Angiolymphoid Hyperplasia With Eosinophilia 

Updated: Apr 11, 2019
Author: Gauri Panse, MBBS, MD; Chief Editor: William D James, MD 

Overview

Background

Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon, vasoproliferative, idiopathic condition that manifests in adults as isolated or grouped papules, plaques, or nodules in the skin of the head and neck. Most patients present with lesions in the skin of the periauricular region,[1] forehead, or scalp. Rare sites of involvement include the hands,[2] shoulders, breasts, penis, oral mucosa, the scrotum.[3] Extracutaneous sites have also been noted to include the orbit, peripheral arteries, the colon, the mandible, the lacrimal gland, the parotid gland, and throat.

A distinct pathologic entity, ALHE is marked by a proliferation of blood vessels with distinctive large endothelial cells. These blood vessels are accompanied by a characteristic inflammatory infiltrate that includes eosinophils. The lesion is benign but may be persistent and is difficult to eradicate.

While ALHE shows some similarity to Kimura disease, it is generally regarded as a separate entity.[4, 5] While ALHE lesions are superficial, Kimura disease involves deeper tissues such as lymph nodes, salivary glands, and the subcutis. Patients also typically have peripheral blood eosinophilia and elevated serum IgE. However, a 2006 report describes ALHE involving the nail bed and underlying bone.[6] Only one report describes a patient with simultaneous tumors, one consistent with Kimura disease and one consistent with ALHE.[7] Such findings challenge whether or not Kimura disease and ALHE represent a spectrum of the same disease.

Pathophysiology

Although angiolymphoid hyperplasia with eosinophilia (ALHE) may be a benign tumor, numerous factors suggest that it is an unusual reactive process. Approximately half the patients have multifocal lesions that are grouped anatomically. ALHE has occurred following various forms of trauma or infection. Histologically, most cases of ALHE show damaged and/or tortuous arteries and veins at the base of the lesion, suggesting that arteriovenous shunting may play a role in the pathogenesis. Hyperestrogenemia (eg, in pregnancy[8, 9] or with oral contraceptive use) may foster growth. Additionally, the distinctive inflammatory infiltrate in ALHE appears to be an intrinsic (not secondary) component of the lesion. Approximately 20% of patients have blood eosinophilia. However, immunoglobulin E levels are not elevated.[10]

Additionally, three reported cases describe follicular mucinosis and ALHE occurring in the same biopsy specimen.[11] T-cell gene rearrangement was detected in 5 of 7 cases of ALHE in one series, raising the possibility that ALHE or a subset of ALHE may be a low-grade T-cell lymphoma,[12] though T-cell gene rearrangement and monoclonality may be seen in reactive phenomenon. Another recent report of ALHE on the scrotum also demonstrated T-cell clonality.[3] Interestingly, two reports of ALHE occurring in patients with either a subsequent[13] or metasynchronous[14] diagnosis of peripheral T-cell lymphoma pose the question of whether ALHE could be an early form of T-cell lymphoma. It should be stressed that the vast majority of cases are entirely benign.

Etiology

Angiolymphoid hyperplasia with eosinophilia (ALHE) is idiopathic. Whether this condition is a neoplastic or reactive state is uncertain; a reactive cause is favored.

Epidemiology

Frequency

Although frequency is unknown, cases have been reported worldwide. Angiolymphoid hyperplasia with eosinophilia (ALHE) is uncommon but not rare; it may be more common in Japan than in other countries.

Race

ALHE is seen most commonly in Asians, followed by whites. Although less common, blacks can develop ALHE.

Sex

ALHE is slightly more common in females; however, a male predominance has been noted in selected Asian studies.

Age

ALHE presents most commonly in patients aged 20-50 years, with mean onset of 30-33 years. This condition is rare in elderly patients and in the non-Asian pediatric population. It only rarely is seen in children, though its occurrence in a 2-year-old boy on the arm post vaccination[15] and in an 8-month-old Japanese infant[16] have been reported.

Prognosis

Surgical excision is the reported to be the most effective treatment for angiolymphoid hyperplasia with eosinophilia (ALHE). Yet, treatment failure rates as high as 41% are reported for this mode of therapy. Laser approaches are less successful in the management of ALHE, with pulsed-dye laser having the lowest reported failure rate at 50%, followed by carbon dioxide laser at 55%.[17]

ALHE can persist for years, but serious complications do not occur. A few cases of nephropathy have been reported in patients with ALHE; however, the association is not strong. This is in contrast to the related entity, Kimura disease, for which the association with nephrotic syndrome is strong. Of note, although, coexistence of Kimura disease and ALHE in the same patient, along with minimal-change glomerulopathy, has been reported.[18]

 

Presentation

History

Patients with angiolymphoid hyperplasia with eosinophilia (ALHE) typically present with an expanding flesh-color to erythematous nodule or group of nodules, usually in the vicinity of the ear (see the image below). The lesion(s) may be associated with pain or pruritus. Uncommon symptoms include pulsation and spontaneous bleeding.

Angiolymphoid hyperplasia with eosinophilia typica Angiolymphoid hyperplasia with eosinophilia typically exhibits flesh-color to erythematous nodules in the vicinity of the ear.

Physical Examination

Angiolymphoid hyperplasia with eosinophilia (ALHE) typically appears as dome-shaped, smooth-surfaced papules or nodules (see the image below). Approximately 85% of lesions occur in the skin of the head and neck; most of them are on or near the ear or on the forehead or scalp. The extremities are the next most common site. Involvement at other sites is rare. However, case reports have described ALHE affecting the penis[19] and the conjunctiva.[20]

Pronounced erythema and nodularity due to angiolym Pronounced erythema and nodularity due to angiolymphoid hyperplasia with eosinophilia.

The lesions range from erythematous to brown, and they may be eroded or crusted. Approximately 80% of patients present with isolated lesions, while the remaining patients usually demonstrate grouped papules or nodules in a single region. Rarely, the lesions may be pulsatile. Most lesions are 0.5-2 cm in diameter, with a range of 0.2-8 cm. Larger nodules tend to be deeply centered within the subcutis.

Complications

Conductive hearing loss resulting from obstruction of the auditory canal can occur in severe cases of angiolymphoid hyperplasia with eosinophilia (ALHE). Diplopia and proptosis was noted in one patient with orbital involvement.

 

DDx

Diagnostic Considerations

Other considerations include the following:

  • Angiosarcoma

  • Hemangioendothelioma

  • Hemangioma

  • Metastatic carcinoma to the skin

  • Kaposi sarcoma[10]

  • IgG4-related skin disease[21]

Differential Diagnoses

 

Workup

Laboratory Studies

A CBC count reveals eosinophilia in approximately 20% of patients with angiolymphoid hyperplasia with eosinophilia (ALHE). Given that some patients with ALHE have also been found to have renal disease, urinalysis could be considered.

Procedures

The clinical presentation of papules around the ears may suggest angiolymphoid hyperplasia with eosinophilia (ALHE), but a biopsy is required to establish the diagnosis.

Histologic Findings

Angiolymphoid hyperplasia with eosinophilia (ALHE) shows characteristic histologic features, including a proliferation of small blood vessels, many of which are lined by enlarged endothelial cells with uniform ovoid nuclei and intracytoplasmic vacuoles. These distinctive endothelial cells have been described as having a hobnail appearance. In addition, a perivascular and interstitial infiltrate composed primarily of lymphocytes and eosinophils (see the image below) is present. Eosinophils typically comprise 5-15% of the infiltrate. Rarely, they can account for as much as 50% of the infiltrate. Occasionally, the infiltrate is devoid of eosinophils. Lymphoid aggregates with or without follicle formation are typical. A subset of ALHE, including multiple eruptive lesions, may show increased cellularity.[22]

In 2018, immunohistochemical staining for FOSB, with nuclear staining in ALHE, was reported as a useful marker in distinguishing ALHE from its morphologic mimics.[23]

Histologically, angiolymphoid hyperplasia with eosinophilia is marked by thick-walled blood vessels with protuberant endothelium and a prominent inflammatory infiltrate, which typically includes eosinophils.

Histologically, angiolymphoid hyperplasia with eos Histologically, angiolymphoid hyperplasia with eosinophilia is marked by thick-walled blood vessels with protuberant endothelium and a prominent inflammatory infiltrate, which typically includes eosinophils.
 

Treatment

Approach Considerations

The most effective treatment for angiolymphoid hyperplasia with eosinophilia (ALHE) is generally surgical excision, but its success rate is limited. Pulsed dye laser and other destructive modalities are effective treatment options in select patients and topical medications have been reported to be successful.

Medical Care

Treatment of angiolymphoid hyperplasia with eosinophilia (ALHE) is often challenging. Rarely, spontaneous resolution occurs, obviating the need for medical intervention in some cases. While surgery is considered the treatment of choice, management with intralesional corticosteroids may be a viable alternative in some cases, especially in cosmetically sensitive sites on the head and neck.[24] Irradiation has been used but is not optimal. A very promising treatment is oral propranolol, which has been used very successfully for infantile hemangiomas. One report noted no recurrence up to two years after oral propranolol therapy.[25] Topical timolol has also been shown to have some success.[26] Other local treatments that have been reported include topical imiquimod,[27] topical tacrolimus, and intralesional interferon alfa-2a.[28, 29] Systemically, treatment with systemic corticosteroids, anti–interleukin 5 antibody (mepolizumab),[30] and isotretinoin[31] has also been reported.

Surgical Care

Simple surgical excision is sometimes used, but the lesions tend to recur.[17] Mohs micrographic surgery has been attempted in order to address ALHE through better margin control. Excisions that include the arterial and venous segments at the base of the lesion prove most efficacious. The pulsed-dye laser[32] and carbon dioxide laser have been used with some success. 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) has also been reported to show some success.[33] Cryosurgery[34] and electrosurgery have also been reported. More recently, intralesional radiofrequency ablation was also found to produce cosmetically pleasing and lasting results.[35, 36]