. Hosiery (below-knee or full-length filled lymphatics by muscle exercise Monitoring of height and weight, and the stockings, half or full tights, sleeves) usually or surface massage may be the major physical and psychological development

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of the child is important. Surgical VEGFR3 and VEGFC in Milroy disease and reproducibility effect of injection dynamics management of lymphatic abnormalities other primary lymphoedemas. Hum Genet and lymph flow enhancement.J Invest in children is rarely required. Occasionally, 24(6): 625–31 Dermatol 95: 677–82 surgery may be indicated for visceral Daniel-Spiegel E, Ghalamkarpour A, Spiegel Mortimer P, Todd J (2007) Lymphoedema: R, et al (2005) Hydrops fetalis: an unusual involvement or ingrown toenails. In Advice on self-management and treatment. 3rd prenatal presentation of hereditary congenital edn. Beaconsfield Publishers, Beaconsfield males with genital oedema, circumcision . Prenat Diagn 25(11): 1015–8 is sometimes indicated (Damstra and Oliver G, Alitalo K (2005) The lymphatic Damstra RJ, Mortimer PS (2008) Diagnosis vasculature: recent progress and paradigms. Mortimer, 2008). and therapy in children with lymphoedema. Annu Rev Cell Dev Biol 21: 457–83 Phlebology 23(6): 276–86 Radhakrishnan K, Rockson SG (2008) The It is important to integrate Desai N, Heenan S, Mortimer PS (2009) clinical spectrum of . Ann N therapies into the child’s daily life. Sirolimus-associated lymphoedema: eight Y Acad Sci 1131: 155–84 Physical activities should be positively new cases and a proposed mechanism. Br J Dermatol 160(6): 1322–6 [Epub March 16] Rockson SG, Rivera KK (2008) Estimating the encouraged and the child must be population burden of lymphedema. Ann N Y allowed to do recreational activities Evans AL, Bell R, Brice G, Comeglio P, et al Acad Sci 1131: 147–54 as normally as possible (Damstra and (2003) Identification of eight novel VEGFR-3 mutations in families with primary congenital Roddie IC (1990) Lymph transport Mortimer, 2008). JL lymphoedema. J Med Genet 40(9): 697–703 mechanisms in peripheral lymphatics. 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