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Table of Contents
Year : 2021  |  Volume : 39  |  Issue : 2  |  Page : 99-100

Recurrent angiolymphoid hyperplasia with eosinophilia with CCR4 expression

Department of Dermatology, St. Marianna University School of Medicine, Kanagawa, Japan

Date of Submission01-May-2020
Date of Decision02-Dec-2020
Date of Acceptance29-Dec-2020
Date of Web Publication26-Feb-2021

Correspondence Address:
Dr. Tomomitsu Miyagaki
Department of Dermatology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-Ku, Kawasaki, Kanagawa 216-8511
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ds.ds_58_20

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How to cite this article:
Nakajima K, Kuroda E, Takeuchi S, Kadono T, Miyagaki T. Recurrent angiolymphoid hyperplasia with eosinophilia with CCR4 expression. Dermatol Sin 2021;39:99-100

How to cite this URL:
Nakajima K, Kuroda E, Takeuchi S, Kadono T, Miyagaki T. Recurrent angiolymphoid hyperplasia with eosinophilia with CCR4 expression. Dermatol Sin [serial online] 2021 [cited 2023 May 29];39:99-100. Available from: https://www.dermsinica.org/text.asp?2021/39/2/99/310239

Dear Editor,

Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon benign vasoproliferative condition, characterized by solitary or multiple pink to red-brown papules or nodules, most commonly on the head.[1] Histologically, ALHE shows prominent lymphocytic and eosinophilic infiltration in addition to the proliferation of histiocytoid endothelial cells.[1] The etiology and immunological abnormalities are not well-known. Here, we present the case of ALHE with CCR4 expression.

A 54-year-old woman referred to our department with a 2-year history of multiple red nodules without preceding trauma in the right temporal artery region. Clinical examination revealed three dome-shaped purpuric red nodules in line with the right temporal artery region [Figure 1]a. A skin biopsy specimen showed the proliferation of blood vessels with enlarged histiocytoid endothelial cells and massive infiltration of lymphocytes and eosinophils around the vessels in the dermis [Figure 2]a and [Figure 2]b. Lymphatic follicles and evident vasculitis were not found. Based on these findings, the diagnosis of ALHE was made. A careful interview revealed a past history of a red nodule on the right temporal region 10 years ago. Excisional biopsy had found the proliferation of blood vessels with mild infiltration of lymphocytes and eosinophils in the dermis [Figure 2]c and [Figure 2]d. Although she had been diagnosed as having hemangioma at that time, considering that vascular component predominated in early ALHE,[1] we concluded that the nodule 10 years ago was also ALHE. She was treated with intralesional corticosteroids, resulting in flattening of the nodule [Figure 1]b.
Figure 1: Clinical manifestations. (a) Three dome-shaped red nodules arranged along the right temporal artery. (b) Clinical presentation of the patient's right temporal region after intralesional corticosteroids.

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Figure 2: Histopathological findings. (a and b) Histopathology of the nodules showing the proliferation of blood vessels with enlarged histiocytoid endothelial cells and massive infiltration of lymphocytes and eosinophils around the vessels in the dermis (hematoxylin and eosin, ×40 and ×200, respectively). (c and d) Histopathology of the nodule 10 years ago showing the proliferation of blood vessels partially with enlarged endothelial cells and mild infiltration of lymphocytes and eosinophils around the vessels in the dermis (hematoxylin and eosin, ×40 and ×200, respectively). (e-j) Much GATA3 (e and f), less T-bet (g and h), and moderate CCR4 (i and j) expression in infiltrating lymphocytes in the lesion of angiolymphoid hyperplasia with eosinophilia (×100 and ×400, respectively).

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The important differential diagnosis of ALHE is Kimura disease. Kimura disease and ALHE are similar conditions that involve the head and neck region and share several histopathologic features including lymphoeosinophilic infiltration and vascular proliferation. Based on these similarities, ALHE and Kimura disease were once considered to represent a disease spectrum. However, ALHE is currently regarded to be clinically and pathologically distinct from Kimura disease. For example, Kimura disease clinically presents a large subcutaneous mass, while ALHE shows papules or nodules like our case. Pathologically, Kimura disease is characterized by lymphoid follicles with germinal center formation and eosinophilic abscess and lacks the characteristic cytomorphological alterations of the endothelial cells seen in ALHE.

On the other hand, analysis on the differences in the immunological abnormalities between ALHE and Kimura disease has been limited. Katagiri et al. first found that mRNA expression levels of Th2 cytokines, such as interleukin (IL)-4, IL-5, and IL-13 in peripheral blood are increased in Kimura disease and that they decreased after treatment.[2] In addition, Th2 cytokine-producing CD4+ T-cells are increased in the blood and IL-5 expression is upregulated in the lesional lymph node.[3],[4] These reports indicate that polarization to Th2 may be involved in the development of Kimura disease. On the other hand, there have been no reports detecting the presence of Th2 cells or Th2 cytokine expression in patients with ALHE, except for the report describing that Th2 cytokine inhibitor was effective in some ALHE cases.[5] To assess the characters of lymphocytes in ALHE, we performed immunohistochemical analysis for GATA3, a master gene of Th2 cells, and T-bet, a master gene of Th1 cells in our case using mouse anti-GATA3 antibody (Nichirei Biosciences, Tokyo, Japan, clone L50-823) and rabbit anti-T-bet antibody (Cell Signaling, Danvers, MA, USA, clone D6N8B). There was much higher number of GATA3-positive cells compared to T-bet-positive cells in infiltrating lymphocytes [Figure 2]e, [Figure 2]f, [Figure 2]g, [Figure 2]h. GATA3/T-bet ratio was 2.72. We also examined the expression of CCR4, which is a representative Th2 chemokine receptor and express in eosinophil-rich diseases such as atopic dermatitis and asthma,[6],[7] using a CCR4 staining kit (Kyowa Medex, Tokyo, Japan). We found that the moderate number of infiltrating lymphocytes expressed CCR4 [Figure 2]i and [Figure 2]j. Although it is hard to draw a conclusion as polarization toward Th2 cells was demonstrated at one point of the long disease course, these results suggest that Th2 cells might be associated with ALHE. In addition, mogamulizumab, a monoclonal antibody against CCR4, could be used in refractory or relapsing ALHE cases.

ALHE and Kimura disease could share common immunological features in lymphocytes. Consistently, the coexistence of ALHE and Kimura disease in the same patient has been reported.[8] However, further studies with large sample sizes are desirable to establish whether Th2 cells are involved in ALHE development.

Declaration of patient consent

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

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Conflicts of interest

There are no conflicts of interest.

  References Top

Guo R, Gavino AC. Angiolymphoid hyperplasia with eosinophilia. Arch Pathol Lab Med 2015;139:683-6.  Back to cited text no. 1
Katagiri K, Itami S, Hatano Y, Yamaguchi T, Takayasu S. In vivo expression of IL-4, IL-5, IL-13 and IFN-gamma mRNAs in peripheral blood mononuclear cells and effect of cyclosporin A in a patient with Kimura's disease. Br J Dermatol 1997;137:972-7.  Back to cited text no. 2
Ohta N, Fukase S, Suzuki Y, Ito T, Yoshitake H, Aoyagi M. Increase of Th2 and Tc1 cells in patients with Kimura's disease. Auris Nasus Larynx 2011;38:77-82.  Back to cited text no. 3
Yamazaki K, Kawashima H, Sato S, Tsunoda H, Yoshimura Y, Higuchi M, et al. Increased CD45RO+CD62L+CD4+ T-cell subpopulation responsible for Th2 response in Kimura's disease. Hum Immunol 2013;74:1097-102.  Back to cited text no. 4
Bito T, Kabashima R, Sugita K, Tokura Y. Angiolymphoid hyperplasia with eosinophilia on the leg successfully treated with T-helper cell 2 cytokine inhibitor suplatast tosilate. J Dermatol 2011;38:300-2.  Back to cited text no. 5
Sugaya M, Morimura S, Suga H, Kawaguchi M, Miyagaki T, Ohmatsu H, et al. CCR4 is expressed on infiltrating cells in lesional skin of early mycosis fungoides and atopic dermatitis. J Dermatol 2015;42:613-5.  Back to cited text no. 6
Panina-Bordignon P, Papi A, Mariani M, Di Lucia P, Casoni G, Bellettato C, et al. The C-C chemokine receptors CCR4 and CCR8 identify airway T cells of allergen-challenged atopic asthmatics. J Clin Invest 2001;107:1357-64.  Back to cited text no. 7
Marka A, Cowdrey MCE, Carter JB, Lansigan F, Yan S, LeBlanc RE. Angiolymphoid hyperplasia with eosinophilia and Kimura disease overlap, with evidence of diffuse visceral involvement. J Cutan Pathol 2019;46:138-42.  Back to cited text no. 8


  [Figure 1], [Figure 2]

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