Combining Technology for Facial Rejuvenation

Suzanne L. Kilmer, MD

 Clinical Pearls: When Combining Devices with Injectables and Other Devices

In this presentation, Dr Kilmer reviews the techniques for combining the various technologies that are currently available for facial rejuvenation in order to obtain optimal cosmetic improvement for patients.

Dr Kilmer stresses the importance of remembering the 4 Rs:

  • Relax
  • Refill
  • Resurface
  • Redrape

During her initial consult with patients Dr Kilmer discusses the 4 Rs and how the various techniques that she uses in combination for facial rejuvenation can aide in maximizing the outcomes. It is also important, as dermatologists that full disclosure regarding outcomes is presented. Dr Kilmer informs her patients that she does not “have a magic wand or a crystal ball”; therefore, she can’t predict the outcomes of any given patient.


It is important to relax the skin with a botulinum toxin to keep both the muscles and the skin from moving as much as it otherwise would. If she is going to laser the skin, the results are improved when the skin/muscles are not moving. Dr Kilmer also uses fillers, in conjunction with the toxins and lasers to fill in lines, tighten up the skin and remove brown/red spots.

Clinical Pearl: Never use toxins, lasers, or any other device that can cause significant swelling on the same day. This can result in the toxin migrating to other places where you do not want it.

 Refill-Restore Volume Loss

When using dermal fillers, the objective is to restore volume based on a patient’s specific needs. Fillers can be placed in various areas locally such as the nasolabial folds, marionette lines, deep glabellar rhytids, tear troughs, and the nasal bridge. Fillers can also be used globally in the cheeks and temples.  It is important to remember that there may be a lag time resulting in delayed gratification.

It is very important to keep in mind that one can’t massage post poly-L-lactic acid (Sculptra) in areas where Botulinum toxin was placed.

If all of these procedures are being done in one patient, Dr Kilmer typically tries to slow down the movement and relax the muscles. Discussions with patients regarding the overall procedures that could be performed are very important. Considerations for patients include money, down time, and fear factor, i.e., what are they willing to go through? In these consultations, Dr Kilmer and her patients decide on the best approach based upon their issues and the issues that she sees.

 Combination Treatments

  • Best order
    • Start with toxins to stop movement and relax muscles.
      • Relax frown, smile and lip lines when doing facial rejuvenation
      • Relax DAOs and neck bands when doing fillers, tightening or resurfacing
        • May need less filler and patients are happy sooner with tightening devices
        • Then filler or laser depending on a patient’s specific needs (and ability for downtime)
          • Never do toxins and lasers that cause swelling at the same time because toxins can migrate.
          • Typically end with filler if still needed after toxins and laser
            • Sometimes the combination will diminish the need for filler
            • If able to tell that will need volume, can do before or at same time as laser

Caveats of Combining Treatments

  • Toxin with Filler
    • Can’t massage post poly-L-lactic acid (Sculptra) in areas where Botulinum toxin was placed
    • Toxin with Laser
      • Can’t do toxin same day as Fractional lasers – swelling can lead to migration
      • Can do botulinum toxin with PDL, IPL, CoolTouch, SmoothBeam, Thermage, Titan
      • Filler with Laser
        • Can do filler same day but do first if doing fractional as swelling can mask need for filler.
        • Fractional with nonablative RF tightening
          • Same day – do Thermage 1st because need intact skin but when you do the fractional laser the skin may still be sensitive. (wait an hour or two because the sensation will decrease with time)

Combining Fractional with other Devices

  • Fractional laser with other lasers/txs
    • Lentigines – pre-tx QS lasers, KTPs, etc
    • AKs – LN2
    • Sebaceous hyperplasia, nevi – 1450 nm
    • Vascular lesions – PDL, KTP, Alex
    • Downtime from other treatment is simultaneous and shortened
    • Fractional resurfacing with ablative resurfacing
      • Almost always do fully ablative to upper eyelids
        • More tightening/more predictable – do inner canthi
  • Can ablate/sculpt edges of scars, upper lip lines and elevated lesions
  • Ablative fractional and nonablative fractional resurfacing
    • Nonablative fractional to face, ablative to neck for more tightening /crepiness – useful for those with hx ablative resurfacing/chemical peels/dermabrasion

Other Combination Therapy

Other combination therapy includes fat loss and tissue tightening (CoolSculpting + RF tissue tightening, lipo/laser lipo + tissue tightening); Fractionated RF ((ePRime) + QS/KTP/PDL); and Fractionated US ((Ulthera) + QS/KTP/PDL).

Now that the 4Rs have been implemented, dermatologists need to be particularly aware of reassessing. Combination treatments may minimize the need for other treatments; therefore, increasing the interval for maintenance. For example, one can decrease the need for the amount and frequency of dermal fillers and one can conduct fewer fractional treatments when lentigines are specifically targeted. There may also be the possibility of foregoing vascular laser treatment if the fractional laser used to treat facial vessels was sufficient. Patient concerns should be addressed, i.e., were his/her expectations met? Is there anything new on the patient that has become noticeable since the initial treatment needs have been performed and met? Normally, with time, additional needs will become apparent.


In summary, botulinum toxins, fillers and lasers can be used synergistically to minimize the signs and sun damage and aging. To produce the optimal results, expertise in the techniques are required, one should use the best possible modalities and watching and treating for any possible complications is imperative. Combining these modalities may obviate the need for more invasive procedures.

Managing Pemphigus and Pemphigoid: How to Avoid Getting Sued

John J. Zone, MD

In general, Dermatologists see very few blistering diseases. Therefore, managing these autoimmune conditions can often be a challenge in practice.  Dr Zone, an expert in the field of autoimmune blistering diseases, discusses these conditions and optimal strategies for managing these patients from his perspective.

Dr Zone came upon this topic because over the years he has managed a large number of people with both pemphigus and pemphigoid. He always asks himself “what would I do if I was sitting here?”

Virtually, all medications for the treatment of pemphigus and pemphigoid are used off’-label.


Case Study 1

In this first case, we can see a lot of acnatholysis and one would assume that it looks like pemphigus.

The above picture shows the direct immunoflourescence, the epidermis is at the top and is totally black.

This case was actually Hailey Hailey disease; therefore, histology alone does not make a diagnosis. According to Dr Zone, treating people on the basis of histology alone is a mistake.

Pemphigus- How do I biopsy people?

Biopsy of the wrong location for direct immunofluorescence is the single greatest problem that is seen in the specimens that are received. Dr Zone would not biopsy in the crusty area; he would biopsy the clinically normal appearing skin (see circle above) near the lesion. That is where one would find the classical cell surface antibody of pemphigus.

Dr Zone also sees a lot of mucosal pemphigus and pemphigoid. Again, it is important to biopsy the normal appearing mucous membrane immediately adjacent to the lesion. There is antibody all around the lesion so there is no need to get involved in in areas with intense inflammation that disrupt the antibody deposition pattern.

Ocular and Esophageal Pemphigoid

In the case of ocular pemphigoid (above), it is important to biopsy the reddish area NOT the bands of scar tissue called symblepharon that are usually negative on immunofluorescence. This should be done by an ophthalmologist.

Clinical Pearl- Dr Zone believes that rituximab should be used as initial therapy for ocular pemphigoid. Dr Zone has seen seven patients who have gone blind from this disease. Dermatologists should biopsy for direct Immunofluorescence if considering immunobullous disease. It is imperative that the biopsy is performed on clinically normal appearing skin adjacent to a lesion. 

 Pemphigus Antigens

Pemphigus foliaceus  (PF) and pemphigus vulgaris (PV) have different desmoglein antigens. The PF antigen is Dsg 1 and the PV antigen is Dsg 3, both of which are calcium-dependent adherence molecules. Desmoglein causes epithelial cells to stick one to another. Dr Zone finds that these antibody levels correlate extremely well with disease activity.  (see figure below)

In this case, Dr Zone treated this patient with azathioprine; however, he wasn’t fully responding.  The  “dip” in antibody levels reflects plasmapheresis. From there, he stopped the azathioprine and the patient was started on CellCept and the levels went up. Dr Zone, remembering that azathioprine induces thiopurine methyl transferase and patients become resistant to the drug, went back to azathioprine at very large doses, to the point of leucopenia, and eventually the patient went into remission.

These levels allow Dr Zone to predict how the patient is responding to therapy.

This (above) case represents a case where the antibodies were presumably against non-pathogenic epitopes.  Dr. Zone used plasmapheresis at the beginning of her clinical presentation (seen in the antibody titer drop)  In this particular case the high titer antibodies were likely against non pathogenic epitopes, and the patient went into remission without a corresponding decrease in antibody levels.

Indirect Immunofluorescence (IIF). Dr. Zone commented that the pemphigus antibody titers on IIF were found to correlate roughly with disease activity however the correlation with clinical activity was not as good as we now see with the ELISA technique. IIF has low accuracy and reproducibility .

Clinical Pearl- Dermatologists should biopsy for direct Immunofluorescence if  they are considering immunobullous disease. Biopsy clinically normal appearing skin adjacent to a lesion. It is important to monitor response with serial antibody level.


For antigen identification it is important testing using salt-split skin or ELISA.  This allows identification of specific antibodies that can then be used as an index of response to therapy. BP180(BPAg2) is the most common antigen and can be quantified using ELISA.

This patient’s BP180 antibody levels correlated very well with her disease activity.

Several studies have shown the correlation of disease activity with these antibodies.

Why is this important to test for antibodies?

Research has suggested that ant-epiligrin (laminin 332)  usually found in mucous membrane pemphigoid has a strong association with cancer. In a study of 35 patients with laminin V (332) mucous membrane pemphigoid there were 10 solitary solid cancers. There was a temporal association (14 months before or after the onset of the tumor in 9 out of 10 patients). The control groups indicated a relative risk of 15.4 (5.7-33.6). Ascertainment bias and treatment bias are unlikely because of time course. If a patient’s antibody goes the dermal side of salt split skin on indirect immunoflourescence, and binds to laminin 332 on immunoblot, that patient has a one in three chance of having cancer.

Type VII Collagen

The epidermolysis bullosa acquisita antigen (type VII collagen), which is present in the skin, is also present in the wall of the normal human colon. Research has shown that type VII collagen antibodies are associated with Crohns disease.  What does this mean? If you have antibodies to type VII collagen and epidermolysis bullosa acquisita (IgG antibodies that go to the dermal side of salt split skin on indirect immunoflourescence ) then you have a very significant chance of having Crohn’s disease or ulcerative colitis. If Dr Zone finds out that these people have antibodies to type VII collagen, then he screens them for Crohn’s and ulcerative colitis .

Clinical Pearls- Biopsy for direct Immunofluorescence if considering immunobullous disease; Biopsy clinically normal appearing skin adjacent to a lesion; Identify antigen if possible; Monitor response with serial antibody levels

Dr Zone prefers a topical steroidal therapy to control mild disease, especially in the mouth, and little to no systemic steroids. Dr Zone has found that over the years, systemic steroids have caused more problems to patients. If systemic steroids are required, Dr Zone suggests starting patients on a bisphosphonate, prior to starting the steroids, possibly alendronate (70 mg/wk). Patients should also be started on an H2 blocker or a proton pump inhibitor, the risk of gastritis is very high and it is very real.  A study from the New England Journal of Medicine looked at the comparison of oral and topical corticosteroids in elderly patients with bullous pemphigoid. Since the elderly have a low tolerance for oral corticosteroids the researchers evaluated whether potent topical steroids could decrease mortality and morbidity while controlling disease. Topical steroids were associated with significantly fewer problems with infection, diabetes and psychiatric symptoms.

The above table illustrates all the more reason to utilize topical steroids.

Dr Zone’s Algorithm for the Treatment of Pemphigoid

The dose for doxycycline (if tetracycline is not available) is 100 mg PO BID and niacinamide is 500 mg PO BID. This can be used effectively in mild pemphigoid.

Rituximab should be for any ocular or esophageal pemphigoid. For moderate and severe pemphigus rituximab has a definite benefit and Dr. Zone uses it in this clinical situation.

Rituximab and its Use in Autoimmune Disorders

  • Vaccinations before hand for pneumococcus, influenza, DPT boost 4 weeks earlier if possible
  • Stop immunosuppressives if possible (may have increased complications when used in conjunction with rituximab)
  • Premedicate with steroids and antihistamines to minimize infusion reactions
  • Dosing: 375g/m2 weekly x 4
  • OR 1000mg twice – 2 weeks apart (dosing most often used by rheumatologists)

A study by Joly, et al in the New England Journal of Medicine looked at a single cycle of rituximab for the treatment of severe pemphigus vulgaris in resistant patients (14 PV and 7 PF). The patients received a single cycle of rituximab, 18 of the 21 patients were in complete remission at 3 months and 2 of the 21 patients were in complete remission by 12 months. 9 patients experienced a relapse at 12 months and 2 of the patients required a second cycle. 8 of the 21 patients required no systemic therapy afterward. The Dsg antibody levels correlated with treatment response.

In another study looking at rituximab and autoimmune disorders, the researchers found that serious infections do not appear to be substantially increased but isolated reports are bothersome. Progressive Multifocal Leukoencephalopathy in non-HIV autoimmune patients treated with rituximab has created a significant concern.  Their total serum IgG was not significantly lowered.  When studying rituximab for patients with refractory mucous membrane pemphigoid, Le Roux-Villet et al, looked at 25 patients given 1 or 2 cycles of rituximab (375 mg/m2 weekly for 4 weeks). There were complete responses in all affected sites (ocular and/or extraocular) in 17 patients (68%) by a median time of 12 weeks after the first cycle and 5 additional patients responded completely after a second cycle, yielding an 88% complete response rate. 9 of the 10 patients became noninflammatory within a mean of 10 weeks. Severe infection occurred in 3 patients (12%) who developed severe infectious complications, 2 (8%) died; they had been receiving concomitant conventional immunosuppressants and high-dose corticosteroids. The immunosuppressants were discontinued in all other patients and no other infections were observed. 10 patients experienced a relapse after a mean of 4 (range, 1-16) months after achieving a complete response and were re-treated.

In 2009, Jones, et al published a multicenter survey of ritxumab therapy for refractory anti-neutrophil cytoplasmic antibody-associated vasculitis (ANCA vasculitis) in Arthritis and Rheumatism. 49 of the 65 patients (75%) achieved complete remission. 15 of the 65 (23%) achieved a partial response and 1 (2%) had no response. The median time to remission was 2 months (range, 1-5 months). Immunosuppressive therapy was withdrawn in 37 of 60 patients (62%). 28 of 49 patients experienced a relapse (median 11.5 months) and B cell return preceded the relapse in 14 of 27 patients (52%).  Serious adverse events seemed to be associated with the underlying disease so it is important to remember that the underlying disease is still a problem for several months. 46 SAEs occurred in 25 patients, and some patients experienced more than 1 SAE. Most patients received immunosuppression either immediately before (37) or during (14) rituximab therapy.  This study was reviewed to allow understanding of potential side effects of rituximab independent of the presence of pemphigus or pemphigoid.

Take Home Points

  • Make certain of the diagnosis
    • DIF and serology
    • Identify specific antigen whenever possible and follow antibody levels
    • Minimize systemic steroids
      • Use bone and stomach protection
      • Rituximab for severe disease
        • Sooner rather than later
        • Rituximab is the best initial treatment in ocular pemphigoid
        • The underlying disease is still a problem for months
        • Beware of simultaneous immunosuppressive therapy



The future of personalized medicine could be monoclonal antibodies that are directed against antigen specific B cells. Dr Zone feels that we will see a lot more of this over the years to come.