juvenile mycosis fungoides treated with bexarotene and puva

© 2007

The International Society of Dermatology International Journal of Dermatology

2007,

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, 99 –102

99

A 14-year-old Caucasian boy presented with a 4-month history of a slightly pruritic eruption that

began on the hips and later extended to the trunk and upper and lower limbs. The patient did

not present fever, weight loss, or asthenia.

Physical examination revealed multiple, red, desquamative, oval patches with areas of

healthy skin between them, which covered nearly 50% of the body surface area. The palms,

soles, face, and mucosa were not affected. In addition, he presented two violet-colored

infiltrated plaques on the left thigh and right buttock (Fig. 1). There were multiple, > 1 cm, freely

mobile, axillary and inguinal nodes. In follow-up, the patient developed two red-colored, mobile,

well-delimited cutaneous nodules of 2.5 cm in diameter in the right hemithorax and lumbar area.

The lumbar nodule regressed spontaneously before treatment.

The clinical diagnosis was mycosis fungoides. We obtained three skin biopsies, one from a

patch lesion and the others from a nodule; the third was sent to a reference hospital to determine

the rearrangement. Histologic examination was similar in the three biopsies and revealed an

atypical lymphoid infiltrate in the superficial dermis with epidermotropism and a tumoral nodule

of atypical, small-sized lymphocytes in the deep dermis and subcutaneous level (Fig. 2). The

atypical infiltrate was CD3+, CD4+, CD8–, T-cell intracellular antigen (TIA)+/–, Epstein-Barr-

encoded RNA (EBER)–, and CD56–. The biopsy of one left axillary adenopathy was compatible

with mycosis fungoides (Fig. 3).

Amongst the additional tests carried out was a blood analysis showing 5300 leukocytes

(neutrophils, 35%; lymphocytes, 40.7%; monocytes, 16.8%; eosinophils, 6.40%) without

Sézary cells, normal lactate dehydrogenase (LDH), immunoglobulin E (IgE) of 497 U/mL

(normal, 3–100 U/mL), and

β

2

-microglobulin of 3.09 mg/L (normal, 1.64

±

0.58 mg/L). A bone

marrow study and a thoraco-abdomino-pelvic scan were normal. The rearrangement in the skin

was monoclonal, whereas in peripheral blood and lymph nodes it was polyclonal

.

With the diagnosis of mycosis fungoides stage IVA (according to the TNM classification),

treatment was initiated with psoralen plus ultraviolet light A (PUVA), three times a week, plus

oral bexarotene at a dose of 300 mg/m

2

/day. The parents were informed that this treatment was

not approved for this age group and informed consent was obtained. The clinical tolerance to

bexarotene was very good, although low doses of atorvastatin (10 mg/day) and 75–100 mg of

thyroxine were needed to control the expected adverse reactions to oral retinoid. After 32

sessions of PUVA and 6 months of treatment with oral bexarotene, the skin patches regressed,

except for the plaque on the left buttock and the nodule on the right hemithorax (Fig. 4). There

was no evidence of lymphadenopathy clinically or via sonographic evaluation. Bexarotene was

discontinued after patient clearance and resolution of adenopathies.

Nevertheless, 5 months after discontinuation of oral treatment, the patient developed

multiple, scaling, nonconfluent macules on the trunk and arms affecting almost 30% of the body

surface area, which disappeared with the application of methylprednisolone aceponate. He did

not present significant lymphadenopathies.

Blackwell Publishing LtdOxford, UKIJDInternational Journal of Dermatology0011-9059Blackwell Publishing Ltd, 200645

Pharmacology and therapeutics

Treatment of juvenile mycosis fungoides

Rodríguez-Vázquez, García-Arpa, and González-García


Juvenile mycosis fungoides treated with bexarotene and PUVA

María Rodríguez-Vázquez,

MD

, Mónica García-Arpa,

PhD

, and Jesús González-García,

PhD

From the Dermatology Unit, Albacete University Hospital, and Dermatology Unit and Anatomical Pathology Department, Ciudad Real General Hospital, Albacete, Spain

Correspondence

María Rodríguez-Vázquez,

MD

Dermatology Unit (Consultation Room 11)Hospital General de Albacete C/Hermanos Falcó 37 02006-Albacete SpainE-mail: [email protected]

Discussion

Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma (CTCL) and usually affects adults. It has beenestimated, however, that 0.5–5% of cases of MF develop duringchildhood. At this age, MF can be present clinically at any

stage of evolution, but the usual clinical presentation is patchstage, limited or generalized; if there are palpable lymphnodes, they are normally histologically negative (stage IA, IB,or IIA).

1,2

The diagnosis of MF in childhood is often delayed,as its rarity leads to a low index of suspicion and, in the earlystages, it is difficult to differentiate it histologically from more

International Journal of Dermatology

2007,

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, 99 –102 © 2007

The International Society of Dermatology

100 Pharmacology and therapeutics



common inflammatory dermatoses. This often means that mul-tiple skin biopsies must be performed in cases of suspicion.

3

Once the diagnosis of MF is established, the child should becarefully staged using the TNM classification for “cutaneousT-cell lymphoma.” MF in this age group can usually be clas-sified as IA, IB, or IIA at the time of diagnosis. Wain

et al

.

1

reported the largest series of MF with an onset before20 years of age, with 34 patients, 17 of whom were in stageIA, 16 in IB, and one in IIA, data comparable with other largeseries of MF in childhood (24 patients in both series).

2,4

In

this age group, the most frequent clinical presentation ishypopigmented patch MF.

5,6

Although tumoral lesions,

7

granulomatous slack skin syndrome,

8

Sézary’s syndrome,

9

and patients who progress to lymph node involvement

10,11

have been described, to our knowledge, there has been nopreviously reported case of stage IVA MF in childhood at thetime of diagnosis.

A wide variety of therapies have been used in children andadolescents with MF. There are no specific protocols for thetreatment of MF in childhood, however, because it occurs

Figure 1 The patient presented with multiple, red, squamous, oval patches with areas of healthy skin between them. A violaceous plaque of 4.5 cm on the left buttock with superficial desquamation was seen

Figure 2 Skin biopsy showing a dense infiltrate of atypical lymphocytes in the papillary dermis with epidermotropism (hematoxylin and eosin; left, ×10; right, ×40)

Figure 3 Lymph node biopsy with marked effacement of the architecture, and the presence of infiltration by atypical T lymphocytes (hematoxylin and eosin; left, ×10; right, ×40)

© 2007

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, 99 –102

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very rarely, especially in advanced stages. Therefore, weused the guidelines for adults.

3

As initial therapies, potentcorticosteroids, topical nitrogen mustard and carmustine,psoralen plus ultraviolet light A (PUVA), UV-B, interferonplus PUVA,

12

and total-skin electron-beam (TSEB) irradia-tion have been used, switching to mono- and combinationchemotherapy if the disease has progressed.

10

Our case wasjuvenile MF stage IVA at onset. According to the treatmentprotocols of the Spanish Cooperative Group of CutaneousLymphomas of the Spanish Academy of Dermatology andVenereology, the first line of treatment would be mono- orcombination chemotherapy. We chose the experimentaloption of PUVA associated with bexarotene for severalreasons. Bexarotene has achieved a higher rate of partial andcomplete responses than other conventional treatments. Itdoes not expose patients to the risks of immunosuppressionor the carcinogenic effects of chemotherapy, with the second-ary possibility of progression to further stages or transforma-tion into more aggressive lymphomas. It reduces photo-damage to the skin by reducing the number of PUVA sessions,and avoids the adverse reactions associated with radiationand other immunomodulators. The response may be main-tained for years, thus delaying the administration of othermore toxic treatments.

2

Bexarotene may be combined withother treatments for CTCL,

13–16

and can be used again ifnecessary.

Nevertheless, bexarotene is a retinoid that is not approvedfor patients under 18 years of age. Despite this, however, der-matologists have obtained experience with other retinoids thatare also not approved for children, such as acitretin, whichhave been used over long periods of time; their adverse reactionsare minimal compared with the benefits they provide.

17,18

With regard to whether the development of MF in child-hood implies a more aggressive course, it has been concludedthat the prognosis is no worse than in adults at the same stageof presentation. Patients require close follow-up throughout

their lifetime to monitor for recurrence, progression, or develop-ment of second skin neoplasia as an adult.

1–3

We have presented the first case of initial stage IVA MF inchildhood treated with PUVA plus oral bexarotene, and high-light the excellent tolerance to treatment with no influence onthe patient’s daily life. We avoided the administration of aninitial immunosuppressive therapy with its associated risks.Fewer sessions of PUVA were required, and we did not needto use radiotherapy. Should a relapse occur that necessitatessystemic treatment, it is possible to administer bexaroteneagain without any limitation.

We believe that treatment with oral bexarotene, alone orassociated with PUVA, is a good initial therapeutic option incases of advanced-stage MF in childhood. The clinician needsto maintain an index of suspicion for the potential diagnosisof MF when faced with children and adolescents with anasymptomatic, chronic, scaling eruption that is recalcitrant totreatment with topical steroids.

References

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Figure 4 After treatment the skin lesions regressed, except for a plaque on the left buttock and a small nodule on the right hemithorax

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juvenile mycosis fungoides treated with bexarotene and puva

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