Comprehensive Guide to Lymphedema in Children

Primary and secondary lymphedema in children is relatively rare, but carries with it the significant and lifelong burden of having to manage chronic swelling and prevent secondary complications. Here I describe pediatric lymphedema (also called ‘paediatric lymphoedema’), and the special considerations for diagnosis, ongoing monitoring, treatment, and complications.

The majority of patients with lymphedema experience the same basic symptoms, and are managed using the same basic strategy. This is true regardless of whether they are an adult, child or infant. It is also true irrespective of whether they have primary lymphedema arising from a developmental abnormality, or secondary lymphedema acquired due to lymphatic damage (often cancer-related).

Although lymphedema symptoms and management strategies are broadly similar between patients, pediatric lymphedema does present some unique challenges and considerations.

The diagnosis and monitoring of pediatric lymphedema can be more difficult, novel complications can arise, and modifications for ongoing monitoring, treatment and self-management are required.

This brief guide is meant to provide caregivers with an overview of what current research and best practice tells us about the characteristics, diagnosis, and treatment of lymphedema in children (from infants to teenagers). I will also highlight how lymphedema in children differs from adult lymphedema.

What is pediatric lymphedema?

Lymphedema in children falls into two broad categories: (1) primary pediatric lymphedema, and (2) secondary pediatric lymphedema. The former is an abnormality that a patient is born with, while the latter is acquired due to an event or injury that resulted in lymphatic damage.

Type 1: Pediatric primary lymphedema

Primary lymphedema is a chronic swelling condition caused by an abnormal development of the lymphatic system in an area of the body. The prevalence of primary lymphedema in people under 20 is commonly reported as 1.15 per 100,000 people (ref1), but the methodology used to come up with this number is rather questionable (ref2) and it is likely to be significantly higher (ref3), perhaps even as high as 1 in 6000 (ref4).

The extent of lymphatic malformation varies between individuals, as does the area of the body affected. As a result, some patients are born with visible symptoms, while others develop swelling only later in childhood or adolescence. Others still will first develop symptoms of lymphedema as an adult, usually after some aggravating lymphatic event such as weight gain, injury or infection.

I) How does pediatric primary lymphedema occur?

The lymphatic system is comprised of lymphatic vessels and lymph nodes that normally act to clear excess fluid called ‘lymph’ from tissues of the body, recycling it back into the blood stream. Along with the cardiovascular system (your arteries and veins), the lymphatic system is responsible for maintaining a normal fluid balance, clearing cellular waste, and participating in immune surveillance.

If the lymphatic system fails to function properly, lymph fluid will accumulate in the affected area, and swelling will result. The stagnant lymph fluid will also cause local immune system suppression and therefore increase the risk of infection.

If lymphedema is left unchecked, a patient will naturally progress through the stages of lymphedema (see more on the stages in Table 1). This process culminates in substantial swelling and permanent tissue changes to the affected area including fibrosis (scar formation) and adipose deposition (fat accumulation). See our post: “Untreated lymphatic swelling promotes weight gain by altering stem cell behaviour”.

Congenital lymphatic abnormalities that create primary lymphedema include:

1. A decrease in the number of lymphatic vessels or lymph nodes.
2. Changes in the size of lymphatic vessels or lymph nodes (either too big or too small).
3. Poorly formed lymphatic vessels or lymph nodes.

II) When does pediatric primary lymphedema begin to show symptoms?

This varies. In some cases swelling caused by primary lymphedema can be seen by ultrasound in utero during the third trimester of pregnancy (ref5).

Looking at the data from recent clinical studies, it appears that about one-third to one-half of children with pediatric primary lymphedema are born with symptoms or develop them as an infant (ages 0-1) (ref3,5,6). A smaller proportion of children appear to first develop symptoms during childhood (ages 1-8 in girls and 1-9 in boys), and the sizable remainder during adolescence (ages 9-21 in girls and 10-21 in boys).

But these numbers mask an apparent gender difference. The majority of boys with lymphedema have been found to be born with it or develop it in infancy, while the majority of girls develop it in early adolescence (around 10-12 years old) (ref5,6).

The timing, area affected, and extent of swelling depends on the location and degree of lymphatic malformation, which varies person to person.  It may only initiate in a child or teenager after a growth spurt, while other patients with primary lymphedema only develop symptoms later in life as an adult.

III) How did my child get primary lymphedema?

Primary lymphedema is the result of abnormalities in the lymphatic system likely caused by one or more genetic mutations. But the exact underlying cause of the condition is unclear. Since a wide selection of genes have been potentially implicated in the development of primary lymphedema (ref5), the underlying reason for its appearance could differ between patients.

A genetic mutation implicated in primary lymphedema may be inherited from a parent, thereby predisposing them to getting the condition, or it may arise sporadically in the patient (occurring by chance rather than inherited). Primary lymphedema could also be just one symptom of a larger inherited genetic disorder.

Recent evidence suggests that possibly as many as one quarter of pediatric primary lymphedema patients inherited their condition. In three recent independent studies of pediatric primary lymphedema, 12-27% of patients were found to have a family history of the disease, or found to suffer from an inherited genetic disorder that can include lymphedema as a symptom (ref3,5,6). Some of these inherited disorders are listed below.

IV) Other genetic syndromes that have been linked to primary lymphedema in children

1. Gorham disease
2. Hennekam syndrome
3. Klippel Trenaunay Weber syndrome
4. Lymphedema-distichiasis syndrome
5. Meige disease
6. Milroy’s disease
7. Noonan syndrome
8. Triple-X syndrome
9. Turner’s syndrome

V) How similar is my child’s experience of primary lymphedema to that of other children?

How does primary lymphedema usually present in children? Is my child’s lymphedema ‘typical’? Below is a breakdown of how primary lymphedema in children typically manifests:

1. Girls appear to get primary pediatric lymphedema more frequently than boys (58-70% of patients in three recent studies were female (ref3,5,6).
2. Girls usually first exhibit symptoms during early adolescence, rather than being born with it or developing it as an infant, which is the more common pattern seen in boys (ref5,6).
3. Primary lymphedema in children tends to occur in specific areas of the body, but at different frequencies (data compiled from ref3,5,6 unless otherwise noted):
   1. Limbs. Primary lymphedema usually involves a limb (88-96% of the time), sometimes the arms (8-12%), but most frequently in one or both legs (92-97% ref3,6).  About half the time if lymphedema is present in one arm or leg, it will also be present in the other.  Lymphedema of the leg can affect the foot only, the foot and calf, the thigh only, or the whole leg.
   2. Genitalia. Genitalia is another frequent site of lymphedema (6-14%), although it usually occurs in combination with leg lymphedema. The vulva, scrotum, penis and testicles can be affected.
   3. Other sites. Total body lymphedema has been reported, but very rarely (0.5%). Primary lymphedema has also been reported in the torso (8%) and the face (5%) (ref3).
4. Lymphedema in infants does not progress differently nor have a worse prognosis than lymphedema that develops later in life (ref6).

VI) Triggers of swelling onset in children with primary lymphedema

For a child with primary lymphedema, initial onset may have no apparent triggering event. As a result, the swelling is discovered by chance and is not accompanied by any other symptoms, nor is it painful.  In such cases it is likely that lymphatic function has been suboptimal for some time, but not enough to be symptomatic.

Triggers for the initial onset of primary lymphedema in children include events that cause local swelling:

1. Minor trauma, such as a sprained ankle. Children with primary lymphedema have a reduced capacity to remove lymph fluid. This reduced capacity may only be revealed after a minor injury that causes acute inflammation and swelling, which in turn overloads the lymphatic system with fluid. The result is swelling that does not subside normally, thereby initiating lymphedema symptoms. Minor trauma could also initiate lymphedema by temporarily damaging functioning lymphatic vessels themselves, thereby overloading the already sub-optimal lymphatic system.
2. Medical procedures. Much like minor trauma, minor surgery can cause swelling and inflammation, and thereby initiate the symptoms of lymphedema. For example, this could include circumcision in the case of genital lymphedema.
3. Insect bites cause local swelling and inflammation, and could therefore initiate lymphedema symptoms.
4. Infection in the area of the body with reduced lymphatic capacity can initiate primary lymphedema. Even before symptoms of primary lymphedema are apparent, decreased lymphatic capacity may be contributing to suppressed immune function, thus predisposing the area to infection.
5. Sedentary periods. Immobility for a prolonged period of time, such as during an airplane flight, can cause swelling in the legs. In patients with asymptomatic primary lymphedema, this swelling might overwhelm a child’s already reduced lymphatic functional capacity, thereby initiating lymphedema symptoms.

Type 2: Pediatric secondary lymphedema

Secondary lymphedema is a chronic swelling condition caused by damage to lymphatic vessels or nodes in an area of the body. While commonly thought of as an affliction of adults, secondary lymphedema can occur at any age.

I) How does pediatric secondary lymphedema occur?

The lymphatic system is comprised of lymphatic vessels and lymph nodes that normally act to clear excess fluid called ‘lymph’ from tissues of the body, and recycle it back into the blood stream. Along with the cardiovascular system (your arteries and veins), the lymphatic system is responsible for maintaining a healthy fluid balance, clearing cellular waste, and participating in immune surveillance.

If the lymphatic system fails to work properly, lymph fluid will accumulate in the affected area of the body, and swelling will occur. The stagnant lymph also results in local immune system suppression and increased susceptibility to infection.

If left unchecked, a patient will normally progress through the stages of lymphedema (see Table 1 below) culminating in permanent changes to the area including fibrosis (scar formation) and adipose deposition (fat accumulation). See our post: “Untreated Lymphatic Swelling Promotes Weight Gain by Altering Stem Cell Behaviour”.

Lymphatic injuries that can cause secondary lymphedema in children include:

1. Malignant tumours which physically interfere with lymphatic function.
2. Lymphatic damage caused by medical interventions including cancer treatment, or surgery such as to correct an undescended testicle (ref6).
3. Severe traumatic injury that permanently damages lymphatic vessels or nodes.
4. Infection causing severe inflammation.
5. Other syndromes and disorders that can cause lymphatic damage:
   1. Amniotic band syndrome and hair-tourniquet syndrome in newborns.
   2. Congenital vascular malformations (of small arteries and veins).
   3. Lipedema.

Stages of primary and secondary lymphedema in children

The progression of lymphedema in children follows the same general pattern as for adults, regardless of the origin of the lymphedema (primary or secondary), or the location of the body region affected. The stages of lymphedema are described in Foldi’s scale (see Table 1). For head and neck lymphedema some modification to the stages has been proposed (see: “Patient Guide to Head and Neck Lymphedema Following Cancer Treatment“).

Table 1: Foldi’s scale describing the stages of lymphedema progression in children and adults.

If left untreated and unmanaged, children with lymphedema will normally progress to stage 2 of the condition, and in some cases to stage 3.

Thankfully, age of lymphedema onset does not appear to influence how the disease progresses, nor its prognosis. Infants with lymphedema do not appear to have worse outcomes than children who develop it later in life (ref5,6).

Diagnosis of primary and secondary lymphedema in children

Physical Examination and Medical History

If a practitioner is knowledgeable about lymphedema, the diagnosis of lymphedema in adults can most often be made based on medical history, visual inspection, and examining the skin and underlying tissue with their hands alone.

For children this can be more of a challenge. For example, the reason for a swollen leg in a child can be difficult to determine as various potential causes must be first ruled out (ref7).

For this reason, medical history, visual inspection and hands-on palpation alone may not suffice for a diagnosis of lymphedema in children.

Lymphoscintigraphy

Lymphoscintigraphy is a very effective diagnostic tool for confirming the presence of lymphedema in both adults and children, as well as for understanding the location and degree of lymphatic obstruction. In the case of leg lymphedema, lymphoscintigraphy involves injecting a radioactive tracing agent into the feet of a patient and mapping the flow of the tracer over time as it travels through the legs’ lymphatics, using a radiation detecting camera or scanner.

Guidelines on when to use lymphoscintigraphy in children are unclear. Some groups do not consider lymphoscintigraphy to be appropriate or effective in young children (ref8, ref9). It has been proposed by another group to be suitable for children over 10, in order to ensure that the child can understand and effectively participate in the procedure (ref5).

Genetic testing

Genetic testing can be useful for establishing the presence of a genetic syndrome linked to primary lymphedema in children. See above for a list of syndromes potentially implicated.

MRI

Magnetic resonance imaging (MRI) with or without contrast agents may be useful for ruling in lymphedema in infants and young children where lymphoscintigraphy is inappropriate, or to rule out other causes of swelling including tissue hypertrophy (ref3,9). It can be used to look for physical issues such as missing lymph nodes, or other vascular or lymphatic abnormalities.

Other Diagnostic Tools

• Physicians may order various additional tests, often in order to rule out alternative diagnoses. Recent studies indicate that physicians commonly order ultrasonography, as well as X-ray studies (computed tomography, and plain films) to better understand the source of swelling in children with lymphedema (ref6).
• Ultrasound can be used to determine if swelling is an accumulation of fluid, and of what type, or to look for vascular clots as an alternative cause. Doppler ultrasound can be used to help evaluate fluid flow in arteries, veins and lymphatic vessels.
• Prenatal ultrasound can be used to identify the presence of lymphedema in the third trimester of pregnancy.
• Common blood tests may also be helpful to rule out other potential causes of swelling, such as hypoproteinaemia.

Diagnosis and treatment of childhood lymphedema is often delayed

The diagnosis of lymphedema in children is often delayed, and so too is proper care and management of the condition. This can result in considerable stress for the family, and can create less favourable outcomes for the child.

Patients with primary lymphedema appear to wait longer for diagnosis and subsequent treatment than their peers with secondary lymphedema.

One study in Victoria Australia showed that people (of all ages) with primary lymphedema waited on average 9.4 years for a diagnosis, compared with 1.5 years for patients with secondary lymphedema (ref2). The delay in diagnosis for primary lymphedema patients is presumably in part due to the relative rarity of the condition, in part due to its transient nature at early stages, and in part due to having to rule out various alternative diagnoses.

Treatment of lymphedema in children may also be delayed due to a lack of knowledge about the condition and the available services to treat it. In the UK one study showed that after diagnosis, 16% of patients waited less than 6 months for referral, and 55% waited less than 2 years, but 16% reported waiting 10-17 years after first showing symptoms (ref3).

Ongoing measurement and monitoring of primary and secondary lymphedema in children

As with lymphedema in an adult, lymphedema in children needs to be actively monitored to ensure it is being effectively managed. In adults lymphedema can be monitored effectively through subjective and objective measures.

Subjective measures of lymphedema include skin firmness and patient reports about how the affected area feels (such as “heaviness” or “tightness”). Objective measures include physical measurement of the area or limb, preferably in comparison to an unaffected area or limb (when possible), as well as hands-on evaluation of the tissue quality for the presence and nature of the swelling, any areas of density or firmness indicating fibrosis, and so on.

Objective measures of lymphedema in children are difficult because children are actively growing, however relative changes in volume compared to an unaffected side of the body (if possible) can be helpful. In many cases the monitoring of lymphedema in children needs to rely on subjective metrics such as the patient’s experience of their lymphedema, as well as changes in the firmness of the swelling.

Common health complications in children with primary or secondary lymphedema

Unmanaged lymphedema will progress through the stages of lymphedema (see Table 1 above), creating irreversible skin and tissue changes, and associated symptoms. In addition to these changes, children with lymphedema are at risk of secondary complications.

Secondary complications of lymphedema

I) Infection

The lymphatic system plays a key role in monitoring and responding to infection. So it is not surprising that the accumulation of stagnant lymph fluid during lymphedema progression predisposes the patient to infection. As a result, infection of the skin and underlying tissues, called cellulitis, is a common complication (for an example, please see Figure 1). This is often experienced as an area of redness that is tender and warm, and can usually be rapidly resolved with a course of antibiotics. For more information on the risk factors for developing cellulitis, see our post: “Risk Factors for Cellulitis in Patients with Lymphedema“.

In three recent studies of primary lymphedema in children, 12.5%-18% of the children were found to have experienced cellulitis, with many having recurring infection (ref3,5,6). These rates appear to be lower than those reported for adults, suggesting that children may be less prone to developing infection (ref 3). However, a very recent study following 128 children with primary lymphedema over an 8 year period contradicts this conclusion (ref 11). The authors of this study found the incidence rate in children to be similar to that of adults, and also found that 45% of the children in their study were hospitalized at least once for signs of severe infection or sepsis. Unfortunately, the first incidence of cellulitis was observed to typically occur quite early in life (at a median age of 11.5 years in their study), despite good skin care practices. Of the children who experienced cellulitis, 29% had a second episode, and 26% had three or more episodes.

In addition to cellulitis, infection within the lymph vessels, called lymphangitis can also occur, but is more rare.

Figure 1: Cellulitis in the left leg of a four year old child with lymphedema. Image adapted from Schook C.C., 2011 (ref6).

II) Other complications

1. Psychological issues including self-consciousness with respect to the swelling, or fear and avoidance of physical activities.
2. Upslanting toenails was reported in one study to be a frequent complication for children with lymphedema (ref5,6). Approximately one third of children with leg lymphedema exhibited it. Upslanted toenails can increase the likelihood of pulling off a nail when putting on clothes or compression garments, and along with ingrown toenails, can increase the risk of infection. For an example of upslanting toenails, see Figure 2.
3. Skin changes including hardening and the formation of small bumps.
4. Orthopaedic issues such as difficulty with walking in advanced cases of leg lymphedema.
5. Genital and urinary symptoms for cases of genital lymphedema, such as painful or difficult urination and urethral inflammation.
6. Lymphorrhea, which is leakage of lymph fluid through openings in the skin, can increase the risk of infection due to the skin breach and the presence of the nutrient-rich lymph fluid acting as a food source for bacteria.
7. Ulceration. Swelling causes the skin to become stretched and more fragile, increasing the risk of skin ulcers.

Figure 2: Upslanting toenails in a child with lymphedema. Image adapted from Vidal F., 2016 (ref5).

Treatment of primary and secondary lymphedema in children

Differences in the treatment of lymphedema in children and adults

The treatment of lymphedema in children is essentially the same as that for adults, with three key modifications necessary to ensure good outcomes (ref10):

1. Parents and caregivers need to be fully educated on and intimately involved in monitoring and managing the symptoms of lymphedema and secondary complications. They should also encourage the child to practice proper self-management techniques, which they will need to learn as a life skill.
2. Parents and caregivers need to actively encourage and support child participation in normal physical activities.
3. Parents and caregivers need to provide strong emotional and psychological support to their child, and seek professional help as necessary.

Lymphedema treatment approaches

I) Why can’t we simply elevate a limb to drain out the excess fluid?

In early lymphedema (stage 1) swelling can be partially or fully eliminated by elevating a limb, or may be found to be reduced in the morning after sleep. At this stage the lymphatic system is retaining enough function to sufficiently clear lymph fluid when the total limb fluid load is reduced through the help of gravity and inactivity.

However, if lymphedema remains untreated, the swelling will continue to progress. Eventually elevation and sleep will have no effect on the swelling. Why is this?

To understand why, we need to understand the difference between the cardiovascular system and lymphatic system. The cardiovascular system uses the pumping action of the heart (with assistance from muscle activity and gravity) to push blood through the body.

Instead of having one large heart to do the pumping, the lymphatic system relies primarily on the pumping action of many small fluid chambers that make up the lymphatic vessels. These lymphatic vessels then connect into larger vessels at fluid basins called lymph nodes.

Rather than fluid simply “draining” out of the tissues, the lymphatic system actively, and continuously, sucks up lymphatic fluid.

We rely on the lymphatic system because the venous system alone is incapable of collecting all of this excess fluid that would otherwise accumulate in the tissues. This is why simply raising a lymphedematous arm (which helps venous flow) will not eliminate more advanced cases of lymphedema.

II) Complex Decongestive Therapy

The standard treatment for lymphedema is Complex (or Combined) Decongestive Therapy (CDT), which includes manual lymphatic drainage, compression wrapping and/or compression garments, and education on skin safety and exercise provided by a certified lymphedema therapist.

CDT can be very effective at reducing the volume of swelling, softening areas of fibrosis, and preventing flare-ups. A CDT therapist should also provide guidance to the child and caregiver for self-management, including wrapping and garment use, manual lymphatic drainage exercises, and education on preventing flare-ups and secondary complications, skin care, and other information.

Effective management of lymphedema requires active ongoing self-management, caregiver management or co-management.

One specialized clinic recommended compression bandages be worn as much as possible each day, overnight for children who walk, and 24 hours a day for non-walking children (ref5).

For more information on lymphedema treatment and prevention of lymphedema flare-ups and secondary complications, please see: “Patient Guide to Lymphedema Symptoms, Prevention and Management”.

III) Surgery

Surgical interventions for lymphedema are still relatively new, are not curative, are typically not covered by health insurance, and are still not widely available. They are also generally only considered for advanced cases that do not respond to Complex Decongestive Therapy.

Surgery in lymphedematous children may be warranted for specific reasons, on a case-by-case basis. Use of surgery in children appears to be more common with genital lymphedema than for those with limb lymphedema (ref6).

Surgical interventions in children may be used to:

1. Repair damage caused by swelling (such as damage to genitalia caused by a testicular hydrocele).
2. De-bulk advanced cases of hardened lymphedema by direct excision or liposuction of accumulated adipose and fibrotic tissue. Specialized liposuction has been shown to be very effective at reducing the excess adipose tissue found in stage 3 patients. This procedure can offer these patients significant functional and cosmetic improvement, and with appropriate life-long management, re-progression of the disease can be prevented. See “Patient Guide: Liposuction for Lymphedema“.
3. Repair lymphatic damage in secondary lymphedema by lymphovenous bypass. In this procedure, still healthy lymphatic vessels that have been disrupted or obstructed are connected to very small nearby veins in an attempt to improve lymph drainage. Alternatively, lymphatic vessels may be attached to nearby still functional lymphatic vessels.
4. Repair missing or damaged lymph nodes in secondary lymphedema through lymph node or lymph vessel transfer (along with artery and vein transfer) from another site in the body. As you might expect, this procedure has the risk of resulting in donor site lymphedema.

Triggers of swelling flare-up in children with primary or secondary lymphedema

Events that cause local swelling can initiate a flare-up of lymphedema in patients with early stage 1 lymphedema, be it primary or secondary lymphedema.

In stage 1 lymphedema the swelling is spontaneously reversible, meaning that it can come and go on its own. It is also usually reduced or absent in the morning after sleeping, or if the area of the body is elevated.

The same factors that can initiate the onset of asymptomatic primary lymphedema (as we saw above), can also trigger the temporary bouts of increased swelling observed in early lymphedema (stage 1).

Triggers of swelling flare-up in children:

1. Minor trauma, such as a sprained ankle.
2. Medical procedures, such as minor surgery.
3. Insect bites.
4. Infection. Infection causes inflammation and swelling, and lymphedematous areas of the body are predisposed to infection due to local immune suppression caused by lymph fluid stagnation.
5. Sedentary periods. Immobility for a prolonged period of time, such as during an airplane flight, can cause swelling in the legs.

References

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2. Phillips J.J., Gordon S.J. Conservative management of lymphoedema in children: a systematic review. J Pediatr Rehabil Med. 2014;7(4):361-72. abstract
3. Todd J., Craig G., Todd M., et al. Audit of childhood lymphoedema in the United Kingdom undertaken by members of the Children’s Lymphoedema Special Interest Group. J of Lymphoedema. 2014;9(2):14-19.
4. Dale R.F. The inheritance of primary lymphoedema. J Med Genet. 1985;22:274-278. abstract
5. Vidal F., Arrault M., Vignes S. Pediatric primary lymphoedema: a cohort of 155 children and newborns. Br J Dermatol. 2016 Mar 16. [Epub ahead of print].  https://doi.org/10.1111/bjd.14556
6. Schook C.C., Mulliken J.B., Fishman S.J. et al. Primary lymphedema: clinical features and management in 138 pediatric patients. Plast Reconstr Surg. 2011 Jun;127(6):2419-31. abstract
7. Wright N.B., Carty H.M. The swollen leg and primary lymphoedema. Arch Dis Child. 1994 Jul;71(1):44-49. abstract
8. Baulieu F, Vaillant L, Gironet N et al. Intérêt de la lymphoscintigraphie dans l’exploration des lymphoedèmes de l’enfant. J Mal Vasc 2003;28:269–76.
9. Browse N, Burnand KG, Mortimer PS (2003) Diseases of the Lymphatics. CRC Press, Boca Raton; FL 142–3
10. Damstra R.J., Mortimer P.S. Diagnosis and therapy in children with lymphoedema. Phlebology. 2008;23(6):276-86. https://doi.org/10.1258/phleb.2008.008010
11. Quere I., Nagot N., Vikkula M. Incidence of Cellulitis among Children with Primary Lymphedema. N Engl J Med. 2018 May 24;378(21):2047-2048. article