Autoimmune Skin Conditions

Alopecia areata and vitiligo are two common autoimmune skin conditions seen in the pediatric population. Although generally asymptomatic, both conditions can have negative effects on patients’ psychosocial well-being. Additionally, these conditions suggest a risk for other autoimmune conditions.

The following autoimmune skin conditions are reviewed in this section:

• Alopecia Areata

• Vitiligo

Alopecia Areata

Alopecia areata is one of the most common causes of nonscarring hair loss in children and is a significant cause of psychosocial distress. It frequently presents with the relatively sudden onset of well-circumscribed oval-to-round patches of hair loss on normal-appearing skin. Nail pitting is also an associated clinical feature.

Alopecia areata is the third most common dermatosis in children. An estimated 20% of alopecia areata cases occur in infancy, however, it can occur at any age. The lifetime risk in the global population is estimated at 2%.

In the majority of cases, the patches of hair loss are singular or limited; however, some patients have more-extensive hair loss. Alopecia totalis refers to hair loss of the entire scalp. Alopecia universalis refers to hair loss of the entire body.

A young child with alopecia areata. The areas of hair loss are well-circumscribed, and the involved skin does not have erythema or scale. (Photograph courtesy of Elizabeth Dupuy, MD.)

Nail pitting that is uniformly distributed can be found in some patients with alopecia areata. (Source: Alopecia Areata. N Engl J Med 2012.)

Diagnosis

The diagnosis of alopecia areata is usually established clinically; however, a skin biopsy is occasionally helpful for diagnostically challenging cases.

Differential diagnosis:

• tinea capitis

• trichotillomania

• telogen effluvium

• alopecia syphilitica

Clinical Course

The course of alopecia areata is variable and unpredictable. Onset at a younger age (<3 years) generally portends a poorer prognosis. In patients with limited patches of hair loss, 68% experience complete regrowth.

Pathogenesis

The pathogenesis of alopecia areata is not completely understood. However, it is a T-cell-mediated autoimmune disorder that results from loss of immunologic protection of the hair follicle.

Normally, hair undergoes a process of cyclic regeneration with the following phases:

• anagen: active growth phase

• catagen: phase of involution

• telogen: quiescent or resting phase

In alopecia areata, inflammatory cells attack anagen-stage hair follicles. This immune attack is thought to occur in people with a genetic predisposition who experience some proinflammatory trigger. The following figure explains the proposed pathobiology of alopecia areata.

(Source: Alopecia Areata. N Engl J Med 2012.)

Familial cases of alopecia areata are often associated with poorer prognosis, more-rapid progression, frequent relapses, and treatment resistance. Alopecia areata is strongly associated with atopic dermatitis, particularly in prepubertal children and those with alopecia totalis and universalis, and with autoimmune disorders (e.g., systemic lupus erythematosus, vitiligo, and thyroid disease).

Management

Screening for thyroid disease: In a recent retrospective, single-center study, the authors concluded that screening for thyroid disease should be considered in pediatric patients with alopecia areata and the following risk factors:

• personal history of Down syndrome

• personal history of atopy

• family history of thyroid disease

• signs or symptoms of thyroid disease

Treatment: Large, randomized, controlled studies of treatment for alopecia areata are lacking, particularly in children. The majority of treatments are based on local or systemic immune modification. See this 2020 international expert consensus statement on the use and efficacy of current therapeutic options for the management of alopecia areata.

Treatment options include:

• mid- to high-potency topical glucocorticoids

• topical Janus kinase (JAK) inhibitors

• topical minoxidil

• topical immunotherapy

• topical calcineurin inhibitors

• topical prostalglandin analogues

• systemic glucocorticoids

• oral minoxidil

• methotrexate

• cyclosporin

• azathioprine

• oral JAK inhibitors (ritlecitinib is FDA approved for patients aged >12 years)

Topical immunotherapy is a unique treatment option for patients with more-extensive scalp involvement. The principle of topical immunotherapy is immunomodulation, whereby the allergens squaric acid dibutylester (SADBE) or diphenylcyclopropenone (DPCP) are used to induce an allergic contact dermatitis on the affected areas. The resultant contact dermatitis is thought to change the immunologic milieu.

A 12-year-old female with alopecia areata who was noted on the initial examination to have sparse hairs only on the top of her scalp and who was treated with 1.5% diphenylcyclopropenone. (Source: Alopecia Areata. J Am Acad Dermatol 2018.)

Vitiligo

Vitiligo is an acquired disorder of skin depigmentation with an estimated worldwide prevalence of 0.5%. Childhood vitiligo, defined as disease onset before age 12 years, constitutes 32%-40% of vitiligo patients. Vitiligo is caused by immune-mediated loss of epidermal melanocytes. Similar to psoriasis, vitiligo can be exacerbated or triggered by trauma, known as the Koebner phenomenon. It is a polygenic disorder with prominent clustering in families.

Presentation

Vitiligo is usually asymptomatic and characterized by well-circumscribed macules and patches of depigmentation. The affected skin does not have associated textural changes such as scale. Poliosis, which is depigmentation of the hair, may be an associated finding.

In 2012, the Vitiligo Global Issues Consensus Conference established a classification scheme for vitiligo. Broadly, vitiligo is either nonsegmental or segmental. The term “vitiligo” in medical literature refers to nonsegmental vitiligo. Mixed segmental refers to the coexistence of segmental and nonsegmental vitiligo and falls under the category of nonsegmental vitiligo. Other vitiligo phenotypes, including focal vitiligo, fall outside of this classification scheme and are considered undetermined or unclassified.

(Source: Vitiligo. N Engl J Med 2009.)

Nonsegmental vitiligo is characterized by white patches that are often symmetric. (Source: Vitiligo. N Engl J Med 2009.)

Segmental vitiligo typically has a unilateral distribution. In the past, segmental vitiligo was thought to follow a dermatomal distribution; however, this is no longer believed to be true. Segmental vitiligo can involve more than one body segment. (Source: Vitiligo. N Engl J Med 2009.)

Diagnosis

The diagnosis of vitiligo is usually made clinically based on history and physical exam. A Wood lamp (a handheld ultraviolet A light or “black light”) enhances the areas of depigmentation and can be used to aid in evaluation.

A Wood lamp is a handheld ultraviolet A irradiation device that emits at approximately 365 nm. Examination with a Wood lamp is best performed in a completely dark room. The examiner should allow at least 30 seconds for adapting to the darkness before starting the examination. A Wood lamp provides bright reflection of white patches and enhanced details on intermediate pigment tones (Panel A), as compared with normal light (Panel B). Some lamps incorporate a magnifying lens that is useful in evaluating terminal and vellus pigmentation of hair. For patients with darker skin types, a Wood lamp examination is less useful. (Source: Vitiligo. N Engl J Med 2009.)

Patients with vitiligo may have halo nevi, which are moles surrounded by a patch of depigmentation. (Photograph courtesy of Marcia Hogeling, MD.)

A thorough history and physical examination, including examination with a Wood lamp, should focus on ruling out other disorders as described in the following table:

(Source: Vitiligo. N Engl J Med 2009.)

Clinical Course

The clinical course of vitiligo is variable. Segmental vitiligo is generally regarded as initially rapidly progressive and then stable. Nonsegmental vitiligo has an unpredictable clinical course with periods of stability and relapse.

Few clinical trials have been performed on the treatment of vitiligo in children. There is no known cure, and current therapies are used to stabilize disease or facilitate some degree of repigmentation. The majority of treatments target the immune system.

Generally, depigmentation on the face and neck is more responsive to treatment than acral sites, areas of bony prominence, and areas with lower hair density (e.g., the wrists, ankles).

Treatment

Treatments for vitiligo:

• topical glucocorticoids

• topical calcineurin inhibitors

• topical vitamin D analogs

• systemic glucocorticoids

• systemic immunosuppressants

• phototherapy

• excimer laser

• surgery

• chemical depigmentation

• topical JAK inhibitors (ruxolitinib, tofacitinib)

First-line therapy for vitiligo is usually twice-daily application of mid- to high-potency topical glucocorticoids, topical calcineurin inhibitors, or both.

Narrow-band ultraviolet B (NBUVB) phototherapy was first reported to be safe and effective in an open trial of 51 children with generalized vitiligo. More recent trials have confirmed the safety and efficacy of NBUVB (see expert recommendations on the use of phototherapy in vitiligo).

• UVB phototherapy refers to the use of ultraviolet light to treat skin conditions. Practically, this can be achieved by having patients sit or stand in a phototherapy unit multiple times per week. This treatment is generally reserved for older children and adolescents. For vitiligo specifically, the hypothesized mechanism of action is activation of melanocyte reserves in the hair sheaths. Ultraviolet light induces local immunosuppression through its effects on cutaneous lymphocytes, macrophages, and cytokines. There is currently insufficient evidence to demonstrate that rates of melanoma or nonmelanoma skin cancer are elevated in patients who receive UVB phototherapy. This therapy can be used to treat other skin conditions, such as psoriasis, atopic dermatitis, and mycosis fungoides.

• Excimer laser treatment can be helpful in treating vitiligo in younger children. It has the advantage of exposing only the affected areas to NBUVB and requires less frequent treatments than the phototherapy unit.

(Repigmentation in vitiligo tends to come from melanocytes in hair follicles. Photograph courtesy of Marcia Hogeling, MD.)