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Chronic itch, defined as an itching sensation that persists for more than 6 weeks, is a common complaint that is associated with a high burden of disease. Chronic itch can occur due to a variety of skin diseases, but can also feature as prominent symptom in various internal, neurologic, and psychiatric disorders. Importantly, chronic itch can be drug-related. Determining the underlying cause can be challenging, yet it is an essential step in the management of chronic itch. When generalized chronic itch presents with no primary skin lesions and/or secondary skin lesions, the diagnostic work-up should consist of a detailed history and physical examination with an initial limited screening of laboratory tests. Subsequent additional screening should be dictated by clinical suspicion. In 8% of patients, no underlying cause can be identified: pruritus of unknown origin. The management of chronic itch of unknown origin preferably follows a multimodal approach.

The next step in the treatment of immune diseases: jakinibs, inhibitors of the intracellular Janus kinase The intracellular Janus kinase (JAK) and the signal transduction and activator of transcription (STAT) proteins are involved in the whole spectrum of immune-mediated diseases. Currently, agents are developed that influence the JAK-STAT mechanism. JAK inhibitors (jakinibs) have only recently made their way into clinical practice. These agents exhibit both similarities and differences in terms of effectiveness and safety. In the coming years, results from basic and clinical research will improve our knowledge of these agents. For patients who suffer from immune-mediated diseases, their introduction appears to be a breakthrough that will offer new treatment options. One advantage over biologicals is that jakinibs can be taken orally. As with all new innovative medicines, with jakinibs one cannot escape a discussion over costs as well. The balance between the added value of jakinibs compared to biologicals, and the actual purchase prices for each of these treatment modalities, will influence the eventual positioning of jakinibs.

Fibrosis is one of the leading causes of morbidity and mortality in the Western world. This disorder is characterised by an abnormal and increased rate of fibroblast proliferation and by an excessive deposition of connective tissue. The key player in fibrosis is the myofibroblast. Fibrosis leads to loss of organ structure and, eventually, to decrease in organ function. To date, there are hardly any effective therapies for the treatment of patients with fibrosis. Pirfenidone targets the myofibroblast and is effective in the treatment of idiopathic pulmonary fibrosis. Tyrosine kinase inhibitors are effective for the treatment of patients with some forms of systemic sclerosis. Here we describe various novel therapeutic targets, such as transforming growth factor beta (TGF-β), platelet-derived growth factor (PDGF), interleukin-13 (IL-13), lysyloxidase-2 and macrophage-fibroblast interactions. These new therapies are currently under investigation in pre-clinical and clinical studies.

The multidisciplinary guideline 'Diagnostics of small-vessel vasculitis' gives recommendations for the diagnostics of small-vessel vasculitis, which is often associated with cutaneous manifestations. The aim of this guideline is to accelerate the diagnostic process to prevent or reduce irreversible organ damage. The clinical presentation of small-vessel vasculitis is variable and often atypical. The most common general symptoms are general malaise, unexplained fever, weight loss, fatigue, loss of appetite, and night sweats. If these symptoms are accompanied by one or more organ-specific symptoms, the probability of the diagnosis 'small-vessel vasculitis' is increased. When small-vessel vasculitis is suspected a comprehensive history should be taken and a physical examination focused on internal organs, joints, skin and nervous system should be performed. With additional laboratory investigations possible organ involvement can be demonstrated and the small-vessel vasculitis can be further classified. To make a definite diagnosis histological examination of an affected organ is necessary. Because of the possible involvement of multiple organ systems, multidisciplinary collaboration is essential in the diagnostic work-up.

A male neonate was born with a defect of the skin and subcutaneous tissue on the back. The pregnancy started as a gemelli pregnancy but in the 12th week 1 fetus deceased. The diagnosis of truncal aplasia cutis was made.

A 71-year-old man was referred to our outpatient clinic because of arthralgia and swelling of his right hand. He also showed a subcutaneous nodule on his left knee. A second patient, a 57-year-old woman, was referred because of painful skin of her legs. Dermatologic examination revealed erythematous livid discoloration on both feet and legs. There were reticular varices, corona flebectatia paraplantaris medialis and minimal pitting oedema. Serology tested positive in both patients for Borrelia and they both recalled tick bites. A third patient, a 73-year-old woman, was referred because of erythema and maculae located at her lower legs and positive Borrelia serology. Pathologic examination was typical for acrodermatitis chronica atrophicans, a late skin manifestation of Lyme borreliosis. In all patients, symptoms improved after treatment with doxycycline for four weeks. A lack of familiarity with this skin condition may lead to unnecessary vascular investigations and considerable delay in adequate treatment.

Sarcoidosis is a granulomatous disease of unknown etiology. Standard treatment with immune suppressants such as glucocorticoids is started when vital organ function is threatened. Biotechnology has resulted in new treatments ('biologicals'), in particular monoclonal antibodies, that may be effective in the treatment of sarcoidosis. In patients with sarcoidosis, only the use of monoclonal antibodies that block tumour necrosis factor (TNF) has been studied scientifically, other biologicals hardly at all. TNF-blockers are used at present in patients with therapy refractory sarcoidosis.

Two patients, a 96-year-old woman and a 94-year-old man, were diagnosed with metastatic cutaneous melanoma. The first patient had undergone radical excision of the primary tumour 18 months before. The second patient presented with neurological symptoms caused by a metastatic melanoma; the primary tumour had recently been resected. Both patients died within three weeks of the diagnosis. Cutaneous melanomas have a high metastatic rate. Treatment options are limited for metastatic disease. The incidence of melanoma increases with age. Old age is an independent risk factor, which is also associated with a poor prognosis. Older patients more often present with more serious histological characteristics and more aggressive types of melanoma. The Breslow thickness is also higher in patients aged 65 or over. Nodular melanoma, lentigo maligna or acral lentiginous melanoma are observed more frequently in this group of patients. Moreover, elderly people more frequently present with liver or cerebral metastases. Early diagnosis improves the prognosis, also in the elderly.

The chronic skin disease psoriasis frequently requires long-term systemic treatment with agents that suppresses the immune system with little specificity, which can lead to systemic side effects. Today, using recombinant techniques, it is possible to produce modified proteins, the so-called biologicals, that target specific molecules in the inflammatory process. For the biologicals etanercept, infliximab, adalimumab, efalizumab and alefacept, the clinical efficacy expressed in the rates of partial remission (75% reduction in skin lesions) in patients with plaque psoriasis range from 12 to 88%, compared with 22 to 87% for existing systemic therapies for psoriasis. The side effects of biologicals are usually mild to moderate, but can sometimes be severe. The biologicals should be prescribed with caution, given that they have been on the market for a relatively short period, and because all forms of immune suppression carry an increased risk of oncologic degeneration. The guideline of the Dutch Society of Dermatology and Venereology states that the use of a biological may be considered when a patient cannot tolerate or is unresponsive to conventional systemic therapy, or has an increased risk of adverse events. Biologicals increase the number of options for treatment-resistant plaque psoriasis, which allows therapy to be tailored to the individual patient.

The skin contains a variety of cell types and mediators, which together constitute the skin's immune system and play a key role in protecting the human body against dangers from outside. Dysregulation of the skin's immune system, however, frequently occurs and can result in undesirable inflammatory processes in the skin. A typical example of an undesirable inflammation in the skin is the chronic inflammatory skin disease psoriasis. In the pathogenesis of psoriasis, both genetic and environmental factors play a key role. In psoriasis, the complex interactions between T-lymphocytes, antigen-presenting cells, keratinocytes and pro-inflammatory cytokines and chemokines are disturbed. The two most widely accepted hypotheses are: (a) psoriasis is a T-cell mediated autoimmune disease, and (b) psoriasis is the result of a too finely adjusted system for regulating inflammation in the skin. The result of both mechanisms is a chronic inflammatory reaction fuelled by pro-inflammatory type-I cytokines that lead to the psoriasis-skin phenotype. With the development ofbiologicals, it has become feasible to target specific molecules in the immune process, for example type-I cytokines and the molecules present on pathogenic T-cells. This approach has already proved successful in the treatment of rheumatoid arthritis and Crohn's disease, creating novel therapeutic options for psoriasis and other inflammatory dermatoses.