1. TWO DECADES OF USING THE COMBINATION OF TETRACYCLINE DERIVATIVES AND NIACINAMIDE AS STEROID-SPARING AGENTS IN THE MANAGEMENT OF PEMPHIGUS: DEFINING A NICHE FOR THESE LOW TOXICITY AGENTS MORGAN MCCARTY, DO, AND DAVID FIVENSON, MD ANN ARBOR, MICHIGAN BS. Vương Thế Bích Thanh

2. Background:  The treatment of pemphigus vulgaris (PV) and pemphigus foliaceous (PF): systemic, topical steroids, immunosuppressive, immunomodulatory agents  Twin goals: long-term disease control, minimizing toxicities related to immunosuppression → effective steroid-sparing agents  TCN/NAM: a steroid-sparing therapy for bullous pemphigoid.  Pemphigus: 1993, Chaffins: reported 11 patients (5 complete responders, 4 partial responders, and 2 nonresponders). 1995, Alpsoy reported 10 patients (2 complete responders, 3 partial responders, and 5 nonresponders)

3. Objectives:  This retrospective review details 20 years of 1 practitioner’s experience using TCN/NAM as steroid sparing agents in the management of pemphigus, determine the effects of TCN/NAM on autoantibody levels during the long-term treatment of pemphigus

4. Methods :  All pemphigus patients in a private medical dermatology office setting, from 1993 to 2013  All newly diagnosed or flaring pemphigus patients who were treated with TCN/NAM after initial oral steroid induction therapy for active pemphigus  Excluded: Patients who underwent all other therapies  Defined TCN/NAM responder: disease remission, control on minimal therapy, or only transient lesions within 3 months of starting this regimen  Side effects related to TCN/NAM therapy  Anti-desmoglein 1 (DSG1), anti-desmoglein 3 (DSG3) ELISAs  Statistical analysis: correlate the clinical response with antibody levels

5. Results:  83 patients, 32 excluded: taking a variety of therapeutic agents  51 active disease (43 PV, 7 PF, 1 PE) : oral corticosteroids (1-2 mg/kg/day) with TCN/NAM (tetracycline 500 mg 4 times daily, doxycycline 100 mg twice daily, or minocycline 100 mg twice daily) initiated as soon as active blistering had stopped. Oral corticosteroids: tapered 10% per week over 2 to 3 months  duration of clinical response: 1 to 13 years (mean, 3.14 ± 2.97 years), disease duration: 1 to 23 years (mean, 8.63 ± 4.63 years)  46: responded with disease control after 3 months, 3 lost to follow-up

6. Results:  13 (9 PV+4 PF): completely controlled on TCN/NAM alone  28 (23 PV + 4 PF + 1 PE): partially controlled  5 PV (10%): nonresponders  →46 of 51 (90%): disease control on minimal therapy  Antidesmoglein titers trended lower in TCN/NAM responders  desmoglein 3 approached statistical significance (antiedesmoglein 1,P=0.21; antiedesmoglein 3, P= 0.02)

7. Discussion:

8.  Tetracyclines: decrease interleukin (IL)-1b, matrix metalloproteinases (matrix metalloproteinase-13)  Niacinamide: inhibition of serum phosphodiesterase, increasing cyclic adenosine monophosphate, inhibiting antigen-immunoglobulin E-induced histamine release (ie, mast cell stabilization), inhibition of ILs-1b, -6, and -8, tumor necrosis factor alfa, transforming growth factor beta- 2, macrophage chemotactic protein -> decreased leukocyte chemotaxis and lymphocyte transformation

9. Conclusion:  TCN/NAM may be useful as a steroid-sparing therapy for pemphigus  Help avoid /delay the use of stronger immunosuppressive agents and their associated toxicities.

10. Limitations:  retrospective analysis from a single practice  lack of serial autoantibody titers limited statistical analyses

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