Pigmentary Sequelae of AIDS-Related Cutaneous ...

THE CUTTING EDGE: CHALLENGES IN MEDICAL AND SURGICAL THERAPIES SECTION EDITOR: EDWARD W. COWEN, MD, MHSc; ASSISTANT SECTION EDITORS: MURAD ALAM, MD; WILLIAM D. AUGHENBAUGH, MD

Pigmentary Sequelae of AIDS-Related Cutaneous Kaposi Sarcoma Successful Treatment by Q-switched 755-nm Alexandrite and 532-nm Nd:YAG Lasers Rosalind Hughes, MD; Jean-Philippe Lacour, MD; Thierry Passeron, MD, PhD; Department of Dermatology, University Hospital of Nice (Drs Hughes, Lacour, and Passeron), and Institut National de la Sante´ et de la Re´cherche Me´dicale Unite´ 895 Team 1 (Dr Passeron), Nice, France REPORT OF A CASE

A 53-year-old man with human immunodeficiency virus was diagnosed as having cutaneous Kaposi sarcoma (KS). He was seen by his family physician with rapid onset of multiple dark blue-to-purple nodules and plaques on the arms, ankles, lower legs, and dorsal feet. The diagnosis was confirmed by biopsy, and he was referred to an oncologist for treatment. The patient was already taking highly active antiretroviral therapy (HAART). Because of the extent of his disease, he had received systemic vincristine sulfate chemotherapy. He had a complete response to the treatment; however, the KS lesions left disfiguring large purple-to-brown patches on the shins, ankles, and calves that remained unchanged 1 year after cessation of chemotherapy. HAART was well tolerated and resulted in normalization of the T-cell (CD4) count and an undetectable viral load. The patient was significantly perturbed by the unsightly pigmentary sequelae, which were suggestive of his underlying diagnosis (Figure, A). THERAPEUTIC CHALLENGE

HAART remains the first-line treatment for AIDSrelated KS. Cytotoxic systemic chemotherapy is typically reserved for patients with rapidly progressive mucocutaneous disease, as well as those with symptomatic visceral involvement, pulmonary involvement, and debilitating KS-related symptoms.1 This patient had a complete response to systemic chemotherapy and HAART; however, he was left with extensive disfiguring pigmentation that significantly impaired his quality of life. The therapeutic challenge was to find a treatment that would clear the remaining pigmentation without potential adverse effects. SOLUTION

Pigmentary sequelae of KS are mostly due to hemosiderosis. The neoplastic vascular proliferation induces extravasation of red blood cells, leading to iron deposition into the skin. 2 Like several other pigments, iron-

induced tattoos can be targeted by Q-switched lasers.3 On the right shin of our patient, a test session was performed on a large plaque using the Q-switched 532-nm Nd:YAG laser (2-mm spot size and fluency of 6 J/cm2), the 1064-nm Nd:YAG laser (2-mm spot size and fluency of 6 J/cm2), the Q-switched 755-nm alexandrite laser (3-mm spot size and fluency of 6.5 J/cm2) (Trivantage; Candela, Wayland, Massachusetts), and the Q-switched 694-nm ruby laser (3-mm spot size and fluency of 8.4 J/cm2) (Paragon Elite; Lynton, Cheshire, England). Two months later, the area treated by Qswitched 755-nm alexandrite laser was a significantly paler shade of purple. The area treated by the Q-switched 532-nm Nd:YAG laser was also paler, as was (to a lesser extent) the area treated by the Q-switched 694-nm ruby laser. No appreciable change was noted in the area treated by the 1064-nm Nd:YAG laser. All lesions were subsequently treated at 2-month intervals using the Qswitched 755-nm alexandrite laser. Topical anesthesia was administered using lidocaine-prilocaine cream. Treatment was started with a 3-mm spot size and a fluency of 6.5 J/cm2. At each session, the fluency was increased as tolerated to a maximum of 18 J/cm2 as the pigment faded. For each session, approximately 30 minutes were required to treat all the lesions. After 3 sessions (Figure, B), all treated lesions showed a lightening in pigmentation by 50% to 70%. The degree of lightening was assessed using sequential standardized photographs by one of us who served as a blinded rater (J.-P.L.). Because the third session induced only slight improvement, we decided to change to the Q-switched 532-nm Nd:YAG laser. Two additional sessions were performed using this laser (2-mm spot size and fluency of 10 J/cm2). This resulted in further reduction of discoloration such that most lesions were barely visible. Treatment was well tolerated, with no adverse events and no recurrence of pigmentation at 6 months’ follow-up (Figure, C). The patient is satisfied with the cosmetic outcome. COMMENT

Kaposi sarcoma is an angioproliferative tumor characterized by slitlike neovascular processes and the pres-

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A

B

C

Figure. Patient. A, Pigmentary sequelae of Kaposi sarcoma lesion on the lower right leg. B, Marked improvement after 3 sessions using the Q-switched 755-nm alexandrite laser. C, Clinical aspect 6 months after 2 additional sessions using the Q-switched 532-nm Nd-YAG laser.

ence of proliferating endothelial cells, fibroblasts, infiltrating leukocytes, and spindle-shaped tumor cells. In the early stages, cutaneous KS demonstrates an inflammatory cell infiltration, extravasation of red blood cells, endothelial cell activation, and angiogenesis.2 Red blood cell extravasation may ultimately lead to deposition of the iron-containing pigment hemosiderin into the skin and to subsequent residual hemosiderosis, as described in this patient. Various lasers have been used to treat KS lesions, including carbon dioxide,4 argon,5 Nd:YAG,6,7 and pulseddye 8,9 lasers. These have been used in the setting of active disease as locally destructive or ablative therapy or as selective photothermolysis in the case of pulsed-dye laser. Postinflammatory hemosiderosis may occur in any condition that results in local destruction of red blood cells, and there is little in the literature about its treatment. Hemosiderin has an absorption spectrum throughout the visible range, with major peaks at 410 to 415 nm. Pimentel and Rodriguez-Salido10 reported a case of pigmentation following stasis dermatitis that was successfully treated using an intense pulsed-light source. Q-switched lasers are frequently used to treat pigmented skin lesions. Owing to the lack of information in the literature, we performed a session to test the 4 types of wavelengths used to

target pigmentation. Two months after treatment, there was significant lightening of pigmentation in the areas treated by the Q-switched 755-nm alexandrite and 532 Nd:YAG lasers. The patient was subsequently treated using a combination of these 2 lasers. After 6 sessions, all lesions has faded by 90% to 100%, and there was no recurrence of pigmentation at 6 months’ follow-up. Adverse effects were limited totransientpetechiaeusingtheQ-switched532-nmNd:YAG laser. However, the sessions were painful, rated by the patient as 7 on a 10-point visual analog scale. Although the patient’s active KS lesions had been successfully treated by systemic vincristine sulfate chemotherapy, the subsequent pigmentary sequelae were aesthetically displeasing and reflected the patient’s underlying diagnosis. Therefore,substantiallighteningofthepigmentationresulted in a high degree of patient satisfaction. The color, clinical aspect, and stability of the lesions and the marked response to laser treatment were suggestive of hemosiderin deposition. However, we cannot rule out that postinflammatory hyperpigmentation could have been associated at least partially in some lesions. These 2 types of pigmentation must be distinguished, as postinflammatory hyperpigmentation may be resistant to laser ablation. The development of KS has been reported in a surgical wound11 and at other sites of trauma.12 It is postulated that inflammatory change may recruit human herpesvirus 8–infected macrophages to the damaged tissue.11,12 Therefore, laser therapy may paradoxically have the same effect. It seems reasonable to initiate laser therapy only when a complete clinical response (ie, resolution of all lesions) and a biochemical response (ie, normalization of the T-cell count and an undetectable viral load) have been achieved. Despite that the pigmentation in our patient remained unchanged over several months and began to fade only after laser treatment, spontaneous improvement cannot be excluded. A combination of the Q-switched 755-nm alexandrite and 532-nm Nd:YAG lasers represents a safe and effective treatment for such patients. However, a larger case series is required to confirm our findings. Accepted for Publication: January 21, 2011. Correspondence: Thierry Passeron, MD, PhD, Department of Dermatology, University Hospital of Nice, Archet 2 Hospital, Rte de St-Antoine de Ginestiere, 06200 Nice, France ([email protected]). Author Contributions: Drs Hughes and Passeron had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Lacour and Passeron. Acquisition of data: Hughes and Passeron. Analysis and interpretation of data: Hughes, Lacour, and Passeron. Drafting of the manuscript: Hughes and Passeron. Critical revision of the manuscript for important intellectual content: Hughes, Lacour, and Passeron. Administrative, technical, or material support: Lacour and Passeron. Study supervision: Lacour and Passeron. Financial Disclosure: None reported. Previous Presentation: This study was presented as a scientific poster at the 31st Annual Conference and Courses of the American Society for Laser Medicine and Surgery; March 30-April 3, 2011; Grapevine, Texas.




REFERENCES 1. Vanni T, Sprinz E, Machado MW, de Carvalho Santana R, Fonseca BA, Schwartsmann G. Systemic treatment of AIDS-related Kaposi sarcoma: current status and perspectives. Cancer Treat Rev. 2006;32(6):445-455. 2. Aboulafia DM. Kaposi’s sarcoma. Clin Dermatol. 2001;19(3):269-283. 3. Suchin KR, Greenbaum SS. Successful treatment of a cosmetic tattoo using a combination of lasers. Dermatol Surg. 2004;30(1):105-107. 4. Webster GF. Local therapy for mucocutaneous Kaposi’s sarcoma in patients with acquired immunodeficiency syndrome. Dermatol Surg. 1995;21(3):205-208. 5. Wheeland RG, Bailin PL, Norris MJ. Argon laser photocoagulative therapy of Kaposi’s sarcoma: a clinical and histologic evaluation. J Dermatol Surg Oncol. 1985; 11(12):1180-1185. 6. Landthaler M, Szeimies RM, Hohenleutner C. Laser therapy of skin tumors. Recent Results Cancer Res. 1995;139:417-421.

7. Rosenfeld H, Wellisz T, Reinisch JF, Sherman R. The treatment of cutaneous vascular lesions with the Nd:YAG laser. Ann Plast Surg. 1988;21(3):223-230. 8. Marchell N, Alster TS. Successful treatment of cutaneous Kaposi’s sarcoma by the 585-nm pulsed dye laser. Dermatol Surg. 1997;23(10):973-975. 9. Tappero JW, Grekin RC, Zanelli GA, Berger TG. Pulsed-dye laser therapy for cutaneous Kaposi’s sarcoma associated with acquired immunodeficiency syndrome [published correction appears in J Am Acad Dermatol. 1993;28(2, pt 1):188]. J Am Acad Dermatol. 1992;27(4):526-530. 10. Pimentel CL, Rodriguez-Salido MJ. Pigmentation due to stasis dermatitis treated successfully with a noncoherent intense pulsed light source. Dermatol Surg. 2008; 34(7):950-951. 11. Webster-Cyriaque J. Development of Kaposi’s sarcoma in a surgical wound. N Engl J Med. 2002;346(16):1207-1210. 12. Yarchoan R, Davis DA. Development of Kaposi’s sarcoma at the site of a biopsy. N Engl J Med. 2002;347(10):763-764.

Notable Notes The KL Concentration Camp Tattoo Place: Mielec Concentration Camp, Poland; Date: Early 1940s. A Nazi SS officer tattoos the letters KL on the distal outer right forearm of the Jewish prisoner Joseph, age 16 years. Joseph wears a striped prisoner shirt bearing the serial number 118580. His daily diet consists of a slice of bread, a small amount of margarine, and a quart of soup. He is forced to work at the nearby Heinkel aircraft manufacturing facility constructing airplane parts. Mielec is a brutal camp: 15 prisoners die daily, excluding sick prisoners, who are routinely shot.1 Joseph survives 2 to 3 years at Mielec. Place: Dachau Concentration Camp, Germany; Date: April 29, 1945. Joseph has now endured nearly 5 years of hellish conditions as a prisoner at multiple Nazi labor camps and concentration camps. He is shot in the legs by his Nazi captors while trying to escape and is taken to Dachau to die. The US Army liberates Dachau, and Joseph is found critically ill, emaciated, and with badly infected leg wounds. He is rushed to a makeshift hospital for emergency surgery, where his life and limbs are saved. He is carefully nursed back to health with a diet of milk and sugar. For the first time in almost 5 years, he is able to take a hot shower. Place: Pembroke Pines, Florida; Date: January 2011. Joseph, who is now 85 years old, is my patient. He is married with 3 children, 9 grandchildren, and 4 great-grandchildren. His Holocaust remembrances were videotaped for the Shoah Foundation, which was established by filmmaker Steven Spiel-

berg. He hopes that his story will be heard and that we will all try harder to rid the world of hatred and inhumanity. Comment. During World War II, the Nazis tattooed prisoners with the letters KL at 3 concentration camps in Poland: Mielec, Wieliczka, and Budzyn.2 All 3 of these camps provided prisoners for forced labor at adjacent Heinkel airplane manufacturing facilities. The letters KL stood for the German term Konzentrationslager, or concentration camp. KL tattooing was used by the Nazis to identify prisoners as concentration camp inmates if they tried to escape. Tattooing of inmates was also performed at AuschwitzBirkenau, Poland, the only Nazi concentration camp in which prisoners were tattooed with their assigned serial numbers.3 During the Second World War, 6 million Jews perished in the Holocaust. Millions of innocent non-Jews were also killed by the Nazis. The noted philosopher George Santayana4 wrote, “Those who cannot remember the past are condemned to repeat it.” Let the account of the KL concentration camp tattoo, therefore, be an everlasting reminder to us and to all future generations that it is the duty and responsibility of every human being to ensure that no one ever again experiences such horrors. Leonard J. Hoenig, MD Author Affiliation: Dr Hoenig is in private practice, Pembroke Pines, Florida. Contact Dr Hoenig at 601 N Flamingo Rd, Ste 201, Pembroke Pines, FL 33028 ([email protected]).

1. Skolnik F, ed. Encyclopedia Judaica. Vol 14. 2nd ed. New York, NY: Thomson Gale Publishers; 2007:205. 2. Megargee GP, ed. The United States Holocaust Memorial Museum Encyclopedia of Camps and Ghettos, 1933-1945. Vol 1. Bloomington: Indiana University Press; 2009:869-872, 882-884. 3. Hoenig LJ. Tattoo, Auschwitz style. Int J Dermatol. In press. 4. Santayana G. The Life of Reason. Amherst, NY: Prometheus Books; 1998:82.


