Correspondence
Successful Treatment of Langerhans'-Cell Histiocytosis with Etanercept
N Engl J Med 2001; 345:1577-1578November 22, 2001
- Article
To the Editor:
Langerhans'-cell histiocytosis, previously called histiocytosis X, is an accumulation of dendritic Langerhans' cells and granulomatous lesions in various organs; its cause is unknown. The three-year survival rate among children with Langerhans'-cell histiocytosis has not improved during the past two decades and remains around 80 percent.1 In children younger than two years old who have involvement of the liver, spleen, hematopoietic system, or lungs and who do not have a response to induction therapy over the course of six weeks, the probability of survival at three years is less than 20 percent.1 We describe a child with Langerhans'-cell histiocytosis that progressed during conventional treatment but responded to treatment with an agent (etanercept) that neutralizes tumor necrosis factor α (TNF-α).
In January 2000, a five-month-old girl with a diagnosis of multifocal CD1a-positive Langerhans'-cell histiocytosis of the bone initially had a response to oral betamethasone, which was administered for six weeks. However, within one month thereafter, the disease spread to the spleen, liver, bone marrow, thymus, and skin; fever, anemia (a hemoglobin concentration of 7.2 g per deciliter), hypoalbuminemia (a serum albumin concentration of 2.1 g per deciliter), and an elevated sedimentation rate2 (18 to 45 mm per hour) developed. After six weeks of induction treatment with vinblastine and corticosteroids and during subsequent continuation therapy, there was fever (>39°C), an increasing sedimentation rate (40 mm per hour), and new lesions in vertebral bodies. Intensified continuation therapy (with vinblastine, mercaptopurine, methotrexate, and high doses of corticosteroids) stabilized the disease, but every attempt to reduce the dose of corticosteroids was followed by fever and reactivation of the disease.
An elevation in the expression of the inflammatory cytokine TNF-α has been reported in lesional T cells in Langerhans'-cell histiocytosis3 and was observed in Langerhans' cells from our patient with the use of immunostaining methods4 (Figure 1Figure 1
Detection of Intracellular TNF-α Protein by Immunostaining in a Diagnostic Specimen.). Because anti–TNF-α treatment has had beneficial effects in other inflammatory disorders,5 etanercept (a soluble TNF receptor:Fc fusion protein), at a dose of 0.4 mg per kilogram of body weight subcutaneously twice weekly, was added to the infant's ongoing therapy in August 2000. The fever abated, the sedimentation rate decreased from 50 to 6 mm per hour in 11 days, the spleen and thymus involvement regressed, and signs of healing were evident in bone lesions. Moreover, the corticosteroid dosage could be substantially reduced. To clarify the effect of etanercept, treatment was withheld in March 2001. Within three weeks, fever and an elevated sedimentation rate developed. When etanercept was reintroduced, the patient's temperature and sedimentation rate returned to normal. No side effects of etanercept were observed.This case indicates that anti–TNF-α therapy, in combination with conventional treatment, may substantially improve the outcome of Langerhans'-cell histiocytosis. Moreover, our data support the view that Langerhans'-cell histiocytosis is an inflammatory disease.
5 ReferencesJan-Inge Henter, M.D., Ph.D.
Jonas Karlén, M.D., Ph.D.
Ulrika Calming, M.D.
Cecilia Bernstrand, M.D.
Ulf Andersson, M.D., Ph.D.
Bengt Fadeel, M.D., Ph.D.
Karolinska Institute, S-171 76 Stockholm, Sweden
jan-inge.henter@kbh. ki. se 1
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Full Text | Web of Science | Medline
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