1. In the name of the GOD

2. Fatemeh Mokhtari Associate Professor of Dermatology
Vitiligo
Fatemeh Mokhtari
Associate Professor of Dermatology

3. Introduction Vitiligo is an acquired depigmenting disorder
Affecting 0·5% of the world population
Without sex or racial differences
It affects all age groups

4. Vitiligo Vulgaris/NSV

5. Vitiligo Vulgaris/NSV
Characterized by:
White patches
Often symmetrical
Usually increase in size with time
Corresponding to a substantial loss of functioning epidermal and sometimes hair follicle melanocytes

6. Segmental Vitiligo (SV)

7. Segmental Vitiligo (SV)
A unilateral distribution (asymmetric vitiligo) that may totally or partially match a cutaneous segment (e.g. dermatomal-like)
Some specific features of SV are rapid onset and involvement of the hair follicle pigmentary system
One unique segment is involved in most patients
Not associated with thyroid or other autoimmune disorders.
Segmental vitiligo and an age of onset younger than 14 years have been associated with more refractory disease

8. Diagnostic Consideration
Vitiligo and ocular disease
Vitiligo and autoimmune disorders
Vitiligo and auditory abnormalities
Vitiligo and melanoma

9. Vitiligo and ocular disease
The uveal tract and retinal pigment epithelium contain pigment cells
Uveitis is the most significant ocular abnormality.

10. Vitiligo and autoimmune disorders
Frequently associated with disorders of autoimmune origin
Thyroid abnormalities being the most common
Vitiligo usually precedes the onset of thyroid dysfunction
A significant incidence of thyroid dysfunction has been found in pediatric patients with non segmental vitiligo
Suggesting that it may be prudent to screen thyroid function and antibody levels in pediatric patients with vitiligo

11. Vitiligo and auditory abnormalities
Melanin may play a significant role in the establishment and/or maintenance of the structure and function of the auditory system
Because vitiligo affects all melanocytes, auditory disturbances may result, albeit rarely
Several studies have described familial vitiligo to be associated with hearing abnormalities and hypoacusis

12. Vitiligo and melanoma
Vitiligo like depigmentation can occure in patients with malignant melanoma
Believed to result from a T-cell-mediated reaction to antigenic melanoma cells and cross-reactivity to healthy melanocytes
Believed that active vitiligo in patients with melanoma may indicate a better prognosis
A melanoma patients with vitiligo have been shown to have longer survival than otherwise expected

13. Laboratory Studies
Diagnosis of vitiligo generally is made on the basis of clinical finding
In cases of uncertain diagnosis, additional noninvasive and invasive procedures may be needed:
Punch biopsy from lesional and nonlesional skin
Other tests if needed (mycology, molecularbiology to detect lymphoma cells, etc)

14. Laboratory Studies
Further testing may be necessary in patients with suggestive signs and symptoms
Laboratory work for vitiligo may include the following:
CBC/diff
TSH, Free T4, Free T3
Anti TPO
ANA

15. Approach Considerations
As the care often extends over a long period of time, patients are frequently frustrated by the failure of previous treatments
Psychological stress is common
The treatment plan should be discussed with the patient to obtain a high level of compliance
It must be remembered that some therapies are not licensed for vitiligo and can only be prescribed ‘off-label’
It is important to note that in patients with lighter skin, no intervention may be needed
Instead, diligent sun protection may be the best strategy in order to avoid the surrounding normal skin from becoming more tan and making the lesions more obvious

16. Approach Considerations
Various types of medications, phototherapy, laser therapy, and surgical therapy exist
When therapy is necessary, topical steroids, topical calcineurin inhibitors, and narrow-band UV are widely used and now considered the mainstays of treatment
Treatment must be individualized
No single therapy for vitiligo produces predictably good results in all patients
The response to therapy is highly variable
Some types of vitiligo or lesions in cetain locations may be more or less responsive to treatment

17. Guideline for the Treatment of SV and NSV Vitiligo

18. Topical Corticosteroids (TCS)

19. Topical Corticosteroids (TCS)
Applied since the 1950s for their anti-inflammatory and immunomodulating effects
As first-line treatment for limited forms of vitiligo:
TCS
Topical calcineurin inhibitors (TCI)

20. Topical Corticosteroids (TCS)
Efficacy:
Topical corticosteroids have the best results (75% of repigmentation) on:
Sun-exposed areas (face and neck)
In dark skin
In recent lesions
Acral lesions respond poorly
No differences in efficacy were found between:
Clobetasol and tacrolimus
Between clobetasol or mometasone and pimecrolimus
Although TCI might be less effective for extrafacial lesions

21. Topical Corticosteroids (TCS)
Efficacy:
When used in the short term, TCS appear to be safe and effective treatment for both children and adults
Local side-effects (skin atrophy, telangiectasia, hypertrichosis, acneiform eruptions and striae) of potent or very potent TCS are well known
Lower potency classes of TCS and newer class III TCS, such as mometasone furoate and methylprednisolone aceponate, are largely devoid of these side- effects
No studies available on optimal duration of TCS therapy and on discontinuous applications that could improve the therapeutic index

22. Expert recommendations: TCS
In children and adults:
Once-daily application of potent TCS can be advised for patients with limited
Extrafacial involvement for a period:
No longer than 3 months, according to a continuous treatment scheme
A discontinuous scheme (15 days per month for 6 months with a strict assessment of response based on photographs)

23. Expert recommendations: TCS
Facial lesions can be treated as effectively and with lesser side-effects by TCI
As potent TCS appear to be at least as effective as very potent TCS, the first category should be the first and safest choice
Systemic absorption is a concern when:
Large areas of skin
Regions with thin skin
Children are treated for a prolonged time with potent steroids
TCS with negligible systemic effects should be preferred, such as:
Mometasone furoate
Methylprednisolone aceponate

24. Calcineurin Inhibitors

25. Calcineurin Inhibitors
Since 2002, report of beneficial effects, particularly in areas where prolonged use of potent TCS is contraindicated
Tacrolimus and pimecrolimus are topical immunomodulator
Mechanism of action:
Affecting the activation/maturation of T cells and subsequently inhibiting the production of cytokines, such as TNF-α
The enhancement of melanocyte migration and differentiation

26. Calcineurin Inhibitors
Efficacy
beneficial results mainly in the head and neck, both in adults and children
UV exposure during TCI may play a synergistic role, but long- term safety studies are not available
The association between TCI and UV is currently not recommended, (‘black box’ warning of the FDA for AD)

27. Calcineurin Inhibitors
Efficacy
 Comparing topical pimecrolimus and tacrolimus, not detect significant differences in the efficacy
A slightly higher response rate in patients treated with tacrolimus (61%) than in those treated with pimecrolimus (54·6%)
Tacrolimus could be effective even in SV

28. Calcineurin Inhibitors
Efficacy
Twice-daily applications of tacrolimus ointment have shown more efficacy than once- daily applications
 Duration ranged from 10 weeks up to 18 months
Information about the minimal or ideal treatment period is not available
The treatment should be prescribed initially for 6 months
If effective, prolonged treatment (e.g. longer than 12 months) may be proposed

29. Calcineurin Inhibitors
Tolerance
The most common early reported side-effects for TCI are:
Local reactions:
Burning sensation
Pruritus
Erythema

30. Phototherapies

31. Phototherapies
PUVA
Combines the use of psoralens with long-wave (320–340 nm) UVA
Psoralens can be given orally or topically
PUVA:
Proliferation of melanocytes
Increased synthesis of tyrosinase
Increased transfer of melanosomes to keratinocytes

32. Phototherapies NB-UVB:
311 nm: phototherapy of choice for active and/or widespread vitiligo
Side-effects: less frequent than PUVA therapy
Efficacy: least equivalent

33. Phototherapies Excimer laser:
308 nm, particularly suitable for treating localized disease
This new treatment is an efficacious, safe, and well-tolerated treatment
Therapy is expensive
Twice weekly for an average of sessions
Eximer laser has been combined with both topical tacrolimus and short term systemic corticosteroids in the setting of segmental vitiligo
Segmental vitiligo has a better repigmentation response with excimer laser treatment used at earlier stages of the disease

34. Phototherapies
PUVA
Not recommended in children aged < 10–12 years (risk of retinal toxicity)
Patients should be motivated to:
Therapy for at least 6 months before being considered nonresponsive
12–24 months of continuous therapy may be necessary to acquire maximal repigmentation

35. Phototherapies Efficacy of PUVA For topical PUVA:
A thin coat of 8-MOP cream or ointment
At very low concentration (0·001%) should be applied 30 min before UVA exposure
With possible further concentration increments
The advantage of topical therapy:
The need for fewer treatments
Considerably smaller cumulative UVA doses
Lower plasma levels and consequently less systemic and ocular phototoxicity.
 The main disadvantages:
Severe blistering reactions
Perilesional hyperpigmentation

36. Phototherapies Efficacy of NB-UVB:
Twice or three times weekly and is continued until repigmentation
More effective than other phototherapies
Superior to oral PUVA
First-line treatment for NSV

37. Phototherapies Tolerance of phototherapies:
The long-term risk of skin cancer is well established for PUVA
NB-UVB are well tolerated
The most common acute adverse reaction:
Skin type- and dose-dependent erythema
Occurring 12–24 h after irradiation
Continuing within another 24 h
Disappearing before the next session
It is essential to ask the patients about erythema in response to the previous irradiation

38. Expert Recommendations: Phototherapies
NB-UVB:
Indicated for generalized NSV
Total body treatment: involving >15–20% of the body area
Total NB-UVB: treatment for active spreading vitiligo

39. Expert Recommendations: Phototherapies
NB-UVB:
No consensus as to the optimum treatment duration
Stop irradiation if:
No repigmentation occurs within the first 3 months of treatment
In case of unsatisfactory response (< 25% repigmentation) after 6 months of treatment
Usually continued:
ongoing repigmentation
Maximum period of 1 or 2 years
Maintenance irradiation is not recommended
Regular follow-up examinations are suggested for detecting relapse

40. Combination Treatments

41. Combination Treatments
With lesions refractory or resistant to monotherapies
Phototherapies with different topical or systemic drugs
Surgical and medical treatments

42. Expert recommendations: combination therapies
Topical steroids and phototherapy:
The anti-inflammatory properties of the steroids may act on the immune/inflammatory component, mainly in recent and active lesions, lowering the total amount of administered UV radiation
The combination of TCS and UVB sources (NB-UVB and 308 nm excimer lasers) may be promising for difficult-to-treat areas, e.g. over bony prominences
Potent topical steroids applied once a day (3 weeks out of 4) can be used on vitiligo lesions for the first 3 months of phototherapy

43. Oral steroids

44. Oral steroids Oral steroid minipulse therapy:
Oral minipulse (OMP) of moderate doses of betamethasone/dexamethasone
Can arrest the activity of the disease
Not effective in repigmenting stable vitiligo
Betamethasone or dexamethasone was given as a single oral dose of 5 mg on two consecutive days per week

45. Oral steroids Oral steroid minipulse therapy:
In adult nonresponders to the standard dose:
The dose was increased to 7·5 mg daily
Then reduced to 5 mg daily when disease progression was arrested
Within 1–3 months of treatment, 89% of patients with progressive disease stabilized
While within 2–4 months, repigmentation was observed in 80% of the patients
The optimal duration needed to stop vitiligo progression is between 3 and 6 months

46. Oral steroids Oral steroid minipulse therapy: Side-effects:
Weight gain
Insomnia
Agitation
Acne
Menstrual disturbances
Hypertrichosis

47. Surgery

48. Surgery
Replace the melanocytes with ones from a normally pigmented autologous donor site
Several melanocyte transplantation techniques can be performed under local anaesthesia
Transplantation for extensive areas may require general anaesthesia
All methods require strict sterile condition
Punch grafting (tissue graft) is the easiest and least expensive method, but it is not suitable for large lesions

49. Surgery The best indications are:
Stabilized segmental vitiligo
Stabilized focal vitiligo
SV with leucotrichia
 In NSV various recommendations suggest:
A period of disease inactivity ranging from 6 months to 2 years
No history of a Koebner isomorphic response

50. Other interventions

51. Other interventions Camouflage:
important part of the global management
impact of the disease on the patient’s self-body image
Permanent camouflage, micropigmentation and tattoos should be considered with particular caution, due to the unpredictable course of the vitiligo

52. Depigmentation

53. Depigmentation In patients with extensive And refractory vitiligo
depigmenting the remaining islands through
chemical or
physical methods
may be cosmetically acceptable

54. Monobenzone ethyl ester (MBEH)
A derivative of hydroquinone (HQ)
Unlike HQ, MBEH almost always causes nearly irreversible depigmentation
The patients with the highest skin phototypes (V and VI), for which the contrast may be the best candidates
Patients with phototypes I and II may also obtain better cosmetic improvement on exposed areas
The patients must be extensively informed that most approaches lead to irreversible depigmentation

55. Monobenzone ethyl ester (MBEH)
MBEH is applied topically as a 20% cream
A thin layer of cream should be applied uniformly and rubbed into the pigmented area two to three times daily
Prolonged exposure to sunlight should be avoided during treatment, or a sunscreen should be used, as exposure to sunlight reduces the depigmenting effect
Depigmentation is usually obtained after 1–4 months of treatment
After 4 months of treatment without success, the drug should be discontinued
When the desired degree of depigmentation is obtained, monobenzone should be applied as often as needed to maintain depigmentation (usually only two times weekly)

56. Monobenzone ethyl ester (MBEH)
Mild transient skin irritation or eczema may occur
The treatment should be discontinued if irritation, burning sensation or dermatitis occurs
Sometimes areas of normal skin distant to the site of application have become depigmented

57. Depigmentation The Q-switched laser has been proposed
Cryotherapy has been reported as:
An inexpensive depigmentation therapy
But due to the risk of scarring, it should be used only by experienced dermatologists
Limited published information is available

58. Psychological interventions
Depigmentation exerts a negative impact on the patient’s appearance and self-esteem
Additional discomforting aspects are:
The chronic
Unpredictable nature of the disease
The lack of a universally effective treatment

59. Conclusions

60. Conclusions
Vitiligo is a disease lacking definitive and completely effective therapies
Counselling patients to avoid some therapies of dubious efficacy is a major step
The environmental factors should always be discussed:
Occupation
Koebner phenomenon
Sustained stress or anxiety

61. Conclusions
Phototherapy and combined treatments are the most effective treatments
Therapy should stop the progression of the lesions and provide complete or almost complete repigmentation to be satisfactory for the patient
A stepwise treatment approach divided by type of vitiligo and extent
A zero line is always possible, meaning no treatment if the disease is not bothering the patient

62. Stepwise Treatment Approach Divided by Type of Vitiligo and Extent

63. Stepwise Treatment Approach Divided by Type of Vitiligo and Extent
SV or limited NSV (< 2–3% of body surface)
First line
Avoidance of triggering factors
Local therapies:
corticosteroids
calcineurin inhibitors
Second line
Localized NB-UVB therapy, especially excimer monochromatic lamp or laser
Third line
Consider surgical techniques if repigmentation cosmetically unsatisfactory on visible areas

64. Stepwise Treatment Approach Divided by Type of Vitiligo and Extent
NSV
First line
Avoidance of triggering/aggravating factors.
Stabilization with NB-UVB therapy
At least 3 months
Optimal duration at least 9 months, if response.
Combination with topical therapies

65. Stepwise Treatment Approach Divided by Type of Vitiligo and Extent
NSV
Second line (if rapidly progressing disease or absence of stabilization under NB-UVB)
Systemic steroids (e.g. 3–4month minipulse therapy)
Third line
Graft in non responding areas especially with high cosmetic impact.

66. Stepwise Treatment Approach Divided by Type of Vitiligo and Extent
NSV
Fourth line
Depigmentation techniques
In non responding widespread (> 50%) or highly visible recalcitrant facial/hands vitiligo
Hydroquinone monobenzyl ether or 4-methoxyphenol alone or associated with Q-switched ruby laser

67. Stepwise Treatment Approach Divided by Type of Vitiligo and Extent
For all subtypes of disease or lines of treatment, psychological support and counselling, including access to camouflage instructors, is needed.

68. Thanks for your attention