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A Prospective Study of Cutaneous Intolerance to Topical Mechlorethamine Therapy in Patients With Cutaneous T-Cell Lymphomas
Eric Estève, MD;
Martine Bagot, MD, PhD;
Pascal Joly, MD, PhD;
Pierre Souteyrand, MD, PhD;
Marie Beylot-Barry, MD;
Loic Vaillant, MD, PhD;
Michèle Delaunay, MD;
Marie Françoise Avril, MD;
Liliane Laroche, MD, PhD;
Florent Grange, MD;
Elisabeth Thomine, MD;
Janine Wechsler, MD, PhD;
for the French Study Group of Cutaneous Lymphomas
Arch Dermatol. 1999;135:1349-1353.
Objective To study the exact frequency and the histological features of cutaneous intolerance to mechlorethamine (CIM) hydrochloride therapy in patients with cutaneous T-cell lymphomas, including Langerhans cell histiocytosis.
Design A multicenter prospective study was conducted from January 1, 1994, to May 31, 1996, in 12 different hospitals in France.
Patients Of the 52 patients with cutaneous T-cell lymphomas or Langerhans cell histiocytosis, 35 were men and 17 were women, aged 18 to 87 years. Of the 52 patients, 35 had mycosis fungoides, 8 had nonepidermotropic cutaneous lymphoma, 7 had lymphomatoid papulosis, 1 had Sézary syndrome, and 1 had Langerhans cell histiocytosis.
Methods Patients were treated with topical applications of a 0.02% aqueous solution of mechlorethamine. The diagnosis of CIM was determined by the presence of erythema and pruritus. Patients who developed CIM underwent closed patch testing with three 10-fold dilutions of 0.02% mechlorethamine solution. A positive patch test result was the presence of erythema and pruritus, a weak result was the presence of simple erythema without pruritus, and a negative result was the absence of erythema and pruritus. Skin biopsy specimens from patients with positive patch test results were obtained in patients who developed CIM. The biopsy specimens were reviewed, and the results determined by 2 pathologists (E.T. and J.W.). The histopathological findings were classified in 3 categories: (1) spongiotic dermatitis, (2) irritant dermatitis, and (3) insignificant or normal. In September 1998, the referring physicians were contacted if mechlorethamine therapy had been continued in patients with CIM.
Results Of the 52 patients, 43 were evaluated for tolerance to mechlorethamine therapy. Of the 43 patients, CIM developed in 23, from 4 days to 9 months after the initiation of mechlorethamine therapy. Of those 23 patients, CIM developed within 3 months in 21 and within 1 month in 13. Closed patch tests were performed in 21 of the 23 patients who developed CIM. The results of the patch test were positive in 12, weak in 4, and negative in 5. Of these 21 patients, 14 skin biopsy specimens were obtained in 14 different patients who had positive or weak patch test results. The specimens showed histological features that were consistent with spongiotic dermatitis in 9 patients, irritant dermatitis in 2, and insignificant or normal in 3. All 9 patients with histological features of spongiotic dermatitis discontinued mechlorethamine therapy. All 5 patients without histological features of spongiotic dermatitis were able to resume mechlorethamine therapy. These results do not correlate with those of previous study results.
Conclusions Mechlorethamine therapy is a cost-effective and easily administered treatment for cutaneous T-cell lymphomas. Our study shows that allergic dermatitis caused by mechlorethamine therapy is an early and frequent adverse reaction in patients with cutaneous T-cell lymphomas. The most common histological feature of patients with CIM is spongiotic dermatitis.
From the Department of Dermatology, Hôpital R. Debré, Reims and Hôpital Porte Madeleine, Orléans (Dr Estève); the Departments of Dermatology (Dr Bagot) and Pathology (Dr Wechsler), Hôpital H. Mondor, Créteil; the Departments of Dermatology (Dr Joly) and Pathology (Dr Thomine), Hôpital C. Nicolle, Rouen; the Department of Dermatology, Hôpital Hôtel Dieu, Clermont-Ferrand (Dr Souteyrand); Hôpital du Haut-Leveque, Pessac (Dr Beylot-Barry); Hôpital Trousseau, Tours (Dr Vaillant); Cente J. Perrin, Bordeaux (Dr Delaunay); Institut G. Roussy, Villejuif (Dr Avril); Hôpital Avicenne, Bobigny (Dr Laroche); Hôpital L. Pasteur, Colmar (Dr Grange), France.
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