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  • Two men aged 60 years (case 1) and 41 years (case 2) presented with DD for 20 and 15 years, respectively. Both had crusted papules, plaques, and verrucous lesions nearly all over the body, with papillomatous vegetation pronounced in the flexures (Figure 1). Histologically, suprabasal lacunae and dyskeratosis with corps ronds and grains were consistent with the diagnosis of DD. Biopsy specimens from the vegetative lesions of the 2 cases showed papillomatous proliferation and vacuolated keratinocytes in the upper stratum malpighii, in addition to acantholysis and dyskeratosis (Figure 2). We detected DNA sequences of (1) HPV-5, HPV-36, and HPV-38 (case 1) and HPV-5 and HPV-36 (case 2) in the nested polymerase chain reaction products from the biopsy specimen of the papules and (2) HPV-5 and HPV-8 from the vegetative lesions of case 1, all using consensus primers CP65/70 and CP66/69, which are designed for epidermodysplasia verruciformis-associated HPV. In another polymerase chain reaction assay using the primer MY09/11 (designed for mucous-type HPV), all the specimens were negative. Figure 1. Crusted papules, plaques, and verrucous lesions on the trunk in case 1. Figure 2. Histopathologic section of the biopsy specimen taken from a vegetative lesion in case 1 before treatment. Note the vacuolated keratinocytes, acantholytic cells, and suprabasal lacunae (hematoxylin-eosin, original magnification 100). Arotinoid ethylester, 0.03 mg once or twice daily, was given to them. In about 2 months, most lesions subsided except for some pink or brown papules. Biopsy specimens from the previously lesional skin showed no hyperkeratosis, dyskeratosis, or acantholysis; only slight acanthosis in the epidermis and some mononuclear cells infiltrating the dermis remained. Polymerase chain reaction assay results for detecting HPV in the biopsy specimens became negative. A maintenance dosage of arotinoid ethylester, 0.03 mg twice a week, was prescribed. No new rashes have occurred, and monthly measures of triglyceride, lipoprotein, and cholesterol levels have been normal. Adverse effects consisted of slight itching, dryness, and hair loss. Comment We found koilocytes in the papillomatous lesions of DD and detected HPV DNA from the biopsy specimens of both cases. Thus, it seems likely that HPV may be a pathogen for DD or the papillomatous lesions of DD on the genetic background. On the other hand, DD with thickened epidermis may be a reservoir for HPV, such as in psoriatic lesions as suggested by recent studies. Also, patients with DD may be susceptible to HPV infection, just as they are susceptible to herpes simplex, poxvirus, and pyogenic infection. Therefore, whether (1) HPV is a pathogen for DD on the genetic background, (2) DD is a reservoir for HPV, (3) DD favors HPV infection, or (4) HPV in the 2 cases was just detected by accident needs further studies. Arotinoid ethylester has powerful antipapillomavirus activity, 8000 times stronger than all-trans-retinoic acid, 16000 times stronger than 13-cis-retinoic acid, and 500 to 1000 times stronger than etretinate, while its adverse effects are only one tenth of all-trans-retinoic acid. We have shown in 2 cases that arotinoid ethylester seems to be relatively safe and helpful for the treatment of DD. RJM Berkhout LM Tieben HL Smits Nested PCR approach for detection and typing of epidermodysplasia verruciformis-associated human papillomavirus types in cutaneous cancers from renal transplant recipients. J Clin Microbiol. 1995;33:690-695. MM Manos Y Ting DK Wright Use of polymerase chain reaction amplification for the detection of genital human papillomaviruses. Cancer Cells. 1989;7:209-214. M Favre G Orth S Majewski Psoriasis: a possible reservoir for human papillomavirus type 5, the virus associated with skin carcinomas of epidermodysplasia verruciformis. J Invest Dermatol. 1998;110:311-317. JG Marks DE Thor RS Lowe Darier's disease: an immunologic study. Arch Dermatol. 1978;114:1336-1339. W Bollag Arotinoids: a new class of retinoids with activities in oncology and dermatology. Cancer Chemother Pharmacol. 1981;7:27-29. Rapid Development of Nonmelanoma Skin Cancer After CO2 Laser Resurfacing Adverse Reaction adverse reaction Carcinoma, Squamous Cell carcinoma, squamous cell Carcinoma, Basal Cell carcinoma, basal cell Case Report case report Laser Surgery laser surgery Skin Resurfacing skin resurfacing Alexander J. Stratigos Athens, Greece Steven Tahan Boston, Mass Jeffrey S. Dover SkinCare Physicians of Chestnut Hill 1244 Boylston St Suite 302 Chestnut Hill, MA 02467 (e-mail: jdover@skincarephysicians.net) Not Available Various medical and surgical modalities exist to rejuvenate the skin and reverse the effects of photoaging. The most recent development involves high-power pulsed and scanned carbon dioxide (CO2) lasers, which are effective in the treatment of actinically damaged skin and function because they can be used to vaporize the photodamaged epidermis, to stimulate the production of new collagen in the dermis, and to remove lesions associated with aging or photoaging, such as lentigines, actinic keratoses, squamous cell carcinoma (SCC) in situ, and seborrheic keratoses. While laser skin resurfacing has been used extensively for the treatment of wrinkled photoaged skin, little has been reported regarding its effectiveness for the treatment of patients with premalignant skin conditions, such as actinic keratoses. One study suggested that laser skin resurfacing effectively clears actinic damage and decreases the rate of formation of new actinic keratoses. We describe 2 patients with photoaging without visible actinic keratoses or other premalignant skin lesions who developed nonmelanoma skin cancer on the resurfaced areas less than 6 months after the procedure. Report of Cases Case 1 A 63-year-old healthy woman with skin type II was referred to us for evaluation of moderate to severe photodamage. She had no history of skin cancer or precancerous lesions. She had had a face-lift procedure years earlier. The initial evaluation revealed significant photoaging and rhytides but no actinic keratoses or skin cancers. The patient underwent full-face resurfacing with a high-power, short-pulsed CO2 laser (Ultrapulse; Coherent, Santa Clara, Calif). Two full-face passes were performed with the computer pattern generator at settings of 60 W, 300 mJ per pulse, pattern of 2, size of 9, and density of 6, and then 1 pass in selected areas with similar parameters, followed by 1 to 2 passes in individual photodamaged areas using 500 mJ and 4 W with a 3-mm collimated beam handpiece. Five months after the procedure, the patient presented with a telangiectatic erythematous papule on her left temple. One month later, she developed a 1-cm indurated plaque on the left side of her forehead. A biopsy specimen demonstrated an infiltrating nodulocystic basal cell carcinoma (BCC). Excision was performed and revealed a large infiltrating BCC completely filling the reticular dermis, with no papillary dermal involvement or any visible epidermal origin. The excision was successful. The patient has remained free of skin cancer but has had occasional actinic keratoses during 2 years of follow-up. Case 2 A 48-year-old woman with skin type II was evaluated for laser skin resurfacing of severely photodamaged facial skin. She had a history of multiple facial actinic keratoses that had been treated with cryotherapy, as well as several facial BCCs that had been treated with surgical excision. The initial evaluation revealed extensive photoaging with scattered lentigines, rhytides, and dermatoheliosis. No actinic keratoses or skin cancers were identified. The patient underwent full-face resurfacing with a high-energy, short-pulsed CO2 laser using 2 full-face passes at settings of 60 W, 300 mJ per pulse, pattern of 2, size of 9, and density of 6, and then 1 pass in select areas with the same parameters, followed by 2 to 3 passes in using 500 mJ and 4 W with a 3-mm collimated beam handpiece. Her postoperative course was uncomplicated, and the cosmetic result was excellent. Six months after the resurfacing, the patient developed an asymptomatic scaly erythematous plaque on the right side of her jawline, a site distant from her previous skin cancers. A biopsy specimen revealed SCC in situ, which was surgically excised. No other precancerous or cancerous lesions have developed on the resurfaced areas during 1 year of follow-up. Comment We report 2 cases of nonmelanoma skin cancer (BCC and SCC) that developed on resurfaced facial skin within 6 months of CO2 laser resurfacing. The occurrence of skin cancers in our patients after resurfacing contradicts the general belief that resurfacing of the skin reverses the process of photodamage and delays the formation of epithelial skin tumors in sun-exposed areas. Both laser and other resurfacing procedures have been used in the past as a prophylactic maneuver for precancerous lesions. High-power scanned and pulsed CO2 lasers have been used effectively to treat 14 patients with extensive actinic keratoses or actinic damage and a history of facial skin cancers. All treated patients remained free of malignant or precancerous lesions during a follow-up period of 6 to 24 months. In another study, 2 patients with histories of multiple facial skin cancers were treated with CO2 laser resurfacing for skin cancer prophylaxis and remained free of tumors in the treated areas for 33 and 52 months, respectively, while developing new skin cancers in the untreated areas. In addition to lasers, chemical peels and dermabrasion have been used to treat sun-damaged skin and diffuse actinic keratoses, with encouraging results. Dermabrasion, dermatome shaving, and radical excision of large areas of the skin, followed by graft replacement, have been performed in patients with xeroderma pigmentosum to delay the development of malignant changes. van Zuuren et al resurfaced the dorsal surface of the hands of 11 immunosuppressed renal transplant recipients with skin cancers, followed by skin graft replacements. The patients were followed up for a mean period of 4.7 years, with no skin cancer recurrence on the resurfaced skin itself. Histologic studies have shown that laser resurfacing ablates the epidermis and the upper dermis in a precise controlled manner to a depth that depends on the number of laser passes. An average of 2 to 3 passes with short-pulsed, high-energy CO2 lasers at the settings described above removes the photodamaged epidermis and part of the papillary dermis, while stimulating the production of new collagen and causing remodeling of the extracellular space in the dermis. Theoretically, any precancerous lesions (actinic keratosis) or superficial epithelial tumors, such as superficial BCC or SCC in situ, should be removed with this procedure. Also, reepithelialization of resurfaced skin occurs from adnexal cells, such as follicular cells, that are deeper in the skin and, presumably, have had less exposure to the carcinogenic effects of UV radiation. Biopsy specimens of sun-damaged skin treated with CO2 laser have shown a marked histologic improvement 4 weeks after treatment, with regeneration of a normal epidermis free of atypia. Based on these considerations, it is surprising that 2 of our approximately 700 patients (younger than 60 years) who have undergone full-face laser resurfacing developed facial skin cancer shortly after the procedure. In fact, these observations are in agreement with the results of a previous study in which 5 (14%) of 35 patients with severe actinic damage who underwent laser CO2 resurfacing developed actinic keratoses and basal cell skin cancers within 12 months after the procedure. In our 2 cases, the number of laser passes applied should have vaporized the skin to the level of the middle to deep papillary dermis, leaving a residual zone of 50 to 150 m of residual thermal necrosis. It is possible, in fact likely, that the tumors existed before the procedure was performed but were not clinically obvious. This scenario is most likely in the case of the large infiltrating BCC found 6 months after resurfacing, in which there was had no epidermal or papillary dermal involvement. In the nodulocystic lesions, atypical cells were most likely located deep in the follicular epithelium and, unaffected by the resurfacing procedure, continued to grow postoperatively under the influence of various tumor-promoting growth factors that are released during the regenerative phase of the skin. This hypothesis is based on recent studies that indicate a role of follicular cells in the formation of skin cancers. Experimental evidence from the use of chemical carcinogens in mice suggests that some epidermal tumors derive from stem cells in the hair follicle. If these observations prove to be true in humans, it may indicate that skin cancers can originate from follicular cells, which, because of their location, remain undamaged during resurfacing. Further studies are needed to determine the effectiveness of skin resurfacing in the treatment of photoaged skin and its ability to prevent malignant degeneration or to delay the progression of skin tumors. The fact, however, that nonmelanoma skin cancers appeared in relatively recently resurfaced skin suggests that CO2 laser resurfacing is not as effective in the prophylaxis of these tumors as previously thought. Skin cancer surveillance is therefore essential in cases in which there is photoaging after laser skin resurfacing. Also, sun-protection measures, including the use of sunscreens and appropriate clothing, may be even more important not only in the postoperative healing phase but also for a prolonged period after laser skin resurfacing. RE Fitzpatrick MP Goldman J Ruiz-Esparza Clinical advantage of the CO2 laser superpulsed mode: treatment of verruca vulgaris, seborrheic keratoses, lentigenes, and actinic cheilitis. J Dermatol Surg Oncol. 1994;20:449-456. SJ Trimas DAF Ellis RD Metz The carbon dioxide laser: an alternative for the treatment of actinically damaged skin. Dermatol Surg. 1997;23:885-889. PA Massey YD Eliezri A case report of laser resurfacing as a skin cancer prophylaxis. Dermatol Surg. 1999;25:513-516. K Atabay C Celebi S Cenetoglu NK Baran Z Kiymaz Facial resurfacing in xeroderma pigmentosum with monoblock full-thickness skin graft. Plast Reconstr Surg. 1991;87:1121-1125. EJ van Zuuren AN Posma RE Scholtens BJ Vermeer FJ van der Woude JN Bouwes Bavinck Resurfacing of the back of the hand as treatment and prevention of multiple skin cancers in kidney transplant recipients. J Am Acad Dermatol. 1994;31:760-764. ANB Kauvar HA Waldorf RG Geronemus A histopathological comparison of "char-free" carbon dioxide lasers. Dermatol Surg. 1996;22:343-348. LM David GP Lask E Glassberg R Jacoby RP Abergel Laser ablation for cosmetic and medical treatment of facial actinic damage. Cutis. 1989;43:583-587. JE Fulton AD Rahimi P Helton K Dahlberg AG Kelly Disappointing results following resurfacing of facial skin with CO2 lasers for prophylaxis of keratoses and cancers. Dermatol Surg. 1999;25:729-732. SJ Miller ZG Wei C Wilson L Dzubow TT Sun RM Lavker Mouse skin is particularly susceptible to tumor initiation during early anagen of the hair cycle: possible involvement of hair follicle stem cells. J Invest Dermatol. 1993;101:591-594. Raynaud Phenomenon and Behet Disease: Diagnosis With Technetium Tc 99m Methylene Diphosphonate Bone Scan and Treatment With Continuous Sympathetic Block Behcet's Syndrome behcet's syndrome Case Report case report Radionuclide Imaging radionuclide imaging Raynaud Disease raynaud disease Scintigraphy scintigraphy Technetium Tc 99m Methylene Diphosphonate technetium tc 99m methylene diphosphonate Meltem nder Gazi University School of Medicine Department of Dermatology 11 kat Beevler Ankara, Turkey (e-mail: monder@med.gazi.edu.tr) Mge Gler zden A. Burhan Aksakal Didem Akali Avni Babacan Tamer Atasever Ankara Not Available Behet disease (BD) is a multisystem disorder of unknown cause characterized by mucocutaneous, ocular, articular, gastrointestinal, neurologic, and vascular involvement. The association of BD and Raynaud phenomenon has not been previously reported. Report of a Case A 33-year-old man with BD (Figure 1A) for 7 years was admitted to the hospital with a 10-day history of severe pain and redness on his hands and fingers, especially triggered by cold, and a digital ulcer on the second finger (Figure 1B). He had a stasis ulcer on his left medial malleolus for 6 months and a history of recurrent oral and genital ulcers, uveitis, erythema nodosum, and joint pain. Pathergy test findings were positive. Blood was analyzed for anemia, polycythemia, leukopenia, erythrocyte sedimentation rate, serum protein (electrophoresis), antinuclear antibodies, antidouble-stranded DNA, anticentromeres, anti-Scl 70 and anticardiolipin antibodies, rheumatoid factor, cryoglobulins and cold agglutinins, and protein C and S activities to exclude connective tissue disorders. Results were all normal. Bilateral upper extremity arterial and venous Doppler ultrasonographic results showed no evidence of atherosclerotic plaque or venous thrombosis. Flow rate was normal. Bilateral lower extremity venous Doppler ultrasonographic findings showed varicosity of the popliteal veins. Both saphena magna veins were of thin caliber. No thrombus formation was detected. Figure 1. A, Patient with Behet disease and recurrent aphthous ulcer (arrow); B, digital ulcer (arrow) caused by Raynaud phenomenon on the second finger. Three-phase bone scintigraphy was performed after intravenous administration of 740 mBq of technetium Tc 99m methylene diphosphonate (Medrocis; Biocis International, Vienna, Austria) into the left dorsal foot vein. Early blood pool phase images showed decreased tracer uptake (hypoperfusion) in the second, third, and fourth fingers (Figure 2A). The patient's pain intensity according to the visual analog scale was 8. He was diagnosed as having primary Raynaud phenomenon. Figure 2. A, Blood pool phase of technetium Tc 99m methylene diphosphonate bone scan showing decreased activity in the second, third, and fourth fingers (arrows); B, after the sympathetic block treatment, the scan findings show improved perfusion. We tried conservative treatment with nifedipine and diosmin-hesperidin combination and these were ineffective to control the pain and digital ulcer. A sympathetic block was planned for the advanced treatment. The pain was relieved after a stellate ganglion block was administered via paratracheal (anterior) approach with 1% lidocaine. A continuous brachial plexus block was performed after the second stellate ganglion block. A vertical infraclavicular block technique was used, and a catheter was placed. The plexus was identified by a nerve stimulator. Ten milliliters of 0.125% bupivacaine hydrochloride was injected through the catheter 3 times a day for 30 days. The patient was comfortable, and there were no complications. The digital ulcer healed, and the cyanosis disappeared after 3 months. Pain was relieved and the patient's visual analog scale pain intensity was reduced to 2. The bone scan was repeated after sympathetic block treatment, and blood pool phase images revealed totally normal perfusion in the affected fingers (Figure 2B). There has been no sign of pain or new finger ulcer for 6 months. Comment Vascular findings in BD involve blood vessels of all sizes in both the arterial and venous systems. Thrombophlebitis, thrombosis of the superior vena cava, peripheral vein thrombosis, caval system occlusion, arterial aneurysms, and arterial occlusion can be found. The dramatic large vessel involvements fortunately occur in only a minority of patients. Patients with cardiovascular involvement generally have a poor prognosis. As far as we know, there is no case of BD with Raynaud phenomenon in the literature, and we do not know the relationship between them, if any. Raynaud phenomenon has a multifactorial origin. Its symptoms include vasospasm, erythema, whiteness of the skin, cyanosis, and sometimes ulcers on the fingers. It can be caused by occupational hazards, occlusive diseases, connective tissue disorders, and traumatic or drug-related factors. However, we could not find any related factor causing the Raynaud syndrome in our case. Our patient was being treated with colchicine and symptomatic treatment with topical steroids for oral and genital ulcers. Although several drugs may cause Raynaud phenomenon, we did not find any relationship between colchicine treatment and Raynaud phenomenon. Nifedipine, diltiazem, reserpine, guanethidine, prazosin, nitrates, and parenteral prostacyclins are beneficial drugs in the treatment of Raynaud phenomenon. Although in classic references, upper extremity sympathetic blocks are not recommended for treatment of Raynaud phenomenon because of the short symptom-free period (from 6 months to 2 years), there are reports of patients who benefited from sympathetic block. In our case, the patient benefited from stellate ganglion block, and we decided to perform a continuous sympathetic block via an infraclavicular catheter. Sympathetic function can be determined by evaluation of blood flow and pain. A bone scan is useful in diagnosing and monitoring the patients with reflex sympathetic dystrophy. For this purpose we used the bone scan for diagnosis. We also compared blood flow using a 3-phase technetium Tc 99m methylene diphosphonate bone scan before and after the treatment. A repeated bone scan revealed improvement in perfusion of the affected fingers as seen Figure 2B. The pathogenic mechanisms underlying these vascular events in BD are not well understood, but roles of genetic anticipation, autoimmunity, vasculitic endothelial cell injury, defective fibrinolysis, and/or arachidonic acid metabolites have been argued. Antibodies to endothelial cells have been identified in some patients. Endothelial cell damage causes auto-oxidative damage. Elevation of fibrinopeptide-A levels has also been found during the active disease, suggesting that abnormal fibrinolysis contributes to the pathogenesis of the disease. Endothelial damage due to leukocytoclastic vasculitis and leading to defective prostacyclin generation or defective fibrinolysis has been suggested in the pathogenesis of thrombosis in BD, but the exact mechanism is not fully understood. In recent studies an imbalance between prostaglandin I2 and thromboxane A2 has been detected in Raynaud phenomenon. It has been shown that prostacyclin synthesis is impaired in the vessel walls of patients with BD as well. Autoimmune mechanisms may be the other factor, but Raynaud phenomenon secondary to connective tissue diseases and/or BD and their relevance to the etiopathology of Raynaud phenomenon is uncertain. This interesting common point between BD and Raynaud phenomenon needs further evaluation. M nder MA Grer Behet's disease: an enigmatic vasculitis. Clin Dermatol. 1999;17:571-576. A Kuzu C zaslan C Kksoy Vascular involvement in Behet's disease: 8-year audit. World J Surg. 1994;18:948-954. B Wechsler T Dul E Kieffer Cardiovascular manifestations of Behet's disease. Ann Intern Med. 1999;150:542-554. M Engelhart The effect of sympathetic blockade and cooling in Raynaud's phenomenon. Clin Physiol. 1990;10:131-136. C Schiepers Clinical value of dynamic bone and vascular scintigraphy in diagnosing reflex sympathetic dystrophy of the upper extremity. Hand Clin. 1997;13:423-429. T Saito T Hanma Y Sato Y Fujioka Autoimmune mechanisms as a possible aetiology of Behet's syndrome: an electron microscopic study of the oral mucosa. Virchows Arch Pathol Anat. 1971;353:261-272.
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  • Yuan-Hong Li MD, PhD, Xing-Hua Gao MD, PhD, Chun-Di He MD, PhD, Guowei Zhang MD, Xiaoping Dong MD, PhD, Hong-Duo Chen MD, Alexander J. Stratigos MD, Steven Tahan MD, Jeffrey S. Dover MD, FRCPC, Meltem nder MD, Mge Gler zden MD, A. Burhan Aksakal MD, Didem Akali MD, Avni Babacan MD, Tamer Atasever MD
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  • Li, Y.-H., Gao, X.-H., He, C.-D., Zhang, G., Dong, X., Chen, H.-D., Stratigos, A. J., Tahan, S., Dover, J. S., nder, M., zden, M. G., Aksakal, A. B., Akali, D., Babacan, A., & Atasever, T. VIGNETTES. , N/A.
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  • Yuan-Hong Li MD, PhD, Xing-Hua Gao MD, PhD, Chun-Di He MD, PhD, Guowei Zhang MD, Xiaoping Dong MD, PhD, Hong-Duo Chen MD, Alexander J. Stratigos MD, Steven Tahan MD, Jeffrey S. Dover MD, FRCPC, Meltem nder MD, Mge Gler zden MD, A. Burhan Aksakal MD, Didem Akali MD, Avni Babacan MD, Tamer Atasever MD
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