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CASE REPORT
Year : 2019  |  Volume : 64  |  Issue : 4  |  Page : 324-327
Follicular graft-versus-host disease: A rare manifestation in a patient with the overlap subtype of chronic graft-versus-host disease


1 Department of Dermatology, Taipei Veterans General Hospital; Department of Dermatology, National Yang-Ming University, Taipei, Taiwan
2 Department of Dermatology, Taipei Veterans General Hospital; Department of Dermatology, National Yang-Ming University; Department of Dermatology, National Defense Medical Center, Taipei, Taiwan

Date of Web Publication5-Jul-2019

Correspondence Address:
Han-Nan Liu
Department of Dermatology, Taipei Veterans General Hospital, 201, Section 2, Shih-Pai Road, 112, Taipei
Taiwan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijd.IJD_412_18

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   Abstract 


Graft-versus-host disease (GVHD) is a frequent and potentially life-threatening complication of hematopoietic stem cell transplantation (HSCT). Although skin involvement is common, generalized follicular eruption as the major clinical manifestation is rare. However, it is important for clinicians to recognize it at the earliest to initiate an appropriate therapy. We report a case of a patient with multiple myeloma who developed extensive hyperkeratotic, lichenoid folliculocentric papules with perifollicular erythema on day 53 following an allogeneic HSCT. The overall clinical and histological findings were consistent with the overlap subtype of chronic follicular GVHD.


Keywords: Allogeneic hematopoietic stem cell transplantation, follicular graft-versus-host disease, overlap subtype


How to cite this article:
Ho YH, Chiu YW, Liu HN. Follicular graft-versus-host disease: A rare manifestation in a patient with the overlap subtype of chronic graft-versus-host disease. Indian J Dermatol 2019;64:324-7

How to cite this URL:
Ho YH, Chiu YW, Liu HN. Follicular graft-versus-host disease: A rare manifestation in a patient with the overlap subtype of chronic graft-versus-host disease. Indian J Dermatol [serial online] 2019 [cited 2019 Jul 19];64:324-7. Available from: http://www.e-ijd.org/text.asp?2019/64/4/324/262173





   Introduction Top


Graft-versus-host disease (GVHD) is the major complication of hematopoietic stem cell transplantation (HSCT), and a high mortality rate is observed in patients with severe GVHD.[1] The skin is one of the most frequently affected organs in both acute and chronic GVHD.[1] However, lichenoid follicular eruption as a major clinical manifestation of chronic cutaneous GVHD is rare; to our best knowledge, only seven cases have been reported to date [Table 1].[2],[3],[4],[5],[6] Here, we describe a patient with multiple myeloma who had a generalized follicular eruption that appeared on day 53 following HSCT.
Table 1: Reported cases of chronic follicular graft-versus-host disease

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   Case Report Top


A 51-year-old male Taiwanese patient was diagnosed as having kappa-light chain multiple myeloma, Durie-Salmon stage IIIB in February 2012. He had undergone several cycles of chemotherapy from 2012 to 2016 and had undergone autologous HSCT in 2012 and 2014 with partial response.

Owing to disease progression, he received an allogeneic HSCT in December 2016. Unfortunately, on day 53 following allogeneic HSCT, the patient developed extensive hyperkeratotic lichenoid folliculocentric papules with perifollicular erythema on the scalp, neck, trunk, and four limbs [Figure 1]a, [Figure 1]b, [Figure 1]c, and a dermoscopic examination showed a diffuse folliculocentric pattern with marked keratin plug formation [Figure 1]d. In addition, mottled hyperpigmentation on the face [Figure 1]e and a white lace-like pattern on the buccal mucosae and lips [Figure 1]f were also noted.
Figure 1: Hyperkeratotic, lichenoid folliculocentric papules with perifollicular erythema on the anterior chest wall, abdominal wall, and thighs (a and b); a higher magnification of the hyperkeratotic follicular papules with keratin plugging (arrows) on the anterior chest wall, (c) dermoscopic examination highlighted some marked keratin plugging (arrows), (d) mottled hyperpigmentation on the face, (e) a white lace-like pattern was noted on the surface of the lips (f)

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Histological examination of the follicular papules on the left anterior chest wall showed follicular infundibular dilatation with keratotic plugs, basal layer vacuolization, and few apoptotic keratinocytes in the follicular epidermis. Perivascular and perifollicular mononuclear cell infiltration and pigment incontinence in the upper dermis were also seen [Figure 2]a and [Figure 2]b. The histological picture was consistent with Grade 2 GVHD.
Figure 2: Histopathological findings showed follicular infundibular dilatation with keratotic plugs, basal layer vacuolization, and a few apoptotic keratinocytes in the follicular epidermis. Perivascular and perifollicular mononuclear cell infiltration and pigment incontinence in the upper dermis were also seen (a and b) (a: H and E, ×100, b: H and E, ×200)

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The patient also developed persistent upper abdominal pain with nausea and vomiting. Upper gastrointestinal (GI) endoscopy was performed which showed reflux esophagitis, LA Grade A, and duodenal ulcers. Computerized tomography of the abdomen revealed segmental wall thickening at the terminal ileum and proximal ascending colon that was suggestive of ileocolitis. Routine laboratory studies on day 60 following allogeneic HSCT revealed anemia (hemoglobin: 9.1 g/dl), thrombocytopenia (87 × 103/μl), elevated liver transaminases (aspartate aminotransferase, 194 U/l; alanine aminotransferase, 114 U/l), and serum alkaline phosphatase (106 IU/l). However, the total bilirubin level was in the normal range. In addition, blood cultures for microorganisms and polymerase chain reaction assay for the detection of serum cytomegalovirus or Epstein-Barr virus both showed negative findings.

A diagnosis of chronic follicular GVHD with the overlap syndrome was made according to the criteria of the National Institutes of Health (NIH) consensus project. The patient was then treated with oral cyclosporine 120 mg 12 hourly for 2 weeks and intravenous methylprednisolone 2 mg/kg/day for 2 weeks with a tapering regimen. Unfortunately, the patient died on day 130 after the allogeneic HSCT due to pneumonia with septic shock and acute respiratory and renal failure, when he was on oral sirolimus 2 mg/day and oral prednisolone 15 mg/day.


   Discussion Top


GVHD was previously classified into acute and chronic forms according to the symptoms that occur within or after 100 days following HSCT, respectively.[1],[2] However, this conventional classification has been challenged because of the recognition that signs of acute and chronic GVHD may occur outside these designated periods.[1],[2],[7] In an effort to more appropriately categorize the disease, the NIH consensus project has emphasized the clinical manifestations, rather than a set period, for classification.[1],[2],[7]

Therefore, acute GVHD is defined by the characteristic skin findings, GI tract or liver abnormalities, and the absence of any diagnostic or distinctive features of chronic GVHD.[1],[7] However, chronic GVHD is now classified into (i) classic chronic GVHD, with the presence of at least one diagnostic or distinctive manifestation of chronic GVHD and (ii) the overlap syndrome with features of both chronic and acute GVHD.[1],[7]

Cases of lichenoid follicular eruptions as a major clinical manifestation of GVHD are rare.[2],[6] The cause and pathogenesis of follicular GVHD are presently unclear. Sale et al. (1994) found that the parafollicular bulge was related to the presence of stem cell populations in that area, and it has been suggested that this region is an early target of GVHD.[3],[8]

Follicular GVHD could occur in both acute and chronic cutaneous GVHD.[2] Our case falls into the category of the overlap subtype of chronic follicular GVHD because the patient had clinical manifestations of chronic GVHD such as mottled hyperpigmentation on the face, lichen planus-like lesions on the lips and buccal mucosae, and thrombocytopenia. Moreover, the patient had some clinical features of acute GVHD such as abdominal pain, nausea, vomiting, and liver abnormalities.

The overlap subtype of chronic GVHD is thought to be associated with an adverse prognosis compared with classic chronic GVHD.[9],[10] A nine-center prospective analysis also found that patients with the overlap syndrome had a lower platelet count at the onset of GVHD.[10] Our patient had a low platelet count at the onset of GVHD and died shortly after the diagnosis was made.


   Conclusion Top


The follicular epithelium is rarely involved in cutaneous GVHD. It is important for clinicians to recognize a follicular involvement as early as possible to initiate an appropriate therapy.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Industry-University Cooperative Research Project, Taiwan (MOST 105-2628-B-010-016-MY3).

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
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. 1
    
2.
Llamas-Velasco M, Solano-López Morel GE, Gruber-Wackernagel A, Concha-Garzón MJ, Requena L, Cerroni L, et al. Comedonal graft-vs-host disease: A distinct clinical expression of a lichenoid follicular GVHD. J Cutan Pathol 2014;41:853-8.  Back to cited text no. 2
    
3.
Martí N, Martin JM, Monteagudo C, López V, Jordá E. Follicular graft-versus-host disease: A rare manifestation of chronic cutaneous graft-versus-host disease. Am J Dermatopathol 2008;30:620-1.  Back to cited text no. 3
    
4.
Miyazaki K, Higaki S, Maruyama T, Takahashi S, Morohashi M, Ito K, et al. Chronic graft-versus-host disease with follicular involvement. J Dermatol 1993;20:242-6.  Back to cited text no. 4
    
5.
Valks R, Vargas E, Fraga J, Penas PF, Fernandez-Herrera J. A follicular lichenoid eruption as manifestation of chronic graft-vs-host disease. Acta Dermatol Venereol 1998;78:386.  Back to cited text no. 5
    
6.
Cornejo CM, Kim EJ, Rosenbach M, Micheletti RG. Atypical manifestations of graft-versus-host disease. J Am Acad Dermatol 2015;72:690-5.  Back to cited text no. 6
    
7.
Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, et al. National institutes of health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 diagnosis and staging working group report. Biol Blood Marrow Transplant 2015;21:389-4010.  Back to cited text no. 7
    
8.
Sale GE, Beauchamp MD, Akiyama M. Parafollicular bulges, but not hair bulb keratinocytes, are attacked in graft-versus-host disease of human skin. Bone Marrow Transplant 1994;14:411-3.  Back to cited text no. 8
    
9.
Socié G, Ritz J. Current issues in chronic graft-versus-host disease. Blood 2014;124:374-84.  Back to cited text no. 9
    
10.
Pidala J, Vogelsang G, Martin P, Chai X, Storer B, Pavletic S, et al. Overlap subtype of chronic graft-versus-host disease is associated with an adverse prognosis, functional impairment, and inferior patient-reported outcomes: A chronic graft-versus-host disease consortium study. Haematologica 2012;97:451-8.  Back to cited text no. 10
    


    Figures

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