How Common is Gout?

Patient Presentation
A 12-year-old female came to clinic with a 3 month history of ankle pain. It initially started in the right ankle after she had turned her ankle during dancing. This got somewhat better but then her left ankle and foot also became more painful. She had continued her activities which included multiple dance activities, gymnastics, Tae Kwon Do and two weeks previously she had started cross-country running. The pain had increased in the couple of days after she started cross-country. The running occurred mainly on sidewalks and roads. She said she had no pain in the morning but it slowly increased over the day and was worse when she started her activities in the afternoon or evening. Sometime she would limp during practices. The pain decreased with rest after the activities and with warm baths. She denied any pain at night, swelling or warmth of the joint, night sweats, weight loss, rashes, fevers or chills. She denied any other joints being affected. The past medical history was non-contributory. The family history had no specific orthopaedic, rheumatologic or immune problems. The pertinent physical exam revealed a healthy female with growth parameters in the 10-50%. She was tall and thin. The ankles, feet and toes did not show any erythema or edema. No specific pain could be elicited. The joints were freely mobile. The rest of her extremities, back, and TMJ joints were negative. She had no skin changes.

The radiologic evaluation showed no bony changes in the feet or ankles. The diagnosis of general overuse resulting in ankle pain was made. The patient was instructed to significantly decrease or stop her activities and let her body rest more until the pain subsided. She then could increase her activities as tolerated. She had a health maintenance examination already scheduled in 3 weeks so followup would be done then. After the visit the medical student was reviewing the differential diagnosis of joint pain with the attending and included gout as one of the entities. “I’ve only seen hyperuricemia with patients with tumor lysis syndrome or with a metabolic problem. I’ve never seen gout. It’s really an adult disease and certainly on the differential diagnosis for adults, but we really don’t see it in children,” the attending noted.

Discussion
Purines are heterocyclic aromatic organic compounds. Common ones are adenine, guanine, xanthine, hypoxanthine, uric acid and caffeine. The most common sources of purines are meat (especially liver, kidney, and brain), certain fish (herring, mackerel, anchovies, sardines), and in lower amounts in beans, and certain plants and yeast. Purines are synthesized, used by the body, then they are degraded by a variety of enzymes. They then can be salvaged to resynthesize purines or are eliminated primarily by the kidney.

When intake or synthesis outweighs elimination then hyperuricemia can result. Hyperuricemia can occur in patients with obesity and metabolic syndrome, psoriasis, medications (thiazide diuretics), genetic diseases such as Lesch Nyhan disease, and kidney disease including transplantation. Myeloproliferative disease including leukemia, lymphoma and tumor lysis syndrome also have increased risk of hyperuricemia.

Hyperuricemia can lead to the deposition of monosodium urate crystals in the joint and periarticular tissue. Crystal deposition stimulates interleukin-1 release from monocytes that causes an inflammatory response. Painful joints and gout are the result. Overtime gouty trophi may occur that can cause bony erosions. As it can take 20 years or more for this process of hyperuricemia and crystal deposition to occur, gout generally does not occur often in the typical pediatric patient. Therefore gout is not usually considered in the differential diagnosis of joint or limb pain in the pediatric population as it is in the adult population.

The causes of leg pain can be reviewed here.

The causes of limp can be reviewed here.

Learning Point
In the adult population, gout had a prevalence rate of 1.4 – 4% in the western countries of the United States, United Kingdom, Germany and Australia.
Juvenile gouty arthritis is uncommon in the pediatric population. A review found only 66 cases of primary gout over a period from 1769-1971.

Secondary gout occurs more often but is uncommon too occurring in the diseases listed above. In adult renal transplant patients hyperuricemia (80%) and gout (10%) are frequent complications. In the pediatric renal transplant populations, one study found 50% of patients had hyperuricemia, but rarely had gout. The gout occurred > 5 years after transplant.

Questions for Further Discussion
1. What is the differential diagnosis of joint swelling?
2. What signs and symptoms are consistent with idiopathic juvenile arthritis?
3. What is pseudogout?

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: Gout and Sports Injuries.

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.

Wikipedia. Purine.
Available from the Internet at http://en.wikipedia.org/wiki/Purine (rev. 1/2/15, cited 1/12/15).

Wikipedia. Purine metabolism.
Available from the Internet at http://en.wikipedia.org/wiki/Purine_metabolisme (rev.11/3/14 cited 1/12/15).

Treadwell BL. Juvenile gout. Ann Rheum Dis. 1971 May;30(3):279-84.

Yarom A, Rennebohm RM, Strife F, Levinson JE. Juvenile gouty arthritis. Two cases associated with mild renal insufficiency. Am J Dis Child. 1984 Oct;138(10):955-7.

Sparta G, Kemper MJ, Neuhaus TJ.
Hyperuricemia and gout following pediatric renal transplantation. Pediatr Nephrol. 2006 Dec;21(12):1884-8.

Truck J, Laube GF, von Vigier RO, Goetschel P. Gout in pediatric renal transplant recipients. Pediatr Nephrol. 2010 Dec;25(12):2535-8.

Kim HK, Zbojniewicz AM, Merrow AC, Cheon JE, Kim IO, Emery KH. MR findings of synovial disease in children and young adults: Part 2. Pediatr Radiol. 2011 Apr;41(4):512-24

Robinson PC, Taylor WJ, Merriman TR. Systematic review of the prevalence of gout and hyperuricaemia in Australia. Intern Med J. 2012 Sep;42(9):997-1007.

Author

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

How Do You Treat Water for Cryptosporidium?

Patient Presentation
A 16-year-old male came to clinic with several days of diarrhea that he describes as loose and watery and occurred with some urgency. He denied blood in the stool, fevers, chills, nausea, emesis, abdominal cramping or rashes. He denied any significant weight loss and was urinating well. He had been camping with several other teenage boys just before the diarrhea occurred. They had camped on farmland that was used for dairy animals and crops. “We drank the water from the creek but we did boil it,” he said. He said at least one other camper also had diarrhea. The past medical history showed a healthy male with several athletically-related orthopaedics injuries.

The pertinent physical exam showed a well-developed male. His weight was the same as at a recent well-child examination. His abdominal examination was negative. The diagnosis of a diarrheal illness caused by viral, bacterial or protozoan organisms was made. As he was otherwise well and was well-hydrated, no specific treatment was done but continued hydration and good hygiene was advised. The laboratory evaluation of stool cultures for bacteria and parasites were sent because of the illness duration. The state epidemiology laboratory did extended testing because of the history and diagnosed Cryptosporidium. The state epidemiology team followed up with the patient and the contacts but all had improved when contacted.

Discussion
Cryptosporidium is an oocyte-forming coccidian protozoan. It is transmitted through ingestion of contaminated food, water, or contact with infected persons or animals (particularly preweaned calves). It is a common cause of diarrhea from contaminated recreational water supplies including lakes, ponds, streams, and pool and waterpark water. It has been associated with occupational exposures in agricultural settings and veterinary schools. Emergencies where calves or biological samples are involved have caused transmission of Cryptosporium to first responders. Others at risk include young children and those who care for them (i.e. parents, child care professionals), swimmers who swallow contaminated water, those exposed to human feces through sexual contact, and domestic and international travelers. Travelers who drink unfiltered, untreated water are at higher risk. People who are immunocompromised are also at higher risk.

The most common symptom is watery diarrhea that begins about 7-10 days (range 2-26 days) after infection and is self-limited. Excretion can be intermittent and last for weeks. Other symptoms are abdominal cramps, decreased appetite and weight loss, emesis, fever, fatigue, headache and joint pain. Cryptosporidium testing is usually not included in routine ova and parasite testing so specific testing often needs to be requested. Multiple stool samples may be needed because of the intermittent excretion.

Immunocompetent patients are usually not treated, but nitazoxanide can be used for both immunocompetent and immunocompromised patients.

Common causes of diarrhea can be found here.

Learning Point
Recreational water supplies are a common source as the pool chemicals (often halogens such as chlorine and bromine) are ineffective against Cryptosporidium. Even well maintained facilities can have tainted water and small amounts can cause disease. Cryptosporium can lives for days outside the host. It is a very hearty organism and difficult to kill.

Bathers should not use recreational water if they have open cuts, or sores to help prevent transmission. Swallowing water is never recommended. Inadequately treated water should be avoided. This includes ice or water from lakes, streams, ponds, rivers, springs or shallow wells where the water may be unsafe. Water supplies can be appropriately treated for Cryptosporidum by:

  • Using bottled water instead including for personal hygiene and food preparation.
  • Heating the water to a rolling boil and boiling for 1 minute.
  • Using a water filter. This should be with an absolute pore size of 1 micrometer or smaller or use of an NSF Standard 53 or NSF Standard 58 filter for cyst and oocyst reduction. If a filter is used, then the water will still need additional treatment to kill or inactivate viruses and bacteria.
  • Using chlorine dioxide (not the pool chemical) appropriately
  • Using ultraviolet light appropriately

Detailed information regarding water disinfection for travelers can be found here.

Questions for Further Discussion
1. List other infectious diseases transmitted primarily through water.
2. What are the common causes of traveler’s diarrhea and how is it treated?

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: Cryptosporidiosis.

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.

Centers for Disease Control. Parasites – Cryptosporidium. Available from the Internet at http://www.cdc.gov/parasites/crypto/ (rev. 3/9/11, cited 1/6/15).

American Academy of Pediatrics. Cryptosporidiosis, In Pickering LD, Baker CJ, Kimberlin DW, Long SS, eds. Red Book: 2012 Report of the Committee on Infectious Diseases. 29th edit. Elk Grove Village, IL: American Academy of Pediatrics; 2012;296-98.

Centers for Disease Control. Traveler’s Health Cryptosporidiosis. http://wwwnc.cdc.gov/travel/yellowbook/2014/chapter-3-infectious-diseases-related-to-travel/cryptosporidiosis. (rev. 8/1/13, cited 1/6/15)

Webb LM, Tubach SA, Hunt DC. Outbreak of cryptosporidiosis among responders to a rollover of a truck carrying calves – Kansas, April 2013. MMWR Morb Mortal Wkly Rep. 2014 Dec 19;63(50):1185-8.

Author

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

How Good is 5-Fluorouracil to Treat Plantar Warts?

Patient Presentation
A 4-year-old male came to clinic for treatment of plantar warts that had been present for less than a month. His mother had tried salicylic acid inconsistently and wanted cryotherapy. The past medical history showed a healthy male and the review of systems was normal.

The pertinent physical exam a healthy male with normal vital signs and growth parameters. On the ball of the left foot and great toe he had two flat, but cauliflower-like lesions of ~3-4 mm in size that were relatively superficial. The diagnosis of plantar warts was made. The resident was reviewing his treatment plan with his attending and said that he was going to write a prescription for “WartPEEL®” as one of his other attendings liked that medication instead of plain salicylic acid. His current supervisor asked him what was in the medication and a website showed that it was 5-Fluorouracil and salicylic acid in a proprietary formula. The attending asked the resident about if there was any data that 5FU was more efficacious than plain salicylic acid and what was the difference in cost. The resident wasn’t sure so he said he would try to look into this over the next few days.

Discussion
Veruccae plantaris or plantar warts are caused by Human papillomavirus which causes benign epidermal tumors that often have a cauliflower pattern on the foot that may be elevated or flush with the surrounding skin. Lesions may resemble calluses but the normal footprint pattern is disrupted. The lesions often have pinpoint hemorrhages that appear as black dots. In an immunocompetent individual, the lesions usually have spontaneous resolution within 2 years but the infection may spread to create additional lesions. The lesions may also cause pain or discomfort because of their size or location.

Plantar warts are often difficult to treat. Treatments include keratolytics (e.g. salicylic acid (SA) or tricholoacetamic acid), cryotherapy with liquid nitrogen, electrodesiccation, or direct surgical removal. Suffocation by duct tape and plastic have also been used. Immunotherapy with candida, mumps or trichophytin antigens have been used more recently. These are felt to induce a local and distant immunoresponse that destroys the lesions.

5-Fluorouracil (5FU) is an antineoplastic and antimetabolite that inhibits DNA and RNA synthesis which is believed to be the mechanism that stops wart proliferation WartPEEL®. WartPEEL® is a compounded medication available only in certain locations in the United States and is not FDA approved currently.

Learning Point
Warts are difficult to treat. It takes a long time to treat them. Relapse and spread are common. There can be pain and discomfort with each treatment or with no treatment also. Cost and often daily treatments makes the treatment often difficult to comply with.

Placebo cure rates for wart treatment are around 20-40% for many trials and trials often have end points between 3-6 months.

Topical 5FU compared to placebo shows ~50% cure rate for several trials. Topical 5FU/SA compared to placebo shows 46% versus 19% cure rate. Topical 5FU versus occlusion with duct tape showed 85% cure versus 10% after 6 months of treatment.

5FU is also used as an intralesional treatment. Studies have found intralesional 5FU compared to placebo have a cure rate of 64-70% versus 29-35%.

Questions for Further Discussion
1. 5FU is used for what other disease processes?
2. How effective is intralesional candida treatment? 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: Warts and Human Papillomavirus.

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.

Zschocke I, Hartmann A, Schlöbe A, Cummerow R, Augustin M. Efficacy and benefit of a 5-FU/salicylic acid preparation in the therapy of common and plantar warts–systematic literature review and meta-analysis. J Dtsch Dermatol Ges. 2004 Mar;2(3):187-93. [Abstract only in English]

Salk RS, Grogan KA, Chang TJ. Topical 5% 5-fluorouracil cream in the treatment of plantar warts: a prospective, randomized, and controlled clinical study. J Drugs Dermatol. 2006 May;5(5):418-24.

Kwok CS, Gibbs S, Bennett C, Holland R, Abbott R. Topical treatments for cutaneous warts. Cochrane Database Syst Rev. 2012 Sep 12;9:CD001781.

Author

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

What is the Remission Rate for Antithyroid Drug Treatment for Hyperthyroidism in Children?

Patient Presentation
A 12-year-old female came to clinic for her health maintenance examination. She had no complaints and her mother had no concerns until her daughter was weighed and there was a slower increase in her weight over the year. The patient had normal eating and activity and they denied weight loss. She was sleeping well without night sweats, had normal elimination and was doing well in school. She had a history of being a more anxious child but this was unchanged. The family also denied any skin or hair changes. The past medical history was negative except for some normal acute illnesses. The family history was positive for diabetes, stroke and arthritis. The review of systems was otherwise normal.

The pertinent physical exam showed a well-appearing Asian female with a heart rate of 108 beats/minute, blood pressure of 106/56, respiratory rate of 20 and she was afebrile. Her height was 90% and tracking normally. Her weight had always been at the 95% and was now at the 90%. HEENT revealed very subtle proptosis with the eyelids still covering part of the irises. Her thyroid was diffusely enlarged without palpable nodes and there was no murmur over the organ. She had some shoddy anterior cervical adenopathy. Heart was mildly tachycardic without a murmur. She had normal skin without hair loss or increased perspiration. Neurological examination found a mild tremor of her hands when they were outstretched and she seemed somewhat anxious to the examiner. She also had mild hyperreflexia in all extremities. The laboratory evaluation showed a thyroid stimulating hormone of < 0.1 microU/mL (normal 0.5-4.7 microU/mL), and a free T4 of 3.9 ng/dL (normal 0.8-2.7 ng/dL).

The diagnosis of hyperthyroidism with thyrotoxicosis was made and pediatric endocrinology was consulted by telephone. An appointment for evaluation was made for 2 days later. The radiologic evaluation of a thyroid ultrasound found a mildly diffusely enlarged organ without nodules. Additional laboratory testing was positive for TSH receptor antibodies consistent with Grave’s disease. She began treatment with the antithyroid drug methimazole.

Discussion

The thyroid gland secrets two hormones – T4 which is a prohormone and T3 which is the biologically active hormone. Receptors for T3 are found in nearly all body tissues. T3 regulates metabolism and energy production. Organs most affected are the heart, liver and central nervous system as well as growth of the fetus and child. Hyperthyroidism is common with a prevalence rate of about 1-2% for women and 0.2% for men. The most common cause of thyrotoxicosis is Grave’s disease where autoantibodies to thyroid stimulating hormone (TSH) exist. These autoantibodies attach to thyroid tissue TSH receptors and increase the production of T4 and T3. Grave’s disease often co-occurs with other autoimmune diseases such as diabetes, Hashimoto’s thyroiditis, rheumatoid arthritis and also with Turner’s, Down’s and Di George syndromes. Children only account for about 1-2% of all patients with Grave’s disease.

Signs and symptoms of thyrotoxicosis include:

  • Cardiovascular – tachycardia, palpitations, shortness of breath, arrhythmias, hypertension and high output failure
  • Eyes – soreness and irritation, staring, eyelid retraction, periorbital edema, ophthalmoplegia, conjunctival injection
  • Gastrointestinal – weight loss, increased appetite
  • Genital system – Oligomenorrhea, decreased fertility, reduced libido in men
  • Musculoskeletal – muscle weakness or tremor, muscle wasting
  • Neck – neck swelling
  • Nervous system – hyperactivity, anxiety, concentration problems, fatigue and nervousness, hyperreflexia
  • Skin and Hair – heat intolerance, increased perspiration, warm, moist skin, thinning or hair loss

Treatment options for thyrotoxicosis includes:

  • Antithyroid drugs (ATD) – The most common drugs used are carbimazole and its active metabolite methimazole (MMI) and propylthiouracil. Propylthiouracil is usually not used because of the risk of severe hepatitis.
    MMI is the most common first line drug used and is taken orally daily. Side effects include hives, rashes, gastrointestinal problems and arthritis.
    The goal is to create a euthyroidism condition which then stops the autoimmune response and the thyrotoxicosis. This is defined as the clinical remission.

  • Radioactive iodine (RAI) – it is often used as a more radical treatment if clinical remission cannot be obtained or sustained with ATDs. It may be used as a first line treatment for patients with a large goiter or opthalmopathy.
    A single dose if often used, but the patient may need additional treatments. It is not used in young children, or pregnant or lactating mothers because of the potential risk of neoplasia.

  • Surgery – total or near total thyroidectomy is the most common surgery. RAI may be needed if hyperthyroidism continues after surgery. Surgery causes hypothyroidism and the need for lifelong replacement thyroid medication.

Learning Point
Only about 30% of children achieve clinical remission with ATD treatment, whereas 60-70% of adults achieve remission.
Longer term ATD may be necessary to achieve and keep children in clinical remission. If remission cannot be achieved or sustained, then other treatment is necessary.

Favorable predictors of Grave’s disease remission are older age group, presence of other autoimmune conditions and duration of ATD treatment more than 2 years.
Unfavorable predictors are younger age, large goiter, non-Caucasian race, biochemical severity and ATD medication non-compliance.

Questions for Further Discussion
1. How is Hashimoto’s thyroiditis different from Grave’s Disease?
2. What causes thyrotoxicosis?

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: Hyperthyroidism

.

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.

Franklyn JA, Boelaert K. Thyrotoxicosis. Lancet. 2012 Mar 24;379(9821):1155-66.

Leger J, Carel JC. Hyperthyroidism in childhood: causes, when and how to treat. J Clin Res Pediatr Endocrinol. 2013;5 Suppl 1:50-6.

Leger J, Kaguelidou F, Alberti C, Carel JC. Graves’ disease in children. Best Pract Res Clin Endocrinol Metab. 2014 Mar;28(2):233-43.

Author

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