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 Table of Contents  
CASE REPORT
Year : 2022  |  Volume : 9  |  Issue : 1  |  Page : 51-54

Vitiligo: an uncommon cutaneous manifestation of graft versus host disease


Department of Dermatology, Armed Forces Medical College, Pune, India

Date of Submission25-Apr-2020
Date of Decision21-Oct-2020
Date of Acceptance06-Jan-2021
Date of Web Publication16-May-2022

Correspondence Address:
Dr. Preema Sinha
Department of Dermatology, Armed Forces Medical College, Pune 411040
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/Pigmentinternational.Pigmentinternational_

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  Abstract 


Graft versus host disease (GVHD) is the most serious complication of hematopoietic stem cell transplantation. Skin is the most commonly affected organ, in both acute and chronic GVHD with a variable clinical spectrum of presentation with the typical skin lesions being either lichenoid or sclerodermatous. Antibodies developing in chronic GVHD act as triggering factors in the development of autoimmune diseases and can manifest as vitiligo that is an autoimmune disease resulting in melanocyte destruction. Vitiligo as sequelae and manifestation of GVHD is infrequently reported in the literature. Herein, we report the case of a lady who developed vitiligo post hematopoietic stem cell transplant.

Keywords: graft versus host disease, vitiligo


How to cite this article:
Sinha P, Sinha A, Radhakrishnan S, Bhatia JK. Vitiligo: an uncommon cutaneous manifestation of graft versus host disease. Pigment Int 2022;9:51-4

How to cite this URL:
Sinha P, Sinha A, Radhakrishnan S, Bhatia JK. Vitiligo: an uncommon cutaneous manifestation of graft versus host disease. Pigment Int [serial online] 2022 [cited 2022 Jul 1];9:51-4. Available from: https://www.pigmentinternational.com/text.asp?2022/9/1/51/345299




  Introduction Top


Graft versus host disease (GVHD) is a complex multi-organ disease that occurs in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Conventionally, GVHD has been divided into acute and chronic forms, with symptoms developing during or after 100 days of the hematopoietic stem cell transplant respectively. The most commonly involved organ system in GVHD is the skin, in approximately 75% of patients, followed by oral mucosa, liver, and eye. The characteristic skin manifestations of GVHD are lichen planus like eruptions, lichen-sclerosus, and morphea-like lesions, poikiloderma, and deep sclerosis or fasciitis. Less typical cutaneous manifestations are ichthyosiform lesions, keratosis pilaris like eruptions, annular erythematous lesions, psoriasiform plaques, and nail dystrophy.[1] The occurrence of vitiligo as a manifestation of chronic GVHD has been rarely reported in the literature.[2] Vitiligo associated with GVHD likely develops secondary to the long-term immune dysregulation that may provoke predisposed autoimmunity resulting in the destruction of melanocytes as a dependent response of cytotoxic T-lymphocytes.[3] We herein report a case of vitiligo in a lady with chronic GVHD post allogeneic stem cell transplant.


  Case history Top


A 43-year-old lady, a case of acute myeloid leukemia managed with allogeneic peripheral blood stem cell transplant presented with complaints of red itchy lesions over her body 4 months post-transplant. There was a history of loose stools and dryness of eyes of 10 days duration. Examination revealed multiple discrete erythematous to violaceous papules and plaques present over the trunk and extremities. A clinical differential of GVHD was kept and skin biopsy was done from the violaceous plaque, which revealed basal cell vacuolar degeneration with lymphoplasmacytic infiltrate in superficial dermis along with scattered melanophages. Deep dermis showed sclerosis of dermal collagen [Figure 1]. The patient was diagnosed as a case of lichenoid GVHD and was started on Cyclosporine and Methylprednisolone along with topical steroids for the skin lesions. The lesions regressed with hyperpigmentation. She had multiple episodes of worsening of lesions on tapering of immunosuppressive therapy.
Figure 1 (H&E 100×) Basal cell vacuolar degeneration with lymphoplasmacytic infiltrate in superficial dermis along with scattered melanophages. Deep dermis showed sclerosis of dermal collagen.

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Six months post-transplant, the patient presented with rapidly progressive depigmented lesions over upper and lower lips and a focal area of depigmentation over the scalp [Figure 2] and [Figure 3]. No personal or family history of vitiligo was present. Oral and genital mucosa were not involved. Nail examination revealed Beau’s lines on multiple fingernails. Investigations revealed a normal thyroid and antinuclear antibody profile. The patient was diagnosed as having vitiligo as a manifestation of GVHD and managed with topical tacrolimus for lip and scalp lesions and is on regular follow up.
Figure 2 Hyperpigmented macules over the face and neck (lichenoid graft versus host disease) and depigmented macules over scalp and lips.

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Figure 3 Vitiligo over the lips in the form of depigmented macules.

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  Discussion Top


GVHD is one of the most frequent and devastating complications arising after allo-HSCT and is the major cause of mortality and morbidity in survivors.[1] Pathogenic mechanisms implicated in GVHD are an interaction between donor immunocompetent T lymphocytes and the recipient tissue antigens. Skin is the most commonly affected organ in GVHD with presentations ranging from non-sclerotic epidermal involvement (such as lichen planus–like eruptions or poikiloderma) to deep sclerotic or morphea-like lesions resembling fasciitis.[4]

Vitiligo is an uncommon disease accompanying GVHD in allo-HSCT recipients. In a retrospective cross-sectional analysis of 282 patients with chronic GVHD, Zuo et al.[2] reported 4.9% of patients developing vitiligo with one patient having both vitiligo and alopecia areata. The majority of patients in the above study had been diagnosed as having chronic GVHD for more than 1 year and had a sclerotic disease. The authors also hypothesized the risk factors for vitiligo being donor-recipient sex mismatch resulting in autoimmunity, with a higher risk for vitiligo if the graft recipient was male and the donor female.[2] In contrast to the findings of Zuo et al., the donor in our case was male and the recipient female. Nevertheless, donor-recipient sex mismatch leading to autoimmunity could still be a possible triggering factor in our case.

In another prospective cohort of 50 patients with chronic GVHD, Čeović et al..[5] reported 8% of patients developing vitiligo. However, in this study, the authors did not find any significant association of vitiligo with the sex of the donor, transplant cell source, the onset of GVHD, or GVHD classification.[5] Our patient had lichenoid GVHD and developed vitiligo 6 months post-HSCT. Similar to our report, Nagler et al.[6] and Aubin et al.[7] have reported vitiligo occurring in a patient with lichenoid GVHD 3 and 5 months post-transplant, respectively.

Nagler et al.[6] hypothesized that vitiligo occurs as an immune response selectively against melanocytes in the skin and hair. There is the appearance of antibodies in chronic GVHD, which could act as a triggering factor in the development of autoimmune diseases, and in the case of vitiligo to start an autoimmune response focused on the destruction of melanocytes. Adaptive immunity, particularly infiltrative cytotoxic CD8+, and CD4+ T cells, most likely plays a key role in melanocyte destruction.[8] The association of GVHD with multiple autoimmune diseases, such as scleroderma, Sjogren syndrome, Hashimoto thyroiditis, and Grave disease support this theory.[2] Our patient was not found to have any other autoimmune disease apart from vitiligo.

Adoptive passive transfer of donor immunity after allo-HSCT has also been hypothesized as an underlying mechanism leading to vitiligo.[9] However, our patient donor was HLA matched brother who never had vitiligo. Several additional theories have been proposed for depigmentation after allogeneic HSCT, including chemoradiation therapy and donor lymphocyte infusion induced vitiligo.[10]

Another possible pathogenesis mentioned in the literature is of T cell-mediated vitiligo in a patient with melanoma who developed melanocyte destruction after antigen-specific immunotherapy of melanoma.[11] The same mechanism could explain vitiligo developing in GVHD.

In the study by Čeović et al.,[5] the factors associated with the onset and progression of vitiligo were found to be the severity of GVHD and systemic immunosuppressants used, with vitiligo developing in patients with a higher National Institutes of Health (NIH) skin score and higher intensity of immunosuppressive treatment. For each increase in the level of NIH skin scoring, patients are 3.67 times more likely to have alopecia and/or vitiligo. Our patient had extensive skin involvement with an NIH skin score of 3, and had a recalcitrant course of cutaneous GVHD despite being on immunosuppressant, thus falling in high risk for vitiligo.

The most commonly affected sites of vitiligo in GVHD are periorbital, perioral, and acrofacial distributions.[2] Our patient had localized vitiligo limited to lips and scalp. Also, patients with vitiligo have been found to have more severe nail changes than other GVHD patients.[2] Our patient manifested with Beau’s lines on multiple fingernails.

The management options for vitiligo in the setting of chronic GVHD with a patient already on immunosuppressive therapy, are topical calcineurin inhibitors, and phototherapy. Transplantation and melanocyte grafting are other potential therapies. Our patient is being managed with 0.1% Tacrolimus ointment for both lip and scalp lesions and is on regular follow up.


  Conclusion Top


Vitiligo is an autoimmune disease developing in patients with chronic cutaneous GVHD, possibly secondary to the long-term immune dysregulation in chronic GVHD. The severity and activity of vitiligo in patients with GVHD depends on the magnitude of skin involvement. The psychological impact of the disease is immense and the stigma associated with vitiligo further impairs the quality of life of these patients and hence the need for prompt treatment. Further, close monitoring and screening are required for such patients as other autoimmune diseases can occur concurrently with vitiligo.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Rodrigues KS, Oliveira-Ribeiro C, Gomes SdAF, Knobler R. Cutaneous graft-versus-host disease: diagnosis and treatment. Am J Clin Dermatol 2018;19:33-50.  Back to cited text no. 1
    
2.
Zuo RC, Naik HB, Steinberg SM et al. Risk factors and characterization of vitiligo and alopecia areata in patients with chronic graft-vs-host disease. JAMA Dermatol 2015;151:23-32.  Back to cited text no. 2
    
3.
Gálvez K, Muñoz P, Vera V, Arce C. Vitiligo type cutaneous manifestation of chronic graft-versus-host disease. Case report. Rev Chil Pediatr 2018;89:113-7.  Back to cited text no. 3
    
4.
Kavand S, Lehman JS, Hashmi S, Gibson LE, El-Azhary RA. Cutaneous manifestations of graft versus host disease: role of the dermatologist. Int J Dermatol 2017;56:131-40.  Back to cited text no. 4
    
5.
Čeović R, Desnica L, Pulanić D, Serventi Seiwerth R, Ilić I, Grce M et al. High frequency of cutaneous manifestations including vitiligo and alopecia areata in a prospective cohort of patients with chronic graft-vs-host disease. Croat Med J 2016;57:229-38.  Back to cited text no. 5
    
6.
Nagler A, Goldenhersh M, Levi-Schaffer F, Bystryn JC, Klaus S. Total leucoderma: a rare manifestation of cutaneous chronic graft versus host disease. Br J Dermatol 1996;134:780-3.  Back to cited text no. 6
    
7.
Aubin F, Cahn JY, Ferrand C, Angonin R, Humbert P, Tiberghien P. Extensive vitiligo after ganciclovir treatment of GvHD in a patient who had received donor T cells expressing herpes simplex virus thymidine kinase. Lancet 2000;355:626-7.  Back to cited text no. 7
    
8.
Van Den Boorn JG, Konijnenberg D, Dellemijn TA et al. Autoimmune destruction of skin melanocytes by perilesional T cells from vitiligo patients. J Invest Dermatol 2009;129:2220-32.  Back to cited text no. 8
    
9.
Alajlan A, Alfadley A, Pedersen KT. Transfer of vitiligo after allogeneic bone marrow transplantation. J Am Acad Dermatol 2002;46:606-10.  Back to cited text no. 9
    
10.
Au W, Yeung C, Chan H, Lie A. Generalized vitiligo after lymphocyte infusion for relapsed leukaemia. Br J Dermatol 2001;145:1015-7.  Back to cited text no. 10
    
11.
Yee C, Thompson JA, Roche P et al. Melanocyte destruction after antigen-specific immunotherapy of melanoma: direct evidence of T cell–mediated vitiligo. J Exp Med 2000;192:1637-44.  Back to cited text no. 11
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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