SNPping Razor Bumps
Razor bumps (pseudofolliculitis barbae, or PFB) are a common problem in African-American males, although they are not limited to any ethnic group. PFB is especially vexing to men in the US military who are required to be closely shaved. Tightly curved hairs seem to penetrate the skin and induce chronic inflammation. Basic science identified, or rediscovered, the companion layer in the hair follicle that has a specific hair keratin, K6hf. The companion layer is tightly connected to the Henle layer of the internal root sheath, and it may guide and stabilize the ascending hair. An alanine to threonine substitution (a single nucleotide polymorphism, a.k.a. "a SNP") in the 1A 
-helical segment of K6hf has a significant association with PFB (odds ratio 6.1; 95% confidence interval 2.1–17.8). This is independent of the association of curved hair follicles with PFB. How the identification of this molecular association will lead to new therapies is a challenge for hair biologists. It is an important example of how molecular defects can be important in common disorders as well as in rare diseases. J Invest Dermatol 122:652–657, 2004
Hot Hurting Feet Respond to Prostaglandin E1 Analog (Misoprostol)
Erythromelalgia—with its nocturnal paroxysms of painful feet, eased by standing on cold floors or the use of non-steroidal inflammatory agents—is a well-characterized clinical syndrome with primary (unknown) and secondary causes. A group from a country with cold winters has been studying the physiology of erythromelalgia for over a decade, and suggests that increased microvascular shunting in the skin is an important feature of the disorder. Mørk and co-workers performed a blinded cross-over placebo-controlled study with oral misoprostol, with satisfactory safety studies and pain reduction. They report a decreased response to body heating with misoprostol compared with placebo, during a Duvet stress test to increase central body temperature, designed to mimic sleeping conditions during the Norwegian winter (mean temperature 0.1°C). The heterogeneity of conditions associated with erythromelalgia should not detract from a potential new therapy for this vexing disorder. J Invest Dermatol 122:587–593, 2004
Watch the Skin Clock
The skin, like many other tissues, has circadian (Latin for "almost a day") and ultradian rhythms (operationally defined as 20 or fewer hours). These rhythms may be driven (and or fixed) by catecholamines and potentially by environmental light. Studying normal men and women under highly controlled environmental conditions, Yosipovitch and coauthors showed that neither tape stripping nor mid-potency (mometasone) or high-potency (clobetasol) steroid ointments interfered with circadian rhythms, barrier function, or blood flow. Low blood flow in the morning hours might affect the systemic uptake of drugs from the epidermis; in other organ systems detailed timing of drug administration has been studied, and it seems warranted in humans with skin disease to see if the differences in basic skin physiology may affect the pharmacological efficacy of topical agents. J Invest Dermatol 122:824–829, 2004
Superoxide Dismutase Antibodies in Localized Scleroderma
Autoantibodies can function as a diagnostic aid for a disease and may also indicate the fundamental pathophysiology associated with a disorder. Antibodies against Cu/Zn superoxide dismutase (SOD) were positive in 89% of localized scleroderma patients, and were positive in all 13 patients with generalized morphea, but were only positive in 15% of patients with classical autoimmune diseases, including the autoimmune blistering diseases. The antibodies inhibited SOD enzymatic activity, and Nagai and co-workers postulate that the antibodies can thus contribute to fibrosis. SOD has been used in the therapy of other models of fibrosing disorders, and there may be therapeutic implications to these antibody findings in addition to the diagnostic implications. J Invest Dermatol 122:594–601, 2004
