What is the Recurrence Rate for Guillian-Barré Syndrome and Should She Get An Influenza Vaccine?

Patient Presentation
An 18-year-old female came to clinic with bilateral leg soreness that she felt was not increasing over the past 4 days. She was actually improving at presentation. It worsened with walking up stairs, or when moving from a seated or squatted position to an upright position. She denied pain in other muscle groups or in the actual lower extremity joints. She also denied any paresthesia, difficulty with walking, urinating or defecating, or changes in urine color. She denied any fever, chills, nausea, or difficulty breathing, speaking or swallowing. She had upper respiratory symptoms the week before but had greatly improved. The family was concerned because her past medical history was positive for classic Guillian-Barré syndrome (GBS) when she was 9 years old that was not associated with influenza vaccine and no specific infectious disease was identified by culture at the time. She had slowly improved over 5 months and had no residual symptoms since that time. With more questioning, she noted that she had a big weight lifting workout for gym class the same day as she helped a friend move some boxes on the day before the pain began. “I guess that could be the cause. I didn’t really think about that,” she noted. The family history was negative for neurological disease. The review of systems was negative.

The pertinent physical exam showed a healthy female with normal growth parameters and vital signs. HEENT showed some residual minor rhinorrhea. Her neurological examination was normal including normal sensation and brisk lower and upper extremity reflexes. She had normal strength and tone. She endorsed some minor pain with palpation of the bilateral quadriceps muscles.

The diagnosis of muscle overuse was made. “You have a normal neurological examination and all the other things I would be worried about are negative. No problems with sensing things, walking, breathing, etc. I think you overused your muscles and are sore but getting better,” the pediatrician noted. He went on, “Its influenza season and I know that you and your parents haven’t given you a vaccine usually, but I just want to make sure you don’t have some other reason that would make you high risk now and then you should really get it.” After reviewing high risk individuals, he remarked, “We don’t give the vaccine for people with Guillian-Barré syndrome if they got it within 6 weeks of influenza vaccination. Your Guillian-Barre was not within 6 weeks, so you can get the vaccine. Especially if you become high risk then it is recommended to get it. One thing is if you want to go to medical school as you have told me, that would put you at high risk for flu.”

Guillian-Barré syndrome (GBS) is an acquired, acute, inflammatory, demyelinating polyneuropathy. It is the most common cause of acute and subacute flaccid paralysis in children. GBS causes about 0.4-1.3 cases per 100,000 persons/year in children. It can occur in any age group and the incidence increases among all age groups until a peak in the 50s. Both genders are affected and there may be a slight increase in males.

GBS usually occurs 2-4 weeks after a prodromal gastroenteritis or respiratory illness. GBS causes autoantibody production against Schwann cells of the neuron and the axon itself. There is an increase in anti-ganglioside antibodies which can be specifically identified in about 50% of children.

Classically GBS is a symmetric, progressive ascending muscle weakness and/or paralysis usually first occurring in the legs and then ascending to the upper extremities usually over days to weeks. Areflexia or diminished deep tendon reflexes are early signs (usually first week) if the patient comes to attention. Reflexes can be preserved in some patients though. Sensory changes including pain or paraesthesia can be a first sign in up to 50% of children. The pain can be poorly localized or vocalized because of the children’s age and development. Patients can appear to be ataxic but with further examination this is due to muscle weakness and sensory changes, not actual ataxia. Patients are afebrile.

The nadir when symptoms are the worst is usually around 2 weeks after symptoms begin and most patients begin improving after that. Most have significant improvement by 4 months and most have full recovery. Persistent symptoms can occur with fatigue being the most common, but also paresthesia and pain. Some still have problems including fatigue and sensory issues long term. A review of GBS can be found here.

Learning Point
Recurrences of GBS where patients have 2 or more attacks with an acute inflammatory demyelinating neuropathy are rare. The recurrence rate is quoted as 1-6% with asymptomatic periods ranging from a few months to years (2 months – 37 years depending on the study).

Some studies have demonstrated no incidence of recurrent GBS after seasonal influenza vaccination, and that at the minimum the risk is very small. Therefore GBS has a precaution against seasonal influenza vaccine. The Centers for Disease Control state that “A history of Guillain-Barre Syndrome (GBS) within 6 weeks following a previous dose of any type of influenza vaccine is considered a precaution to vaccination…. Persons who are not at higher risk for severe influenza complications…and who are known to have experienced GBS within 6 weeks of a previous influenza vaccination generally should not be vaccinated. As an alternative to vaccination, physicians might consider using influenza antiviral chemoprophylaxis for these persons…. However, the benefits of influenza vaccination might outweigh the risks for certain persons who have a history of GBS and who also are at higher risk for severe complications from influenza.”

Questions for Further Discussion
1. What groups or individuals are considered high risk for influenza?
2. What causes ataxia? Click here for a differential diagnosis.
3. What causes muscle weakness with and without hypotonia? Click here for a differential diagnosis.

Related Cases

    Symptom/Presentation: Pain

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: Guillian-Barre Syndrome


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.

Baba M, Matsunaga M, Narita S, Liu H. Recurrent Guillain-Barre syndrome in Japan. Intern Med. 1995 Oct;34(10):1015-8.

Koul R, Chacko A, Ahmed R, Varghese T, Javed H, Al-Lamki Z. Ten-year prospective study (clinical spectrum) of childhood Guillain-Barre syndrome in the Arabian peninsula: comparison of outcome in patients in the pre- and post-intravenous immunoglobulin eras. J Child Neurol. 2003 Nov;18(11):767-71.

Stowe J, Andrews N, Wise L, Miller E. Investigation of the temporal association of Guillain-Barre syndrome with influenza vaccine and influenza like illness using the United Kingdom General Practice Research Database. Am J Epidemiol. 2009 Feb 1;169(3):382-8.

Kuitwaard K, Bos-Eyssen ME, Blomkwist-Markens PH, van Doorn PA. Recurrences, vaccinations and long-term symptoms in GBS and CIDP. J Peripher Nerv Syst. 2009 Dec;14(4):310-5.

Roodbol J, de Wit MC, Aarsen FK, Catsman-Berrevoets CE, Jacobs BC. Long-term outcome of Guillain-Barre syndrome in children. J Peripher Nerv Syst. 2014 Jun;19(2):121-6.

Gunatilake SS, Gamlath R, Wimalaratna H. An unusual case of recurrent Guillain-Barre syndrome with normal cerebrospinal fluid protein levels: a case report. BMC Neurol. 2016 Sep 5;16:161.

Centers for Disease Control. Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices – United States, 2018-19 Influenza Season. Recommendations and Reports. MMWR. August 24, 2018. 67(3);1-20. Available from the Internet at: https://www.cdc.gov/mmwr/volumes/67/rr/rr6703a1.htm (cited 9/24/18)

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

What Causes Post-Inflammatory Hypopigmentation?

Patient Presentation
A 7-year-old Asian female came to clinic because of diffuse white spots on her elbows, upper arms, legs and neck. Her mother had noticed them for about 2 months and they were getting worse over the summertime, because they were getting whiter. They had not tried any treatment including medications. They denied any new soaps, lotions, detergents, insect repellents, etc. There were no exposures to animals including dogs or farm animals and they had not traveled out of the immediate area. She had been outside at several day camps and spent other days at the swimming pool. She sometimes wore sunscreen but it was a new bottle and of the same brand she had previously used. The past medical history was positive for atopic dermatitis. The family history was positive for atopic dermatitis and seasonal allergic rhinitis.

The pertinent physical exam showed a healthy female with normal vital signs and growth parameters. Her examination was normal except for her skin. She looked tanned overall. She had diffuse lighter areas on the extensor areas of her lower and upper arms, outer thighs, and neck/upper back. She had similar lesions on her central cheeks. They were not punched out/demarcated and there was no scale. There was general xerosis is the same areas.

The diagnosis of post-inflammatory hypopigmentation was made. The patient and parent confirmed that the same areas were her “bad” areas of atopic dermatitis. She also said that she was itchy at times and had been scratching the areas also occasionally over the summer. The natural history was explained to the family, along with instructions on consistent and frequent sunscreen and emollient use.

Hypopigmentation can be worrisome for many families because of cosmesis and the worry that “something is wrong.” The normal natural changes in skin-tone over the year due to different light exposure and wide variations within individuals is not something that many people are aware of.
Post-inflammatory hypopigmentation is a common cause of hypopigmentation. Vitiligo is the most common cause of depigmentation.

Vitiligo is an acquired, depigmenting disorder with typical lesions appearing as milky white macules with distinct margins that are not scaly. Hair (including eyebrows and eyelashes) can be depigmented if it occurs in a particular area. It occurs in about 0.5-1% of the population and is the most common cause of depigmentation. Melanocytes are absent from the affected skin area. All ages and genders are affected. Vitiligo usually is of the non-segmental form where lesions are bilateral and symmetrical across the body. The segmental form is unilateral, band or segmental in distribution. The lesions can occur in any part of the body and for some people they are increased because of skin trauma (clothing constrictions in certain areas, i.e. Koebner phenomenon)

Vitiligo has been known for centuries and social discrimination because of the white lesions has been intense at different times and in different cultures. Vitiligo was often confused with leprosy for instance in the past, leading to social stigma based similarities between the white skin lesions. Even today there is higher social stigma for patients whose vitiligo lesions are visible versus not visible. Patients need general social support and may need professional counseling as part of their treatment. Treatments include using topical corticosteroids or calcineurin inhibitors as a first line treatment usually for at least 6 months to be able to view results. Phototherapy with UVA and UVB can also be used for at least for 3-6 months to view results. Other more invasive treatments potentially include surgery such as grafts or depigmenting treatments.

Other causes of hypopigmentation include:

  • Vitiligo – most common depigmentation disease
  • Endocrine – Cushing’s syndrome, hypopituitarism
  • Incontientia pigmenti
  • Hypomelanosis of Ito
  • Halo nevus
  • Hypomelanosis – idiopathic guttate
  • Leukoderma – chemical or drugs, puncta
  • Normal – fair skin-tone individual
  • Nutrition – kwashiokor
  • Post-inflammatory hypopigmentation
  • Pityriasis alba
  • Piebaldism

Learning Point
Post inflammatory hypopigmentation is very common. It can be localized or diffuse, but is more prominent in darker skin-toned individuals. “Melanocytes can react with normal, increased or decreased melanin production in response to cutaneous inflammation or trauma. The chromatic tendency is genetically determined, and inherited in an autosomal dominant pattern. People with weak melanocytes, which have high susceptibility to damage, are more likely to develop hyperpigmentation, whereas those with strong melanocytes develop hypopigmentation.” The areas affected usually correspond to the original areas of inflammation. Wood’s lamp examination highlights the lesions. Treatment is identification of the cause and preventing recurrence (the most important part), steroid creams along with tar preparation, calcineurin inhibitors, and sun or UV exposure are also options.

Causes of post-inflammatory hypopigmentation include:

  • Skin inflammation
    • Atopic dermatitis
    • Contact dermatitis
    • Graft vs host reaction
    • Hypopigmented mycosis fungoides
    • Insect bites
    • Lichen planus
    • Lichen striatus
    • Lichen sclerosis et atrophicus, extragenital
    • Lupus erythematosus
    • Paget’s disease, extramammary
    • Psoriasis
    • Sarcoidosis
    • Scleroderma
    • Stevens-Johnson syndrome
  • Infections
    • Herpes zoster
    • Impetigo
    • Leprosy
    • Onchocerciasis
    • Pityriasis versicolor
    • Syphilis
    • Varicella
  • Medical interventions
    • medications – corticosteroid
    • Chemical peels
    • Cryotherapy
    • Dermabrasion
    • Laser treatment
  • Other
    • Burns

Questions for Further Discussion
1. What causes hyperpigmentation? A review can be found here
2. What are indications for referral to a dermatologist?
3. What causes albinism?

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 and the Cochrane Database of Systematic Reviews.
Information prescriptions for patients can be found at MedlinePlus for this topic: Skin Pigmentation Disorders

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.

Vachiramon V, Thadanipon K. Postinflammatory hypopigmentation. Clin Exp Dermatol. 2011 Oct;36(7):708-14.

Bodemer C. Incontinentia pigmenti and hypomelanosis of Ito. Handb Clin Neurol. 2013;111:341-7.

Nicolaidou E, Katsambas AD. Pigmentation disorders: hyperpigmentation and hypopigmentation. Clin Dermatol. 2014 Jan-Feb;32(1):66-72.

Ezzedine K, Eleftheriadou V, Whitton M, van Geel N. Vitiligo. Lancet. 2015 Jul 4;386(9988):74-84.

Roh MR, Oh SH. Acquired hypopigmentation disorders other than vitiligo. UpToDate. (rev. 1/17/18, cited 9/18/18y).

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

What is the Dutch Protocol for Gender Dysphoria?

Patient Presentation
A 14-year-old girl came to clinic with her mother for her well-child appointment. She had moved to the area 2 years ago and had been seen in the school clinic for primary care, but had also been referred to the LGBTQ multidisciplinary clinic at the regional medical center. She had diagnoses of anxiety and gender dysphoria that were currently being treated with psychotherapy and hormonal pubertal suppression. The past 4 months she had been feeling very well, doing better in school with As and Bs, and had joined a school club. She attended a church but did not participate in its teen-related activities. The chart showed the LGBTQ clinic was discussing gender affirming treatment with cross-sex hormones with her. She did not want to discuss it at this time with the new pediatrician. She said was comfortable with her LGBTQ providers, mental health progress and felt good about her herself, her body and her relationships at school and home.

The past medical and social history showed her natal gender as male. She had a broken wrist from a skateboarding accident. Throughout childhood she had engaged in activities that were characteristic of both genders. When she started puberty around 12 years of age, she became quite distressed with how her body looked and felt to her. It was around that time they moved and she did social transitioning, taking on a female name, clothing etc. Her mother was very supportive of her and there were only the 2 of them in the family unit. The family history was positive for diabetes, and kidney disease.

The pertinent physical exam showed normal vital signs. Height and weight were consistent with the 10-25% but she did appear to be starting to increase her height velocity. Her physical examination was normal. Her genitalia was male and Tanner staging was 2-3 for genitals and pubic hair.

The diagnosis of a healthy female with anxiety and gender dysphoria was made. She was being provided good support and medical care. The pediatrician reiterated the confidential care that he provided. She needed a seasonal influenza vaccine in about 4 months. “You can get that at school or at the other doctors’ office. We also offer nursing appointments but you can also can come back and check in with me and I can do that for you,” he said. The pediatrician noted later that she had made an appointment for a followup appointment and an influenza vaccine.

Terminology related to gender∂has changed over time and with newer more specific terminology developing more consensus. Also terminology used by patients to describe themselves or their situation may be different than below.

  • “Gender – denotes the public (and usually legally recognized) lived role as boy or girl, man or woman. Biological factors combined with social and psychological factors contribute to gender development.”
    Gender is not dichotomous and other terms such as third gender, agender or gender queer reflect this.

  • “Assigned gender – refers to a person’s initial assignment as male or female at birth [sometimes called birth gender or natal gender, as in “natal female” or “natal male”]. It is based on the child’s genitalia and other visible physical sex characteristics.”
  • “Gender identity – is a category of social identity and refers to an individual’s identification as male, female or, …, some category other than male or female. It is one’s deeply held core sense of being male, female, some of both or neither, and does not always correspond to biological sex.”
  • “Gender-atypical [or gender non-conforming, or gender variant] – refers to physical features or behaviors that are not typical of individuals of the same assigned gender in a given society.”
  • “Cisgender – describes individuals whose gender identity or expression aligns with the sex assigned to them at birth.”
  • “Transgender – refers to the broad spectrum of individuals who transiently or persistently identify with a gender different from their gender at birth.”
  • Gender dysphoria – when an individual’s gender identity is incongruent with their assigned gender or sexual body characteristics and this incongruence causes extreme distress.
    If the incongruence does not cause distress it is not diagnosed as dysphoria. Distress caused by social stigma, bullying, and family non-acceptance also is not diagnosed as gender dysphoria.

  • Sexual orientation – “is the personal quality inclining persons to be romantically or physically attracted to persons of the same sex, opposite sex, both sexes or neither sex.”
  • “Gender expression – the manner in which a person communicates about gender to others through external means such as clothing, appearance, or mannerisms.”
  • Transitioning is “…the process where individuals change their social and/or physical characteristics for the purpose of living in their desired gender role.” It includes social and/or general affirming treatment.
  • Social transitioning is when a person “…starts to live in the experienced gender role and encompasses clothing, gender role behavior, and the use of a name and pronouns of that gender.” This is a reversible process.
  • “Gender affirming treatment is the clinical approach that supports the expression of one’s experienced gender of which puberty blockers, hormone treatment, and surgeries may be a part.” This can be a reversible or non-reversible process.

A review of the use of gender neutral language in interviews can be found here.
Note that even from 2008 when it was published until now some terminology has been updated.

The gender identity published literature has been increasing in the last couple of decades but still there are major gaps in areas of understanding. Estimates often cite ~1.2% of 8000 high school students said that they wished to be the opposite sex or were transgender. About 2.5% were not sure about their gender. Many estimates are thought to be underestimates.

Gender identity is a developmental process. At 3-7 years are when children typically develop a sense of being a boy, being a girl or something else. By age 6-7 years the child realizes that their gender is likely to remain constant. Ages 10-13 years are very important for gender identity development as this is the time when physical puberty, gendered social relationships and romantic feelings arise. Many youth who are gender non-conforming, do not have gender dysphoria and are happy with their lived experiences. Other youth may be distressed but it may be difficult to discern if gender dysphoria will persist or desist over time. Having some experience with their own physical changes at puberty appears to be important in determining (at least partially) if gender dysphoria will persist or resolve.

According to the American Psychiatric Association the DSM 5 criteria for gender dysphoria are:

“In adolescents and adults gender dysphoria diagnosis involves a difference between one’s experienced/expressed gender and assigned gender, and significant distress or problems functioning. It lasts at least six months and is shown by at least two of the following:

1. A marked incongruence between one’s experienced/expressed gender and primary and/or secondary sex characteristics
2. A strong desire to be rid of one’s primary and/or secondary sex characteristics
3. A strong desire for the primary and/or secondary sex characteristics of the other gender
4. A strong desire to be of the other gender
5. A strong desire to be treated as the other gender
6. A strong conviction that one has the typical feelings and reactions of the other gender

In children, gender dysphoria diagnosis involves at least six of the following and an associated significant distress or impairment in function, lasting at least six months.

1. A strong desire to be of the other gender or an insistence that one is the other gender
2. A strong preference for wearing clothes typical of the opposite gender
3. A strong preference for cross-gender roles in make-believe play or fantasy play
4. A strong preference for the toys, games or activities stereotypically used or engaged in by the other gender
5. A strong preference for playmates of the other gender
6. A strong rejection of toys, games and activities typical of one’s assigned gender
7. A strong dislike of one’s sexual anatomy
8. A strong desire for the physical sex characteristics that match one’s experienced gender”

Learning Point
A Dutch multidisciplinary protocol for treatment for gender dysphoria with gender affirming treatment centers on appropriate diagnosis and extensive supportive mental health treatment if/when appropriate. Youth who are peripubertal (11/12 up to 15/16 years) may be offered reversible puberty suppression with gonadotropin releasing hormone analogues (GnRH). This can be done for up to 3-4 years. Youth (15/16 up to 18 years) then may be offered gender affirming treatment with cross-sex hormones, the effects of which can be partially reversible. Young adults (18+ years) may be offered gender affirming treatment with cross-sex hormones and/or surgeries. The outcomes “…found that after surgery the psychological function and well-being had steadily improved and were similar or better than same-age young adults from the general population.”

Patients need counseling to have a healthy lifestyle. Obesity or cardiovascular problems can increase risks of hormonal treatments. Smoking can cause problems with surgeries. Hormonal treatments can lead to bone loss so appropriate diet and exercise is imperative. Families also need information, counseling and support themselves to better understand their family member and support them.

Questions for Further Discussion
1. What types of psychological problems are gender atypical individuals are at risk for?
2. What is the primary care pediatrician’s role for patients and families with gender identity issues?
3. Where in your local area would you send patient’s for gender identity specialty care?

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, and the Cochrane Database of Systematic Reviews.
Information prescriptions for patients can be found at MedlinePlus for this topic: Gay, Lesbian, Sexual and Transgender 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.

Delemarre-van de Waal HA, Cohen-Kettenis PT. Clinical management of gender identity disorder in adolescents: a protocol on psychological and pediatric endocrinology aspects. Eur J Endocrinol 2006;155:131-37.

de Vries AL, Cohen-Kettenis PT. Clinical management of gender dysphoria in children and adolescents: the Dutch approach. J Homosex. 2012;59(3):301-20.

Bonifacio HJ, Rosenthal SM. Gender Variance and Dysphoria in Children and Adolescents. Pediatr Clin North Am. 2015 Aug;62(4):1001-16.

de Vries AL, Klink D, Cohen-Kettenis PT. What the Primary Care Pediatrician Needs to Know About Gender Incongruence and Gender Dysphoria in Children and Adolescents. Pediatr Clin North Am. 2016 Dec;63(6):1121-1135.

Fuss J, Auer MK, Briken P. Gender dysphoria in children and adolescents: a review of recent research. Curr Opin Psychiatry. 2015 Nov;28(6):430-4.

Parekh R. Gender Dysphoria. American Psychiatric Association.
Available from the Internet at https://www.psychiatry.org/patients-families/gender-dysphoria/what-is-gender-dysphoria (rev. 2/2016, cited 9/11/18).

American Academy of Pediatrics Policy Statement. Ensuring Comprehensive Care and Support for Transgender and Gender-Diverse Children and Adolescents. Available from the Internet at: http://pediatrics.aappublications.org/content/early/2018/09/13/peds.2018-2162 (rev. 9/17/18, cited 9/17/18).

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

Frostbite After Cryotherapy?

Patient Presentation
A 17-year-old male came to the emergency room after being treated with cryotherapy for recalcitrant plantar warts the day before. He had been treated on the right great toe and the medial aspect of the left great toe. The night prior there had been small blisters around both treated areas. The next morning he had significant blistering and some pain with walking. He had cut out part of his tennis shoe to accommodate the blister with much pain relief. The past medical history was non-contributory and his tetanus shot was current.

The pertinent physical exam showed a healthy male in no distress unless he was walking or pressure was placed on the left foot lesion. The right great toe lesion was unchanged from the previous night and was about 5-7 mm across that coincided with the verrucous tissue with a small amount of clear fluid in the blister. There was minimal pain. The left foot lesion was about 3 cm across and 1 cm elevation with dark fluid (see Figure 124a). The tissue around the blister was slightly erythematous but there was no cyanosis. He had normal sensation in the areas around the lesions and was able to move his toes fully.

The diagnosis of localized frostbite (grade II-III) was made. The surgical resident was consulted and after discussion with the attending and the parents who were both nurses it was decided to not disrupt the blister and treat it conservatively with rest, elevation and pain management. He and his parents were instructed to loosely cover the blister with a non-adherent bandage (antibiotic ointment with loose gauze) and to monitor it closely for extension of the lesion and infection. He returned to the surgical clinic for followup. At 1 week followup the pain was greatly diminished but there continued to be some hemorrhagic fluid. At 2-3 weeks, the fluid had mostly dissipated and he was wearing normal shoes (see Figure 124b). At 4.5 weeks, the top of the blister separated by itself from the healthy healing underlying tissue (see Figure 124c).

Case Image
Figure 124a – Verrucous lesion 24 hours after treatment with cryotherapy with blistered extension of the treatment area.

Case Image

Figure 124b – Resolving frostbite after 2-3 weeks.

Case Image
Figure 124c – Healing granulated tissue after 4.5 weeks>

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.

There are numerous potential treatments for common warts. A 2012 Cochrane Collaboration evaluation found salicylic acid to be better than placebo especially for hand lesions. Cryotherapy overall for all sites was not better than control, but for hands may have slightly better outcomes. More aggressive cryotherapy was more effective than gentle cryotherapy but had increased side effects.

In general, cryotherapy for verrucous lesions tries to include the actual lesion and a 1-2 mm halo of normal tissue around the lesion. Even with professional equipment it still can be difficult to control the precise application of the cryotherapy to the verrucous lesions because of the lesion location, lesion depth, width of the liquid nitrogen spray from the applicator, and the length of time the cryotherapy is applied. Cryotherapy application by cotton bud is more precise as it is a direct application but it does not freeze more than ~ 3 mm in depth. Spray application, especially a longer application time, has a better chance of getting deeper into the tissues to destroy the verrucae but increases the risks of side effects. Cryotherapy is known to have higher incidence of side effects than other types of verrucous lesion treatments. Side effects include burning, pruritus, pain, erythema, and blister formation. Frostbite is also a potential complication and can occur with professional or over-the-counter cryotherapy devices.

Learning Point
Burns are caused by direct chemical, electrical, radiation or thermal sources resulting in tissue injury. Most people view burns as caused by heat injuries but cold application can also cause injuries by direct damage to cells, and progressive dermal ischemia. It is the dermal ischemia which is usually more harmful. When frostbite is first seen it can be difficult to estimate its severity. Frostbite is categorized after rewarming into 4 categories:

  • Grade 1 – Superficial with central area of pallor and area of erythema/edema. Usually has no sequelae.
  • Grade 2 – Large blisters with clear fluid with surrounding erythema/edema. Usually occurs within 24 hours of the injury. Blisters slough off with healthy granulation tissue. Heals very well.
  • Grade 3 – Smaller hemorrhagic blisters with escars that form over several weeks. Damage is deeper and may have long term sequelae.
  • Grade 4 – Frostbite that extends to muscle and bone with tissue necrosis. Mummification occurs in 4-10 days.

Prevention is always better than treatment. Treatment for frostbite includes treating the entire individual especially when hypothermia and other injuries are concomitant. Wet clothing should be removed and the area rewarmed with body temperature or slightly warmer water (do not use stoves/fire as the tissue is insensate and these can cause additional thermal injury). This usually takes 15-30 minutes and can be quite painful so pain management is needed. Areas should not be rubbed and walking or movement should be limited as appropriate. Wound care includes using non-adherent dressings, sterile fluffed gauze, inserting pledgets between digits to prevent maceration as appropiate and avoiding occlusive dressings. Protection from additional mechanical damage is also important. Blister treatment is controversial depending on the type of blister and location. Some recommend draining, debriding and bandaging while others recommend aspiration only or leaving them intact. Tetanus prophylaxis is recommended and prophylactic antibiotics are also controversial. Especially in the cases of severe injury, imaging studies may help determine the extent of tissue damage and response to treatment, and other treatment includes thrombolysis or vasodilitation for severe injuries.

Questions for Further Discussion
1. What are risk factors for frostbite?
2. In addition to frostbite, what are other cold-related disease processes?

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, and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Frostbite and Warts.

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.

Sammut SJ, Brackley PT, Duncan C, Kelly M, Raraty C, Graham K. Frostbite following use of a commercially available cryotherapy device for the removal of viral warts. Dermatol Online J. 2008 Jun 15;14(6):9.

Dall’oglio F, D’Amico V, Nasca MR, Micali G. Treatment of cutaneous warts: an evidence-based review. Am J Clin Dermatol. 2012 Apr 1;13(2):73-96.

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

Sarwar U, Tickunas T. Frostbite developing secondary to cryotherapy for viral warts. Br J Gen Pract. 2013 May;63(610):239-40.

Hutchison RL. Frostbite of the hand. J Hand Surg Am. 2014 Sep;39(9):1863-8.

Zafren K. Frostbite. UpToDate. (rev. 2/15/18, cited 8/27/18).

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