What is the significance of shifting immunity in a patient with concomitant plaque psoriasis and eczema, and how effective is cyclosporine (cyclosporin) in managing both conditions, particularly in cases where etanercept (etanercept) therapy has failed?

From the Guidelines

Cyclosporine is a highly effective treatment option for patients with concomitant plaque psoriasis and eczema, particularly in cases where etanercept therapy has failed, due to its broad inhibition of T-cell activation and cytokine production, addressing both Th1-driven psoriasis and Th2-driven atopic conditions. The phenomenon of multiple autoimmune conditions coexisting or sequentially developing in the same patient is known as polyautoimmunity or autoimmune diathesis, and the immunological basis involves a concept called "cytokine switching" where blocking TNF-α (with etanercept) can sometimes lead to a shift toward Th2-dominant immune responses, potentially triggering atopic conditions like eczema and asthma 1.

Key Considerations

• The typical dosing for cyclosporine in this scenario would be 2.5-5 mg/kg/day divided into two doses, with regular monitoring of blood pressure, renal function, and drug levels 1.
• Cyclosporine has been shown to be effective in treating severe, recalcitrant psoriasis, with response rates of up to 80-90% of patients achieving significant improvement 1.
• The treatment approach should address the immunological imbalance rather than just targeting specific cytokines, and consider periodic attempts at dose reduction to minimize nephrotoxicity risks, and monitor for infections and other side effects.

Monitoring and Management

• Regular monitoring of cyclosporine blood levels is not necessary at the doses used for the treatment of psoriasis, but certain conditions may warrant closer attention, such as patients taking medications that might interfere with cyclosporine metabolism or those with liver disease 1.
• Patients should regularly monitor their blood pressure to avoid chronic hypertension as well as kidney damage, and early morning resting blood pressure is a more sensitive indicator of early nephrotoxicity than elevated creatinine 1.
• Calcium channel blockers are the antihypertensive of choice due to their ability to relax vascular smooth muscles, and β-Blockers can also be used for blood pressure control 1.

From the FDA Drug Label

The effectiveness of cyclosporine results from specific and reversible inhibition of immunocompetent lymphocytes in the G0- and G1-phase of the cell cycle. T-lymphocytes are preferentially inhibited. The T-helper cell is the main target, although the T-suppressor cell may also be suppressed. Cyclosporine also inhibits lymphokine production and release including interleukin-2 In clinical trials, cyclosporine doses at the lower end of the recommended dosage range were effective in maintaining a satisfactory response in 60% of the patients. Doses below 2.5 mg/kg/day may also be equally effective.

The significance of shifting immunity in a patient with concomitant plaque psoriasis and eczema is not directly addressed in the provided drug labels. However, cyclosporine is effective in managing psoriasis by inhibiting immunocompetent lymphocytes and suppressing T-helper cells. The recommended initial dose of cyclosporine for psoriasis is 2.5 mg/kg/day, and the dose can be adjusted based on patient response.

• Key points:
  • Cyclosporine inhibits immunocompetent lymphocytes and suppresses T-helper cells.
  • Effective in managing psoriasis.
  • Initial dose for psoriasis: 2.5 mg/kg/day.
  • Dose adjustments based on patient response. There is no direct information on the effectiveness of cyclosporine in managing eczema or the specific scenario of a patient with concomitant plaque psoriasis and eczema who has failed etanercept therapy 2, 2, 2.

From the Research

Shifting Immunity in Concomitant Plaque Psoriasis and Eczema

• The significance of shifting immunity in a patient with concomitant plaque psoriasis and eczema is not directly addressed in the provided studies.
• However, it is known that both psoriasis and eczema are immune-mediated diseases, and changes in the immune system can affect the course of these diseases 3, 4.

Effectiveness of Cyclosporine in Managing Both Conditions

• Cyclosporine (cyclosporin) has been shown to be effective in managing plaque psoriasis, with higher doses producing better responses 4, 5.
• The use of cyclosporine in eczema is not directly addressed in the provided studies, but it is known to be effective in treating other immune-mediated diseases.
• Cyclosporine can be used as an alternative therapy to other available therapeutic agents, such as etanercept, in cases where etanercept therapy has failed 4, 6.

Safety and Efficacy of Cyclosporine

• The safety and efficacy of cyclosporine in managing plaque psoriasis have been established, but its use is limited by its adverse effects, especially nephrotoxicity 3, 5.
• The risk of kidney toxicity is a major concern with long-term use of cyclosporine, and regular monitoring of serum creatinine is necessary 4, 5.
• Cyclosporine can be effective in achieving significant improvement in psoriasis symptoms, but its use should be carefully considered due to its potential side effects 7, 6.