Eosinophilic Dermatosis of Hematological Malignancy

Dear Editor, Eosinophilic dermatosis of hematological malignancy (EDHM) is a cutaneous manifestation reported with various hematoproliferative and lymphoproliferative disorders. It is characterized by a nonspecific pruritic eruption with pleomorphic clinical presentations, making an accurate diagnosis difficult.[1] A 60-year-old male patient presented to the dermatology outpatient department with a 2-year history of pruritic eruptions all over the body. The itch was severe enough to interfere with his sleep, and severely compromised his quality of life. Cutaneous examination revealed localized indurated plaques with tiny tense vesicles over the surface, diffuse urticarial papules and plaques, and widespread excoriations on both exposed and non-exposed body sites [Figure 1a and b]. The mucous membrane examination was normal. General examination of the patient revealed a frail-looking man. Lymphadenopathy affecting cervical, axillary, and inguinal lymph nodes were present.Figure 1: (a) Multiple papules and excoriations over trunk (non-exposed site). (b) Multiple papules, plaques, tiny vesicles, and excoriations over legs (exposed site)A thorough laboratory workup was done. The patient’s hemogram showed leukocytosis with eosinophilia (21.3%). Renal and liver function tests were normal. Chest X-ray reported a mild pleural effusion on the right side. Ultrasound abdomen revealed a few subcentimeter-sized right retroperitoneal lymph nodes. The patient was non-reactive to enzyme-linked immunosorbent assay (ELISA) for human immunodeficiency virus (HIV) and venereal disease research laboratory (VDRL). A lymph node biopsy from the cervical lymph node, however, suggested a diagnosis of diffuse non-Hodgkin lymphoma, small cell type. Histopathology from the skin lesion showed an eroded epidermis with diffuse inflammatory infiltrate in the entire dermis extending to the subcutaneous layer also [Figure 2a]. Eosinophils were markedly aggregated in perivascular, periappendageal, and perifollicular regions [Figure 2b]. The biopsy was suggestive of EDHM. An initial differential diagnosis of bullous pemphigoid was ruled out by direct immunofluorescence, which did not show any immunoreactant at the dermo-epidermal junction. The patient was referred to hemato-oncologist for further evaluation. The immunohistochemistry of the tumor cells was positive for CD20, BCL2, cyclin D1, SOX 11, and CD5 and negative for CD3, CD10, BCL6, and Ki 67: 30%. A final diagnosis of mantle cell lymphoma was made. The patient responded to oral prednisolone 30 mg once daily for a period of 7–10 days. He was referred to the hemato-oncology department for further management of his lymphoma. However, the patient did not come for follow-up.Figure 2: (a) Histopathology from a papular lesion showed an eroded epidermis with diffuse inflammatory infiltrate in entire dermis extending to subcutaneous layer (H and E; 40x). (b) Eosinophils were markedly aggregated in perivascular, periappendageal, and perifollicular region (H and E; 100x)EDHM is a chronic, relapsing pruritic skin disorder occurring in patients with various hematologic neoplasms. Although most often associated with chronic lymphocytic leukemia (CLL), the condition has also been described in acute monocytic leukemia, acute lymphoblastic leukemia, myelofibrosis, chronic myelogenous leukemia, large cell lymphoma, mantle cell lymphoma, mucosa-associated lymphoid tissue (MALT) lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, small lymphocytic lymphoma, lymphoplasmacytic lymphoma, marginal zone lymphoma, aggressive T-cell lymphoma, and multiple myeloma/monoclonal gammopathy of undermined significance. The cutaneous lesions are polymorphic and range from erythematous papules, nodules, blisters and vesicles, urticarial or cellulitis-like plaques, and cutaneous ulcerations. The clinical differential diagnosis includes arthropod bite, dermatitis herpetiformis, drug reaction, eosinophilic cellulitis, eosinophilic folliculitis, leukemia cutis, papular urticaria, scabies, and urticarial stage of bullous pemphigoid.[2] Atopic dermatitis may present as prurigo or prurigo-like lesions. The pathogenesis of EDHM remains poorly understood. One of the most controversial issues of EDHM is the role of insect bites, and the dermatosis was initially interpreted as a delayed hypersensitivity reaction to insect bites. However, many authors have argued against this association in subsequent reports, as most patients failed to recall insect bites.[3] A causal role has been attributed to the immune dysregulation accompanying hematoproliferative disorders and a cytokine imbalance, specifically an excess of interleukin 4 (IL-4), which plays a major role in type 2 immune responses, and of interleukin 5 (IL-5), which facilitates the production, differentiation, and migration of eosinophils.[4] Histologically, this condition displays a superficial and deep dense perivascular infiltrate of lymphocytes and eosinophils. Vesicles or bullae may also present due to intraepidermal or subepidermal edema.[2] Treatment of EDHM includes topical and systemic steroids, narrow-band ultraviolet B (UVB) phototherapy, oral antihistamines, dapsone, and antibiotics. However, only a limited data exist regarding the efficacy of these different treatments. Dupilumab, a monoclonal antibody approved for atopic dermatitis that targets the alpha subunit of the IL-4 receptor to inhibit IL-4 and IL-13 signaling, has been used off-label in patients with EDHM. Recent therapeutic advances have led to the development of novel IL-13-specific monoclonal antibodies, such as lebrikizumab and tralokinumab.[5] EDHM can often be missed as insect bite hypersensitivity due to lack of familiarity with the condition. Long-standing insect bite like itchy skin eruptions in an elderly person, can be a presenting sign of hematological malignancy. In this context, early recognition of this entity and performing an oriented evaluation may help to diagnose this condition early and improve the overall quality of life of the patient. This is particularly true for the adult population; in the pediatric population, persistent insect bite -like reactions, is a common occurrence. 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