Phacomatosis pigmentokeratotica (PPK) is a rare epidermal nevus syndrome characterized by the co-occurrence of a sebaceous nevus and a speckled lentiginous nevus. The coexistence of an epidermal and a melanocytic nevus has been explained by two homozygous recessive mutations, according to the twin spot hypothesis, of which PPK has become a putative paradigm in humans. However, the underlying gene mutations remained unknown. Multiple tissues of six patients with PPK were analyzed for the presence of RAS, FGFR3, PIK3CA, and BRAF mutations using SNaPshot assays and Sanger sequencing. We identified a heterozygous HRAS c.37G>C (p.Gly13Arg) mutation in four patients and a heterozygous HRAS c.182A>G (p.Gln61Arg) mutation in two patients. In each case, the mutations were present in both the sebaceous and the melanocytic nevus. In the latter lesion, melanocytes were identified to carry the HRAS mutation. Analysis of various nonlesional tissues showed a wild-type sequence of HRAS, consistent with mosaicism. Our data provide no genetic evidence for the previously proposed twin spot hypothesis. In contrast, PPK is best explained by a postzygotic-activating HRAS mutation in a multipotent progenitor cell that gives rise to both a sebaceous and a melanocytic nevus. Therefore, PPK is a mosaic RASopathy.
Skin ageing is characterized by small and fine wrinkles, roughness, laxity, and pigmentation as a result of epidermal thinning, collagen degradation, dermal atrophy, and fewer fibroblasts. Plasma rich in growth factors (PRGF) is an autologous plasma preparation enriched in proteins obtained from patient's own blood aimed at accelerating tissue repair and regeneration. To evaluate the benefits of PRGF in skin photodamage, 10 healthy volunteers were treated with three consecutive intradermal injections of PRGF in the facial area. Clinical outcomes and histological analysis were performed. A statistically significant increase in the epidermis and papillary dermis thickness was seen after PRGF treatment (p < 0.001). Skin thickening was observed in all patients studied, being more intense in the group of patients with photodamage (p < 0.001). After PRGF treatment, a reduction of the average area fraction of solar elastosis was observed in patients with clinical and histological signs of skin photodamage (p < 0.05).No changeswere observed in the number of CD31, XIIIa factor, cKit, CD10, nor p53-positive cells. The improvement score after PRGF use was 0.75 (9/12) for the group of patients with signs of skin photodamage. Intradermal PRGF infiltration appears to be an effective treatment for the photodamaged skin.
RCM may safely detect the dynamic biological changes that the skin undergoes in response to ionizing radiation, even before than clinical onset of acute radiation dermatitis. Therefore, RCM may be useful to make an early and non-invasive diagnosis of radiation dermatitis during radiotherapy, allowing an early selection of patients needing treatment or close monitoring and avoiding skin biopsies.
Kaposi's sarcoma (KS) is an angioproliferative disorder caused by human herpesvirus 8 (HHV-8). Current research efforts have focused on the study of the relative role of KSHV-encoded genes in Kaposi's sarcomagenesis in order to identify novel mechanism-based therapies for patients suffering from this tumor. Although several viral genes have potential for KS pathogenesis, compelling data point to the KSHV-encoded G protein-coupled receptor (vGPCR) as a leading candidate viral gene for the initiation of KS. Interestingly, the oncogenic potential of vGPCR seems to correlate with its capacity to activate the mammalian target of rapamycin (mTOR) signaling pathway. Rapamycin, the prototypical inhibitor of the mTOR signaling pathway, has recently emerged as an effective treatment for KS when administered orally. In this case report, we present an immunocompetent patient with KS lesions treated with topical rapamycin achieving clinical and histologic healing after 16 weeks of treatment. The topical application of rapamycin could be a novel therapeutic option for the treatment of KS.
Reed et al. 1 reported the first drug-induced subacute cutaneous lupus erythematosus (SCLE) cases in 1985. These cases were related to the intake of thiazidic diuretics and were accompanied by positive anti-Ro antibodies. Multiple cases related to different drugs have been published since then. Typical clinical and histological features of SCLE were present with positive anti-Ro antibodies in most cases. 2 The most commonly implicated drugs were anti-hypertensive drugs (thiazide diuretics, angiotensin-converting enzyme inhibitors, beta-blockers and calcium channel blockers), terbinafine and bupropion. [3][4][5] Until now, only a case series of four patients with chemotherapy-induced SCLE have been published. These four patients were treated with taxanes (paclitaxel and docetaxel 6 ). We describe a patient who was treated with cyclofosfamide and adriamycine for a relapse of her breast carcinoma and developed a few days later cutaneous lesions, both clinical and histological, compatible with SCLE and positive anti-Ro antibodies.A 58-year-old female who had been diagnosed with breast cancer in 1997. The cancer was excised, and she was treated with tamoxifen for 5 years. In September 2001, a relapse was detected with bone, breast, lung and liver metastasis. One month later, she started a chemotherapy regimen with adriamycine 100 mg and ciclofosfamide 1000 mg every 21 days (three doses). She developed an erythematous and scaling plaque on her right forearm 2 weeks after the first dose. After the second dose similar lesions appeared on both forearms, the legs and the chest and upper part of the back (Figure 1). There was no history of prior photoexposure.A cutaneous biopsy was performed showing vacuolar interface changes with marked mucinosis in the dermis, features consistent with SCLE. Routine blood tests including blood cells count, biochemistry and autoantibodies revealed only positive ANA (1/160) and anti-Ro antibodies. Antihystone antibodies were negative. Systemic involvement was ruled out. Despite finishing the chemotherapy regimen, cutaneous lesions continued to appear.
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