Doris Helbig

Immunohistochemical investigation of wound healing in response to fractional photothermolysis

Despite growing clinical evidence of ablative fractional photothermolysis (AFP), little is known about the spatiotemporal molecular changes within the targeted compartments. Six subjects received three different single AFP treatments using a scanned 250 mum CO(2)-laser beam. Spatiotemporal changes of skin regeneration were estimated by immunohistochemical investigation (HSP70, HSP72, HSP47, TGFbeta, procollagen III, CD3, CD20, and CD68) in skin samples 1 h, 3 days, and 14 days postintervention. The remodeling was uniformly started by regrowth of the epidermal compartment followed by partial to complete replacement of the microscopic ablation zones (MAZ) by newly synthesized condensed procollagen III. From day 3 to 14, the number of macrophages as well as giant cells surrounding the MAZ increased. TGFbeta expression was highest 1 h to 3 days following AFP. HSP70 and HSP72 expressions were highest 3-14 days postintervention in the spinocellular layer leading to an upregulation of HSP47. AFP performed by a scanned CO(2)-laser results in an early epidermal remodeling, which is followed by a dermal remodeling leading to a replacement of the MAZ with newly synthesized (pro)-collagen. During this, an inflammatory infiltrate with CD3(+) and CD20(+) cells surrounds the MAZ. The count of macrophages and giant cells involved in the replacement of the necrotic zones seems to be crucial for wound healing.

Molecular changes during skin aging and wound healing after fractional ablative photothermolysis

Photo‐damaged skin is characterized by major alterations of the extracellular matrix and collagen network, leading to clinically obvious signs of skin aging. UV radiation increases the levels of matrix metalloproteinase (MMP) 1, which initiates the cleavage of fibrillar collagen types I and III. The developing collagen fragments are further degraded by MMPs 2 and 9. Various ablative, non‐ablative, thermal and non‐thermal rejuvenation modalities have been tested for their capacity to reverse epidermal and dermal signs of photo‐ and chronological‐aging. Light and laser therapies are among the most effective treatment options for skin rejuvenation. Conventional laser therapy treats entire surface areas by selective photothermolysis or ablation. Recently, intervention with a fractional ablative laser leads to fast wound healing, and hence, a substantial amount of the target skin area is left untreated. It is not known if the efficacy of a particular ablative skin rejuvenation treatment depends on the extent of microwounding and/or the amount of heat produced. The underlying molecular changes are not fully understood but have been postulated to be induced by time‐dependent changes in heat shock proteins, transforming growth factor β, MMPs, hyaluronic acid synthethases, hyaluronidases and HA, among others.

Nonablative skin rejuvenation devices and the role of heat shock protein 70: results of a human skin explant model

Nonablative thermal laser therapy with a 1,540-nm laser induces controlled, spatially determined thermal damage, allowing subsequent collagen remodeling while preserving the epidermis. A photorejuvenation effect using nonthermal nonablative stimulation of cells with low energy and narrow band light has been termed photomodulation. Light emitting diodes (LEDs) are narrow band emitters that lead to photomodulation via stimulation of mitochondrial cell organelles. In a previous study, we demonstrated in a human skin explant model that heat shock protein 70 (HSP70) plays a pivotal role in the initiation of skin remodeling after ablative fractional photothermolysis. To test its importance in nonablative laser therapy and photomodulation, the spatio-temporal expression of HSP70 is investigated in response to a 1540-nm laser treatment and six different LED therapies. An Er:glass laser is used with a 1-Hz repetition rate, 30-J/cm(2) fluence, and a hand piece with a 2-mm spot size. Nonthermal nonablative treatment is performed using two LED (LEDA SCR red light: 635 nm, 40 to 120 W/cm(2), 40 to 120 J/cm(2); LEDA SCR yellow light: 585 nm, 16 to 35 W/cm(2), 20 to 100 J/cm(2); spot size 16 x 10 cm). Immediate responses as well as responses 1, 3, or 7 days postprocedure are studied; untreated skin explants serve as control. Immunohistochemical investigation (HSP70) is performed in all native, nontreated, and Er:glass laser- or LED-treated samples (n=175). Nonablative laser therapy leads to a clear time-dependent induction of epidermally expressed HSP70, peaking between one to three days post-treatment. In contrast, none of the various LED treatments up-regulated the HSP70 expression in our skin explant model. HSP70 is up-regulated by nonablative but thermal laser devices, but does not seem to play a significant role in the induction of skin remodeling induced by photomodulation. The maximum of HSP70 expression is reached later after Er:glass laser intervention compared to ablative fractional (AFP) treatment.

Complete remission of cutaneous and subcutaneous melanoma metastases of the scalp with imiquimod therapy.

Multiple cutaneous and subcutaneous melanoma metastases represent a therapeutic challenge. A 63‐year‐old man presented with multiple cutaneous and subcutaneous melanoma metastases on his right parieto‐occipital region that appeared ten weeks after surgical excision of the primary tumor. Staging showed no further metastases. Because of the large area of cutaneous metastatic spread, the location and the limited possibility of a complete excision, we decided to begin immunomodulatory therapy with imiquimod applied for eight hours daily five days a week. After six weeks of imiquimod monotherapy, a partial remission of the cutaneous metastases had occurred. After 17 months, the remission of these metastases was complete. Four months later the patient is still free of cutaneous, visceral, cerebral and lymph node metastases.

Side effects of HIV therapy

The use of highly active effective antiretroviral therapies (ART) has dramatically decreased the morbidity and mortality of the HIV infection. Over 20 anti‐retroviral substances are available in four different classes. Side effects of HIV therapy are common and may influence the prognosis, as the medications are required lifelong for the still incurable infection. ART‐associated allergic reactions, lipodystrophy syndrome and immune reconstitution syndrome are side effects frequently seen by dermatologists. Exanthems are challenging as drug reactions must be separated from immune reconstitution, syphilis and viral exanthems and then the causative agent must be identified from a long list of medications. Non‐nucleoside reverse transcriptase inhibitors typically cause allergic exanthems. Mitochondrial toxicity caused by nucleoside reverse transcriptase inhibitors is responsible for lipoatrophy and fatty changes in the liver. Protease inhibitors cause diarrhea, abnormalities of glucose and fat metabolism and lipohypertrophy. Before other medications or surgical measures are undertaken to address side effects of ART, the regimen should be adjusted to include alternative but equally effective agents.

Photodynamic therapy and the role of heat shock protein 70

Photodynamic therapy (PDT) is an effective treatment for superficial epithelial skin cancers and is also being utilised for skin rejuvenation. PDT with porphyrin-derived photosensitisers may be capable of inducing rapid cytochrome c release initiating apoptotic cascade via an activation of different caspases. Hsp70 has been demonstrated to directly bind to the caspase recruitment domain (CARD) of apoptotic-protease activating factor 1 (Apaf-1), thereby preventing the recruitment of oligomerisation of Apaf-1 and association of Apaf-1 with procaspase 9. Further, cytoplasmic Hsp70 rapidly translocates to the cell surface where it stabilises damaged membranes and preserves their integrity depending on the PDT dose. The induced cell surface expression and release of Hsp70 and its relevance for tumor response or skin rejuvenation is not fully understood, but seems to be of interest for monitoring, predicting or optimising treatment regimens. This review aims to summarise the current knowledge on PDT mediated cell signalling.

Nodular localized primary cutaneous amyloidosis and primary marginal zone B‐cell lymphoma on the nose: treatment with microscopically controlled surgery

Amyloidosis is a term that describes a group of disorders characterized by the abnormal deposition of proteins causing alterations of tissue architecture and function. Amyloid may be deposited throughout many organs of the body as in systemic amyloidosis, or it may be restricted to a single tissue site as in localized amyloidosis. Nodular localized primary cutaneous amyloidosis (NLPCA) is the rarest variant of cutaneous amyloidoses. Primary cutaneous marginal zone B-cell lymphoma (PCMZL) is a low-grade malignant B-cell lymphoma of the skin, and it is considered part of the broad group of extranodal marginal zone B-cell lymphomas (EMZL) commonly involving mucosal sites, called MALT (mucosa-associated lymphoid tissue) lymphomas. We present a patient who developed in one lesion of the nose an NLPCA and a PCMZL. To our knowledge, NLPCA and PCMZL in one lesion and following therapy with microscopically controlled surgery have not previously been reported.

Epidermal and dermal changes in response to various skin rejuvenation methods.

During the last years, a number of new devices have been developed to improve the dermal and epidermal signs of photo‐ and chronological skin ageing. There are well‐established ablative and non‐ablative skin resurfacing options using different lasers and light sources, but side effects have been observed frequently. A recently developed photorejuvenation method using non‐thermal stimulation of skin cells with low energy and narrow band light has been termed photomodulation. Light emitting diodes are the ideal source of this kind of light that stimulate mitochondrial cell organelles leading to up‐regulation of cytochrome electron transport pathway leading to mitochondrial DNA gene modulation. This paper reviews the most current knowledge of intrinsic and extrinsic changes of ageing and summarizes different systems for skin rejuvenation with focus on non‐thermal non‐ablative skin rejuvenation modalities.

Haut- und Schleimhautulzerationen bei heparininduzierter Thrombozytopenie (HIT) II

About 0.1-2% of patients receiving heparin develop heparin-induced thrombocytopenia type II (HIT II) which is caused by antibodies directed against heparin-platelet factor 4 (PF4) complexes. Activation of thrombocytes and endothelial cells can lead to thrombocytopenia, venous and arterial thrombosis or thromboembolic events 10-14 days after the first dose. HIT II has a high mortality rate because of pulmonary emboli, cerebrovascular accidents, myocardial and limb infarctions. A 55-year-old patient with HIT II presented with arterial and venous thromboses and a silent myocardial infarction. In addition, he showed extensive skin and mucosal necrosis, an uncommon complication. Rheologic therapy with danaparoid Natrium, alprostadil alfadex and acetylsalicylic acid in combination with percutaneous transluminal angioplasties as well as local and systemic antiinflammatory therapy prevented further progression of the disease.

Comparative treatment of multiple vellus hair cysts with the 2940 nm Er:YAG and 1540 nm Er:Glass laser

Abstract Eruptive vellus hair cysts occur sporadically, hereditarily or in association with other diseases due to developmental anomalies of vellus hair follicles. Here, we report on a 41-year-old male with multiple vellus hair cysts of the forehead, who was successfully treated three times with a non-ablative, non-fractional 1540 nm Er:Glass laser on one side of his face, and with an ablative non-fractional 2940 nm Er:YAG laser on the other side, at intervals of 6–12 weeks. Over the whole treatment period of about 9 months, we could observe a marked reduction in the total number of cysts. The bigger and painful inflammatory cysts were reduced significantly. There was a slight tendency for better clinical outcome in the area in which the Er:YAG laser had been used. Clinical and histopathological findings, pathogenesis and treatment options are discussed with a review of the literature.