Eruption of lymphocyte recovery

ARTICLE

A 63 year-old man diagnosed with laryngeal squamous carcinoma (Stage IV, T3N2MO) was treated with fluorouracil, leucovorin, and cisplatin. Two weeks after the end of the fourth chemotherapy cycle, the patient presented an asymptomatic, symmetrical rash of erythematous infiltrated papules and plaques located on palms and back of the hands, wrists, and forearms (Fig. 1 and 2). The patient denied taking any drug and had not noticed fever or malaise. He had not been treated with cytokines. There was no lymphadenopathy. His white blood cell count at that time was 4,930/µL with 66% neutrophils, and 21% lymphocytes (2,360/µL with 47% neutrophils, and 33% lymphocytes at the end of the fourth chemotherapy cycle). A skin biopsy specimen was taken from a lesion, and the histological picture is shown in Figures 3 and 4. A spontaneous recovery after desquamation occured three weeks later. What is your diagnosis ?

Eruption of lymphocyte recovery

Histological examination showed a moderate perivascular infiltrate of lymphocytes in the upper dermis and a mild exocytosis of lymphocytes and intercellular edema in the epidermis. The lymphocytes had a normal appearance. Isolated dyskeratotic epidermal cells were present. Cultures for bacteria and fungi from blood and biopsy sample were negative.

Comments

In 1989, Horn et al. [1] described 10 patients with a peculiar cutaneous reaction that they called eruption of lymphocyte recovery (ELR). ELR typically occurs in leukemia patients 1 to 4 weeks after receiving chemotherapy, coinciding with the return of lymphocytes to the peripheral circulation and skin. Clinically, the ELR is characterized by a variably distributed, confluent, or widespread erythematous macular and papular rash, that occasionally can evolve to erythroderma. It is frequently associated with a transient low-grade fever. The histological picture of ELR is not specific and shows an upper dermal perivascular infiltrate composed of small lymphocytes, predominantly of the helper type, and mild epidermal changes consisting of variable exocytosis of lymphocytes and intercellular edema. A case of an ELR that histologically resembled mycosis fungoides has been reported, with intraepidermal collections of lymphocytes mimicking Pautrier microabscesses [2]. The administration of human recombinant cytokines (such as granulocyte-macrophage colony stimulating factor and interleukine-3) in combination with the chemotherapeutic drugs alters the histological appearance of ELR: the infiltrate is relatively heavy and it is characterized by lymphocytes with hyperchromatic and pleomorphic nuclei, eosinophilic to amphophilic cytoplasm, and scattered mitotic figures. These lymphocytes display an "activated" phenotype, expressing CD30, HLA-DR, and CD25 [3]. The rash fades spontaneously with desquamation and slight hyperpigmentation within 1-3 weeks.

The diagnosis of ELR requires clinicopathological correlation because both clinical and histological findings are not specific. The differential diagnosis is very important and includes adverse drug effets, viral exanthems, and fungal or bacterial sepsis. In our patient the clinicopathological picture resembled an erythema multiforme induced by drugs, but the absence of mucous membrane involvement, extravasated red blood cells, eosinophils, and, especially, of hydropic degeneration of basal epidermal cells led us to reject that possibility.

The ELR is caused by the return of immunocompetent lymphocytes to peripheral circulation and skin. The same pathogenetic mechanism is advocated for other cutaneous eruptions after marrow ablation: graft vs host reactions and eruptions associated with the administration of human recombinant cytokines. These eruptions are considered as variations on the theme of the ELR [1, 4]. In fact, Bauer et al. [5] were unable to distinguish between an ELR and a grade 2 graft vs host reaction in approximately 30% of the cases, and they believe that cutaneous eruptions after autologous marrow transplantation are best considered as an ELR.

Our patient presented an eruption of lymphocyte recovery, but it differs from typical ELR in three points: 1) our patient did not suffer from leukemia, 2) bone marrow aplasia was not achieved, and 3) the rash was not widespread.

REFERENCES

1. Horn TD, Redd JV, Karp JE, Beschorner WE, Burke PJ, Hood AF. Cutaneous eruptions of lymphocyte recovery. Arch Dermatol 1989; 125: 1512-7.

2. Gibney MD, Penneys NS, Nelson-Adesokan P. Cutaneous eruption of lymphocyte recovery mimicking mycosis fungoides in a patient with acute myelocytic leukemia. J Cutan Pathol 1995; 22: 472-5.

3. Horn T, Lehmukuhle MA, Gore S, Hood A, Burke P. Systemic cytokine administration alters the histology of the eruption of lymphocyte recovery. J Cutan Pathol 1996; 23: 242-6.

4. Horn TD. Acute cutaneous eruptions after marrow ablation: roses by other names? J Cutan Pathol 1994; 21: 385-92.

5. Bauer DJ, Hood AF, Horn TD. Histologic comparison of autologous graft vs host reaction and cutaneous eruption of lymphocyte recovery. Arch Dermatol 1993; 129: 855-8.