Lymphomatoid papulosis in children

ARTICLE

Lymphomatoid papulosis (LyP) was originally described by Macaulay [1] as a continuing, self-healing eruption that is characterized by a benign clinical course, but malignant histology. The initial eruption consists of small papules that progress to papulonecrotic lesions and finally regress [1-3]. However, 10% to 20% of patients have been reported to subsequently develop systemic lymphomas [4-7].

Based on histological features, LyP is classified into A and B types [8]. The dermal infiltrates in the type A lesions show considerable numbers of large atypical cells expressing CD30 and mostly CD25, CD71, and HLA-DR molecules, whereas type B lesions are predominantly composed of small to medium-sized lymphocytes [9-11].

LyP lesions usually first occur in adult life (20 to 70 years, mean 43 years) [12]. In some cases, however, this condition has been reported to start in childhood. We report on a patient who was 2 years old at onset of the disease, with a review of the literature for such early-onset cases.

Case report

A 12-year-old boy had a 10 year history of asymptomatic papules on his face, trunk, and four extremities. The individual lesions became necrotic and healed spontaneously in 2 to 4 weeks with slight scarring and hypopigmentation. He was otherwise in good health. His family history was unremarkable.

Physical examination showed multiple, erythematous papules, 5 to 10 mm in diameter, predominantly on his trunk and extremities (Fig. 1). Some of these papules were superficially eroded or covered with a crust. Neither lymphadenopathy nor hepatosplenomegaly was noted. Results of the following laboratory tests were normal or negative: complete blood cell counts, differential leukocyte count, blood chemistry studies, and antibody against human T-cell lymphotropic virus type 1. Chest X-ray was unremarkable.

A biopsy specimen taken from an active lesion on his back revealed a dense perivascular infiltrate of large atypical cells, small lymphoid cells, and eosinophils (Fig. 2). There was no epidermotropism, except for mild single cell invasion of small lymphoid cells. Atypical cells had a large nucleus containing prominent eosinophilic nucleoli with abundant cytoplasm. Some cells closely resembled Reed-Sternberg cells. Half of the biopsy specimen was fixed in periodate-lysine-paraformaldehyde solution and cryostat sections were processed for immunophenotypic analysis using the three-step immunoperoxidase technique, as described elsewhere [13]. A series of monoclonal antibodies (Becton Dickinson, Sunnyvale, CA) were used as primary antibodies. Large atypical cells were positive for CD3, CD4, CD7, CD25, CD30, CD45RO, CD71, and HLA-DR, but not CD8, CD20, or CD45RA, whereas small lymphoid cells expressed CD3 and CD4. Southern blotting for rearrangement of T-cell receptor (TCR) Cß1 was not successful because of the scarcity of DNA extracted from lesional skin.

On the basis of clinical outcome and histologic and immunohistochemical findings, we diagnosed the patient as having LyP type A. The patient was treated with topical ibuprofen piconol ointment with no improvement. Currently, 2 years later, he remains in good health, but the papular lesions continue to recur as before.

Review of the literature

Although the chronological pediatric norm is 15 years 3 months or less, we looked for reported cases younger than 20 years old at onset of the disease. To the best of our knowledge, there have been 44 patients reported with LyP who were younger than 20 years old at onset in Western and Japanese literature over the period 1956 to 1995 [4, 14-40]. In these reports, distinction between types A and B is poorly characterized. In 5, well-described cases, 2 cases were of
type A [19, 39], 2 cases type B [21, 22], and one case was a combination of both types [23]. The age of onset in 42 well-documented cases is shown in Figure 3. Patients younger than 5 years of age at onset are the most frequent, and the youngest patient is an 8-month-old boy [15]. The number of patients decreased gradually with age.

Concerning the distribution of the eruption in 34 documented cases [4, 14-27, 29, 32, 33, 35-40], lesions tended to occur simultaneously on the trunk and limbs with or without involvement of the face, and the face and limbs (Table I). Occasionally, the eruptions were present on the axillae, buttocks, hands and feet, and perianal area.

In 36 patients [4, 15-17, 19, 21-27, 31-40] whose clinical courses were well-described in the literature (Table II), 24 patients showed chronic, self-healing, and recurrent papular lesions during follow-up periods. Eight cases showed spontaneous remission without substantial treatment. Two patients developed systemic malignant lymphomas. In one of them, the skin eruption started in childhood although only diagnosed as LyP in adult life, and Hodgkin's disease developed at the age of 57 years [4]. In the other case, lesions appeared at the age of 10 years, he was diagnosed with LyP at 34 years, and went on to develop undifferentiated lymphoma at approximately 50 years old [16].

We looked at therapeutic modalities in 22 cases [4, 17-19, 22-26, 33, 36-40] (Table III). Topical application of corticosteroids alone and the combination of topical corticosteroids and others were frequently used, but most of them reportedly had no beneficial effect on the clinical courses. Neither systemic corticosteroids nor systemic antibiotics (tetracycline, erythromycin, or others) produced considerable clinical improvement [13, 15, 17, 21, 23, 33, 36, 39, 40]. In one patient, the systemic administration of indomethacin, 50 mg daily for one month resulted in complete remission [38]. A combination therapy of ultraviolet B (UVB) irradiation and topical corticosteroids was also effective in one case [17]. In addition, psoralen plus UVA (PUVA) therapy [18] or PUVA-bath therapy [19] showed therapeutic effectiveness to some degree.

Discussion

An immunohistochemical study of the self-healing, multiple papules in our case demonstrated infiltration of a great number of large, atypical cells bearing CD30, CD25, CD71 and HLA-DR. Since this antigen expression pattern is typical in LyP type A [12, 41], we diagnosed our case as LyP in a child. The clinical features of LyP resemble those of pityriasis lichenoides et varioliformis acuta, but the relationship between these two conditions is a matter of controversy [2], since some child cases of pityriasis lichenoides show infiltration of CD30⁺ atypical cells [42, 43] and clonal T-cell receptor (TCR) rearrangement [43-45]. Moreover, T-cell lymphoma developed in two children with pityriasis lichenoides [43]. Therefore, it is speculated that LyP and pityriasis lichenoides belong to a spectrum of cutaneous, CD30⁺ lymphoproliferative disorders [42]. In our case however, the 10-year persistence of the self-healing papular eruption with infiltration of a large number of CD30⁺ cells favors a diagnosis of LyP rather than pityriasis lichenoides.

Although LyP usually affects adults [12, 20], there have been a considerable number of cases with LyP with an age of onset less than 20 years. Our review of the literature revealed that in 42.9% of these cases, the disease had started by the age of 5 years. On the other hand, the age of onset in adult cases peaks at around 40 years [12, 20]. Therefore, it is assumed that LyP has two peaks regarding age of onset. There was no remarkable difference in the predilection of eruptions between child and adult cases, as trunk, limbs and face are frequently affected sites in both groups [12, 20].

Ten to 20% of patients with LyP develop malignant lymphomas [4-7]. It has been reported that the average period from the onset of LyP to development of malignant lymphoma is 17.5 years in adult patients [20]. Currently, we can not exactly estimate the risk of development of malignant lymphomas in early-onset LyP, because of the paucity of well-documented cases. In 2 patients, however, malignant lymphoma occurred at the age of 50 and 57 years, respectively [4, 16]. In addition, given that some cases of pityriasis lichenoides are virtually part of the same spectrum as LyP, the development of T-cell lymphoma in two patients with pityriasis lichenoides [43] may strengthen the possibility of the malignant change in LyP.

In spite of various attempts, there is no effective therapy for LyP. Therefore, LyP patients should be followed up periodically in order to detect the possible development of malignant lymphomas as early as possible. Demonstration of T-cell receptor (TCR) rearrangement in lesional skin is not necessarily evidence for malignant change, since clonal expansion of T-cells in the eruptions was found in some patients showing the ordinary, self-healing clinical course [46, 47]. Because of the difficulty in long-term follow-up, the natural clinical course of early-onset LyP has been poorly investigated. Further accumulation of patient documentation may clarify this important issue.

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