Abstract
Purpose
Hemangiomas are benign vascular anomalies characterized by benign proliferation of blood vessels. There are no well-defined criteria for the diagnosis and treatment of oral capillary hemangioma (OCH). The objective of this study is to report a safe, effective, and low-cost protocol for diagnosis and treatment of OCH.
Materials and methods
Eight patients were diagnosed with OCH, through two physical examination maneuvers—the diascopy and head lowering maneuver with abdominal compression (HLMAC). The treatment performed was sclerotherapy with ethanolamine oleate, weekly, until the disappearance of the lesion. No local anesthetics were administered prior to the sclerosing agent injection.
Results
All cases showed a complete remission of the lesions after sclerotherapy. There were no visible scars or compromise esthetics or normal function, and there was no evidence of recurrence. Only one patient had superficial ulceration, which remained asymptomatic and healed without specific treatment.
Conclusions
This protocol was effective in the diagnosis of OCH through two physical examination maneuvers with low-cost and easy implementation, the diascopy and the HLMAC. The low concentration associated with a reduced amount of the sclerosing agent was responsible for the excellent results in the cases treated.
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Introduction
The hemangioma is a vascular anomaly characterized by benign proliferation of blood vessels and is rated by many authors as a benign vascular neoplasm [1–12]. Hemangioma is a clinical term to designate a benign vascular neoplasm or vascular malformation of endothelial origin. They may be classified by the type of blood vessels involved in capillary, juvenile, cavernous, and arteriovenous hemangioma [4]. The most common type is the capillary hemangioma, and it occurs as a small localized lesion and has the less-aggressive clinical behavior. Moreover, cavernous hemangioma is the most aggressive type of hemangiomas and generates large and infiltrated lesions [12].
The etiology of hemangioma has not been fully elucidated, but two hypotheses are more accepted. The first suggests that hemangiomas originate from placental trophoblast embolism, which originates from a household embryonic cell called trophectoderm. This theory is based on similarities at the expression of endothelial markers and transcriptomes between hemangiomas and placental trophoblasts. Trophoblasts have high angiogenic potential and promote angiogenesis in the placenta through the production of angiogenic and vasoactive substances [13].
The second theory is related to endothelial progenitor cells, which have a potential to clonally duplicate in a precise milieu of cytokines and estrogen [13]. These cells are present in the bloodstream and have great ability to differentiate and proliferate. The endothelial progenitor cells not only play an important role in the repair of damaged blood vessels but also are associated with vascular pathologies [14].
Hemangiomas have a predilection for the head and neck [4], although they may be present in one or more body parts, such as limbs, bladder, genital area, and the central nervous system [15]. They are more common in women and children, being considered the most common tumor in newborns [5]. In some cases, the lesions tend to be self-limiting and may resolve spontaneously without any therapeutic intervention [9].
In specific situations, hemangiomas can become symptomatic and may need therapeutic intervention, for example, in the presence of ulcers, pain, bleeding, secondary infections, and tissue deformations [1].
The diagnosis of hemangiomas, in most cases, can be achieved by clinical examination of the lesion [3]. The treatment may be carried out without requiring prior diagnostic confirmation, such as histological and imaging examination [7, 16, 17]. However, hemangiomas may present clinical features similar to those of other oral lesions such as racial melanosis, oral melanoma, melanosis induced by tobacco and drugs [18], retention cysts, mucoceles, Kaposi's sarcoma, and pyogenic granuloma [3]. Due to the similarity of clinical findings, diagnostic errors may occur. For this reason, other diagnostic methods should be done besides clinical appearance, because the correct choice of the therapy lies in the accurate diagnosis of the lesion [3].
If there is a need for treatment, a wide variety of therapeutic methods can be used, of which one can refer the surgical excision, sclerotherapy, surgery associated with sclerotherapy, embolization, laser therapy, cryotherapy, and corticosteroid therapy [7, 11]. Each method has advantages and disadvantages, and so far, there is no treatment that is widely accepted and is considered the gold standard [19, 20].
This paper aims to present a simple, safe, low-cost, and minimally invasive protocol for the treatment of oral capillary hemangiomas (OCH), ranging from diagnosis to treatment, using physical examination maneuvers and a treatment with sclerotherapy. This protocol was easy to implement and was used effectively in eight cases OCH. The diagnosis was established by clinical examination associated with diascopy and head lowering maneuver with abdominal compression (HLMAC). The treatment protocol followed a sclerotherapy protocol of ethanolamine oleate using a 1:4 dilution with distilled water.
Materials and methods
This was a retrospective study that included eight patients from the Department of Oral Pathology and Oral and Maxillofacial Surgery, School of Dentistry, University Center of Pará, who underwent to the same diagnostic criteria that included anamnesis, physical examination of the lesion, and two maneuvers: diascopy and HLMAC. These two maneuvers were performed to observe the physical changes which occurred in the lesion after its enforcement. This study was approved by the ethics committee of the Institute of Health Sciences at University Center of Pará (number 184.068).
The diascopy was performed with a glass slide used in the laboratory for histological study. The mucosa was dried, applied with a gradually increasing pressure, and was held with the thumb on the glass sheet on the hemangioma. Changes in volume and staining were observed. A significant reduction on the intensity of the coloration or discoloration by total lesion was considered positive. After the diagnostic procedure, retention of shape, size, and color intensity was considered negative (Fig. 1).
The HLMAC was performed in the dental chair that was adjusted to an angle of approximately 90°. The lesion was inspected and then the patient was oriented to lower his head as much as possible toward his legs and squeeze his abdomen. This position was maintained for about 60 s, and the lesion was inspected again. An increase in volume and/or staining intensity of the lesion was considered positive. If the lesion did not suffer changes and its original characteristics were preserved, the result of the maneuver was considered negative (Fig. 2).
After having the clinical diagnosis of OCH, the patients were submitted to sessions of sclerotherapy with ethanolamine oleate (50 mg/ml). Each session consisted of a single injection of the solution with a total volume variable according to the size of the lesion. The solution of ethanolamine oleate was diluted 1:4 in distilled water without previous anesthesia. The procedure of sclerotherapy was performed weekly until the clinical disappearance of the lesion. After clinical remission of the lesions, the patients were followed up for a total period of 12 months, with scheduled returns on the 1st, 3rd, 6th, and 12th month.
Results
All patients presented remission of the lesion, and no prior local anesthesia was needed. The patients were subjected to sclerotherapy sessions weekly, requiring one to three sessions for clinical remission. Most patients were treated with one or two sessions; only one patient needed a third session, who presented the largest lesion (18 mm). Table 1 shows the characteristics of the treatment for each patient.
Some patients reported a burning sensation at the site during administration. Analgesics were prescribed for patients if they had pain, but no patient reported the need for postoperative use. Only one patient developed a superficial ulceration, which remained asymptomatic and healed without specific treatment. There were no visible scars or impairment of normal function and esthetics. There was no evidence of recurrence in any of the lesions (Fig. 3).
Discussion
Hemangioma is one of the most common vascular anomalies in the head and neck, which may need a specific treatment when it does not have a spontaneous regression [4]. Despite its high frequency, there is no one established protocol that serves as a reference for diagnosis and treatment of OCH.
The diagnosis of OCH can be clinical [3]; however, two physical examination maneuvers were demonstrated. Together, they provide important information and reinforce the clinical diagnosis: the diascopy and the HLMAC.
The diascopy is to compress a glass plate or blade over the lesion with finger pressure [2, 4]. The pressure exerted by the glass on the hemangioma compresses the blood vessels that it forms, causing the extravasation of the blood to the periphery vessels. The result of this maneuver causes a temporarily color change of the lesion, changing an important clinical feature of the lesion which is its usual reddish or purplish color, and after the maneuver, it resembles the color of the adjacent normal mucosa. After removing the pressure, the blood returns to the inside of this hemangioma and regains its original appearance.
The HLMAC is based on the principle of blood redistribution to other body parts, including the head [21]. Thus, when the head is lowered, there is an accumulation of blood in the head. This is due to the absence of valves in the venous system of the head and neck [22], which is naturally aided by gravity in an upright posture, but during the execution of this maneuver, the head is near to the horizontal plane. This combination of factors promotes more blood supply to the OCH located in the head [23], which its clinical manifestation may present an increase in the volume and/or intensity of the red or purple color, or both of the OCH.
The association of diascopy with HLMAC is extremely useful in clinical diagnosis, with diascopy being an important alternative since it is a noninvasive procedure and because of its low cost. The histopathological methods and imaging tests have higher costs and cause local trauma [7, 16, 17], which are considerable disadvantages when compared with these simple maneuvers.
Positive results in these two maneuvers, associated with a clinical feature suggestive of OCH, were safe enough for clinical diagnosis and allowed for an indication of an appropriate treatment for each case. These simple maneuvers can help in the differential diagnosis of other pigmented lesions such as nevus, malignant melanoma, Peutz–Jeghers syndrome, Addison's disease, amalgam tattoo, and melanosis induce by drugs [18].
Once the clinical diagnosis of OCH is established, it becomes necessary to decide which treatment should be indicated. A wide variety of therapeutic methods can be used, many of these shows a satisfactory final result [3, 4, 24]. Thus, it becomes difficult to determine which method could be considered the gold standard, since each has its advantages and disadvantages, and most of them have their limitations when compared with each other [9].
The therapeutic modalities used in the treatment of hemangiomas present a risk of serious complications, which must be analyzed before each indication [9]. Among these, surgical treatment is indicated in cases that compromise the esthetic or interfere with the function of the region involved [25, 26]. Also, it is closely related to the possibility of complications such as bleeding, scarring, organ, and tissue dysfunction [1, 14, 27, 28]. Surgical treatment has a high rate of recurrence and exacerbation of lesion in the postoperative period [29].
Steroid therapy acts to reduce blood flow in the lesion due to nonspecific inhibitory effect on angiogenesis and the action by contraction of pre-capillary sphincters; however, this mechanism has not yet been fully clarified [11]. Corticosteroids administered orally have adverse effects such as cushingoid, irritability, hypertension, gastrointestinal disorders, reduced growth rate and the head circumference, and weight gain [30]. After drug interruption, the rebound effect can occur, leading to recurrence of the lesion. Application of intralesional corticosteroids presents side effects such as atrophy and pigmentary changes of the skin, vision impairment, skin necrosis, and trophic changes in the skin [11].
Interferon alpha is indicated for the treatment of hemangiomas when they do not respond to corticotherapy. It acts as an inhibitor of endothelial proliferation, although its side effects are superimposed on its therapeutic effects, such as the neurological disorder (spastic diplegia), fever, malaise, diarrhea, neutropenia, anemia, and elevated transaminases [11].
Laser therapy is widely used as a therapeutic modality of hemangioma. Laser therapy provides the excision of the lesion with low degree of bleeding. The reduction of bleeding is caused by obliteration of blood vessels caused by the treatment; however, this surgical procedure can cause tissue necrosis, tissue atrophy, hyperpigmentation (transient or permanent), and scars, in addition to its high cost and high recurrence rate [31–35].
Cryotherapy has been indicated as a treatment for minor injuries but is rarely used as a therapeutic protocol for hemangiomas. It is a procedure that can be quite painful and can result in tissue atrophy, scarring, and hyperpigmentation. Cryotherapy also has a high cost because it requires specific equipment [1, 2, 36].
Embolization and radiotherapy are normally indicated for cases of intraosseous hemangiomas and/or large lesions, in which there is presence of blood vessels with large diameter [37]. These procedures are associated with very important side effects [10, 27].
The use of sclerosing agents in the treatment of vascular abnormalities has been practised for a long time [38, 39]. It is considered conservative, effective, safe, and inexpensive [5, 6, 38, 40], being the more suitable for treatment of minor lesions [4]. The sclerosing agents most widely used are ethanolamine oleate, sodium morrhuate, polidocanol, sodium tetradecyl sulfate, absolute ethanol, sodium psylliate, quinidine urethane, hypertonic saline, and ethibloc [8, 15, 35, 39]. These substances may exhibit local and systemic complications potentially serious, such as anaphylactic shock and allergic reactions after administration of sodium morrhuate [41] and tetradecyl sulfate [42].
The polidocanol produces a reduced sclerosing effect on endothelium in comparison with ethanolamine oleate [43], with less effective results. The absolute ethanol offers high risk of complications and can cause tissue damage in case of leakage of the solution [29, 44]. There are reports that the substance ethibloc caused pain, severe inflammation, and leakage, with consequent need for surgical drainage [45].
Ethanolamine oleate primarily causes irritation in the endothelial intimal layer of the vein, producing an inflammatory response culminating in fibrosis of the vessel wall and possibly vein occlusion. Ethanolamine can diffuse through the venous wall, producing an extravascular inflammatory reaction and thus may induce venous sclerosis. The components of ethanolamine oleate have different properties. Oleic acid may have procoagulant activity through the release of Hageman factor. However, the component of ethanolamine can inhibit the formation of the fibrin clot by chelation of calcium [8]. Ethanolamine oleate may have adverse effects when used in the treatment of esophageal varices, such as anaphylactic shock [46], renal failure, hemolytic anemia, hemoglobinuria, pleural effusion, pneumonia, infiltration, edema, pyrexia, and transient pain in the chest [47]. These conditions are typically self-resolutive and resolve spontaneously over a period of 48 h [48]. There are reports of generalized urticaria that occurred after sclerotherapy for varicose veins with ethanolamine oleate in doses larger than 12 ml per session, but this reaction can be controlled with antihistamines [47].
Adverse reactions associated with the administration of ethanolamine oleate are related to the amount of the applied dose; it is being considered the amount of (0.4 ml/kg) the maximum safe dosage per patient [16, 29, 44]. In this study, the treatment of choice was sclerotherapy with ethanolamine oleate in small amounts (0.1 to 0.5 ml) and reduced concentration (1:4 distilled water). When using this amount and dilution, the results were satisfactory, with a good margin of safety regarding the recommended dosage. The solution of ethanolamine oleate was diluted in a ratio of 1:4 with distilled water and administered intralesionally, weekly until disappearance thereof. We opted for dilution with distilled water, and this did not result in great discomfort to patients who merely reported a burning sensation at the site during administration. The postoperative period was painless, and despite analgesics are being prescribed in cases of painful events, their use was not necessary.
Only in one case transient appearance of an ulcer was observed, but in this case, the patient had a lesion on the lip associated with actinic cheilitis. The ulcer healed without requiring any special treatment and without any residual complication.
The authors present a protocol of treatment for patients with OCH, in which diagnostic maneuvers and a therapeutic method are low cost and easy to implement. The protocol used included clinical examinations of the lesion and is associated with physical examination maneuvers, the diascopy and HLMAC. The clinical appearance of OCH associated with positive results in at least one of the maneuvers was sufficiently reliable for the diagnosis and treatment of the lesions. The cases were treated with sclerotherapy with ethanolamine oleate with efficient outcome in this study. The protocol used was effective in the diagnosis of OCH with low cost and easy implementation, as it does not require invasive tests, expensive equipment, or even materials for its execution. The low concentration associated with a reduced amount of the sclerosing agent was responsible for the excellent results in cases treated. This protocol has been effective in the treatment with minimal side effects.
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da Silva, W.B., Ribeiro, A.L.R., de Menezes, S.A.F. et al. Oral capillary hemangioma: A clinical protocol of diagnosis and treatment in adults. Oral Maxillofac Surg 18, 431–437 (2014). https://doi.org/10.1007/s10006-013-0436-z
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DOI: https://doi.org/10.1007/s10006-013-0436-z