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| CORRESPONDENCE |
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| Year : 2021 | Volume
: 39
| Issue : 4 | Page : 218-219 |
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Successful treatment of disseminated cutaneous lesions of classic type Kaposi sarcoma with low-dose peginterferon alfa-2a: A case report
Wei-Ting Liu1, Chaw-Ning Lee1, Yin-Yu Ho1, Hsiang-Ying Lu2, Chia-Jui Yen3, Tak-Wah Wong4
1 Department of Dermatology, National Cheng Kung University Hospital, College of Medicine; National Cheng Kung University Hospital Cancer Center, National Cheng Kung University, Tainan, Taiwan
2 National Cheng Kung University Hospital Cancer Center; Department of Nursing, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
3 National Cheng Kung University Hospital Cancer Center, National Cheng Kung University; Division of Hematology and Oncology, Department of Internal Medicine, Cheng Kung University Hospital, College of Medicine, National National Cheng Kung University, Tainan, Taiwan
4 Department of Dermatology, National Cheng Kung University Hospital, College of Medicine; National Cheng Kung University Hospital Cancer Center; Department of Molecular Biology and Biochemistry, College of Medicine; Center of Applied Nanomedicine, National Cheng Kung University, Tainan, Taiwan
| Date of Submission | 31-Jul-2021 |
| Date of Decision | 23-Oct-2021 |
| Date of Acceptance | 02-Nov-2021 |
| Date of Web Publication | 29-Dec-2021 |
Correspondence Address:
Dr. Chia-Jui Yen
Division of Hematology and Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, No. 138, Sheng-Li Road, Tainan 704
Taiwan
Dr. Tak-Wah Wong
Department of Dermatology, National Cheng Kung University Hospital, No. 138, Sheng-Li Road, Tainan 704
Taiwan
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/ds.ds_47_21
How to cite this article:
Liu WT, Lee CN, Ho YY, Lu HY, Yen CJ, Wong TW. Successful treatment of disseminated cutaneous lesions of classic type Kaposi sarcoma with low-dose peginterferon alfa-2a: A case report. Dermatol Sin 2021;39:218-9 |
How to cite this URL:
Liu WT, Lee CN, Ho YY, Lu HY, Yen CJ, Wong TW. Successful treatment of disseminated cutaneous lesions of classic type Kaposi sarcoma with low-dose peginterferon alfa-2a: A case report. Dermatol Sin [serial online] 2021 [cited 2023 Mar 23];39:218-9. Available from: https://www.dermsinica.org/text.asp?2021/39/4/218/334165 |
Dear Editor,
Kaposi sarcoma (KS) is a multifocal neoplasm of lymphatic endothelium-derived cells infected with human herpesvirus 8 (HHV 8).[1] It is classified into different clinical subtypes based on patient characteristics and epidemiology, namely classic, epidemic (HIV-associated), endemic (African), and iatrogenic. Classic KS predominates in elderly men, presenting as violaceous papules and plaques with predilection over lower extremities, and having a chronic and indolent course. It is sometimes associated with lymphedema, bleeding, ulceration, can be disseminated with cutaneous involvement, and rarely with mucosal, lymph node, or visceral organ involvement.[1],[2] We report the success of low-dose peginterferon alfa-2a treatment for a case of classic KS with disseminated cutaneous lesions.
A 73-year-old male suffering from recurrent disseminated nontuberculous mycobacterial infection involving multiple lymph nodes for 2 years was diagnosed of anti-interferon-γ immunodeficiency syndrome. After antibiotic treatment, the infections were fairly controlled. A melanoma in situ on his left nasal ala was excised 4 years ago without recurrence. In September 2019, he visited our clinic due to multiple violaceous papules and plaques on both feet over a month. KS was confirmed by a skin biopsy done over a papule on the left ankle [Figure 1]a. The histopathology showed many slit-like vascular spaces formed by the proliferation of endothelial cells with extravasated erythrocytes in the dermis [Figure 1]b, and immunohistochemically the tumor cells were focally positive for HHV-8 [Figure 1]c. A comprehensive evaluation showed negative for HIV and HHV-8 infections, and white blood cells including CD4 lymphocytes were within normal limits. No lymph nodes were palpable. Due to the rapid progression of his tumors, the clinical stage was diagnosed as stage 1b of classic type KS.[3] The patient received radiation therapy with 3000 cGy in 10 fractions with complete clinical response. However, new disseminated KSs grew over bilateral feet, dorsal hands, trunk, and his right chest wall shortly posttreatment. A whole-body positron emission tomography scan revealed no visceral organ involvement. Since the tumors extended beyond the lower extremities, the clinical stage was stage 4 disseminated classic KS.[1],[3] Systemic chemotherapy treatment was suggested but was refused by the patient. Instead, he received radiation therapy with 3000 cGy in 10 fractions again which had stable disease. Two months later, however, new lesions grew over his right arm and the chest wall adjacent to the irradiated field associated with lymphedema on the right arm [Figure 1]d and [Figure 1]f. After thoroughly discussing the benefits and risks of all possible treatments, including additional radiation or systemic chemotherapy, he decided to receive peginterferon alfa-2a (Pegasys, Roche, Kaiseraugst, Switzerland) through a weekly low dose (45 mcg) of subcutaneous injection. The patient reported no side effects except mild general malaise a few hours after the injection, and to our surprise, the tumors began to shrink within 2 weeks. A month later, the treatment was put to a halt for 4 weeks due to anemia, which might have been attributed to oral linezolid for the control of disseminated NTM infection, and the hemoglobin level returned to normal after discontinuation of linezolid. Interferon (45 mcg) was resumed but injected every 2 weeks upon seeing the patient's significant improvement. After 4 months of injections, all tumors were subsided with hyperpigmentation [Figure 1]d, [Figure 1]e, [Figure 1]f, [Figure 1]g, so a monthly maintenance dose (45 mcg) was proceeded. After 9 months of peginterferon alfa-2a, no tumors were observed. The patient is currently under this regular treatment. | Figure 1: A 73-year-old male with disseminated cutaneous lesions of classic Kaposi sarcoma was successfully treated with peginterferon-alpha 2a. He had received 2 courses of radiations. Eruptive, multiple reddish to violaceous papules have grown over the patient's right chest wall and right upper extremity around the radiation fields. A skin biopsy was taken from one of the tumors on his left ankle (a). The histopathology showed many slit-like vascular spaces formed by the proliferation of endothelial cells with extravasated erythrocytes in the dermis (b) (H and E stain, ×200 magnification). The tumor cell nuclei were focally stained positive with a monoclonal antibody against human herpesvirus 8 (×400 magnification) (c). The patient's skin conditions before weekly low dose interferon injections (d and f). The subsided papules with residual hyperpigmentation 6 months after peginterferon alfa-2a treatments (e and g). Note the improvement of tissue swelling of tumorous areas after treatments.
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Recently, the European Dermatology Forum, the European Association of Dermato-Oncology, and the European Organization for Research and Treatment of Cancer have published their guidelines on the diagnosis and treatment of KS, including classic variant.[1],[4] The philosophy of managing classic KS does not intend to cure, but to achieve disease control and improve patients' quality of life. Although pegylated liposomal doxorubicin and paclitaxel are recommended as the first-line chemotherapy agents for KS, a cytotoxic agent usually causes significant side effects, especially in elderly patients. Our patient was an immunocompromised host with active disseminated NTM infection; therefore, chemotherapy may not be an appropriate choice. Although all different skin-directed treatments exert excellent treatment response in KS, namely cryotherapy, laser ablation, topical therapy, and intralesional chemotherapy, when targeting a large number of tumors, all could cause significant pain, carry a risk of scarring, and cannot modulate immunity against new tumor. On the other hand, interferon therapy exhibits antiviral and antitumor effects and can also modulate immune responses against tumors. Interferon alfa-2a is a type I interferon exerting powerful antiviral and immunomodulatory effects.[5] Peginterferon alfa-2a is currently approved to exclusively treat chronic hepatitis B and hepatitis C infections in Taiwan. It is recommended to start short-acting interferon alfa-2a (e.g., Roferon-A, Roche, Kaiseraugst, Switzerland) with doses of 3 MU, and up to 36 MU of daily injections throughout 10–12 weeks in the case of AIDS-related KS. Common adverse events of interferon alfa-2a including gastrointestinal complaints, fever, fatigue, skin reaction, depressive symptoms, musculoskeletal pain, and alopecia are dose-dependent, especially in Asian patients.[6],[7] We decided to treat him with a minimal effective dose. Even with this low dose (45 mcg), he experienced mild fatigue in the first few hours after injection. Peginterferon alfa-2a has a long serum half-life due to its pegylated structure. Rokx et al. reported the encouraging results of weekly 135–180 mcg peginterferon alfa-2a treatment of advanced-stage AIDS-associated KS, with nine out of ten patients showing a median progression-free survival of 645 days.[6] While a few case series utilizing short-acting interferon alfa-2a in classic KS, the present report is the first English-written research article using peginterferon alfa-2a to treat classic advance KS with success.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms.
Acknowledgments
We sincerely thank Miss Yun Chang for English editing.
Financial support and sponsorship
The study was supported by National Cheng Kung University Hospital NCKUH-1106018, Ministry of Science and Technology, Taiwan MOST-110-2314-B-006-086-MY3, MOST-109-2327-B-006-005, and the Center of Applied Nanomedicine, National Cheng Kung University from the Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education in Taiwan to T.W.W.
Conflicts of interest
Prof. Tak-Wah Wong, an editorial board member at Dermatologica Sinica, had no role in the peer review process of or decision to publish this article. The other authors declared no conflicts of interests in writing this article.
| References | |  |
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| 2. | Vangipuram R, Tyring SK. Epidemiology of Kaposi sarcoma: Review and description of the nonepidemic variant. Int J Dermatol 2019;58:538-42. |
| 3. | Brambilla L, Boneschi V, Taglioni M, Ferrucci S. Staging of classic Kaposi's sarcoma: A useful tool for therapeutic choices. Eur J Dermatol 2003;13:83-6. |
| 4. | Cetin B, Aktas B, Bal O, Algin E, Akman T, Koral L. Classic Kaposi's sarcoma: A review of 156 cases. Dermatol Sin 2018;36:185-9. |
| 5. | Lin FC, Young HA. Interferons: Success in anti-viral immunotherapy. Cytokine Growth Factor Rev 2014;25:369-76. |
| 6. | Rokx C, van der Ende ME, Verbon A, Rijnders BJ. Peginterferon alfa-2a for AIDS-associated Kaposi sarcoma: Experience with 10 patients. Clin Infect Dis 2013;57:1497-9. |
| 7. | Wong TW, Chiu HC, Yip KM. Intralesional interferon alpha-2b has no effect in the treatment of keloids. Br J Dermatol 1994;130:683-5. |
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