Skin Biopsy in the Pediatric Age Group

Abstract

Skin biopsy has a crucial place in arriving at a definitive diagnosis in many pediatric dermatologic conditions. The need to perform a skin biopsy on a child may provoke apprehension in the parents/caregivers, which can be alleviated by establishing a good rapport with them. The details of the procedure, including benefits and risks involved, and the expected result should be communicated to the parents in an easy-to-understand language to have an informed decision. In this review, literature search was done across the PubMed database from January 1992 to January 2022 using the following keywords “skin biopsy in children,” “skin biopsy in pediatric age group,” “pediatric dermatopathology,” “dermatologic surgery in children,” “dermatologic surgery in pediatric age group,” “pediatric dermatologic surgery,” and “procedures in pediatric dermatology.” Articles not written in the English language were excluded.

Introduction

Although many skin diseases seen in children are similar to those in adults, there are some that are exclusively limited to the pediatric age group. Pediatric dermatoses encompass a wide range of conditions, most of which such as infections and eczemas can be diagnosed clinically.[¹] Skin biopsy is a minor surgical procedure that is less commonly performed in children than in adults, due to parents’ reservations and also because children may be treated by pediatricians without performing a skin biopsy.[¹] The frequency of skin biopsies performed in outpatient pediatric dermatology departments has been reported to be 1.7%–3.7%, while it was much higher 17.5%–35% for inpatient pediatric consultations.[²] Skin biopsy was most frequently obtained in the adolescent age group (12–17 years).[¹] Nevi, genodermatoses, tumors, and either benign or malignant are some of the conditions that may warrant histopathologic confirmation. A great degree of patience and empathy is required by the treating dermatologist toward children and their accompanying parents to allay any anxiety and fear regarding skin biopsy. This review discusses the indications and contraindications of performing skin biopsy in children, preparation of child and parents during the procedure, choice of local anesthesia, biopsy techniques, tips for obtaining biopsy specimens in specific conditions, associated complications, and postbiopsy care.

Materials and Methods

A comprehensive literature search was done using the following keywords “skin biopsy in children,” “skin biopsy in pediatric age group,” “pediatric dermatopathology,” “dermatologic surgery in children,” “dermatologic surgery in pediatric age group,” “pediatric dermatologic surgery,” and “procedures in pediatric dermatology.” PubMed database was used for search strategy, and only English language full-text articles were included during the period from January 1992 to January 2022. A total of twenty articles/book chapters were screened, of which eight articles (original and review) and book chapters were selected.

Discussion

Indications of skin biopsy

Although a diagnosis is often reached by means of history and clinical examination in the pediatric age group, a skin biopsy may be performed in the following situations: When the condition is suspected to be serious, when the diagnosis cannot be made in a less invasive manner, to confirm the clinical diagnosis with histopathology expected to give a specific diagnosis, the prognosis and treatment are likely to be guided by biopsy findings or if the patient fails to respond to initial diagnosis and therapy given.[³] The specific disorders where a biopsy may be indicated in children include epidermal, dermal and melanocytic nevi, cutaneous mastocytosis, epidermolysis bullosa, immunobullous diseases, infections comprising of tuberculosis and leprosy, erythrodermas, panniculitis, vasculitis, histiocytoses, metabolic and nutritional conditions, and soft-tissue tumors. In a retrospective review of 506 pediatric cases <16 years of age, 82% of the biopsies/excisions were done for tumors, cysts, and hamartomas and 18% for other skin disorders. Biopsy was done as a therapeutic intervention in 75% of the patients, while in 36%, it was performed on the family’s or patients’ request. The biopsy findings had a direct impact on the management of the patients in 24% of cases. In 12%, it was done to exclude a severe disease and in 7% to confirm the diagnosis of severe disease.[³] The most common diagnosis was congenital or acquired melanocytic nevus in 35% of the biopsies/excisions, followed by pyogenic granuloma and infantile hemangioma. Among inflammatory dermatoses, eczema was the most frequent condition.[³]

Contraindications of skin biopsy in children include the history of allergic reaction to local anesthetics, active infection at the site of biopsy, history of bleeding/clotting disorder, or use of any drugs known to impair hemostasis. Special sites such as the face, palms, and soles should be avoided relatively if lesions are involving other areas also.[⁴] It may be worthwhile to obtain a good history of any previous procedure done on the patient and whether there was any complication related to that in the past.

Preparation for biopsy

A written informed consent form is to be signed by the parents or guardians. They have to be told in detail about the need for skin biopsy, how it will be done, the duration of the procedure, any associated complications, and when to expect the result to ameliorate their fear.[⁴] If parents are not anxious, they should be present with the child during the procedure or else they can wait outside the biopsy room during the procedure. When present inside the biopsy room, the parents can talk to the child with their calming and soothing words. Infants can be restrained by wrapped up in sheet and exposing the site to be biopsied.[⁵] It is difficult to make young children understand why a biopsy is needed, that a medicine will be used to numb the area and pain will not occur once the procedure is over. The room temperature should be comfortable for the child. It is important to cover the instruments and block the sight of the needle and the procedure as much as possible. Distraction using mobile phones to show some cartoon, video game and music, books, and magazines are a good means of allaying the pain.[⁵] Children can also bring some toys from home. Counterstimulation techniques such as pinching the child can also be of help. Another technique that can be employed is rewarding gifts to children at the end of the procedure. Older children may want the entire procedure to be explained to them well in advance. They may be worried about cosmetic appearance after obtaining a biopsy.

Topical anesthesia

The biopsy site is cleaned first using isopropyl alcohol. Topical anesthesia may be used alone or before infiltrative anesthesia to reduce pain. Eutectic mixture of lidocaine and prilocaine (EMLA), a topical anesthetic cream containing lidocaine 2.5% and prilocaine 2.5%, can be applied to the lesion to be biopsied by the parents at home.[⁶] It should be applied to the intact skin to avoid the risk of systemic absorption. A thick layer is applied and occluded with a cover/dressing that is easy to remove without causing much pain. The cream can be removed and the site cleaned with a gauze using alcohol-based solution. The duration of analgesia depends on the duration for which EMLA is applied. The effect is achieved after 1 h of application and lasts for 1–2 h. The onset is faster at mucosal sites (<30 min). Anesthesia up to 3-mm depth in the skin is achieved after 1 h and up to 5 mm after 2 h of application.[⁷]

Prilocaine can lead to methemoglobinemia due to immaturity of NADH reductase enzyme in infants. Because of this risk, the maximum safe limit recommended is 2 g in children aged 2–11 months, 10 g in children aged 1–5 years, and 20 g for those above 6 years of age.[⁶] Disadvantages include the risk of toxicity when applied on larger areas and blanching of vascular lesions, thereby interfering with biopsy. Topical 4% liposomal lidocaine for 30 min under occlusion has also been used before infiltration anesthesia. In children with a history of allergic reaction to lidocaine or prilocaine, vapor coolants may be used before needle insertion, though they are less effective than EMLA.[⁶] Infiltration of local anesthetic agent is done immediately after spraying coolant onto the skin. Cooling effect results in pain control. Inflammable nature of these sprays is a significant disadvantage.

Infiltration anesthesia

Local anesthetic agents produce pain relief without affecting consciousness. Agents used for infiltration anesthesia include lidocaine, bupivacaine, ropivacaine, prilocaine, and articaine.[⁶] Vasoconstrictors such as adrenaline (maximum concentration of 1:100,000) are added to local anesthetics to increase the duration of anesthesia, reduce their systemic absorption, and minimize blood loss. Vasoconstriction can occur when adrenaline is used with lignocaine for port wine stains and other vascular lesions, thereby interfering with the identification of vascular structures. Adrenaline should be avoided in acral sites and genitals. Lidocaine is the most commonly used agent and has a rapid onset of action (<2 min). Duration of effect lasts for 30–60 min. It is available in 0.5%, 1%, and 2% concentrations.[⁶⁷] Both the needle penetration and infiltration of the drug can cause transient pain. The following practices may reduce the pain associated with needle insertion: distant skin can be pinched, rubbed, or a vibratory instrument applied before infiltration, icing the area 2 min before injection, and using a 30-gauge needle at 90° to the skin.[⁶] Subcutaneous injection is given using the spider technique, and biopsy is taken after waiting for about 2 min. Pain due to drug infiltration can be reduced by slow administration of the drug, injecting at room temperature, and the addition of sodium bicarbonate. The addition of sodium bicarbonate, however, inactivates adrenaline.

Allergy to local anesthetics is an absolute contraindication for their use. Low concentration of a-1 acid glycoprotein, a serum protein which binds the anesthetic agents, can lead to increased blood levels of unbound local anesthetic and hence the risk of toxicity in neonates. Although rare, it can manifest as seizures and cardiovascular collapse. Infusion of lipid emulsions and symptomatic treatment are useful in the management.[⁶]

Commonly used topical and infiltration anesthetics are summarized in Table 1.[⁶⁷]

Table 1: Details of common topical and infiltration anesthetic agents used before skin biopsy in pediatric patients

Sedation

It may be required before performing biopsy in rare circumstances when children are extremely uncooperative or have significant anxiety related to the procedure. Conscious sedation refers to decreased consciousness induced pharmacologically, in which protective respiratory reflexes are maintained, and the patient can be aroused by physical or verbal stimuli.[⁸] Sedatives are generally used in combination with anesthetics and analgesics and under the supervision of an anesthesiologist. Common sedatives used include first-generation antihistamines and benzodiazepines.

Biopsy Techniques

Multiple techniques of biopsy are used depending on the differential diagnosis considered, location of the lesion, and expertise of the dermatologist. These include:

1. Punch biopsy
2. Shave biopsy
3. Incisional biopsy
4. Excisional biopsy.

Punch biopsy is the most frequently performed technique. Punches of varying sizes can be used, and the wound is closed with sutures or can be even left to heal by secondary intention. It is generally used for smaller lesions and includes epidermis, dermis, and sometimes even subcutaneous fat.[⁴⁷] Shave biopsy is a superficial biopsy that usually includes epidermis and part of the papillary dermis. It is easy to perform using 15 number blade for removal of melanocytic nevi that are not suspicious. It can also be used to obtain intact large bullae in bullous diseases. Suturing is not required to close the wound. If there is suspicion of melanoma, incisional or excisional biopsy should be taken. Incisional biopsy is preferred when a part of the lesion is sampled from a large lesion which cannot be excised as in infections or when biopsy up to subcutis is required in suspected panniculitis. Excisional biopsy is suitable for benign or malignant lesions that need to be completely removed for histopathologic examination such as congenital nevi.[⁴⁷]

Recommendations for biopsy site and technique in specific conditions are enlisted in Table 2.[⁹¹⁰]

Table 2: Special considerations in selecting biopsy site in different indications

Complications and Postbiopsy Care

Instructions should be given verbally and in written format to the parents after the completion of the procedure. Immediate complications include bleeding, oozing, and pain, which are often self-limiting.[¹¹] The child should be asked to rest on the day of the procedure with no exertional activities to prevent wound dehiscence and other complications. Pain is usually not troublesome due to the use of local anesthetics, but if the child is in discomfort, oral acetaminophen (10–15 mg/kg/day) can be given for the management of pain.[¹¹] For bleeding, pressure can be applied at the site of biopsy for 10–15 min. Sutures are often needed for hemostasis especially if more than 3–4 mm size punch is used. Sometimes, the bleeder may need to be sutured. Wound infection can present as pus discharge associated with redness and swelling. Pus should be sent for culture and antibacterial susceptibility testing and accordingly treated with oral antibiotics. The dressing can be removed after 24 h; thereafter bandage applied should be changed every day for 2–3 days and then left open for healing. The wound should be kept dry and topical antibiotics applied. Rarely, allergic contact dermatitis can occur due to topical antiseptics or dressing material used, which can be managed with topical corticosteroids.[¹¹] The biopsy site should be examined and sutures removed after 1 week. Delayed complications include scarring and pigmentary changes.

Conclusion

Skin biopsy is performed in children to confirm a specific diagnosis, rule out a serious disease, or even as a therapeutic intervention. It is often a significant source of anxiety for both the child and the parents. A patient and understanding attitude of the treating dermatologist during pre- and postbiopsy period is essential in reducing the stress and ensuring cooperation from the child and his parents. Topical anesthesia alone or along with infiltration anesthesia is effective in minimizing the pain associated with the procedure. The type of biopsy is determined by the indication and site of the lesion.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.