casereport repigmentation of tenacious vitiligo on...

Case ReportRepigmentation of Tenacious Vitiligo on Apremilast

Sara B Huff1 and Lorie D Gottwald2

1University of Toledo College of Medicine and Life Sciences 3000 Arlington Avenue Toledo OH 43614 USA2Department of Dermatology University of Toledo Medical Center 3000 Arlington Avenue Toledo OH 43614 USA

Correspondence should be addressed to Sara B Huff saramonroeutoledoedu

Received 26 July 2017 Accepted 8 October 2017 Published 6 November 2017

Academic Editor Kowichi Jimbow

Copyright copy 2017 Sara B Huff and Lorie D Gottwald This is an open access article distributed under the Creative CommonsAttribution License which permits unrestricted use distribution and reproduction in any medium provided the original work isproperly cited

Vitiligo is a common pigment disorder characterized by acquired loss of function or absence of melanocytes leading to distinctareas of depigmentation Physical exam reveals sharply demarcated depigmented macules or patches on otherwise normal skinVitiligo can present at any age in any skin color There is no specific serologic marker for diagnosis but patients often have otherautoimmune problems Treatment options are limited and are difficult given the fact that the pathogenesis of the disease is not wellelucidated We present the case of a 52-year-old woman with vitiligo for over 2 decades The patientrsquos medical history reveals a lackof response to many different approaches This case highlights the ability of apremilast an FDA-approved drug for the treatmentof psoriasis and psoriatic arthritis to achieve repigmentation in a case a vitiligo that has been extremely recalcitrant

1 Introduction

Vitiligo is a common pigment disorder characterized byacquired development of white macules on the skin due tothe loss of functioning melanocytes in the skin the hairor both [1] Although the pathogenesis is not known it isthought to be a cumulative effect of different mechanismsincluding autoimmune neurohormonal genetic oxidativestress and cytotoxic [1ndash3] The areas of depigmentation areusually symmetrical sharply demarcated and enlarged overtime Vitiligo affects all ages races and ethnic groups [2]Considering the distinct contrast in white patches with thenormal skin vitiligo is more prominent in darker skinnedpersons Vitiligo can greatly impact the quality of life foranyone afflicted no matter what age Patients report feelingstigmatized being isolated and having low self-esteem [1 4]

Although topical and systemic glucocorticoids topicalcalcineurin inhibitors and narrowband ultraviolet B pho-totherapy are used to promote repigmentation they allhave varying degrees of success [2 5 6] The response totreatments is lengthy and may be highly different amongpatients and even inconsistent in different body areas inthe same patient Vitiligo is a chronic disease with a highlyunpredictable progression Studies regarding these treatment

options are generally poor or uncontrolled resulting in theinability to amalgamate conclusions because of the consid-erable heterogeneity in study design and outcome measureHence alternative and more efficacious therapies are neededfor the study and treatment of vitiligo

2 Case Report

A 52-year-old woman presented for a follow-up of chronicvitiligo No other concomitant autoimmune diseases areknown in this patient She developed vitiligo in 1995 andhas been seen in this clinic since 1998 She used topicaltacrolimus pimecrolimus mometasone furoate cream clo-betasol propionate cream topical psoralen combined withphotochemotherapy withUVA intramuscular triamcinoloneacetonide intramuscular alefacept subcutaneous etanerceptoral cyclosporine oral dapsone and oral prednisone in thepast The patient stopped the use of medications for 5 yearsprior to re-presenting due to lack of success with repigmen-tation with the previously listed medications Her attemptat multiple non-FDA-approved medications illustrates herfrustration At the first visit the diagnosis of chronic vitiligowas readdressed The recent data suggesting that apremilastmay have a broad effect on inflammation was reviewed and

HindawiCase Reports in Dermatological MedicineVolume 2017 Article ID 2386234 3 pageshttpsdoiorg10115520172386234

2 Case Reports in Dermatological Medicine

Figure 1 Clinical appearance of the right dorsal hand 5 and a halfmonths after beginning apremilast

the patient was willing to try apremilast in a non-FDA-approved fashion [7] After six weeks of apremilast treatmentshe reported she believed she was starting to repigment Shecontinued treatment with apremilast at 30mg twice dailyThreemonths after initiating treatment the patient presentedfor a follow-up with mild improvement The patient was bol-stered at this time with 60mg intramuscular triamcinoloneacetonide and apremilast 30mg twice daily was maintainedNote that many years of attempts at steroids as a solo therapyhad yielded no improvement Six weeks following this visitshe started to note repigmentation of hands but felt that nor-mal skin was darkening as well secondary to ambient sun-light and she had a bit more pronounced hypopigmentationof perioral area She received a repeat 60mg intramusculartriamcinolone acetonide injection andmaintained apremilast30mg twice daily Five and a half months after beginningthe apremilast treatment she continued to have areas ofimprovement but with a few new areas of hypopigmentationon her feet The patient felt that repigmentation of handsand forearms was progressing slowly as seen in Figures 1and 2 At follow-up 6 and a half months after beginningapremilast treatment the patient reports repigmentation inbilateral arms legs hands feet chest and face The areasappear red before repigmenting She had no sun exposure inthe interim At her next follow-up 8 months after beginningapremilast treatment the patient experienced fairly signifi-cant repigmentation It was important to continue followingthe patient without steroids to monitor her progress Ather last visit 5 months without triamcinolone acetonidesupplementation and 11 months after beginning apremilast30mg twice daily treatment the patient was doing extremelywell She is tolerating the apremilast and is repigmenting onher chest and arms 60ndash70 and now also on her face Thepatient provided images of 7 months without triamcinoloneacetonide and 13 months after beginning apremilast 30mgtwice daily as shown in Figures 3 and 4 Side effects andrationale regarding apremilast treatment were reviewed ateach visit The patient reported no side effects throughout

Figure 2 Clinical appearance of the right anterior forearm 5 and ahalf months after beginning apremilast

Figure 3 Clinical appearance of the right dorsal hand 13 monthsafter using apremilast 30mg twice daily

3 Discussion

The treatment of vitiligo is challenging given the lack ofwell controlled studies and inability to pool results basedon considerable heterogeneity in study design and outcomemeasure Apremilast has been shown to help in autoimmu-nity from alopecia areata [7] Our case shows a patient whowas treated with apremilast 30mg twice daily and achievedsignificant repigmentation in the presence of initial steroidbolstering and continued repigmentation without steroids

Apremilast is a phosphodiesterase-4 enzyme (PDE-4)inhibitor Apremilast is FDA-approved for the treatment ofpatients with moderate to severe plaque psoriasis who arecandidates for phototherapy or systemic therapy as wellas for use in psoriatic arthritis PDE-4 normally degradescyclic adenosine monophosphate (cAMP) into 51015840-adenosinemonophosphate By inhibiting the PDE-4 enzyme specificfor cAMP degradation this results in increased intracellularcAMP levels and thereby regulation of numerous inflamma-tory mediators through the cAMP second messenger effect

Case Reports in Dermatological Medicine 3

Figure 4 Clinical appearance of the right anterior forearm 13months after using apremilast 30mg twice daily

(eg decreased expression of TNF-120572 and interleukin- (IL-)17 IL-23 and interferon gamma as well as increased IL-10)[8] When intracellular cAMP is elevated inflammatory sig-naling and cytokines are suppressed and anti-inflammatorymodulators such as IL-10 are increased Vitiligo like psoria-sis is linked to a dysregulated immune system governed by aproinflammatory cytokine network involving local and sys-temic chronic inflammatory processes [8ndash10] Melanocytescultured from vitiligo patient skin samples have been shownto express high levels of cytokines including IL-6 and IL-17[9] Positive correlations between levels of IL-17 and diseaseextent and activity have been found [9] IL-6 and IL-8 canattract immune components to the skin and may be thelink between the triggering event and the initiation of theautoimmune response that results in vitiligo progression[9] Recent observations have indicated the critical role ofaltered cellular immunity autoimmunity and cytokines inthe etiopathogenesis of vitiligo [11] The use of apremilastan oral PDE-4 inhibitor for chronic inflammatory diseaseswhich does not target any single mediator but rather has abroad range of effects has been shown to be helpful in thetreatment of vitiligo in our patient [8] There are possiblerisks to every intervention for vitiligo Common side effects ofapremilast are diarrhea headache nausea vomiting weightloss and depression these adverse events typically presentearly and are self-limitingThe advantages of using apremilastinclude ease of oral administrationminimal drug interactionpotential and safety adverse event profile It should be notedthat vitiligo can spontaneously be repigmented Spontaneousrepigmentation would be unlikely in this case given thechronicity of disease A PubMed search of articles indexedfor MEDLINE using the terms vitiligo apremilast and re-pigmentation revealed that there currently are no knowncases of repigmentation in patients with vitiligo on apremilastthat have been reported Our patient presented with chronicvitiligo that was extremely recalcitrant to many differentclasses of drugs and modalities of delivery

4 Conclusion

Psoriasis alopecia areata and vitiligo share a common path-way of autoimmunity inflammatory signals and cytokinespresent although their pathogenesis is not completely under-stoodApremilast is FDA-approved for psoriasis and psoriaticarthritis Apremilast has also been shown to inhibit the devel-opment of alopecia areata [7]We present this case to demon-strate the ability of apremilast to allow for repigmentation in apatient with chronic recalcitrant vitiligo in conjunction withinitial systemic glucocorticoids More clinical studies ideallya randomized placebo-controlled trial would be needed toprove that apremilast leads to repigmentation in vitiligo

Conflicts of Interest

The authors declare that there are no conflicts of interestregarding the publication of this paper

References

[1] G F Mohammed A H Gomaa and M S Al-DhubaibildquoHighlights in pathogenesis of vitiligordquoWorld Journal of ClinicalCases vol 3 no 3 pp 221ndash230 2015

[2] C K Sharma M Sharma B Aggarwal and V SharmaldquoDifferent advanced therapeutic approaches to treat vitiligordquoJournal of Environmental Pathology Toxicology and Oncologyvol 34 no 4 pp 321ndash334 2015

[3] J F Rork M Rashighi and J E Harris ldquoUnderstandingautoimmunity of vitiligo and alopecia areatardquo Current Opinionin Pediatrics vol 28 no 4 pp 463ndash469 2016

[4] C M Nguyen K Beroukhim M J Danesh A Babikian JKoo and A Leon ldquoThe psychosocial impact of acne vitiligoand psoriasis A reviewrdquo Clinical Cosmetic and InvestigationalDermatology vol 9 pp 383ndash392 2016

[5] B S Daniel and R Wittal ldquoVitiligo treatment updaterdquo Aus-tralasian Journal of Dermatology vol 56 no 2 pp 85ndash92 2015

[6] K Ezzedine V Eleftheriadou M Whitton and N van GeelldquoVitiligordquoThe Lancet vol 386 no 9988 pp 74ndash84 2015

[7] A Gilhar A G Schrum A Etzioni H Waldmann andR Paus ldquoAlopecia areata Animal models illuminate autoim-mune pathogenesis and novel immunotherapeutic strategiesrdquoAutoimmunity Reviews vol 15 no 7 pp 726ndash735 2016

[8] P Schafer ldquoApremilast mechanism of action and applicationto psoriasis and psoriatic arthritisrdquo Biochemical Pharmacologyvol 83 no 12 pp 1583ndash1590 2012

[9] P Manga N Elbuluk and S J Orlow ldquoRecent advances inunderstanding vitiligordquo F1000Research vol 5 2016

[10] P H Schafer A Parton L Capone et al ldquoApremilast isa selective PDE4 inhibitor with regulatory effects on innateimmunityrdquo Cellular Signalling vol 26 no 9 pp 2016ndash20292014

[11] M Kidir A A Karabulut M E Ercin and P Atasoy ldquoRegu-latory T-cell cytokines in patients with nonsegmental vitiligordquoInternational Journal of Dermatology vol 56 no 5 pp 581ndash5882017

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2 Case Reports in Dermatological Medicine

Figure 1 Clinical appearance of the right dorsal hand 5 and a halfmonths after beginning apremilast

the patient was willing to try apremilast in a non-FDA-approved fashion [7] After six weeks of apremilast treatmentshe reported she believed she was starting to repigment Shecontinued treatment with apremilast at 30mg twice dailyThreemonths after initiating treatment the patient presentedfor a follow-up with mild improvement The patient was bol-stered at this time with 60mg intramuscular triamcinoloneacetonide and apremilast 30mg twice daily was maintainedNote that many years of attempts at steroids as a solo therapyhad yielded no improvement Six weeks following this visitshe started to note repigmentation of hands but felt that nor-mal skin was darkening as well secondary to ambient sun-light and she had a bit more pronounced hypopigmentationof perioral area She received a repeat 60mg intramusculartriamcinolone acetonide injection andmaintained apremilast30mg twice daily Five and a half months after beginningthe apremilast treatment she continued to have areas ofimprovement but with a few new areas of hypopigmentationon her feet The patient felt that repigmentation of handsand forearms was progressing slowly as seen in Figures 1and 2 At follow-up 6 and a half months after beginningapremilast treatment the patient reports repigmentation inbilateral arms legs hands feet chest and face The areasappear red before repigmenting She had no sun exposure inthe interim At her next follow-up 8 months after beginningapremilast treatment the patient experienced fairly signifi-cant repigmentation It was important to continue followingthe patient without steroids to monitor her progress Ather last visit 5 months without triamcinolone acetonidesupplementation and 11 months after beginning apremilast30mg twice daily treatment the patient was doing extremelywell She is tolerating the apremilast and is repigmenting onher chest and arms 60ndash70 and now also on her face Thepatient provided images of 7 months without triamcinoloneacetonide and 13 months after beginning apremilast 30mgtwice daily as shown in Figures 3 and 4 Side effects andrationale regarding apremilast treatment were reviewed ateach visit The patient reported no side effects throughout

Figure 2 Clinical appearance of the right anterior forearm 5 and ahalf months after beginning apremilast

Figure 3 Clinical appearance of the right dorsal hand 13 monthsafter using apremilast 30mg twice daily

3 Discussion

The treatment of vitiligo is challenging given the lack ofwell controlled studies and inability to pool results basedon considerable heterogeneity in study design and outcomemeasure Apremilast has been shown to help in autoimmu-nity from alopecia areata [7] Our case shows a patient whowas treated with apremilast 30mg twice daily and achievedsignificant repigmentation in the presence of initial steroidbolstering and continued repigmentation without steroids

Apremilast is a phosphodiesterase-4 enzyme (PDE-4)inhibitor Apremilast is FDA-approved for the treatment ofpatients with moderate to severe plaque psoriasis who arecandidates for phototherapy or systemic therapy as wellas for use in psoriatic arthritis PDE-4 normally degradescyclic adenosine monophosphate (cAMP) into 51015840-adenosinemonophosphate By inhibiting the PDE-4 enzyme specificfor cAMP degradation this results in increased intracellularcAMP levels and thereby regulation of numerous inflamma-tory mediators through the cAMP second messenger effect




4 Conclusion




References

















of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of



















4 Conclusion




References

















of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of





















of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















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