Vitiligo  - Sally O'Shea. Ireland
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Vitiligo - Sally O'Shea. Ireland

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58-year-old man...

58-year-old man
PMHx: psoriasis
Clinical findings
Areas of hypopigmentation
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This PPT is loaded as student material "as is", from the VRF Vitiligo Master Class Barcelona November 2011; VRF does not endorse or otherwise approve it.

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  • Good evening, Mr./Madam Chairman, ladies and gentlemen.
  • A 58-year-old man presented with a progressive flare of psoriasis, resistant to topical treatment. He was otherwise systemically well. On examination, there were scaly, well-demarcated, erythematous plaques involving 10% of his body surface area, consistent with psoriasis. This responded well to a course of narrowband UVB, however, it soon became evident that he also had extensive hypopigmentation.
  • Here is a photograph of the patient’s back, taken at the end of his course of TL-01. As you can see, there are large areas of hypopigmentation and new islands of repigmentation.
  • Similarly, there was patchy loss of pigment overlying the metacarpophalyngeal joints, in a symmetrical distribution.
  • This image again highlights the extent of the condition with evidence of freckle repigmentation.
  • The diagnosis of vitiligo was made clinically and showed a positive response to treatment with NBUVB. The patient was content that his psoriasis had now resolved. Taking into account his skin type, the decision was made to stop phototherapy.
  • The coexistence of psoriasis and vitiligo was first reported in 1955 by Selenyi et al and in 1989, Menter described a case of guttate psoriasis that localized to patches of vitiligo in the same patient. Since then, there have been cases of vitiligo that developed following PUVA and NBUVB treatment for psoriasis. Why this happens is not entirely clear. It is thought to be due to similarities in the immune pathways between the two conditions, or indeed the Koebner phenomenon.
  • It is generally accepted that a genetic basis for vitiligo exists and that autoimmunity plays a central role.
  • Many treatments used for vitiligo have limited results. In the clinical setting, reassurance and photoprotection advice forms the mainstay of management but some of the newer grafting techniques have shown promise.
  • Yet, clearly, there is a missing link as no one treatment has been globally effective.
  • So what do we know at this point?
  • This photograph shows abandoned land and this is similar to the histology of vitiligo. Melanocytes have largely abandoned the skin but if we look closer, a few remain, near hair follicles and at the periphery of the lesions.
  • The melanin produced by this small reservoir of melanocytes is not adequate. The presence of Langerhans’ cells and T lymphocytes suggests invasion by these inflammatory cells and the melanocytes have fled for cover.
  • Although depigmentation can affect the hair, the pattern of perifollicular repigmentation in vitiligo suggests that the hair follicle is preferentially spared or represents some type of ‘safe haven’ for melanocytes but why is this so?
  • As we all know, phototherapy has local immunosuppressive effects on the skin and it stimulates residual melanocytes. Irritants such as diphenylcyclopropenone (DPCP) can cause repigmentation but pain is a limiting factor. Grafting can replenish the melanocytes but again the results vary and may not be cosmetically acceptable.
  • The use of heat to produce pigment is an appealing option as we can avoid the risks of UV radiation and it can be applied to small or larger areas of the skin but it is likely to produce a mottled effect such as that seen in erythema ab igne. Many medications are often avoided due to the pigmentation that they produce but this could be used to an advantage in patients with vitiligo. In 2010, Parsad published a study on the use of minocycline in the treatment of vitiligo. In 29 of the 32 patients enrolled, disease progression was halted. Minocycline is thought to work by reducing the oxidative stress on melanocytes.
  • Limited results suggest calcipotriene combined with phototherapy can cause some repigmentation. Disruption of the basal layer of the epidermis also causes pigmentation , for example, in lichen planus and lupus. In addition, many disorders where hyperpigmentation is a prominent feature are due to increased melanin in the basal layer of the epidermis. It would seem reasonable that immunosuppression should produce a good result. It is therefore surprising that there is very little data about this in inducing remission in vitiligo. Although genomewide studies suggest susceptibility loci, if a causative gene were found, it could be targeted.
  • So where should we direct our efforts? The mechanism for post-inflammatory pigmentation is thought to be mediated by IL-1 alpha, IL-1 beta, IL-6 and TNF-alpha. So perhaps, we should investigate this further if we want to produce pigmentation with a uniform result.
  • Many treatments cause partial repigmentation that rarely lasts. Certain immunosuppressants may prove worthwhile but this must be weighed up against the potential risks involved. The challenge that we face today is to find a therapy that will lead to satisfactory repigmentation that will endure.
  • Studies report increased levels of TNF-alpha and IL-1 alpha in patients with vitiligo. It was incidentally found that vitiligo improved in a patient who was receiving infliximab for ankylosing spondylitis. There have also been case reports of vitiligo improving in patients on etanercept for psoriasis. Conflicting with this was a report of one patient who developed vitiligo after treatment with adalimumab for Crohn’s disease and another report of worsening vitiligo on infliximab.
  • If we consider that IL-1 plays an important role in vitiligo, then it would seem plausible that an IL-1 inhibitor should be effective in the treatment of vitiligo. Anakinra is such an inhibitor and is currently being used in the treatment of rheumatoid arthritis. It is prepared from genetically modified E. Coli and is given by daily subcutaneous injection. To date, I am not aware of any studies looking at its effects on vitiligo.
  • Larger research trials investigating the role of anti-TNF or anti-IL 1 therapy for vitiligo should be done. Considering its cytokine profile, immunomodulators may well prove useful in the future for this condition that is so difficult to treat.

Transcript

  • 1. SJ O’Shea, S Rogers Ireland
  • 2. History
    • 58-year-old man
    • PMHx: psoriasis
    • Clinical findings
    • Areas of hypopigmentation
  • 3.  
  • 4.  
  • 5.  
  • 6. Diagnosis
    • Clinical diagnosis
    • Phototherapy
    • Skin type
  • 7. Psoriasis and vitiligo
    • Coexistence known since 1950s 1
    • 1989 Menter et al. 2
    • Vitiligo after phototherapy 3,4
    • Similar immune pathway
    • Koebner phenomenon
    • Selenyi A. Vitiligo and psoriasis on the same side with syringomyelia. Borgyogy Vener Szemle 1955; 9: 94-6.
    • Menter A, Boyd AS. Silverman AK. Guttate psoriasis and vitiligo: Anatomic cohabitation. JAAD 1989; 20: 698-9.
    • Halcin C, Hann S-K, Kauh YC. Vitiligo following the resolution of psoriatic plaques during PUVA therapy. Int J Dermatol 1997; 36: 534–6.
    • Goodwin RG, Finlay AY, Anstey AV. Vitiligo following narrow-band TL-01 phototherapy for psoriasis. Br J Dermatol. 2001; 144: 1264-66.
  • 8. Hypotheses
    • Genetic factors
    • Autoimmunity
    • Neurogenic
    • Self-destruct theory of Lerner
  • 9. Treatments
    • Camouflage
    • SPF
    • Phototherapy
    • Excimer laser
    • Topical steroids
    • Tacrolimus
    • Bleaching
    • Grafts
  • 10. Missing link?
  • 11. What do we know?
    • Absent melanocytes
  • 12.  
  • 13. What do we know?
    • Absent melanocytes
    • Melanin production
    • Langerhans’ cells
    • T cells
    • Perifollicular repigmentation
  • 14. Why is the hair follicle special?
    • Pigment changes can occur
    • Tendency to spare follicles
    • Site of immune privilege
  • 15. What have we tried?
    • Stimulating melanocytes
    • Replacing melanocytes
    • Irritants
    • Destroying residual pigment
    • Minimizing UV exposure
  • 16. Where do we go now?
    • Thermal-induced changes
    • Medications
    • 2010 Parsad et al 5
    5. Parsad D, Kanwar A. Oral minocycline in the treatment of vitiligo – a preliminary study. Dermatol Ther. 2010; 23(3): 305-7
  • 17. Where do we go now?
    • Vitamin D
    • Basal layer disruption
    • Immunosuppression
    • Molecular genetics
  • 18. Where do we go now?
    • Induction of mediators
  • 19. Potential difficulties
    • Duration
    • Unpredictable
    • Immunosuppression vs. disease
  • 20. How do we target the mediators?
    • TNF-alpha and IL-1-alpha increased in vitiligo 6,7
    • Improvement with infliximab 8
    • Progression with infliximab 9
    • New onset with adalimumab 10
    • Birol A, Kisa U, Kurtipek GS, Kara F, Kocak M, Erkek E, Caglayan O. Increased tumour necrosis factor alpha (TNF-alpha) and interleukin 1 alpha (IL-1 alpha) levels in the lesional skin of patients with nonsegmental vitiligo. Int J Dermatol. 2006; 45: 992-3.
    • Moretti S, Spallanzani A, Amato L, Hautmann G, Gallerani I, Fabbri P. New insights into the pathogenesis of vitiligo: imbalance of epidermal cytokines at sites of lesions. Pigment Cell Res 2002; 15: 87–92.
    • Lv Y, Li Q, Wang L, Gao T. Use of anti-tumour necrosis factor agents: a possible therapy for vitiligo. Med Hypotheses 2009; 72: 546–547.
    • Alghamdi KM, Khurram H, Rikabi A. Worsening of vitiligo and onset of new psoriasiform dermatitis following treatment with infliximab. J Cutan Med Surg. 2011; 15(5): 280-4.
    • Posada C, Florez A, Batalla A, Alcazar JJ, Carpio D. Vitiligo during treatment of Crohn’s disease with adalimumab: adverse effect or co-occurrence? Case Rep Dermatol. 2011; 3(1): 28-31.
  • 21. Anakinra
    • Recombinant IL-1 receptor antagonist
  • 22. Conclusion
    • Limited treatments
    • ? Role of immunomodulators
    • More research