Allergy - 5: Allergy and the skin: eczema and chronic urticaria

Eczema is common, occurring in 15%-20% of infants and young children. For some infants it can be a severe chronic illness with a major impact on the child's general health and on the family. A minority of children will continue to have eczema as adults. The exact cause of eczema is not clear, but precipitating or aggravating factors may include food allergens (most commonly, egg) or environmental allergens/irritants, climatic conditions, stress. and genetic predisposition. Management of eczema consists of education; avoidance of triggers and allergens; liberal use of emollients or topical steroids to control inflammation; use of antihistamines to reduce itch; and treatment of infection if present. Treatment with systemic agents may be required in severe cases, but must be supervised by an immunologist. Urticaria (hives) may affect up to a quarter of people at some time in their lives. Acute urticaria is more common in children, while chronic urticaria is more common in adults. Chronic urticaria is not life-threatening, but the associated pruritus and unsightly weals can cause patients much distress and significantly affect their daily lives. Angioedema coexists with urticaria in about 50% of patients. It typically affects the lips, eyelids, palms, soles and genitalia. Management of urticaria is through education; avoidance of triggers and allergens (where relevant); use of antihistamines to reduce itch; and short-term use of corticosteroids when antihistamine therapy is ineffective. Referral is indicated for patients with resistant disease.

Uses for JNK: the many and varied substrates of the c-Jun N-terminal kinases

The c-Jun N-terminal kinases (JNKs) are members of a larger group of serine/ threonine (Ser/Thr) protein kinases from the mitogen-activated protein kinase family. JNKs were originally identified as stress-activated protein kinases in the livers of cycloheximide-challenged rats. Their subsequent purification, cloning, and naming as JNKs have emphasized their ability to phosphorylate and activate the transcription factor c-Jun. Studies of c-Jun and related transcription factor substrates have provided clues about both the preferred substrate phosphorylation sequences and additional docking domains recognized by JNK There are now more than 50 proteins shown to be substrates for JNK These include a range of nuclear substrates, including transcription factors and nuclear hormone receptors, heterogeneous nuclear ribonucleoprotein K and the Pol I-specific transcription factor TIF-IA, which regulates ribosome synthesis. Many nonnuclear substrates have also been characterized, and these are involved in protein degradation (e.g., the E3 ligase Itch), signal transduction (e.g., adaptor and scaffold proteins and protein kinases), apoptotic cell death (e.g., mitochondrial Bcl2 family members), and cell movement (e.g., paxillin, DCX, microtubule-associated proteins, the stathmin family member SCG10, and the intermediate filament protein keratin 8). The range of JNK actions in the cell is therefore likely to be complex. Further characterization of the substrates of JNK should provide clearer explanations of the intracellular actions of the JNKs and may allow new avenues for targeting the JNK pathways with therapeutic agents downstream of JNK itself.