Insect bite-like reaction associated with the relapse of non-Hodgkin B cell-lymphoma

ARTICLE

Auteur(s) : Rym Benmously¹, Houda Hammami¹, Mondher Rouatbi¹, Achraf Debbiche², Adnane Souissi², Inçaf Mokhtar¹, Sammy Fenniche¹

¹Dermatology Department, Habib Thameur Hospital, 8, Ali Ben Ayed Sreet Montfleury-1008 Tunis-Tunisia
²Histopathology Department, Habib Thameur Hospital, Tunis

An exaggerated reaction to an insect bite is a non specific phenomenon described mostly with chronic lymphocytic leukemia [1]. This dermatosis has been described in about 40 patients affected by lymphoproliferative disorders [1, 2]. We report herein a new case.

A 74-year-old woman was referred to our department for evaluation of a generalized pruritic skin eruption of 2 years’ duration. She had been diagnosed 5 years previously with stage III low-grade nodal non-Hodgkin lymphoma of B-cell origin (NHBCL). She received at that date chemotherapy including CEOP and Alkeran (6 cycles). A total remission was achieved. She presented for recurrent urticarial plaques involving the face (figure 1A) and limbs, erythematous papules covered by vesicles (figure 1B) and bullae associated with infiltrated nodules on the limbs. The patient denied having an arthropod bite preceding the lesions. There was no history of drug intake. There were no clinical or biological signs of lymphoma relapse (no adenopathy, or splenomegaly). Blood tests showed no evidence of lymphocytosis but demonstrated elevated lactate dehydrogenase at 791 U/L and an elevated eosinophilic count of 900 cells/mm³. Stool analysis for parasites proved negative. A skin biopsy of a bullous lesion showed intraepidermal spongiotic bullae containing numerous eosinophils and fibrin exsudates (figure 1C) associated with a perivascular and interstitial eosinophilic infiltrate through the dermis. Blue Alcian staining revealed no mucinosis deposit. Histological examination of a nodular lesion revealed a dense perivascular and interstitial eosinophilic infiltrate of the dermis and the subcutis (figure 1D). No Flame figures were observed. Direct immunofluorescence tested negative. These findings support the diagnosis of an insect bite-like reaction. Treatment with topical corticosteroids led to a partial improvement. Dapsone was administered at 100 mg/day, but stopped because of the appearance of hemolytic anemia. One week later, we observed an increase in white blood cell count (20,300/μL with 12,600/μL lymphocytes). A relapse of NHBCL was diagnosed. The patient was referred to the oncology department. A complete remission of her cutaneous lesions was observed after 2 cycles of new chemotherapy treatment.

Exaggerated reaction to an insect bite was first described in 1965 by Weed [2]. A debate has ensued as to whether this phenomenon is due to exaggerated delayed hypersensitivity to mosquito bites. In fact, most of the patients could not recall have been bitten [1, 3]. Therefore, Barzilai et al. proposed new terms to describe this eruption such as insect bite-like reaction or eosinophilic eruption of hematoproliferative disease [1]. Byrd et al. proposed the following diagnostic criteria: (i) pruritic papules, nodules and/or vesiculobullous eruption resistant to conservative treatment; (ii) eosinophilic-rich dermal lymphohistiocytic infiltrate; (iii) exclusion of the other causes of tissue eosinophilia; and (iiii) preexisting diagnosis of a hematologic malignancy or dyscrasia or its subsequent development [4]. Our patient bore a striking resemblance to these findings. The pathogenesis of this entity remains unknown. A cytokine imbalance with an excess of interleukin IL-4 and IL-5, leading to a proliferation of malignant B cells and to a modified immune response characterized by eosinophilic infiltration, has been proposed. Another suggestion is that neoplastic B cells may be responsible for the skin hypersensitivity reaction [5]. Treatment failure of insect bite-like reactions has been reported with antibiotics, topical corticosteroids, systemic antihistamines, UV-B phototherapy, isolated chemotherapy, and interferon therapy [1]. Prednisolone may suppress the eruption but lesions recur when the dose is reduced [1]. Treatment with dapsone may lead to marked improvement [6]. Improvement of skin lesions in our patient is probably due to the fact that corticosteroids were included in the chemotherapy regimen [1].

In conclusion, this disease should be considered in patients affected by NHBCL. As the eruption may precede the occurrence or relapse of the hematoproliferative malignancy, a thorough follow-up in patients with eosinophilic dermatosis is recommended.

Acknowledgements

References

2 Weed RI. Exaggerated delayed hypersensitivity to mosquito bites in chronic lymphocytic leukemia. Blood 1965; 26: 257-68.

3 Davis MD, Perniciaro C, Dahl PR, Randle HW, McEvoy MT, Leiferman KM. Exaggerated arthropod-bite lesions in patients with chronic lymphocytic leukemia: a clinical, histopathologic, and immunopathologic study of eight patients. J Am Acad Dermatol 1998; 39: 27-35.

4 Byrd JA, Scherschun L, Chaffins ML, Fivenson DP. Eosinophilic dermatosis of myeloproliferative disease: characterization of a unique eruption in patients with hematologic disorders. Arch Dermatol 2001; 137: 1378-80.

5 Dodiuk-Gad RP, Dann EJ, Bergman R. Insect bite-like reaction associated with mantle cell lymphoma: a report of two cases and review of the literature. Int J Dermatol 2004; 43: 754-8.

6 Ulmer A, Metzler G, Schanz S, Fierlbeck G. Dapsone in the management of "insect bite-like reaction" in a patient with chronic lymphocytic leukaemia. Br J Dermatol 2007; 156: 172-4.