What Are the Complications and Treatment for Lymphedema?

Patient Presentation
A 10-year-old female came to clinic for her health maintenance examination. She was a survivor of childhood leukemia and it was 3 years after her last chemotherapy. She was followed by her oncologist and did not have any obvious side effects of her treatment other than some mild lymphedema. It had begun about 15 months after a lymph node biopsy in her left inguinal area and was relatively mild. She was using a compression garment most days and was followed by the pediatric surgeons. She was current on all of her immunizations. The review of systems was negative.

The pertinent physical exam showed a healthy female with normal vital signs and growth parameters were 50-75%. She had no obvious lymphadenopathy, masses or hepatosplenomegaly. She had well-healed scars in her upper right chest from a port placement, and a scar in her left inguinal area. Her left foot and calf were mildly enlarged compared to her right (3 cm difference in calf size) with a symmetric outline of the anatomical structures. There was no pitting edema and pulses were strong and symmetric. The rest of her examination was normal.

The diagnosis of a healthy girl who was a cancer survivor with mild lymphedema was made. The pediatrician reiterated that it was important to continue to use the compression garments all or most of the time to help with the lymphedema. He also reminded the girl to make sure she wore shoes to protect her feet.

Discussion
Lymphedema occurs because of abnormal development or damage to the lymphatic structures. It is a chronic often progressive swelling of tissues starting distally and advancing more proximally. Extremities are the most common sites followed by genitalia. Fluid accumulation in the interstitial, superficial spaces causes adipose deposition and fibrosis. This causes the lymphedematous tissue to then enlarge. Edema is pitting early on and later is non-pitting.

Causes of lymphedema can be primary (~1%) or secondary (~99%). Primary lymphedema has been associated with several genetic mutations. Milroy disease is a primary lower extremity lymphedema that occurs in infants with a positive family history or who have a positive mutation for VEGFR3. Familial lymphedema with onset in the adolescent age group is called Meige disease and its mutation is not known at this time.

Secondary lymphedema is most common after trauma (e.g. penetrating trauma, lymph node excision, radiation) or infectious disease (especially the round worms of Filarioidea family).

The term “lymphedema” is often generically used for causes of extremity overgrowth or misdiagnosed for other vascular anomalies. For a review of overgrowth syndromes click here. A review of lymphatic malformations can also be found here.

In addition to history and physical examination, genetic studies can be done and lymphoscintigraphy is considered the standard for lymphatic function evaluation.

Learning Point
Complications of lymphedema include an increased risk of infections, skin changes (often thickening) and potentially but rarely malignancy. Patients with lymphedema do not have skin ulceration but do have an increased risk of skin infections often with Streptococcus species.

Lymphedema can’t be cured but can be treated. Treatment is conservative if at all possible. The affected area should have good skin hygiene of washing/drying and moisturizing to help prevent infections. Protective clothing is also helpful, especially wearing long pants/sleeves and foot wear or gloves. Compression garments (usually custom made) are a main treatment modality and can help to reduce the extremity volume and help to slow the disease progression. Patients need enough garments so they can be laundered regularly and they need to be replaced when worn (usually every 6 months). Other compression treatments can be offered including using pneumatic pumps. Regular exercise to maintain conditioning and normal body mass also helps treatment. Muscle contraction is the primary way that lymph fluid is transported centrally to the body. Elevation of the extremity when non weight bearing and when convenient to the patient can also help. Specific massage techniques from a trained professional can also provide some relief but can be time consuming and expensive.

Surgical treatments are used when the lymphedema is causing significant morbidity. They include lipectomy to remove adipose tissue and skin/subcutaneous resections. Microsurgical techniques can also be used to help reconstruct or reconnect lymphatic drainage.

Questions for Further Discussion
1. How is lymphedema different than generalized edema?
2. What are complications of cancer treatment that survivors need to be monitored for?
3. What are indications for surgical consultations?

Related Cases

    Symptom/Presentation: Edema

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Lymphedema

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Schook CC, Mulliken JB, Fishman SJ, Alomari AI, Grant FD, Greene AK. Differential diagnosis of lower extremity enlargement in pediatric patients referred with a diagnosis of lymphedema. Plast Reconstr Surg. 2011 Apr;127(4):1571-81.

Blatt J, Powell CM, Burkhart CN, Stavas J, Aylsworth AS. Genetics of hemangiomas, vascular malformations, and primary lymphedema. J Pediatr Hematol Oncol. 2014 Nov;36(8):587-93.

Maclellan RA, Greene AK. Lymphedema. Semin Pediatr Surg. 2014 Aug;23(4):191-7.

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital

Look What I Got On Summer Vacation – Giardia!

Patient Presentation
A 6-year-old male came to clinic with 5 days of diarrhea. They were loose watery stools occurring several times a day without blood or mucous. He denied abdominal pain or emesis but said sometimes he felt a little nauseous. He had recently been on vacation in the northern United States to visit his grandparents who lived on a farm with various animals and crops. He also had been swimming in 2 different lakes and had been to a family reunion potlock dinner during the past 2 weeks. He was drinking well and was urinating normally. The family wasn’t sure but maybe a cousin also had diarrhea. He had no recent antibiotic exposure. He was previously healthy and his review of systems revealed he had no fever, chills, or muscle aches.

The pertinent physical exam showed a well-appearing male in no distress. His vital signs were normal and his growth parameters were 25-50% for age. His mucous membranes were moist and he had good skin turgor. His abdominal examination showed slightly hyperactive bowel sounds. He had no abdominal tenderness, hepatosplenomegaly or masses. Genitourinary examination was normal as was his anus.

The diagnosis of diarrhea with significant exposure to potential infectious disease pathogens was made. As the patient was well hydrated, the family was counseled about prolonged diarrhea and recommendations for fluid intake and diet. A laboratory evaluation of stool studies for common bacterial pathogens along with stool for ova and parasites, Giardia and Clostridium difficile was made. The stool was positive for giardia and he was treated with Flagyl®. The diarrhea improved and repeated cultures were negative. The cousin had diarrhea but his resolved and he was not tested.

Discussion
People often don’t think that developed countries have parasitic diseases but this is not true. The major parasitic infections endemic in the United States can be thought of as:

  • Intestinal parasitic infections
    • Seen throughout the US but especially in the northern states during the summer
    • Often occur through recreational water use
    • Cryptosprodiosis, Dientamoebiasis and Giardiasis are the most common.
  • Neglected tropical diseases
    • Seen especially in the southern states (especially Texas) and are linked to extreme poverty
    • Chagas disease, Cutaneous Leishmaniasis, Toxocariasis, and Toxoplasmosis are the most common.

Learning Point
Giardia intestinalis (also known as Giardia lambia or Giardia duodenalis) is considered a zoonotic disease sometimes known as Beaver Fever. It was one of the first organisms Antonie van Leewenhoek saw under the microscope. It is a flagllated protozoan found globally that usually affects the cells in the duodenum and jejunum. It is most commonly found in children ages 1-9 years old. The number of cases is slightly decreasing in last few years in the U.S. with about 16-19,000 cases depending on the year. Cases cluster often in the northern states in the summer. Contaminated water and fecal-oral contamination of the cysts spread the disease. The cysts are difficult to kill as they are chlorine tolerant. Cysts can be killed by boiling water for more than 1 minute, or using a filter with an absolute pore size of 1 micron or smaller to remove the cysts. Incubation is 9-15 days.

The disease can be asymptomatic, have mild to severe diarrhea. Other symptoms can include anorexia, bloating, abdominal pain and cramping and explosive diarrhea. Unfortunately about 50% of patients may not clear the organisms and have chronic disease which may include anorexia, malabsorption, diarrhea and weight loss which can last years. Giardia should be considered when diarrhea lasts more than 3 days in the appropriate setting. Routine ova and parasite tests may not test for Giardia so specific testing should be ordered. Testing is by direct fluorescent antibody testing of the stool. Giardia is not continually shed and therefore 3 negative stool tests from different days are considered the standard for a negative test. Treatment is usually with nitroimidazole compounds such as metronidazole (Flagyl®), ornidazole, secnidazole or tinidazole. Other treatments are available to try if there is initial treatment failure.

Questions for Further Discussion
1. For what indications do you consider testing for stool pathogens?
2. When do you consider testing for Clostridium difficile?
3. What is in the differential diagnosis of diarrhea? Click here

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Giardia Infections and Parasitic Diseases.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Muhsen K, Levine MM. A systematic review and meta-analysis of the association between Giardia lamblia and endemic pediatric diarrhea in developing countries. Clin Infect Dis. 2012 Dec;55 Suppl 4:S271-93.

Barry MA, Weatherhead JE, Hotez PJ, Woc-Colburn L. Childhood parasitic infections endemic to the United States. Pediatr Clin North Am. 2013 Apr;60(2):471-85.

Painter JE, Gargano JW, Collier SA, Yoder JS; Centers for Disease Control and Prevention. Giardiasis surveillance — United States, 2011-2012. MMWR Suppl. 2015 May 1;64(3):15-25.

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital

What Are Some of the Classes of Environmental Pollutants Affecting Children?

Patient Presentation
A 6-month-old female came to clinic for her health supervision visit. She was sitting up, making vowel and some consonant sounds and loving playing with toys she could put into her mouth. Her mother said that she continued to nurse well but was very interested in people eating foods and wanted to know when she could start solid foods. The past medical history showed an uneventful pregnancy and delivery. The infant was fully immunized.

The pertinent physical exam revealed a playful infant with growth parameters around the 25%. During the exam she showed that she could roll both ways, sit without difficulty and had no head lag. She said “m” and “b” sounds and the rest of her examination was normal. The diagnosis of of a healthy infant was made. The pediatrician recommended starting solid foods by introducing thinned cereals or other easily swallowed foods one at a time to allow for any potential allergies. The mother had been reading about potential arsenic in rice cereal and asked what types of cereal she could use. The pediatrician offered, “her most important food now is breastmilk, but learning to eat a variety of foods is also important. In addition to rice cereal there are also barley, oat and multigrain cereals that you can use. Check to make sure the cereals are iron-fortified. She is getting some iron from the breastmilk but it isn’t enough anymore for her. She needs more and cereals are usually the way for her to get that.” She went on, “just take a small amount of the cereal and thin it with breastmilk, or water and try it with a spoon. She how she does and over time you can thicken it more as she learns.”

Discussion
Children are particularly susceptible to heavy metals in the environment and while arsenic is not regarded as a heavy metal by chemists (it is a semi-metal) it is often lumped in with mercury and lead because all have similar toxic affects. Elemental arsenic is not toxic itself, but inorganic and organic compounds are toxic. Inorganic compounds are particularly toxic because they are highly lipid soluble. Arsenic sources include water, air, marine animals, and fossil fuels. Fruits, vegetables, milk and rice can also be contaminated. As rice plants grow they can absorb more arsenic than some other grains. The American Academy of Pediatrics recommends, “Parents commonly feed infants rice cereal as a first food, but other foods are equally acceptable as a first food. Finely chopped meat provides a source of iron. Cereals made from other grains may be given first, or vegetable purees. For older children, the advice is the same: A varied diet will decrease a child’s exposure to environmental toxins in any one food, while providing a wide variety of nutrients.” To learn more about environmental arsenic, click here.

Learning Point
Environmental pollution includes those that are more traditional such as air or water pollution, but also include more modern problems including toxic chemicals, climate change, and e-waste. Environmental pollution is a large contributor to morbidity and mortality for the fetus, children and adults.

  • Air Pollution
    • Air pollution both outside and inside the home has health affects.
    • Main problems are ozone, nitrogen oxide and particulate matter.
    • Problems include respiratory disease, cancer and neurodevelopmental problems
    • Can be transported across large areas because of dispersal (outdoor) or concentrated (indoor) where solid fuel cookstoves and fires increase particulate matter substantially.
      Tobacco products and their smoke also are large contributors to respiratory diseases.
  • E-waste
    • There is rapidly increasing amounts of electronic waste or e-waste.
    • Hazardous materials include barium, cadmium, lead, lithium, mercury, nickel, flame retardants and organic pollutants such as polychlorinated biphenyls (PCBs).
    • There are also many e-waste components which are recycled and therefore exposure to these other chemicals often takes place then. Children are used in the e-waste recycling industry.
  • Climate change
    • Can cause direct effects such as heat stress, air pollution, increase in infectious diseases (diarrhea and vector-borne diseases), and extreme weather events.
    • Indirect effects include water insecurity (including increased water salinity), malnutrition, and population displacement.
  • Heavy Metal Pollution
    • See above
  • Pesticides
    • Are chemicals that are made to kill or repel living things therefore are designed to be toxic.
    • While many chemicals have been abandoned, others believed to be less toxic are still necessarily used.
    • Over time, adverse problems of many of these compounds become known or better understood. For example, organochlorine pesticides have been associated with chronic health problems and glyphosate may be carcinogenic.
    • Regulations are not consistent world-wide and storage and use locally can be problems. Use in homes is one of the major exposures.
  • Water Pollution
    • Microbial contamination continues to be a problem where consistent safe drinking water is not available.
    • Other contaminants include lead (neurotoxic effects), nitrates (causing methemoglobin), and perchlorate (inhibits iodine uptake). Radionuclides and arsenic can also be problems in addition to local contaminations from chemicals and pesticides.

Questions for Further Discussion
1. What environmental pollution risks do you have in your local environment?
2. How do you counsel your patients and families to mitigate these potential risks?
3. How do you counsel your families to start solid foods?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Environmental Health

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

American Academy of Pediatrics. AAP Offers Advice For Parents Concerned About Arsenic in Food. Available from the Internet at https://www.aap.org/en-us/about-the-aap/aap-press-room/pages/AAP-Offers-Advice-For-Parents-Concerned-About-Arsenic-in-Food.aspx (rev. 9/6/13, cited 5/2/16)

Vieira SE. The health burden of pollution: the impact of prenatal exposure to air pollutants. Int J Chron Obstruct Pulmon Dis. 2015 Jun 10;10:1111-21.

Suades-Gonzalez E, Gascon M, Guxens M, Sunyer J. Air Pollution and Neuropsychological Development: A Review of the Latest Evidence. Endocrinology. 2015 Oct;156(10):3473-82.

Miller MD, Marty MA, Landrigan PJ. Children’s Environmental Health: Beyond National Boundaries. Pediatr Clin North Am. 2016 Feb;63(1):149-65.

AAP Welcomes FDA Announcement on Limiting Arsenic in Infant Rice Cereal. Available from the Internet at https://www.aap.org/en-us/about-the-aap/aap-press-room/Pages/AAP-Welcomes-FDA-Announcement-on-Limiting-Arsenic-in-Infant-Rice-Cereal.aspx (rev. 4/1/16, cited 5/2/16).

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital