hemangioma

Editor's Notes

1. InternationalSocietyfortheStudyofVascularAnomalies (ISSVA)atthe1996 Theclassification systemwasrecentlyexpandedatthe2014 ISSVAworkshopinMelbourne
2. that appear during first months of life characterizedby a pattern of rapid proliferation, followed by a slower period of involution most common paediatric tumour, affecting 10–12% of infants by first year of life more commonly in girls than boys (3 and 5 : 1) premature infants
3. , red plaque overlying a bluish nodule.
4. focal : Discrete, usually oval or round, and appear to grow from a single focal point. Multifocal Segmental : Geographic shape and involve a broad anatomic region or a recognized developmental unit Indeterminate type
5. present as a precursor lesion in immediate perinatal period, very subtle, with a faint telangiectatic patch or even a patch of naevus anemicus-like pallor. Soon after this, the precursor lesion begins to become palpable, often in a cluster giving rise to the ‘strawberry’ appearance. They may occur anywhere on the skin or mucosal surface clinical appearance is dependent on how deep into the skin they extend. This may be superficial (50–60%), where they are bright red in the period of proliferation, deep, in which they have a more blue appearance, or a combination of both superficial and deep (25–35%) During the early phase of growth, haemangiomas have solid groups of endothelial cells with few lumina and nonpleomorphic nuclei. The endothelial cells then fl atten out as lumina develop and start to bulge outward. The cells are surrounded by a thickened basement membrane. As involution proceeds, the haemangioma has a more obvious lobular appearance, with islands of fi brous and fatty tissue separating these lobules.
6. The mean period of proliferation - 5 months with deeper lesions often proliferating up to 12 months of age Involution may begin in the first year
7. The anatomical location is of major importance in determining the potential for complications such as airway obstruction, visual disturbance and ulceration
8. referred to by different acronyms— SACRAL - spinal dysraphism, anogenital, cutaneous, renal and urological anomalies, with angioma of lumbosacral localization syndrome PELVIS -perineal hemangioma, external genitalia malformations, lipo myelomeningocele, vesicorenal abnormalities, imperforate anus, and skin tag Lower-body counterpart to PHACES syndrome.
9. Diagnosis of IH is usually made on clinical basis But following workup may be required
10. Laryngoscopy - Cephalic hemangioma or if there are associated respiratory symptoms, to investigate possible laryngeal or tracheal involvement.
11. Most hemangiomas are small tumors Natural course of IH - spontaneously involutes, therapeutic intervention is usually not required in 70 to 80% of cases. Evaluation - with dangerous, or potentially dangerous IH - every 2weeks during the first 2–3 months of life, and every month during the phase of growth. Close contact with parents is important.
12. Life threatening complications - airway obstruction, congestive cardiac failure or gastrointestinal bleeding Functional impairement - difficulty in feeding, urination or defecation, or gross impairment of hearing or vision Hemangiomas over nose, lip, glabellar area, ear likely to result in disfigurement Ulcerated hemangiomas Large facial hemangiomas, those with a large dermal component Exophytic hemangiomas likely to leave significant fibrofatty residue Visceral hemangioma Active non-intervention should be done as can regress spontaneously- so close followup
13. NO FDA APPROVED DRUG FOR HEMNAGIOMA Propranolol- rct Int J Pediatr Otorhinolaryngol. 2011 Apr;75(4):455-60. doi: 10.1016/j.ijporl.2011.01.028. Epub 2011 Feb 17. A meta-analysis on the effectiveness of propranolol for the treatment of infantile airwayhaemangiomas. Peridis S1, Pilgrim G, Athanasopoulos I, Parpounas K. Author information Abstract OBJECTIVE: To study the effectiveness of propranolol in infantile airway haemangiomas and compare the effectiveness of propranololvs. different therapies. METHODS: A literature search of Ovid, Embase, the Cochrane database, Google™ Scholar, and Medline using PubMed as the search engine was performed to identify studies that analysed the effect of propranolol treatment in children with airway haemangiomas. Random-effect meta-analytical techniques were conducted for the outcome measures. RESULTS: Thirteen studies, comprising 36 patients were included in the analysis. Propranolol was found to be an effective intervention for the resolution of infantile airway haemangiomas (P<0.00001). Meta-analysis of effectiveness of propranolol vs. steroids, CO(2) laser, or vincristine showed that propranolol is the most effective treatment. CONCLUSIONS: This meta-analysis demonstrated that propranolol should be recommended as a first-line treatment in infantile airwayhaemangiomas. However, because of the possible side effects of propranolol, current infantile haemangioma treatment centres recommend a full cardiovascular and respiratory review be performed prior to initiation of therapy. Steroid- SYSTEMATIC REVIEW Arch Dermatol. 2001 Sep;137(9):1208-13. Oral corticosteroid use is effective for cutaneous hemangiomas: an evidence-based evaluation. Bennett ML1, Fleischer AB Jr, Chamlin SL, Frieden IJ. Author information Abstract OBJECTIVES: To determine the efficacy of systemic corticosteroid therapy in treating enlarging, problematic cutaneous hemangiomas and to assess the relationship of dose to response and adverse effects. DESIGN: A quantitative systematic literature review was performed and inclusion and exclusion criteria were applied. SETTING: Patients were treated in primary care, referral centers, and institutional practices. Most patients were ambulatory, although some required hospitalization. PATIENTS: Inclusion criteria were original case series with a minimum of 5 patients with enlarging, problematic cutaneous hemangiomas treated with systemic corticosteroids. Exclusion criteria were being older than 2 years, receiving simultaneous other treatments, being lost to follow-up, or having insufficient information. Twenty-four original case series met inclusion criteria; 10 case series remained (184 patients) after exclusion criteria were applied. INTERVENTION: Patients were given a mean prednisone equivalent daily dose of 2.9 mg/kg (95% confidence interval [CI], 2.7-3.1 mg/kg) for a mean of 1.8 months (95% CI, 1.5-2.2 months). MAIN OUTCOME MEASURES: Response and rebound rates and dose-response and adverse effects-response relationships in responders vs nonresponders. RESULTS: Response was 84% (95% CI, 78%-89%; range, 60%-100%) and rebound was 36% (95% CI, 29%-44%; range, 0%-65%). A significant difference was found between the mean dose administered to responders vs nonresponders (P<.001). No significant difference was observed as to the occurrence of adverse effects (P =.3). CONCLUSION: Systemic corticosteroid treatment seems to be effective for problematic cutaneous hemangiomas of infancy Timolol- rct Pediatrics. 2013 Jun;131(6):e1739-47. doi: 10.1542/peds.2012-3828. Epub 2013 May 6. RCT of timolol maleate gel for superficial infantile hemangiomas in 5- to 24-week-olds. Chan H1, McKay C, Adams S, Wargon O. Author information Abstract OBJECTIVE: Timolol maleate 0.5% gel is a safe and effective medication for treating superficial infantile hemangiomas (IHs) in infants with a median age of 9 weeks. METHODS: Forty-one infants who had superficial IHs without ulceration and not near mucosal surfaces were recruited and randomly assigned to placebo and treatment (timolol maleate 0.5% gel) groups. Efficacy was assessed by performing blinded volume measurements at weeks 0, 1, 2, 3, 4, 8, 12, 16, 20, and 24 and blinded investigator photograph scoring at weeks 0, 12, and 24. Safety was assessed by measuring heart rate and systolic and diastolic blood pressure at weeks 0, 1, 2, 3, 4, 8, 12, 16, 20, and 24. RESULTS: Fifteen of the 19 infants receiving treatment and 17 of the 22 infants receiving placebo completed the study. Significant color change on the blinded photographic scores was noted at week 24 of the study (P = .003). There was a significantly higher proportion of treated IHs that reduced in size by >5% at weeks 20 and 24 (P < .02). The predicted proportion of IH volume change was also significantly less for treated IHs from week 16 onward when compared with placebo (P < .05). There was no significant variation in blood pressure and heart rate between the groups. CONCLUSIONS: Topical timolol maleate 0.5% gel with a maximum dose of 0.5 mg per day is a safe and effective option for small superficial IHs that have not ulcerated and are not on mucosal surfaces. STEROIDS VS PROPRANOLOL J Pediatr Surg. 2013 Dec;48(12):2453-9. doi: 10.1016/j.jpedsurg.2013.08.020. Effect of propranolol vs prednisolone vs propranolol with prednisolone in the management of infantilehemangioma: a randomized controlled study. Malik MA1, Menon P, Rao KL, Samujh R. Author information Abstract AIMS AND OBJECTIVES: The purpose of this study was to compare the efficacy of orally administered propranolol versus prednisolone versus both in the treatment of potentially disfiguring or functionally threatening infantile hemangiomas. MATERIAL AND METHODS: A prospective study of 30 patients aged 1 week-8 months was randomized into three equal groups. These were as follows: A, propranolol (2-3 mg/kg/d); B, prednisolone (1-4 mg/kg/d); and C, receiving both for a minimum duration of 3 months. Dimensions, color, consistency, ultrasonography, photographic documentation based on Visual Analogue Scale (VAS) were recorded before and periodically after starting treatment. A minimum 75% improvement was considered as success with no regrowth up to 1 month of stopping treatment. RESULTS: Mean initial response time (days) in A (4.1±3.3 SD) and C (4.7±3.4SD) was significantly lower than B (9.78±7.8SD) (p<0.047). Significant change in consistency was noted very early in A (24 hours) compared to B and C (8 days). VAS results are as follows: (a) color fading--significant reduction in A within 48 hours compared to B and C (p=0.025), (b) flattening--more significant and earlier in A and C than B (p<0.05), and (c) mean reduction in size: significant in A and C at 3 months (p=0.005, p=0.005), 6 months (p=0.005, p=0.008), 12 months (p=0.005, p=0.008), and 18 months (p=0.02, p=0.04), whereas in B, it was seen only at 6 months (p=0.008). CONCLUSIONS: Propranolol had a consistent, rapid therapeutic effect compared to prednisolone. A combination of the two had a comparable but not higher efficacy than propranolol alone. Prednisolone was associated with a higher number of complications, thereby decreasing patient compliance. PDL Dermatol Surg. 2013 Mar;39(3 Pt 1):414-21. doi: 10.1111/dsu.12081. Epub 2012 Dec 26. Superficial hemangioma: pulsed dye laser versus wait-and-see. Kessels JP1, Hamers ET, Ostertag JU. Author information Abstract BACKGROUND AND OBJECTIVES: Childhood hemangioma is the most common soft tissue tumor of infancy, occurring in 10% of children younger than 1 year old. Ten percent of these infantile hemangiomas involute yearly without intervention. Treatment with the pulsed dye laser (PDL) is the criterion standard for treating vascular lesions. It is well established as the most effective, safest treatment for port-wine stains. Previous studies of the use of PDL treatment in superficial hemangioma showed inconsistent results. Main objectives were to compare the efficacy and adverse effects of PDL treatment with those of observation in the treatment of superficial hemangiomas. Parental quality of life was also assessed. MATERIALS AND METHODS: This was a prospective, randomized, controlled trial in which we enrolled 22 infants aged 1.5 to 5 months old with early hemangiomas with a maximum diameter of 5 cm. We assigned the infants to PDL treatment (n = 11) or observation (n = 11), and followed up until the age of 1 year. Patients in the intervention group were treated using a 595-nm PDL (VBEAM, Candela Corp., Wayland, MA) with a 7-mm spot diameter, 30/10 to 40/10-ms epidermal cooling, a 7- to 15-J/cm(2) fluence range, and a pulse duration of 0.45 to 40.0 ms. During follow-up, color measurements were made (Colori meter; Minolta, Tokyo, Japan), and surface area and echo depth of the hemangioma were determined. RESULTS: No significant differences were seen between the groups at time of inclusion or at the age of 1 year in echo depth (p = .66) or surface area (p = .62). Results were significant for color difference (p = .03) between PDL treatment and observation. Cosmetic outcome judged by an independent panel consisting of a dermatologist, physician assistant, dermatology resident, dermatology nurse, and plastic surgery resident was significantly better in the PDL treatment group (46%) than in the observation group (18%) (p = .006). CONCLUSIONS: Pulsed dye laser is only to be considered as an alternative treatment up to the age of 6 months, at which time parents and physicians consider cosmetic outcome to be a relevant factor, but laser therapy plays a major role in the treatment of residual lesions at older ages Imiquimod- retrospective study Clin Exp Dermatol. 2013 Dec;38(8):845-50. doi: 10.1111/ced.12150. Epub 2013 Apr 30. Imiquimod 5% cream versus timolol 0.5% ophthalmic solution for treating superficial proliferating infantile haemangiomas: a retrospective study. Qiu Y1, Ma G, Yang J, Hu X, Chen H, Jin Y, Lin X. Author information Abstract BACKGROUND: Infantile haemangiomas (IHs) are the most common vascular tumours of infancy. Topical therapies are a possible treatment for superficial IHs. AIM: To determine the efficacy and safety of topical therapy in the treatment of superficial proliferating IHs. METHODS: The medical records of all the patients with proliferating superficial IHs were reviewed. All lesions had been treated either with imiquimod 5% cream or timolol 0.5% ophthalmic solution. Lesions were classified into pairs, with one of each treatment in each pair, matched by anatomical location, colour and size. A visual analogue scale (VAS) and the Haemangioma Activity Score (HAS) were used to evaluate the efficacy of the two drugs. The paired Student t-test was used to test for differences in recovery with these two treatments. RESULTS: In total, 51 patients treated with timolol and 94 treated with imiquimod met the inclusion criteria, and 20 lesions treated with timolol were successfully matched to a lesion treated with imiquimod. The paired t-test indicated that there was no significant difference in either VAS score (P = 0.11) or HAS (P = 0.49). For the imiquimod-treated patients, crusting was the most common reaction (65.0%, 13/20). This did not cause any superficial scarring or skin pigmentation in the matched pairs; however, superficial scars (14.9%, 14/94) and skin pigmentation disorders (28.7%, 27/94) were reported for some of the unmatched cases. There were no adverse events (AEs) during the treatment with timolol. CONCLUSIONS: Both imiquimod 5% cream or timolol 0.5% ophthalmic solution showed equivalent clinical efficacy after 4 months of treatment. Timolol appeared to have fewer AEs than imiquimod in the management of superficial IHs. Larger, prospective controlled trials with long-term treatment are needed to confirm these results.
14. maintained at this until cessation of growth or shrinkage, f/b gradual taper Taper schedule is determined by : age of patient Growth characteristics adverse effects rebound growth Treatment response
15. Pediatrics. 2007 Jun;119(6):e1239-47. Epub 2007 May 7. Oral versus high-dose pulse corticosteroids for problematic infantile hemangiomas: a randomized, controlledtrial. Pope E1, Krafchik BR, Macarthur C, Stempak D, Stephens D, Weinstein M, Ho N, Baruchel S. Author information Abstract OBJECTIVES: Oral systemic corticosteroids are the mainstay of treatment for problematic hemangiomas; however, current information is based on anecdotal experience and retrospective studies. We aimed to determine whether systemic steroids are efficacious in proliferating hemangioma and to compare the efficacy and safety of 2 corticosteroid treatment modalities. PATIENTS AND METHODS: Twenty patients with problematic hemangiomas of infancy were randomly assigned to either daily oral prednisolone or monthly intravenous pulses of methylprednisolone. Their clinical outcomes (improvement using a visual analog score) and adverse events were compared at 3 months from baseline and 1 year of age. Data on possible surrogate markers of angiogenesis were available for the first 3 months. RESULTS: At 3 months, orally treated patients had a median visual analog score of 70 compared with 12 in the intravenous group. This response pattern was similar at the patients' first birthday: 50.0 vs -1.5. Additional treatment beyond 3 months was needed for 65% of the patients (7 in the intravenous and 6 in the oral group). Six of 8 patients with impaired vision at enrollment had an improved function at 1 year (4 patients in the intravenous group and 3 patients in the oral group). Of the 4 surrogate markers of angiogenesis measured (plasma basic fibroblast growth factor, vascular endothelial growth factor, vascular cellular adhesion molecule 1, endoglin, and urine basic fibroblast growth factor), the only 2 that decreased over time were vascular cellular adhesion molecule 1 and endoglin. Patients in the oral group had a higher rate of adverse effects, such as hypertension (18.6% vs 13.1%), abnormal cortisol (78% vs 60%), and growth retardation. CONCLUSIONS: Systemic corticosteroids are efficacious in stopping the proliferation of hemangiomas. The oral corticosteroids offered more clinicaland biological benefit than the pulse steroids with higher risk of adverse effect
16. Oral propranolol has three different pharmacological effects: Early, intermediate and long-term effects. The early effect of a visible change in colour and considerable softening of the lesion occurs within 1-3 days, after the initiation of therapy. This is related to the β2 inhibitory effect of propranolol that decreases the release of the vasodilator transmitters such as nitric oxide. The resulting vasoconstriction of the feeding capillaries is responsible for the early changes in haemangiomas. In view of its immediate clinical effect, propranolol is nowadays considered as the promising therapy in IH with ulceration or haemangiomas involving vital structures such as eyes, airways, genitalia etc. In the proliferative phase of IH there is an increased expression of pro-angiogenic factors in particular the vascular endothelial growth factors (VEGF) and basic fibroblast growth factors (bFGF). The intermediate effects of propranolol are due to a downregulation of both VEGF and bFGF resulting in inhibition of proangiogenic cascade and angiogenesis. The long term effect of propranolol is due to apoptosis resulting in regression of haemangiomas.[41] This may be the reason for its use in the post proliferative phase
17. Relapse after discontinuation of propranolol therapy occurred in 2 of the 68 patients; however, both patients responded to propranolol therapy on reinitiation of treatment
18. Hydrophilic cardioselective beta-blocker that acts principally on β 1 receptors, does not cross the blood-brain barrier and has less β 2 effects. To date, some authors have demonstrated that atenolol is safe and effective in children with cardiologic pathologies. ADVANTAGES OVER PROPANOLOL Less bronchial adverse events No sleep disturbances Can be used in cardiac conditions Single daily dose required Less risk of hypoglycaemia
19. Pediatrics. 2013 Jun;131(6):e1739-47. doi: 10.1542/peds.2012-3828. Epub 2013 May 6. RCT of timolol maleate gel for superficial infantile hemangiomas in 5- to 24-week-olds. Chan H1, McKay C, Adams S, Wargon O. Author information Abstract OBJECTIVE: Timolol maleate 0.5% gel is a safe and effective medication for treating superficial infantile hemangiomas (IHs) in infants with a median age of 9 weeks. METHODS: Forty-one infants who had superficial IHs without ulceration and not near mucosal surfaces were recruited and randomly assigned to placebo and treatment (timolol maleate 0.5% gel) groups. Efficacy was assessed by performing blinded volume measurements at weeks 0, 1, 2, 3, 4, 8, 12, 16, 20, and 24 and blinded investigator photograph scoring at weeks 0, 12, and 24. Safety was assessed by measuring heart rate and systolic and diastolic blood pressure at weeks 0, 1, 2, 3, 4, 8, 12, 16, 20, and 24. RESULTS: Fifteen of the 19 infants receiving treatment and 17 of the 22 infants receiving placebo completed the study. Significant color change on the blinded photographic scores was noted at week 24 of the study (P = .003). There was a significantly higher proportion of treated IHs that reduced in size by >5% at weeks 20 and 24 (P < .02). The predicted proportion of IH volume change was also significantly less for treated IHs from week 16 onward when compared with placebo (P < .05). There was no significant variation in blood pressure and heart rate between the groups. CONCLUSIONS: Topical timolol maleate 0.5% gel with a maximum dose of 0.5 mg per day is a safe and effective option for small superficial IHs that have not ulcerated and are not on mucosal surfaces.
20. Cyclophosphamide has also been used with success in cases with multiple cutaneous and hepatic hemangiomas
21. Imiquimod, an immune response modifier with anti-angiogenic and pro-apoptotic properties, has been used in the treatment of superficial IH. Imiquimod 5% cream is applied on alternate days at bed time and left for 8 hours. It is washed with mild soap the next morning. The duration of therapy is about 4 months. Severe inflammatory reactions may occur with application of imiquimod. Qiu et al. studied the efficacy and safety of imiquimod in their retrospective comparative study of imiquimod versus timolol in superficial proliferative IH. They found that the efficacy of imiquimod was comparable with timolol. However, inflammatory changes were seen in 13 of 20 (65%) cases in the imiquimod group while none of cases in the timolol group had side effects. Qiu Y, Ma G, Yang J, Hu X, Chen H, Jin Y, et al. Imiquimod 5% cream versus timolol 0.5% ophthalmic solution for treating superficial proliferating infantile haemangiomas: A retrospective study. Clin Exp Dermatol. 2013;38:845–50. [PubMed: 23627540]
22. Controversial Adverse outcomes including Ulceration and scarring described Use of PDL for intact IH limited by depth of laser’s penetration (1 mm) Studies described benefit in treatment of ulcerated hemangiomas in terms of increasing reepithelialization and decreasing pain. Greatest consensus surrounding use of PDL for IH is in treatment of residual telangiectases after involution
23. Small, Translucent Nodules On Head And Neck Around Ear Or Hairline Less frequently, involve trunk and extremities Individual nodules rarely exceed 2–3 cm in diameter occasionally deeper extension and larger subcutaneous lesions occur. Spontaneous regression is seen in the majority of cases after a variable period of time. Peripheral blood eosinophilia may be present but only in < 10% patients
24. Poorly circumscribed lobular lesion Clusters of proliferating capillaries and thicker blood vessels lined by plump, epithelioid endothelial cells with little cytological atypia and rare mitotic figures cellular inflammatory infiltrate composed mainly of lymphocytes and eosinophils Around blood vessels
25. anecdotal report of response to imiquimod cream [17].
26. Vascular, bright red to brownish red or blue-black tumour Nonblanchable Not show pulsation Lesion- sessile/ pedunculated Surrounded by a collar of acanthotic epidermis
27. retinoids are known to decrease the attachments between keratinocytes and cause nail brittleness that allows for fragment penetration between the nail bed and adjacent tissue.10 Retinoids also promote the early stages of wound healing, cause the accumulation of mononuclear cells in the dermis, and stimulate collagen synthesislesions appeared to be idiosyncratic and unrelated to daily dose and total cumulative dose
28. Lobular proliferation of small blood vessels Which erupt through a breach in epidermis to produce a globular pedunculated tumour. Epidermis forms collarette at base of lesion and covers part, or all, of the tumour in a thin layer. Proliferating vessels are set in a myxoid stroma Plump endothelial cells line vessels in a single layer. Surrounded by a mixed cell population of fibroblasts, mast cells, lymphocytes, plasma cells and where surface is eroded, polymorphonuclear leukocytes
29. A considerable proportion of pyogenic granulomas recur after such treatment, because the proliferating vessels in the base extend in a conical manner into the deeper dermis, Wherever possible, it is desirable to excise a narrow, but deep, ellipse of skin beneath the lesion and close the wound with sutures.
30. collagen is characteristically lined by tumour cells in a pattern that has been described ‘dissection of collagen
31. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes typical case are striking, consisting of a multifocal dermal proliferation of clusters of closely packed dilated capillaries with a striking similarity to renal glomeruli. single layer of endothelial cells lining intraluminal papillary projections. These cells have a hobnail (‘matchstick’) appearanc