DERMATOLOGICA SINICA xxx (2016) 1e2 Contents lists available at ScienceDirect Dermatologica Sinica journal homepage: http://www.derm-sinica.com CORRESPONDENCE Insect bite-like reaction in a patient with chronic lymphocytic leukemia Dear Editor, A 60-year-old woman, who had no history of skin problems, entered our clinic having experienced multiple itchy erythematous papules that had covered her face and extremities for year Two weeks before visiting our dermatology clinic, she developed severe itchy papulovesicular lesions (Figure 1) She claimed to have no history of insect bites or taking any drugs The laboratory examinations revealed a white blood cell count of 8.7 Â 109/L; hemoglobin, 123 g/L; platelet count, 179 Â 109/L; and C-reactive protein, 17.0 mg/dL Serum chemistry such as the prothrombin time, serum bilirubin level, urinalysis, and serologic evaluations of the liver and renal functions revealed normal results, as with the levels of anti-intercellular substance antibodies and antibasement membrane zone antibodies The skin biopsy revealed an ulceration in the epidermis with marked subepidermal edema formation and superficial, deep perivascular, interstitial lymphoeosinophilic infiltration in the dermis (Figure 2) Direct immunofluorescence studies had negative results The immunohistochemical (IHC) staining results were as follows: (1) the T cell markers CD3 and CD5 showed a T cell pattern, whereas the dendritic cell marker CD23 showed a dendritic cell pattern; (2) the B cell marker CD20 revealed scattered B cells; and (3) CD 30ỵ cells and CD79a cells were not present Based on our IHC staining, the predominant T cell infiltrate contained only a few B cells Under the impression of an insect-bite reaction, we prescribed systemic prednisolone at 10 mg daily However, her symptoms recurred intermittently during months of treatment A follow-up examination showed an elevated white blood cell count of 30.5 Â 109/L The patient was referred to a hematologist and subsequently diagnosed by bone marrow biopsy as having chronic lymphocytic leukemia (CLL) Chemotherapy was administered using cyclophosphamide, bendamustin, and rituximab High-dose systemic prednisolone (40 mg/d) resulted in the remission of the skin lesions within month However, until the CLL went into remission under chemotherapy, she had quick and frequent recurrences when the systemic prednisolone dose was tapered After months of CLL treatments, no recurrence of skin lesions occurred We eventually diagnosed the patient as having an insect bite-like reaction associated with CLL Chronic lymphocytic leukemia has an annual incidence rate of 3e5 cases/100,000 patients, which makes it the most common form of adult leukemia in Europe and North America.1 Cutaneous seeding from cutaneous lesions by neoplastic cells or by a nonmetastatic phenomenon occurs in up to 25% of these patients.2 Cutaneous seeding manifests as generalized pruritus, vasculitis, paraneoplastic pemphigus, erythema nodosum, erythroderma, Sweet's syndrome, and insect bite-like reactions Hypersensitivity to insect bites is a rare nonspecific phenomenon that accompanies lymphoproliferative disorders Many patients cannot recall having been bitten; therefore, these lesions may present a therapeutic challenge for clinicians.3 Weed4 first described an exaggerated reaction to a mosquito bite as a central punctum, a lesion that can be more than 20 mm in diameter, with induration edema, erythema, and intense pruritus; the reaction reaches its peak within 12e24 hours Bullae up to 10 cm in diameter can develop in severe cases Weed4 identified eight (8.3%) patients experiencing such reactions from among 97 CLL patients These eight patients showed intense reactions to mosquito antigens, but they had normal cutaneous reactions to common delayed hypersensitivity antigens Most of these patients similarly could not recall having been bitten by insects, and no insect body parts were in their lesions.2 Recurrent papulovesicular Figure An example of the patient’s lesions (A) Multiple erythematous papules and vesicles cover the left forearm (B) The near view Conflicts of interest: The authors declare that they have no financial or non-financial conflicts of interest related to the subject matter or materials discussed in this article http://dx.doi.org/10.1016/j.dsi.2016.10.004 1027-8117/Copyright © 2016, Taiwanese Dermatological Association Published by Elsevier Taiwan LLC This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/) Please cite this article in press as: Ma C-M, et al.Insect bite-like reaction in a patient with chronic lymphocytic leukemia, Dermatologica Sinica (2016), http://dx.doi.org/10.1016/j.dsi.2016.10.004 Correspondence / Dermatologica Sinica xxx (2016) 1e2 Figure Skin biopsy findings (A) The tissue contains subepidermal edema formation and dense inflammatory infiltrate (hematoxylin and eosin; original magnification, 40Â) (B) The infiltrate is predominantly composed of lymphocytes and eosinophil (hematoxylin and eosin; original magnification, 400Â) (C) The CD3 marker shows a T cell pattern (immunohistochemical staining; original magnification, 100Â) (D) The CD20 marker shows scattered B cells (immunohistochemical staining; original magnification, 100Â) lesions predominantly affect the upper and lower extremities, and can appear on unexposed skin areas The histopathologic features are superficial, deep inflammation containing eosinophils, which is consistent with the features of insect bites The pathogenesis of insect bite-like reaction in CLL patients is not fully understood Some medical authors theorize that an excess of interleukin-4 and interleukin-5 induces the proliferation of malignant B cells, thereby triggering eosinophilic infiltration However, B cell infiltrates may also cause skin lesions.2 Another retrospective study5 indicated that eruptions usually appear months to years after the diagnosis of leukemia, and are unrelated to the therapies or hematologic disease activities Some skin lesions may develop before the diagnosis of any hematologic diseases Various treatments for skin lesions include local ointments, antihistamine, oral steroids, antibiotics, phototherapy, and dapsone; however, treatment results vary.6 Oral glucocorticoids (40 mg/d) results in an effective but variable improvement.2 Whether an insect bite-like reaction has prognostic implications on CLL patients is questionable Robak and Robak concluded that the prognosis of CLL is unaffected by specific skin infiltrates However, Bairey et al5 noted that a significantly high percentage of patients with cutaneous lesions had an adverse prognosis of CLL Therefore, the pathogenesis and impact of insect bite-like reactions on the prognosis of hematologic diseases, although rare, are worthy of further investigation Chia-Man Ma Department of Dermatology, Taichung Veterans General Hospital, Taichung, Taiwan Wen-Chi Chen Jui-Lung Shen Department of Dermatology, Taichung Veterans General Hospital, Taichung, Taiwan Fang-Yi Lee Department of Pathology, Taichung Veterans General Hospital, Taichung, Taiwan Chao-Kuei Juan Department of Dermatology, Taichung Veterans General Hospital, Taichung, Taiwan Yi-Ju Chen* Department of Dermatology, Taichung Veterans General Hospital, Taichung, Taiwan Department of Dermatology, National Yang-Ming University, Taipei, Taiwan * Corresponding author Department of Dermatology, National Yang-Ming University and Taichung Veterans General Hospital, Number 1650, Section 4, Taiwan Boulevard, Taichung 40705, Taiwan E-mail address: yjchenmd@vghtc.gov.tw (Y.-J Chen) References Redaelli A, Laskin BL, Stephens JM, Botteman MF, Pashos CL The clinical and epidemiological burden of chronic lymphocytic leukaemia Eur J Cancer Care (Engl) 2004;13:279e87 Robak E, Robak T Skin lesions in chronic lymphocytic leukemia Leuk Lymphoma 2007;48:855e65 Cocuroccia B, Gisondi P, Gubinelli E, Girolomoni G An itchy vesiculobullous eruption in a patient with chronic lymphocytic leukaemia Int J Clin Pract 2004;58:1177e9 Weed RI Exaggerated delayed hypersensitivity to mosquito bites in chronic lymphocytic leukemia Blood 1965;26:257e68 Bairey O, Goldschmidt N, Ruchlemer R, et al Insect bite-like reaction in patients with chronic lymphocytic leukemia: a study from the Israeli Chronic Lymphocytic Leukemia Study Group Eur J Haematol 2012;89:491e6 Barzilai A, Shpiro D, Goldberg I, et al Insect bite-like reaction in patients with hematologic malignant neoplasms Arch Dermatol 1999;135:1503e7 Graduate Institute of Integrated Medicine, College of Chinese Medicine, Taichung, Taiwan Graduate Institute of Clinical Medical Science, College of Chinese Medicine, Taichung, Taiwan Department of Urology, China Medical University and Hospital, Taichung, Taiwan Received: Jun 17, 2016 Revised: Oct 26, 2016 Accepted: Oct 31, 2016 Please cite this article in press as: Ma C-M, et al.Insect bite-like reaction in a patient with chronic lymphocytic leukemia, Dermatologica Sinica (2016), http://dx.doi.org/10.1016/j.dsi.2016.10.004 ... Dermatologica Sinica xxx (2016) 1e2 Figure Skin biopsy findings (A) The tissue contains subepidermal edema formation and dense in? ??ammatory in? ??ltrate (hematoxylin and eosin; original magnification,... extremities, and can appear on unexposed skin areas The histopathologic features are superficial, deep in? ??ammation containing eosinophils, which is consistent with the features of insect bites The pathogenesis... Lymphocytic Leukemia Study Group Eur J Haematol 2012;89:491e6 Barzilai A, Shpiro D, Goldberg I, et al Insect bite- like reaction in patients with hematologic malignant neoplasms Arch Dermatol 1999;135:1503e7