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A Lymphocytic Variant of Hypereosinophilic Syndrome Presenting With Isolated Cutaneous Manifestations

Hypereosinophilic syndrome (HES) is a rare disease defined by a persistent increase in eosinophilic cells associated with organ damage without any underlying cause. Three variants have been identified: myeloproliferative, lymphocytic, and idiopathic syndrome. The symptomatology is variable because it depends on the involvement of different organs, including the circulatory system, skin, lungs, digestive tract, peripheral and central nervous system, and eyes. Although cutaneous involvement may frequently reveal an underlying HES. We report a case of a 52-year-old man with a 12-year history of skin lesions with intense pruritus. On examination, the patient presented with erythroderma, extensive infiltrated plaques, excoriated itchy papules, palmoplantar pustules, ear infiltration, periorbital edema, and cutaneous xerosis. Histopathology showed lichenoid dermatitis without epidermotropism. Inflammatory infiltrates in the dermis were principally composed of eosinophilic cells and lymphocytes. Serum immunoglobulin E and peripheral blood immunophenotyping showed atypical T lymphocyte proliferation CD4+CD3-, and clonal TCR gene rearrangement was in favor of lymphocytic HES. The patient was treated with prednisone (1 mg/kg/day) and pegylated interferon alpha with improvement. This case shows that HES should be suspected in patients with dermatological lesions and hypereosinophilia, without obvious cause. Elimination of secondary causes of eosinophilia, evaluation of deep organ involvement, and cytogenetic studies to assess prognosis are paramount. Pegylated interferon alpha 2a may be an effective treatment option for steroid-resistant or refractory patients with lymphocytic HES.


Introduction
Hypereosinophilic syndrome (HES) is an uncommon, multisystem, heterogeneous group of disorders with significant morbidity and mortality. It is characterized by persistently elevated peripheral blood eosinophilia associated with symptomatic organ involvement, excluding secondary causes of eosinophilia [1].
HES is classified as myeloproliferative, lymphocytic, and idiopathic [2]. The lymphocytic variant of HES (L-HES) is a distinct subtype, characterized by aberrant clonal T-cell populations that produce eosinophilpromoting cytokines [3].
We present a case of a lymphocytic variant of HES with cutaneous manifestations, treated with pegylated interferon alpha 2a.

Case Presentation
A 52-year-old male presented with a three-year history of periodic pruritic and generalized erythema that had been diagnosed as mycosis fungoid, which was suspected in a single histological study and whose immunohistochemical study did not allow the diagnosis to be fully retained. He had received many treatments, such as systemic and topical corticosteroids, systemic methotrexate, and antihistamines, with no improvement. Physical examination showed erythroderma with extensively infiltrated plaques ( Figure  1), excoriated itchy papules (Figure 2), palmoplantar pustules ( Figure 3), ear infiltration, periorbital edema, and cutaneous xerosis with multiple axillary lymphadenopathies. There was no abdominal organomegaly and examination for central nervous, respiratory, cardiovascular, and musculoskeletal systems was normal. Hepatitis serology, human T-lymphotropic virus type I (HTLV-I), and HIV antibodies were negative. No antinuclear antibody or antineutrophil cytoplasmic antibody was detected. Stool examination for parasites was negative. Serum immunoglobulin E was elevated at 3382. Peripheral blood immunophenotyping showed atypical T lymphocyte proliferation CD4+CD3-, and T-cell receptor rearrangement studies revealed a clonal population of T lymphocytes.
Computed tomography of the chest and ultrasonography of the abdomen showed normal findings. Echocardiography and electrocardiogram were normal. Skin biopsy showed nonspecific lichenoid dermatitis without epidermotropism. Inflammatory infiltrates consisted mainly of lymphocytes and eosinophils. Myelogram and bone marrow biopsy showed moderate eosinophilia without evidence of lymphoma. A lymph node biopsy demonstrated dermopathic lymphadenitis but no evidence of malignancy.
The diagnosis of lymphocytic HES was retained. The patient was treated with prednisone 1 mg/kg/day without significant improvement. Pegylated interferon alpha 2a administered subcutaneously weekly was added. Two months later, we noted an important resolution of cutaneous lesions and a decrease in eosinophilia. The Working Conference on Eosinophil Disorders and Syndromes updates the criteria and definitions for eosinophilic disorders. They defined HE as >1.5 eosinophils × 109/L blood on two examinations (interval ≥ one month) and/or tissue HE. HES includes (i) criteria for peripheral blood (HE) fulfilled, (b) organ damage and/or dysfunction attributable to tissue HE, and (c) exclusion of other disorders or conditions as the major reason for organ damage [1]. HES is rare with an estimated incidence of 0.036 per 100,000. The usual age of diagnosis for HES is 20-50 years old [4].

HES was introduced by
Before retaining the diagnosis of HES, a significant number of diagnoses should be eliminated. From a dermatological perspective, it is necessary to look for dermatological lesions suggestive of a specific dermatological pathology with histopathological confirmation such as autoimmune bullous dermatoses, eczema, or atopic dermatitis [5]. When the cutaneous manifestations do not allow a diagnosis, the etiological investigation must be systematic. We will always keep in mind the major etiological lines: infectious diseases; drug, toxic, or allergic causes; neoplasias or malignant hemopathy; and systemic