An 8-year follow-up of IgG4-related skin disease presented with generalized ALHE-like eruptions: successful treatment of glucocorticoid and cyclophosphamide.

Immunoglobulin gamma (IgG) type 4-related disease (IgG4-RD) is a chronic immunologic systemic disorder that could affect multiple organs, which may cause irreversible organ damage or even death. Skin involvement is rare and associated especially with systemic disease. The dermatologist must be equipped to recognize IgG4-RD to prevent delayed identification and treatment. This case reports a very rare case of IgG4-related skin disease (IgG4-RSD) presenting with a generalized angiolymphoid hyperplasia with eosinophilia (ALHE)-like lesions in a middle-aged male patient with no other organ involvement. He was treated with oral glucocorticoid and cyclophosphamide, which resulted in complete remission. No relapse and disease progression were seen with a follow-up for 8 years.

Enfermedad de Kimura en paciente no asiática / Kimura’s disease in a non-asian patient

La enfermedad de Kimura es un trastorno inflamatorio benigno poco frecuente, de etiología desconocida y que afecta principalmente a sujetos de origen asiático. Clínicamente se manifiesta como masas subcutáneas, indoloras, sobre todo en la zona de cabeza y el cuello. Suele acompañarse de linfadenopatías, y aumento de los niveles de eosinófilos e IgE en sangre periférica. Se presenta un caso de enfermedad de Kimura, diagnosticado en una mujer caucásica tras la exéresis-biopsia de una masa mandibular de gran tamaño. Describir esta patología ayudará a incluir la misma en el diagnóstico diferencial de masas, sobre todo a nivel cervico-facial, favoreciendo así su adecuado manejo diagnóstico-terapéutico. (AU)

Kimura’s disease is a rare benign inflammatory disorder of unknown etiology that mainly affects individuals of Asian origin. Clinically it manifests as subcutaneous, painless masses, especially in the head and neck area. It is usually accompanied by lymphadenopathies and an increase in eosinophil and IgE levels in peripheral blood. A case of Kimura’s disease is presented, diagnosed in a Caucasian woman after the excision-biopsy of a large mandibular mass. Describing this pathology will help to include it in the differential diagnosis of masses, especially at the cervico-facial area, thus favoring its adequate diagnostic-therapeutic management. (AU)

[Diagnostic challenges in Kimura's disease]. / Wyzwania w diagnostyce choroby Kimury.

Ultra-rare diseases occur with a frequency of 2 in 100 000 people or less. Kimura's disease (KD) affects less than 1 in 1 000 000 people. It is a benign, chronic inflammatory soft tissue disorder, accompanied by eosinophilia, raised immunoglobulin E (IgE) titer and the presence of painless subcutaneous masses, usually in the head and neck region. The disease was first described in 1948 and occurs at higher rates in Asia than in America or Europe. A CASE REPORT: A 35-year-old man without past medical history presented to his family doctor for bilateral cervical lymphadenopathy accompanied by eosinophilia. Despite subsequent in-depth diagnostics, including fine-needle aspiration biopsy (FNAB) of the lymph nodes, the definitive diagnosis was not initially established. After following 2 months, a selective lymphadenectomy was performed, putting Hodgkin's lymphoma under suspicion. The image of positron emission tomography coupled with computed tomography (PET-CT) corresponded to this diagnosis. Due to the lack of all the criteria necessary to make a diagnosis, another histopathological consultation was done. The image of the lymph nodes suggested reaction-inflammatory changes. Due to the presence of a triad of signs (reactive lymphadenopathy, several eosinophils in the paracortic zone, vascular proliferation), differential diagnosis was recommended, among others towards the Kimura's disease. A series of examinations allowed to exclude lymphadenopathy of parasitic, allergic and hyperplastic hematopoietic system aetiology. The patient started steroid therapy with a good effect at first. However, after the recurrence of the disease, the patient was qualified to intensify the immunosuppressive treatment. CONCLUSIONS: In the described case, the intensive diagnostic process and the thorough analysis of the test results relatively quickly led to the correct diagnosis. This enabled the implementation of appropriate treatment and prevented the initiation of empirical therapy for the originally diagnosed Hodgkin's lymphoma.

A retrospective study of 20 patients with Kimura's disease from China.

BACKGROUND: Kimura's disease (KD) is an eosinophilic proliferative lymphoid disease with rare incidence rate and nonspecific clinical symptoms. OBJECTIVES: To investigate the clinical characteristics, diagnosis, treatment, and prognosis of KD. MATERIALS AND METHODS: The clinical manifestations, laboratory examination, imaging examination, proposed treatment, and prognosis of 20 patients with KD treated in our hospital were retrospectively analyzed. RESULTS: All cases showed painless masses. The proportion of peripheral blood eosinophils rose in 18 cases (90%), the eosinophil count increased in 14 cases (70%) and the serum immunoglobulin E (IgE) levels were significantly increased in 5 patients (100%). Pathological examination revealed follicular hyperplasia, eosinophils infiltration, and tiny vessels proliferation in KD samples. CONCLUSIONS: KD should be considered when the patients suffered head and neck subcutaneous painless mass, increased peripheral blood eosinophils and raised serum IgE level. Pathological examination is the golden standard for diagnosing KD. Surgical intervention, medical treatments, and radiotherapy may be effective for KD treatment. SIGNIFICANCE: This study might shed a light on improving the diagnosis and treatment for KD.

Percutaneous ethanol sclerotherapy is a promising treatment for recalcitrant angiolymphoid hyperplasia with eosinophilia.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare benign vascular proliferation, which manifests as characteristic red nodules and papules, mostly located on the scalp and periauricular regions. Patients seek treatment for both aesthetic and functional reasons, as lesions may ulcerate, bleed and itch. Many therapeutic approaches have been reported, with variable success, and relapse remains a troublesome issue. The aim of this study was to report our experience treating ALHE using percutaneous ethanol sclerotherapy (PES). We present a retrospective case series of three patients treated with PES (1-2 treatment sessions each). All patients had tried and failed other treatments prior to this intervention, but following PES treatment, all patients demonstrated significant improvement, which was sustained at follow-up (range 8-17 months after first treatment). Adverse effects were tolerable and transient. This case series demonstrates PES as a promising treatment for recalcitrant ALHE.

The clinicopathological characteristics of Kimura disease in Chinese patients.

INTRODUCTION: Kimura disease (KD) is a rare idiopathic inflammatory disorder of unknown etiology. Unusual presentations of KD might cause diagnostic difficulty or be misdiagnosed as malignancy if clinical suspicion is insufficiently high. Here, we aimed to determine the clinicopathological features of Chinese KD patients to reveal further insights into the natural history and treatment of this disease. METHOD: The clinical data of 46 cases of KD diagnosed at Peking Union Medical College Hospital from January 1980 to December 2018 were analyzed retrospectively through case record review. RESULTS: Of 46 cases, 40 were male and six were female. The age at onset ranged from 2 to 56 years (median 27 years). All patients presented with either single (26.1%) or multi-focal (73.9%) subcutaneous masses. Twenty-nine (63.0%) cases presented with head and neck subcutaneous masses, and 9 cases (19.6%) involved different parts of the body. Parotid, submandibular, and lacrimal gland involvement occurred in 17 (37.0%), 3 (6.5%), and 2 cases (4.3%), respectively. Nephrotic syndrome was present in three cases (6.5%), and thromboembolism was present in five cases (10.9%). During follow-up, thirteen patients (13/28, 46.4%) relapsed over 1-13 years (median 8.5 years). The recurrence rate in patients receiving corticosteroids, surgery, and combined surgery and radiotherapy was 30.8%, 66.7%, and 50.0%, respectively. One patient was diagnosed with T cell lymphoma 1 year after diagnosis of KD. CONCLUSIONS: KD is characterized by subcutaneous masses but it is also a systemic disease. Given the high rate of recurrence and reported association with lymphoma, patients require careful long-term follow-up.Key Points• Kimura disease (KD) is a rare inflammatory disorder of unknown etiology that is endemic in Asia.• Clinicians must regard and manage KD as a systemic disease.• There is no consensus on optimal treatments and further studies are necessary to improve outcomes.• Given the high rate of recurrence and reported association with lymphoma, patients require careful long-term follow-up.

Combination of electrocoagulation and photodynamic therapy for angiolymphoid hyperplasia with eosinophilia in the external ear.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is an inflamed vascular tumefaction of uncertain pathogenesis and is characterized by higher recurrence rates after surgical excision or other approaches. In the present study, we performed a new approach by combining electrocoagulation with photodynamic therapy (PDT) for the treatment of two ALHE patients. They had multiple treatments in the past and had poor therapeutic effects with relapse each time. After informed consent was obtained, electrocoagulation was used to remove the superficial lesions of ALHE, and the first session of PDT was immediately applied to the lesion. A total of three sessions of PDT were applied to each patient with an interval of 7-10 days. Through more than 12 months of follow-up, the two patients showed complete regression, and no recurrence was observed. Meanwhile, patients were very satisfied with the cost and cosmetic outcomes of the combination treatment. Based on our results, we strongly recommend the combination of electrocoagulation with PDT as a favourable treatment for ALHE, especially in the external ear and other areas that are inconvenient for routine surgery.

An Unusual Cause of Papules on the Face.

Dear Editor, Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare, locally proliferating disorder that affects predominantly the head and neck region (1,2). There seems to be a higher incidence in middle-aged Caucasian women (2,3). A 28-year-old female patient with no relevant personal or family medical history and only taking an oral contraceptive, presented to our department with multiple, well delimited, infracentimetric erythematous papules with a smooth surface on the left frontal, temporal, and preauricular regions (Figure 1). The lesions had appeared 7 months earlier, with progressive growth in number and dimensions since. The patient reported pruritus and denied previous trauma, topical application of any sort, insect bite at these locations, and any other accompanying symptoms. A thorough physical examination revealed no additional abnormalities. An excisional biopsy of one of the left temporal papules revealed a prominent lymphoid component, with a dense multinodular infiltrate in the superficial and deep dermis, with reactive germinative centers of considerable dimensions (Figure 2). Large and atypical lymphocytes were confined to the germinative centers, with reactive characteristics. Lymphocytes surrounding the germinative centers were predominantly small, accompanied by a significant number of scattered eosinophils. CD3 and CD20 immunohistochemical staining revealed B-cells predominantly in the nodular areas corresponding to the germinative centers, while T-cells displayed a diffuse peripheral distribution. There was severe neovascularization, with thick-walled vascular channels lined by enlarged plump endothelial cells with an "epithelioid" appearance. These findings supported the diagnosis of angiolymphoid hyperplasia with eosinophilia (ALHE). Laboratory workup did not show any abnormalities, including eosinophilia or elevation of immunoglobulin E levels. Due to pruritus and aesthetic concerns, surgical excision of the larger and most symptomatic papules was performed. The patient was assured of the benign nature of the disease and informed about the possible development of new lesions. Kept under clinical surveillance, the patient remained free of new lesions at 6-month follow-up. ALHE generally presents as solitary or multiple erythematous or hyperpigmented dome-shaped papulonodules. Lesions can be pruritic or painful and do not tend to resolve spontaneously (4). The pathogenesis of ALHE remains controversial, although some theories have been suggested. The most widely accepted hypothesis is that it is an angioproliferative process, accompanied by an inflammatory infiltrate, reactive to several stimuli (3). Some authors believe it is an allergic reaction, but no specific sole agent has been identified (5). Others claim ALHE may represent a T-cell lymphoproliferative disorder of benign or low-grade malignant nature (6). Some recent studies suggest that ALHE pathogenesis may be related to a vascular malformation secondary to a subcutaneous arteriovenous shunt (1-3). Histologically there are both vascular and inflammatory components, with an abnormal vascular proliferation and diffuse lymphocytic infiltrates with eosinophils. The vascular component is formed by capillaries clustered around arterial or venous vessels, dilated and atypical, with a protruded endothelium (3). The main differential diagnosis of ALHE is Kimura's disease, and there has been some discussion regarding the relationship between these two entities due to their clinical and histopathological similarities. However, most studies currently agree that they are distinct diseases. The differential diagnosis also includes angiosarcoma, particularly the epithelioid variant, epithelioid hemangioendothelioma, Kaposi sarcoma, pyogenic granuloma, and cutaneous metastasis (3). ALHE usually requires treatment as spontaneous regression, although reported in the literature, is rare (1,3). Many options have been suggested, with variable levels of success, but there is no definitive treatment for this condition (2). Surgical excision is the preferred choice, but recurrence may happen if the excision is incomplete (1). Mohs micrographic surgery with excision of abnormal vessels at the base of the lesion may be more effective in reducing recurrences (4). Other treatments reported include laser therapy (pulsed dye, CO2, copper vapor), systemic or intralesional corticosteroid injection, cryotherapy, imiquimod, tacrolimus, isotretinoin, radiotherapy, interferon alfa 2a, anti-interleukin-5 antibody, photodynamic therapy, and methotrexate (1). In the present case the diagnosis of ALHE was established through the conjunction of clinical and histological findings. Although a rare entity, its predominantly facial involvement in young adults and the absence of a satisfactory treatment can produce a significant impact that can include the quality of life of the patients.

Angiolymphoid hyperplasia with eosinophilia: a case report.

BACKGROUND: Angiolymphoid hyperplasia with eosinophilia is a benign neoplasm that includes blood vessel proliferation and a dense eosinophilic inflammatory infiltrate. Mostly, it affects middle-aged adults manifesting as flesh/plum-colored pruritic nodules and papules, most commonly affecting the ear and the periauricular area. CASE PRESENTATION: In this case, we report a 13-year-old Caucasian girl with bilateral, huge, protruding, and yellowish nostril masses which were peculiar in location and of gross appearance. At first, the disease proved to be a diagnostic dilemma. After making a diagnosis of angiolymphoid hyperplasia with eosinophilia, the disease also proved to be a therapeutic dilemma. It did not respond to oral prednisolone or to oral indomethacin, and it proved to be resistant to topical steroids. Although surgery is the standard therapeutic approach, it recurred despite multiple surgical attempts. However, the only regimen that seemed to partially control the lesion was intralesional steroids combined with topical tacrolimus ointment. CONCLUSIONS: Angiolymphoid hyperplasia with eosinophilia proves a therapeutic dilemma, because there is a large variety of proposed treatments, yet there is not enough data on most of them. Although the disease is not deadly by itself, it usually presents with disfiguring lesions that grimly affect the patient's quality of life. This warrants further research and efforts to find an effective cure and a unified therapeutic approach.

Multiple Grouped Scalp Nodules in a Middle-Aged Man: A Rare Case of Angiolymphoid Hyperplasia with Eosinophilia.

An otherwise healthy man in his 50s presented complaining of pruritic lesions on the left side of his scalp. The lesions had slowly been growing in size over the preceding 30 years. They would occasionally bleed, and this is what ultimately prompted him to seek medical advice. Physical examination revealed multiple aggregated and soft, flesh-colored nodules on the left posterior auricular area of the scalp (Figure 1). No appreciable clinical lymphadenopathy was identified on examination. A shave biopsy of one of the nodules was performed for diagnostic clarification.

Eosinophilic hyperplastic lymphogranuloma: Clinical diagnosis and treatment experience of 41 cases.

PURPOSE: The purpose of this study was to investigate the clinical features of eosinophilic hyperplastic lymphogranuloma (EHLG) in the head and neck. MATERIALS AND METHODS: Collecting the patients who diagnose with EHLG by pathological examination. The EHLG patients with the masses involved regions, such as involved inguinal region, chest wall, abdominal wall, anterior superior iliac spine or clavicle, instead of head and neck were excluding. All of the participants will sign the informed consent form. The history data includes: clinical history, blood routine test, pathological examination, and recurrence will be collected. RESULTS: A total of 41 patients of EHLG were included. These patients predominantly presented as an enlarging and painless single or multiple masses with a history of repeated swelling. There were the complaint of itchy skin and pigmentation. The routine blood test showed that the percentage value of eosinophil increased in almost patients including 26 cases had raised absolute eosinophil count. The serum level of lgE was increased in 29 cases remarkably. With the methods of treatments, 36 patients received surgical excision, 3 patients accepted hormonotherapy, and another 2 patients for radiotherapy. The recurrence of EHLG was in 9 patients. CONCLUSIONS: EHLG is a rare disease. The clinical manifestation (itchy skin and pigmentation) and increased eosinophil play critical values to the diagnosis of EHLG. Confirmed diagnosis always depends on pathological examination. Surgery is a preferred treatment, while low dose of radiotherapy is necessary for preventing relapse after operation and hormonotherapy.

Comparison of the efficacy of different treatment modalities for Kimura's disease.

The objective of this study was to investigate the clinical features of Kimura's disease in the head and neck region and to compare the local recurrence rate between three therapies used for the treatment of this disease. The clinicopathological information of 46 hospitalized patients suffering from Kimura's disease in the head and neck region over a 10-year period was reviewed retrospectively. All lesions were clinically observed in the head and neck region. These 46 patients underwent a total of 58 treatments; nine patients underwent multiple treatments due to local recurrence. Of the 58 treatments, 32 involved surgical excision alone, 24 involved surgical excision and postoperative low-dose radiotherapy (20-40Gy), one was a combination of ultrasound-guided core needle biopsy and radiotherapy, and one was a combination of incisional biopsy and subsequent radiotherapy. During the follow-up period, nine patients suffered 16 local recurrences. The recurrence rate of surgical excision combined with low-dose radiotherapy was much lower than that of surgical excision alone or radiotherapy alone (both P<0.05). It is concluded that Kimura's disease is a benign condition with a good prognosis, and surgical excision combined with postoperative low-dose radiotherapy is associated with the lowest local recurrence rate in the treatment of this disease.

Comparison of Local Recurrence Rate of Three Treatment Modalities for Kimura Disease.

Eosinophilic hyperplastic lymphogranuloma, also known as Kimura disease, is a benign and chronic inflammatory condition, predominantly involving the head and neck region. Surgical excision, radiotherapy (RA), surgical resection combined with low-dose postoperative radiotherapy and oral corticosteroids are 4 treatment modalities reported to control this disease effectively. Local recurrence, however, is common and the optimum treatment for Kimura disease is controversial. Thus, the present meta-analysis was performed to identify the treatment modality associated with the lowest local recurrence. Electronic databases (Cochrane Library, Wiley Online Library, PubMed, Chinese National Knowledge Infrastructure, and Wanfang Data) were searched. Data were also obtained from other sources such as related references and communication with the relevant authors. Two reviewers screened the literature according to preselected criteria. All studies involving different treatments for Kimura disease were collected. After data extraction and research quality assessment, the meta-analysis of 22 studies involving 570 patients was conducted using STATA 12.1 software. Meta-analysis revealed that administration of RA or surgical excision alone were inferior in controlling local recurrence compared with surgical resection combined with postoperative RA (risk ratio (RR) = 2.72; 95% confidence interval (CI), 1.47-5.04 and RR = 4.72; 95% CI, 2.53-8.82). Surgical excision alone did not show significant advantage in controlling local recurrence compared with RA alone (RR = 2.13; 95% CI, 0.88-5.17). Surgical resection combined with postoperative RA is superior to either surgery or RA alone in treating Kimura disease. More large scale prospective randomized controlled trials, however, should be conducted to assess the long-term effects and safety issues.

Epidemiology and treatment of angiolymphoid hyperplasia with eosinophilia (ALHE): A systematic review.

BACKGROUND: Current knowledge of angiolymphoid hyperplasia with eosinophilia (ALHE) derives from retrospective reports and case series, leading to a nonevidence-based treatment approach. OBJECTIVE: We sought to systematically review the literature relating to cutaneous ALHE to estimate its epidemiology and treatment outcomes. METHODS: A literature search of PubMed, EMBASE, Web of Science, and Google Scholar was conducted. Articles detailing cases of histologically confirmed cutaneous ALHE were included. RESULTS: In all, 416 studies were included in the review, representing 908 patients. There was no sex predominance among patients with ALHE. Mean age at presentation was 37.6 years. There was a significant association between presence of multiple lesions and pruritus, along with bleeding. Surgical excision was the most commonly reported treatment for ALHE. Treatment failure was lowest for excision and pulsed dye laser. Mean disease-free survival after excision was 4.2 years. There were higher rates of recurrence postexcision with earlier age of onset, longer duration of disease, multiple lesions, bilateral lesions, pruritus, pain, and bleeding. LIMITATIONS: Potential for publication bias is a limitation. CONCLUSIONS: Surgical excision appears to be the most effective treatment for ALHE, albeit suboptimal. Pulsed dye and other lasers may be effective treatment options. More studies are needed to improve the treatment of ALHE.

Retrospective Multicentric Study of 25 Kimura Disease Patients: Emphasis on Therapeutics and Shared Features with Cutaneous IgG4-Related Disease.

BACKGROUND: Kimura disease (KD) is a rare lymphoproliferative inflammatory disease of unknown etiology. Data regarding therapeutic modalities and pathophysiology are scarce. OBJECTIVES: Analyze therapeutic and follow-up data and compare KD with cutaneous IgG4-related disease (IgG4-RD). METHODS: Multicentric retrospective study of 25 KD patients with analysis of treatment, follow-up and IgG4 immunostaining. Comparison with published cases of cutaneous IgG4-RD. RESULTS: Patients were mostly male (84%), median-aged 42 years with lymph node, lacrimal/salivary gland and kidney involvements in 45, 24 and 12%, respectively. Surgical excision had 100% complete response and 60% relapse. Oral corticosteroids had 100% response with 50% relapse. Thalidomide, cyclosporine or interferon-α had 100% response, but 100, 20 and 50% relapse, respectively. KD showed clinicopathological similarities with 27 published cases of cutaneous IgG4-RD. CONCLUSION: Surgery may be used in resectable KD cases, whereas cyclosporine or thalidomide may represent interesting alternatives to oral corticosteroids in other cases. KD shares features with cutaneous IgG4-RD.