In this post, I will talk about Vitiligo in children, its causes, and available treatment.
Vitiligo is a chronic disease characterized by the progressive loss of cutaneous melanocytes and changes in their normal function. The result is hypopigmented and, over time, increasingly amelanotic, depigmented skin areas.
Classification and pathogenesis
According to the consensus definition of the European Vitiligo Task Force, vitiligo is classified into generalized (Vulgaris) or non-segmental vitiligo (NSV) and segmental vitiligo (SV). Mixed vitiligo is when segmental and non-segmental lesions are present in the same patient at the same time. Various subphenotypes are described within NSI, including acrofacial (limited to the face, hands, feet, and body orifices), mucosal (oral and/or genital), focal, generalized, and universal vitiligo (more than 60 to 90% of the Body surface) as well as rare forms (punctiform, minor, follicular). 7)
About the pathogenesis, the current leading theory is that generalized vitiligo is a multifactorial, polygenetic, T-cell mediated autoimmune disease that is only manifest in a minority of genetically susceptible individuals and is strongly dependent on environmental factors as triggers. In contrast, isolated SV occurs focally based on local disease susceptibility and is not associated with autoimmune phenomena. 2)
The global prevalence ranges from 0.5% to 2.16% of the population. The disease affects people of all ages and both sexes equally. In around a third to half of all cases, the onset of the disease occurs in childhood, of which around 25% develop the disease before the age of 10. 8) 9)
At the onset of the disease in childhood, the average age is between 5 and 10 years, depending on the study. The disease is quite rare in children younger than 2 years (11% of pediatric cases), in contrast to congenital pigment disorders such as the pigment mosaic. 2) Whether congenital vitiligo exists is still controversial. 9)
Vitiligo patients have an increased risk of developing other autoimmune diseases, namely alopecia areata, autoimmune hemolytic anemia, autoimmune thyroid disease, diabetes mellitus, inflammatory bowel disease, morphea, multiple sclerosis, pemphigus Vulgaris, rheumatoid arthritis, pernicious anemia, psoriasis or systemic lupus erythematosus. The more extensive and prolonged the disease, the higher the prevalence of associated autoimmune diseases. 10)
Family history is positive for vitiligo in up to 30% of cases. 10) Associated autoimmune diseases have also been reported in family members, such as vitiligo itself, an autoimmune thyroid disease, pernicious anemia, Addison’s disease, systemic lupus erythematosus, and inflammatory bowel disease.
There appear to be two subsets of Vitiligo patients: those with early-onset (12 years or younger) with more halo naevi, Koebner phenomenon (development of a lesion in response to trauma), positive family history, segmental disease, and atopy. Then there are those with a late-onset (after age 12) with more acrofacial lesions and thyroid disorders. 2) In children, non-segmental or generalized vitiligo is the most common form of manifestation. Nonetheless, the percentage of segmental vitiligo (SV) is higher in children compared to adults. 9)
The clinical picture of a Vitiligo Vulgaris (note the symmetrical distribution, the poliosis, and the infestation of exposed areas such as the elbow) (A), a Vitiligo Vulgaris with leukonychia of the eyelashes (B), a Halo nevus (C), a Vitiligo of the mucous membrane (D), segmental vitiligo (E) with leukonychia (F) and follicular repigmentation in the face (G)
The vitiligo lesion is clinically defined as an asymptomatic, ivory-white, well-circumscribed, non-palpable, and non-scaling lesion, usually with an oval or linear outline. The convex edges are typical (Fig. 2A). The location, size (from a few millimeters to large spots), and shape of the individual lesions can vary considerably. When assessing a patient for the first time, it is essential to differentiate between SV and NSI, as the prognosis, the course, and the therapeutic response differ significantly. 2)
In the NSV the depigmented macules concerning bilateral multiple areas of the body, usually in a symmetrical pattern. The disease can start anywhere on the body, but often exposed areas such as the back of the hand and extensor fingers, neck, and face are initially affected. Other sites of predilection are the body folds (axillae and groin), body orifices (eyes, nostrils, mouth, navel, areoles, genital and perianal regions), and skin over protruding bones such as the elbows, knees, ankles, and shins. In some patients, the hair in Vitiligo lesions also turns white (leukonychia or poliosis), which can help to confirm the diagnosis if the diagnosis is unclear (e.g. in early lesions that are not yet completely depigmented)
Patients with vitiligo, especially those with prepubertal onset, often also have halo nevi (pigmented nevi surrounded by a depigmented zone) (Fig. 2C). Leukotrichia in the scalp area can precede the onset of vitiligo for several months or years and often goes unnoticed, especially if it occurs locally or corresponds to a halo nevus. 9)
Around 15% of affected children show a Koebner phenomenon in association with trauma/friction or sunburn. Places such as the knees, elbows, shins, arms, and hands are often scraped and scratched in children and are often the areas of initial depigmentation. In small children, an initial manifestation in the perianal region and on the buttocks is not uncommon and often goes undetected. It may be a Koebner phenomenon triggered by irritative diaper rash. 9)
A few rare forms have been described within the spectrum of NSI: Vitiligo punctata refers to pea-sized depigmented macules that can affect any area of the body. The vitiligo minor, rarely described in children, is characterized by predominantly localized in the face hypopigmented macules. The Follicular Vitiligo is primarily concerned with the follicular reservoir of melanocytes and rarely leads to white are the most body hair, also depigmented macules. The vitiligo mucosa, also rare in children, describes the involvement of oral and/or genital mucosa as part of generalized vitiligo or as an isolated state (Fig. 2D).In the case of whitish spots limited to the mucous membrane, lichen sclerosis should always be considered as a differential diagnosis.
In SV, the depigmented lesions unilaterally (asymmetrical vitiligo) follow a segmental or band-shaped distribution. As a rule, only a single segment is affected in SV, although two or more segments with ipsi- or contralateral distribution have been described in the literature. Typical is the rapid appearance of the finding and the early involvement of the melanocyte reservoir of the hair follicle (Fig. 2E). However, the disease typically stabilizes quickly over a few months. SV must be differentiated from focal vitiligo with a solitary small lesion without a clear segmental distribution and from hypopigmented mosaic (see above). 2)
Diagnostics and special laboratory tests
No medical clarification is necessary for SV in everyday clinical practice. For children with NSI, however, a routine basic examination is recommended. This includes a complete blood count, metabolic profile (if clinically justified), screening of thyroid function (TSH), the determination of thyroid antibodies (anti-thyroperoxidase and anti-thyroglobulin), and 25- (OH) -vitamin D. A deep vitamin D identifies a subset of patients with a higher tendency for secondary autoimmunity. Screening for antinuclear antibodies (ANA) is only recommended before any light therapy. Additional screening exams should be performed if there are signs and symptoms of another autoimmune disorder or if there is a clear family history of autoimmunity. 2) 9)
Vitiligo must be distinguished from numerous other entities, which are mentioned elsewhere in this review work. If the depigmented spots appear congenital and accompanied by a white forelock, genetic diseases such as piebaldism or Waardenburg syndrome should be suspected.
Piebaldism is characterized as an autosomal dominant disorder and epidermal by the absence of melanocytes. The lesions are present at birth and almost always remain stable throughout life. The depigmented areas contain the typical white lock of hair over the forehead (the so-called ‘white forehead lock’) and are classically distributed over ventral surfaces (forehead center, anterior trunk, and middle extremities), hardly ever near the midline on the back, on trauma-prone or trauma-prone areas to find intertriginous localization. The lesions do not have convex edges and there are normal to hyperpigmented islands within and in the edge area of the depigmented spots.
In patients with signs of piebaldism (white forelock and depigmentation of the skin), characteristics of Waardenburg syndrome (WS) should be looked for. The WS is based on a disturbance of the melanocytes to migration and survival in the epidermis, the hair follicles, the iris, and the inner ear. It is a heterogeneous group of autosomal diseases ( WS types 1 to 4) which include heterochromia of the iris, a broad nasal root, and congenital inner ear hearing loss (Fig. 3).
Course and prognosis
SV is rapidly progressive (over 6 months to 2 years) with early onset of leukonychia, but stabilizes rapidly even without treatment. It responds more poorly to treatment than other variants, possibly because of the frequent association with leukonychia and the resulting lack of follicular melanocyte reservoir for repigmentation. 2)
In contrast, the course of the NSV cannot be foreseen and shows a tendency towards cyclical behavior. This includes quiet periods (minimal melanocyte destruction) and accelerated phases (rapid progression over weeks and months) followed by stable phases or even partial repigmentation, which occurs without any therapeutic intervention or after exposure to the sun. The whitening of the hair tends to occur later in the course of the disease. Repigmentation occurs in most cases as perifollicular freckle-like points (due to the migration of melanocytes from the hair follicles), but diffuse repigmentation starting from the edge area is also possible. The higher tendency to repigmentation in the face and neck area compared to other locations, such as the hands,(Fig. 2F) 2).
The psychological effects of childhood vitiligo can be profound. While small children are hardly ever bothered by vitiligo, it often has considerable psychological effects in older children. Although there are no visible physical accompanying symptoms (compared to other common, chronic dermatological diseases such as eczema or psoriasis), vitiligo leads to an enormous emotional burden from a certain (variable) age. It not only restricts the quality of life of patients but also that of their parents. Patients often complain about the lack of knowledge of doctors about possible treatment options and that they perceive Vitiligo as only a “cosmetic disease”. 2)
The treatment options for childhood vitiligo are limited and pose a therapeutic challenge for dermatologists, as there is no approved or intended therapy for this indication. In addition, there are only a few randomized clinical studies that have explicitly examined the effectiveness of various treatment options for Vitiligo in children. 11)