Publisher Summary This chapter focuses on interleukin-8 (IL-8) and related chemotactic cytokines—namely, CXC and CC chemokines. IL-8 is the best known member of a new class of cytokines that are widely studied because of their ability to attract and activate leukocytes, and their potential role as mediators of inflammation. IL-8 was originally isolated from the culture supernatants of stimulated human blood monocytes and was identified as a protein of 72 amino acids with a molecular weight of 8383. The three-dimensional structure of IL-8 has been studied by nuclear magnetic resonance spectroscopy and X-ray crystallography. In concentrated solution, and on crystallization, IL-8 is present as a dimer. The first CC chemokine was identified after cloning by differential hybridization from human tonsillar lymphocytes and was termed LD78. The CC and CXC chemokines are similar in size and have an overall structure that is characterized by the two intrachain disulfide bonds, short N-terminal and long C-terminal sequences. It discusses the role of chemokines in pathology with skin inflammation because psoriasis was the first disease to be linked to overproduction of IL-8. Several independent studies document the occurrence of high levels of IL-8 in the synovial fluid of inflamed joints of patients with different forms of rheumatic diseases, osteoarthritis, and gout.

Interleukin-8 and related chemotactic cytokines--CXC and CC chemokines.

Microemulsion-based media as novel drug delivery systems

Vitamin B12 deficiency causes reversible megaloblastic anemia, demyelinating disease, or both. Current assays have insufficient sensitivity and specificity; methylmalonic acid levels are useful to confirm diagnosis. Parenteral or high-dose oral vitamin B12 is effective therapy.

https://www.nejm.org/doi/pdf/10.1056/NEJMcp1113996

Vitamin B12 Deficiency

Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, randomised, double-blinded, placebo-controlled, phase 3 trial

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/0014-5793%2892%2980909-Z

Interleukin-8, a chemotactic and inflammatory cytokine.

Tacrolimus (FK506) is an effective and well tolerated immunosuppressant used to prevent allograft rejection. We describe the evaluation of two tacrolimus ointment formulations for treatment of chronic plaque-type psoriasis. This was a microplaque assay with randomized, double-blind design. Sixteen patients (15 men, one woman, all white and 28-69 years old) with chronic plaque-type psoriasis participated. Six different ointments were applied to discrete microplaques, 17 mm in diameter, on a descaled psoriasis lesion: these were tacrolimus ointment with diisopropyl adipate as penetration enhancer, tacrolimus ointment without diisopropyl adipate, 0.1% betamethasone 17alpha-valerate ointment, 0.005% calcipotriol ointment and, as controls, the ointment bases for tacrolimus and betamethasone. Ointments were reapplied and the area was sealed every 2-3 days during the 14-day treatment period. After 7 and 14 days, erythema and infiltration were graded on a scale of 0-4, and superficial blood flow was measured with a laser Doppler flowmeter. Epidermal thickness was measured histologically at the end of treatment. Compared with the vehicle controls, sites treated with tacrolimus ointment (with or without penetration enhancer) showed a significant reduction in erythema and infiltration (P < 0. 001), a significant reduction in superficial blood flow (P < 0.01) and a significant decrease in epidermal thickness (P < or = 0.001). Results for betamethasone and calcipotriol, when compared with the vehicle controls, were similar. These results suggest that, under conditions of descaling and occlusion, tacrolimus ointment is effective in the treatment of psoriasis.

Tacrolimus ointment improves psoriasis in a microplaque assay.

Topical corticosteroids are the standard treatment for hand eczema. However, in chronic forms of the disease they are often ineffective or lose their efficacy due to tachyphylaxis. In a previous open study cyclosporine showed efficacy in chronic hand eczema. The aim of this study was to compare oral cyclosporine at 3 mg/kg/day with topical 0.05% beta-methasone-17,21-dipropionate (BDP) cream in the treatment of chronic hand eczema. In a randomized, double-blind study 41 patients with chronic hand eczema resistant to conventional treatment were assigned to either cyclosporine or BDP for 6 weeks. Both cyclosporine and BDP improved the eczema. The total disease activity score decreased to 57% of baseline in the cyclosporine group (mean change -6, SD 4.3; p < 0.001) and to 58% of baseline in the BDP group (mean change -5.7, SD 4; p < 0.001) at the end of treatment. However, between the groups there was no significant difference. Adverse events occurred in 68% of the patients during cyclosporine and in 56% during BDP treatment. With cyclosporine no case of hypertension or increase in serum creatinine above normal levels was recorded. In two patients the serum creatinine levels increased to values 30% above their own baseline values. Relapses occurred to the same extent in both groups. Cyclosporine at 3 mg/kg/day is as effective as topical BDP in the treatment of chronic hand eczema. Low-dose cyclosporine could be useful as an alternative treatment for severe chronic hand eczema in patients unresponsive to conventional treatment.

Comparison of cyclosporine and topical betamethasone-17,21-dipropionate in the treatment of severe chronic hand eczema.

The efficacy of cyclosporin (CyA) in the induction of remission in atopic dermatitis has been documented in controlled studies. However, little information is available on the duration of remission after CyA treatment. We studied the length of remission in 43 patients with severe atopic dermatitis after a 6-week treatment period with CyA at 5 mg/kg per day. After a follow-up of 6-26 weeks, depending on the time-point of relapse, a second treatment period with CyA, identical to the first, was performed. Disease activity was evaluated bi-weekly, using six different parameters: 1, a total body disease activity score; 2, the extent of the disease; 3, the occurrence of itch; 4, the occurrence of sleep disturbance; 5, the use of topical emollients; and 6, the use of topical hydrocortisone. A significant decrease in disease activity was observed. The total body disease activity score decreased from the baseline score of 31 to 11.6 at the end of the first part and to 13.4 at the end of the second part of the study. An almost maximal response to treatment was already apparent after 2 weeks of treatment. All the other efficacy parameters studied also showed a significant response to CyA treatment. A similar response to CyA was seen when the patients were re-treated. After both treatment periods, approximately half of the patients relapsed after 2 weeks (42% first part; 54% second part). After 6 weeks follow-up, the relapse rates were 71 and 90%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclosporin in atopic dermatitis: time to relapse and effect of intermittent therapy.

Interleukin-8 Immunoreactivity in the Skin of Healthy Subjects and Patients with Palmoplantar Pustulosis and Psoriasis

Background and Design: Palmoplantar pustulosis (PPP) is an inflammatory skin disease characterized by pustule formation, erythema, induration, and scaling of the affected skin of the palms and soles. Palmoplantar pustulosis is usually resistant to treatment. In a double-blind study (phase 1) of 4 weeks, 40 patients with PPP were randomized to receive oral cyclosporine, 2.5 mg/kg per day, or placebo. An open-label dose-finding phase 2 with cyclosporine doses of 1.25, 2.5, and 3.75 mg/kg per day was performed in the following 3 months. The patients were then followed for at least 2 months after termination of cyclosporine treatment. Response to treatment was judged by the number of fresh pustules. Patients displaying a reduction of 50% or greater in the number of pustules, compared with baseline, were defined as responders. Results: Of the patients who completed phase 1, 17 of 19 patients in the cyclosporine group and four of 15 in the placebo group were classified as responders ( P P =.001). In the subsequent open phase, a daily cyclosporine dose of 1.25 mg/kg appeared to be an effective treatment of PPP in approximately half of the treated patients. Many patients relapsed after initial success with cyclosporine. However, only one patient studied totally failed to respond to cyclosporine treatment. At the end of phase 3, most of the studied parameters had returned to pretreatment levels. The most common side effect was headache in the 2.5 mg/kg per day dosage group; no significant side effects were observed in the 1.25 mg/kg per day dosage group. Conclusions: Low-dose cyclosporine treatment (1.25 to 2.5 mg/kg per day) is effective in PPP. ( Arch Dermatol. 1993;129:1273-1279)

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=derm&articleId=555280&pdfFileName=archderm_129_10_006.pdf

Cyclosporine in the Treatment of Palmoplantar Pustulosis: A Randomized, Double-blind, Placebo-Controlled Study

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