Pathogenesis

The pathogenesis of vitiligo is multifaceted , and encompasses elements of melanocyte stress , autoimmunity and adaptive immunity , all set against the backdrop of genetics and environmental factors . 5 , 6

Melanocytes isolated from vitiligo patients are intrinsically abnormal , which lowers the tolerance for oxidative stress . 7 , 8 With cellular injury , these rogue melanocytes are more likely to release danger signals called damage-associated molecular patterns ( DAMPs ) which activate the innate immune system , triggering autoimmunity . 9 Persistence of these signals recruits the adaptive immune system , resulting in melanocytic death by CD8 + T cells .

These lesions are maintained by resident memory T cells , perpetuating relapse . 10 Thus , the depigmentation seen in vitiligo results from a complex interplay between abnormal melanocytes and overactive immune systems .

This is clinically relevant , as genes involved in any of the steps described , or environmental exposures which increase melanocyte stress , can initiate vitiligo . 9

Immunotherapies such as programmed cell death inhibitors , tumour necrosis factor inhibitors and others can induce vitiligo-like depigmentation ( VLD ). 11 VLD has been associated with better long-term survival in these patients . 11 Patients with VLD will not typically have a personal or family history of autoimmune conditions , which means a targeted drug history will help distinguish vitiligo from VLD . 11

Clinical features

Vitiligo is diagnosed clinically . Early identification

of vitiligo is directly correlated to better treatment response and quality of life ( QoL ) underlining the importance of vitiligo recognition by primary care providers . 1 , 12

Well-demarcated , non-scaly , white macules or patches with irregular borders are characteristic of vitiligo lesions . 1 Usually , these are asymptomatic , and are not associated with preceding erythema , pruritis or pain . 13 Typical affected sites are the mouth , lips , fingers , feet , genitalia , and sites of frequent injury / trauma such as elbows and wrists . 1

Differential diagnosis

There are numerous hypopigmenting and

depigmenting disorders of the skin which can mimic vitiligo , but they often have distinguishing features .

When there is uncertainty , a Wood ’ s lamp can help clarify the diagnosis , as depigmented lesions seen in vitiligo emit blue-white fluorescence and appear sharply demarcated . 1

Pityriasis versicolor manifests with scaly , hypopigmented macules , usually on the trunk , due to the overgrowth of the Malassezia yeast . 14 This is commonly seen in young individuals and is associated with sweating , heat and humidity .

Post-inflammatory hypopigmentation ( PIH ) occurs after an inflammatory skin condition . Therefore , history of rash , erythema or itch preceding the spots is typically evident . The lesions do not progress and tend to fade over weeks and months . On examination , PIH spots are poorly demarcated , unlike the sharp demarcation of vitiligo .

Idiopathic guttate hypomelanosis ( IGH )

Vitiligo-affected skin is no longer thought to be at increased risk of skin cancers .

typically appears in older individuals , primarily on sun-exposed areas like the limbs and neck . It is characterised by small , scattered macules that remain stable . 15

Pityriasis alba causes hypopigmented macules or patches often accompanying dry skin and atopic dermatitis in children and adolescents .

Lesions are scaly , poorly demarcated , and often located on the face . It may be preceded by itch and erythema .

It is important to note that eczema and vitiligo may coexist . 16

Comorbidities

Vitiligo patients commonly experience other autoimmune conditions . 1 , 12 , 17 These may include rheumatoid arthritis , Sjogren ’ s

syndrome , systemic lupus erythematosus and thyroid disorders . Even in the absence of clinical signs and symptoms , patients with vitiligo warrant investigation for evidence of these conditions ( See box 1 ).

12 , 17

Eczema , psoriasis , contact dermatitis and alopecia areata are common dermatological comorbidities . 17

Patients with vitiligo are also more likely to develop metabolic syndrome and insulin resistance , highlighting the importance of regular assessment of weight , waist

circumference , blood pressure , lipids and glucose monitoring for all patients . 18

Nutritional deficiencies including vitamin B12 , folate , iron and vitamin D may be associated with vitiligo . Therefore , initial screening and correction of these deficits are important . Aim for levels in the mid-reference range . 19-21

Assessment of vitiligo

A suggested workup for patients diagnosed

with vitiligo is shown in box 1 . Along with these baseline investigations , photo-documentation of lesions on the patient ’ s device is helpful for diagnosis and monitoring .

Location : Generally , lesions on the face and neck respond best to treatment , followed by those on the trunk and limbs . 12 Special locations , such as the eyelids , lips , hands , feet , nipples and genitals can be challenging to treat . 12

Duration : Self-report of vitiligo onset can be helpful , as early vitiligo spots typically respond better to treatment . 12

Size : Evaluation of vitiligo involvement using percentage body surface area ( BSA ), or Vitiligo Area Scoring Index ( VASI ) can help determine severity , disease progression and appropriate treatment . 12

Disease activity : New or enlarging macules reflect vitiligo activity . 1 Confetti-like depigmentation ( see figure 1 ) and Koebnerisation ( vitiligo associated with sites of injury / trauma ; see figures 1 and 2 ) are indicative of active disease , requiring prompt intervention . 1

Treatment

The goal of vitiligo treatment is to prevent disease progression , repigment lesions and maintain the pigment .

General measures External precipitants which exacerbate vitiligo should be identified and avoided . Common triggers include chemicals , injury and

6 , 22 , 23 psychological stress .

Vitiligo-affected skin was thought to be at increased risk of skin cancers ; however , research indicates that these patients actually have a lower risk compared to the background population . 24 , 25 Off-peak sunlight exposure for a limited time is safe and may improve repigmentation . 26

Camouflage products and tanning solutions can be helpful for exposed sites . 1

Given the psychological impacts of vitiligo , appropriate referrals and supports

1 , 12 , 17 should be offered .

Preventing disease progression Immunomodulators are used to prevent disease progression . These include topical corticosteroids for a short duration , and topical calcineurin inhibitors , like

Vitiligo is a treatable condition . Management options include topical and systemic medications , used in conjunction with phototherapy . For localised and stable disease , surgical options can be considered .

Best outcomes are achieved with early diagnosis and intervention , which GPs can facilitate through clinical suspicion and appropriate referrals .

Box 1 . Recommended initial investigations in vitiligo

• Metabolic panel — Serum insulin ( fasting ) — HbA1c and blood glucose — Lipids — LFTs

• Nutritional panel — FBC — Iron studies — B12 , folate — Vitamin D

• Autoimmune panel — TSH , thyroid antibodies — ANA , ENA

pimecrolimus and tacrolimus , for children or disease on flexures and face .

Topical tacrolimus 0.1 % is highly effective and safe ; however , it is expensive in Australia , as it needs to be compounded . Pimecrolimus is on the PBS but may not be as effective . Progress can be reviewed in three months .

For rapidly spreading and widespread disease , systemic treatments using oral corticosteroids may be required . 12 Other immune modulators such as methotrexate , azathioprine and JAK inhibitors may also be used by the treating dermatologist .

Repigmenting therapy Phototherapy is the mainstay of treatment for inducing repigmentation and disease stabilisation . If the patient has widespread vitiligo , narrowband UV-B ( NBUVB ) in the booth , targeted hand and foot machines or home-based phototherapy devices are often used .

It is safe for children , the elderly and pregnant women . According to Australian guidelines , treatments are delivered three times a week and response is evaluated after 36 sessions . 27 It may require a year or