Pedro Redondo

Skin cancer in heart transplant recipients

BACKGROUND The frequency of skin cancer in organ transplant recipients is high, up to 15%. OBJECTIVE Our purpose was to determine the incidence of skin cancer in patients who underwent immunosuppression after heart transplantation and to determine the factors important in the appearance of skin cancer. METHODS We studied the frequency of skin cancer in 92 of 111 patients after they underwent heart transplantation between January 1984 and December 1993. RESULTS At least one cutaneous neoplasm (squamous cell carcinoma and/or basal cell carcinoma) developed in 14 patients (15.2%). The basal cell carcinoma to squamous cell carcinoma ratio was 1:1.5. The skin cancer appeared an average of 31.5 months after transplantation; the average was 36 months for squamous cell carcinoma and 25.3 months for basal cell carcinoma. Cumulative risk rose from 4.3% at 1 year up to 43.8% at 7 years after transplantation. The overall incidence of both types of skin cancer was 45.3 per 1000 posttransplant person-years, with an incidence of 25.8 for basal cell carcinoma and 29.1 for squamous cell carcinoma. Most skin cancers developed between 2 and 3 years after transplantation. All patients were exposed to a significant amount of ultraviolet radiation and had skin type II or III. We did not find a significant association between skin cancer and haplotype HLA-A3, HLA-A11, HLA-DR, and the number of mismatches for HLA-B. CONCLUSION We found an increased progressive cumulative incidence of skin cancer in heart transplant recipients for two reasons: (1) immunosuppression and increased exposure to ultraviolet radiation in some patients, and (2) the skin type of certain patients. We emphasize the need for photoprotection in this group of patients and regular skin cancer screening examinations.

Expression and serum levels of MMP‐2 and MMP‐9 during human melanoma progression

Matrix metalloproteinases (MMP)‐2 and ‐9 have been implicated in malignant tumour progression, partly because they degrade collagen type IV, a major component of basement membranes. Biopsy specimens from 56 patients with primary melanoma and 7 with cutaneous or nodal metastases were studied by immunohistochemistry. Of 39 patients with estimated good prognosis, 70.5% of melanomas were negative for MMP‐2, compared with only 47% of 17 melanomas in patients who developed metastasis during the 3‐year follow‐up. All skin and nodal metastases were negative for MMP‐2 and positive for MMP‐9. Of 14 thick melanomas, 9 were mostly positive for MMP‐2 expression, suggesting a possible association with the invasiveness of the melanoma. MMP‐2 and MMP‐9 plasma levels were analysed in another 29 patients with melanoma (10 stage I and II, 9 stage III, and 10 stage IV) and in 10 healthy controls. No difference in MMP‐9 plasma levels was found among the groups. Higher MMP‐2 concentrations were observed in patients with metastatic disease (stage IV) than in those with primary melanoma (stage I) or in controls. Serial levels in two patients who passed from stage I to stage III or IV showed no significant difference in MMP‐2 or ‐9 values. We conclude that MMP‐2 expression might be associated with progression of the melanoma. Circulating MMP‐2 and ‐9 levels have shown low sensitivity and specificity, so they do not seem to be good tumour markers in patients with melanoma.

α-MSH regulates interleukin-10 expression by human keratinocytes

Abstract Normal human keratinocytes (HKC) are able to synthesize α-MSH. Because the production of α-MSH by HKC is induced significantly by ultraviolet B radiation, the involvement of keratinocyte-derived α-MSH in UV-induced immunosuppression has been suggested. The induction of the antiinflammatory cytokine IL-10 in monocytes is a major mechanism in the antiinflammatory actions of α-MSH. In the present study, HKC were investigated for their ability to produce IL-10 after α-MSH stimulation. HKC were obtained from the skin of human female breast sections and either left untreated or treated with 0.01 or 0.1 μg/ml α-MSH for different times. Using RT-PCR, HKC were shown to express IL-10 mRNA even under basal conditions, and treatment with α-MSH increased expression. Only minimal concentrations of IL-10 protein were detected in supernatants from the α-MSH-stimulated cultures. To the best of our knowledge this is the first report of IL-10 expression by cultured HKC after α-MSH stimulation. Further studies are needed to determine the biological and therapeutic relevance of these findings.

Diagnosis and management of extensive vascular malformations of the lower limb: Part I. Clinical diagnosis

There is significant confusion in the literature when describing vascular anomalies, and vascular malformations are often misnamed or incorrectly classified. Part I of this two-part series on the diagnosis and management of extensive vascular malformations of the lower limbs will discuss the dermatologists role in the diagnosis of these lesions. At least nine types of vascular malformations with specific clinical and radiologic characteristics must be distinguished in the lower limbs: Klippel-Trénaunay syndrome, port-wine stain with or without hypertrophy, cutis marmorata telangiectatica congenita, macrocephaly-capillary malformation, Parkes Weber syndrome, Stewart-Bluefarb syndrome, venous malformation, glomuvenous malformation, and lymphatic malformation. This article highlights the differences in clinical appearance and discusses the differential diagnosis of extensive vascular malformations in an attempt to ensure earlier diagnosis and better outcomes for these patients.

Immunologic escape and angiogenesis in human malignant melanoma

BACKGROUND Melanoma escape mechanisms include immunosuppressive and angiogenic cytokine production. OBJECTIVE We sought to determine vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) expression by immunohistochemistry, and soluble circulating plasma levels of VEGF, bFGF, IL-10, and transforming growth factor-beta2 in patients with different stages of melanoma. METHODS Biopsy specimens from 42 patients with primary melanoma and 9 with cutaneous metastases were studied by immunohistochemistry. In another 46 patients with melanoma (8 stage I and II; 18, III; and 20, IV) and in 10 healthy control participants, bFGF, VEGF, IL-10, and transforming growth factor-beta2 circulating levels were analyzed. RESULTS bFGF was positive in 85% and VEGF in 47.5% of 42 primary melanomas. Of 10 patients with primary melanoma (Breslow depth 1.5-3 mm) 6 were VEGF positive and had metastases develop, whereas 4 were VEGF negative and had no metastases at 5 years of follow up. VEGF, bFGF, and IL-10 plasma levels in patients with stages III and IV melanoma were higher than the control group (P <.05 and P <.01, respectively). An inverse relationship was found between VEGF and IL-10. Specifically, in 7 patients with IL-10 levels higher than 10 pg/mL, VEGF levels were less than 49 pg/mL (P <.05); in 9 patients with VEGF levels higher than 100 pg/mL, IL-10 levels were less than 6.7 pg/mL (P <.01). CONCLUSION VEGF expression in 1.5- to 3.0-mm Breslow depth melanomas may be considered as an unfavorable prognostic factor. Immunosuppressive (IL-10, transforming growth factor-beta2) and proangiogenic (bFGF, VEGF) cytokines are increased in metastatic melanoma. Inverse plasma levels between IL-10 and VEGF in patients with metastatic melanoma are shown in vivo for the first time, the significance of which must be further investigated.

Topical N-acetylcysteine for lamellar ichthyosis

The antioxidant N-acetylcysteine has an antiproliferative effect on a culture of human keratinocytes. We report a patient with lamellar ichthyosis satisfactorily treated with topical N-acetylcysteine.

Graft-versus-host disease after liver transplantation

We describe a case of graft-versus-host disease that developed in the recipient of an orthotopic liver transplant. A maculopapular eruption developed on postoperative day 25. After the diagnosis of graft-versus-host disease was made aggressive therapy was instituted, which resulted in a complete recovery.

Topical rapamycin combined with pulsed dye laser in the treatment of capillary vascular malformations in Sturge-Weber syndrome: Phase II, randomized, double-blind, intraindividual placebo-controlled clinical trial

BACKGROUND Sturge-Weber syndrome (SWS) is characterized by port-wine stains (PWS) affecting the face, eyes, and central nervous system. Pulsed dye laser (PDL) is the standard treatment for PWS. Unfortunately, recurrence is frequent because of reformation and reperfusion of blood vessels. OBJECTIVE We sought to assess the clinical efficacy of topical rapamycin combined with PDL in PWS of patients with SWS. METHODS We conducted a phase II, randomized, double-blind, intraindividual placebo-controlled, clinical trial. We recruited 23 patients with SWS and facial PWS (12 women; median age 33 years, age range 17-65 years) from the University Clinic of Navarra, Spain. Four interventions were evaluated: placebo, PDL + placebo, rapamycin, and PDL + rapamycin. Clinical and histologic responses were evaluated using a chromatographic computerized system, spectrometry, and histologic analyses at 6, 12, and 18 weeks after the intervention. RESULTS PDL + rapamycin yielded the lowest digital photographic image score and the lowest percentage of vessels in histologic analysis, and showed a statistically significant improvement compared with the other interventions. The treatment was generally well tolerated. LIMITATIONS PDL was only applied to the lateral parts of the PWS area. CONCLUSION Topical rapamycin associated with PDL seems to be an effective treatment for PWS in patients with SWS.

Angiolymphoid hyperplasia with eosinophilia successfully treated with imiquimod

SIR, Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon, benign vascular proliferation that primarily affects middle-aged women with particular predilection for the head and especially for the periauricular area. Clinically, it is characterized by solitary or multiple red-brown cutaneous papules or nodules, which are often pruritic or painful with little propensity for spontaneous resolution. Numerous therapeutic approaches have been tried for ALHE including destructive techniques such as electrodesiccation and cryotherapy, surgery, radiotherapy, glucocorticoids (topical or intralesional), retinoids, sclerosing injections, pentoxifylline, pulse dye laser, argon laser, interferon-a2a and cytotoxic agents. We report a patient with refractory ALHE who was successfully treated by topical application of imiquimod cream. A 37-year-old white woman was referred to the Department of Dermatology University Clinic of Navarra with an 8-year history of red-brown itchy and tender nodules located on her left ear and preauricular area. The lesion started insidiously with no tendency for spontaneous resolution. There were no regional lymphadenopathy or laboratory abnormalities, especially peripheral eosinophilia. At the time of our first examination, the patient had erythematous papulonodules, tan, dull red in colour, located around the tragus, with involvement of meatus acusticus externus (Fig. 1a). Magnetic resonance imaging showed no arteriovenous malformation. She had previously been treated with excision and with intralesional and topical glucocorticoids, which all provided temporary improvement but no lasting benefits. Histopathological examination confirmed a diagnosis of ALHE. The lesion was composed of small abnormal blood vessels lined by prominent cells with abundant cytoplasm or solid aggregates of epithelioid cells. This abnormal vascular proliferation was disposed around a smallsized artery showing fibrotic change. Mitotic figures were not observed. Surrounding the abnormal vessels was a dense inflammatory infiltrate characterized by lymphocytes intermixed with abundant eosinophils (Fig. 2). The patient started treatment with 5% imiquimod cream five times a week. By

Photo-induced toxic epidermal necrolysis caused by clobazam

Toxic epidermal necrolysis (TEN) is a life‐threatening disease, the pathogenesis of which remains largely unknown. We describe a 23‐year‐old woman under treatment with clobazam who developed lesions of TEN In light‐exposed areas. Patch and photopatch tests with clobazam were negative. The cellular phenotype and cytokines were studied in blister fluid. The cellular infiltrate was composed mainly of T lymphocytes with a predominant cyloloxic phenotype. Tbere was an increase in the level of tumour necrosis factor (TNF)‐α in blister fluid compared with the control (a patient with bullous pemphigoid).