Interactions between the epidermis and the immune system govern epidermal tissue homeostasis. These epidermis-immune interactions are altered in the inflammatory disease psoriasis; however, the pathways that underlie this aberrant immune response are not well understood. Here, we determined that Ras-related C3 botulinum toxin substrate 1 (RAC1) is a key mediator of epidermal dysfunction. RAC1 activation was consistently elevated in psoriatic epidermis and primary psoriatic human keratinocytes (PHKCs) exposed to psoriasis-related stimuli, but not in skin from patients with basal or squamous cell carcinoma. Expression of a constitutively active form of RAC1 (RACV12) in mice resulted in the development of lesions similar to those of human psoriasis that required the presence of an intact immune system. RAC1V12-expressing mice and human psoriatic skin showed similar RAC1-dependent signaling as well as transcriptional overlap of differentially expressed epidermal and immune pathways. Coculture of PHKCs with immunocytes resulted in the upregulation of RAC1-dependent proinflammatory cytokines, an effect that was reproduced by overexpressing RAC1 in normal human keratinocytes. In keratinocytes, modulating RAC1 activity altered differentiation, proliferation, and inflammatory pathways, including STAT3, NFκB, and zinc finger protein 750 (ZNF750). Finally, RAC1 inhibition in xenografts composed of human PHKCs and immunocytes abolished psoriasiform hyperplasia and inflammation in vivo. These studies implicate RAC1 as a potential therapeutic target for psoriasis and as a key orchestrator of pathologic epidermis-immune interactions.

Neurofibromatosis (NF) is one of the most common genetic disorders. Inherited in an autosomal dominant fashion, this phacomatosis is classified into two genetically distinct subtypes characterized by multiple cutaneous lesions and tumors of the peripheral and central nervous system. Neurofibromatosis type 1 (NF1), also referred to as Recklinghausen's disease, affects about 1 in 3500 individuals and presents with a variety of characteristic abnormalities of the skin and the peripheral nervous system. Neurofibromatosis type 2 (NF2), previously termed central neurofibromatosis, is much more rare occurring in less than 1 in 25 000 individuals. Often first clinical signs of NF2 become apparent in the late teens with a sudden loss of hearing due to the development of bi-or unilateral vestibular schwannomas. In addition NF2 patients may suffer from further nervous tissue tumors such as meningiomas or gliomas. This review summarizes the characteristic features of the two forms of NF and outlines commonalities and distinctions between NF1 and NF2.

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A 22-year-old woman presented with a superficial spreading melanoma on her right thigh (tumor thickness 1.0 mm, Clark-Level III). She also had decorative tattoos on her right ankle, right groin and coccyx. The staging results gave no indication for metastases. Intra-operatively, we observed a black pigmented lymph node highly suspicious for metastatic disease, but histological examination excluded metastatic spread and detected the accumulation of black pigment within the lymph node. Clinical differentiation between tattoo pigments and metastatic disease within lymph nodes is not possible. Histological confirmation of an enlarged pigmented lymph node is therefore essential before radical surgery is performed. Hence, accumulation of tattoo pigment within enlarged and pigmented lymph nodes needs to be included into the differential diagnosis and the documentation of decorative tattoos is important during skin cancer screening as well as during the follow-up of melanoma patients.

A 29-old man presented with severe chronic urticaria and angioedema. Routine evaluation including history, laboratory parameters and imaging procedures did not reveal any pathologic findings. We tried combined therapy regimes including high-dose systemic corticosteroids and antihistamines, leukotriene antagonist, cyclosporine and antibiotics. Because of a poor response and dramatic escalation of symptoms, we initiated therapy with omalizumab resulting in the complete remission of the chronic urticaria after two weeks.