Asymptomatic Macules and An Ulcerated Shoulder in an Elderly Woman

Antonio Giovanni Richetta, MD, PhD; Simona Giancristoforo, MD; Carlo Mattozzi, MD; Sara D'Epiro, MD; Stefano Calvieri, MD


December 09, 2016

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Treatment of primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma has proven extremely challenging, with even the most aggressive modalities proving ineffective in establishing a long-term cure. In addition, statistically significant evaluations of the different treatment options are not possible due to the rarity of the diagnosis. In general, initial treatment with skin-directed therapy including topical chemotherapy, psoralen plus UV-A (PUVA), and local radiotherapy is ineffective, and patients often require escalation to systemic, multiagent chemotherapy. Generally, doxorubicin-based regimens are used, including cyclophosphamide, doxorubicin, vincristine, and prednisone, but patients often fail to respond to even the most aggressive polychemotherapy regimens.

Histone deacetylase (HDAC) inhibitors have activity in CTCL. Romidepsin has demonstrated overall response rates of 35% in CTCL and is approved by the US Food and Drug Administration for the treatment of CTCL in patients with progressive, persistent, or recurrent disease on or following at least 1 prior systemic therapy.

A multi-institutional phase II trial evaluated the use of single-agent intravenous romidepsin in 71 patients with CTCL.The overall and complete response rates were 34% and 6%,[12] respectively. The median duration of response was 11.1 months. Among those with a major response, the median time to progression was 15.1 months. Severely affected patients (grade 3 of 4) saw drug-related toxicities of granulocytopenia and lymphopenia in 10% and 21% of instances, respectively. The nonhematologic side effects were generally mild but included nausea, vomiting, fatigue, electrolyte abnormalities, and electrocardiographic changes.

Another study evaluated the use of romidepsin in 96 patients with CTCL who had received a median of 2 prior therapies. Overall and complete response rates were 34% and 6%, respectively. The median duration of response was 14.9 months.[13]

Vorinostat is another HDAC inhibitor that has activity in CTCL. In one study it did provide pruritus relief in 32% of patients. Toxicities of vorinostat included diarrhea (46%), fatigue (49%), nausea (43%), anorexia (26%), and dysgeusia (24%).[14] Hematologic abnormalities include anemia, thrombocytopenia (22%), and neutropenia, most of which were grade 1 or 2 in severity. The most common severe adverse event was pulmonary embolus, seen in 4 patients (5%).[14]

HDAC inhibitors should be used with caution in patients with cardiac arrhythmias and should not be used in patients with prolonged QT intervals.

The patient was scheduled to undergo medical treatment with bexarotene 450 mg a day. During the treatment, the brownish macules healed and disappeared while the nodular lesion on her shoulder remained ulcerated. The skin ulcer was treated with advanced dressing to prevent bacterial superinfection, and a partial clinical improvement was seen. After 7 months of bexarotene therapy, this therapy had to be discontinued due to alterations in her the lipid profile (Figure 2). Subsequently, the patient developed a severe recurrence of the disease, leading to a progressive ulceration of her lesion with exposure of muscles and tendinous structures (as seen in Figure 3). She was then started on gemcitabine 1000 mg a week for 3 weeks and, after the first infusion, notable improvement of the wound with significant reduction in the size of the lesion was observed. Purine analogs, such as gemcitabine, do not have a high immunosuppressive capacity and may be the most appropriate agents for these patients.

The protocol was repeated 4 times and, ultimately, 4 months later she had complete resolution of the skin ulcer (Figure 4). Currently, the patient remains without any signs or symptoms of disease recurrence, and all side effects of the treatment protocols have resolved.


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