Pemetrexed-induced scleroderma-like conditions in the lower legs of a patient with non-small cell lung carcinoma

Our plain-English summary of Pemetrexed-induced scleroderma-like conditions in the lower legs of a patient with non-small cell lung carcinoma, by K. Ishikawa, T. Sakai, T. Saito-Shono, et al (The Journal of Dermatology, 2016).

The study

• Authors: K. Ishikawa, T. Sakai, T. Saito-Shono, M. Miyawaki, A. Osoegawa, K. Sugio, A. Ono, H. Mori, H. Nishida, S. Yokoyama, O. Okamoto, S. Fujiwara, Y. Hatano
• Journal: The Journal of Dermatology
• Published: 2016;43(9):1071-4
• Type of article: Case report
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Pemetrexed, which is used for the treatment of non-small cell lung carcinoma and malignant mesothelioma, induces cutaneous adverse reactions in approximately 20% of patients. There are also reports of the induction of fibrosing disorders. We describe a case of pemetrexed-induced scleroderma-like conditions in the lower legs of a patient whose pulmonary carcinoma has been relatively well controlled, with prolongation of the dose interval, in spite of the discomfort in both his legs. Skin biopsy revealed dermal fibrosis and dilated lymph vessels in the dermis, but lymphocytic infiltration around the lymph vessels, in contrast to the blood vessels, was minimal. Immunohistochemical staining revealed that the major subsets of T cells that had infiltrated around blood vessels were CD3 and CD45Ro, but no B cells were detected. High serum levels of interleukin (IL)-4 and IL-6 suggested that T cells, which secrete these cytokines, may be involved in the pathogenesis of this condition. Magnetic resonance imaging of the lower extremities revealed muscular and fascial involvement. Several chemotherapeutic agents, such as taxanes, gemcitabine and bleomycin, are known to induce scleroderma-like changes, and we should also keep the side-effects of pemetrexed in mind when we encounter patients with fibrosing conditions.

© 2016 Japanese Dermatological Association.

In plain English

This was a case report from Oita University in Japan about one patient with lung cancer. The article does not study asbestos exposure; mesothelioma is mentioned only as another disease the drug pemetrexed is used to treat. A 63-year-old man with adenocarcinoma of the right lung received pemetrexed (500 mg/m2 every 3 or 4 weeks) from January 2014. At the 18th dose, he began to have skin stiffness in his left lower leg. A skin biopsy showed a thickened dermis, with T cells but no B cells around blood vessels and few lymphocytes around the widened lymph vessels. Blood levels of two immune signaling proteins, IL-4 and IL-6, were high. MRI suggested inflammation and swelling in muscle, fascia and the tissue under the skin. Pemetrexed was continued with the gap between doses lengthened from 3 or 4 weeks to 6 weeks (30 cycles at the time of writing), and the skin condition did not progress. The authors concluded that doctors should keep this side-effect of pemetrexed in mind when they see patients with fibrosing conditions. They said they did not know why this patient tolerated continued treatment.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: case report
• Who was studied: One 63-year-old man with adenocarcinoma of the right lung (non-small cell lung carcinoma), treated at Oita University, Japan; the authors describe it as the first such case reported from Japan
• Exposure: Intravenous pemetrexed chemotherapy, 500 mg/m2 every 3 or 4 weeks starting January 2014. No asbestos exposure is reported or studied.
• Main results:
  • Skin stiffness in the patient's left lower leg began in January 2015, at the 18th dose of pemetrexed. He was referred to dermatology after the 23rd dose (total dose 18 400 mg).
  • A skin biopsy from the lower extremities showed thickening of the dermis, with lymphocytes around the blood vessels.
  • The lymph vessels in the dermis were dilated. Lymphocytic infiltration around the lymph vessels was minimal, in contrast to the blood vessels.
  • T cells (CD3 and CD45Ro), but no B cells, had collected around the vessels in the skin biopsy.
  • In the patient's blood, IL-4 was 10 pg/mL and IL-6 was 11.6 pg/mL (normal values less than 6 and 4 pg/mL, respectively). The other cytokines measured were within the normal range.
  • MRI showed strong signals in the muscle, fascia and subcutaneous tissue, which the authors took to suggest inflammation and edema.
  • The patient's serum hyaluronan was slightly elevated at 93 ng/mL (normal less than 50).
  • Pemetrexed was continued with the dose interval lengthened from 3 or 4 weeks to 6 weeks (30 cycles at the time of writing). The patient's sclerodermic condition did not progress.
  • The patient's condition was rated grade 2 under the Common Toxicity Criteria for Adverse Events version 4.0, because of calf stiffness when going up stairs or a slope.
• The authors' conclusion: The authors concluded that, as with several other chemotherapy drugs, the side-effects of pemetrexed should be kept in mind when doctors encounter patients with fibrosing conditions.
• Limitations the authors state:
  • The authors stated that they do not know why this patient was better able to tolerate continued pemetrexed than previously reported patients.
  • The authors stated that the significance of the patient's low titer of antinuclear antibodies is not known.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Pemetrexed (Alimta), Carcinoma, Malignant Mesothelioma, Biopsy, Fibrosis, Immunohistochemistry, Cytokine, Gemcitabine.

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