INTRODUCTION

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a vascular disease of unknown etiology, also known as epithelioid hemangioma and is a rare clinicopathological entity that associates benign vascular proliferation with an eosinophilic inflammatory infiltrate. Initially described in 1969 by Wells and Whimster, it is a benign acquired vascular tumor. It is a rare condition that mainly affects middle-aged Caucasian women. It poses real diagnostic problems with proliferations of other types and its therapeutic management remains uncodified [1]. In this paper, we report a short series of five cases.

CASE REPORT

Over a period of two years, we collected five cases of lymphoid hyperplasia with eosinophilia. Age ranged from 32 to 54 years, with an average of 39 years. The patients were all female. The skin lesions were erythematous or purple papules or nodules, located at the level of the ear and retro-auricular for all patients, with the presence of a lesion on the scalp in two patients (Figs. 1a and 1b). Dermoscopic examination revealed a polymorphic vascular pattern consisting of dotted and linear vessels and streaks and bright white areas (Figs. 2a and 2b). Pathological studies revealed that all lesions contained a vascular proliferation with an epithelioid appearance of the endothelial cells associated with an inflammatory infiltrate containing mainly PNE, except in one case (Fig. 3). A complete blood count was performed in all patients who showed hypereosinophilia in only one patient. All patients were placed on combined treatment consisting of local β-blockers, short-term oral corticosteroid therapy, and a local topical corticosteroid. The evolution was marked by a complete remission in two patients after one month of beginning treatment. For the three other patients, the evolution is in progress (Figs. 4a and 4b).

	Figures 1: (a and b) Clinical aspect of the retro-auricular angiomatous nodules.
	Figures 2: (a and b) Dermoscopic image showing linear and dotted vessels and bright white strictures.
	Figure 3: Histological appearance showing vascular hyperplasia of variable size in the dermis with a polymorphic inflammatory infiltrate rich in eosinophils.
	Figures 4: (a and b) Clinical control after one month of treatment.

DISCUSSION

ALHE is a rare disease, indolent in nature and with a prolonged clinical course. It predominates in women in 70% of cases and generally occurs during the third to fifth decade of life, with extremes of age varying between 12 and 78 years.

The origin has been variously attributed to previous trauma, hyperestrogenemia, pregnancy or oral contraceptives, infectious agents, and atopy [2]. The clinical presentation is variable, with single or multiple lesions (as in our observation) in the form of papules, subcutaneous angiomatous nodules or erythematous plaques, painless, sometimes hemorrhagic or pruritic, always progressive. It preferentially affects the cervico-facial region, especially the ear area, as illustrated in our cases [3]. Half of the patients develop skin lesions grouped in the same region. Multiple locations are found in only 20% of cases [4]. The extremities may exceptionally be affected. Sometimes, the nodules be associated with lichenoid lesions [5], yet extra cutaneous cases have been reported, affecting the orbit, oral mucosa, parotid gland, colon, and bones. Dermoscopically a polymorphic vascular pattern was described as being composed of dots and red blood cells, regular and irregular linear vessels, reticular vessels on a pinkish-white background, the bright white structures and streaks. The different morphologies described of the bright white structures are white lines, shiny, bright white areas, and rosettes [6]. These patterns were observed in the patients in our series with a predominance of the vascular structure in three patients. The histological study of ALHE finds two components: vascular and inflammatory.

The vascular component consists of a proliferation of vessels whose wall frequently contains smooth muscle fibers and abundant deposits of mucin. Endothelial cells are turgid, protruding into the vessel lumen. They have a large, vesicular nucleus and abundant eosinophilic cytoplasm, hence the epithelioid or histiocytoid appearance that has been given to them. Sometimes endothelial cells form clumps without a detectable vascular lumen. The basal lamina of these vessels is clear, even thickened. By electron microscopy, the presence of Weibel–Pallade bodies is revealed in the cytoplasm of endothelial cells [7].

The inflammatory component is made of a polymorphic inflammatory infiltrate consisting of polyphenotypic lymphocytes, plasma cells, polynuclear eosinophils, and mast cells within a fibrous connective stroma. The relative importance of the signs depends on the stage of the lesion, more vascular in young lesions, richer in lymphocytes, and fibrosis in older lesions [1].

The differential diagnosis of ALHE, based on clinical and histopathological manifestations, may arise with capillary hemangioma, pyogenic granuloma with satellite lesions, bacterial angiomatosis, and Kaposi’s sarcoma [8]. In practice, the main differential diagnosis of ALHE is Kimura disease, initially described in the Chinese literature, then widely known as Kimura disease after the description of a series of patients first by Japanese authors Kimura and Sceto in China in 1937 [3]. This is a rare chronic inflammatory disease of unknown etiology, predominantly affecting people of Asian race. It also presents in the form of nodules deeply embedded in the subcutaneous tissue of the head and neck, associated with regional lymphadenopathy, and damage to the salivary glands [4]. The terms ALHE and Kimura disease have been confused for a long time, currently being described as two distinct entities. Demitsu et al. brought together distinctive epidemiological, clinical, and histopathological elements (Table 1) [3].

Table 1: A comparison of the clinical and histopathological features of Kimura’s disease and angiolymphoid hyperplasia with eosinophilia [3].

The care of ALHE is non-standardized and is based either on specific monotherapy or on combined treatments. Despite the multiplicity of therapeutic means, effectiveness is poor and recurrences are frequent. Surgical excision was the most frequently reported therapeutic intervention, especially for single lesions, yet the margins of the lesions are difficult to identify given the vascular nature of this pathology. Several cases treated effectively by pulsed dye laser, YAG laser, or CO₂ laser, sclerotherapy, photodynamic therapy, radiotherapy, or even radiofrequency have also been reported, particularly for superficial lesions. The most frequently used medical treatments, more or less effectively, are mainly general or intralesional corticosteroid therapy, with partial regressions and frequent recurrences upon discontinuation, and intralesional interferon alpha-2a or -2b, also with recurrences after stopping, oral retinoids, Pentoxyfilline, Indomethacin, Mepolizumab (anti IL-5), Suplatast Tosilate (anti IL-4 and IL-5 available in Japan), Methotrexate, Bevacizumab intra-lesional and intra-lesional bleomycin. Recently, cases treated effectively with imiquimod cream 5% have been reported, and some isolated therapeutic success has also been obtained with propranolol [9]. This is due to their vasoconstrictor, anti-angiogenic and antiproliferative effect leading to the apoptosis of the endothelial cells of the capillaries of β-blockers [10–13]. However, no article has mentioned the use of β-blockers locally, and our series was the first to use a combined treatment consisting of local β-blockers, topical corticosteroids, and oral corticosteroid therapy for a short duration not exceeding a month and a half with significant improvement.

CONCLUSION

In our series, ALHE often affected middle-aged subjects, with a female predominance. The clinical and histological presentation of our patients was consistent with the literature. It appeared from our series that treatment with local β-blockers associated with oral and local corticosteroid therapy could be a therapeutic alternative to surgical treatment, which is not feasible in a topography at the level of the ear, which is predominant.

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