A - EARLY/they occur during the first 3 days/ - they spontaneously withdraw in 10-15 day, maximum within the first month
* redness, swelling, bruising, tension and hardness, pain, itching, discoloration, micro-embolism
B - INTERMEDIATE /they occur after 2-6 moths/
* persistent local symptoms: redness, swelling, hardening, itching, pain, nodule/lump, fistula, ulceration, necrosis, scarring, hypertrophic scarring, keloid
C - LATE/they occur after 6 months and years later /
* dislocation of materials (migration), asymmetry, dicloloraion, telangiectasia, late infection – cellulitis, granuloma, deformity
Early and intermediate complications may occur with absolutely all types of materials, both temporary and permanent, while late occur exclusively with the permanent ones. Of all of the listed complication, the most disturbing one for both the physicians and the patients is the possibility of the so called “lumps” (nodes, clumps), as well as the possibility of the material dislocation.
NODULES AND GRANULOMAS
These are round formations of different sizes which are sometimes not visible, but they are palpable and can be hard and painful, and in more severe cases visible, sometimes very noticeable, and the blemish the natural and attractive appearance of the lips. In the most severe cases, these “pellets” can cause serious deformities. In fact, these are two completely different phenomena, both appearing as smaller or larger, single or multiple, soft or hard – “pellets”:
- nodules can appear during the first 2 months (2-6), usually individually and the size of a lentil grain or a smaller pea. It has a clear edge and is most often hard. It can sometimes be eliminated by a massage, and if that fails, the only solution is to wait for spontaneous resorption (if the material is resorptive) or to excise it surgically. The cause of nodule formation is usually inadequate injection technique.
- granuloma can appears later, after 6 months, a year or more, almost always occurs in a larger number, its mass is greater than the nodule’s, and sometimes it seems as if its spreading to the surrounding tissues (not strictly localized in places where the material was injected). It can grow very quickly, but also slowly, it’s usually soft to the touch, but there are also some that are hard. It does not have clear edges like a nodule. As a treatment, local and systematic corticosteroid administration is recommended and is fairly successful, although recurrences are possible. In time, these changes recede spontaneously, but this can last for years (1-5 years according to different data). The cause of granuloma is still unknown.
Fortunately, the probability of granuloma is relatively low and according to various statistics it ranges from 0.01 – 1.0%. This complication, same as others, may occur regardless of which substance was used, whether permanent or temporary, but what was definitely observed as a rule is the following:
- complications are more frequent when using permanent materials instead of temporary ones
- complications are more frequent if inadequate injection technique is applied (usually inadequate layer, too close to the surface, too deep or in the bolus)
- complications are more frequent when the quantity of injected substance is increased (especially with the permanent one)
In addition, there are some other determined facts that should be stated:
- different fillers give different morphological and histological granulomas
- same filler makes different granulomas in different people
- time between the injection and occurrence of granuloma is variable, most often 6 months to 4 years, but there were individual cases reported after 10-20 years or only in a few days
- granuloma formation is not associated with the injection location
- it is considered that most probably there is no risk of granuloma to become malignant
MORE ON GRANULOMA
All filler which are injected into the tissue cause an inflammatory reaction in it, but this is an immune response to a foreign body (in this case, the foreign body is the injected synthetic substance which the body does not recognize and therefore - foreign). This is considered as a normal and inevitable reaction and its end result is the formation of a Fibrous Capsule around a foreign body. This process is called encapsulation, because the tissue reacts by enveloping, limiting, forming a capsule and thus practically isolating a substance which it cannot eliminate or dissolve. This fibrous capsule primarily consists of collagen fibers layers and can sometimes be thin and soft, but sometimes thick and hard. The problem, however, occurs in those situations, which are not yet sufficiently clarified, when the tissue "assesses" that the degree of a foreign material isolation is insufficient, so it continues to surround it with new layers of collagen fibers. Therefore, granuloma is a special type of inflammatory reaction to a foreign body, some kind of excessive and overly strong reaction of the cell defense system. It is most often in a form of a pellet and histologically consists of macrophages (epithelioid histiocytes) and giant cell types of foreign body (Langhans), as well as large vacuoles; in addition to this, lymphocytes, neutrophils, eosinophils, fibroblasts and collagen can be found in various degrees.
Augmentation Effect Issue
Since a fibrous capsule (collagen fibers) always occurs around the injected material and it can be very thick, there are authors who believe that the effect of lips augmentation (and of other regions as well) is in fact achieved due to the fibrous capsule mass, rather than the injected substances mass! In many cases, this has been confirmed by microscopic analysis, where substantially larger fibrous tissue masses were found around a relatively small amounts of injected substance. Yet, in other cases, an extremely thin, almost nonexistent fibrous capsule was found, so this effect cannot be considered as a general rule.
CAUSES FOR GRANULOMA
Specific causes of granuloma are still unknown and unclear, but it is most likely not just one factor that turns a normal inflammatory reaction into a granuloma. Studies have shown that the following elements, in different ways, have their share in this:
- Excessive doses injected during one procedure
- Incorrect injection technique (unprofessional use)
- Presence of chemical impurities in the substance
- Theory of chronic low-grade bacterial infection (bacteria which are usually present in the skin, sweat glands and follicles, which are not pathogenic in themselves, but in combination with a foreign body can behave as pathogens) – this situation can cause persistently strong reaction to a foreign body and resistance to antibiotics is also common
- Trigger theory (activator) – an external cause may be a trigger which will lead to granuloma on an existing area and in the presence of a foreign material: local trauma, severe system infection (bacterial or viral), some medicines, chemotherapy – cytostatic, vaccination, etc. are stated
- On a microscopic level, it is also important whether the substance is in a form of a homogeneous gel or if it is a suspension of micro-particles, what is the gel’s density and size, and what is the shape of the micro-particles.
MATERIAL DISLOCATION PHENOMENON (and occurrence of nodules)
Dislocation of material from the location where it was injected to a completely different location, closer or farther away, is a premise which brings perhaps the greatest fear to both the patients and the physicians who deal with this. And how would it not? Cases were described when the substance injected in the lower lip gradually moved as far as to the neck! How is it possible for the substance to move, and how does this happen? Unlike the granuloma, for which the cause is still unknown, the substance dislocation mechanism is fairly well understood. The dislocation is also closely related to another phenomenon – the formation and occurrence of nodules. The following factors are considered essential in the material dislocation etiopathogenesis and nodule formation:
- INADEQUATE INJECTION TECHNIQUE - the material was injected either too close to the surface (intradermally) or too deep intramuscularly), or into the bolus
- INADEQUATE QUANTITY – most commonly too large
- FIBROUS CAPSULE FACTOR - some material cause such an immune reaction that the fibrous capsule around them is extremely thin and soft; this is positive in the sense that the lips are therefore soft to the touch, but it is negative because the material is not sufficiently fixed to the tissue and it can move
- GRAVITATION FACTOR - due to the Earths gravitation, a large amount of the material within a thin capsule, which is not able to hold it, starts to travel downward and descend (e.g. from the lower lip to the chin)
- MUSCLE MOVEMENT FACTOR - in those regions where the muscle activity is high, and such is the lips region (speaking, chewing), the injected longitudinal threads” of the substance can be compromised into round shapes by circular muscle movements. This is how nodules – pellets occur. Furthermore, the muscles may push the substance down by their movement (along with the gravity), but also up, contrary to gravity! Also, they can push it toward deeper layers of tissue (e.g. submucosal) or toward the skin surface (subepidermal). The contribution of the thin and soft fibrous capsule is also important here because the muscle can easily push out the material through such capsule and dislocate it outside of the region where it was injected. – Attention: immediate smoking can cause such nodule due to circular muscle movements!
- SKIN AND SUBCUTANEOUS TISSUE QUALITY - if the skin is limp and thin and the subcutaneous tissue loose (“floppy”) then, due to gravity and muscle movements, the substance is moving more easily and quickly – through the subcutaneous and muscle-facial areas
PREVENTION OF COMPLICATIONS
Recommendation for success:
- correct selection of patients (it is important to inform them on the different characteristics of different fillers, on the advantages and disadvantages, as well as possible risks)
- multiple sessions (multi-stage injections)
- adequate time distance between sessions (which is modified depending on the reaction of the tissue)
- limit the amount that is injected during one procedure ("less is more!")
- correct and precise injection technique and sometimes combining several techniques (tunnelling, fanning, micro-droplets, etc.)
- postoperatively: give patients precise instructions (on massages, limited mimics, avoiding tanning beds, etc.)
- Training the physicians by professionals
COMPLICATION THERAPY (and lip volume correction)
There are two groups of patients who come for correction of lips which were already injected with a filler. The first group are those who objectively have some of the complications (granuloma, persistent hardening, dislocation of the material, asymmetry, etc.), while the other group are those patients who have no clinically established complication, but they do not like the size of their lips anymore and they want to reduce them. In both cases, similar principles are applied, which means that conservative therapy is always the first, and only if it has no effect or the effects are unsatisfactory, surgical intervention is used.
Nodules and granulomas therapy itself is still a major problem. One of the reasons is that patients often do not know neither which substance was injected nor how much of it. The microscopic histopathological diagnosis is usually not possible because it would involve surgical sampling of the lips, which patients are usually not ready for. If the material is successfully sent to microscopic analysis, standard histopathological methods can only confirm the granuloma diagnosis, but it is not possible to distinguish which material is in question.
So far, the best and most reliable therapy results were obtained from synthetic corticosteroids: triamcinolone (Kenalog, Kenacort), betamethasone (Diprofos) and methylprednisolone (Depo-Medrol).
They act anti-inflammatory and immunosuppressive, which means they inhibit the fibroblasts and macrophages activity and thus create collagen deposits. This has a softening and "dissolution" effect for both the nodules and granulomas, as well as the effect of reducing the lips volume.
It should be noted that corticosteroids are very powerful substances which must be carefully and professionally handled. The most important thing is to form an injection protocol for each individual patient, which practically means to determine the following on the basis of a clinical (and possibly a pathohistological) findings:
- adequate starting doses to be injected
- adequate concentrations of the mixture, and
- time intervals for injections
The substance must be injected directly into the nodule / granule (intralesional), because the spread of the substance to the surrounding healthy tissue can lead to atrophy and consequential indents in the skin and subcutaneous tissue. It is recommended to immediately start with high-dose substances, as multiple administration of small doses may lead to substance resistance. Intervals between injections are usually two to four weeks.
If this conservative therapy does not give satisfactory results, then surgical intervention is needed. More precisely, it is considered that surgery should be performed only after a minimum of 3 months of conservative treatments. The operation is performed either on targeted localized problematic regions of the lip (pellets, hardenings, asymmetries), or on the entire length of the lip (upper, lower, both). If technically possible, the best surgical approach would be from the mucous side, i.e. with an incision along the wet-dry edge, by a broken zig-zag line, in order to keep the scar unnoticeable and to minimize contractions. It’s not always possible to remove the complete mass of the injected material, and parts of the patient’s own fibrous tissue must often be removed, but it is necessary to preserve muscle structures as well as innervation as much as possible.
Postoperatively, the lips are swollen, and bruising may occur. Numbness, as well as impaired mobility may occur, but these are temporary. If the incisions are placed in the right place, it could be maintained that the scars from this operation, although permanent, are completely discrete.