Nail Changes in Children Undergoing Chemotherapy

Ardelia Dyah Ayu

1,*

, Reti Anggraeni

, Endra Yustin Ellista Sari

, Muh. Riza

, and Suci Widhiati

Dermatovenereology Departement, Dr. Moewardi General Hospital/Faculty of Medicine Sebelas Maret University,

Surakarta

Pediatric Department, Dr. Moewardi General Hospital/ Faculty of Medicine Sebelas Maret University, Surakarta

Keywords: nail changes, nail disorder, children, chemotherapy

Abstract: Many chemotherapeutic agents used in the management of various malignancies. Nail changes are often under

recognized or attributed to other causes. The anticancer chemotherapeutic agents were known to cause a

damage to the nail. This analytical, cross-sectional study was conducted in Dr. Moewardi General Hospital

Surakarta between December 2017 and January 2018. The subjects were taken by consecutive sampling,

consisting of 30 children undergoing chemotherapy and 30 healthy children as a control. History taking and

physical examination in the form of digital photography as well as dermoscopic examination were conducted

in all subjects. The data obtained were then analyzed using Mann-Whitney test, p < 0.05 was considered

significant statistically. Nail changes were observed in 25/30 ( 83.3%) of the children receiving chemotherapy

and they have a statistical significant difference compared to control group, with the p value 0.000. The nail

changes obtained were trachonychia (22,2%), dyscromia (18.5%), melanonychia (14.8%), and Beau’s lines

(14.8%). Combination of methotrexate and vincristine was the most frequent chemotherapeutic agent used in

the subjects (40%). This study is expected to provide knowledge for dermatologist so that it can improve the

promotive health, preventive, curative and education for the patient.

1 INTRODUCTION

The anticancer chemotherapeutic agents were known

to cause various mucocutaneous side effects,

including nail changes. Nail changes are often under-

recognized or attributed to many causes.

Chemotherapy-induced nail changes, though they not

life threatening, are cosmetically distracting and can

be a source of significant distress to patients.

The anti- cancer chemotherapeutic agents may

cause a damage to the nail matrix or the nail bed and

a variety of changes involving the nail plate, nail bed,

hyponychium or the nail folds may be seen (Chen et

al., 2007). Several chemotherapy agents and their

combinations have been reported to induce nail

changes, including taxoids, cyclophosphamide,

doxorubicin/ daunorubicin, 5-fluorouracil and

vincristine. Cyclophosphamide and doxorubicin are

two agents commonly reported to affect the nails

(Hinds & Thomas, 2008).

The nail changes mostly are the result of acute

toxicity to the nail epithelium. Various symptoms will

occur depend on which nail structure is affected and

the severity of the insult (Piraccini et al., 2003).

Pigmentation changes due to chemotherapeutic

agents involving the nail plate are seen secondary to

the damage of the nail matrix melanocytes. The

damage to the nail bed may be as a consequence of

direct damage due to drugs or an indirect damage to

the underlying blood vessels (Reddy et al., 2017).

Nail growth in children is faster than is in adult,

and it is estimated to be at a rate of 0.12 mm / day

(Chen et al., 2007; Balgord & Pardee, 2008; Robert et

al., 2015). However, nail changes in children

undergoing chemotherapy, in comparison to adult

cases, are less well characterized in the literature.

This study was designed to understand and to find out

the pattern of nail changes in children receiving

various chemotherapies.

2 METHODS

An analytical, cross-sectional study conducted in Dr.

Moewardi General Hospital Surakarta between

December 2017 and January 2018. The subjects were

taken by consecutive sampling, consisting of 30

children undergoing chemotherapy and 30 healthy

children as a control.

History taking and physical examination in the

form of digital photography as well as dermoscopic

118

Ayu, A., Anggraeni, R., Sari, E., Riza, M. and Widhiati, S.

Nail Changes in Children Undergoing Chemotherapy.

DOI: 10.5220/0008152101180121

In Proceedings of the 23rd Regional Conference of Dermatology (RCD 2018), pages 118-121

ISBN: 978-989-758-494-7

examination were conducted in all subjects. We

excluded children with nail abnormalities which

occur prior to chemotherapy. Potassium hydroxite

(KOH) test was performed if there was a suspicion of

onychomycosis and or its coincidence in the subjects.

The data obtained were then analyzed using Mann-

Whitney test, p < 0.05 was considered significant

statistically.

3 RESULTS

Table 1. Clinical features of the enrolled subjects

Total

(chemotherapy

group, n = 30)

(control group, n

= 30)

Percentage

(%)

Age (year)

0 – 5

6 – 11

12 - 16

68.3

6.7

Gender

Male

Female

46.7

53.3

Nail changes in

chemotherapy

group

Yes

83.3

16.7

Nail changes in

control group

Yes

The data obtained were than analyzed using

Mann-Whitney test. It is showed that there was a

statistically significant difference in nail changes

between children undergoing chemotherapy and

healthy control group, with the p value 0.016. The age

of most subject is between 6 – 11 years old. The

number of men and women in this study was

proportional.

4 DISCUSSION

Nail dermoscopy (onychoscopy) has initially been

used for the assessment of nail pigmentation, but its

exertion has expanded for the diagnosis of all nail

disorders and it becomes a routine diagnostic

instrument, as it reveals helpful information.

Dermoscopy can be applied to all visible parts of the

nail unit, and even the nail matrix can be studied.

Many nail signs can be magnified by dermoscopy and

combined with clinical examination to establish the

diagnosis (Piraccini et al., 2012). In this study we

used dermoscopy examination to asses the diagnosis

of the nail changes, combining with history taking

and other physical examination.

Numerous mucocutaneous effects result from

inflammatory disorder, systemic drugs, trauma, viral

infection, macronutrient and micronutrients

deficiency, and even product used on the nails

(Kristien, 2015). Three out of 30 children in control

group had nail changes, in the forms of Beau’s lines

and leukonychia. These may occur due to nutritional

deficiency in children, espesially micronutrient

deficiency.

Figure 1. Pattern of nail changes in chemotherapy group

Nail Changes in Children Undergoing Chemotherapy

119

Figure 2. A. Trachonychia, change in nail plate. B. Melanonychia, change in nail pigmentation.

Table 3. The frequency of nail changes based on chemotherapy agents.

Agents of Chemotherapy Frequency Percentage (%)

Methotrexate + vincristine

Etoposide+ carboplatin

Doxorubicin + vincristine + cyclophosphamide

Cyclophosphamide

Cyclophosphamide + metilprednisolone

Vincristine

Cisplatin + bleomycine + vincristine

Nail changes were observed in 25/30 ( 83.3%) of

the children receiving chemotherapy and have a

statistically significance difference to control group.

MEDLINE and EMBASE (1966–2008) databases

reported that nail changes were caused by nail toxicity

which is the adverse effect linked to a number of

chemotherapeutic agents. The continuously dividing

nail matrix cells are easily perturbed by antimitotic

activity so that chemotherapy agents become easier to

affect the nails (Gilbar et al., 2009). Nail changes are

usually temporary and resolve with the cessation of

this therapy , but some may persist (Gupta et al.,

2008).

Chemotherapy-induced nail changes can classified

into nail color changes, changes in the surface of the

nail plate, disruption between the nail plate and the

underlying nail bed, and damage to soft tissue

structures surrounding the nail (Ranawaka, 2009). In

this study, nail color changes occur in 40.7% subjects

and the rest are nail plate changes. The three most

common nail changes found in our study were

trachonychia, dyscromia, and melanonychia.

Trachyonychia is defined as roughness of the nails.

Trachyonychia has been grouped into 2 types: shiny

trachyonychia and opaque trachyonychia, as seen in

Figure 2.A; this likely represent the spectrum of

disease severity. The clinical features of

trachyonychia include a sandpaperlike appearance of

the nails, longitudinal ridging, brittleness, and nail

pitting (Chu & Rubin, 2014).

Rough and brittle nails are caused by decrease in

the nail growth rate, which is common in

chemotherapy course. Trachonycia also have been

suggested to be caused by underlying poor metabolic

or nutritional health of patients with advanced cancers,

but this suggestion has not been formally proven

(Robert et al., 2015).

Nail hyperpigmentation can be brown or black

(melanonychia) or other colours. It commonly

presents as a longitudinal streak (longitudinal

melanonychia) as seen in Figure 2.B, but can also

present as a transverse band (transverse

melanonychia), spotted pigmentation or involve the

entire nail plate (total melanonychia) (Chu & Rubin,

2014). The exact mechanism of chemotherapy-

induced hyperpigmentation is not clearly understood.

But it is postulated that the accumulation of the drug

in the nails can have a direct toxic effect on the

melanocyte causing increased melanin production, or

there may be an associated increase in the

adrenocorticotropic hormone or the melanocyte

stimulating hormone.

Praveen Kumar et all in their

study stated that the statistically significant changes

observed were nail matrix melanocyte changes

including longitudinal pigmentary bands as the most

common change in 67.7% of cases, following

administration of chemotherapy agents with an

average onset of 6 weeks from the start of the course

(Reddy et al., 2017).

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120

Beau’s lines are transverse linear depressions in

the dorsum nail plate that emerge from beneath the

proximal nail fold, and are due to a transitory decrease

in mitotic activity of the nail matrix keratinocytes.

Drug- induced Beau’s lines are usually dose related

and reproducible with readministration of the drug

(Piraccini et al., 2003).

Most of the children (80%) in our chemotherapy

group have undergone 0-6 month course duration.

Drug-induced nail changes could develop within 3-4

weeks after the initiation of chemotherapy and

sometimes they does not need specific treatment,

because they show only past damage to the matrix and

the changes generally resolve as the nails grow out

(Robert et al., 2015). This also explains why in some

subjects who have undergone a long course of

chemotherapy may not develop any nail changes.

In our study methothrexate and vincristine were

the most common combinations of chemotherapeutic

agents used on the subjects (40%) and also the most

frequent agents caused the nail abnormality. Loose

toenails, thickened and discolorization, as well as

onycholysis and nail shedding will occur correspond

to chemotherapeutic cycles of methotrexate. In the

other hand, vincristine has been reported to produce

leukonychia, Beau’s lines, Mees’ lines, and

onychodermal bands (Gilbar et al., 2009).

The evaluation of nail changes in children

undergoing chemotherapy was hampered by some

confounding factors, such as a combination of

multiple agents in most regimens made it difficult to

determine the main culprit drug, opportunistic

infection during chemotherapy, and symptoms often

resolve with or without drug withdrawal.

5 CONCLUSION

This study was conducted in Dr. Moewardi General

Hospital Surakarta between December 2017 and

January 2018. The statistical analysis revealed that

there was a significant difference in nail changes

between children undergoing chemotherapy and

healthy control group, with the p value < 0.05. The

most common nail changes was trachonychia. The

combination of methotrexate and vincristine was the

most frequent chemotherapeutic agent used in the

subjects. The relationship between exposure time of

chemotherapy agents or its combination with the

onset of nail changes cannot be determined yet due to

limited observation of time time research. Research

with a larger number of subjects and longer

observation time is needed to obtain more

representative results and causative relationships

between each parameters.

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