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Sultan Qaboos Univ Med J
Sultan Qaboos Univ Med J
Sultan Qaboos University Medical Journal
2075-051X
2075-0528
Sultan Qaboos University Medical Journal, College of Medicine & Health Sciences

10.18295/squmj.12.2023.090
squmj2408-405-408
Case Report
Successful Treatment of Angiolymphoid Hyperplasia with Eosinophilia Associated with Scalp Demodicosis Using Cryotherapy and Topical Metronidazole
Al Kharusi Salma T. 1*
Al Lamki Aya A. 1
Al Rajaibi Raqiya M. 1
Al Ajmi Zakiya I. 2
1 Dermatology Department, Rustaq Polyclinic, Rustaq, Oman
2 Department of Histopathology, Royal Hospital, Muscat, Oman
* Corresponding Author’s e-mail: s.t.alkharusi@gmail.com
8 2024
29 8 2024
24 3 405408
13 6 2023
03 10 2023
11 10 2023
08 11 2023
© Copyright 2024, Sultan Qaboos University Medical Journal, All Rights Reserved
2024
https://creativecommons.org/licenses/by-nd/4.0/ This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License.
Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare, benign, vasoproliferative tumour. We report a 25-year-old female patient who reported in 2021 to a dermatology clinic in Rustaq, Oman, with multiple, grouped, erythematous dome-shaped papules and nodules of 6 months duration on the left temporo-occipital region. Biopsy findings were consistent with a diagnosis of ALHE with evidence of Demodex mite infestation in the sebaceous ducts. The patient demonstrated significant improvement following 7 weeks of treatment with multiple cryotherapy sessions and topical application of metronidazole gel. This case suggests that scalp demodicosis may represent a novel trigger for the development of ALHE.

Angiolymphoid Hyperplasia with Eosinophilia
Mite
Scalp
Kimura Disease
Cryosurgery
Metronidazole
Case Report
Oman
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pmcAngiolymphoid hyperplasia with eosinophilia (ALHE) is a benign, uncommon, proliferation of blood vessels of uncertain aetiology and pathogenesis.1–3 It is characterised by the presence of single or multiple, cutaneous, or subcutaneous, red-to-brown coloured papules or nodules commonly located in the head and neck region. Although many treatment modalities have been suggested, no standardised approach has yet been established.2 We describe a case of ALHE alongside scalp demodicosis who was successfully treated.

Case Report

A 25-year-old female patient presented to a dermatology clinic in Rustaq, Oman, in 2021 with multiple, itchy, pearly papules on her scalp of approximately 6 months duration. She reported ulcerations and discrete bleeding after scratching due to pruritus and denied any history of systemic symptoms or local trauma. Clinical examination of the scalp showed multiple, grouped, erythematous papules and nodules, with an average diameter of 1 cm, located on the left temporo-occipital region [Figure 1]. The systemic examination was unremarkable and there was no evidence of regional or systemic lymphadenopathy. A complete blood count (including eosinophils), renal function test, serum immunoglobulin E levels, HIV screening and urine analysis were all normal. The patient had not received any previous treatments for these lesions prior to presentation to the current clinic.

Following a biopsy of one of the lesions, the histopathological examination revealed the proliferation of variable-sized blood vessels lined by plump histiocytoid endothelial cells, as well as inflammatory infiltrates comprising lymphocytes and eosinophils in the dermis [Figure 2A–E]. The biopsy also revealed evidence of Demodex mite infestation in the sebaceous ducts [Figure 2F]. Based on these histopathological and clinical features, a diagnosis of ALHE and scalp demodicosis was made.

The patient was treated with 10 sessions of cryotherapy (each session consisted of 2 freeze-thaw cycles per week for each lesion). In addition, twice-daily application of a topical metronidazole gel was incorporated into the treatment regimen. The patient showed remarkable clinical improvement within 7 weeks [Figure 3]. She was subsequently followed-up for the next year with no signs of recurrence or new lesions appearing.

Informed patient consent regarding the publication of this case was obtained.

Discussion

Also known as epithelioid haemangioma, ALHE is a rare, benign, vasoproliferative neoplasm first described in 1969. It is common in the Asian population and usually affects middle-aged adults.1–3

ALHE usually presents as single or multiple well-defined, erythematous or brownish papulonodular lesions and can be pulsatile.4 The condition is usually localised to the head and neck, mainly in the periauricular region; however, it has rarely been reported to affect other parts of the body, such as the colon, hands, penis and oral mucosa.5,6 Overall, ALHE can be asymptomatic but may also present with spontaneous bleeding, itchiness or pain.2

Currently, the aetiology and pathogenesis of ALHE are not fully understood. The commonly accepted hypothesis is that it is a reactive vascular hyperplasia to certain stimuli, such as trauma, hyperoestrogenism, vascular malformation, reaction to insect bite and infections such as scabies or HIV.7–9 However, several researchers have raised concerns with this explanation due to the presence of clonal T-cell populations in many cases, with some authors proposing that certain types of ALHE might be due to a benign- to low-grade malignant T-cell lymphoproliferative disorder.10,11

The differential diagnoses of ALHE include epithelioid haemangioendotheliomas, pyogenic granulomas, Kaposi sarcomas and Kimura disease (KD).4 The latter is considered the main differential diagnosis of ALHE due to their clinical and histopathological similarities.12 Previously, ALHE and KD were assumed to be the same disorder, but now these two entities can be distinguished due to the distinctive features of the latter condition, as KD presents with subcutaneous masses in the head and neck region, alongside regional and, rarely, systemic lymphadenopathy, peripheral eosinophilia and elevated serum immunoglobulin E levels, and is infrequently associated with nephrotic syndrome.12–15 Although ALHE and KD are two separate diseases, there are some reported cases of overlapped presentation, suggesting that both diseases could be a variant of the same reactive vascular lymphoid proliferation disorder.16

The histopathologic picture of the lesion demonstrates deep dermal and subcutaneous lobular proliferation of capillary size blood vessels of variable sizes. These are lined by plump epithelioid endothelial cells exhibiting enlarged vesicular nuclei and some with vacuolated cytoplasm. The surrounding stroma shows foci of haemorrhage and moderate infiltration by lymphocytes and eosinophils. There are no lymphoid follicles identified (KD demonstrates a marked lymphoid follicular hyperplasia). The inflammatory cells may penetrate the lumen of blood vessels, blocking or rupturing them.12 This phenomenon is not seen in the current case’s biopsy, though there is evidence of haemorrhage which may suggest vascular destruction elsewhere in the lesion.

Spontaneous regression of ALHE is sometimes reported.5 In other cases, choice of treatment depends on the position, size, depth and number of lesions, in addition to histological features and skin pigmentation. Many potential treatment modalities have been suggested, with variable success; however, recurrence is commonly noted. Thus, surgical excision remains the best modality of treatment due to low recurrence rates.2 Other modalities include administration of topical and intralesional corticosteroids, topical tacrolimus or imiquimod, oral isotretinoin, interferon alpha-2b, radiotherapy, thalidomide, photodynamic therapy, propranolol, laser therapy (using neodymium-doped yttrium aluminium garnet, carbon dioxide, ultralong pulsed dye or copper vapor lasers), electrosurgery and cryosurgery.4,15–23

In the current case, given that superficial vascular proliferation was a major feature, cryotherapy was deemed the best treatment option as it causes necrosis of vascular lesions, provoking an inflammatory response and lesion clearance.24 In particular, cryotherapy is indicated for multiple ALHE lesions with a prominent vascular component or for lesions located in sites difficult for excision. One of the benefits of cryosurgery is the satisfactory cosmetic result with minimal scarring, as freezing allows for the collagen fibre network of the skin to remain intact.25

To the best of the authors’ knowledge, the current case represents the first report of ALHE associated with scalp demodicosis. Demodex mites have been implicated in other pathological conditions of the scalp, including dermatitis, sebaceous cysts, rosacea, carcinomas and seborrheic keratosis.26 Moreover, the interaction between the pilosebaceous unit cells and Demodex mite antigens is believed to affect the secretion of inflammatory cytokines, such as tumour necrosis factor-alpha and interleukin-8, and toll-like receptor expression.27 Such inflammatory triggers are critical for eosinophil recruitment, itself crucial in the development of ALHE. Eosinophil cytotoxic proteins, such as eosinophil cationic protein, are believed to play a role in AHLE angiogenesis.9

Conclusion

ALHE represents a challenging clinical and histological diagnosis. Despite its benign nature, there is no established therapeutic modality for ALHE because of its uncertain aetiopathogenesis. In the current case, the treatment combination of cryotherapy and topical metronidazole gel was successful in resolving both the ALHE lesions as well as the Demodex mite infestation, presumed to be the primary trigger. The case presented herein serves to emphasise that cryotherapy can be considered a safe, effective and reliable treatment option for ALHE patients in which there is a prominent vascular component. Moreover, the potential role of Demodex mites in the pathogenesis of this condition should be considered in further research.

Figure 1 Photograph of the left temporo-occipital region showing multiple erythematous papules and nodules (angiolymphoid hyperplasia with eosinophilia lesions before treatment).

Figure 2 Haematoxylin and eosin stains of the biopsied lesion at (A) × 2 magnification showing dense deep dermal and subcutaneous proliferation; (B & C) × 5 and × 10 magnification, respectively, showing the lobular proliferation is composed of variable-size blood vessels surrounded by scattered inflammatory cells; (D) × 40 magnification showing the lining endothelial cells exhibiting enlarged vesicular nuclei and vacuolated cytoplasm with evidence of haemorrhage; (E) × 40 magnification showing the surrounding inflammation is composed of lymphocytes admixed with many eosinophils and (F) × 4 magnification showing Demodex mites (arrow) in the sebaceous ducts.

Figure 3 Photograph of the left temporo-occipital region showing significant resolution of angiolymphoid hyperplasia with eosinophilia lesions following 7 weeks of treatment using cryotherapy and topical metronidazole.

AUTHORS’ CONTRIBUTION: STK evaluated and diagnosed the patient, while RMR contributed to managing the patient. STK, AAL and RMR drafted the manuscript and performed the literature review. ZIA contributed with the histopathology diagnosis and reporting. All authors approved the final version of the manuscript.
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References

1 Barnes L Koss W Nieland ML Angiolymphoid hyperplasia with eosinophilia: a disease that may be confused with malignancy Head Neck Surg 1980 2 425 34 10.1002/hed.2890020512 7364594
2 Adler BL Krausz AE Minuti A Silverberg JI Lev-Tov H Epidemiology and treatment of angiolymphoid hyperplasia with eosinophilia (ALHE): A systematic review J Am Acad Dermatol 2016 74 506 12e11 10.1016/j.jaad.2015.10.011 26685720
3 Wells GC Whimster IW Subcutaneous angiolymphoid hyperplasia with eosinophilia Br J Dermatol 1969 81 1 14 10.1111/j.1365-2133.1969.tb15914.x 5763634
4 Granieri G Oranges T Panduri S Loggini B Janowska A Dini V Unusual presentation of angiolymphoid hyperplasia with eosinophilia treated with intralesional and topic corticosteroid combination therapy Dermatol Reports 2021 13 9063 10.4081/dr.2021.9063 34659673
5 Satpathy A Moss C Raafat F Slator R Spontaneous regression of a rare tumour in a child: Angiolymphoid hyperplasia with eosinophilia of the hand: Case report and review of the literature Br J Plast Surg 2005 58 865 8 10.1016/j.bjps.2004.11.014 16086996
6 Bartralot R Garcia-Patos V Hueto J Huguet P Raspall G Castells A Angiolymphoid hyperplasia with eosinophilia affecting the oral mucosa: Report of a case and a review of the literature Br J Dermatol 1996 134 744 8 10.1046/j.1365-2133.1996.88804.x 8733384
7 Onishi Y Ohara K Angiolymphoid hyperplasia with eosinophilia associated with arteriovenous malformation: A clinicopathological correlation with angiography and serial estimation of serum levels of renin, eosinophil cationic protein and interleukin 5 Br J Dermatol 1999 140 1153 6 10.1046/j.1365-2133.1999.02880.x 10354088
8 Chou CY Lee WR Tseng JT Case of angiolymphoid hyperplasia with eosinophilia associated with scabies infestation J Dermatol 2012 39 102 4 10.1111/j.1346-8138.2011.01275.x 21950730
9 D’Offizi G Ferrara R Donati P Bellomo P Paganelli R Angiolymphoid hyperplasia with eosinophils in HIV infection AIDS 1995 9 813 14 10.1097/00002030-199507000-00023 7546431
10 Gonzalez-Cuyar LF Tavora F Zhao XF Wang G Auerbach A Aguilera N Angiolymphoid hyperplasia with eosinophilia developing in a patient with history of peripheral T-cell lymphoma: evidence for multicentric T-cell lymphoproliferative process Diagn Pathol 2008 3 22 10.1186/1746-1596-3-22 18510751
11 Gil F Rato M Monteiro A Parente J Garcia H An unusual cause of papules on the face Acta Dermatovenerol Croat 2019 27 40 1 31032791
12 Bastos JT Rocha CRMD Silva PMCE Freitas BMP Cassia FF Avelleira JCR Angiolymphoid hyperplasia with eosinophilia versus Kimura’s disease: A case report and a clinical and histopathological comparison An Bras Dermatol 2017 92 392 4 10.1590/abd1806-4841.20175318 29186256
13 Seregard S Angiolymphoid hyperplasia with eosinophilia should not be confused with Kimura’s disease Acta Ophthalmol Scand 2001 79 91 3 10.1034/j.1600-0420.2001.079001091.x 11167299
14 Buder K Ruppert S Trautmann A Bröcker EB Goebeler M Kerstan A Angiolymphoid hyperplasia with eosinophilia and Kimura’s disease – a clinical and histopathological comparison J Dtsch Dermatol Ges 2014 12 224 8 10.1111/ddg.12257_suppl 24580875
15 Bahloul E Amouri M Charfi S Boudawara O Mnif H Boudawara T Angiolymphoid hyperplasia with eosinophilia: Report of nine cases Int J Dermatol 2017 56 1373 8 10.1111/ijd.13800 29057451
16 Reddy PK Prasad AL Sumathy TK Shivaswamy KN Ranganathan C An Overlap of Angiolymphoid Hyperplasia with Eosinophilia and Kimura’s Disease: Successful Treatment of Skin Lesions with Cryotherapy Indian J Dermatol 2015 60 216 10.4103/0019-5154.152574
17 Kadurina MI Dimitrov BG Bojinova ST Tonev SD Angiolymphoid hyperplasia with eosinophilia: Successful treatment with the Nd:YAG laser J Cosmet Laser Ther 2007 9 107 11 10.1080/14764170701297440 17558761
18 Vanhooteghem O Flagothier C de la Brassinne M Angiolymphoid hyperplasia with eosinophilia of the scalp: Promising results of long-pulsed tunable dye laser treatment J Eur Acad Dermatol Venereol 2009 23 954 5 10.1111/j.1468-3083.2009.03141.x 19453797
19 Alcántara González J Boixeda P Truchuelo Díez MT Pérez García B Jaén Olasolo P Angiolymphoid hyperplasia with eosinophilia treated with vascular laser Lasers Med Sci 2011 26 285 90 10.1007/s10103-011-0892-3 21347722
20 Wang S Li W Angiolymphoid hyperplasia with eosinophilia successfully treated with tacrolimus ointment J Eur Acad Dermatol Venereol 2010 24 237 10.1111/j.1468-3083.2009.03384.x 19686258
21 Cooper SM Dawber RP Millard P Angiolymphoid hyperplasia with eosinophilia treated by cryosurgery J Eur Acad Dermatol Venereol 2001 15 489 90 10.1046/j.1468-3083.2001.03403.x 11763402
22 Woźniacka A Omulecki A Torzecka JD Cryotherapy in the treatment of angiolymphoid hyperplasia with eosinophilia Med Sci Monit 2003 9 CS1 4 12552249
23 Oguz O Antonov M Demirkesen C Angiolymphoid hyperplasia with eosinophilia responding to interferon-alpha2B J Eur Acad Dermatol Venereol 2007 21 1277 8 10.1111/j.1468-3083.2007.02171.x 17894734
24 Sharma VK Khandpur S Guidelines for cryotherapy Indian J Dermatol Venereol Leprol 2009 75 90
25 Shepherd JP Dawber RP Wound healing and scarring after cryosurgery Cryobiology 1984 21 157 69 10.1016/0011-2240(84)90207-4 6713945
26 Karaman U Celik T Calik S Sener S Aydin NE Daldal UN Saçli Deri Biyopsi Orneklerinde Demodex spp Demodex spp. in hairy skin biopsy specimens Turkiye Parazitol Derg 2008 32 343 5 19156609
27 Aktaş Karabay E Aksu Çerman A Demodex folliculorum infestations in common facial dermatoses: acne vulgaris, rosacea, seborrheic dermatitis An Bras Dermatol 2020 95 187 93 10.1016/j.abd.2019.08.023 32113677
