Post-zygotic alterations in pigment genes occur and can generate localized ovoid areas of hypopigmentation termed nevus depigmentosus. Single areas of pigment loss, similar in shape to a café au lait spot, are not uncommon in children of color, especially Hispanic children; however, multiple areas of pigmentary alteration are uncommon and require genetic work-up for genetic and/or chromosomal abnormalities and conditions such as tuberous sclerosis (ash leaf macules, confetti, and thumbprint-like hypopigmentation) [1, 9, 10]. 34.2 % of lesions are seen at birth and most lesions are noted by 3 years of age [1].

Nevus depigmentosum is a localized ovoid area of hypopigmentation that is non-enhancing with Wood’s lamp (Fig. 5.2). Lesional appearance may be noted at birth or as late as age 3 years due to delayed pigmentary development. Hypopigmentation of the overlying hairs, the adjacent iris, and the mucosa can accompany a nevus depigmentosus [11]. Lesions are most commonly noted on the trunk, followed by the extremities. Wood’s lamp examination can be used to identify early or subclinical lesions. The mexameter can be used to differentiate the nevus depigmentosus from vitiligo, by relative melanin index [12]. Similarly, in vivo confocal reflectance microscopy can be used to differentiate these lesions from vitiligo [13]. Differentiation from the ash leaf macules of tuberous sclerosis can be difficult and requires a high level of vigilance in screening for the stigmata of tuberous sclerosis. Biopsy shows normal number of melanocytes and reduced pigmentation of the epidermis with clumped melanosomes [5, 14].

No current therapy for permanent removal, other than surgery, exists. Suction blister grafts and melanocyte keratinocyte grafts have been described to help clear lesions [15, 16]. Excimer laser has been described to reduce the prominence of these lesions [17]. A treatment trial with excimer laser can produce alterations on mexameter that differentiate such lesions from vitiligo. Pigmentary differences may become less marked with time in some children and disappearance can occur [18].

Lichen striatus is a common, self-limited condition of childhood seen in children of all ages and ethnicities and occurring year round. In a survey of 113 Indian children seen for hypopigmentation, 2 children had lichen striatus [1].

Lichen striatus can be seen in children of all ages after infancy and follows a classical clinical course beginning with raised papular lesions that are erythematous to flesh colored along the lines of Blaschko, starting usually distally and progressing proximally along the lower extremity. It is usual for only one segment to be involved, but multiple segment involvement can occur [23–25]. Involvement of the nail with a non-scarring, self-limited dystrophy can be noted [26]. No seasonality is noted in larger studies. Upon resolution of the first phase, which usually takes 6 months but can rarely persist for 3–4 years, hypopigmentation will be noted in most children of Fitzpatrick types IV or higher (Fig. 5.4), with erythema as a sequela in some Asian children. Facial lichen striatus may resolve more rapidly according to one inner city study from the United States [27]. One case has been reported after allogeneic bone marrow transplant [28].

While natural clearance is expected in most cases, in those individuals with symptoms or prominent lesions, topical pimecrolimus, tacrolimus [29], or retinoids with topical cortisteroids can be used to improve lesional appearance. Photodynamic therapy has been described as well [30, 31].

The incidence of pigmentary mosaicism is unknown, but it is not rare, while hypomelanosis of Ito is uncommon, occurring in only 20–30 % of individuals with pigmentary mosaicism. There is no race or ethnicity more likely to be affected; however, due to lyonization, females may be more likely to manifest pigmentary mosaicism (Fig. 5.3).

Pigmentary mosaicism usually appears at birth in darkly pigmented children, such as Indian or African-American children, or sometime in the first 2 years of life in Hispanic or Asian children. Mosaicism can be accompanied by hypertrichosis or hypotrichosis (Fig. 5.4).

No current therapies are available for this disorder; however, judicious clinical monitoring for structural anomalies is recommended

While pigmentary mosaicism cannot be reversed, clinical monitoring is required developmentally in growth, limb lengths, and/or physical or speech development. Cardiac development, brain structure, and ocular development should be monitored.

Incontinentia pigmenti (IP) is an X-linked dominant disorder that only rarely affects living male children. It results from mutations in the nuclear factor-ΚB (NEMO/IKBKG) [32].

IP is apparent at birth or within a few weeks of birth. There are four well-recognized clinical stages of IP. Stage I is apparent at birth or up to 2 weeks of age and consists of linearly arranged vesicles, bullae, erythematous papules, pustules, and erythematous macules. Stage II of IP occurs between week 2 and week 6 of life consisting of linearly arranged verrucous papules. Hyperpigmentation along the lines of Blaschko characterize Stage III beginning at 3–6 months of age. Stage IV consisting of whorled hypopigmentation +/− atrophy, usually, is apparent by the second to third decade of life [32, 33].

Other clinical findings of IP may include pegged/conical teeth, scarring alopecia, dystrophic nails, ophthalmic abnormalities, seizures, mental retardation, and paralysis [32, 33]. (Also see pages 46-47).

No current treatment exists for IP and treatment is not required clinically. Children who survive infancy have a good prognosis.

Kwashiorkor is due to insufficient protein intake, despite sufficient caloric intake, and is often seen in children with diets consisting entirely of rice or rice-based beverages. The children often develop failure to thrive, edema, and moon facies, as well as, marked muscle atrophy, hepatomegaly, and a distended abdomen with dilated intestinal loops. Frequent superimposed bacterial and fungal infections often complicate this condition. While PEM is rarely seen in developed countries, Lui et al. reported 12 cases of kwashiorkor diagnosed in the US in children without chronic medical illness. Six of the twelve cases were the result of poor nutritional education, fad diets, presumed food allergy and/or specific food avoidance.

Cutaneous manifestations include generalized hypopigmentation, dyschromia, pallor and xerosis. In mild cases, a superficial desquamation resembling flaking paint (“enamel paint spots”) can be seen, while in more severe cases, confluent areas of eroded skin can occur. The hair in these patients can become thin, dry and abnormally pigmented, with a reddish tinge or occasionally even grey/white. The hair can also develop bands of light and dark colors, referred to as a “flag sign” which represents alternating periods of malnutrition and improvement of nutritional status. Clinical diagnosis should be confirmed with more objective markers including: easily detached hair, edema, skin fissures, faulty wound healing and skin anergy, as well as, albumin < 2.8 g/dl, transferrin < 150 mg/dl or total iron binding capacity < 200mcg/dl. Leukopenia can also be seen due to decreased cellular immunity.

Fad diets, restrictive diets and eating disorders can also result in malnutrition and ultimately kwashiorkor. As in classic cases of kwashiorkor as described above, protein-energy malnutrition from diets can lead to similar cutaneous findings, such as xerosis and pigmentary changes of the skin and hair, and may even be the first appreciable signs of an eating disorder. A 2009 report described a 28 year old woman who presented for evaluation of scaly skin rash and lightening of hair color from brown to blond over the course of 4 years. After an extensive GI evaluation was performed, the patient was ultimately found to have combined vitamin and mineral deficiencies as well as kwashiorkor in the setting of anorexia nervosa and alcohol abuse.

Chronic malabsorptive states, such as those secondary to inflammatory bowel disease, celiac disease, pancreatic insufficiency and post GI surgery, can all lead to nutritional deficiencies. Protein-energy malnutrition has been reported in each of these settings resulting in kwashiorkor with associated findings of xerosis and hypopigmentation. Kwashiokor has been reported in the setting of infantile Crohn’s disease with reversal of symptoms noted 2 weeks after treatment with prednisolone, azathioprine and nutritional supplementation. A 2011 case report of a Type 4/5 dark skinned patient with Kwashiokor secondary to a Whipple procedure used to treat chronic pancreatitis with pseudotumor at the head of the pancreas, demonstrated marked hypopigmentation of the skin and hair as well as ichthyosiform, xerotic skin. The patient was treated with a combination of nutritional support (hypercaloric oral diet, hyperproteic and with medium-chain triglycerides), vitamin supplements, oligoelements and oral replacement of pancreatic enzymes and within 3 months his pigmentation had returned to essentially normal.

Treatment must be undertaken with caution, with a focus on correcting electrolyte abnormalities and treating infection. Malnutrition must be corrected with both balanced nutrition and increased caloric intake. Emollients can be used on the skin and cutaneous lesions tend to improve with treatment of the malnutrition.

Vitmain deficiencies have also been implicated in hypopigmentation. A case of hyperpigmented macules on the body, longitundal hyperpigmented streaking on the nails and gingiva hyperpigmentation along with diffuse whitening of the hair in a 55 year old female was seen in the setting of Vitamin B12 deficiency. These pigmentary alterations were reversed in 2-3 months, with correction of her Vitamin B12 deficiency. Additionally, Extensive confetti like vitiligo has been described in association with extremely deficient levels of vitamin D.

Selenium deficiency, though rare, can be seen in cases of total parenteral nutrition (TPN), chronic bowel disease and following gastric bypass surgery. It can also be seen in people who survive on diets derived entirely from selenium deficient soil.

Postinflammatory pigmentary alteration is a pigmentary alteration of the skin that is seen in children of color from early infancy through adolescence. Causes of dyspigmentation include primarily hypopigmentation early on, with the leading insult being seborrheic dermatitis and atopic dermatitis (Fig. 5.1). With increasing age, hyperpigmentation is a common postinflammatory change, seen after bug bites, acne, and eczema lesional clearance.

Waardenburg’s Syndrome types I and III are due to mutations in the PAX3 transcription factor gene. The PAX transcription factor is a key component in neural crest differentiation, melanoblast activation, melanoblast migration, and structures involving the facial bone, facial cartilage, and inner ear. Waardenburg’s Syndrome type II is due to a mutated melanocyte transcription factor, MITF gene. Type IV is due to mutations in SOX10 transcription factor, endothelin-3 gene, and endothelin receptor which all affect neural crest development [32].

The main skin finding in Waardenburg’s Syndrome is depigmented patches with overlying hyperpigmented patches, i.e., islands of repigmentation. Other clinical features may include a white forelock, synophrys, dental caries, broad nasal root, dystopia canthorum (not in type II), heterochromia iridum, congenital sensorineural hearing loss (most common in type II), and Hirschsprung’s disease (type IV) [32, 34, 35]. Cleft lip and palate may be seen in type I and musculoskeletal defects of the upper limb and pectoral muscles may be seen in type III [32].

Waardenburg’s syndrome patients should be screened by specialists for the known features of the syndrome. Hearing screen, rectal examination and genetic testing/counseling are reasonable screening tests for Waardenburg’s syndrome patients. There have been reports of neural tube defects in Waardenberg’s syndrome patients. Folic acid supplementation, though recommended for all women of child bearing age, may be of particular importance in this at risk group [36].