Chronic leg ulcers can be defined as any ulcer on the lower leg (excluding those on the forefoot or toes) lasting for more than six weeks with no tendency of healing after three months or more.Among the various etiological factors leading to leg ulcers, venous disease is responsible for 60-70% of the cases and the gaiters area above the medial malleolus is the classical site of venous leg ulcers. Patient management is largely dependent on understanding the disease pathogenesis.

Presently, ambulatory venous hypertension, due any reason, is the most accepted cause of venous disease. The pressure dynamics of venous system and pathogenesis of venous disease have been schematically explained in figure 1 and 2 respectively.

The first step in management of patients with venous ulcers would be to identify the treatable underlying cause. This includes appropriate history and keen identification of risk factors, followed by complete examination and relevant investigation such as Doppler study or venography. The management of venous disease comprises of the following:

1.      General measures: Aim is to increase the venous return and improve microcirculation

• Leg end elevation- above the level of heart during sleeping
• Graduated compression stockings- must be worn before getting down from bed and continue wearing throughout the day. The ideal compression to overcome venous hypertension would be 40mm Hg at the ankle and the below-knee stockings are preferred over above-knee as the latter are uncomfortable and tend to roll in. Also, the circumference of stocking must be adjusted as per the circumference of ankle as according to the Laplace’s law, larger diameter of ankle would require more pressure from the stockings in order to counteract the internal venous pressure.
• Weight reduction
• Improved nutrition and mobility

2. Ulcer management– Aim is to promote healing and prevent recurrence.This is a challenging task as these patients have high chances of contact sensitivity, especially to wool alcohols, topical antibiotics, cetylstearyl alcohols, parabens, and rubber mixes, which are present in many dressings, ointments, and creams.

• Cleaning the ulcer with sterile saline would generally suffice.
• Non adherent dressings- For mild to moderately oozing ulcers, hydrogel dressings could be used. Alginate dressings are preferred for heavily oozing lesions where they help by exudate absorption as well as promoting the fibroblast proliferation.
• Topical antibiotics- not routinely recommended. Use if there is evidence of infection.
• Analgesia- amitriptyline, gabapentin
• Quinine- particularly useful for night cramps
• Other drugs with variable success- pentoxyfylline, rutoside, stanozolol, sulodexide, aspirin
• Investigational therapies-cytokines that promote healing such as platelet derived growth factor, hepatocyte growth factor, and human keratinocyte growth factor-2
• Skin grafting- for non-healing ulcers.As split skin grafts carry the risk of dislodgement due to exudates, mesh or pinch grafts are preferred.
• Bioengineered skin products, including bilayered skin constructs and frozen human allogeneic epidermal cultures, are being developed and may stimulate wound healing through the release of growth factors and cytokines.

3.      Correcting the underlying pathology-

• Incompetent superficial/perforator vein – sclerotherapy/ surgical removal. The prerequisite for performing any surgery on the superficial varicose veins is the patency of the deep venous system. However, in cases of deep vein insufficiency surgery must be strictly avoided as superficial veins act as major route of venous return in these cases.
• Deep vein insufficiency- Adequate treatment of deep vein thrombosis so as to prevent damage to valves and post DVT syndrome. Pelvic mass/tumor causing extravascular compression can be surgically removed.

As prevention is better than cure, the target must be to identify the patients with venous hypertension at the earliest stage and prompt institution of therapy in the form of lifestyle modification, compression stockings ad limb elevation. This would definitely bring down the incidence of active ulcers in the at-risk population and hence improve the quality of life of patients.

Chemical structure of Deoxycholic acid:

Mechanism Of Action: —Deoxycholic acid is an endogenous bile acid that solubilizes dietary fat in the gut.1 Kybella contains synthetically derived deoxycholic acid. When the drug is injected into subcutaneous fat tissue, it solubilizes lipids in adipocyte membranes. The resulting cytolysis induces an inflammatory response that clears cell debris.2.

Clinical Studies: — Approval of deoxycholic acid was based on the results of two unpublished, randomized, placebo-controlled trials (REFINE-1 and REFINE-2), which are summarized in the package insert. A total of 1,022 healthy adults 19-65 years old with a BMI ≤40 kg/m2 and moderate to severe submental fullness (grade 2 or 3 on a scale of 0 to 4) were randomized to a maximum of 6 treatment sessions with deoxycholic acid or placebo. The mean age was 49 years, mean BMI was 29 kg/m2, and 85% of the subjects were women. In the two trials, a 2-grade improvement on a composite of clinician and patient ratings of submental fat 12 weeks after the final treatment occurred in 13.4% and 18.6% of patients treated with deoxycholic acid, and in <0.1% and 3.0% of those treated with placebo. A 1-grade composite response also occurred in more patients treated with the active drug (70.0% and 66.5% vs 18.6% and 22.2% with placebo). Significantly more patients treated with deoxycholic acid had a ≥10% reduction in submental fat measured by MRI.

Adverse effects: — The most common adverse effects of Kybella injections, occurring in at least 20% of patients and at a higher rate than with placebo, were edema, bruising, pain, numbness, erythema, and induration at the injection site, which sometimes lasted for more than 30 days. Marginal mandibular nerve injury (asymmetric smile, facial muscle weakness) occurred in 4% and dysphagia occurred in 2% of patients treated with the drug; all but one case resolved without treatment.

Kybella does tend to bruise more than fillers. It is difficult  to hold pressure as it is a large area and it would be quite uncomfortable to have pressure held against  hyoid bone or throat area. Inject with a 30 gauge half inch long needle for less bruising.

Before treatment following history to be asked to the patients:

1)Any infection in or around the area to be treated

2)Any History of surgery or other cosmetic treatments on neck, chin or face

3)Trouble swallowing

4)A thyroid disorder

5)swollen lymph nodes

7)A bleeding or clotting disorder such as haemophilia

Klybella is not approved for use by anyone younger than 18 years of old.

Pregnancy: — There are no adequate studies of Kybella in pregnant women. In animal studies, no fetal harm was observed in rats at doses up to 5 times the maximum recommended human dose, but an increased incidence of missing intermediate lung lobe was found in rabbit fetuses at doses 2-fold higher than the maximum recommended human dose.

Dosage and Administration —

·         0.2 ml injections speaced 1 cm apart until all sites in the planned treatment area have been injected.

·         Each 2-mL vial of Kybella contains 20 mg of deoxycholic acid.

·         Up to fifty injection or 10 ml can be given in a single treatment.

·         Upto six single treatment can be administrated at interval no less than one month apart.

Injection Technique;

The safe and effective use of Kybella depends on the use of correct number and locations for injections  proper needle placement and administration techniques.Avoid injection near the area of the marginal mandibular nerve.(A motor branch of facial nerve) Injury to the nerve presents as an asymmetrical  smile due to paresis of lip depressor muscles.

How to avoid injury to the marginal mandibular nerve:

1)Do not inject above the inferior border of the mandible.

2)Do not inject within a region defined by a 1-1.5 cm line below the inferior border(From the angle of mandible to the mentum.)

3)Inject Kybella only within the target submental fat treatment area(see fig1 and fig.3)

Injecting into the treatment area:

Use of ice/cold packs , topical and /or injectable local anesthesia may enhance patient comfort.Outline the planned treatment area with a surgical pen and apply a 1 cm injection grid to mark the injection site. (Figure 2 and 3)

Do not inject Kybella outside the defined parameters.

Limitations: The safe and effective use of deoxycholic acid for the treatment of subcutaneous fat outside the sub mental region has not been established and is not recommended yet.Safety and effectiveness have not been established below 18 and above 65 years of age..

Contraindications:

Deoxycholic acid is contraindicated in the presence of infection at the injection sites.

Conclusion:

Newer RF devices with deeper penetration into sub cutis will accomplish some fat reduction in neck and jaws. But upcoming this new therapy molecule may help clients to reduce the appearance of double chin. More data are awaited about this treatment. There is some issue of nerve damage if used incorrectly with this treatment, so we wish more clinical trial and find better usage of this technique to give good appearance of double chin.

Ref:

1.     U Wollina and A Goldman. ATX-101 for reduction of submental fat. Expert Opin Pharmacother 2015; 16:755.

2.     B Ascher et al. Efficacy, patient-reported outcomes and safety profile of ATX-101 (deoxycholic acid), an injectable drug for the reduction of unwanted submental fat: results from a phase III, randomized, placebo-controlled study. J Eur Acad Dermatol Venereol 2014; 28:1707.

However PRP has been used in the past by orthopedic surgeons for several years to speed up soft-tissue healing from sports injuries like ligament tear as well as to treat burn victims and patients with severe ulcers. It has been since mid-1990s as an adjunct to implant therapy in dentistry and oral surgery.

The therapy involves injecting of blood plasma that contains approximately five times the platelets found in normal circulating blood.

Mechanism of PRP

As a concentrated source of autologous platelets, PRP contains (and releases through degranulation) several different growth factors like PDGF and VGEF and other cytokines that stimulate healing. The growth factors, when released, induce the production of collagen and generation of new capillaries to rejuvenate the skin.

A steady trend over the past 15 years has been for patients to seek less-invasive procedures for facial rejuvenation,making PRP popular.

It also appeals to the patient who is looking for a natural approach to volumizing the face and treating or reducing fine lines.

Indications of PRP in Dermatology

·        Hair restoration, Androgenetic alopecia.

·        Volume loss in the face, hands, and neck — particularly the crepey skin under the eyes and neck.

·        Skin rejuvenation to improve skin texture and elasticity .

·        Fine lines and wrinkles.

·        Acne scars,Post traumatic scars.

·        Stretch marks .

·        Adjuvant with Hair transplants at the recipient site to stimulate growth of transplanted grafts.

PRP preparation.

PRP is prepared either manually or by the use of automated devices just prior to the procedure. The process must be carried under strict aseptic conditions and optimum temperature regulations to ensure platelet viability. An anticoagulant, usually anticoagulant citrate dextrose solution formula A (ACD-A) or sodium citrate is used to prevent platelet aggregation

The Manual double spin method yields much higher concentration of platelets as compared to the single spin method.

This method involves separation of blood cells and plasma by a slow spin which is followed by a fast “hard spin”.

platelet-rich plasma is separated from whole blood by ‘light-spin’ centrifugation and subsequently the platelets are concentrated by ‘heavy-spin’ centrifugation with removal of the supernatant plasma.”

The basic principle behind the PRP separation procedure is as follows.

The slow spin centrifugation process separates blood components owing to their different specific gravities, i.e., RBCs being the heaviest, followed by WBCs, whereas platelets are the lightest. Platelets are concentrated right on top of the buffy coat layer. Subsequent centrifugation is faster, so that platelets are spun down and separate as a pellet at the bottom of the tube. Approximately 3/4 of the supernatant(PPP- platelet poor plasma) is discarded and the platelet-rich pellet is resuspended in remaining amount of plasma. The resulting suspension is used as PRP. Calcium chloride (CaCl 2 ) or thrombin can be used as an activator and is added to Prepared PRP before injecting.

Factors affecting PRP yield and results

·        Patients baseline platelet count.

·        Strict temperature regulations.

·        Rate and time of spin.

·        Size and shape of containers used

·        Anticoagulant used

.Performing PRP

An informed consent should be taken. A baseline complete blood count is done. Patient should be advise against use of NSAIDs or multi vitamins 2 weeks prior to therapy. Patient is applied Topical anesthesia under occlusion.Intradermal injection of Prepared PRP are given. For hair loss the PRP can be done either by direct injections or as scalp mesotherapy along with dermarollers.

Duration of therapy:

A course of treatments involves 3-4 appointments spaced 1 month apart and results can be maintained with a single repeat treatment every 6-12 months

Frequently asked Questions

1.     How long does the treatment take?

Each session takes an approximate of 45 to 60 minutes.

2.     Is it painful?

Since topical anaesthesia is used before injecting, it becomes comfortable.

However patient experiences a burning sensation immediately after injecting      PRP, which subsides in few hours.

3.     Can I go out after the procedure?

Patients develop swelling and bruises over face after the procedure. Swelling takes 24 to 36 hours to settle, while bruising may take 1 to 2 weeks.

4.     When do I see results?

The results are subtle, with gradual improvement in the injected area over a 3- to 5-week period. Full correction occurs at 4-7 weeks and can last as long as 18 months. Better results are seen with a total of 2-3 treatments given 3-4 weeks apart. Patients can expect to see better results as they receive more treatments. With time, the results get better and better.

5.     Can I get it done before a function?

No. since the patients tend to develop bruises due to use of anticoagulants, the procedure is not performed for 2 weeks preceeding any major social occasion.

6.     What are the risks or complications?

Because this is made from the patient’s own blood, there is no risk for rejection, infection, or an allergic reaction.

7.     How does PRP therapy compare with injections of filler/ Botox or surgical facelifts?

PRP is not a substitute to BOTOX/Fillers. This procedure can be combined with dermal fillers, Botox injections, and laser surgery, as well as facial surgery. PRP builds tissue over time, hence natural repairing occurs whereas traditional filler breaks down over time and are temporary.