Published on 18/03/2015 by admin
Filed under Dermatology
Last modified 22/04/2025
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William Y-M Tang and Loi-yuen Chan
Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports
Angiolymphoid hyperplasia with eosinophilia (ALHE) was first described by Wells and Whimster in 1969. It is a benign vascular proliferation of unknown etiology with a characteristic component of epithelioid endothelial cells. It is an uncommon disease, so data on its natural course and treatment response are based on a small number of patients.
ALHE usually affects women in their third decade and presents as cutaneous papules or subcutaneous nodules, sometimes with inflammatory features, on the head, neck, and periauricular region. Involvement elsewhere is rare. Approximately 20% of patients have blood eosinophilia. Malignant transformation has not been observed. Although benign in nature, there may be disfigurement, bleeding, and pain. The etiology of ALHE is unknown, but neoplastic proliferation of vascular tissue, or reactive hyperplasia of vascular tissue secondary to trauma, infection, renin, or hyperestrogenic states have been proposed as causal factors.
The previous alleged overlap with Kimura’s disease is incorrect: ALHE and Kimura’s disease are separate clinicopathological entities. Kimura’s disease is a chronic inflammatory condition of unknown etiology often affecting young male Orientals, and typically presents as cervical lymphadenopathy and subcutaneous nodules in the head and neck region. It is often associated with blood and tissue eosinophilia, and raised serum IgE.
Treatment is usually required for ALHE, as spontaneous remission is rare. Complete surgical excision is preferred for persistent lesions. Recurrence may occur if excision is incomplete. Laser therapy, radiofrequency ablation, and cryotherapy are alternative surgical options. Other treatments that have positive therapeutic effects include topical and intralesional corticosteroids, topical imiquimod, topical tacrolimus, isotretinoin, intralesional interferon-α2b, intravenous anti-IL-5 antibody, suplatast tosilate and photodynamic therapy. Systemic corticosteroid and radiotherapy would seem appropriate only for severely disabling disease unresponsive to less toxic therapies.
Histopathology
Imaging
Microscopically, ALHE is characterized by a proliferation of capillaries and small vessels with plump, round, oval, or cuboidal endothelial cells that protrude into the lumen, creating a cobblestone appearance. There is also a perivascular lymphocytic and eosinophilic infiltrate.
The location and extent of underlying vascular anomalies may be assessed by angiography, angiomagnetic resonance imaging, and angio-computed tomography.
Owing to its predominant occurrence in females, hyper-estrogenic states may have a causative role in ALHE. However, successful treatment of ALHE using hormone therapy has not yet been reported.
Zarrin-Khameh N, Spoden JE, Tran RM. Arch Pathol Lab Med 2005; 129: 1168–71.
The authors report a 33-year-old woman who developed ALHE in her right ear during the second trimester of pregnancy. The lesion was completely excised. The authors also reviewed a total of five other ALHE cases associated with pregnancy. Lesions in some of these patients increased in size during pregnancy. One patient improved with cessation of oral contraceptive pills while another patient had her lesions reduced in size by half during the postpartum period. Two patients had skin biopsy which showed significant amounts of estrogen and progesterone receptors but not detected in the uninvolved skin.
Don DM, Ishiyama A, Johnstone AK, Fu YS, Abemayor E. Am J Otolaryngol 1996; 17: 240–5.
A review of eight patients with confirmed ALHE showed that low-dose irradiation, intralesional corticosteroids, and cryotherapy were not successful. The authors suggested that the preferred treatment is complete surgical extirpation. Recurrence is common when the lesions are inadequately excised.
Kaur T, Sandhu K, Gupta S, Kanwar AJ, Kumar B. J Dermatol Treat 2004; 15: 328–30.
A 35-year-old woman who presented with a 1 cm × 1.5 cm ALHE lesion on her left external ear canal for 1 year was treated with CO2 laser, energy 6 J and pulse duration 0.01 s, repeated at 0.1 s intervals for a total of 140 pulses. There was no recurrence during the 3-month follow-up period after this single treatment session.
Abrahamson TG, Davis DA. J Am Acad Dermatol 2003; 49: S195–6.
A 41-year-old woman with ALHE over her right ear received four treatments with a 585 nm pulsed dye laser (PDL) with a 5 mm spot size at energy densities 6.5–7.25 J/cm2 at 6-week intervals, and showed clearing of lesions. There was no clinical recurrence at 7 months after the fourth treatment.
Angel CA, Lewis AT, Griffin T, Levy EJ, Benedetto AV. Dermatol Surg 2005; 31: 713–16.
A 72-year-old man with ALHE for 1 year not responding to intralesional steroid was successfully treated with two sessions of ultralong PDL (595 nm). There was no recurrence 3 years after treatment. The longer wavelength produces deeper penetration into dermal tissue and more uniform coagulation necrosis across the entire diameter of the targeted blood vessel.
Kadurina MI, Dimitrov BG, Bojinova ST, Tonev SD. J Cosmet Laser Ther 2007; 9: 107–11.
This is the first review of Nd : YAG laser for treating ALHE. A 31-year-old woman with ALHE on her right ear was treated with 1064 nm Nd : YAG, 6 mm round spot size with two pulses of 7.0 ms with a 20 ms interpulse delay, and a fluence of 100–150 J/cm2. A total of five treatments were given altogether with an interval of 30 days between the procedures. The patient showed complete remission after 1 year of follow-up.
Alcántara González J, Boixeda P, Truchuelo Díez MT, Pérez García B, Jaén Olasolo P. Lasers Med Sci 2011; 26: 285–90.
The sequential laser combines 595 nm PDL with 1064 nm Nd : YAG and targets structures at different dermal levels using two different wavelengths. Greater effectiveness and lower recurrence rate are possible with the Nd : YAG laser which allows the destruction of deeper vessels than PDL. Three patients with ALHE were treated with this sequential laser system. Complete resolution was presented in two of them 3 years after their last treatment, and the other one showed a marked improvement.
Treatment using PDL is based on the principle of selective photothermolysis, causing destruction of blood vessels in the lesions. PDL should be a first-line treatment for ALHE due to its reasonably good results with low incidence of side effects. Combination with Nd : YAG laser produces better results. Carbon dioxide and argon laser have also been used with success in treating ALHE, but their use is limited because of the greater chance of post-treatment scarring.
Gencoglan G, Karaca S, Ertekin B. Dermatology 2007; 215: 233–5.
A 48-year-old man with several ALHE lesions behind his right ear, measuring 0.5–1 cm in diameter, was treated with 5% imiquimod cream twice daily, 5 days per week for 2 weeks. He had complete clinical resolution, and no recurrence was observed during 2 years of follow-up. The underlying mechanism may be related to the immunomodulating and anti-angiogenic effect of imiquimod.
Mashiko M, Yokota K, Yamanaka Y, Furuya K. Br J Dermatol 2006; 154: 803–4.
A 33-year-old Japanese woman with ALHE over her left ear for a year was treated with 0.1% tacrolimus ointment twice daily. The lesions disappeared within 4 months. Continuous application resulted in no recurrence in 9 months. The underlying therapeutic mechanism may be due to reduction of eosinophils in tissue and suppressed eosinophil function.
El Sayed F, Dhaybi R, Ammoury A, Chababi M. Head Face Med 2006; 2: 32.
The authors report a 32-year-old man with multiple ALHE lesions treated with isotretinoin 0.5 mg/kg/day for 1 year with complete resolution of scalp nodules. Other lesions on the cheeks and preauricular region remained stable and were surgically removed. The success of isotretinoin was due to its anti-angiogenic properties via a reduction of vascular endothelial growth factor production by keratinocytes.
Khunger N, Pahwa M, Jain RK. Dermatol Surg 2010; 36: 422–5.
Three patients with ALHE were treated with radiofrequency ablation (RFA) after intralesional sclerotherapy with 3% polidocanol. One to four sessions of treatment was required to achieve complete response. No recurrence was seen after a follow-up period of 6 months to 2 years. The synergistic effect is due to sclerosants treating the deeper vascular component while RFA ablates the lesion.
Oguz O, Antonov M, Demirkesen C. J Eur Acad Dermatol Venereol 2007; 21: 1277–8.
Interferon-α is the first-line treatment in benign angioproliferative disorders. Local intralesional injection of interferon-α2b was reported effective for a 27-year-old female with occipital lesions of ALHE. Recurrence of lesions 9 years later were noted but this time the response to repeated interferon-α2b treatment was poor.
Including this one, two cases of ALHE treated by interferon-α2b have been reported so far. In both cases the efficacy was reduced when treating recurrent lesions.
Braun-Falco M, Fischer S, Plötz SG, Ring J. Br J Dermatol 2004; 151: 1103–4.
Interleukin-5 is the major cytokine involved in the production, mobilization, and activation of eosinophils. A single intravenous dose of 750 mg anti-IL-5 antibody was given to a 76-year-old Caucasian man with a painful and itchy pulsatile 7 cm × 6 cm × 3 cm ALHE nodule behind his left ear. The patient became asymptomatic the next day, and there was a slight softening of the lesion. The benefit lasted for approximately 3 weeks.
Harada K, Kambe Y, Takeda H, Nakano H, Hanada K. Dermatology 2004; 208: 176–7.
Suplatast tosilate is an anti-allergic agent on the market in Japan. It was reported to exert an inhibitory effect of IL-4 and -5 production in helper T cells, resulting in reduced eosinophil infiltration and suppression of IgE production in B cells. A 32-year-old man with ALHE not responding to topical steroid, cryotherapy, indomethacin farnesil, and oral betamethasone received suplatast tosilate 300 mg/day. A reduction of pruritus was noted after 1 week and a reduction of nodule size after 1 month of treatment. The skin lesions almost disappeared after 5 months of treatment and the dose was reduced to 200 mg/day.
Sotiriou E, Apalla Z, Patsatsi A, Panagiotidou DD, Ioannides D. Clin Exp Dermatol 2009; 34: e629–31.
Photodynamic therapy (PDT) causes suppression of tumor growth by damaging endothelial cells in the tumor neovasculature. A 60-year-old woman with multiple ALHE lesions on forehead was treated with two sessions of aminolevulinic acid PDT, with a 2-week interval. Marked improvement, though not complete regression, was achieved 8 weeks after treatment and maintained at 4 months after treatment. The moderate response achieved in this study could be due to poor penetration of the photosensitizer to the deep part of the lesion.
Conill C, Toscas I, Mascaro J Jr, Vilalta A, Mascaro J. J Eur Acad Dermatol Venereol 2004; 18: 584–5.
The authors reported a 32-year-old Caucasian woman with multiple ALHE nodules involving the skin, subcutaneous tissue, and bone of the distal phalanx of the fingers treated successfully with orthovoltage radiation therapy (40 Gy in 20 fractions) and without any side effects after 9 years of follow-up.
Considering the benign nature of ALHE and the potential carcinogenicity of radiotherapy, the latter should only be given when other treatment modalities have failed.
Treatment of Skin Disease Comprehensive Therapeutic Strategies 4e
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Surgery
Laser therapy
Corticosteroid, topical or intralesional
Cryotherapy
Imiquimod
Tacrolimus
Isotretinoin
Radiofrequency ablation and sclerotherapy
Interferon-α2b
Anti-IL-5 antibody
Suplatast tosilate
Photodynamic therapy
Radiotherapy
