Pediatric Nail Disorders

Abstract

Background

Pediatric nail disorders encompass a broad range of conditions. This article aimed to consolidate current knowledge on pediatric nail disorders to enhance diagnostic proficiency and clinical management among healthcare professionals.

Summary

Pediatric nail disorders present a diagnostic challenge due to their diverse nature. Non-syndromic congenital nail disorders encompass various anomalies such as anonychia/hyponychia, congenital malalignment of the great toenail, and racket thumbs, each with distinct clinical presentations and genetic associations. Syndromic congenital nail disorders, often part of complex syndromes, are characterized by unique features and associated abnormalities. Acquired nail diseases in children, like Beau’s lines and onychomadesis, typically result from trauma or infection, while melanonychia, although rare in children, requires careful monitoring for potential malignant alterations, with consideration for biopsy in cases with concerning features.

Key Messages

(1) Pediatric nail disorders may pose diagnostic challenges and require a comprehensive understanding of nail anatomy and development. (2) Congenital nail disorders encompass isolated anomalies and syndromic associations, necessitating thorough evaluation for associated systemic conditions. (3) Acquired nail diseases may indicate underlying trauma or systemic illness and require careful assessment.(4) Melanonychia in children requires ongoing monitoring and evaluation, emphasizing the importance of consistent follow-up and histopathological examination when necessary.

Introduction

Pediatric nail disorders encompass a diverse spectrum of conditions that may pose unique diagnostic challenges in clinical practice. Understanding the intricate anatomy and physiology of the nail unit is fundamental to unraveling the complexities of various nail abnormalities seen in pediatric patients. Beyond the structural aspects, this article delves into an array of clinical entities, ranging from congenital anomalies to acquired conditions, including infections, neoplastic processes, syndromes, and systemic nail diseases, all of which manifest through nail alterations [1–4].

Exploring the nuances of pediatric nail disorders requires a comprehensive understanding of the interplay between dermatology, pediatrics, and pathology. By consolidating current knowledge on anatomical nuances, syndromes, infections, neoplastic conditions, and systemic diseases impacting the nails in children, this article aimed to serve as a guide for healthcare professionals, enhancing their diagnostic knowledge and fostering improved clinical management for pediatric patients with nail-related concerns.

Anatomy of the Nail Unit in Newborns and Young Children

The nail unit consists of several components, namely the nail matrix, nail bed, proximal and lateral nail folds, and the hyponychium. The nail matrix serves as the germinal epithelium, giving rise to differentiated nail matrix keratinocytes responsible for the formation of the nail plate. While a significant portion of the nail matrix remains concealed beneath the proximal nail fold, the distal third can sometimes be observed through the proximal area of the nail plate, presenting as a crescent-shaped structure known as the lunula.

Nail development commences around the 12th to 13th week of gestation and undergoes completion by the 25th week [5]. In newborns, the nails are fully formed, yet they appear small, thin, and soft. Nail plate growth continues throughout life, with the growth rate peaking in the age range of 10–14 years and gradually becoming comparable to that of young adults, estimated at around 0.1–0.15 mm per day [6].

Typically, healthy neonates exhibit oval or rectangular-shaped fingernails, primarily with a longitudinal major axis, and in most cases, the nails lie flat. For instance, the index fingernail measures approximately 5 mm in length and 3.5 mm in width, while the thumbnail is approximately 9–10 mm wide. The great toenail often assumes a trapezoid shape with a longitudinal major axis and exhibits a distal width larger than the proximal width. Moreover, the size of nails in infants and older children is influenced by their age, distal phalanx size, and weight.

The ratio between the width of the nail in the middle of its length and the width of the finger is typically around 0.7 [7]. Micronychia, defined as a nail-to-finger width ratio <0.5, indicates that the nail is smaller than usual, while macronychia, defined by a ratio >0.8, suggests that the nail is larger than usual [5–7].

Physiological (Temporary) Nail Changes in Neonates and Young Children

Koilonychia (Spoon Nails)

Koilonychia, commonly known as “spoon nails,” refers to nails with a central depression, both transverse and longitudinal, with raised lateral edges [8]. Although iron deficiency is commonly associated with koilonychia, the severity of the deficiency does not necessarily correlate with the development of this condition. Interestingly, nail iron levels increase with oral supplementation, despite this lack of correlation [8]. In newborns, especially on the big toe, koilonychia is frequently idiopathic and occurs due to the thin and soft nail plate. This condition naturally resolves during late childhood as the nail plate thickens (Fig. 1) [6].

Fig. 1.

Koilonychia or “spoon nails” of toenails in a child.

Leukonychia

Children commonly experience true leukonychia due to trauma affecting the distal matrix. In true leukonychia, the whitish discoloration appears within the nail plate due to clusters of parakeratotic cells embedded within it. The presence of nuclei affects the nail plate’s transparency, causing it to reflect light and appear white. Punctate leukonychia is a widespread manifestation observed across multiple fingernails [6]. Conversely, transverse leukonychia is relatively rare in children, usually confined to the first toenails. This type of true leukonychia arises from shoe-related trauma on a thick nail plate, transmitting the trauma to the distal nail matrix, resulting in intermittent faulty keratinization, leading to one or more transverse white bands that move distally with nail growth [6].

Transient, Light Brown, or Ocher Pigmentation of the Proximal Nail Fold

Newborns with highly pigmented skin may exhibit a transient, light brown or ocher pigmentation on the proximal nail fold, extending to the interphalangeal joint. This pigmentation is a physiological, melanic change that appears within the first 6 months of life. Dermoscopically, it presents as a regular, reticular pattern confined to the periungual skin, without affecting the cuticle or the nail unit [9].

Congenital Hypertrophy of the Lateral Nail Fold of the Hallux

Most newborns exhibit congenital hypertrophy of the lateral nail fold of the hallux, typically associated with an incompletely developed, triangular-shaped toenail [10]. This condition is believed to result from asynchronous growth between the nail plate and surrounding soft tissues. It is generally asymptomatic and tends to improve naturally over time. However, a few cases have reported inflammation resulting from ingrown toenails (Fig. 2) [11, 12].

Fig. 2.

Congenital hypertrophy of the lateral nail fold of the hallux in a 6-year-old child.

Chevron or Herringbone Nails

Chevron or herringbone nails are more commonly observed in children between the ages of five and seven, but they can also occur in infants [13]. This condition presents as oblique and longitudinal, diagonal ridges converging distally towards the center of the nail plate, forming a “V” or chevron pattern. These ridges usually disappear during early adulthood [14].

Non-Syndromic Congenital Nail Disorders

A variety of isolated congenital nail disorders have been documented [15]. However, there is limited data on the genetic alterations underlying these disorders and their inheritance patterns.

Anonychia/Hyponychia

Anonychia/hyponychia congenita is a rare autosomal recessive developmental disorder characterized by the absence (anonychia) or hypoplasia (hyponychia) of finger and/or toenails (it differs from micronychia which is a condition associated with small nails due to several conditions such as trauma, infections or drug eruptions). It is caused by variants in RSPO4, a gene encoding R-spondin 4, a protein involved in the Wnt/beta-catenin signaling pathway [16–18]. On the other hand, Iso-Kikuchi syndrome or congenital onychodysplasia of the index finger (COIF) presents with unilateral or bilateral micronychia of the index finger. The most common bony abnormality associated with this nonhereditary disorder is bifurcation of the underlying phalanx, though other unusual cases have been reported. Iatrogenic congenital anonychia resulting from prenatal phenytoin exposure has also been reported (Fig. 3) [19–22].

Fig. 3.

Anonychia of different digits in 3-year-old child.

Congenital Malalignment of the Great Toenail

Congenital malalignment of the great toenail is a relatively common and often under-recognized condition. It is characterized by lateral deviation of the nail plates, which do not align parallel to the longitudinal axis of the phalanx due to lateral rotation of the nail matrix [23]. Although usually present at birth, the condition may go unnoticed until nail dystrophy becomes evident during early childhood [24]. In older children, the great toenails appear thick with a grossly triangular shape, multiple transverse grooves and ridges, and yellow-brown discoloration. Nails may be partially detached from the nail bed. Spontaneous realignment has been reported in about half of the cases. For optimal cosmetic results, early surgical correction (before the age of two) involving rotation and realignment of the nail apparatus is recommended [23–25].

Clubbing

Typically, the angle formed between the proximal nail fold and the nail plate is referred to as Lovibond’s angle, usually measuring greater than 180°. Any deviation from this angle can result in clubbing, a condition where the nail takes on a shape resembling a convex glass surface with excessive curvature along both its transverse and longitudinal axes. Clubbing can manifest as either congenital or acquired. Acquired clubbing is rare and, in 80% of instances, is linked to pulmonary ailments. Congenital clubbing might be associated with cardiac issues, although more commonly it is connected to lung or bowel diseases [6, 26–31]. Occasionally, at birth, the nail curves over the tip of the finger towards the pulp; in this age group, this curvature might be considered as a form of physiological clubbing [6]. There is a peculiar form of clubbing, known as isolated congenital nail clubbing, which is a rare disorder characterized by enlargement of the nail plate and distal segments of the fingers and toes due to abnormal proliferation of the connective tissue of the nail bed. This condition has been associated with autosomal recessive variants in two genes: HPGD, encoding the prostaglandin-degrading enzyme 15-hydroxyprostaglandin dehydrogenase [26], and SLCO2A1, encoding a major prostaglandin PGE2 transporter [27, 28]. Notably, variants in both HPGD and SLCO2A1 have also been linked to primary hypertrophic osteoarthropathy [29–31].

Racket Thumbs (Racket Nails)

Racket thumbs, or racquet thumbs, refer to an autosomal dominant, congenital malformation of one or both thumbs, characterized by brachyonychia (nail and nail bed wider than the length of the phalanx) and absence of the lateral nail folds. Racket thumbs may occur as an isolated disorder or be associated with various genetic conditions, including Rubinstein-Taybi syndrome, Larsen syndrome, and Brooke-Spiegler syndrome [32].

Syndromic Congenital Nail Disorders

Congenital nail disorders can be part of complex syndromes involving skin anomalies and other epidermal appendages or may be associated with skeletal deformities. Nail abnormalities primarily manifest as nail hypoplasia (anonychia/micronychia) or nail hypertrophy/hyperkeratosis.

Syndromes with Associated Anonychia/Micronychia

Anonychia (absence of nails) and micronychia (nails smaller than usual, which differs from underdeveloped nails or hyponychia) are features observed in several genetic multiple malformation syndromes, ectodermal dysplasia, and epidermolysis bullosa (EB) [33–48].

Cooks Syndrome

Cooks syndrome is a rare disorder characterized by fingernail hypoplasia or complete absence of fingernails, total absence of toenails, hypoplasia of distal phalanges in hands, and absence of all distal phalanges of feet [33, 34].

Nail-Patella Syndrome

Nail-patella syndrome (NPS), also known as hereditary osteo-onychodysplasia, is a rare, autosomal dominant disorder with variable expressivity caused by variants in the LMX1B gene on chromosome 9q34, encoding a transcription factor of the LIM-homeodomain type. It is characterized by the classic clinical tetrad of hypoplastic or absent patella, dysplasia of elbows, iliac horns, and nail and distal digital abnormalities [35]. In nearly 100% of NPS patients, nail abnormalities are evident at birth and include anonychia or micronychia (absent or thin, fragile nail plates) and triangular lunulae, which are pathognomonic findings. The severity of nail changes diminishes from the first to the little finger and exhibits phenotypic variability both within and among families. Accurate nail evaluation is essential to predict any other systemic involvement, such as renal and eye disorders [35]. Onychoscopy aids in visualizing the characteristic triangular lunula, which appears white in color and displays varying dimensions in different digits (e.g., more pronounced in the thumbs and less evident towards the fifth digit) [36].

Epidermolysis Bullosa

Epidermolysis bullosa (EB) comprises a diverse group of skin fragility disorders caused by genetic variants affecting proteins critical to the integrity of the dermal-epidermal junction [37]. Nail abnormalities are observed in all types of EB, with the most severe cases found in junctional epidermolysis bullosa (JEB) and dystrophic epidermolysis bullosa (DEB) [38]. These nail changes can serve as a distinguishing feature when considering other causes of skin blistering. Manifestations range from mild blistering of the periungual tissues and nail bed to more extensive blistering, nail erosions, onychodystrophy with onychogryphosis (thickened, yellowish, longitudinally grooved, markedly curved nail plates), nail thickening and parrot beak nail deformity, or anonychia due to atrophy and scarring of the nail bed and matrix [39, 40]. While blisters of periungual tissues and the nail bed are minimal at birth, they become evident by the age of 18 months. In some instances, nail EB may manifest during adolescence or early adulthood. In rare cases, nail abnormalities may precede skin blistering, as observed in late-onset JEB and the pretibial variant of localized DEB [41]. In certain cases, nail abnormalities may be isolated, such as in the acral “nails only” subtype of localized dominant dystrophic epidermolysis bullosa (DDEB), where the involvement is often restricted to the toenails and can be mild and easily overlooked [42].

Pachyonychia Congenita

Pachyonychia congenita is a rare autosomal dominant disorder of keratinization resulting from variants in KRT6A, KRT6B, KRT6C, KRT16, or KRT17. It is characterized by abnormal keratinization leading to various clinical features, including hypertrophic nail dystrophy, painful palmoplantar blisters, cutaneous cysts, follicular hyperkeratosis, and oral leukokeratosis [43, 44]. Nail and skin changes are often present at birth in around 50 percent of cases, but by the age of five, they become evident in over 75 percent of affected individuals. Nail alterations involve all 20 nails and are characterized by significant nail thickening with increased curvature due to nail bed hyperkeratosis. By the age of 10, severe pain associated with palmoplantar keratoderma becomes a common symptom and significantly affects the quality of life (Fig. 4) [1, 45].

Fig. 4.

Pachyonychia congenita in a 7-year-old child.

Dyskeratosis Congenita

Dyskeratosis congenita (DC) is an uncommon inherited disorder caused by genetic variants affecting genes responsible for maintaining telomere length in rapidly dividing cells. This results in premature cell death, senescence, or genomic instability in various organs and tissues [46]. Clinically, DC is characterized by mucocutaneous abnormalities, bone marrow failure, and an increased risk of cancer. The classic triad of nail dystrophy, leukokeratosis of the oral mucosa, and extensive, net-like pigmentation of the skin is typical of DC [47]. Nail changes are early manifestations of DC, appearing during early childhood (sometimes within the first year of life). They include nail thinning with longitudinal splitting, ridging, and atrophy. Fingernails are more commonly affected than toenails [46–48].

Acquired Nail Diseases in Children

Beau’s Lines and Onychomadesis

Beau’s lines and onychomadesis occur as a result of trauma or infection, leading to significant inflammation or damage within the nail matrix. This damage manifests as a thin transverse groove (Beau’s line) in the nail, growing out at a rate that allows estimation of the time elapsed since the triggering event. If the event affects a single digit, the groove will be limited to that specific digit [6]. However, a more widespread event, such as a systemic illness, might produce grooves in multiple digits. In severe cases, substantial underlying damage may cause the nail plate to detach from the proximal nail fold, resulting in a complete interruption of the nail plate’s thickness transversely, followed by the shedding of the nail, a condition known as onychomadesis. Drug reactions and systemic infections are recognized as triggering factors for the onset of onychomadesis. One of the most common causes of onychomadesis is hand, foot and mouth disease; this viral infection commonly affects children and is characterized by vesicular eruptions involving the palms, soles, and oral cavity. Within the spectrum of hand-foot-mouth disease, a severe variation known as “eczema coxsackium,” characterized by vesicles and erosions within areas affected by atopic dermatitis, may be associated with onychomadesis. Coxsackievirus A6 (CVA16) stands out as the sole enterovirus known to induce such condition [49]. Nail shedding begins without any accompanying pain or inflammation, progressing to complete separation of the nail plate with transverse ridging affecting several or all fingernails and toenails. Although this condition is reversible and self-limiting, the precise mechanism by which the illness causes damage to the nail matrix remains unknown. No specific treatment is necessary, only reassurance for the family is typically advised (Table 1) [6].

Table 1.

Summary of the most common non-infectious acquired nail diseases in children

Condition	Description	Etiology
Beau’s lines	Thin transverse groove in the nail plate	Trauma, infections, drug adverse events
Onychomadesis	Nail plate detachment and shedding	Trauma, drug adverse events, systemic infections
Pitting	Small indentations on nail surface	Nail psoriasis (larger, irregular pits), alopecia areata (regular pits)
Nail involvement in finger sucking	Eczema in the periungual tissues and finger pads, damage to the cuticles, acute paronychia, and onycholysis	Persistent sucking behavior

Pitting

Pitting refers to small indentations on the surface of the nail plate. The size and arrangement of these pits can provide insight into specific diseases. Dermoscopy of pitting is particularly useful in differentiating diseases characterized by this feature, especially when pitting is the sole visible sign. Pitting is commonly seen in nail psoriasis and in the nails of individuals with alopecia areata. Psoriasis-related pits are typically larger, deeper, and irregular in shape, size, and distribution, whereas pits associated with alopecia areata exhibit a regular shape, size, and distribution (Table 1) [6].

Finger Sucking

It is a form of sucking behavior, typically occurring during early childhood, mainly involving the thumb, and it is expected to cease around the age of 4. Its persistence beyond this age is concerning as it can impact dental development and contribute to malocclusion. Dermatologists and pediatricians are often involved in managing the damage caused due to saliva exposure, which can lead to eczema in the periungual tissues and finger pads, damage to the cuticles, acute paronychia, and onycholysis. Additionally, potential complications may include periungual warts and herpetic infections (Table 1) [50].

Nail Infections in Children

Acute Paronychia

Acute paronychia, an inflammation of the nail fold, typically follows trauma allowing pathogens into the skin. Common in children due to habits like biting the cuticle or finger sucking, it often results in skin trauma and maceration around the nails. Staphylococcus aureus is the primary pathogen, though other bacteria or the herpes simplex virus may also be responsible. Symptoms include erythema, swelling, and pain, more pronounced on one side of the affected digit. While abscess formation is rare in young children, severe inflammation might lead to temporary or permanent nail damage like onychomadesis or nail plate dystrophy [1, 51]. A Tzanck smear aids in diagnosing the causative agent, preventing unnecessary antibiotic use. Empirical therapy encompasses the use of antibiotics and antifungal medications. In cases of acute bacterial paronychia, soaking the affected area in warm water and draining any pus through incision may prove advantageous. Antibiotics should be directed towards gram-positive and anaerobic bacteria, such as amoxicillin/clavulanate or clindamycin. Certain instances may involve Candida albicans as the causative agent, which often responds positively to topical ketoconazole cream. However, other factors like irritant dermatitis resulting from exposure to various chemicals can also be responsible (Table 2) [1, 51].

Table 2.

Summary of the most common infections of the nails in children

Condition	Etiology	Clinical features	Diagnosis	Treatment
Paronychia	• S. aureus	• Inflammation of the nail fold following trauma	• Clinical features	• Antibiotics and antifungal medications
	• Herpes simplex virus (HSV)	• Common in children due to habits like biting cuticles or finger sucking	• Tzanck smear
	• Anaerobic bacteria	• Erythema, swelling, pain, more pronounced on one side of the affected digit
	• C. albicans
Viral warts	• Human papilloma virus (HPV)	• Periungual warts appear as hyperkeratotic lesions on the nail fold	• Clinical features	• Cryotherapy
				• Electrocautery
				• Intralesional purified protein derivative (PPD)
				• Intralesional candida antigen
		• Subungual warts manifest as hyperkeratotic masses associated with distal onycholysis	• Dermoscopy	• Topical salicylic acid
				• Imiquimod
				• Laser therapy
				• Bleomycin injection
				• Hyperthermia
Onychomycosis	• T. rubrum	• Distal and lateral subungual onychomycosis	• Clinical features	• Ciclopirox lacquer
	• C. albicans	• Superficial onychomycosis	• Dermoscopy	• Terbinafine
	• T. mentagrophytes complex			• Itraconazole
				• Fluconazole

Blistering Distal Dactylitis

Blistering distal dactylitis (BDD) is a bacterial infection typically observed in children, characterized by fluid-filled lesions appearing on the fingers [52]. Conventionally, BDD affects the volar fat pad of the distal phalanx of the digits, resulting in medium to large blisters filled with a thin, white fluid that are usually painless [53]. Group A beta-hemolytic Streptococcus is the most frequently identified bacteria in cultures taken from the fluid within these blisters [54]. Treatment involves incision and drainage or deflation of tense and tender bullae, followed by wet dressings and topical antibiotics. Systemic antibiotic therapy is often necessary to prevent further lesions and transmission, with B-Lactamase-resistant antibiotics preferred as first-line treatment. In cases of MRSA positivity or systemic symptoms, intravenous vancomycin may be indicated [52].

Viral Warts

Human papillomavirus (HPV) induced warts are prevalent in children aged 6 and above, particularly in the fingernails, often spreading from one nail to another through nail biting. Periungual warts appear as hyperkeratotic lesions on the nail fold, while subungual warts manifest as hyperkeratotic masses associated with distal onycholysis. Dermoscopy proves helpful in diagnosing small warts, revealing irregular surfaces with pointed hemorrhages. While about 30% of warts regress spontaneously, treatment is advisable when causing pain or to prevent spreading [1, 55, 56].

Traditional treatments encompass a variety of methods such as cryotherapy, electrocautery, intralesional purified protein derivative (PPD), intralesional candida antigen, topical salicylic acid, imiquimod, and laser therapy [57]. Salicylic acid preparations are often recommended as a first-line therapy for warts due to their efficacy and relatively low pain compared to other destructive treatments [58]. Several research studies have validated the effectiveness of Bleomycin for treating stubborn warts. Bleomycin can be delivered through multipuncture or direct intralesional injection methods. Nonetheless, there are no universally accepted protocols regarding the dosage, frequency, or injection method for Bleomycin treatment [59]. Additionally, local hyperthermia has emerged as a potential therapeutic option (Table 2) [60].

Onychomycosis

Onychomycosis in children is rare, with a prevalence below 0.5%. Dermatophytes are the leading cause, often linked to factors like tinea pedis or a family history of onychomycosis [1, 61]. Song et al. [61] conducted a comprehensive investigation into the prevalence of onychomycosis among children under 18 years old spanning from 1990 to 2022. Their findings revealed a rising trend of onychomycosis among children over time. Boys exhibited a higher susceptibility to onychomycosis compared to girls, with cases increasing notably in the 16–18 age group. The duration of onychomycosis in children proved to be significantly shorter than in adults, likely attributed to heightened parental vigilance, more proactive treatment, and faster nail growth. Furthermore, lower prevalence in children is attributed to physiological differences like better blood supply and thinner nails [62]. Pediatric onychomycosis predominantly affected toenails rather than fingernails and the common clinical presentation includes distal and lateral subungual onychomycosis due to dermatophytes. Superficial onychomycosis, in both “deep” and “classic” forms, is infrequent, particularly in younger children. Diagnosis confirmation necessitates mycological testing [1, 61]. The prevalent pathogens reported in children mirrored those found in adults, with T. rubrum, C. albicans, and T. mentagrophytes complex being the top three. In addition, children diagnosed with onychomycosis should undergo thorough examinations for concurrent tinea pedis and other superficial infections on other body parts [61, 63].

Managing onychomycosis in children poses significant challenges, often necessitating systemic antifungal therapy over topical options [62]. Topical therapy, such as ciclopirox lacquer, has demonstrated greater efficacy in children due to their thinner, faster-growing nails and may suffice for milder cases, albeit with a higher failure rate. Nevertheless, topical therapy remains a safer option with minimal risk of adverse effects and low systemic exposure, making it suitable for children with mild symptoms or contraindications to oral drugs. Prolonged topical monotherapy post-cure may help reduce recurrence rates [61, 64, 65]. Terbinafine, itraconazole, and fluconazole emerged as the most effective oral antifungal agents for treating pediatric onychomycosis, with terbinafine exhibiting the lowest failure rate. Oral drug administration may be recommended for children with severe clinical pictures, with dosages adjusted based on weight. The duration of treatment varies, emphasizing the importance of tailoring treatment duration to individual circumstances. Baseline liver function tests are recommended for orally treated children, with monitoring protocols akin to those employed for adults [61, 62, 66] Antifungal resistance is a modern problem regarding the approach to onychomycosis. It can arise from clinical or microbiological factors, with the latter encompassing inherent organism defenses and acquired resistance. Clinical resistance may stem from various factors such as misdiagnosis, improper dosing, inadequate drug penetration, and non-compliance. When fungal resistance testing is not standard, identifying the cause of treatment failure becomes challenging [67]. Punchihewa et al. [62] presented a case series of 5 pediatric patients with resistant onychomycosis that underwent combination therapy with terbinafine and itraconazole, with clinical resolution in all cases. Combination therapy could be an alternative strategy when facing resistant pediatric onychomycosis, but it poses risks like drug reactions and superinfection, and it should only be considered after single-agent treatment fails (Table 2).

Systemic Disorders Impact on Children Nails

Cardiac and Circulatory Disorders

Kawasaki Disease

Also known as mucocutaneous lymph node syndrome, Kawasaki disease is an acute systemic vasculitis affecting medium and small blood vessels, primarily observed in young children. Nail alterations manifest as reversible changes throughout its course. The predominant nail sign involves an orange-brown discoloration, termed transverse chromonychia, seen in up to 75% of cases. This distinct nail alteration typically emerges between the 5th and 8th day after the onset of fever, marking the subacute phase of Kawasaki disease. The discoloration mainly affects the fingernails, appearing in the distal half (or distal third) of the nail and gradually fading as the nails grow, usually disappearing within 2–4 weeks [68–71]. Dermoscopy reveals that the orange hue results from nail bed erythema and closely spaced splinter hemorrhages, confirming morphological changes in the skin’s microcirculation. Furthermore, Kawasaki disease can present other nail abnormalities such as onycholysis or transient leukonychia, distinct from the orange-brown chromonychia. Periungual desquamation of fingers and toes is a prevalent nail sign that follows the chromonychia, occasionally accompanied by Beau’s lines or onychomadesis (Fig. 5). While rare, some cases may develop acquired pincer nail deformity, characterized by the transverse curling of the nails along their longitudinal axis. Ischemic necrosis of the extremities, resulting from vasculitis-induced thrombosed aneurysms, represents a rare but severe complication of this condition [68–75]. Mitsuishi et al. [74] have proposed that such nail affections should be considered as novel diagnostic criteria for KD.

Fig. 5.

Onychomadesis of toenails (a) and fingernails (b) due to Kawasaki disease.

Respiratory Disorders

Yellow Nail Syndrome

Yellow nail syndrome (YNS) is a rare condition characterized by a triad of yellow nails, respiratory complications, and lymphedema. Diagnosis can be established when two of these features are present, with nail changes alone sometimes sufficient for diagnosis. The exact cause of YNS remains unknown, with hypotheses suggesting lymphatic abnormalities contributing to lymphedema and pleural effusions but not accounting for all respiratory manifestations [76–78]. Diagnostic nail signs for YNS encompass slowed nail growth, thickened nail plates, lack of cuticles, yellow-green discoloration, and increased transverse curvature of the nails. Children with congenital YNS, a very rare form, may exhibit other anomalies alongside nail changes. Cases of congenital YNS have been linked to genetic transmission and associated with various anomalies, including nonimmune fetal hydrops, facial dysmorphism, mental retardation, seizures, and other physical changes [76–82].

Gastrointestinal Disorders

Celiac Disease

Also known as gluten-sensitive enteropathy, celiac disease (CD) represents an autoimmune chronic condition affecting the digestive tract’s ability to tolerate gliadin, a constituent of gluten. Tissue transglutaminase appears to be the primary autoantigen involved in both intestinal and skin manifestations. Roughly 1% of the population is estimated to be affected by CD. Symptoms include chronic diarrhea, steatorrhea, abdominal discomfort and distension, weight loss, anorexia, and deficiencies in iron, folate, calcium, and vitamin D [83]. Dermatitis herpetiformis is the most common cutaneous presentation, affecting 15–25% of patients, alongside other skin findings such as xerosis, keratosis pilaris, and skin and mucosal pallor. Nail alterations, affecting 10–20% of children, may include features of iron or zinc deficiency like brittle nails and koilonychia, as well as other manifestations such as leukonychia, whose pathogenesis remains less clear. Furthermore, acquired generalized clubbing was observed in 15% of CD cases in a series of 55 patients and was linked to malnutrition [83].

Hematological and Immunological Disorders

Langerhans Cell Histiocytosis

It represents a dendritic cell histiocytosis and is the most prevalent among histiocytic disorders, predominantly affecting children, with a peak incidence of 0.2–1.0/100,000 children annually between 1 and 4 years old [84]. Nail involvement is rare and may present as onycholysis with redness, subungual hyperkeratosis with hemorrhages and pustule formation or cheesy discharge [85]. Other potential symptoms include periungual inflammation causing paronychia, elkonyxis, purpuric striae, and onycholysis. Elkonyxis is a condition characterized by significant fragility of the dorsal nail plate, irregular defects, loss of substance, or depressions that are larger than the typical pitting seen in psoriasis [86]. Its appearance suggests potential differential diagnoses including psoriasis, onychotillomania, and alopecia areata. Severe pulmonary involvement might lead to clubbing, while nail lesions may precede other Langerhans cell histiocytosis symptoms [85, 87–94]. Histologically, nail lesions exhibit similar characteristics to skin lesions and may not regress with treatment [94], or they may regress initially but recur as the disease progresses [95]. Nail involvement is considered a poor prognostic indicator due to its association with multisystem disease and high-risk organ involvement, although its use as an independent prognostic marker lacks substantial evidence [87–95].

Graft-versus-Host Disease

This is an immune-mediated ailment occurring post-allogeneic hematopoietic-cell transplantation. In children, chronic graft-versus-host disease (GVHD), associated with a 41% mortality rate, often manifests after three months post-transplant, primarily affecting the skin [96]. Nail changes occur in approximately half of the affected children, more frequently in the sclerotic variant, observed in about two-thirds of patients [96]. These nail abnormalities, like dorsal pterygium, longitudinal ridging, and distal splitting, may predate the onset of GVHD. Their presence, alongside persistent peripheral edema and eosinophilia, signifies a poor prognosis, with nail dystrophy often associated with steroid-resistant disease and lung GVHD [96].

Melanonychia in Children

Melanonychia

Melanonychia in children manifests as dark pigmentation (black-brown-gray) in the nail due to the presence of melanin within the nail plate. It commonly appears as a longitudinal band (longitudinal melanonychia, LM) but can also take on transverse (transversal melanonychia) or total (total melanonychia) forms. The clinical presentation varies based on factors like the number of bands, color, edges, and width of the lesions. Melanonychia may affect a single or multiple digits, both fingernails and toenails, and can occur at any age from birth to adolescence. Normally, similar to adults, the nail matrix melanocytes in children are inactive [97–104]. However, various triggers can initiate the production of melanin, leading to activation or proliferation. The clinical presentation differs depending on the underlying process. In cases where multiple nails are involved, consideration should be given to normal racial variants, especially in darker-skinned populations, or the possibility that it is a sign of syndromes. Syndromes such as Peutz-Jeghers syndrome and Laugier-Hunziker syndrome exhibit nail involvement. Peutz-Jeghers syndrome is characterized by pigmented macules in multiple areas and is associated with intestinal polyposis, potentially malignant. Laugier-Huntziker syndrome features LM in multiple nails and is linked to pigmented lesions in various body areas [97–104]. Other causes of melanocytic activation in children include trauma, radiation, or medications, often affecting thumbs and index fingers. Although rare in children, drug-induced pigmentation has been reported with medications like doxorubicin or hydroxyurea. Less frequently, it can be associated with drugs like minocycline, zidovudine used in ART therapy for HIV, antimalarials, or cancer chemotherapeutics. Additionally, it might signify arsenic intoxication, hemochromatosis, Addison’s disease, or vitamin B12 deficiency. Dermoscopic patterns indicating melanocytic activation include a gray background with thin, greyish, regular, and parallel lines [97–104].

The primary reason behind LM in a single nail among children is typically a nail matrix nevus (NMN), whereas in adults, melanocytic activation is the usual cause. A study looking at 40 children under 16 years old who underwent biopsies found that lentigo or nevus accounted for 77.5% of cases, with none diagnosed with subungual melanoma (SUM) [105]. Comparatively, in a review of pigmented nail disorders affecting both adults and children, nail unit nevi represent up to 12% of LM in adults compared to 50% in children, while nail unit lentigines represent 9% of LM in adults compared to 30% in children [106, 107]. Whenever only one digit is affected, a proliferative process should be considered, creating a diagnostic dilemma between benign or malignant origins. NMNs are typically observed in childhood, either congenital or acquired, appearing as one or more heavily pigmented longitudinal bands (Fig. 6). The size and degree of pigmentation in LM bands can vary significantly among patients, usually measuring greater than 3 mm. Dark bands often present a pseudo-Hutchinson’s sign, where dark pigmentation becomes visible through the transparent nail fold. The pigmentation can be uniform or darker bands might appear over pale pigmentation. NMN are more common in fingernails, mainly thumbnails [107].

Fig. 6.

Clinical (a) and onychoscopic (b) picture of nail matrix nevus in a 7-year-old child.

In a multicenter, international, prospective registry study encompassing 230 patients with congenital and congenital-type NMN, Pham et al. [108] outlined the predominant clinical and dermatoscopic characteristics of the most extensive case series of LM emerging in children under the age of 5 to date. They distinguished between lesions observed at birth (congenital NMN) and those acquired between birth and age 5 (congenital-type NMN). A notable proportion of congenital or congenital-type NMN exhibited worrisome clinical and dermatoscopic features akin to those found in SUM, including broad bands (33, 14.4%), nail dystrophy (35, 15.2%), triangular shape (30, 13%), microscopic Hutchinson’s sign (36, 15.7%), blurred band borders (78, 33.9%), polychromia (e.g., 159 cases of light brown pigmentation were found, 69.1%) and, notably, irregular longitudinal microlines in terms of pattern (e.g., 142 cases showcased an irregular pattern, 61.7%) and coloration (e.g., 54 cases displayed 3 different colors, 23.5%). These criteria for diagnosing SUM in adults are not applicable to children. Such data is confirmed by a research conducted by Lee et al. [109] involving 43 instances of pediatric LM; out of these 43 cases of LM, 29 cases (67.44%) were histologically confirmed NMN that, upon dermoscopic analysis, exhibited a higher occurrence of irregular patterns (72.41% vs. 7.14%, p < 0.0001), globules (27.59% vs. 0.00%, p = 0.0398), and Hutchinson’s sign (44.83% vs. 0.00%, p = 0.0027).

Regarding differences between congenital and congenital-type NMN characteristics, congenital NMN more frequently manifested periungual pigmentation (32, 46.4%), Hutchinson’s sign (21, 30.4%), and the distal fibrillar (“brush-like”) pattern (27, 39.1%) compared to congenital-type NMN. However, aside from these distinctions, both congenital and congenital-type NMN generally shared common initial features. Unlike SUM, neither congenital nor congenital-type NMN exhibited a parallel ridge pattern or a diffuse irregular pattern of the periungual skin. Instead, the distal fibrillar (“brush-like”) pattern was observed in approximately one-third of cases, showing substantial inter-rater reliability. This pattern, akin to a benign nevus variant found on soles, comprised dense fibrillar pigmentation beneath the hyponychium, composed of multiple thin parallel lines crossing both furrows and ridges [109, 110].

The diagnosis and management of SUM in children are still under debate due to differing opinions on diagnosis, incomplete evidence in literature, and varying clinical presentations. There is uncertainty about when a person transitions from being considered a child to an adult regarding LM assessment. Puberty might signify this transition, but research on this aspect is lacking. Also, there is ambiguity about how LM progresses from childhood to adulthood and whether the risk differs from new onset LM in adults. Additionally, histopathological features used to diagnose NUM in adults may indicate benign conditions in children [107]. The most common situation is a nevus with nests at the dermo epidermal junction. However, there are instances of nevi without nests, potentially mistaken for atypical melanocytes, which can also be present in nail melanoma, making differentiation challenging [111–116]. In their series comprising 29 cases, Lee et al. [109] underscored some of the predominant features of pediatric NMN: a higher occurrence of retraction artifact around nests (30.77%, p = 0.0352), hyperchromatic nuclei (30.77%, p = 0.0352), pagetoid spread (65.38%, p < 0.0001), and transepithelial elimination (53.85%, p < 0.0001). Significantly, 8 cases (30.77%) of pediatric NMN exhibited a notable enlargement in the nuclear size of melanocytes. However, they observed that in all instances, the degree of nuclear atypia identified was mild and insufficient to justify a diagnosis of SUM. In a cohort study of 11 cases of nail unit atypical melanocytic proliferations presenting as LM in patients aged 2–19, with a median width of 4 mm and a history of darkening or widening over time, 2 cases were diagnosed as in situ NUM, while the rest were diagnosed as atypical junctional melanocytic hyperplasia. These cases exhibited atypical histopathologic features similar to adult NUM, including poor circumscription, single-cell growth, and pagetoid scatter. The study examined 4 cases using fluorescence in situ hybridization (FISH), one of which had an 11q13 (CCND1) gain of function mutation, a finding also reported in other cutaneous melanomas in children [117].

A cautious approach is necessary when dealing with melanonychia in children, but it is crucial to ensure ongoing monitoring for the potential emergence of malignant alterations. It is recommended to assess melanonychia in children at intervals of every 6 months [118–122]. It is of utmost importance that these patients receive consistent follow-ups. Additionally, patients should be advised to promptly return for evaluation if there are any rapid changes observed in the lesion during this follow-up period. Any instance where melanonychia in children displays clinical and/or dermoscopic alterations within a short period during follow-up necessitates a biopsy for histopathological examination [107, 118–122].

Conclusion

Pediatric nail disorders represent a multifaceted domain within dermatology and pediatrics, requiring a nuanced approach for accurate diagnosis and effective management. From congenital nail abnormalities to acquired conditions such as infections, inflammations, and neoplastic ailments, understanding the intricacies of pediatric nail disorders is crucial for delivering optimal care to young patients. As the field continues to evolve, further research and collaboration among dermatologists, pediatricians, and researchers will undoubtedly pave the way for enhanced understanding, more refined treatments, and better outcomes for pediatric patients with nail disorders.

Statement of Ethics

Written informed consent was obtained from the parents of patients for publication of the details of their medical case and any accompanying images.

Conflict of Interest Statement

Authors declare no conflict of interests for this article.

Funding Sources

No funding or sponsorship was received for this study or publication of this article.

Author Contributions

Stephano Cedirian and Aurora Alessandrini designed the research study and analyzed the data. Stephano Cedirian and Michela V.R. Starace wrote the paper. Stephano Cedirian, Michela V.R. Starace, and Aurora Alessandrini performed the research, approved the final manuscript as submitted, and agree to be accountable for all aspects of the work.

Funding Statement

No funding or sponsorship was received for this study or publication of this article.